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Myths about smoking, diet, alcohol, and cancer persist
FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.
This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
Is cancer hereditary?
The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.
“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.
Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
Misconceptions about smoking
About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.
Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.
“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.
This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
Overweight and obesity
Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.
“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
Breastfeeding and cancer
About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.
Artificial UV rays
Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.
Daily stress
Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.
Cigarettes and e-cigarettes
About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.
Alcohol consumption
Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.
This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
Is cancer hereditary?
The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.
“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.
Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
Misconceptions about smoking
About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.
Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.
“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.
This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
Overweight and obesity
Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.
“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
Breastfeeding and cancer
About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.
Artificial UV rays
Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.
Daily stress
Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.
Cigarettes and e-cigarettes
About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.
Alcohol consumption
Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.
This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
Is cancer hereditary?
The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.
“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.
Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
Misconceptions about smoking
About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.
Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.
“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.
This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
Overweight and obesity
Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.
“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
Breastfeeding and cancer
About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.
Artificial UV rays
Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.
Daily stress
Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.
Cigarettes and e-cigarettes
About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.
Alcohol consumption
Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
Toxic chemicals we consume without knowing it
Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.
Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.
Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
Microplastics
“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.
Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.
Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.
According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.
Pressure also is mounting for a ban on microbeads in personal care products.
Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
Phthalates
Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.
Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.
To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.
The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.
Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
Bisphenol A (BPA)
BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.
Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.
As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.
Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
Dioxins and polychlorinated biphenyls (PCBs)
Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.
Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.
Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.
The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
Pesticides
The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.
Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.
A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.
Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
Per- and polyfluoroalkyl substances (PFAS)
PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”
PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.
The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.
Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.
To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”
In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”
Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.
Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.
Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.
Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
Microplastics
“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.
Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.
Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.
According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.
Pressure also is mounting for a ban on microbeads in personal care products.
Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
Phthalates
Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.
Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.
To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.
The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.
Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
Bisphenol A (BPA)
BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.
Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.
As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.
Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
Dioxins and polychlorinated biphenyls (PCBs)
Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.
Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.
Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.
The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
Pesticides
The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.
Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.
A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.
Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
Per- and polyfluoroalkyl substances (PFAS)
PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”
PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.
The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.
Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.
To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”
In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”
Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.
Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.
Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.
Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
Microplastics
“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.
Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.
Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.
According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.
Pressure also is mounting for a ban on microbeads in personal care products.
Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
Phthalates
Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.
Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.
To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.
The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.
Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
Bisphenol A (BPA)
BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.
Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.
As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.
Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
Dioxins and polychlorinated biphenyls (PCBs)
Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.
Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.
Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.
The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
Pesticides
The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.
Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.
A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.
Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
Per- and polyfluoroalkyl substances (PFAS)
PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”
PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.
The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.
Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.
To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”
In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”
Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.
No advantage for full-term aspirin in preventing preterm preeclampsia
Stopping aspirin at 24-28 weeks of gestation has no disadvantage, compared with continuing aspirin full term, for preventing preterm preeclampsia in women at high risk of preeclampsia who have a normal fms-like tyrosine kinase 1 to placental growth factor (sFlt-1:PlGF) ratio, a randomized controlled trial has found.
The findings were published online in JAMA.
Editorialists advise careful consideration
However, in an accompanying editorial, Ukachi N. Emeruwa, MD, MPH, with the division of maternal fetal medicine, department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, and colleagues noted that the questions surrounding continuing or discontinuing aspirin in this high-risk population need further consideration.
They added that the results from this study – conducted in nine maternity hospitals across Spain – are hard to translate for the U.S. population.
In this study, Manel Mendoza, PhD, with the maternal fetal medicine unit, department of obstetrics, at the Universitat Autònoma de Barcelona, and colleagues compared the two approaches because of the potential to mitigate peripartum bleeding by discontinuing aspirin before full term (37 weeks’ gestation) and by an accurate selection of women in the first trimester at higher risk of preeclampsia.
Aspirin cuts preterm preeclampsia by 62% in women at high risk
While aspirin might be associated with an increased risk of peripartum bleeding, aspirin has been proven to reduce the incidence of preterm preeclampsia by 62% in pregnant women at high risk of preeclampsia.
In the multicenter, open-label, randomized, phase 3, noninferiority trial, pregnant women who had a high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24-28 weeks’ gestation were recruited between Aug. 20, 2019, and Sept. 15, 2021. Of those, 936 were analyzed (473 in the intervention group [stopping aspirin] and 473 in the control group [continuing]).
Screening for risk of preterm preeclampsia included analyzing maternal factors, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein A, and placental growth factor. Follow-up was until delivery for all participants.
Incidence of preterm preeclampsia was 1.48% in the intervention group (discontinuing aspirin) and 1.73% in the control group (continuing aspirin until 36 weeks of gestation; absolute difference, –0.25%; 95% confidence interval, –1.86% to 1.36%), which indicates noninferiority for stopping aspirin. The bar for noninferiority was less than a 1.9% difference in preterm preeclampsia incidences between groups.
Researchers did find a higher incidence of minor antepartum bleeding in the group that continued aspirin (7.61% in the low-dose aspirin discontinuation group vs. 12.31% in the low-dose aspirin continuation group; absolute difference, –4.70; 95% CI, –8.53 to –0.87).
Differences in U.S. guidelines
Dr. Emeruwa and colleagues noted the study challenges a growing body of evidence favoring increasingly widespread use of low-dose aspirin in pregnancy.
They called the study “well designed and provocative,” but wrote that the findings are hard to interpret for a U.S. population. Some key differences in the U.S. preeclampsia prevention guidelines, compared with the practices of the study’s authors, included the reliance on clinical maternal factors in the United States for screening for low-dose aspirin prophylaxis as opposed to molecular biomarkers; a different aspirin dose prescribed in the United States (81 mg daily), compared with international societies (150 mg daily); and a lack of a recommendation in the United States to stop prophylactic low-dose aspirin at 36 weeks.
Dr. Emeruwa and colleagues also questioned the scope of the outcome measure used.
They wrote that limiting outcomes to preterm preeclampsia dims the effects of all types of preeclampsia on perinatal and maternal outcomes and that early-onset preeclampsia at less than 34 weeks “occurs in just 0.38% of pregnancies, while 3%-5% are affected by late-onset preeclampsia.”
‘Late-onset preeclampsia has a higher overall impact’
Dr. Emeruwa and colleagues wrote: “Though the odds of adverse perinatal and maternal outcomes are higher with preterm preeclampsia, due to its overall higher incidence, late-onset preeclampsia has a higher overall impact on perinatal and maternal morbidity and mortality.”
The study can inform future U.S. approaches, the editorialists wrote, and build on work already being done in the United States.
The study investigators used biophysical and molecular markers to more accurately assess risk for starting low-dose aspirin prophylaxis in the first trimester and applied a growing body of data showing the high negative predictive value of second-trimester biomarkers.
The editorialists noted that the U.S. Preventive Services Task Force recommendations would have captured “less than 50% of the at-risk population” that Dr. Mendoza’s team found eligible for low-dose aspirin.
Those factors, the editorialists wrote, point to the potential to improve guidelines for personalized preeclampsia management in pregnancy.
They concluded: “U.S. practitioners and professional societies should reconsider current risk assessment strategies, which are largely based on maternal factors, and evaluate whether incorporation of molecular biomarkers would improve maternal and fetal/neonatal outcomes.”
The study authors acknowledged that 92% of participants in the study were White, thus limiting generalizability.
The authors and editorialists reported no relevant financial relationships.
Stopping aspirin at 24-28 weeks of gestation has no disadvantage, compared with continuing aspirin full term, for preventing preterm preeclampsia in women at high risk of preeclampsia who have a normal fms-like tyrosine kinase 1 to placental growth factor (sFlt-1:PlGF) ratio, a randomized controlled trial has found.
The findings were published online in JAMA.
Editorialists advise careful consideration
However, in an accompanying editorial, Ukachi N. Emeruwa, MD, MPH, with the division of maternal fetal medicine, department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, and colleagues noted that the questions surrounding continuing or discontinuing aspirin in this high-risk population need further consideration.
They added that the results from this study – conducted in nine maternity hospitals across Spain – are hard to translate for the U.S. population.
In this study, Manel Mendoza, PhD, with the maternal fetal medicine unit, department of obstetrics, at the Universitat Autònoma de Barcelona, and colleagues compared the two approaches because of the potential to mitigate peripartum bleeding by discontinuing aspirin before full term (37 weeks’ gestation) and by an accurate selection of women in the first trimester at higher risk of preeclampsia.
Aspirin cuts preterm preeclampsia by 62% in women at high risk
While aspirin might be associated with an increased risk of peripartum bleeding, aspirin has been proven to reduce the incidence of preterm preeclampsia by 62% in pregnant women at high risk of preeclampsia.
In the multicenter, open-label, randomized, phase 3, noninferiority trial, pregnant women who had a high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24-28 weeks’ gestation were recruited between Aug. 20, 2019, and Sept. 15, 2021. Of those, 936 were analyzed (473 in the intervention group [stopping aspirin] and 473 in the control group [continuing]).
Screening for risk of preterm preeclampsia included analyzing maternal factors, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein A, and placental growth factor. Follow-up was until delivery for all participants.
Incidence of preterm preeclampsia was 1.48% in the intervention group (discontinuing aspirin) and 1.73% in the control group (continuing aspirin until 36 weeks of gestation; absolute difference, –0.25%; 95% confidence interval, –1.86% to 1.36%), which indicates noninferiority for stopping aspirin. The bar for noninferiority was less than a 1.9% difference in preterm preeclampsia incidences between groups.
Researchers did find a higher incidence of minor antepartum bleeding in the group that continued aspirin (7.61% in the low-dose aspirin discontinuation group vs. 12.31% in the low-dose aspirin continuation group; absolute difference, –4.70; 95% CI, –8.53 to –0.87).
Differences in U.S. guidelines
Dr. Emeruwa and colleagues noted the study challenges a growing body of evidence favoring increasingly widespread use of low-dose aspirin in pregnancy.
They called the study “well designed and provocative,” but wrote that the findings are hard to interpret for a U.S. population. Some key differences in the U.S. preeclampsia prevention guidelines, compared with the practices of the study’s authors, included the reliance on clinical maternal factors in the United States for screening for low-dose aspirin prophylaxis as opposed to molecular biomarkers; a different aspirin dose prescribed in the United States (81 mg daily), compared with international societies (150 mg daily); and a lack of a recommendation in the United States to stop prophylactic low-dose aspirin at 36 weeks.
Dr. Emeruwa and colleagues also questioned the scope of the outcome measure used.
They wrote that limiting outcomes to preterm preeclampsia dims the effects of all types of preeclampsia on perinatal and maternal outcomes and that early-onset preeclampsia at less than 34 weeks “occurs in just 0.38% of pregnancies, while 3%-5% are affected by late-onset preeclampsia.”
‘Late-onset preeclampsia has a higher overall impact’
Dr. Emeruwa and colleagues wrote: “Though the odds of adverse perinatal and maternal outcomes are higher with preterm preeclampsia, due to its overall higher incidence, late-onset preeclampsia has a higher overall impact on perinatal and maternal morbidity and mortality.”
The study can inform future U.S. approaches, the editorialists wrote, and build on work already being done in the United States.
The study investigators used biophysical and molecular markers to more accurately assess risk for starting low-dose aspirin prophylaxis in the first trimester and applied a growing body of data showing the high negative predictive value of second-trimester biomarkers.
The editorialists noted that the U.S. Preventive Services Task Force recommendations would have captured “less than 50% of the at-risk population” that Dr. Mendoza’s team found eligible for low-dose aspirin.
Those factors, the editorialists wrote, point to the potential to improve guidelines for personalized preeclampsia management in pregnancy.
They concluded: “U.S. practitioners and professional societies should reconsider current risk assessment strategies, which are largely based on maternal factors, and evaluate whether incorporation of molecular biomarkers would improve maternal and fetal/neonatal outcomes.”
The study authors acknowledged that 92% of participants in the study were White, thus limiting generalizability.
The authors and editorialists reported no relevant financial relationships.
Stopping aspirin at 24-28 weeks of gestation has no disadvantage, compared with continuing aspirin full term, for preventing preterm preeclampsia in women at high risk of preeclampsia who have a normal fms-like tyrosine kinase 1 to placental growth factor (sFlt-1:PlGF) ratio, a randomized controlled trial has found.
The findings were published online in JAMA.
Editorialists advise careful consideration
However, in an accompanying editorial, Ukachi N. Emeruwa, MD, MPH, with the division of maternal fetal medicine, department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, and colleagues noted that the questions surrounding continuing or discontinuing aspirin in this high-risk population need further consideration.
They added that the results from this study – conducted in nine maternity hospitals across Spain – are hard to translate for the U.S. population.
In this study, Manel Mendoza, PhD, with the maternal fetal medicine unit, department of obstetrics, at the Universitat Autònoma de Barcelona, and colleagues compared the two approaches because of the potential to mitigate peripartum bleeding by discontinuing aspirin before full term (37 weeks’ gestation) and by an accurate selection of women in the first trimester at higher risk of preeclampsia.
Aspirin cuts preterm preeclampsia by 62% in women at high risk
While aspirin might be associated with an increased risk of peripartum bleeding, aspirin has been proven to reduce the incidence of preterm preeclampsia by 62% in pregnant women at high risk of preeclampsia.
In the multicenter, open-label, randomized, phase 3, noninferiority trial, pregnant women who had a high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24-28 weeks’ gestation were recruited between Aug. 20, 2019, and Sept. 15, 2021. Of those, 936 were analyzed (473 in the intervention group [stopping aspirin] and 473 in the control group [continuing]).
Screening for risk of preterm preeclampsia included analyzing maternal factors, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein A, and placental growth factor. Follow-up was until delivery for all participants.
Incidence of preterm preeclampsia was 1.48% in the intervention group (discontinuing aspirin) and 1.73% in the control group (continuing aspirin until 36 weeks of gestation; absolute difference, –0.25%; 95% confidence interval, –1.86% to 1.36%), which indicates noninferiority for stopping aspirin. The bar for noninferiority was less than a 1.9% difference in preterm preeclampsia incidences between groups.
Researchers did find a higher incidence of minor antepartum bleeding in the group that continued aspirin (7.61% in the low-dose aspirin discontinuation group vs. 12.31% in the low-dose aspirin continuation group; absolute difference, –4.70; 95% CI, –8.53 to –0.87).
Differences in U.S. guidelines
Dr. Emeruwa and colleagues noted the study challenges a growing body of evidence favoring increasingly widespread use of low-dose aspirin in pregnancy.
They called the study “well designed and provocative,” but wrote that the findings are hard to interpret for a U.S. population. Some key differences in the U.S. preeclampsia prevention guidelines, compared with the practices of the study’s authors, included the reliance on clinical maternal factors in the United States for screening for low-dose aspirin prophylaxis as opposed to molecular biomarkers; a different aspirin dose prescribed in the United States (81 mg daily), compared with international societies (150 mg daily); and a lack of a recommendation in the United States to stop prophylactic low-dose aspirin at 36 weeks.
Dr. Emeruwa and colleagues also questioned the scope of the outcome measure used.
They wrote that limiting outcomes to preterm preeclampsia dims the effects of all types of preeclampsia on perinatal and maternal outcomes and that early-onset preeclampsia at less than 34 weeks “occurs in just 0.38% of pregnancies, while 3%-5% are affected by late-onset preeclampsia.”
‘Late-onset preeclampsia has a higher overall impact’
Dr. Emeruwa and colleagues wrote: “Though the odds of adverse perinatal and maternal outcomes are higher with preterm preeclampsia, due to its overall higher incidence, late-onset preeclampsia has a higher overall impact on perinatal and maternal morbidity and mortality.”
The study can inform future U.S. approaches, the editorialists wrote, and build on work already being done in the United States.
The study investigators used biophysical and molecular markers to more accurately assess risk for starting low-dose aspirin prophylaxis in the first trimester and applied a growing body of data showing the high negative predictive value of second-trimester biomarkers.
The editorialists noted that the U.S. Preventive Services Task Force recommendations would have captured “less than 50% of the at-risk population” that Dr. Mendoza’s team found eligible for low-dose aspirin.
Those factors, the editorialists wrote, point to the potential to improve guidelines for personalized preeclampsia management in pregnancy.
They concluded: “U.S. practitioners and professional societies should reconsider current risk assessment strategies, which are largely based on maternal factors, and evaluate whether incorporation of molecular biomarkers would improve maternal and fetal/neonatal outcomes.”
The study authors acknowledged that 92% of participants in the study were White, thus limiting generalizability.
The authors and editorialists reported no relevant financial relationships.
FROM JAMA
Postpartum urinary retention: Intermittent catheterization may be best
Intermittent catheterization every 6 hours in postpartum women with urinary retention may be a better strategy than extended catheterization over 24 hours, a new prospective, randomized, controlled study suggests.
Patients who were catheterized every 6 hours took significantly less time to reach full relief than those who were catheterized for at least 24 hours (mean 10.2 ± 11.8 hours vs. 26.5 ± 9.0 hours, P < .001, respectively), Israeli researchers found. Their research was released at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
“There was no difference in hospital stay or in the rate of positive urine culture after catheter removal,” said ob.gyn. Dana Vitner, MD, of Rambam Health Care Campus in Haifa, Israel, in a presentation at the conference. “Our conclusion is that intermittent catheterization for postpartum urinary retention results in shorter time to resolution with a higher satisfaction rate and no additional complications.”
The true incidence of postpartum urinary retention is unclear, and estimates vary widely, said ob.gyn. and surgeon Lisa Hickman, MD, of the Ohio State University, Columbus, in an interview. “This is likely because many cases of covert urinary retention – when postpartum women are able to urinate but have incomplete emptying – go undiagnosed unless you are screening for it.”
According to Dr. Hickman, risk factors for postpartum urinary retention include operative vaginal births, having an epidural, obstetric anal sphincter injury, episiotomy, large newborns, first-time births, and prolonged induction of labor. Most cases resolve within 72 hours, she said, but they can lead to rare complications such as bladder injury.
For the new study, researchers defined urinary retention at the bladder holding least 150 mL more than 6 hours after vaginal delivery or removal of an in-dwelling catheter after cesarean delivery. “The treatment is catheterization,” Dr. Vitner said. “However, there is no standard protocol.”
From 2020 to 2022, researchers randomly assigned 73 women to the intermittent catheterization group and 74 to continuous catheterization. The average ages in the groups were 27.7 and 29.1 years, respectively (P = .11) and other characteristics such as body mass index, parity, infant birth weight, and mode of delivery were similar.
Most women in the intermittent catheterization group needed just one catheterization to reach resolution (75.3%); 93.2% had resolution after two, and 95.9% reached it after three. All resolved their urinary retention by 48 hours.
In the continuous catheterization group, 90.5% reached resolution at 24 hours, 97.3% at 48 hours, and 100% at 72 hours. Birth satisfaction scores were higher in the intermittent catheterization group (P < .001).
Dr. Hickman, who did not take part in the study, said the findings are helpful. Randomized, controlled trials are “important to get a better understanding of the natural history of this condition and ways to improve how we manage it clinically,” she said. Should intermittent catheterization become routine? “You need to have the staffing and the resources in order to do that, such as a bladder scanner and intermittent catheterization supplies,” Dr. Hickman said. “It can be time-intensive to continue to follow the patients to make sure they are voiding normally. And there may be many hospitals in the country that just don’t have the resources to do this, especially with all the current workforce issues.”
She added that some patients may not want the intermittent approach: “It can be uncomfortable for patients. They’ve just delivered a baby, they are likely experiencing discomfort from their delivery, and their anatomy can be distorted,” she said. “Some patients may say, ‘I would prefer you not insert a catheter into my bladder every few hours.’ They may just want to rest after having a baby.”
The best approach is to let patients make an informed choice, Dr. Hickman said. She recommended that clinicians say something like, “Because of your delivery, you are not able to empty your bladder all the way. This is typically a self-limited problem, meaning that it will likely resolve within a few days. But in the meantime, we need to let your bladder rest so that it can have time to start functioning on its own.” And then, she said, explain the catheterization options.
Dr. Vitner and Dr. Hickman have no disclosures.
Intermittent catheterization every 6 hours in postpartum women with urinary retention may be a better strategy than extended catheterization over 24 hours, a new prospective, randomized, controlled study suggests.
Patients who were catheterized every 6 hours took significantly less time to reach full relief than those who were catheterized for at least 24 hours (mean 10.2 ± 11.8 hours vs. 26.5 ± 9.0 hours, P < .001, respectively), Israeli researchers found. Their research was released at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
“There was no difference in hospital stay or in the rate of positive urine culture after catheter removal,” said ob.gyn. Dana Vitner, MD, of Rambam Health Care Campus in Haifa, Israel, in a presentation at the conference. “Our conclusion is that intermittent catheterization for postpartum urinary retention results in shorter time to resolution with a higher satisfaction rate and no additional complications.”
The true incidence of postpartum urinary retention is unclear, and estimates vary widely, said ob.gyn. and surgeon Lisa Hickman, MD, of the Ohio State University, Columbus, in an interview. “This is likely because many cases of covert urinary retention – when postpartum women are able to urinate but have incomplete emptying – go undiagnosed unless you are screening for it.”
According to Dr. Hickman, risk factors for postpartum urinary retention include operative vaginal births, having an epidural, obstetric anal sphincter injury, episiotomy, large newborns, first-time births, and prolonged induction of labor. Most cases resolve within 72 hours, she said, but they can lead to rare complications such as bladder injury.
For the new study, researchers defined urinary retention at the bladder holding least 150 mL more than 6 hours after vaginal delivery or removal of an in-dwelling catheter after cesarean delivery. “The treatment is catheterization,” Dr. Vitner said. “However, there is no standard protocol.”
From 2020 to 2022, researchers randomly assigned 73 women to the intermittent catheterization group and 74 to continuous catheterization. The average ages in the groups were 27.7 and 29.1 years, respectively (P = .11) and other characteristics such as body mass index, parity, infant birth weight, and mode of delivery were similar.
Most women in the intermittent catheterization group needed just one catheterization to reach resolution (75.3%); 93.2% had resolution after two, and 95.9% reached it after three. All resolved their urinary retention by 48 hours.
In the continuous catheterization group, 90.5% reached resolution at 24 hours, 97.3% at 48 hours, and 100% at 72 hours. Birth satisfaction scores were higher in the intermittent catheterization group (P < .001).
Dr. Hickman, who did not take part in the study, said the findings are helpful. Randomized, controlled trials are “important to get a better understanding of the natural history of this condition and ways to improve how we manage it clinically,” she said. Should intermittent catheterization become routine? “You need to have the staffing and the resources in order to do that, such as a bladder scanner and intermittent catheterization supplies,” Dr. Hickman said. “It can be time-intensive to continue to follow the patients to make sure they are voiding normally. And there may be many hospitals in the country that just don’t have the resources to do this, especially with all the current workforce issues.”
She added that some patients may not want the intermittent approach: “It can be uncomfortable for patients. They’ve just delivered a baby, they are likely experiencing discomfort from their delivery, and their anatomy can be distorted,” she said. “Some patients may say, ‘I would prefer you not insert a catheter into my bladder every few hours.’ They may just want to rest after having a baby.”
The best approach is to let patients make an informed choice, Dr. Hickman said. She recommended that clinicians say something like, “Because of your delivery, you are not able to empty your bladder all the way. This is typically a self-limited problem, meaning that it will likely resolve within a few days. But in the meantime, we need to let your bladder rest so that it can have time to start functioning on its own.” And then, she said, explain the catheterization options.
Dr. Vitner and Dr. Hickman have no disclosures.
Intermittent catheterization every 6 hours in postpartum women with urinary retention may be a better strategy than extended catheterization over 24 hours, a new prospective, randomized, controlled study suggests.
Patients who were catheterized every 6 hours took significantly less time to reach full relief than those who were catheterized for at least 24 hours (mean 10.2 ± 11.8 hours vs. 26.5 ± 9.0 hours, P < .001, respectively), Israeli researchers found. Their research was released at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
“There was no difference in hospital stay or in the rate of positive urine culture after catheter removal,” said ob.gyn. Dana Vitner, MD, of Rambam Health Care Campus in Haifa, Israel, in a presentation at the conference. “Our conclusion is that intermittent catheterization for postpartum urinary retention results in shorter time to resolution with a higher satisfaction rate and no additional complications.”
The true incidence of postpartum urinary retention is unclear, and estimates vary widely, said ob.gyn. and surgeon Lisa Hickman, MD, of the Ohio State University, Columbus, in an interview. “This is likely because many cases of covert urinary retention – when postpartum women are able to urinate but have incomplete emptying – go undiagnosed unless you are screening for it.”
According to Dr. Hickman, risk factors for postpartum urinary retention include operative vaginal births, having an epidural, obstetric anal sphincter injury, episiotomy, large newborns, first-time births, and prolonged induction of labor. Most cases resolve within 72 hours, she said, but they can lead to rare complications such as bladder injury.
For the new study, researchers defined urinary retention at the bladder holding least 150 mL more than 6 hours after vaginal delivery or removal of an in-dwelling catheter after cesarean delivery. “The treatment is catheterization,” Dr. Vitner said. “However, there is no standard protocol.”
From 2020 to 2022, researchers randomly assigned 73 women to the intermittent catheterization group and 74 to continuous catheterization. The average ages in the groups were 27.7 and 29.1 years, respectively (P = .11) and other characteristics such as body mass index, parity, infant birth weight, and mode of delivery were similar.
Most women in the intermittent catheterization group needed just one catheterization to reach resolution (75.3%); 93.2% had resolution after two, and 95.9% reached it after three. All resolved their urinary retention by 48 hours.
In the continuous catheterization group, 90.5% reached resolution at 24 hours, 97.3% at 48 hours, and 100% at 72 hours. Birth satisfaction scores were higher in the intermittent catheterization group (P < .001).
Dr. Hickman, who did not take part in the study, said the findings are helpful. Randomized, controlled trials are “important to get a better understanding of the natural history of this condition and ways to improve how we manage it clinically,” she said. Should intermittent catheterization become routine? “You need to have the staffing and the resources in order to do that, such as a bladder scanner and intermittent catheterization supplies,” Dr. Hickman said. “It can be time-intensive to continue to follow the patients to make sure they are voiding normally. And there may be many hospitals in the country that just don’t have the resources to do this, especially with all the current workforce issues.”
She added that some patients may not want the intermittent approach: “It can be uncomfortable for patients. They’ve just delivered a baby, they are likely experiencing discomfort from their delivery, and their anatomy can be distorted,” she said. “Some patients may say, ‘I would prefer you not insert a catheter into my bladder every few hours.’ They may just want to rest after having a baby.”
The best approach is to let patients make an informed choice, Dr. Hickman said. She recommended that clinicians say something like, “Because of your delivery, you are not able to empty your bladder all the way. This is typically a self-limited problem, meaning that it will likely resolve within a few days. But in the meantime, we need to let your bladder rest so that it can have time to start functioning on its own.” And then, she said, explain the catheterization options.
Dr. Vitner and Dr. Hickman have no disclosures.
FROM THE PREGNANCY MEETING
Are ‘Momi Pods’ the future of postnatal care?
Mindi Rosen met Seuli Brill, MD, at just the right time.
Ms. Rosen’s firstborn son was in the neointensive natal unit at The Ohio State University Wexner Medical Center in Columbus, and she didn’t have a pediatrician picked out yet for the baby. Nor did she have a primary care physician who could help her manage the gestational diabetes she developed during her pregnancy.
Dr. Brill, a clinical associate professor of internal medicine and pediatrics at Ohio State, suggested Ms. Rosen visit her at the new clinic she was piloting in Columbus. There, she provided pediatric care for newborns and primary care for mothers who had developed gestational diabetes.
“I looked at my husband, my husband looked at me, and I said: ‘Why not?’ “ Ms. Rosen, 38, recalled of that 2019 meeting. “I’m so glad she walked in at that moment.”
The mother of two is still part of the rapidly growing program at the medical facility that provides care for more than 200 mothers and babies.
Launched in 2018, the clinic – called the Multi-Modal Maternal Infant Perinatal Outpatient Delivery System, or “Momi Pods,” started with a focus on helping women with gestational diabetes, which occurs in up to 10% of pregnancies.
The program allows moms to book regular checkups for their baby, and then a follow-up appointment immediately after for themselves. Women are seen for the first 1,000 days (just under 3 years) after giving birth.
The idea was simple. Dr. Brill wanted to develop a more formalized program for the work she was already doing as a primary care physician and pediatrician. At the time, she was fielding referrals from specialists for young women who didn’t have a physician. She’d often develop a relationship with the patient over the years, go on to help oversee their care during pregnancy, then new mothers would select her as their newborn’s pediatrician.
“I would have a relationship with the mom when they did have the newborn, and then I would see the baby because I’m a pediatrician,” Dr. Brill said.
Dr. Brill was serving on the Ohio Gestational Diabetes Mellitus Collaborative, a state-backed program that aims to raise awareness about the condition and encourage more preventative care for patients. She presented her proposal to launch the program to the Ohio Department of Medicaid, which helped to fund the pilot.
The idea, she hoped, would improve postpartum follow-up care for mothers diagnosed with the condition.
Follow-up care is especially important for women who develop gestational diabetes because the condition raises their lifetime risk of developing type 2 diabetes up to 10-fold.
Yet most of those mothers don’t get the appropriate follow-up care during the crucial postpartum period, said Maya Subbalakshmi Venkataramani, MD, MPH, an assistant professor of medicine at Johns Hopkins University in Baltimore, who has researched parental care.
“Things get very busy after you have a child. There’s just the general logistics of a mom having to take care of a newborn and thinking about themselves,” Dr. Venkataramani, a primary care clinician and pediatrician, said. “A lot of parents in general may not put a lot of emphasis on their own health.”
Seeking care may be especially difficult for low-income mothers who might not have consistent health care coverage, she added.
In fact, only half of women who developed gestational diabetes received primary follow-up care, according to a study published in JAMA Network Open. The study, which examined more than 280,000 insurance claims between 2015 and 2018, found only 36% of women with gestational diabetes received the recommended blood glucose testing in the first 12 weeks of the postpartum period.
In the Momi Pods program, Dr. Brill checked in on Ms. Rosen’s gestational diabetes regularly during pediatric office visits for her newborn’s care. Ms. Rosen said whenever she brought her baby in for a visit during the postpartum period, Dr. Brill measured her blood sugar.
Dr. Brill and her team also asked how Ms. Rosen was doing physically and mentally during each visit. The screenings helped to catch a bout of postpartum depression Ms. Rosen experienced after the birth of her first son.
“I thought it was great, because honestly as a new mom I wouldn’t have followed up with myself so much,” Ms. Rosen said. “Every time you went into the doctor appointments, they’d ask you how you are doing. As a new mom, it’s so much easier to do it at the same time.”
Those who participate in the program are also more likely to complete postpartum visits with their ob.gyn. (95% vs. 58%, respectively; P < .001) than those who don’t participate, according to research Dr. Brill and colleagues published.
Dr. Brill began expanding the program’s reach nearly 2 years after its launch, targeting the services for women who are at risk for poor postpartum outcomes, including those with a history of depression, preterm labor, diabetes and congenital heart disease. Ob.gyns. in Ohio State’s network can refer their patients to the program, which now has 43 doctors trained to provide primary and pediatric care through Momi Pods. Soon-to-be moms can be referred to the program as early as the second trimester, Dr. Brill said.
Many of the mothers referred to the program don’t have a primary care clinician when they talk to Paola Beamon, RN, at Ohio State. Ms. Beamon reaches out to each referred patient over voicemail, a MyChart message, and even regular mail in hopes of helping them navigate the postpartum period. She also provides education on what a primary care clinician can offer new moms.
“Really, we’re pursuing these moms and doing everything we can so there’s less of a burden for them,” Ms. Beamon said. “A lot of them don’t even know what a primary care office does.”
One of the biggest perks to the program for new moms is that they don’t have to spend time and money traveling to a different doctor’s office, take time off work, or secure childcare in order to schedule a separate appointment for themselves, she said.
The program, which receives funding from the university and the state, even helps women get bus passes to a doctor’s appointment if needed.
Dyad programs targeting women with substance abuse disorders or mental health conditions have existed for many years. But catering to women with gestational diabetes or other medical conditions appears to be new. In part, Dr. Venkataramani said, because scheduling and space can be big hurdles to launch such a program, as well as finding doctors who can care for both baby and mother.
“There are logistical challenges to even doing this that makes it less common,” she said.
Dr. Brill said she is not aware of any other programs that are structured like the tandem care clinic at Ohio State. She hopes, however, that the program can be a model for other hospital systems to consider, and she is working to expand the program regionally. Her team is collecting data – including on the best way to schedule patients – to help other clinics develop something similar.
“We really want to leverage that expertise to make it easier for moms to get care with their infants and remove barriers to care,” she said.
A version of this article first appeared on Medscape.com.
Mindi Rosen met Seuli Brill, MD, at just the right time.
Ms. Rosen’s firstborn son was in the neointensive natal unit at The Ohio State University Wexner Medical Center in Columbus, and she didn’t have a pediatrician picked out yet for the baby. Nor did she have a primary care physician who could help her manage the gestational diabetes she developed during her pregnancy.
Dr. Brill, a clinical associate professor of internal medicine and pediatrics at Ohio State, suggested Ms. Rosen visit her at the new clinic she was piloting in Columbus. There, she provided pediatric care for newborns and primary care for mothers who had developed gestational diabetes.
“I looked at my husband, my husband looked at me, and I said: ‘Why not?’ “ Ms. Rosen, 38, recalled of that 2019 meeting. “I’m so glad she walked in at that moment.”
The mother of two is still part of the rapidly growing program at the medical facility that provides care for more than 200 mothers and babies.
Launched in 2018, the clinic – called the Multi-Modal Maternal Infant Perinatal Outpatient Delivery System, or “Momi Pods,” started with a focus on helping women with gestational diabetes, which occurs in up to 10% of pregnancies.
The program allows moms to book regular checkups for their baby, and then a follow-up appointment immediately after for themselves. Women are seen for the first 1,000 days (just under 3 years) after giving birth.
The idea was simple. Dr. Brill wanted to develop a more formalized program for the work she was already doing as a primary care physician and pediatrician. At the time, she was fielding referrals from specialists for young women who didn’t have a physician. She’d often develop a relationship with the patient over the years, go on to help oversee their care during pregnancy, then new mothers would select her as their newborn’s pediatrician.
“I would have a relationship with the mom when they did have the newborn, and then I would see the baby because I’m a pediatrician,” Dr. Brill said.
Dr. Brill was serving on the Ohio Gestational Diabetes Mellitus Collaborative, a state-backed program that aims to raise awareness about the condition and encourage more preventative care for patients. She presented her proposal to launch the program to the Ohio Department of Medicaid, which helped to fund the pilot.
The idea, she hoped, would improve postpartum follow-up care for mothers diagnosed with the condition.
Follow-up care is especially important for women who develop gestational diabetes because the condition raises their lifetime risk of developing type 2 diabetes up to 10-fold.
Yet most of those mothers don’t get the appropriate follow-up care during the crucial postpartum period, said Maya Subbalakshmi Venkataramani, MD, MPH, an assistant professor of medicine at Johns Hopkins University in Baltimore, who has researched parental care.
“Things get very busy after you have a child. There’s just the general logistics of a mom having to take care of a newborn and thinking about themselves,” Dr. Venkataramani, a primary care clinician and pediatrician, said. “A lot of parents in general may not put a lot of emphasis on their own health.”
Seeking care may be especially difficult for low-income mothers who might not have consistent health care coverage, she added.
In fact, only half of women who developed gestational diabetes received primary follow-up care, according to a study published in JAMA Network Open. The study, which examined more than 280,000 insurance claims between 2015 and 2018, found only 36% of women with gestational diabetes received the recommended blood glucose testing in the first 12 weeks of the postpartum period.
In the Momi Pods program, Dr. Brill checked in on Ms. Rosen’s gestational diabetes regularly during pediatric office visits for her newborn’s care. Ms. Rosen said whenever she brought her baby in for a visit during the postpartum period, Dr. Brill measured her blood sugar.
Dr. Brill and her team also asked how Ms. Rosen was doing physically and mentally during each visit. The screenings helped to catch a bout of postpartum depression Ms. Rosen experienced after the birth of her first son.
“I thought it was great, because honestly as a new mom I wouldn’t have followed up with myself so much,” Ms. Rosen said. “Every time you went into the doctor appointments, they’d ask you how you are doing. As a new mom, it’s so much easier to do it at the same time.”
Those who participate in the program are also more likely to complete postpartum visits with their ob.gyn. (95% vs. 58%, respectively; P < .001) than those who don’t participate, according to research Dr. Brill and colleagues published.
Dr. Brill began expanding the program’s reach nearly 2 years after its launch, targeting the services for women who are at risk for poor postpartum outcomes, including those with a history of depression, preterm labor, diabetes and congenital heart disease. Ob.gyns. in Ohio State’s network can refer their patients to the program, which now has 43 doctors trained to provide primary and pediatric care through Momi Pods. Soon-to-be moms can be referred to the program as early as the second trimester, Dr. Brill said.
Many of the mothers referred to the program don’t have a primary care clinician when they talk to Paola Beamon, RN, at Ohio State. Ms. Beamon reaches out to each referred patient over voicemail, a MyChart message, and even regular mail in hopes of helping them navigate the postpartum period. She also provides education on what a primary care clinician can offer new moms.
“Really, we’re pursuing these moms and doing everything we can so there’s less of a burden for them,” Ms. Beamon said. “A lot of them don’t even know what a primary care office does.”
One of the biggest perks to the program for new moms is that they don’t have to spend time and money traveling to a different doctor’s office, take time off work, or secure childcare in order to schedule a separate appointment for themselves, she said.
The program, which receives funding from the university and the state, even helps women get bus passes to a doctor’s appointment if needed.
Dyad programs targeting women with substance abuse disorders or mental health conditions have existed for many years. But catering to women with gestational diabetes or other medical conditions appears to be new. In part, Dr. Venkataramani said, because scheduling and space can be big hurdles to launch such a program, as well as finding doctors who can care for both baby and mother.
“There are logistical challenges to even doing this that makes it less common,” she said.
Dr. Brill said she is not aware of any other programs that are structured like the tandem care clinic at Ohio State. She hopes, however, that the program can be a model for other hospital systems to consider, and she is working to expand the program regionally. Her team is collecting data – including on the best way to schedule patients – to help other clinics develop something similar.
“We really want to leverage that expertise to make it easier for moms to get care with their infants and remove barriers to care,” she said.
A version of this article first appeared on Medscape.com.
Mindi Rosen met Seuli Brill, MD, at just the right time.
Ms. Rosen’s firstborn son was in the neointensive natal unit at The Ohio State University Wexner Medical Center in Columbus, and she didn’t have a pediatrician picked out yet for the baby. Nor did she have a primary care physician who could help her manage the gestational diabetes she developed during her pregnancy.
Dr. Brill, a clinical associate professor of internal medicine and pediatrics at Ohio State, suggested Ms. Rosen visit her at the new clinic she was piloting in Columbus. There, she provided pediatric care for newborns and primary care for mothers who had developed gestational diabetes.
“I looked at my husband, my husband looked at me, and I said: ‘Why not?’ “ Ms. Rosen, 38, recalled of that 2019 meeting. “I’m so glad she walked in at that moment.”
The mother of two is still part of the rapidly growing program at the medical facility that provides care for more than 200 mothers and babies.
Launched in 2018, the clinic – called the Multi-Modal Maternal Infant Perinatal Outpatient Delivery System, or “Momi Pods,” started with a focus on helping women with gestational diabetes, which occurs in up to 10% of pregnancies.
The program allows moms to book regular checkups for their baby, and then a follow-up appointment immediately after for themselves. Women are seen for the first 1,000 days (just under 3 years) after giving birth.
The idea was simple. Dr. Brill wanted to develop a more formalized program for the work she was already doing as a primary care physician and pediatrician. At the time, she was fielding referrals from specialists for young women who didn’t have a physician. She’d often develop a relationship with the patient over the years, go on to help oversee their care during pregnancy, then new mothers would select her as their newborn’s pediatrician.
“I would have a relationship with the mom when they did have the newborn, and then I would see the baby because I’m a pediatrician,” Dr. Brill said.
Dr. Brill was serving on the Ohio Gestational Diabetes Mellitus Collaborative, a state-backed program that aims to raise awareness about the condition and encourage more preventative care for patients. She presented her proposal to launch the program to the Ohio Department of Medicaid, which helped to fund the pilot.
The idea, she hoped, would improve postpartum follow-up care for mothers diagnosed with the condition.
Follow-up care is especially important for women who develop gestational diabetes because the condition raises their lifetime risk of developing type 2 diabetes up to 10-fold.
Yet most of those mothers don’t get the appropriate follow-up care during the crucial postpartum period, said Maya Subbalakshmi Venkataramani, MD, MPH, an assistant professor of medicine at Johns Hopkins University in Baltimore, who has researched parental care.
“Things get very busy after you have a child. There’s just the general logistics of a mom having to take care of a newborn and thinking about themselves,” Dr. Venkataramani, a primary care clinician and pediatrician, said. “A lot of parents in general may not put a lot of emphasis on their own health.”
Seeking care may be especially difficult for low-income mothers who might not have consistent health care coverage, she added.
In fact, only half of women who developed gestational diabetes received primary follow-up care, according to a study published in JAMA Network Open. The study, which examined more than 280,000 insurance claims between 2015 and 2018, found only 36% of women with gestational diabetes received the recommended blood glucose testing in the first 12 weeks of the postpartum period.
In the Momi Pods program, Dr. Brill checked in on Ms. Rosen’s gestational diabetes regularly during pediatric office visits for her newborn’s care. Ms. Rosen said whenever she brought her baby in for a visit during the postpartum period, Dr. Brill measured her blood sugar.
Dr. Brill and her team also asked how Ms. Rosen was doing physically and mentally during each visit. The screenings helped to catch a bout of postpartum depression Ms. Rosen experienced after the birth of her first son.
“I thought it was great, because honestly as a new mom I wouldn’t have followed up with myself so much,” Ms. Rosen said. “Every time you went into the doctor appointments, they’d ask you how you are doing. As a new mom, it’s so much easier to do it at the same time.”
Those who participate in the program are also more likely to complete postpartum visits with their ob.gyn. (95% vs. 58%, respectively; P < .001) than those who don’t participate, according to research Dr. Brill and colleagues published.
Dr. Brill began expanding the program’s reach nearly 2 years after its launch, targeting the services for women who are at risk for poor postpartum outcomes, including those with a history of depression, preterm labor, diabetes and congenital heart disease. Ob.gyns. in Ohio State’s network can refer their patients to the program, which now has 43 doctors trained to provide primary and pediatric care through Momi Pods. Soon-to-be moms can be referred to the program as early as the second trimester, Dr. Brill said.
Many of the mothers referred to the program don’t have a primary care clinician when they talk to Paola Beamon, RN, at Ohio State. Ms. Beamon reaches out to each referred patient over voicemail, a MyChart message, and even regular mail in hopes of helping them navigate the postpartum period. She also provides education on what a primary care clinician can offer new moms.
“Really, we’re pursuing these moms and doing everything we can so there’s less of a burden for them,” Ms. Beamon said. “A lot of them don’t even know what a primary care office does.”
One of the biggest perks to the program for new moms is that they don’t have to spend time and money traveling to a different doctor’s office, take time off work, or secure childcare in order to schedule a separate appointment for themselves, she said.
The program, which receives funding from the university and the state, even helps women get bus passes to a doctor’s appointment if needed.
Dyad programs targeting women with substance abuse disorders or mental health conditions have existed for many years. But catering to women with gestational diabetes or other medical conditions appears to be new. In part, Dr. Venkataramani said, because scheduling and space can be big hurdles to launch such a program, as well as finding doctors who can care for both baby and mother.
“There are logistical challenges to even doing this that makes it less common,” she said.
Dr. Brill said she is not aware of any other programs that are structured like the tandem care clinic at Ohio State. She hopes, however, that the program can be a model for other hospital systems to consider, and she is working to expand the program regionally. Her team is collecting data – including on the best way to schedule patients – to help other clinics develop something similar.
“We really want to leverage that expertise to make it easier for moms to get care with their infants and remove barriers to care,” she said.
A version of this article first appeared on Medscape.com.
Maternal infection in pregnancy ups risk for childhood leukemia?
Children born to mothers who had urinary or genital tract infections during pregnancy appear to have an increased risk for childhood leukemia, said researchers reporting a Danish registry analysis that may point to preventive strategies for the disease.
The research was published online in JAMA Network Open.
The team studied more than 2.2 million children born in Denmark over more than 3 decades, linking their records across multiple national registries to examine both later cancer risk and maternal infection rates.
They found that, overall, at least one maternal infection during pregnancy was associated with a 35% increased risk for leukemia in the children, rising to 65% for urinary tract infections, and 142% for genital infections.
“The findings of this large population-based cohort study suggest that maternal urinary and genital tract infections during pregnancy are associated with a higher risk of childhood leukemia in offspring,” said lead author Jian-Rong He, DPhil, division of birth cohort study, Guangzhou (China) Women and Children’s Medical Center.
However, he added, “the associated absolute risk remained small given the rarity” of the disease. In absolute terms, the risk difference between exposed and unexposed children was 1.8 cases per 100,000 person-years for any infection, 3.4 cases per 100,000 person-years for urinary traction infection, and 7.1 cases per 100,000 person-years for genital tract infection.
Maternal infections during pregnancy may be associated with chromosomal and immunologic alterations in the fetus, the authors speculated.
“Given that little is known about the etiology of childhood leukemia,” these results “suggest an important direction for research on the etiology of childhood leukemia as well as development of potential preventive measures,” they wrote.
In many countries, pregnant women are tested for urinary tract infection and bacterial vaginosis, and treated with antibiotics in antenatal care, as these infections are linked to adverse perinatal outcomes, they pointed out.
Study details
The team conducted a large population-based study that included all live births in Denmark between 1978 and 2015.
After exclusions, they gathered information on 2,222,797 children, linking data from several national registries, including the Danish Medical Birth Register, the Danish National Patient Registry, and the Danish National Cancer Registry, to identify cases of childhood cancers and maternal infection during pregnancy.
The results were then validated by comparing them with those in 2.6 million live births in Sweden between 1988 and 2014, for whom similar data were available through linkage with several Swedish registries.
The Danish cohort was followed up for a mean of 12 years per person, yielding a total of 27 million person-years. Just over half (51.3%) were boys.
Cancer was diagnosed in 4,362 children before 15 years of age, of whom 1,307 had leukemia (1,050 had acute lymphocytic leukemia), 1,267 had a brain tumor, 224 had lymphoma, and 1,564 had other cancers.
At least one infection during pregnancy was diagnosed in 81,717 mothers (3.7%). Urinary tract infections were the most common (in 1.7% of women), followed by genital tract infection (in 0.7%), digestive system infection (in 0.5%), and respiratory tract infection (in 0.3%).
Women with any infection during pregnancy were more likely to be younger and primiparous than were women who did not have infections, and they were also more likely to have fewer years of education, higher prepregnancy BMI, diabetes, and to smoke during early pregnancy.
Preterm delivery and low-birth-weight infants were also more common in women with infections during pregnancy.
Cox proportional hazards regression models revealed that, after adjustment for confounders, any maternal infection was associated with a hazard ratio of childhood leukemia of 1.35.
Further analysis revealed that the association was driven by genital tract infection, at a hazard ratio for childhood leukemia of 2.42, and urinary tract infection, at a hazard ratio 1.65.
Moreover, children born to women who had a sexually transmitted infection during pregnancy had a hazard ratio for developing leukemia of 3.13 compared with unexposed children.
There were no associations between other maternal infections and childhood leukemia.
The patterns of association between maternal infections and childhood leukemia were similar when looking at disease subtypes, as well as in the Swedish validation cohort, they added.
When interpreting the results, the researchers caution that, as data on maternal infection were drawn from hospital data, “milder infections and those not diagnosed or treated in specialized health care facilities were not captured.”
“Also, some infections could be captured because the mother sought care for other, more serious conditions, which might bias the association of maternal infections and childhood leukemia.”
The study was supported by grants from the China Scholarship Council–University of Oxford; National Natural Science Foundation of China; Danish Council for Independent Research; Nordic Cancer Union; Novo Nordisk Fonden; and the Swedish Council for Working Life and Social Research. Dr He reported receiving a PhD scholarship from the China Scholarship Council during the conduct of the study. Several other coauthors have disclosures; the full list can be found with the original article.
A version of this article originally appeared on Medscape.com.
Children born to mothers who had urinary or genital tract infections during pregnancy appear to have an increased risk for childhood leukemia, said researchers reporting a Danish registry analysis that may point to preventive strategies for the disease.
The research was published online in JAMA Network Open.
The team studied more than 2.2 million children born in Denmark over more than 3 decades, linking their records across multiple national registries to examine both later cancer risk and maternal infection rates.
They found that, overall, at least one maternal infection during pregnancy was associated with a 35% increased risk for leukemia in the children, rising to 65% for urinary tract infections, and 142% for genital infections.
“The findings of this large population-based cohort study suggest that maternal urinary and genital tract infections during pregnancy are associated with a higher risk of childhood leukemia in offspring,” said lead author Jian-Rong He, DPhil, division of birth cohort study, Guangzhou (China) Women and Children’s Medical Center.
However, he added, “the associated absolute risk remained small given the rarity” of the disease. In absolute terms, the risk difference between exposed and unexposed children was 1.8 cases per 100,000 person-years for any infection, 3.4 cases per 100,000 person-years for urinary traction infection, and 7.1 cases per 100,000 person-years for genital tract infection.
Maternal infections during pregnancy may be associated with chromosomal and immunologic alterations in the fetus, the authors speculated.
“Given that little is known about the etiology of childhood leukemia,” these results “suggest an important direction for research on the etiology of childhood leukemia as well as development of potential preventive measures,” they wrote.
In many countries, pregnant women are tested for urinary tract infection and bacterial vaginosis, and treated with antibiotics in antenatal care, as these infections are linked to adverse perinatal outcomes, they pointed out.
Study details
The team conducted a large population-based study that included all live births in Denmark between 1978 and 2015.
After exclusions, they gathered information on 2,222,797 children, linking data from several national registries, including the Danish Medical Birth Register, the Danish National Patient Registry, and the Danish National Cancer Registry, to identify cases of childhood cancers and maternal infection during pregnancy.
The results were then validated by comparing them with those in 2.6 million live births in Sweden between 1988 and 2014, for whom similar data were available through linkage with several Swedish registries.
The Danish cohort was followed up for a mean of 12 years per person, yielding a total of 27 million person-years. Just over half (51.3%) were boys.
Cancer was diagnosed in 4,362 children before 15 years of age, of whom 1,307 had leukemia (1,050 had acute lymphocytic leukemia), 1,267 had a brain tumor, 224 had lymphoma, and 1,564 had other cancers.
At least one infection during pregnancy was diagnosed in 81,717 mothers (3.7%). Urinary tract infections were the most common (in 1.7% of women), followed by genital tract infection (in 0.7%), digestive system infection (in 0.5%), and respiratory tract infection (in 0.3%).
Women with any infection during pregnancy were more likely to be younger and primiparous than were women who did not have infections, and they were also more likely to have fewer years of education, higher prepregnancy BMI, diabetes, and to smoke during early pregnancy.
Preterm delivery and low-birth-weight infants were also more common in women with infections during pregnancy.
Cox proportional hazards regression models revealed that, after adjustment for confounders, any maternal infection was associated with a hazard ratio of childhood leukemia of 1.35.
Further analysis revealed that the association was driven by genital tract infection, at a hazard ratio for childhood leukemia of 2.42, and urinary tract infection, at a hazard ratio 1.65.
Moreover, children born to women who had a sexually transmitted infection during pregnancy had a hazard ratio for developing leukemia of 3.13 compared with unexposed children.
There were no associations between other maternal infections and childhood leukemia.
The patterns of association between maternal infections and childhood leukemia were similar when looking at disease subtypes, as well as in the Swedish validation cohort, they added.
When interpreting the results, the researchers caution that, as data on maternal infection were drawn from hospital data, “milder infections and those not diagnosed or treated in specialized health care facilities were not captured.”
“Also, some infections could be captured because the mother sought care for other, more serious conditions, which might bias the association of maternal infections and childhood leukemia.”
The study was supported by grants from the China Scholarship Council–University of Oxford; National Natural Science Foundation of China; Danish Council for Independent Research; Nordic Cancer Union; Novo Nordisk Fonden; and the Swedish Council for Working Life and Social Research. Dr He reported receiving a PhD scholarship from the China Scholarship Council during the conduct of the study. Several other coauthors have disclosures; the full list can be found with the original article.
A version of this article originally appeared on Medscape.com.
Children born to mothers who had urinary or genital tract infections during pregnancy appear to have an increased risk for childhood leukemia, said researchers reporting a Danish registry analysis that may point to preventive strategies for the disease.
The research was published online in JAMA Network Open.
The team studied more than 2.2 million children born in Denmark over more than 3 decades, linking their records across multiple national registries to examine both later cancer risk and maternal infection rates.
They found that, overall, at least one maternal infection during pregnancy was associated with a 35% increased risk for leukemia in the children, rising to 65% for urinary tract infections, and 142% for genital infections.
“The findings of this large population-based cohort study suggest that maternal urinary and genital tract infections during pregnancy are associated with a higher risk of childhood leukemia in offspring,” said lead author Jian-Rong He, DPhil, division of birth cohort study, Guangzhou (China) Women and Children’s Medical Center.
However, he added, “the associated absolute risk remained small given the rarity” of the disease. In absolute terms, the risk difference between exposed and unexposed children was 1.8 cases per 100,000 person-years for any infection, 3.4 cases per 100,000 person-years for urinary traction infection, and 7.1 cases per 100,000 person-years for genital tract infection.
Maternal infections during pregnancy may be associated with chromosomal and immunologic alterations in the fetus, the authors speculated.
“Given that little is known about the etiology of childhood leukemia,” these results “suggest an important direction for research on the etiology of childhood leukemia as well as development of potential preventive measures,” they wrote.
In many countries, pregnant women are tested for urinary tract infection and bacterial vaginosis, and treated with antibiotics in antenatal care, as these infections are linked to adverse perinatal outcomes, they pointed out.
Study details
The team conducted a large population-based study that included all live births in Denmark between 1978 and 2015.
After exclusions, they gathered information on 2,222,797 children, linking data from several national registries, including the Danish Medical Birth Register, the Danish National Patient Registry, and the Danish National Cancer Registry, to identify cases of childhood cancers and maternal infection during pregnancy.
The results were then validated by comparing them with those in 2.6 million live births in Sweden between 1988 and 2014, for whom similar data were available through linkage with several Swedish registries.
The Danish cohort was followed up for a mean of 12 years per person, yielding a total of 27 million person-years. Just over half (51.3%) were boys.
Cancer was diagnosed in 4,362 children before 15 years of age, of whom 1,307 had leukemia (1,050 had acute lymphocytic leukemia), 1,267 had a brain tumor, 224 had lymphoma, and 1,564 had other cancers.
At least one infection during pregnancy was diagnosed in 81,717 mothers (3.7%). Urinary tract infections were the most common (in 1.7% of women), followed by genital tract infection (in 0.7%), digestive system infection (in 0.5%), and respiratory tract infection (in 0.3%).
Women with any infection during pregnancy were more likely to be younger and primiparous than were women who did not have infections, and they were also more likely to have fewer years of education, higher prepregnancy BMI, diabetes, and to smoke during early pregnancy.
Preterm delivery and low-birth-weight infants were also more common in women with infections during pregnancy.
Cox proportional hazards regression models revealed that, after adjustment for confounders, any maternal infection was associated with a hazard ratio of childhood leukemia of 1.35.
Further analysis revealed that the association was driven by genital tract infection, at a hazard ratio for childhood leukemia of 2.42, and urinary tract infection, at a hazard ratio 1.65.
Moreover, children born to women who had a sexually transmitted infection during pregnancy had a hazard ratio for developing leukemia of 3.13 compared with unexposed children.
There were no associations between other maternal infections and childhood leukemia.
The patterns of association between maternal infections and childhood leukemia were similar when looking at disease subtypes, as well as in the Swedish validation cohort, they added.
When interpreting the results, the researchers caution that, as data on maternal infection were drawn from hospital data, “milder infections and those not diagnosed or treated in specialized health care facilities were not captured.”
“Also, some infections could be captured because the mother sought care for other, more serious conditions, which might bias the association of maternal infections and childhood leukemia.”
The study was supported by grants from the China Scholarship Council–University of Oxford; National Natural Science Foundation of China; Danish Council for Independent Research; Nordic Cancer Union; Novo Nordisk Fonden; and the Swedish Council for Working Life and Social Research. Dr He reported receiving a PhD scholarship from the China Scholarship Council during the conduct of the study. Several other coauthors have disclosures; the full list can be found with the original article.
A version of this article originally appeared on Medscape.com.
Are there long-term benefits to infants born to patients after bariatric surgery?
Rives-Lange C, Poghosyan T, Phan A, et al. Risk-benefit balance associated with obstetric, neonatal, and child outcomes after metabolic and bariatric surgery. JAMA Surg. 2023;158:36-44. doi:10.1001/jamasurg.2022.5450.
EXPERT COMMENTARY
Prepregnancy obesity continues to rise, with approximately 40% of reproductive-aged patients having a body mass index greater than 30 kg/m2.1 Several adverse perinatal outcomes are more common in pregnant patients with obesity.2 In addition, their infants have a higher risk of obesity, insulin resistance, hypertension, and neurodevelopmental disorders in the long term.
Bariatric surgery is an effective procedure for weight loss and has been shown to lower adverse pregnancy outcomes, such as hypertensive disorders of pregnancy and gestational diabetes.5,6 Benefits to newborns, however, have been debated.5 In addition, long-term benefits to infants were unknown until a recent study evaluated neonatal and child outcomes up to 2 years after pregnancy among patients who had undergone bariatric surgery.
Details of the study
Using the French nationwide database, Rives-Lange and colleagues performed a population-based study that included patients who had at least 1 pregnancy before and 1 pregnancy after bariatric surgery. Their objective was to compare pregnancy, neonatal, and child outcomes between pregnancies pre- and post-bariatric surgery.
Results. Among 3,686 patients who had at least 1 pregnancy before and after bariatric surgery, the authors found that pregnancies after bariatric surgery had lower rates of several adverse pregnancy outcomes, including preeclampsia (OR, 0.19), gestational hypertension (OR, 0.16), and gestational diabetes (OR, 0.39), compared with pregnancies before bariatric surgery. Regarding neonatal and child outcomes up to 2 years after pregnancy, there were lower rates of birth injuries (OR, 0.27), convulsions (OR, 0.43), newborn carbohydrate metabolism disorders (OR, 0.54),and viral intestinal infections (OR, 0.56) in pregnancies after bariatric surgery compared with those before surgery.
Notably, respiratory failure rates associated with bronchiolitis increased in pregnancies after bariatric surgery (OR, 2.42). This finding remained associated after adjusting for prematurity and small for gestational age as well as including 2 successive pregnancies before bariatric surgery (OR, 1.37).
Study strengths and limitations
A limitation of this study is the use of an administrative database, which may be biased and missing relevant variables. However, the study’s major strength was the large sample of patients serving as their own control to compare outcomes from pre-bariatric surgery with those of post-bariatric surgery. In addition, to account for confounders such as age and parity, the authors also evaluated for associations between 2 consecutive pregnancies among patients before bariatric surgery. They did not consider diagnoses found to be associated with bariatric surgery if they were also significant in the analysis between 2 consecutive pregnancies before bariatric surgery.
The finding of increased risk of respiratory failure from bronchiolitis after bariatric surgery is surprising given that obesity is a risk factor for the severity of bronchiolitis.7 Although this risk remained significant after including the analysis that used 2 consecutive pregnancies pre-bariatric surgery, the risk was lower (from an OR of 2.42 to an OR of 1.37). Thus, more data are required to confirm this potential risk. Despite this concerning finding, the overwhelming pregnancy, neonatal, and child benefits found and confirmed in this large, well-designed study support the continued practice of counseling on the benefits of bariatric surgery to our obese patients. ●
Bariatric surgery remains an effective procedure for weight loss, and it lowers the risks of several important perinatal, neonatal, and child outcomes, including hypertensive disorders, birth injuries, convulsions, and viral intestinal infections. Clinicians should include the benefits of neonatal and child outcomes in their counseling of bariatric surgery for their obese patients who are planning pregnancy.
RODNEY A. MCLAREN JR, MD
- Hales CM, Carroll MD, Fryar CD, et al. Prevalence of obesity and severe obesity among adults: United States, 2017-2018. NCHS Data Brief. 2020;(360):1-8.
- Sagi-Dain L. Obesity in pregnancy: ACOG practice bulletin, number 230. Obstet Gynecol. 2021;138:489. doi:10.1097 /AOG.0000000000004527.
- O’Reilly JR, Reynolds RM. The risk of maternal obesity to the long-term health of the offspring. Clin Endocrinol (Oxf). 2013;78:9-16. doi:10.1111/cen.12055.
- Edlow AG. Maternal obesity and neurodevelopmental and psychiatric disorders in offspring. Prenat Diagn. 2017;37:95-110. doi:10.1002/pd.4932.
- Johansson K, Cnattinguius S, Näslund I, et al. Outcomes of pregnancy after bariatric surgery. N Engl J Med. 2015;372:814-824. doi:10.1056/NEJMoa1405789.
- Getahun D, Fassett MJ, Jacobsen SJ, et al. Perinatal outcomes after bariatric surgery. Am J Obstet Gynecol. 2022;226:121.e1-121.e16. doi:10.1016/j.ajog.2021.06.087.
- James T, Samakar K, Martin MJ. Special delivery—metabolic bariatric surgery as a key component of maternal-fetal health care. JAMA Surg. 2023;158:44-45. doi:10.1001 /jamasurg.2022.5458.
Rives-Lange C, Poghosyan T, Phan A, et al. Risk-benefit balance associated with obstetric, neonatal, and child outcomes after metabolic and bariatric surgery. JAMA Surg. 2023;158:36-44. doi:10.1001/jamasurg.2022.5450.
EXPERT COMMENTARY
Prepregnancy obesity continues to rise, with approximately 40% of reproductive-aged patients having a body mass index greater than 30 kg/m2.1 Several adverse perinatal outcomes are more common in pregnant patients with obesity.2 In addition, their infants have a higher risk of obesity, insulin resistance, hypertension, and neurodevelopmental disorders in the long term.
Bariatric surgery is an effective procedure for weight loss and has been shown to lower adverse pregnancy outcomes, such as hypertensive disorders of pregnancy and gestational diabetes.5,6 Benefits to newborns, however, have been debated.5 In addition, long-term benefits to infants were unknown until a recent study evaluated neonatal and child outcomes up to 2 years after pregnancy among patients who had undergone bariatric surgery.
Details of the study
Using the French nationwide database, Rives-Lange and colleagues performed a population-based study that included patients who had at least 1 pregnancy before and 1 pregnancy after bariatric surgery. Their objective was to compare pregnancy, neonatal, and child outcomes between pregnancies pre- and post-bariatric surgery.
Results. Among 3,686 patients who had at least 1 pregnancy before and after bariatric surgery, the authors found that pregnancies after bariatric surgery had lower rates of several adverse pregnancy outcomes, including preeclampsia (OR, 0.19), gestational hypertension (OR, 0.16), and gestational diabetes (OR, 0.39), compared with pregnancies before bariatric surgery. Regarding neonatal and child outcomes up to 2 years after pregnancy, there were lower rates of birth injuries (OR, 0.27), convulsions (OR, 0.43), newborn carbohydrate metabolism disorders (OR, 0.54),and viral intestinal infections (OR, 0.56) in pregnancies after bariatric surgery compared with those before surgery.
Notably, respiratory failure rates associated with bronchiolitis increased in pregnancies after bariatric surgery (OR, 2.42). This finding remained associated after adjusting for prematurity and small for gestational age as well as including 2 successive pregnancies before bariatric surgery (OR, 1.37).
Study strengths and limitations
A limitation of this study is the use of an administrative database, which may be biased and missing relevant variables. However, the study’s major strength was the large sample of patients serving as their own control to compare outcomes from pre-bariatric surgery with those of post-bariatric surgery. In addition, to account for confounders such as age and parity, the authors also evaluated for associations between 2 consecutive pregnancies among patients before bariatric surgery. They did not consider diagnoses found to be associated with bariatric surgery if they were also significant in the analysis between 2 consecutive pregnancies before bariatric surgery.
The finding of increased risk of respiratory failure from bronchiolitis after bariatric surgery is surprising given that obesity is a risk factor for the severity of bronchiolitis.7 Although this risk remained significant after including the analysis that used 2 consecutive pregnancies pre-bariatric surgery, the risk was lower (from an OR of 2.42 to an OR of 1.37). Thus, more data are required to confirm this potential risk. Despite this concerning finding, the overwhelming pregnancy, neonatal, and child benefits found and confirmed in this large, well-designed study support the continued practice of counseling on the benefits of bariatric surgery to our obese patients. ●
Bariatric surgery remains an effective procedure for weight loss, and it lowers the risks of several important perinatal, neonatal, and child outcomes, including hypertensive disorders, birth injuries, convulsions, and viral intestinal infections. Clinicians should include the benefits of neonatal and child outcomes in their counseling of bariatric surgery for their obese patients who are planning pregnancy.
RODNEY A. MCLAREN JR, MD
Rives-Lange C, Poghosyan T, Phan A, et al. Risk-benefit balance associated with obstetric, neonatal, and child outcomes after metabolic and bariatric surgery. JAMA Surg. 2023;158:36-44. doi:10.1001/jamasurg.2022.5450.
EXPERT COMMENTARY
Prepregnancy obesity continues to rise, with approximately 40% of reproductive-aged patients having a body mass index greater than 30 kg/m2.1 Several adverse perinatal outcomes are more common in pregnant patients with obesity.2 In addition, their infants have a higher risk of obesity, insulin resistance, hypertension, and neurodevelopmental disorders in the long term.
Bariatric surgery is an effective procedure for weight loss and has been shown to lower adverse pregnancy outcomes, such as hypertensive disorders of pregnancy and gestational diabetes.5,6 Benefits to newborns, however, have been debated.5 In addition, long-term benefits to infants were unknown until a recent study evaluated neonatal and child outcomes up to 2 years after pregnancy among patients who had undergone bariatric surgery.
Details of the study
Using the French nationwide database, Rives-Lange and colleagues performed a population-based study that included patients who had at least 1 pregnancy before and 1 pregnancy after bariatric surgery. Their objective was to compare pregnancy, neonatal, and child outcomes between pregnancies pre- and post-bariatric surgery.
Results. Among 3,686 patients who had at least 1 pregnancy before and after bariatric surgery, the authors found that pregnancies after bariatric surgery had lower rates of several adverse pregnancy outcomes, including preeclampsia (OR, 0.19), gestational hypertension (OR, 0.16), and gestational diabetes (OR, 0.39), compared with pregnancies before bariatric surgery. Regarding neonatal and child outcomes up to 2 years after pregnancy, there were lower rates of birth injuries (OR, 0.27), convulsions (OR, 0.43), newborn carbohydrate metabolism disorders (OR, 0.54),and viral intestinal infections (OR, 0.56) in pregnancies after bariatric surgery compared with those before surgery.
Notably, respiratory failure rates associated with bronchiolitis increased in pregnancies after bariatric surgery (OR, 2.42). This finding remained associated after adjusting for prematurity and small for gestational age as well as including 2 successive pregnancies before bariatric surgery (OR, 1.37).
Study strengths and limitations
A limitation of this study is the use of an administrative database, which may be biased and missing relevant variables. However, the study’s major strength was the large sample of patients serving as their own control to compare outcomes from pre-bariatric surgery with those of post-bariatric surgery. In addition, to account for confounders such as age and parity, the authors also evaluated for associations between 2 consecutive pregnancies among patients before bariatric surgery. They did not consider diagnoses found to be associated with bariatric surgery if they were also significant in the analysis between 2 consecutive pregnancies before bariatric surgery.
The finding of increased risk of respiratory failure from bronchiolitis after bariatric surgery is surprising given that obesity is a risk factor for the severity of bronchiolitis.7 Although this risk remained significant after including the analysis that used 2 consecutive pregnancies pre-bariatric surgery, the risk was lower (from an OR of 2.42 to an OR of 1.37). Thus, more data are required to confirm this potential risk. Despite this concerning finding, the overwhelming pregnancy, neonatal, and child benefits found and confirmed in this large, well-designed study support the continued practice of counseling on the benefits of bariatric surgery to our obese patients. ●
Bariatric surgery remains an effective procedure for weight loss, and it lowers the risks of several important perinatal, neonatal, and child outcomes, including hypertensive disorders, birth injuries, convulsions, and viral intestinal infections. Clinicians should include the benefits of neonatal and child outcomes in their counseling of bariatric surgery for their obese patients who are planning pregnancy.
RODNEY A. MCLAREN JR, MD
- Hales CM, Carroll MD, Fryar CD, et al. Prevalence of obesity and severe obesity among adults: United States, 2017-2018. NCHS Data Brief. 2020;(360):1-8.
- Sagi-Dain L. Obesity in pregnancy: ACOG practice bulletin, number 230. Obstet Gynecol. 2021;138:489. doi:10.1097 /AOG.0000000000004527.
- O’Reilly JR, Reynolds RM. The risk of maternal obesity to the long-term health of the offspring. Clin Endocrinol (Oxf). 2013;78:9-16. doi:10.1111/cen.12055.
- Edlow AG. Maternal obesity and neurodevelopmental and psychiatric disorders in offspring. Prenat Diagn. 2017;37:95-110. doi:10.1002/pd.4932.
- Johansson K, Cnattinguius S, Näslund I, et al. Outcomes of pregnancy after bariatric surgery. N Engl J Med. 2015;372:814-824. doi:10.1056/NEJMoa1405789.
- Getahun D, Fassett MJ, Jacobsen SJ, et al. Perinatal outcomes after bariatric surgery. Am J Obstet Gynecol. 2022;226:121.e1-121.e16. doi:10.1016/j.ajog.2021.06.087.
- James T, Samakar K, Martin MJ. Special delivery—metabolic bariatric surgery as a key component of maternal-fetal health care. JAMA Surg. 2023;158:44-45. doi:10.1001 /jamasurg.2022.5458.
- Hales CM, Carroll MD, Fryar CD, et al. Prevalence of obesity and severe obesity among adults: United States, 2017-2018. NCHS Data Brief. 2020;(360):1-8.
- Sagi-Dain L. Obesity in pregnancy: ACOG practice bulletin, number 230. Obstet Gynecol. 2021;138:489. doi:10.1097 /AOG.0000000000004527.
- O’Reilly JR, Reynolds RM. The risk of maternal obesity to the long-term health of the offspring. Clin Endocrinol (Oxf). 2013;78:9-16. doi:10.1111/cen.12055.
- Edlow AG. Maternal obesity and neurodevelopmental and psychiatric disorders in offspring. Prenat Diagn. 2017;37:95-110. doi:10.1002/pd.4932.
- Johansson K, Cnattinguius S, Näslund I, et al. Outcomes of pregnancy after bariatric surgery. N Engl J Med. 2015;372:814-824. doi:10.1056/NEJMoa1405789.
- Getahun D, Fassett MJ, Jacobsen SJ, et al. Perinatal outcomes after bariatric surgery. Am J Obstet Gynecol. 2022;226:121.e1-121.e16. doi:10.1016/j.ajog.2021.06.087.
- James T, Samakar K, Martin MJ. Special delivery—metabolic bariatric surgery as a key component of maternal-fetal health care. JAMA Surg. 2023;158:44-45. doi:10.1001 /jamasurg.2022.5458.
Hormonal contraception and lactation: Reset your practices based on the evidence
CASE Patient concerned about hormonal contraception’s impact on lactation
A 19-year-old woman (G2P1102) is postpartum day 1 after delivering a baby at 26 weeks’ gestation. When you see her on postpartum rounds, she states that she does not want any hormonal contraception because she heard that it will decrease her milk supply. What are your next steps?
The American Academy of Pediatrics recently updated its policy statement on breastfeeding and the use of human milk to recommend exclusive breastfeeding for 6 months and continued breastfeeding, with complementary foods, as mutually desired for 2 years or beyond given evidence of maternal health benefits with breastfeeding longer than 1 year.1
Breastfeeding prevalence—and challenges
Despite maternal and infant benefits associated with lactation, current breastfeeding prevalence in the United States remains suboptimal. In 2019, 24.9% of infants were exclusively breastfed through 6 months and 35.9% were breastfeeding at 12 months.2 Furthermore, disparities in breastfeeding exist, which contribute to health inequities. For example, non-Hispanic Black infants had lower rates of exclusive breastfeeding at 6 months (19.1%) and any breastfeeding at 12 months (24.1%) compared with non-Hispanic White infants (26.9% and 39.4%, respectively).3
While many new mothers intend to breastfeed and initiate breastfeeding in the hospital after delivery, overall and exclusive breastfeeding continuation rates are low, indicating that patients face challenges with breastfeeding after hospital discharge. Many structural and societal barriers to breastfeeding exist, including inadequate social support and parental leave policies.4 Suboptimal maternity care practices during the birth hospitalization may lead to challenges with breastfeeding initiation. Health care practitioners may present additional barriers to breastfeeding due to a lack of knowledge of available resources for patients or incomplete training in breastfeeding counseling and support.
To address our case patient’s concerns, clinicians should be aware of how exogenous progestins may affect breastfeeding physiology, risk factors for breastfeeding difficulty, and the available evidence for safety of hormonal contraception use while breastfeeding.
Physiology of breastfeeding
During the second half of pregnancy, secretory differentiation (lactogenesis I) of mammary alveolar epithelial cells into secretory cells occurs to allow the mammary gland to eventually produce milk.5 After delivery of the placenta, progesterone withdrawal triggers secretory activation (lactogenesis II), which refers to the onset of copious milk production within 2 to 3 days postpartum.5 Most patients experience secretory activation within 72 hours; however, a delay in secretory activation past 72 hours is associated with cessation of any and exclusive breastfeeding at 4 weeks postpartum.6
Impaired lactation can be related to a delay in secretory activation or to insufficient lactation related to low milk supply. Maternal medical comorbidities (for example, diabetes mellitus, thyroid dysfunction, obesity), breast anatomy (such as insufficient glandular tissue, prior breast reduction surgery), pregnancy-related events (preeclampsia, retained placenta, postpartum hemorrhage), and infant conditions (such as multiple gestation, premature birth, congenital anomalies) all contribute to a risk of impaired lactation.7
Guidance on breastfeeding and hormonal contraception initiation
Early initiation of hormonal contraception poses theoretical concerns about breastfeeding difficulty if exogenous progestin interferes with endogenous signals for onset of milk production. The Centers for Disease Control and Prevention US Medical Eligibility Criteria (MEC) for Contraceptive Use provide recommendations on the safety of contraceptive use in the setting of various medical conditions or patient characteristics based on available data. The MEC uses 4 categories in assessing the safety of contraceptive method use for individuals with specific medical conditions or characteristics: 1, no restrictions exist for use of the contraceptive method; 2, advantages generally outweigh theoretical or proven risks; 3, theoretical or proven risks usually outweigh the advantages; and 4, conditions that represent an unacceptable health risk if the method is used.8
In the 2016 guidelines, combined hormonal contraceptives are considered category 4 at less than 21 days postpartum, regardless of breastfeeding status, due to the increased risk of venous thromboembolism in the immediate postpartum period (TABLE 1).8 Progestin-only contraception is considered category 1 in nonbreastfeeding individuals and category 2 in breastfeeding individuals based on overall evidence that found no adverse outcome with breastfeeding or infant outcomes with early initiation of progestin-only contraception (TABLE 1, TABLE 2).8
Since the publication of the 2016 MEC guidelines, several studies have continued to examine breastfeeding and infant outcomes with early initiation of hormonal contraception.
- In a noninferiority randomized controlled trial of immediate versus delayed initiation of a levonorgestrel intrauterine device (LNG IUD), any breastfeeding at 8 weeks in the immediate group was 78% (95% confidence interval [CI], 70%–85%), which was lower than but within the specified noninferiority margin of the delayed breastfeeding group (83%; 95% CI, 75%–90%), indicating that breastfeeding outcomes with immediate initiation of an LNG IUD were not worse compared with delayed initiation.9
- A secondary analysis of a randomized trial that compared intracesarean versus LNG IUD placement at 6 or more weeks postpartum showed no difference in breastfeeding at 6, 12, and 24 weeks after LNG IUD placement.10
- A randomized trial of early (up to 48 hours postpartum) versus placement of an etonogestrel (ENG) implant at 6 or more weeks postpartum showed no difference between groups in infant weight at 12 months.11
- A randomized trial of immediate (within 5 days of delivery) or interval placement of the 2-rod LNG implant (not approved in the United States) showed no difference in change in infant weight from birth to 6 months after delivery, onset of secretory activation, or breastfeeding continuation at 3 and 6 months postpartum.12
- In a prospective cohort study that compared immediate postpartum initiation of ENG versus a 2-rod LNG implant (approved by the FDA but not marketed in the United States), there were no differences in breastfeeding continuation at 24 months and exclusive breastfeeding at 6 months postpartum.13
- In a noninferiority randomized controlled trial that compared ENG implant initiation in the delivery room (0–2 hours postdelivery) versus delayed initiation (24–48 hours postdelivery), the time to secretory activation in those who initiated an ENG implant in the delivery room (66.8 [SD, 25.2] hours) was noninferior to delayed initiation (66.0 [SD, 35.3] hours). There also was no difference in ongoing breastfeeding over the first year after delivery and implant use at 12 months.14
- A secondary analysis of a randomized controlled trial examined breastfeeding outcomes with receipt of depot medroxyprogesterone acetate (DMPA) prior to discharge in women who delivered infants who weighed 1,500 g or less at 32 weeks’ or less gestation. Time to secretory activation was longer in 29 women who received DMPA (103.7 hours) compared with 141 women who did not (88.6 hours; P = .028); however, there was no difference in daily milk production, lactation duration, or infant consumption of mother’s own milk.15
While the overall evidence suggests that early initiation of hormonal contraception does not affect breastfeeding or infant outcomes, it is important for clinicians to recognize the limitations of available data with regard to the populations included in these studies. Specifically, most studies did not include individuals with premature, low birth weight, or multiple gestation infants, who are at higher risk of impaired lactation, and individuals with a higher prevalence of breastfeeding were not included to determine whether early initiation of hormonal contraception would impact breastfeeding. Furthermore, while these studies enrolled participants who planned to breastfeed, data indicate that intentions to initiate and continue exclusive breastfeeding can vary.16 As the reported rates of any and exclusive breastfeeding are consistent with or lower than current US breastfeeding rates, any decrease in breastfeeding exclusivity or duration that may be attributable to hormonal contraception may be unacceptable to those who are strongly motivated to breastfeed.
Continue to: How can clinicians integrate evidence into contraception counseling?...
How can clinicians integrate evidence into contraception counseling?
The American College of Obstetricians and Gynecologists and the Academy of Breastfeeding Medicine offer guidance for how clinicians can address the use of hormonal contraception in breastfeeding patients. Both organizations recommend discussing the risks and benefits of hormonal contraception within the context of each person’s desire to breastfeed, potential for breastfeeding difficulty, and risk of pregnancy so that individuals can make their own informed decisions.17,18
Obstetric care clinicians have an important role in helping patients make informed infant feeding decisions without coercion or pressure. To start these discussions, clinicians can begin by assessing a patient’s breastfeeding goals by asking open-ended questions, such as:
- What have you heard about breastfeeding?
- What are your plans for returning to work or school after delivery?
- How did breastfeeding go with older children?
- What are your plans for feeding this baby?
In addition to gathering information about the patient’s priorities and goals, clinicians should identify any risk factors for breastfeeding challenges in the medical, surgical, or previous breastfeeding history. Clinicians can engage in a patient-centered approach to infant feeding decisions by anticipating any challenges and working together to develop strategies to address these challenges with the patient’s goals in mind.17
When counseling about contraception, a spectrum of approaches exists, from a nondirective information-sharing only model to directive counseling by the clinician. The shared decision-making model lies between these 2 approaches and recognizes the expertise of both the clinician and patient.19 To start these interactions, clinicians can ask about a patient’s reproductive goals by assessing the patient’s needs, values, and preferences for contraception. Potential questions include:
- What kinds of contraceptive methods have you used in the past?
- What is important to you in a contraceptive method?
- How important is it to you to avoid another pregnancy right now?
Clinicians can then share information about different contraceptive methods based on the desired qualities that the patient has identified and how each method fits or does not fit into the patient’s goals and preferences. This collaborative approach facilitates an open dialogue and supports patient autonomy in contraceptive decision-making.
Lastly, clinicians should be cognizant of their own potential biases that could affect their counseling, such as encouraging contraceptive use because of a patient’s young age, parity, or premature delivery, as in our case presentation. Similarly, clinicians also should recognize that breastfeeding and contraceptive decisions are personal and are made with cultural, historical, and social contexts in mind.20 Ultimately, counseling should be patient centered and individualized for each person’s priorities related to infant feeding and pregnancy prevention. ●
- Meek JY, Noble L; Section on Breastfeeding. Policy statement: breastfeeding and the use of human milk. Pediatrics. 2022;150:e2022057988.
- Centers for Disease Control and Prevention. Breastfeeding report card, United States 2022. Accessed November 8, 2022. https://www.cdc.gov/breastfeeding/pdf/2022-Breast feeding-Report-Card-H.pdf
- Centers for Disease Control and Prevention. Rates of any and exclusive breastfeeding by sociodemographic characteristic among children born in 2019. Accessed November 8, 2022. https://www.cdc.gov/breastfeeding/data/nis_data/data-files/2019/rates-any-exclusive-bf-socio-dem-2019.html
- American College of Obstetricians and Gynecologists. Committee opinion no. 821: barriers to breastfeeding: supporting initiation and continuation of breastfeeding. Obstet Gynecol. 2021;137:e54-e62.
- Pang WW, Hartmann PE. Initiation of human lactation: secretory differentiation and secretory activation. J Mammary Gland Biol Neoplasia. 2007;12:211-221.
- Brownell E, Howard CR, Lawrence RA, et al. Delayed onset lactogenesis II predicts the cessation of any or exclusive breastfeeding. J Pediatr. 2012;161:608-614.
- American College of Obstetricians and Gynecologists. Committee opinion no. 820: breastfeeding challenges. Obstet Gynecol. 2021;137:e42-e53.
- Curtis KM, Tepper NK, Jatlaoui TC, et al. US Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(RR-3):1-104.
- Turok DK, Leeman L, Sanders JN, et al. Immediate postpartum levonorgestrel intrauterine device insertion and breast-feeding outcomes: a noninferiority randomized controlled trial. Am J Obstet Gynecol. 2017;217:665.e1-665.e8.
- Levi EE, Findley MK, Avila K, et al. Placement of levonorgestrel intrauterine device at the time of cesarean delivery and the effect on breastfeeding duration. Breastfeed Med. 2018;13:674-679.
- Carmo LSMP, Braga GC, Ferriani RA, et al. Timing of etonogestrel-releasing implants and growth of breastfed infants: a randomized controlled trial. Obstet Gynecol. 2017;130:100-107.
- Averbach S, Kakaire O, McDiehl R, et al. The effect of immediate postpartum levonorgestrel contraceptive implant use on breastfeeding and infant growth: a randomized controlled trial. Contraception. 2019;99:87-93.
- Krashin JW, Lemani C, Nkambule J, et al. A comparison of breastfeeding exclusivity and duration rates between immediate postpartum levonorgestrel versus etonogestrel implant users: a prospective cohort study. Breastfeed Med. 2019;14:69-76.
- Henkel A, Lerma K, Reyes G, et al. Lactogenesis and breastfeeding after immediate vs delayed birth-hospitalization insertion of etonogestrel contraceptive implant: a noninferiority trial. Am J Obstet Gynecol. 2023; 228:55.e1-55.e9.
- Parker LA, Sullivan S, Cacho N, et al. Effect of postpartum depo medroxyprogesterone acetate on lactation in mothers of very low-birth-weight infants. Breastfeed Med. 2021;16:835-842.
- Nommsen-Rivers LA, Dewey KG. Development and validation of the infant feeding intentions scale. Matern Child Health J. 2009;13:334-342.
- American College of Obstetricians and Gynecologists. Committee opinion no. 756: optimizing support for breastfeeding as part of obstetric practice. Obstet Gynecol. 2018;132:e187-e196.
- Berens P, Labbok M; Academy of Breastfeeding Medicine. ABM Clinical Protocol #13: contraception during breastfeeding, revised 2015. Breastfeed Med. 2015;10:3-12.
- American College of Obstetricians and Gynecologists, Committee on Health Care for Underserved Women, Contraceptive Equity Expert Work Group, and Committee on Ethics. Committee statement no. 1: patient-centered contraceptive counseling. Obstet Gynecol. 2022;139:350-353.
- Bryant AG, Lyerly AD, DeVane-Johnson S, et al. Hormonal contraception, breastfeeding and bedside advocacy: the case for patient-centered care. Contraception. 2019;99:73-76.
Dr. Chen is Associate Professor, Department of Obstetrics and Gynecology, University of California, Davis.
Dr. Crowe is Clinical Professor, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California.
The authors report no financial relationships relevant to this article.
Dr. Chen is Associate Professor, Department of Obstetrics and Gynecology, University of California, Davis.
Dr. Crowe is Clinical Professor, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California.
The authors report no financial relationships relevant to this article.
Dr. Chen is Associate Professor, Department of Obstetrics and Gynecology, University of California, Davis.
Dr. Crowe is Clinical Professor, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California.
The authors report no financial relationships relevant to this article.
CASE Patient concerned about hormonal contraception’s impact on lactation
A 19-year-old woman (G2P1102) is postpartum day 1 after delivering a baby at 26 weeks’ gestation. When you see her on postpartum rounds, she states that she does not want any hormonal contraception because she heard that it will decrease her milk supply. What are your next steps?
The American Academy of Pediatrics recently updated its policy statement on breastfeeding and the use of human milk to recommend exclusive breastfeeding for 6 months and continued breastfeeding, with complementary foods, as mutually desired for 2 years or beyond given evidence of maternal health benefits with breastfeeding longer than 1 year.1
Breastfeeding prevalence—and challenges
Despite maternal and infant benefits associated with lactation, current breastfeeding prevalence in the United States remains suboptimal. In 2019, 24.9% of infants were exclusively breastfed through 6 months and 35.9% were breastfeeding at 12 months.2 Furthermore, disparities in breastfeeding exist, which contribute to health inequities. For example, non-Hispanic Black infants had lower rates of exclusive breastfeeding at 6 months (19.1%) and any breastfeeding at 12 months (24.1%) compared with non-Hispanic White infants (26.9% and 39.4%, respectively).3
While many new mothers intend to breastfeed and initiate breastfeeding in the hospital after delivery, overall and exclusive breastfeeding continuation rates are low, indicating that patients face challenges with breastfeeding after hospital discharge. Many structural and societal barriers to breastfeeding exist, including inadequate social support and parental leave policies.4 Suboptimal maternity care practices during the birth hospitalization may lead to challenges with breastfeeding initiation. Health care practitioners may present additional barriers to breastfeeding due to a lack of knowledge of available resources for patients or incomplete training in breastfeeding counseling and support.
To address our case patient’s concerns, clinicians should be aware of how exogenous progestins may affect breastfeeding physiology, risk factors for breastfeeding difficulty, and the available evidence for safety of hormonal contraception use while breastfeeding.
Physiology of breastfeeding
During the second half of pregnancy, secretory differentiation (lactogenesis I) of mammary alveolar epithelial cells into secretory cells occurs to allow the mammary gland to eventually produce milk.5 After delivery of the placenta, progesterone withdrawal triggers secretory activation (lactogenesis II), which refers to the onset of copious milk production within 2 to 3 days postpartum.5 Most patients experience secretory activation within 72 hours; however, a delay in secretory activation past 72 hours is associated with cessation of any and exclusive breastfeeding at 4 weeks postpartum.6
Impaired lactation can be related to a delay in secretory activation or to insufficient lactation related to low milk supply. Maternal medical comorbidities (for example, diabetes mellitus, thyroid dysfunction, obesity), breast anatomy (such as insufficient glandular tissue, prior breast reduction surgery), pregnancy-related events (preeclampsia, retained placenta, postpartum hemorrhage), and infant conditions (such as multiple gestation, premature birth, congenital anomalies) all contribute to a risk of impaired lactation.7
Guidance on breastfeeding and hormonal contraception initiation
Early initiation of hormonal contraception poses theoretical concerns about breastfeeding difficulty if exogenous progestin interferes with endogenous signals for onset of milk production. The Centers for Disease Control and Prevention US Medical Eligibility Criteria (MEC) for Contraceptive Use provide recommendations on the safety of contraceptive use in the setting of various medical conditions or patient characteristics based on available data. The MEC uses 4 categories in assessing the safety of contraceptive method use for individuals with specific medical conditions or characteristics: 1, no restrictions exist for use of the contraceptive method; 2, advantages generally outweigh theoretical or proven risks; 3, theoretical or proven risks usually outweigh the advantages; and 4, conditions that represent an unacceptable health risk if the method is used.8
In the 2016 guidelines, combined hormonal contraceptives are considered category 4 at less than 21 days postpartum, regardless of breastfeeding status, due to the increased risk of venous thromboembolism in the immediate postpartum period (TABLE 1).8 Progestin-only contraception is considered category 1 in nonbreastfeeding individuals and category 2 in breastfeeding individuals based on overall evidence that found no adverse outcome with breastfeeding or infant outcomes with early initiation of progestin-only contraception (TABLE 1, TABLE 2).8
Since the publication of the 2016 MEC guidelines, several studies have continued to examine breastfeeding and infant outcomes with early initiation of hormonal contraception.
- In a noninferiority randomized controlled trial of immediate versus delayed initiation of a levonorgestrel intrauterine device (LNG IUD), any breastfeeding at 8 weeks in the immediate group was 78% (95% confidence interval [CI], 70%–85%), which was lower than but within the specified noninferiority margin of the delayed breastfeeding group (83%; 95% CI, 75%–90%), indicating that breastfeeding outcomes with immediate initiation of an LNG IUD were not worse compared with delayed initiation.9
- A secondary analysis of a randomized trial that compared intracesarean versus LNG IUD placement at 6 or more weeks postpartum showed no difference in breastfeeding at 6, 12, and 24 weeks after LNG IUD placement.10
- A randomized trial of early (up to 48 hours postpartum) versus placement of an etonogestrel (ENG) implant at 6 or more weeks postpartum showed no difference between groups in infant weight at 12 months.11
- A randomized trial of immediate (within 5 days of delivery) or interval placement of the 2-rod LNG implant (not approved in the United States) showed no difference in change in infant weight from birth to 6 months after delivery, onset of secretory activation, or breastfeeding continuation at 3 and 6 months postpartum.12
- In a prospective cohort study that compared immediate postpartum initiation of ENG versus a 2-rod LNG implant (approved by the FDA but not marketed in the United States), there were no differences in breastfeeding continuation at 24 months and exclusive breastfeeding at 6 months postpartum.13
- In a noninferiority randomized controlled trial that compared ENG implant initiation in the delivery room (0–2 hours postdelivery) versus delayed initiation (24–48 hours postdelivery), the time to secretory activation in those who initiated an ENG implant in the delivery room (66.8 [SD, 25.2] hours) was noninferior to delayed initiation (66.0 [SD, 35.3] hours). There also was no difference in ongoing breastfeeding over the first year after delivery and implant use at 12 months.14
- A secondary analysis of a randomized controlled trial examined breastfeeding outcomes with receipt of depot medroxyprogesterone acetate (DMPA) prior to discharge in women who delivered infants who weighed 1,500 g or less at 32 weeks’ or less gestation. Time to secretory activation was longer in 29 women who received DMPA (103.7 hours) compared with 141 women who did not (88.6 hours; P = .028); however, there was no difference in daily milk production, lactation duration, or infant consumption of mother’s own milk.15
While the overall evidence suggests that early initiation of hormonal contraception does not affect breastfeeding or infant outcomes, it is important for clinicians to recognize the limitations of available data with regard to the populations included in these studies. Specifically, most studies did not include individuals with premature, low birth weight, or multiple gestation infants, who are at higher risk of impaired lactation, and individuals with a higher prevalence of breastfeeding were not included to determine whether early initiation of hormonal contraception would impact breastfeeding. Furthermore, while these studies enrolled participants who planned to breastfeed, data indicate that intentions to initiate and continue exclusive breastfeeding can vary.16 As the reported rates of any and exclusive breastfeeding are consistent with or lower than current US breastfeeding rates, any decrease in breastfeeding exclusivity or duration that may be attributable to hormonal contraception may be unacceptable to those who are strongly motivated to breastfeed.
Continue to: How can clinicians integrate evidence into contraception counseling?...
How can clinicians integrate evidence into contraception counseling?
The American College of Obstetricians and Gynecologists and the Academy of Breastfeeding Medicine offer guidance for how clinicians can address the use of hormonal contraception in breastfeeding patients. Both organizations recommend discussing the risks and benefits of hormonal contraception within the context of each person’s desire to breastfeed, potential for breastfeeding difficulty, and risk of pregnancy so that individuals can make their own informed decisions.17,18
Obstetric care clinicians have an important role in helping patients make informed infant feeding decisions without coercion or pressure. To start these discussions, clinicians can begin by assessing a patient’s breastfeeding goals by asking open-ended questions, such as:
- What have you heard about breastfeeding?
- What are your plans for returning to work or school after delivery?
- How did breastfeeding go with older children?
- What are your plans for feeding this baby?
In addition to gathering information about the patient’s priorities and goals, clinicians should identify any risk factors for breastfeeding challenges in the medical, surgical, or previous breastfeeding history. Clinicians can engage in a patient-centered approach to infant feeding decisions by anticipating any challenges and working together to develop strategies to address these challenges with the patient’s goals in mind.17
When counseling about contraception, a spectrum of approaches exists, from a nondirective information-sharing only model to directive counseling by the clinician. The shared decision-making model lies between these 2 approaches and recognizes the expertise of both the clinician and patient.19 To start these interactions, clinicians can ask about a patient’s reproductive goals by assessing the patient’s needs, values, and preferences for contraception. Potential questions include:
- What kinds of contraceptive methods have you used in the past?
- What is important to you in a contraceptive method?
- How important is it to you to avoid another pregnancy right now?
Clinicians can then share information about different contraceptive methods based on the desired qualities that the patient has identified and how each method fits or does not fit into the patient’s goals and preferences. This collaborative approach facilitates an open dialogue and supports patient autonomy in contraceptive decision-making.
Lastly, clinicians should be cognizant of their own potential biases that could affect their counseling, such as encouraging contraceptive use because of a patient’s young age, parity, or premature delivery, as in our case presentation. Similarly, clinicians also should recognize that breastfeeding and contraceptive decisions are personal and are made with cultural, historical, and social contexts in mind.20 Ultimately, counseling should be patient centered and individualized for each person’s priorities related to infant feeding and pregnancy prevention. ●
CASE Patient concerned about hormonal contraception’s impact on lactation
A 19-year-old woman (G2P1102) is postpartum day 1 after delivering a baby at 26 weeks’ gestation. When you see her on postpartum rounds, she states that she does not want any hormonal contraception because she heard that it will decrease her milk supply. What are your next steps?
The American Academy of Pediatrics recently updated its policy statement on breastfeeding and the use of human milk to recommend exclusive breastfeeding for 6 months and continued breastfeeding, with complementary foods, as mutually desired for 2 years or beyond given evidence of maternal health benefits with breastfeeding longer than 1 year.1
Breastfeeding prevalence—and challenges
Despite maternal and infant benefits associated with lactation, current breastfeeding prevalence in the United States remains suboptimal. In 2019, 24.9% of infants were exclusively breastfed through 6 months and 35.9% were breastfeeding at 12 months.2 Furthermore, disparities in breastfeeding exist, which contribute to health inequities. For example, non-Hispanic Black infants had lower rates of exclusive breastfeeding at 6 months (19.1%) and any breastfeeding at 12 months (24.1%) compared with non-Hispanic White infants (26.9% and 39.4%, respectively).3
While many new mothers intend to breastfeed and initiate breastfeeding in the hospital after delivery, overall and exclusive breastfeeding continuation rates are low, indicating that patients face challenges with breastfeeding after hospital discharge. Many structural and societal barriers to breastfeeding exist, including inadequate social support and parental leave policies.4 Suboptimal maternity care practices during the birth hospitalization may lead to challenges with breastfeeding initiation. Health care practitioners may present additional barriers to breastfeeding due to a lack of knowledge of available resources for patients or incomplete training in breastfeeding counseling and support.
To address our case patient’s concerns, clinicians should be aware of how exogenous progestins may affect breastfeeding physiology, risk factors for breastfeeding difficulty, and the available evidence for safety of hormonal contraception use while breastfeeding.
Physiology of breastfeeding
During the second half of pregnancy, secretory differentiation (lactogenesis I) of mammary alveolar epithelial cells into secretory cells occurs to allow the mammary gland to eventually produce milk.5 After delivery of the placenta, progesterone withdrawal triggers secretory activation (lactogenesis II), which refers to the onset of copious milk production within 2 to 3 days postpartum.5 Most patients experience secretory activation within 72 hours; however, a delay in secretory activation past 72 hours is associated with cessation of any and exclusive breastfeeding at 4 weeks postpartum.6
Impaired lactation can be related to a delay in secretory activation or to insufficient lactation related to low milk supply. Maternal medical comorbidities (for example, diabetes mellitus, thyroid dysfunction, obesity), breast anatomy (such as insufficient glandular tissue, prior breast reduction surgery), pregnancy-related events (preeclampsia, retained placenta, postpartum hemorrhage), and infant conditions (such as multiple gestation, premature birth, congenital anomalies) all contribute to a risk of impaired lactation.7
Guidance on breastfeeding and hormonal contraception initiation
Early initiation of hormonal contraception poses theoretical concerns about breastfeeding difficulty if exogenous progestin interferes with endogenous signals for onset of milk production. The Centers for Disease Control and Prevention US Medical Eligibility Criteria (MEC) for Contraceptive Use provide recommendations on the safety of contraceptive use in the setting of various medical conditions or patient characteristics based on available data. The MEC uses 4 categories in assessing the safety of contraceptive method use for individuals with specific medical conditions or characteristics: 1, no restrictions exist for use of the contraceptive method; 2, advantages generally outweigh theoretical or proven risks; 3, theoretical or proven risks usually outweigh the advantages; and 4, conditions that represent an unacceptable health risk if the method is used.8
In the 2016 guidelines, combined hormonal contraceptives are considered category 4 at less than 21 days postpartum, regardless of breastfeeding status, due to the increased risk of venous thromboembolism in the immediate postpartum period (TABLE 1).8 Progestin-only contraception is considered category 1 in nonbreastfeeding individuals and category 2 in breastfeeding individuals based on overall evidence that found no adverse outcome with breastfeeding or infant outcomes with early initiation of progestin-only contraception (TABLE 1, TABLE 2).8
Since the publication of the 2016 MEC guidelines, several studies have continued to examine breastfeeding and infant outcomes with early initiation of hormonal contraception.
- In a noninferiority randomized controlled trial of immediate versus delayed initiation of a levonorgestrel intrauterine device (LNG IUD), any breastfeeding at 8 weeks in the immediate group was 78% (95% confidence interval [CI], 70%–85%), which was lower than but within the specified noninferiority margin of the delayed breastfeeding group (83%; 95% CI, 75%–90%), indicating that breastfeeding outcomes with immediate initiation of an LNG IUD were not worse compared with delayed initiation.9
- A secondary analysis of a randomized trial that compared intracesarean versus LNG IUD placement at 6 or more weeks postpartum showed no difference in breastfeeding at 6, 12, and 24 weeks after LNG IUD placement.10
- A randomized trial of early (up to 48 hours postpartum) versus placement of an etonogestrel (ENG) implant at 6 or more weeks postpartum showed no difference between groups in infant weight at 12 months.11
- A randomized trial of immediate (within 5 days of delivery) or interval placement of the 2-rod LNG implant (not approved in the United States) showed no difference in change in infant weight from birth to 6 months after delivery, onset of secretory activation, or breastfeeding continuation at 3 and 6 months postpartum.12
- In a prospective cohort study that compared immediate postpartum initiation of ENG versus a 2-rod LNG implant (approved by the FDA but not marketed in the United States), there were no differences in breastfeeding continuation at 24 months and exclusive breastfeeding at 6 months postpartum.13
- In a noninferiority randomized controlled trial that compared ENG implant initiation in the delivery room (0–2 hours postdelivery) versus delayed initiation (24–48 hours postdelivery), the time to secretory activation in those who initiated an ENG implant in the delivery room (66.8 [SD, 25.2] hours) was noninferior to delayed initiation (66.0 [SD, 35.3] hours). There also was no difference in ongoing breastfeeding over the first year after delivery and implant use at 12 months.14
- A secondary analysis of a randomized controlled trial examined breastfeeding outcomes with receipt of depot medroxyprogesterone acetate (DMPA) prior to discharge in women who delivered infants who weighed 1,500 g or less at 32 weeks’ or less gestation. Time to secretory activation was longer in 29 women who received DMPA (103.7 hours) compared with 141 women who did not (88.6 hours; P = .028); however, there was no difference in daily milk production, lactation duration, or infant consumption of mother’s own milk.15
While the overall evidence suggests that early initiation of hormonal contraception does not affect breastfeeding or infant outcomes, it is important for clinicians to recognize the limitations of available data with regard to the populations included in these studies. Specifically, most studies did not include individuals with premature, low birth weight, or multiple gestation infants, who are at higher risk of impaired lactation, and individuals with a higher prevalence of breastfeeding were not included to determine whether early initiation of hormonal contraception would impact breastfeeding. Furthermore, while these studies enrolled participants who planned to breastfeed, data indicate that intentions to initiate and continue exclusive breastfeeding can vary.16 As the reported rates of any and exclusive breastfeeding are consistent with or lower than current US breastfeeding rates, any decrease in breastfeeding exclusivity or duration that may be attributable to hormonal contraception may be unacceptable to those who are strongly motivated to breastfeed.
Continue to: How can clinicians integrate evidence into contraception counseling?...
How can clinicians integrate evidence into contraception counseling?
The American College of Obstetricians and Gynecologists and the Academy of Breastfeeding Medicine offer guidance for how clinicians can address the use of hormonal contraception in breastfeeding patients. Both organizations recommend discussing the risks and benefits of hormonal contraception within the context of each person’s desire to breastfeed, potential for breastfeeding difficulty, and risk of pregnancy so that individuals can make their own informed decisions.17,18
Obstetric care clinicians have an important role in helping patients make informed infant feeding decisions without coercion or pressure. To start these discussions, clinicians can begin by assessing a patient’s breastfeeding goals by asking open-ended questions, such as:
- What have you heard about breastfeeding?
- What are your plans for returning to work or school after delivery?
- How did breastfeeding go with older children?
- What are your plans for feeding this baby?
In addition to gathering information about the patient’s priorities and goals, clinicians should identify any risk factors for breastfeeding challenges in the medical, surgical, or previous breastfeeding history. Clinicians can engage in a patient-centered approach to infant feeding decisions by anticipating any challenges and working together to develop strategies to address these challenges with the patient’s goals in mind.17
When counseling about contraception, a spectrum of approaches exists, from a nondirective information-sharing only model to directive counseling by the clinician. The shared decision-making model lies between these 2 approaches and recognizes the expertise of both the clinician and patient.19 To start these interactions, clinicians can ask about a patient’s reproductive goals by assessing the patient’s needs, values, and preferences for contraception. Potential questions include:
- What kinds of contraceptive methods have you used in the past?
- What is important to you in a contraceptive method?
- How important is it to you to avoid another pregnancy right now?
Clinicians can then share information about different contraceptive methods based on the desired qualities that the patient has identified and how each method fits or does not fit into the patient’s goals and preferences. This collaborative approach facilitates an open dialogue and supports patient autonomy in contraceptive decision-making.
Lastly, clinicians should be cognizant of their own potential biases that could affect their counseling, such as encouraging contraceptive use because of a patient’s young age, parity, or premature delivery, as in our case presentation. Similarly, clinicians also should recognize that breastfeeding and contraceptive decisions are personal and are made with cultural, historical, and social contexts in mind.20 Ultimately, counseling should be patient centered and individualized for each person’s priorities related to infant feeding and pregnancy prevention. ●
- Meek JY, Noble L; Section on Breastfeeding. Policy statement: breastfeeding and the use of human milk. Pediatrics. 2022;150:e2022057988.
- Centers for Disease Control and Prevention. Breastfeeding report card, United States 2022. Accessed November 8, 2022. https://www.cdc.gov/breastfeeding/pdf/2022-Breast feeding-Report-Card-H.pdf
- Centers for Disease Control and Prevention. Rates of any and exclusive breastfeeding by sociodemographic characteristic among children born in 2019. Accessed November 8, 2022. https://www.cdc.gov/breastfeeding/data/nis_data/data-files/2019/rates-any-exclusive-bf-socio-dem-2019.html
- American College of Obstetricians and Gynecologists. Committee opinion no. 821: barriers to breastfeeding: supporting initiation and continuation of breastfeeding. Obstet Gynecol. 2021;137:e54-e62.
- Pang WW, Hartmann PE. Initiation of human lactation: secretory differentiation and secretory activation. J Mammary Gland Biol Neoplasia. 2007;12:211-221.
- Brownell E, Howard CR, Lawrence RA, et al. Delayed onset lactogenesis II predicts the cessation of any or exclusive breastfeeding. J Pediatr. 2012;161:608-614.
- American College of Obstetricians and Gynecologists. Committee opinion no. 820: breastfeeding challenges. Obstet Gynecol. 2021;137:e42-e53.
- Curtis KM, Tepper NK, Jatlaoui TC, et al. US Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(RR-3):1-104.
- Turok DK, Leeman L, Sanders JN, et al. Immediate postpartum levonorgestrel intrauterine device insertion and breast-feeding outcomes: a noninferiority randomized controlled trial. Am J Obstet Gynecol. 2017;217:665.e1-665.e8.
- Levi EE, Findley MK, Avila K, et al. Placement of levonorgestrel intrauterine device at the time of cesarean delivery and the effect on breastfeeding duration. Breastfeed Med. 2018;13:674-679.
- Carmo LSMP, Braga GC, Ferriani RA, et al. Timing of etonogestrel-releasing implants and growth of breastfed infants: a randomized controlled trial. Obstet Gynecol. 2017;130:100-107.
- Averbach S, Kakaire O, McDiehl R, et al. The effect of immediate postpartum levonorgestrel contraceptive implant use on breastfeeding and infant growth: a randomized controlled trial. Contraception. 2019;99:87-93.
- Krashin JW, Lemani C, Nkambule J, et al. A comparison of breastfeeding exclusivity and duration rates between immediate postpartum levonorgestrel versus etonogestrel implant users: a prospective cohort study. Breastfeed Med. 2019;14:69-76.
- Henkel A, Lerma K, Reyes G, et al. Lactogenesis and breastfeeding after immediate vs delayed birth-hospitalization insertion of etonogestrel contraceptive implant: a noninferiority trial. Am J Obstet Gynecol. 2023; 228:55.e1-55.e9.
- Parker LA, Sullivan S, Cacho N, et al. Effect of postpartum depo medroxyprogesterone acetate on lactation in mothers of very low-birth-weight infants. Breastfeed Med. 2021;16:835-842.
- Nommsen-Rivers LA, Dewey KG. Development and validation of the infant feeding intentions scale. Matern Child Health J. 2009;13:334-342.
- American College of Obstetricians and Gynecologists. Committee opinion no. 756: optimizing support for breastfeeding as part of obstetric practice. Obstet Gynecol. 2018;132:e187-e196.
- Berens P, Labbok M; Academy of Breastfeeding Medicine. ABM Clinical Protocol #13: contraception during breastfeeding, revised 2015. Breastfeed Med. 2015;10:3-12.
- American College of Obstetricians and Gynecologists, Committee on Health Care for Underserved Women, Contraceptive Equity Expert Work Group, and Committee on Ethics. Committee statement no. 1: patient-centered contraceptive counseling. Obstet Gynecol. 2022;139:350-353.
- Bryant AG, Lyerly AD, DeVane-Johnson S, et al. Hormonal contraception, breastfeeding and bedside advocacy: the case for patient-centered care. Contraception. 2019;99:73-76.
- Meek JY, Noble L; Section on Breastfeeding. Policy statement: breastfeeding and the use of human milk. Pediatrics. 2022;150:e2022057988.
- Centers for Disease Control and Prevention. Breastfeeding report card, United States 2022. Accessed November 8, 2022. https://www.cdc.gov/breastfeeding/pdf/2022-Breast feeding-Report-Card-H.pdf
- Centers for Disease Control and Prevention. Rates of any and exclusive breastfeeding by sociodemographic characteristic among children born in 2019. Accessed November 8, 2022. https://www.cdc.gov/breastfeeding/data/nis_data/data-files/2019/rates-any-exclusive-bf-socio-dem-2019.html
- American College of Obstetricians and Gynecologists. Committee opinion no. 821: barriers to breastfeeding: supporting initiation and continuation of breastfeeding. Obstet Gynecol. 2021;137:e54-e62.
- Pang WW, Hartmann PE. Initiation of human lactation: secretory differentiation and secretory activation. J Mammary Gland Biol Neoplasia. 2007;12:211-221.
- Brownell E, Howard CR, Lawrence RA, et al. Delayed onset lactogenesis II predicts the cessation of any or exclusive breastfeeding. J Pediatr. 2012;161:608-614.
- American College of Obstetricians and Gynecologists. Committee opinion no. 820: breastfeeding challenges. Obstet Gynecol. 2021;137:e42-e53.
- Curtis KM, Tepper NK, Jatlaoui TC, et al. US Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(RR-3):1-104.
- Turok DK, Leeman L, Sanders JN, et al. Immediate postpartum levonorgestrel intrauterine device insertion and breast-feeding outcomes: a noninferiority randomized controlled trial. Am J Obstet Gynecol. 2017;217:665.e1-665.e8.
- Levi EE, Findley MK, Avila K, et al. Placement of levonorgestrel intrauterine device at the time of cesarean delivery and the effect on breastfeeding duration. Breastfeed Med. 2018;13:674-679.
- Carmo LSMP, Braga GC, Ferriani RA, et al. Timing of etonogestrel-releasing implants and growth of breastfed infants: a randomized controlled trial. Obstet Gynecol. 2017;130:100-107.
- Averbach S, Kakaire O, McDiehl R, et al. The effect of immediate postpartum levonorgestrel contraceptive implant use on breastfeeding and infant growth: a randomized controlled trial. Contraception. 2019;99:87-93.
- Krashin JW, Lemani C, Nkambule J, et al. A comparison of breastfeeding exclusivity and duration rates between immediate postpartum levonorgestrel versus etonogestrel implant users: a prospective cohort study. Breastfeed Med. 2019;14:69-76.
- Henkel A, Lerma K, Reyes G, et al. Lactogenesis and breastfeeding after immediate vs delayed birth-hospitalization insertion of etonogestrel contraceptive implant: a noninferiority trial. Am J Obstet Gynecol. 2023; 228:55.e1-55.e9.
- Parker LA, Sullivan S, Cacho N, et al. Effect of postpartum depo medroxyprogesterone acetate on lactation in mothers of very low-birth-weight infants. Breastfeed Med. 2021;16:835-842.
- Nommsen-Rivers LA, Dewey KG. Development and validation of the infant feeding intentions scale. Matern Child Health J. 2009;13:334-342.
- American College of Obstetricians and Gynecologists. Committee opinion no. 756: optimizing support for breastfeeding as part of obstetric practice. Obstet Gynecol. 2018;132:e187-e196.
- Berens P, Labbok M; Academy of Breastfeeding Medicine. ABM Clinical Protocol #13: contraception during breastfeeding, revised 2015. Breastfeed Med. 2015;10:3-12.
- American College of Obstetricians and Gynecologists, Committee on Health Care for Underserved Women, Contraceptive Equity Expert Work Group, and Committee on Ethics. Committee statement no. 1: patient-centered contraceptive counseling. Obstet Gynecol. 2022;139:350-353.
- Bryant AG, Lyerly AD, DeVane-Johnson S, et al. Hormonal contraception, breastfeeding and bedside advocacy: the case for patient-centered care. Contraception. 2019;99:73-76.
Is it time to reconsider Rh testing and Rh D immune globulin treatment for miscarriage and abortion care in early pregnancy?
All obstetrician-gynecologists know that pregnant patients who are Rh negative and exposed to a sufficient quantity of fetal red blood cells expressing Rh D antigen may become sensitized, producing Rh D antibodies that adversely impact future pregnancies with an Rh D-positive fetus, potentially causing hemolytic disease of the fetus and newborn. In countries where Rh D immune globulin is available, there is a consensus recommendation to administer Rh D immune globulin to Rh-negative pregnant patients at approximately 28 weeks’ gestation and at birth in order to decrease the risk of alloimmunization and hemolytic disease of the fetus and newborn in future pregnancies.1 In contrast to this global consensus, there is no worldwide agreement about how to manage Rh testing and Rh D immune globulin administration in cases of early pregnancy loss or abortion care before 12 weeks’ gestation. This editorial examines the evolving guidelines of major professional societies.
Guidelines consistent with the routine use of Rh D immune globulin in all cases of early pregnancy loss and abortion care
As of the publication date of this editorial, the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin on prevention of Rh D alloimmunization provides the following guidance based on consensus and expert opinion2:
- “Although the risk of alloimmunization is low, the consequences can be significant, and administration of Rh D immune globulin should be considered in cases of spontaneous first trimester miscarriage, especially those that are later in the first trimester.”
- “Because of the higher risk of alloimmunization, Rh D-negative women who have instrumentation for their miscarriage should receive Rh D immune globulin prophylaxis.”
- “Rh D immune globulin should be given to Rh D-negative women who have pregnancy termination either medical or surgical.”
The Society of Obstetricians and Gynaecologists of Canada (SOGC) recommends that, “After miscarriage or threatened abortion or induced abortion during the first 12 weeks of gestation, non-sensitized D-negative women should be given a minimum anti-D of 120 µg.”3
The liberal use of Rh D immune globulin in all cases of early pregnancy loss and abortion care is based, in part, on the following considerations:
- the recognized safety of Rh D immune globulin administration2,3
- the report that fetal megaloblasts may express Rh antigen as early as 38 days of gestation4
- the observation that 0.1 mL of Rh D-positive red cells may provoke an immune response in some Rh D-negative patients5-7
- the estimate that in some patients with threatened miscarriage a significant quantity of fetal blood may enter the maternal circulation.8
Guidelines that suggest restricted use of Rh D immune globulin before 7 to 8 weeks’ gestation
The Reproductive Care Program of Nova Scotia guideline from 2022 notes that “the benefits of administering Rh immune globulin before 8 weeks gestation have not been demonstrated.” Given the burden of Rh testing and Rh D immune globulin administration they suggest that clinicians may withhold Rh testing and Rh D immune globulin administration in cases less than 8 weeks’ gestation (less than 56 days) for spontaneous, threatened, or medication abortions if there is reliable pregnancy dating.9
The Dutch Association of Abortion Specialists guidelines from 2018 suggest to not provide Rh D immune globulin treatment in the following clinical situations: patients under 10 weeks’ gestation with spontaneous miscarriage or patients under 7 weeks’ gestation having an induced abortion.10
Continue to: Guidelines that suggest restricted use of Rh D immune globulin before 10 to 12 weeks’ gestation...
Guidelines that suggest restricted use of Rh D immune globulin before 10 to 12 weeks’ gestation
There are a growing number of guidelines that recommend restricting the use of Rh testing and Rh D immune globulin treatment in the management of early miscarriage and induced abortion. In 2019, the United Kingdom’s National Institute for Health and Care Excellence (NICE) recommended that for patients having a spontaneous miscarriage, Rh testing and Rh D immune globulin are not necessary before 10 weeks 0 days of gestation.11 In addition, NICE recommends, “Do not offer anti-D prophylaxis to women who are having a medical abortion up to and including 10+0 weeks’ gestation.…Consider anti-D prophylaxis for women who are rhesus D negative and are having a surgical abortion up to and including 10+0 weeks’ gestation.”11
In 2019, the National Abortion Federation (NAF) Clinical Policies Committee recommended that “…it is reasonable to forgo Rh testing and anti-D immunoglobulin for women having any type of induced abortion before 8 weeks from the last menstrual period. Prior to 8 weeks, the likelihood of fetal-maternal hemorrhage adequate to cause sensitization is negligible. Given that medication abortion is more similar to spontaneous abortion with less risk of fetal-maternal hemorrhage, forgoing Rh testing and anti-D immunoglobulin for medication abortion under 10 weeks may be considered.”12 In 2022, NAF noted, “Emerging epidemiologic and clinical evidence indicates that the risk of maternal-fetal hemorrhage caused by early abortion is negligible and Rh testing and provision of Rh immune globulin may not be necessary. It is reasonable to forego Rh testing and anti-D immunoglobulin for people having any type of abortion before 56 days and medication abortion before 70 days since the last menstrual period. The pregnancy dating at which people need Rh testing and anti-D immunoglobulin is not well established. Foregoing Rh testing and anti-D immunoglobulinfor those using medication abortion through 11 to 12 weeks may be considered.”13
In 2020 the International Federation of Gynaecology and Obstetrics (FIGO) Committee for Safe Motherhood and Newborn Health recommended, “The risk for sensitization is most probably extremely low for spontaneous abortions before 10 gestational weeks; however, data are scarce. Based on the clinical expertise of the guideline committee from the UK’s National Institute for Health and Care Excellence (NICE), it is suggested that prophylaxis should be given only to women who are having a spontaneous abortion or medical management of miscarriage after 10 and 0/7 gestational weeks. Moreover, for women who have surgical management, prophylaxis may also be considered before 10 gestational weeks.”14
In 2022 the Royal College of Obstetricians and Gynaecologists recommended that for induced abortion, medication or surgical, “a determination of Rhesus blood status may be considered if the duration of pregnancy is over 12 weeks and anti-D is available.”15 “If available, anti-D should be offered to non-sensitised RhD-negative individuals from 12 weeks of pregnancy and provided within 72 hours of the abortion.”15
In 2022, the Society of Family Planning recommended that “Rh testing and administration are not recommended prior to 12 weeks gestation for patients undergoing spontaneous, medication or uterine aspiration abortion.” “For patients under 12 weeks gestation, although not recommended, Rh testing and Rh D immune globulin administration may be considered at patient request as part of a shared decision making process.”16
In 2022, the World Health Organization (WHO) reported “There are few studies examining Rh isoimmunization in unsensitized Rh-negative individuals seeking abortion before 12 weeks of gestation.” “The evidence on the effectiveness of the intervention may favor the intervention, because fewer women in the intervention group (anti-D administration) had antibody formation after the initial pregnancy compared to women in the comparison group (no anti-D) and no harms (undesirable effects) of the intervention were noted.”17 The evidence referenced for these statements are two low-quality studies from 1972.18,19 The WHO continues, “…after consideration of the resources required, cost-effectiveness and feasibility of administering anti-D, as well as the very low certainty of evidence on effectiveness, the expert panel concluded that overall, the evidence does not favor the intervention and decided to recommend against it for gestational ages < 12 weeks, rather than < 9 weeks, as mentioned in the 2012 guidance.”17 In conclusion, the WHO recommended that “for both medical and surgical abortion at < 12 weeks: Recommend against anti-D immunoglobulin administration.”17
Guidelines that recommend restricted use of Rh D immune globulin during the first trimester, are based, in part, on the following considerations:
- there are no high-quality clinical trials demonstrating the benefit of Rh D immune globulin treatment in first trimester miscarriage and abortion care
- the Kleihauer-Betke technique cannot distinguish between maternal red blood cells expressing fetal hemoglobin (maternal F cells) and fetal cells, which has resulted in the over-estimation of the number of fetal cells in the maternal circulation20
- using a dual-label flow cytometry method that distinguishes maternal F cells and fetal red blood cells, maternal F cells usually far outnumber fetal red blood cells in the maternal circulation in the first trimester20
- among women in the first trimester undergoing uterine aspiration, the number of fetal cells in the maternal circulation is very low both before and after the procedure20
- Rh testing and Rh immune globulin administration is burdensome and expensive.16
Implications for your practice
The fundamental reason for the proliferation of divergent guidelines is that there is no evidence from high-quality randomized clinical trials demonstrating that Rh testing and Rh D immune globulin treatment in early pregnancy miscarriage or induced abortion care reduces the risk of hemolytic disease of the fetus and newborn. The Cochrane review on Rh D immune globulin administration for preventing alloimmunization among patients with spontaneous miscarriage concluded, “There are insufficient data available to evaluate the practice of anti-D administration in an unsensitized Rh-negative mother after spontaneous miscarriage.”21
Given divergent guidelines, obstetrician-gynecologists must decide on which guideline to use in their practice. Clinicians may conclude that absent high-quality evidence from clinical trials, they will continue to use the ACOG/SOGC guidelines2,3 in their practice, providing universal Rh testing and Rh D immune globulin treatment for all miscarriages and abortions, regardless of the gestational age. Other clinicians may conclude that Rh testing and Rh D immune globulin is not warranted before 8 to 12 weeks’ gestation, because the number of fetal red blood cells in the maternal circulation in cases of miscarriage and induced abortion is too low in early pregnancy to induce a maternal immune response.22 Based on recent studies demonstrating a low number of fetal red blood cells in the maternal circulation in the first trimester, family planning specialists are reducing the use of Rh testing and Rh immune globulin administration in both early pregnancy medication abortion and uterine aspiration abortion.16 With regard to Rh testing and Rh D immune globulin treatment, the future will definitely be different than the past. It is likely that many clinicians will reduce the use of Rh testing and Rh D immune globulin treatment in patients with miscarriage or induced abortion in early pregnancy. ●
- Sperling JD, Dahlke JD, Sutton D, et al. Prevention of Rh D alloimmunization: a comparison of four national guidelines. Am J Perinatol. 2018;35:110-119.
- Prevention of Rh D alloimmunization. Practice Bulletin No. 181. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2017;130:e57-e70.
- Fung KFK, Eason E. No. 133-Prevention of Rh alloimmunization. J Obstet Gynaecol Can. 2018;40: e1-e10.
- Bergstrom H, Nilsson LA, Nilsson L, et al. Demonstration of Rh antigens in a 38-day-old fetus. Am J Obstet Gynecol. 1967;99:130-133.
- Bowman JM. The prevention of Rh Immunization. Transfus Med Rev. 1988;2:129-150.
- Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J. 1967;97:1245-1257.
- Pollack W, Ascari WQ, Kochesky RJ, et al. Studies on Rh prophylaxis. 1. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion. 1971;11:333-339.
- Von Stein GA, Munsick RA, Stiver K, et al. Feto-maternal hemorrhage in threatened abortion. Obstet Gynecol. 1992;79:383-386.
- Rh Program of Nova Scotia. Guideline for Rh prophylaxis before 8 weeks (56 days) gestation for Early Pregnancy Complications and Medical Abortions. http://rcp.nshealth.ca/sites/default /files/rh/RhIg%20before%208%20weeks%20 Guideline_%20Jun2022_Final_2page.pdf. Accessed January 24, 2023.
- Wiebe ER, Campbell M, Aiken ARA, et al. Can we safety stop testing for Rh Status and immunizing Rh-negative women having early abortions? A comparison of Rh alloimmunization in Canada and the Netherlands. Contraception. 2019;100001. https://doi.org/10.1016/j.conx.2018.100001.
- Abortion care. National Institute for Health and Care Excellence. https://www.nice.org .uk/guidance/ng140/resources/abortion-care -pdf-66141773098693. Accessed January 24, 2023.
- Mark A, Foster AM, Grossman D. Foregoing Rh testing and anti-D immunoglobulin for women presenting for early abortion: a recommendation from the National Abortion Federation’s Clinical Policies Committee. Contraception. 2019;99:265-266.
- National Abortion Federation. 2022 Clinical Policy Guidelines for Abortion Care. https: //prochoice.org/wp-content/uploads/2022 -CPGs.pdf. Accessed January 24, 2023.
- Visser GHA, Thommesen T, Di Renzo GC, et al. FIGO Safe Motherhood and Newborn Health Committee. Int J Gynecol Obstet. 2021;152: 144-147.
- Making abortion safe: RCOG’s global initiative to advocate for women’s health. https://www .rcog.org.uk/media/geify5bx/abortion-care-best -practice-paper-april-2022.pdf. Accessed January 24, 2023.
- Horvath S, Goyal V, Traxler S, et al. Society of Family Planning committee consensus on Rh testing in early pregnancy. Contraception. 2022;114:1-5.
- World Health Organization. Abortion care guideline. https://www.who.int/publications/i/ item/9789240039483. Accessed January 24, 2023.
- Gavin P. Rhesus sensitization in abortion. Obstet Gynecol. 1972;39:37-40.
- Goldman J, Eckerling B. Rh immunization in spontaneous abortion. Acta Eur Fertil. 1972;3:253254.
- Horvath S, Tsao P, Huang ZY, et al. The concentration of fetal red blood cells in first-trimester pregnant women undergoing uterine aspiration is below the calculated threshold for Rh sensitization. Contraception. 2020;102:1-6.
- Karanth L, Jaafar SH, Kanagasabai S, et al. Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunization. Cochrane Database Syst Rev. 2023;CD009617.
- Gilmore E, Sonalkar S, Schreiber CA. Use of Rh immune globulin in first-trimester abortion and miscarriage. Obstet Gynecol. 2023;141:219-222.
Robert L. Barbieri, MD
Editor in Chief, OBG Management
Chair Emeritus, Department of Obstetrics and Gynecology
Brigham and Women’s Hospital
Kate Macy Ladd Distinguished Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Boston, Massachusetts
The author reports no conflict of interest related to this article.
Robert L. Barbieri, MD
Editor in Chief, OBG Management
Chair Emeritus, Department of Obstetrics and Gynecology
Brigham and Women’s Hospital
Kate Macy Ladd Distinguished Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Boston, Massachusetts
The author reports no conflict of interest related to this article.
Robert L. Barbieri, MD
Editor in Chief, OBG Management
Chair Emeritus, Department of Obstetrics and Gynecology
Brigham and Women’s Hospital
Kate Macy Ladd Distinguished Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Boston, Massachusetts
The author reports no conflict of interest related to this article.
All obstetrician-gynecologists know that pregnant patients who are Rh negative and exposed to a sufficient quantity of fetal red blood cells expressing Rh D antigen may become sensitized, producing Rh D antibodies that adversely impact future pregnancies with an Rh D-positive fetus, potentially causing hemolytic disease of the fetus and newborn. In countries where Rh D immune globulin is available, there is a consensus recommendation to administer Rh D immune globulin to Rh-negative pregnant patients at approximately 28 weeks’ gestation and at birth in order to decrease the risk of alloimmunization and hemolytic disease of the fetus and newborn in future pregnancies.1 In contrast to this global consensus, there is no worldwide agreement about how to manage Rh testing and Rh D immune globulin administration in cases of early pregnancy loss or abortion care before 12 weeks’ gestation. This editorial examines the evolving guidelines of major professional societies.
Guidelines consistent with the routine use of Rh D immune globulin in all cases of early pregnancy loss and abortion care
As of the publication date of this editorial, the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin on prevention of Rh D alloimmunization provides the following guidance based on consensus and expert opinion2:
- “Although the risk of alloimmunization is low, the consequences can be significant, and administration of Rh D immune globulin should be considered in cases of spontaneous first trimester miscarriage, especially those that are later in the first trimester.”
- “Because of the higher risk of alloimmunization, Rh D-negative women who have instrumentation for their miscarriage should receive Rh D immune globulin prophylaxis.”
- “Rh D immune globulin should be given to Rh D-negative women who have pregnancy termination either medical or surgical.”
The Society of Obstetricians and Gynaecologists of Canada (SOGC) recommends that, “After miscarriage or threatened abortion or induced abortion during the first 12 weeks of gestation, non-sensitized D-negative women should be given a minimum anti-D of 120 µg.”3
The liberal use of Rh D immune globulin in all cases of early pregnancy loss and abortion care is based, in part, on the following considerations:
- the recognized safety of Rh D immune globulin administration2,3
- the report that fetal megaloblasts may express Rh antigen as early as 38 days of gestation4
- the observation that 0.1 mL of Rh D-positive red cells may provoke an immune response in some Rh D-negative patients5-7
- the estimate that in some patients with threatened miscarriage a significant quantity of fetal blood may enter the maternal circulation.8
Guidelines that suggest restricted use of Rh D immune globulin before 7 to 8 weeks’ gestation
The Reproductive Care Program of Nova Scotia guideline from 2022 notes that “the benefits of administering Rh immune globulin before 8 weeks gestation have not been demonstrated.” Given the burden of Rh testing and Rh D immune globulin administration they suggest that clinicians may withhold Rh testing and Rh D immune globulin administration in cases less than 8 weeks’ gestation (less than 56 days) for spontaneous, threatened, or medication abortions if there is reliable pregnancy dating.9
The Dutch Association of Abortion Specialists guidelines from 2018 suggest to not provide Rh D immune globulin treatment in the following clinical situations: patients under 10 weeks’ gestation with spontaneous miscarriage or patients under 7 weeks’ gestation having an induced abortion.10
Continue to: Guidelines that suggest restricted use of Rh D immune globulin before 10 to 12 weeks’ gestation...
Guidelines that suggest restricted use of Rh D immune globulin before 10 to 12 weeks’ gestation
There are a growing number of guidelines that recommend restricting the use of Rh testing and Rh D immune globulin treatment in the management of early miscarriage and induced abortion. In 2019, the United Kingdom’s National Institute for Health and Care Excellence (NICE) recommended that for patients having a spontaneous miscarriage, Rh testing and Rh D immune globulin are not necessary before 10 weeks 0 days of gestation.11 In addition, NICE recommends, “Do not offer anti-D prophylaxis to women who are having a medical abortion up to and including 10+0 weeks’ gestation.…Consider anti-D prophylaxis for women who are rhesus D negative and are having a surgical abortion up to and including 10+0 weeks’ gestation.”11
In 2019, the National Abortion Federation (NAF) Clinical Policies Committee recommended that “…it is reasonable to forgo Rh testing and anti-D immunoglobulin for women having any type of induced abortion before 8 weeks from the last menstrual period. Prior to 8 weeks, the likelihood of fetal-maternal hemorrhage adequate to cause sensitization is negligible. Given that medication abortion is more similar to spontaneous abortion with less risk of fetal-maternal hemorrhage, forgoing Rh testing and anti-D immunoglobulin for medication abortion under 10 weeks may be considered.”12 In 2022, NAF noted, “Emerging epidemiologic and clinical evidence indicates that the risk of maternal-fetal hemorrhage caused by early abortion is negligible and Rh testing and provision of Rh immune globulin may not be necessary. It is reasonable to forego Rh testing and anti-D immunoglobulin for people having any type of abortion before 56 days and medication abortion before 70 days since the last menstrual period. The pregnancy dating at which people need Rh testing and anti-D immunoglobulin is not well established. Foregoing Rh testing and anti-D immunoglobulinfor those using medication abortion through 11 to 12 weeks may be considered.”13
In 2020 the International Federation of Gynaecology and Obstetrics (FIGO) Committee for Safe Motherhood and Newborn Health recommended, “The risk for sensitization is most probably extremely low for spontaneous abortions before 10 gestational weeks; however, data are scarce. Based on the clinical expertise of the guideline committee from the UK’s National Institute for Health and Care Excellence (NICE), it is suggested that prophylaxis should be given only to women who are having a spontaneous abortion or medical management of miscarriage after 10 and 0/7 gestational weeks. Moreover, for women who have surgical management, prophylaxis may also be considered before 10 gestational weeks.”14
In 2022 the Royal College of Obstetricians and Gynaecologists recommended that for induced abortion, medication or surgical, “a determination of Rhesus blood status may be considered if the duration of pregnancy is over 12 weeks and anti-D is available.”15 “If available, anti-D should be offered to non-sensitised RhD-negative individuals from 12 weeks of pregnancy and provided within 72 hours of the abortion.”15
In 2022, the Society of Family Planning recommended that “Rh testing and administration are not recommended prior to 12 weeks gestation for patients undergoing spontaneous, medication or uterine aspiration abortion.” “For patients under 12 weeks gestation, although not recommended, Rh testing and Rh D immune globulin administration may be considered at patient request as part of a shared decision making process.”16
In 2022, the World Health Organization (WHO) reported “There are few studies examining Rh isoimmunization in unsensitized Rh-negative individuals seeking abortion before 12 weeks of gestation.” “The evidence on the effectiveness of the intervention may favor the intervention, because fewer women in the intervention group (anti-D administration) had antibody formation after the initial pregnancy compared to women in the comparison group (no anti-D) and no harms (undesirable effects) of the intervention were noted.”17 The evidence referenced for these statements are two low-quality studies from 1972.18,19 The WHO continues, “…after consideration of the resources required, cost-effectiveness and feasibility of administering anti-D, as well as the very low certainty of evidence on effectiveness, the expert panel concluded that overall, the evidence does not favor the intervention and decided to recommend against it for gestational ages < 12 weeks, rather than < 9 weeks, as mentioned in the 2012 guidance.”17 In conclusion, the WHO recommended that “for both medical and surgical abortion at < 12 weeks: Recommend against anti-D immunoglobulin administration.”17
Guidelines that recommend restricted use of Rh D immune globulin during the first trimester, are based, in part, on the following considerations:
- there are no high-quality clinical trials demonstrating the benefit of Rh D immune globulin treatment in first trimester miscarriage and abortion care
- the Kleihauer-Betke technique cannot distinguish between maternal red blood cells expressing fetal hemoglobin (maternal F cells) and fetal cells, which has resulted in the over-estimation of the number of fetal cells in the maternal circulation20
- using a dual-label flow cytometry method that distinguishes maternal F cells and fetal red blood cells, maternal F cells usually far outnumber fetal red blood cells in the maternal circulation in the first trimester20
- among women in the first trimester undergoing uterine aspiration, the number of fetal cells in the maternal circulation is very low both before and after the procedure20
- Rh testing and Rh immune globulin administration is burdensome and expensive.16
Implications for your practice
The fundamental reason for the proliferation of divergent guidelines is that there is no evidence from high-quality randomized clinical trials demonstrating that Rh testing and Rh D immune globulin treatment in early pregnancy miscarriage or induced abortion care reduces the risk of hemolytic disease of the fetus and newborn. The Cochrane review on Rh D immune globulin administration for preventing alloimmunization among patients with spontaneous miscarriage concluded, “There are insufficient data available to evaluate the practice of anti-D administration in an unsensitized Rh-negative mother after spontaneous miscarriage.”21
Given divergent guidelines, obstetrician-gynecologists must decide on which guideline to use in their practice. Clinicians may conclude that absent high-quality evidence from clinical trials, they will continue to use the ACOG/SOGC guidelines2,3 in their practice, providing universal Rh testing and Rh D immune globulin treatment for all miscarriages and abortions, regardless of the gestational age. Other clinicians may conclude that Rh testing and Rh D immune globulin is not warranted before 8 to 12 weeks’ gestation, because the number of fetal red blood cells in the maternal circulation in cases of miscarriage and induced abortion is too low in early pregnancy to induce a maternal immune response.22 Based on recent studies demonstrating a low number of fetal red blood cells in the maternal circulation in the first trimester, family planning specialists are reducing the use of Rh testing and Rh immune globulin administration in both early pregnancy medication abortion and uterine aspiration abortion.16 With regard to Rh testing and Rh D immune globulin treatment, the future will definitely be different than the past. It is likely that many clinicians will reduce the use of Rh testing and Rh D immune globulin treatment in patients with miscarriage or induced abortion in early pregnancy. ●
All obstetrician-gynecologists know that pregnant patients who are Rh negative and exposed to a sufficient quantity of fetal red blood cells expressing Rh D antigen may become sensitized, producing Rh D antibodies that adversely impact future pregnancies with an Rh D-positive fetus, potentially causing hemolytic disease of the fetus and newborn. In countries where Rh D immune globulin is available, there is a consensus recommendation to administer Rh D immune globulin to Rh-negative pregnant patients at approximately 28 weeks’ gestation and at birth in order to decrease the risk of alloimmunization and hemolytic disease of the fetus and newborn in future pregnancies.1 In contrast to this global consensus, there is no worldwide agreement about how to manage Rh testing and Rh D immune globulin administration in cases of early pregnancy loss or abortion care before 12 weeks’ gestation. This editorial examines the evolving guidelines of major professional societies.
Guidelines consistent with the routine use of Rh D immune globulin in all cases of early pregnancy loss and abortion care
As of the publication date of this editorial, the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin on prevention of Rh D alloimmunization provides the following guidance based on consensus and expert opinion2:
- “Although the risk of alloimmunization is low, the consequences can be significant, and administration of Rh D immune globulin should be considered in cases of spontaneous first trimester miscarriage, especially those that are later in the first trimester.”
- “Because of the higher risk of alloimmunization, Rh D-negative women who have instrumentation for their miscarriage should receive Rh D immune globulin prophylaxis.”
- “Rh D immune globulin should be given to Rh D-negative women who have pregnancy termination either medical or surgical.”
The Society of Obstetricians and Gynaecologists of Canada (SOGC) recommends that, “After miscarriage or threatened abortion or induced abortion during the first 12 weeks of gestation, non-sensitized D-negative women should be given a minimum anti-D of 120 µg.”3
The liberal use of Rh D immune globulin in all cases of early pregnancy loss and abortion care is based, in part, on the following considerations:
- the recognized safety of Rh D immune globulin administration2,3
- the report that fetal megaloblasts may express Rh antigen as early as 38 days of gestation4
- the observation that 0.1 mL of Rh D-positive red cells may provoke an immune response in some Rh D-negative patients5-7
- the estimate that in some patients with threatened miscarriage a significant quantity of fetal blood may enter the maternal circulation.8
Guidelines that suggest restricted use of Rh D immune globulin before 7 to 8 weeks’ gestation
The Reproductive Care Program of Nova Scotia guideline from 2022 notes that “the benefits of administering Rh immune globulin before 8 weeks gestation have not been demonstrated.” Given the burden of Rh testing and Rh D immune globulin administration they suggest that clinicians may withhold Rh testing and Rh D immune globulin administration in cases less than 8 weeks’ gestation (less than 56 days) for spontaneous, threatened, or medication abortions if there is reliable pregnancy dating.9
The Dutch Association of Abortion Specialists guidelines from 2018 suggest to not provide Rh D immune globulin treatment in the following clinical situations: patients under 10 weeks’ gestation with spontaneous miscarriage or patients under 7 weeks’ gestation having an induced abortion.10
Continue to: Guidelines that suggest restricted use of Rh D immune globulin before 10 to 12 weeks’ gestation...
Guidelines that suggest restricted use of Rh D immune globulin before 10 to 12 weeks’ gestation
There are a growing number of guidelines that recommend restricting the use of Rh testing and Rh D immune globulin treatment in the management of early miscarriage and induced abortion. In 2019, the United Kingdom’s National Institute for Health and Care Excellence (NICE) recommended that for patients having a spontaneous miscarriage, Rh testing and Rh D immune globulin are not necessary before 10 weeks 0 days of gestation.11 In addition, NICE recommends, “Do not offer anti-D prophylaxis to women who are having a medical abortion up to and including 10+0 weeks’ gestation.…Consider anti-D prophylaxis for women who are rhesus D negative and are having a surgical abortion up to and including 10+0 weeks’ gestation.”11
In 2019, the National Abortion Federation (NAF) Clinical Policies Committee recommended that “…it is reasonable to forgo Rh testing and anti-D immunoglobulin for women having any type of induced abortion before 8 weeks from the last menstrual period. Prior to 8 weeks, the likelihood of fetal-maternal hemorrhage adequate to cause sensitization is negligible. Given that medication abortion is more similar to spontaneous abortion with less risk of fetal-maternal hemorrhage, forgoing Rh testing and anti-D immunoglobulin for medication abortion under 10 weeks may be considered.”12 In 2022, NAF noted, “Emerging epidemiologic and clinical evidence indicates that the risk of maternal-fetal hemorrhage caused by early abortion is negligible and Rh testing and provision of Rh immune globulin may not be necessary. It is reasonable to forego Rh testing and anti-D immunoglobulin for people having any type of abortion before 56 days and medication abortion before 70 days since the last menstrual period. The pregnancy dating at which people need Rh testing and anti-D immunoglobulin is not well established. Foregoing Rh testing and anti-D immunoglobulinfor those using medication abortion through 11 to 12 weeks may be considered.”13
In 2020 the International Federation of Gynaecology and Obstetrics (FIGO) Committee for Safe Motherhood and Newborn Health recommended, “The risk for sensitization is most probably extremely low for spontaneous abortions before 10 gestational weeks; however, data are scarce. Based on the clinical expertise of the guideline committee from the UK’s National Institute for Health and Care Excellence (NICE), it is suggested that prophylaxis should be given only to women who are having a spontaneous abortion or medical management of miscarriage after 10 and 0/7 gestational weeks. Moreover, for women who have surgical management, prophylaxis may also be considered before 10 gestational weeks.”14
In 2022 the Royal College of Obstetricians and Gynaecologists recommended that for induced abortion, medication or surgical, “a determination of Rhesus blood status may be considered if the duration of pregnancy is over 12 weeks and anti-D is available.”15 “If available, anti-D should be offered to non-sensitised RhD-negative individuals from 12 weeks of pregnancy and provided within 72 hours of the abortion.”15
In 2022, the Society of Family Planning recommended that “Rh testing and administration are not recommended prior to 12 weeks gestation for patients undergoing spontaneous, medication or uterine aspiration abortion.” “For patients under 12 weeks gestation, although not recommended, Rh testing and Rh D immune globulin administration may be considered at patient request as part of a shared decision making process.”16
In 2022, the World Health Organization (WHO) reported “There are few studies examining Rh isoimmunization in unsensitized Rh-negative individuals seeking abortion before 12 weeks of gestation.” “The evidence on the effectiveness of the intervention may favor the intervention, because fewer women in the intervention group (anti-D administration) had antibody formation after the initial pregnancy compared to women in the comparison group (no anti-D) and no harms (undesirable effects) of the intervention were noted.”17 The evidence referenced for these statements are two low-quality studies from 1972.18,19 The WHO continues, “…after consideration of the resources required, cost-effectiveness and feasibility of administering anti-D, as well as the very low certainty of evidence on effectiveness, the expert panel concluded that overall, the evidence does not favor the intervention and decided to recommend against it for gestational ages < 12 weeks, rather than < 9 weeks, as mentioned in the 2012 guidance.”17 In conclusion, the WHO recommended that “for both medical and surgical abortion at < 12 weeks: Recommend against anti-D immunoglobulin administration.”17
Guidelines that recommend restricted use of Rh D immune globulin during the first trimester, are based, in part, on the following considerations:
- there are no high-quality clinical trials demonstrating the benefit of Rh D immune globulin treatment in first trimester miscarriage and abortion care
- the Kleihauer-Betke technique cannot distinguish between maternal red blood cells expressing fetal hemoglobin (maternal F cells) and fetal cells, which has resulted in the over-estimation of the number of fetal cells in the maternal circulation20
- using a dual-label flow cytometry method that distinguishes maternal F cells and fetal red blood cells, maternal F cells usually far outnumber fetal red blood cells in the maternal circulation in the first trimester20
- among women in the first trimester undergoing uterine aspiration, the number of fetal cells in the maternal circulation is very low both before and after the procedure20
- Rh testing and Rh immune globulin administration is burdensome and expensive.16
Implications for your practice
The fundamental reason for the proliferation of divergent guidelines is that there is no evidence from high-quality randomized clinical trials demonstrating that Rh testing and Rh D immune globulin treatment in early pregnancy miscarriage or induced abortion care reduces the risk of hemolytic disease of the fetus and newborn. The Cochrane review on Rh D immune globulin administration for preventing alloimmunization among patients with spontaneous miscarriage concluded, “There are insufficient data available to evaluate the practice of anti-D administration in an unsensitized Rh-negative mother after spontaneous miscarriage.”21
Given divergent guidelines, obstetrician-gynecologists must decide on which guideline to use in their practice. Clinicians may conclude that absent high-quality evidence from clinical trials, they will continue to use the ACOG/SOGC guidelines2,3 in their practice, providing universal Rh testing and Rh D immune globulin treatment for all miscarriages and abortions, regardless of the gestational age. Other clinicians may conclude that Rh testing and Rh D immune globulin is not warranted before 8 to 12 weeks’ gestation, because the number of fetal red blood cells in the maternal circulation in cases of miscarriage and induced abortion is too low in early pregnancy to induce a maternal immune response.22 Based on recent studies demonstrating a low number of fetal red blood cells in the maternal circulation in the first trimester, family planning specialists are reducing the use of Rh testing and Rh immune globulin administration in both early pregnancy medication abortion and uterine aspiration abortion.16 With regard to Rh testing and Rh D immune globulin treatment, the future will definitely be different than the past. It is likely that many clinicians will reduce the use of Rh testing and Rh D immune globulin treatment in patients with miscarriage or induced abortion in early pregnancy. ●
- Sperling JD, Dahlke JD, Sutton D, et al. Prevention of Rh D alloimmunization: a comparison of four national guidelines. Am J Perinatol. 2018;35:110-119.
- Prevention of Rh D alloimmunization. Practice Bulletin No. 181. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2017;130:e57-e70.
- Fung KFK, Eason E. No. 133-Prevention of Rh alloimmunization. J Obstet Gynaecol Can. 2018;40: e1-e10.
- Bergstrom H, Nilsson LA, Nilsson L, et al. Demonstration of Rh antigens in a 38-day-old fetus. Am J Obstet Gynecol. 1967;99:130-133.
- Bowman JM. The prevention of Rh Immunization. Transfus Med Rev. 1988;2:129-150.
- Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J. 1967;97:1245-1257.
- Pollack W, Ascari WQ, Kochesky RJ, et al. Studies on Rh prophylaxis. 1. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion. 1971;11:333-339.
- Von Stein GA, Munsick RA, Stiver K, et al. Feto-maternal hemorrhage in threatened abortion. Obstet Gynecol. 1992;79:383-386.
- Rh Program of Nova Scotia. Guideline for Rh prophylaxis before 8 weeks (56 days) gestation for Early Pregnancy Complications and Medical Abortions. http://rcp.nshealth.ca/sites/default /files/rh/RhIg%20before%208%20weeks%20 Guideline_%20Jun2022_Final_2page.pdf. Accessed January 24, 2023.
- Wiebe ER, Campbell M, Aiken ARA, et al. Can we safety stop testing for Rh Status and immunizing Rh-negative women having early abortions? A comparison of Rh alloimmunization in Canada and the Netherlands. Contraception. 2019;100001. https://doi.org/10.1016/j.conx.2018.100001.
- Abortion care. National Institute for Health and Care Excellence. https://www.nice.org .uk/guidance/ng140/resources/abortion-care -pdf-66141773098693. Accessed January 24, 2023.
- Mark A, Foster AM, Grossman D. Foregoing Rh testing and anti-D immunoglobulin for women presenting for early abortion: a recommendation from the National Abortion Federation’s Clinical Policies Committee. Contraception. 2019;99:265-266.
- National Abortion Federation. 2022 Clinical Policy Guidelines for Abortion Care. https: //prochoice.org/wp-content/uploads/2022 -CPGs.pdf. Accessed January 24, 2023.
- Visser GHA, Thommesen T, Di Renzo GC, et al. FIGO Safe Motherhood and Newborn Health Committee. Int J Gynecol Obstet. 2021;152: 144-147.
- Making abortion safe: RCOG’s global initiative to advocate for women’s health. https://www .rcog.org.uk/media/geify5bx/abortion-care-best -practice-paper-april-2022.pdf. Accessed January 24, 2023.
- Horvath S, Goyal V, Traxler S, et al. Society of Family Planning committee consensus on Rh testing in early pregnancy. Contraception. 2022;114:1-5.
- World Health Organization. Abortion care guideline. https://www.who.int/publications/i/ item/9789240039483. Accessed January 24, 2023.
- Gavin P. Rhesus sensitization in abortion. Obstet Gynecol. 1972;39:37-40.
- Goldman J, Eckerling B. Rh immunization in spontaneous abortion. Acta Eur Fertil. 1972;3:253254.
- Horvath S, Tsao P, Huang ZY, et al. The concentration of fetal red blood cells in first-trimester pregnant women undergoing uterine aspiration is below the calculated threshold for Rh sensitization. Contraception. 2020;102:1-6.
- Karanth L, Jaafar SH, Kanagasabai S, et al. Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunization. Cochrane Database Syst Rev. 2023;CD009617.
- Gilmore E, Sonalkar S, Schreiber CA. Use of Rh immune globulin in first-trimester abortion and miscarriage. Obstet Gynecol. 2023;141:219-222.
- Sperling JD, Dahlke JD, Sutton D, et al. Prevention of Rh D alloimmunization: a comparison of four national guidelines. Am J Perinatol. 2018;35:110-119.
- Prevention of Rh D alloimmunization. Practice Bulletin No. 181. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2017;130:e57-e70.
- Fung KFK, Eason E. No. 133-Prevention of Rh alloimmunization. J Obstet Gynaecol Can. 2018;40: e1-e10.
- Bergstrom H, Nilsson LA, Nilsson L, et al. Demonstration of Rh antigens in a 38-day-old fetus. Am J Obstet Gynecol. 1967;99:130-133.
- Bowman JM. The prevention of Rh Immunization. Transfus Med Rev. 1988;2:129-150.
- Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J. 1967;97:1245-1257.
- Pollack W, Ascari WQ, Kochesky RJ, et al. Studies on Rh prophylaxis. 1. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion. 1971;11:333-339.
- Von Stein GA, Munsick RA, Stiver K, et al. Feto-maternal hemorrhage in threatened abortion. Obstet Gynecol. 1992;79:383-386.
- Rh Program of Nova Scotia. Guideline for Rh prophylaxis before 8 weeks (56 days) gestation for Early Pregnancy Complications and Medical Abortions. http://rcp.nshealth.ca/sites/default /files/rh/RhIg%20before%208%20weeks%20 Guideline_%20Jun2022_Final_2page.pdf. Accessed January 24, 2023.
- Wiebe ER, Campbell M, Aiken ARA, et al. Can we safety stop testing for Rh Status and immunizing Rh-negative women having early abortions? A comparison of Rh alloimmunization in Canada and the Netherlands. Contraception. 2019;100001. https://doi.org/10.1016/j.conx.2018.100001.
- Abortion care. National Institute for Health and Care Excellence. https://www.nice.org .uk/guidance/ng140/resources/abortion-care -pdf-66141773098693. Accessed January 24, 2023.
- Mark A, Foster AM, Grossman D. Foregoing Rh testing and anti-D immunoglobulin for women presenting for early abortion: a recommendation from the National Abortion Federation’s Clinical Policies Committee. Contraception. 2019;99:265-266.
- National Abortion Federation. 2022 Clinical Policy Guidelines for Abortion Care. https: //prochoice.org/wp-content/uploads/2022 -CPGs.pdf. Accessed January 24, 2023.
- Visser GHA, Thommesen T, Di Renzo GC, et al. FIGO Safe Motherhood and Newborn Health Committee. Int J Gynecol Obstet. 2021;152: 144-147.
- Making abortion safe: RCOG’s global initiative to advocate for women’s health. https://www .rcog.org.uk/media/geify5bx/abortion-care-best -practice-paper-april-2022.pdf. Accessed January 24, 2023.
- Horvath S, Goyal V, Traxler S, et al. Society of Family Planning committee consensus on Rh testing in early pregnancy. Contraception. 2022;114:1-5.
- World Health Organization. Abortion care guideline. https://www.who.int/publications/i/ item/9789240039483. Accessed January 24, 2023.
- Gavin P. Rhesus sensitization in abortion. Obstet Gynecol. 1972;39:37-40.
- Goldman J, Eckerling B. Rh immunization in spontaneous abortion. Acta Eur Fertil. 1972;3:253254.
- Horvath S, Tsao P, Huang ZY, et al. The concentration of fetal red blood cells in first-trimester pregnant women undergoing uterine aspiration is below the calculated threshold for Rh sensitization. Contraception. 2020;102:1-6.
- Karanth L, Jaafar SH, Kanagasabai S, et al. Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunization. Cochrane Database Syst Rev. 2023;CD009617.
- Gilmore E, Sonalkar S, Schreiber CA. Use of Rh immune globulin in first-trimester abortion and miscarriage. Obstet Gynecol. 2023;141:219-222.
Immunodeficiencies tied to psychiatric disorders in offspring
new research suggests.
Results from a cohort study of more than 4.2 million individuals showed that offspring of mothers with PIDs had a 17% increased risk for a psychiatric disorder and a 20% increased risk for suicidal behavior, compared with their peers with mothers who did not have PIDs.
The risk was more pronounced in offspring of mothers with both PIDs and autoimmune diseases. These risks remained after strictly controlling for different covariates, such as the parents’ psychiatric history, offspring PIDs, and offspring autoimmune diseases.
The investigators, led by Josef Isung, MD, PhD, Centre for Psychiatry Research, department of clinical neuroscience, Karolinska Institutet, Stockholm, noted that they could not “pinpoint a precise causal mechanism” underlying these findings.
Still, “the results add to the existing literature suggesting that the intrauterine immune environment may have implications for fetal neurodevelopment and that a compromised maternal immune system during pregnancy may be a risk factor for psychiatric disorders and suicidal behavior in their offspring in the long term,” they wrote.
The findings were published online in JAMA Psychiatry.
‘Natural experiment’
Maternal immune activation (MIA) is “an overarching term for aberrant and disrupted immune activity in the mother during gestation [and] has long been of interest in relation to adverse health outcomes in the offspring,” Dr. Isung noted.
“In relation to negative psychiatric outcomes, there is an abundance of preclinical evidence that has shown a negative impact on offspring secondary to MIA. And in humans, there are several observational studies supporting this link,” he said in an interview.
Dr. Isung added that PIDs are “rare conditions” known to be associated with repeated infections and high rates of autoimmune diseases, causing substantial disability.
“PIDs represent an interesting ‘natural experiment’ for researchers to understand more about the association between immune system dysfunctions and mental health,” he said.
Dr. Isung’s group previously showed that individuals with PIDs have increased odds of psychiatric disorders and suicidal behavior. The link was more pronounced in women with PIDs – and was even more pronounced in those with both PIDs and autoimmune diseases.
In the current study, “we wanted to see whether offspring of individuals were differentially at risk of psychiatric disorders and suicidal behavior, depending on being offspring of mothers or fathers with PIDs,” Dr. Isung said.
“Our hypothesis was that mothers with PIDs would have an increased risk of having offspring with neuropsychiatric outcomes, and that this risk could be due to MIA,” he added.
The researchers turned to Swedish nationwide health and administrative registers. They analyzed data on all individuals with diagnoses of PIDs identified between 1973 and 2013. Offspring born prior to 2003 were included, and parent-offspring pairs in which both parents had a history of PIDs were excluded.
The final study sample consisted of 4,294,169 offspring (51.4% boys). Of these participants, 7,270 (0.17%) had a parent with PIDs.
The researchers identified lifetime records of 10 psychiatric disorders: obsessive-compulsive disorder, ADHD, autism spectrum disorders, schizophrenia and other psychotic disorders, bipolar disorders, major depressive disorder and other mood disorders, anxiety and stress-related disorders, eating disorders, substance use disorders, and Tourette syndrome and chronic tic disorders.
The investigators included parental birth year, psychopathology, suicide attempts, suicide deaths, and autoimmune diseases as covariates, as well as offsprings’ birth year and gender.
Elucidation needed
Results showed that, of the 4,676 offspring of mothers with PID, 17.1% had a psychiatric disorder versus 12.7% of offspring of mothers without PIDs. This translated “into a 17% increased risk for offspring of mothers with PIDs in the fully adjusted model,” the investigators reported.
The risk was even higher for offspring of mothers who had not only PIDs but also one of six of the individual psychiatric disorders, with incident rate ratios ranging from 1.15 to 1.71.
“In fully adjusted models, offspring of mothers with PIDs had an increased risk of any psychiatric disorder, while no such risks were observed in offspring of fathers with PIDs” (IRR, 1.17 vs. 1.03; P < .001), the researchers reported.
A higher risk for suicidal behavior was also observed among offspring of mothers with PIDS, in contrast to those of fathers with PIDs (IRR, 1.2 vs. 1.1; P = .01).
The greatest risk for any psychiatric disorder, as well as suicidal behavior, was found in offspring of mothers who had both PIDs and autoimmune diseases (IRRs, 1.24 and 1.44, respectively).
“The results could be seen as substantiating the hypothesis that immune disruption may be important in the pathophysiology of psychiatric disorders and suicidal behavior,” Dr. Isung said.
“Furthermore, the fact that only offspring of mothers and not offspring of fathers with PIDs had this association would align with our hypothesis that MIA is of importance,” he added.
However, he noted that “the specific mechanisms are most likely multifactorial and remain to be elucidated.”
Important piece of the puzzle?
In a comment, Michael Eriksen Benros, MD, PhD, professor of immunopsychiatry, department of immunology and microbiology, health, and medical sciences, University of Copenhagen, said this was a “high-quality study” that used a “rich data source.”
Dr. Benros, who is also head of research (biological and precision psychiatry) at the Copenhagen Research Centre for Mental Health, Copenhagen University Hospital, was not involved with the current study.
He noted that prior studies, including some conducted by his own group, have shown that maternal infections overall did not seem to be “specifically linked to mental disorders in the offspring.”
However, “specific maternal infections or specific brain-reactive antibodies during the pregnancy period have been shown to be associated with neurodevelopmental outcomes among the children,” such as intellectual disability, he said.
Regarding direct clinical implications of the study, “it is important to note that the increased risk of psychiatric disorders and suicidality in the offspring of mothers with PID were small,” Dr. Benros said.
“However, it adds an important part to the scientific puzzle regarding the role of maternal immune activation during pregnancy and the risk of mental disorders,” he added.
The study was funded by the Söderström König Foundation and the Fredrik and Ingrid Thuring Foundation. Neither Dr. Isung nor Dr. Benros reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Results from a cohort study of more than 4.2 million individuals showed that offspring of mothers with PIDs had a 17% increased risk for a psychiatric disorder and a 20% increased risk for suicidal behavior, compared with their peers with mothers who did not have PIDs.
The risk was more pronounced in offspring of mothers with both PIDs and autoimmune diseases. These risks remained after strictly controlling for different covariates, such as the parents’ psychiatric history, offspring PIDs, and offspring autoimmune diseases.
The investigators, led by Josef Isung, MD, PhD, Centre for Psychiatry Research, department of clinical neuroscience, Karolinska Institutet, Stockholm, noted that they could not “pinpoint a precise causal mechanism” underlying these findings.
Still, “the results add to the existing literature suggesting that the intrauterine immune environment may have implications for fetal neurodevelopment and that a compromised maternal immune system during pregnancy may be a risk factor for psychiatric disorders and suicidal behavior in their offspring in the long term,” they wrote.
The findings were published online in JAMA Psychiatry.
‘Natural experiment’
Maternal immune activation (MIA) is “an overarching term for aberrant and disrupted immune activity in the mother during gestation [and] has long been of interest in relation to adverse health outcomes in the offspring,” Dr. Isung noted.
“In relation to negative psychiatric outcomes, there is an abundance of preclinical evidence that has shown a negative impact on offspring secondary to MIA. And in humans, there are several observational studies supporting this link,” he said in an interview.
Dr. Isung added that PIDs are “rare conditions” known to be associated with repeated infections and high rates of autoimmune diseases, causing substantial disability.
“PIDs represent an interesting ‘natural experiment’ for researchers to understand more about the association between immune system dysfunctions and mental health,” he said.
Dr. Isung’s group previously showed that individuals with PIDs have increased odds of psychiatric disorders and suicidal behavior. The link was more pronounced in women with PIDs – and was even more pronounced in those with both PIDs and autoimmune diseases.
In the current study, “we wanted to see whether offspring of individuals were differentially at risk of psychiatric disorders and suicidal behavior, depending on being offspring of mothers or fathers with PIDs,” Dr. Isung said.
“Our hypothesis was that mothers with PIDs would have an increased risk of having offspring with neuropsychiatric outcomes, and that this risk could be due to MIA,” he added.
The researchers turned to Swedish nationwide health and administrative registers. They analyzed data on all individuals with diagnoses of PIDs identified between 1973 and 2013. Offspring born prior to 2003 were included, and parent-offspring pairs in which both parents had a history of PIDs were excluded.
The final study sample consisted of 4,294,169 offspring (51.4% boys). Of these participants, 7,270 (0.17%) had a parent with PIDs.
The researchers identified lifetime records of 10 psychiatric disorders: obsessive-compulsive disorder, ADHD, autism spectrum disorders, schizophrenia and other psychotic disorders, bipolar disorders, major depressive disorder and other mood disorders, anxiety and stress-related disorders, eating disorders, substance use disorders, and Tourette syndrome and chronic tic disorders.
The investigators included parental birth year, psychopathology, suicide attempts, suicide deaths, and autoimmune diseases as covariates, as well as offsprings’ birth year and gender.
Elucidation needed
Results showed that, of the 4,676 offspring of mothers with PID, 17.1% had a psychiatric disorder versus 12.7% of offspring of mothers without PIDs. This translated “into a 17% increased risk for offspring of mothers with PIDs in the fully adjusted model,” the investigators reported.
The risk was even higher for offspring of mothers who had not only PIDs but also one of six of the individual psychiatric disorders, with incident rate ratios ranging from 1.15 to 1.71.
“In fully adjusted models, offspring of mothers with PIDs had an increased risk of any psychiatric disorder, while no such risks were observed in offspring of fathers with PIDs” (IRR, 1.17 vs. 1.03; P < .001), the researchers reported.
A higher risk for suicidal behavior was also observed among offspring of mothers with PIDS, in contrast to those of fathers with PIDs (IRR, 1.2 vs. 1.1; P = .01).
The greatest risk for any psychiatric disorder, as well as suicidal behavior, was found in offspring of mothers who had both PIDs and autoimmune diseases (IRRs, 1.24 and 1.44, respectively).
“The results could be seen as substantiating the hypothesis that immune disruption may be important in the pathophysiology of psychiatric disorders and suicidal behavior,” Dr. Isung said.
“Furthermore, the fact that only offspring of mothers and not offspring of fathers with PIDs had this association would align with our hypothesis that MIA is of importance,” he added.
However, he noted that “the specific mechanisms are most likely multifactorial and remain to be elucidated.”
Important piece of the puzzle?
In a comment, Michael Eriksen Benros, MD, PhD, professor of immunopsychiatry, department of immunology and microbiology, health, and medical sciences, University of Copenhagen, said this was a “high-quality study” that used a “rich data source.”
Dr. Benros, who is also head of research (biological and precision psychiatry) at the Copenhagen Research Centre for Mental Health, Copenhagen University Hospital, was not involved with the current study.
He noted that prior studies, including some conducted by his own group, have shown that maternal infections overall did not seem to be “specifically linked to mental disorders in the offspring.”
However, “specific maternal infections or specific brain-reactive antibodies during the pregnancy period have been shown to be associated with neurodevelopmental outcomes among the children,” such as intellectual disability, he said.
Regarding direct clinical implications of the study, “it is important to note that the increased risk of psychiatric disorders and suicidality in the offspring of mothers with PID were small,” Dr. Benros said.
“However, it adds an important part to the scientific puzzle regarding the role of maternal immune activation during pregnancy and the risk of mental disorders,” he added.
The study was funded by the Söderström König Foundation and the Fredrik and Ingrid Thuring Foundation. Neither Dr. Isung nor Dr. Benros reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Results from a cohort study of more than 4.2 million individuals showed that offspring of mothers with PIDs had a 17% increased risk for a psychiatric disorder and a 20% increased risk for suicidal behavior, compared with their peers with mothers who did not have PIDs.
The risk was more pronounced in offspring of mothers with both PIDs and autoimmune diseases. These risks remained after strictly controlling for different covariates, such as the parents’ psychiatric history, offspring PIDs, and offspring autoimmune diseases.
The investigators, led by Josef Isung, MD, PhD, Centre for Psychiatry Research, department of clinical neuroscience, Karolinska Institutet, Stockholm, noted that they could not “pinpoint a precise causal mechanism” underlying these findings.
Still, “the results add to the existing literature suggesting that the intrauterine immune environment may have implications for fetal neurodevelopment and that a compromised maternal immune system during pregnancy may be a risk factor for psychiatric disorders and suicidal behavior in their offspring in the long term,” they wrote.
The findings were published online in JAMA Psychiatry.
‘Natural experiment’
Maternal immune activation (MIA) is “an overarching term for aberrant and disrupted immune activity in the mother during gestation [and] has long been of interest in relation to adverse health outcomes in the offspring,” Dr. Isung noted.
“In relation to negative psychiatric outcomes, there is an abundance of preclinical evidence that has shown a negative impact on offspring secondary to MIA. And in humans, there are several observational studies supporting this link,” he said in an interview.
Dr. Isung added that PIDs are “rare conditions” known to be associated with repeated infections and high rates of autoimmune diseases, causing substantial disability.
“PIDs represent an interesting ‘natural experiment’ for researchers to understand more about the association between immune system dysfunctions and mental health,” he said.
Dr. Isung’s group previously showed that individuals with PIDs have increased odds of psychiatric disorders and suicidal behavior. The link was more pronounced in women with PIDs – and was even more pronounced in those with both PIDs and autoimmune diseases.
In the current study, “we wanted to see whether offspring of individuals were differentially at risk of psychiatric disorders and suicidal behavior, depending on being offspring of mothers or fathers with PIDs,” Dr. Isung said.
“Our hypothesis was that mothers with PIDs would have an increased risk of having offspring with neuropsychiatric outcomes, and that this risk could be due to MIA,” he added.
The researchers turned to Swedish nationwide health and administrative registers. They analyzed data on all individuals with diagnoses of PIDs identified between 1973 and 2013. Offspring born prior to 2003 were included, and parent-offspring pairs in which both parents had a history of PIDs were excluded.
The final study sample consisted of 4,294,169 offspring (51.4% boys). Of these participants, 7,270 (0.17%) had a parent with PIDs.
The researchers identified lifetime records of 10 psychiatric disorders: obsessive-compulsive disorder, ADHD, autism spectrum disorders, schizophrenia and other psychotic disorders, bipolar disorders, major depressive disorder and other mood disorders, anxiety and stress-related disorders, eating disorders, substance use disorders, and Tourette syndrome and chronic tic disorders.
The investigators included parental birth year, psychopathology, suicide attempts, suicide deaths, and autoimmune diseases as covariates, as well as offsprings’ birth year and gender.
Elucidation needed
Results showed that, of the 4,676 offspring of mothers with PID, 17.1% had a psychiatric disorder versus 12.7% of offspring of mothers without PIDs. This translated “into a 17% increased risk for offspring of mothers with PIDs in the fully adjusted model,” the investigators reported.
The risk was even higher for offspring of mothers who had not only PIDs but also one of six of the individual psychiatric disorders, with incident rate ratios ranging from 1.15 to 1.71.
“In fully adjusted models, offspring of mothers with PIDs had an increased risk of any psychiatric disorder, while no such risks were observed in offspring of fathers with PIDs” (IRR, 1.17 vs. 1.03; P < .001), the researchers reported.
A higher risk for suicidal behavior was also observed among offspring of mothers with PIDS, in contrast to those of fathers with PIDs (IRR, 1.2 vs. 1.1; P = .01).
The greatest risk for any psychiatric disorder, as well as suicidal behavior, was found in offspring of mothers who had both PIDs and autoimmune diseases (IRRs, 1.24 and 1.44, respectively).
“The results could be seen as substantiating the hypothesis that immune disruption may be important in the pathophysiology of psychiatric disorders and suicidal behavior,” Dr. Isung said.
“Furthermore, the fact that only offspring of mothers and not offspring of fathers with PIDs had this association would align with our hypothesis that MIA is of importance,” he added.
However, he noted that “the specific mechanisms are most likely multifactorial and remain to be elucidated.”
Important piece of the puzzle?
In a comment, Michael Eriksen Benros, MD, PhD, professor of immunopsychiatry, department of immunology and microbiology, health, and medical sciences, University of Copenhagen, said this was a “high-quality study” that used a “rich data source.”
Dr. Benros, who is also head of research (biological and precision psychiatry) at the Copenhagen Research Centre for Mental Health, Copenhagen University Hospital, was not involved with the current study.
He noted that prior studies, including some conducted by his own group, have shown that maternal infections overall did not seem to be “specifically linked to mental disorders in the offspring.”
However, “specific maternal infections or specific brain-reactive antibodies during the pregnancy period have been shown to be associated with neurodevelopmental outcomes among the children,” such as intellectual disability, he said.
Regarding direct clinical implications of the study, “it is important to note that the increased risk of psychiatric disorders and suicidality in the offspring of mothers with PID were small,” Dr. Benros said.
“However, it adds an important part to the scientific puzzle regarding the role of maternal immune activation during pregnancy and the risk of mental disorders,” he added.
The study was funded by the Söderström König Foundation and the Fredrik and Ingrid Thuring Foundation. Neither Dr. Isung nor Dr. Benros reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM JAMA PSYCHIATRY