Women's Health

TOPLINE:

Women with steatotic liver disease (SLD) related to alcohol consumption are at greater risk of mortality than men with the same condition, new research suggested.

METHODOLOGY:

• Researchers analyzed data from the US National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), which included standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake.
• Among 10,007 participants aged 20 years and older (mean age, 42 years; 50.3% men) who were included and followed for a median of 26.7 years, 1461 had metabolic dysfunction–associated steatotic liver disease (MASLD), 105 alcohol-related liver disease (ALD), 225 metabolic dysfunction-associated and alcohol-related liver disease (MetALD), 180 other types of SLD, and 8036 no SLD.
• Researchers examined SLD-associated risks for all-cause mortality after adjustment for baseline age, smoking status, systolic blood pressure, antihypertensives, type 2 diabetes, diabetic medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, lipid-lowering therapy, race, and family income.

TAKEAWAY:

• In men, the prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, whereas the corresponding prevalence among women was 10.3%, 1.2%, and 0.3%, respectively.
• In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex compared with those without SLD.
• In contrast, MetALD was associated with an 83% higher hazard of all-cause mortality in women (hazard ratio [HR], 1.83), but not significantly associated with mortality in men.
• ALD was significantly associated with all-cause mortality in both sexes, with a greater magnitude in women than men (HRs, 3.49 vs 1.89, respectively) — the equivalent of about a 160% higher mortality risk for women.
• With regard to SLD severity, the trend across worsening phenotypes (ie, MASLD, MetALD, or ALD) was significant for sex differences in mortality but not in prevalence.

IN PRACTICE:

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” the authors wrote.

SOURCE:

The study, led by Hongwei Ji of Qingdao University, Qingdao, Shandong, China, and Susan Cheng, MD, Cedars-Sinai Medical Center, Los Angeles, was published in the February issue of Journal of Hepatology.

LIMITATIONS:

The study data came from NHANES III, which was conducted between 1988 and 1994. This is a potential limitation, as the prevalence of metabolic dysfunction and alcohol use may have changed since then.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, the National Institutes of Health, and the NIH National Center for Advancing Translational Sciences UCLA Clinical and Translational Research Center. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with steatotic liver disease (SLD) related to alcohol consumption are at greater risk of mortality than men with the same condition, new research suggested.

METHODOLOGY:

• Researchers analyzed data from the US National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), which included standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake.
• Among 10,007 participants aged 20 years and older (mean age, 42 years; 50.3% men) who were included and followed for a median of 26.7 years, 1461 had metabolic dysfunction–associated steatotic liver disease (MASLD), 105 alcohol-related liver disease (ALD), 225 metabolic dysfunction-associated and alcohol-related liver disease (MetALD), 180 other types of SLD, and 8036 no SLD.
• Researchers examined SLD-associated risks for all-cause mortality after adjustment for baseline age, smoking status, systolic blood pressure, antihypertensives, type 2 diabetes, diabetic medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, lipid-lowering therapy, race, and family income.

TAKEAWAY:

• In men, the prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, whereas the corresponding prevalence among women was 10.3%, 1.2%, and 0.3%, respectively.
• In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex compared with those without SLD.
• In contrast, MetALD was associated with an 83% higher hazard of all-cause mortality in women (hazard ratio [HR], 1.83), but not significantly associated with mortality in men.
• ALD was significantly associated with all-cause mortality in both sexes, with a greater magnitude in women than men (HRs, 3.49 vs 1.89, respectively) — the equivalent of about a 160% higher mortality risk for women.
• With regard to SLD severity, the trend across worsening phenotypes (ie, MASLD, MetALD, or ALD) was significant for sex differences in mortality but not in prevalence.

IN PRACTICE:

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” the authors wrote.

SOURCE:

The study, led by Hongwei Ji of Qingdao University, Qingdao, Shandong, China, and Susan Cheng, MD, Cedars-Sinai Medical Center, Los Angeles, was published in the February issue of Journal of Hepatology.

LIMITATIONS:

The study data came from NHANES III, which was conducted between 1988 and 1994. This is a potential limitation, as the prevalence of metabolic dysfunction and alcohol use may have changed since then.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, the National Institutes of Health, and the NIH National Center for Advancing Translational Sciences UCLA Clinical and Translational Research Center. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with steatotic liver disease (SLD) related to alcohol consumption are at greater risk of mortality than men with the same condition, new research suggested.

METHODOLOGY:

• Researchers analyzed data from the US National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), which included standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake.
• Among 10,007 participants aged 20 years and older (mean age, 42 years; 50.3% men) who were included and followed for a median of 26.7 years, 1461 had metabolic dysfunction–associated steatotic liver disease (MASLD), 105 alcohol-related liver disease (ALD), 225 metabolic dysfunction-associated and alcohol-related liver disease (MetALD), 180 other types of SLD, and 8036 no SLD.
• Researchers examined SLD-associated risks for all-cause mortality after adjustment for baseline age, smoking status, systolic blood pressure, antihypertensives, type 2 diabetes, diabetic medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, lipid-lowering therapy, race, and family income.

TAKEAWAY:

• In men, the prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, whereas the corresponding prevalence among women was 10.3%, 1.2%, and 0.3%, respectively.
• In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex compared with those without SLD.
• In contrast, MetALD was associated with an 83% higher hazard of all-cause mortality in women (hazard ratio [HR], 1.83), but not significantly associated with mortality in men.
• ALD was significantly associated with all-cause mortality in both sexes, with a greater magnitude in women than men (HRs, 3.49 vs 1.89, respectively) — the equivalent of about a 160% higher mortality risk for women.
• With regard to SLD severity, the trend across worsening phenotypes (ie, MASLD, MetALD, or ALD) was significant for sex differences in mortality but not in prevalence.

IN PRACTICE:

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” the authors wrote.

SOURCE:

The study, led by Hongwei Ji of Qingdao University, Qingdao, Shandong, China, and Susan Cheng, MD, Cedars-Sinai Medical Center, Los Angeles, was published in the February issue of Journal of Hepatology.

LIMITATIONS:

The study data came from NHANES III, which was conducted between 1988 and 1994. This is a potential limitation, as the prevalence of metabolic dysfunction and alcohol use may have changed since then.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, the National Institutes of Health, and the NIH National Center for Advancing Translational Sciences UCLA Clinical and Translational Research Center. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Women may gain greater health benefits from regular physical activity at equivalent or lower doses of activity, compared with men, according to data from more than 400,000 US adults. 

Over two decades, with any regular physical activity, all-cause mortality risk was reduced by 24% in women vs 15% in men, and cardiovascular mortality risk was reduced by 36% and 14%, respectively, compared with inactivity, researchers found. 

Participating in strength training exercises (vs not) was associated with a reduced risk for all-cause death of 19% in women and 11% men and reductions in cardiovascular death of 30% and 11%, respectively.

“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” co–lead author Martha Gulati, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement. “The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivizing notion that we hope women will take to heart.”

The study was published online February 19 in the Journal of the American College of Cardiology. 
 

Sex-Specific Exercise Advice? 

The findings are based on leisure-time physical activity data collected over roughly 20 years via the National Health Interview Survey for 412,413 US adults aged 27-61 years. During roughly 4.9 million person-years of follow-up, there were 39,935 all-cause deaths and 11,670 cardiovascular deaths.

Both men and women achieved a peak survival benefit at 300 minutes of weekly moderate to vigorous aerobic physical activity. But the mortality reduction was substantially greater in women than in men for the same amount of regular exercise (24% vs 18%). 

Similarly, for any given dose of physical activity leading up to 300 minutes per week, women derived proportionately greater survival benefits than did men, the authors reported. 

“Importantly, the greater magnitude of physical activity-related survival benefit in women than men was consistently found across varied measures and types of physical activity including frequency, duration per session, and intensity of aerobic physical activity, as well as frequency of muscle strengthening activities,” they wrote. 

They say multiple factors, including variations in anatomy and physiology, may account for the differences in outcomes between men and women. For example, compared with men, women may use more respiratory, metabolic, and strength demands to conduct the same movement and in turn, reap greater health benefits.

The study also showed only 33% of women and 43% of men regularly engaged in aerobic physical activity, whereas only 20% of women and 28% of men completed a weekly strength training session.

“We hope this study will help everyone, especially women, understand they are poised to gain tremendous benefits from exercise,” senior author Susan Cheng, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement.

In an accompanying editorial, Wael A. Jaber, MD, and Erika Hutt, MD, from Cleveland Clinic Ohio, wrote that this analysis “brings us one step farther in gaining insights into the role and influence of physiological responses to exercise with a sex-specific lens.” 

The study is “well designed and adds important information to the body of literature that can potentially close the gender gap and optimize sex-specific physical activity recommendations by policy makers and societal guidelines,” they wrote. 

“This study emphasizes that there is no singular approach for exercise. A person’s physical activity needs and goals may change based on their age, health status, and schedule — but the value of any type of exercise is irrefutable,” Eric J. Shiroma, ScD, with the National Heart, Lung, and Blood Institute, said in a statement. 

The study was supported in part by grants from the National Institutes of Health. The authors and editorial writers have declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Women may gain greater health benefits from regular physical activity at equivalent or lower doses of activity, compared with men, according to data from more than 400,000 US adults. 

Over two decades, with any regular physical activity, all-cause mortality risk was reduced by 24% in women vs 15% in men, and cardiovascular mortality risk was reduced by 36% and 14%, respectively, compared with inactivity, researchers found. 

Participating in strength training exercises (vs not) was associated with a reduced risk for all-cause death of 19% in women and 11% men and reductions in cardiovascular death of 30% and 11%, respectively.

“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” co–lead author Martha Gulati, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement. “The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivizing notion that we hope women will take to heart.”

The study was published online February 19 in the Journal of the American College of Cardiology. 
 

Sex-Specific Exercise Advice? 

The findings are based on leisure-time physical activity data collected over roughly 20 years via the National Health Interview Survey for 412,413 US adults aged 27-61 years. During roughly 4.9 million person-years of follow-up, there were 39,935 all-cause deaths and 11,670 cardiovascular deaths.

Both men and women achieved a peak survival benefit at 300 minutes of weekly moderate to vigorous aerobic physical activity. But the mortality reduction was substantially greater in women than in men for the same amount of regular exercise (24% vs 18%). 

Similarly, for any given dose of physical activity leading up to 300 minutes per week, women derived proportionately greater survival benefits than did men, the authors reported. 

“Importantly, the greater magnitude of physical activity-related survival benefit in women than men was consistently found across varied measures and types of physical activity including frequency, duration per session, and intensity of aerobic physical activity, as well as frequency of muscle strengthening activities,” they wrote. 

They say multiple factors, including variations in anatomy and physiology, may account for the differences in outcomes between men and women. For example, compared with men, women may use more respiratory, metabolic, and strength demands to conduct the same movement and in turn, reap greater health benefits.

The study also showed only 33% of women and 43% of men regularly engaged in aerobic physical activity, whereas only 20% of women and 28% of men completed a weekly strength training session.

“We hope this study will help everyone, especially women, understand they are poised to gain tremendous benefits from exercise,” senior author Susan Cheng, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement.

In an accompanying editorial, Wael A. Jaber, MD, and Erika Hutt, MD, from Cleveland Clinic Ohio, wrote that this analysis “brings us one step farther in gaining insights into the role and influence of physiological responses to exercise with a sex-specific lens.” 

The study is “well designed and adds important information to the body of literature that can potentially close the gender gap and optimize sex-specific physical activity recommendations by policy makers and societal guidelines,” they wrote. 

“This study emphasizes that there is no singular approach for exercise. A person’s physical activity needs and goals may change based on their age, health status, and schedule — but the value of any type of exercise is irrefutable,” Eric J. Shiroma, ScD, with the National Heart, Lung, and Blood Institute, said in a statement. 

The study was supported in part by grants from the National Institutes of Health. The authors and editorial writers have declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Women may gain greater health benefits from regular physical activity at equivalent or lower doses of activity, compared with men, according to data from more than 400,000 US adults. 

Over two decades, with any regular physical activity, all-cause mortality risk was reduced by 24% in women vs 15% in men, and cardiovascular mortality risk was reduced by 36% and 14%, respectively, compared with inactivity, researchers found. 

Participating in strength training exercises (vs not) was associated with a reduced risk for all-cause death of 19% in women and 11% men and reductions in cardiovascular death of 30% and 11%, respectively.

“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” co–lead author Martha Gulati, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement. “The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivizing notion that we hope women will take to heart.”

The study was published online February 19 in the Journal of the American College of Cardiology. 
 

Sex-Specific Exercise Advice? 

The findings are based on leisure-time physical activity data collected over roughly 20 years via the National Health Interview Survey for 412,413 US adults aged 27-61 years. During roughly 4.9 million person-years of follow-up, there were 39,935 all-cause deaths and 11,670 cardiovascular deaths.

Both men and women achieved a peak survival benefit at 300 minutes of weekly moderate to vigorous aerobic physical activity. But the mortality reduction was substantially greater in women than in men for the same amount of regular exercise (24% vs 18%). 

Similarly, for any given dose of physical activity leading up to 300 minutes per week, women derived proportionately greater survival benefits than did men, the authors reported. 

“Importantly, the greater magnitude of physical activity-related survival benefit in women than men was consistently found across varied measures and types of physical activity including frequency, duration per session, and intensity of aerobic physical activity, as well as frequency of muscle strengthening activities,” they wrote. 

They say multiple factors, including variations in anatomy and physiology, may account for the differences in outcomes between men and women. For example, compared with men, women may use more respiratory, metabolic, and strength demands to conduct the same movement and in turn, reap greater health benefits.

The study also showed only 33% of women and 43% of men regularly engaged in aerobic physical activity, whereas only 20% of women and 28% of men completed a weekly strength training session.

“We hope this study will help everyone, especially women, understand they are poised to gain tremendous benefits from exercise,” senior author Susan Cheng, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement.

In an accompanying editorial, Wael A. Jaber, MD, and Erika Hutt, MD, from Cleveland Clinic Ohio, wrote that this analysis “brings us one step farther in gaining insights into the role and influence of physiological responses to exercise with a sex-specific lens.” 

The study is “well designed and adds important information to the body of literature that can potentially close the gender gap and optimize sex-specific physical activity recommendations by policy makers and societal guidelines,” they wrote. 

“This study emphasizes that there is no singular approach for exercise. A person’s physical activity needs and goals may change based on their age, health status, and schedule — but the value of any type of exercise is irrefutable,” Eric J. Shiroma, ScD, with the National Heart, Lung, and Blood Institute, said in a statement. 

The study was supported in part by grants from the National Institutes of Health. The authors and editorial writers have declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Screening mammograms miss close to one in eight breast cancers. But early research suggests artificial intelligence (AI) could close this detection gap and markedly improve early diagnosis of the disease. Still, questions remain regarding how to best incorporate AI into screenings and whether it’s too soon to deploy the technology.

Already, some radiology clinics are offering AI analysis of mammograms through an add-on cost method.

Mammography patients who visit RadNet facilities, for example, have the option of an additional AI screening of their images. RadNet, the largest national owner and operator of fixed-site diagnostic imaging centers in the United States with more than 370 locations, first launched its AI program in the Northeast. The company has now rolled out its product across all regions in the country.

Because the AI is not reimbursed by insurers, patients must pay a $40 out-of-pocket fee if they want the AI analysis.

“RadNet practices have identified more than 400 women whose cancer was found earlier than it would have been had the AI not been present,” said Greg Sorensen MD, chief science officer for RadNet.
 

How RadNet’s AI Program Works

Patients coming to RadNet facilities for screening mammography undergo 3D high-resolution mammography that includes the use of 70-micron resolution detector technology, said Dr. Sorensen. The mammogram is reviewed by a qualified radiologist with assistance from two Food and Drug Administration–cleared AI programs, Saige-Q and Saige-Density. The radiologist then makes an interpretation.

Saige-Q is an AI tool that helps identify more suspicious mammograms by providing a quick signal to radiologists if the AI considers a given mammogram to be in a suspicious category, according to Dr. Sorensen. Saige-Density provides a density rating for each mammogram using one of the four standard categories:

• A. Almost entirely fatty
• B. Scattered areas of fibroglandular density
• C. Heterogeneously dense
• D. Extremely dense

Starting in September 2024, the FDA will require all mammogram reports to indicate density.

For patients who choose the $40 add-on service, called Enhanced Breast Cancer Detection, two other FDA-registered AI programs are also applied: Saige-Dx and Saige-Assure. These AI programs go a step further by placing marks on areas within the images that they find suspicious. Mammograms flagged as “high-suspicion” by the AI are then reviewed by a second human radiologist. The first and second radiologists confer to agree on a final diagnosis, Dr. Sorensen explained.

“Our research shows that approximately 20% more cancers are found when the safeguard review process is in place,” Dr. Sorensen said. “We also have seen [30%] decreases in recall rates” — the percentage of screening cases in which further tests are recommended by the radiologist.

Bethesda radiologist Janet Storella, MD, has used the AI program for about 3 years and said the technology has improved her screening performance.

The AI is linked to her practice’s imaging software, and radiologists have the option of turning the AI on at any time during their reading of screening mammograms, Dr. Storella explained. Some radiologists review the mammogram first and then initiate the AI, while others like Dr. Storella turn it on at the start, she said. Once initiated, the AI draws bounding boxes — or outlines — around areas that it deems suspicious.

The AI helps focus Dr. Storella’s attention on suspicious areas and grades the level of suspicion into one of four categories: high, intermediate, low, and minimal, she said.

“I find it especially useful in patients who have dense breast tissue,” said Dr. Storella, medical director of women’s imaging at Community Radiology Associates, a RadNet practice. “In these situations, the tissue on the mammogram is a field of white, and cancers are also white, so you’re looking for that little white golf ball on a sea of snow. The AI really helps hone that down to specific areas.”

About 35% of RadNet’s screening mammography patients have enrolled in the Enhanced Breast Cancer Detection program, according to RadNet data. In a recent study of nine general radiologists and nine breast imaging specialists, all radiologists improved their interpretation performance of DBT screening mammograms when reading with RadNet’s AI versus without it. (An average AUC [area under the receiver operating characteristic curve] of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI, 0.04-0.08; P < .001)
 

Is Mammography Ready for AI?

RadNet is among a growing number of commercial companies offering AI solutions for mammography. MammoScreen and Hologic, for example, are two other companies that provide AI programs to assist radiologists in reading screening mammograms.

“We are at the start of the AI integration into breast imaging at this point,” said Laura Heacock, MD, a breast imaging radiologist and associate professor of radiology at NYU Langone Health. “There are multiple commercial AI models now available to radiologists to use in their practice [ and] there will likely be more. We’re in the transition stage where people are still deciding: Which is the best model to go with? How do I put it in my system? How do I ensure it works they way it was intended? Every practice and medical system will have a different answer to that question.”

At NYU Langone Health, researchers have been developing and studying optimal AI models for breast imaging for several years, Dr. Heacock said. Researchers thus far, have developed AI models for 2D digital mammography, 3D mammograms, breast ultrasound, and breast MRI. Similar to commercial AI systems, the AI is embedded into the picture archiving and communication (PACS) system used by radiologists to review images. Radiologists press a button to launch the AI, which draws a box around suspicious areas of the image and scores the suspicion.

“I take a look of where it is on the mammogram and decide whether that fits my level of suspicion,” Dr. Heacock said. The AI may not understand things about the mammogram like we do. For example, surgical scars look very suspicious to an AI model. But if I’m looking at a mammogram where [the patient] has had a stable scar that hasn’t changed in 10 years, I’m not concerned that the AI found it suspicious. My clinical judgment is the ultimate decider. This is just an additional piece of information that’s helpful to me.”

Research by New York University (NYU) has shown that when used by an expert radiologist the AI models have improved breast cancer detection in all four modalities, she said.

However, the AI has not yet launched at NYU Langone. More research is needed before deploying the technology, according to Dr. Heacock.

“At NYU, we are still testing the benefits to patients,” she said. “We know it improves cancer detection, but we want to make sure there are no drawbacks. We are still exploring the best ways to put it into effect at our institution.”

Dr. Heacock pointed to recent studies on AI in screening mammography that show promise.

An analysis of more than 80,000 women, for example, published in The Lancet Oncology in August, found that AI-supported screen reading led to a similar cancer detection rate as compared with a two-person reader system. This screening resulted in 244 screen-detected cancers, 861 recalls, and a total of 46,345 screen readings, according to the study. Standard screening resulted in 203 screen-detected cancers, 817 recalls, and a total of 83,231 screen readings.

The AI system also reduced the screen-reading workload for radiologists by 44%, the study found.

Meanwhile, a September 2023 study, published in The Lancet Digital Health, found that replacing one radiologist with AI resulted in more cancer detection without a large increase in false-positive cases. The AI led to a 4% higher, noninferior cancer detection rate, compared with radiologist double reading, the study found.

Dr. Heacock emphasized that both studies were conducted in Europe where the standard is for two radiologists to evaluate mammograms.

“That makes the results exciting, but not directly applicable to US practice just yet,” she said.
 

What Do the Experts Recommend?

Stamatia V. Destounis, MD, FACR, chair of the American College of Radiology (ACR) Breast Imaging Commission, said the college welcomes ongoing research into the efficacy of AI technologies and that AI may prove to be beneficial as an improved workflow tool.

The ACR has not released any guidance about the use of AI for radiologists and have no recommendation about best practices, Dr. Destounis said.

“The decisions regarding which technologies that various health systems and radiology sites choose to use are made by those facilities,” she said.

Dr. Destounis said more research is needed to demonstrate whether or not AI technologies help radiologists produce better results in identifying disease, injury, and illnesses among the general population or in specific groups — whether based on age, physical characteristics, race, ethnicity or risk status for breast cancer.

“Also, a way to measure each AI product is needed so that we can be certain they are relatively equivalent in their efficacy and accuracy — initially and over a prolonged period of time,” she said.

No consensus or concrete recommendation exists about the use of AI in mammography screening, adds Peter P. Yu, MD, FACP, FASCO, physician-in-chief at the Hartford HealthCare Cancer Institute and a member of the newly-created American Society of Clinical Oncology AI task force.

One of the many discussions concerning AI is to what degree patients should be aware that AI is being used in their healthcare and whether they should be required to give consent to its use, Dr. Yu said.

If AI is used to assist radiologists with mammographic interpretation, radiologists should discuss with patients how it’s being used and explain the ultimate reading is in the hands of their physician radiologist, he said.

“In the unlikely situation where there wasn’t a human in the loop and AI was in effect making a medical decision, the patient needs to be aware,” he said. “I’m not aware that any such situation exists today. AI is more likely to be subtly embedded in the software that operates technology, much like it is embedded in manufacturing and transportation.”
 

Who Will Pay for AI?

When it comes to payment, Dr. Yu said shifting the cost of AI to patients creates serious risk.

“It has enormous potential to increase health inequities,” he said. “If we believe health care is a fundamental human right, AI should inure to the benefit of all, not just those who can afford it. Healthcare should not be a luxury item; if it works, it works for all.”

In general, the issue of payment for AI is still pretty “thorny,” Dr. Heacock noted. Currently, there’s no way for physicians to request direct reimbursement for AI reads of mammograms.

While Dr. Heacock says she is sympathetic to the companies that spend significant time and effort on their AI technology, she doesn’t think charging patients is the right solution.

“We know that many women already have difficulty in paying for mammography-related services and this is just one more charge to confuse them or that they can’t pay,” she said.

Dr. Sorensen expects that, similar to 3D mammography, payers will eventually cover RadNet’s AI technology and that patients will no longer need to pay out of pocket. One Blue Cross carrier will start covering the AI in April 2024, he said.

Screening mammograms miss close to one in eight breast cancers. But early research suggests artificial intelligence (AI) could close this detection gap and markedly improve early diagnosis of the disease. Still, questions remain regarding how to best incorporate AI into screenings and whether it’s too soon to deploy the technology.

Already, some radiology clinics are offering AI analysis of mammograms through an add-on cost method.

Mammography patients who visit RadNet facilities, for example, have the option of an additional AI screening of their images. RadNet, the largest national owner and operator of fixed-site diagnostic imaging centers in the United States with more than 370 locations, first launched its AI program in the Northeast. The company has now rolled out its product across all regions in the country.

Because the AI is not reimbursed by insurers, patients must pay a $40 out-of-pocket fee if they want the AI analysis.

“RadNet practices have identified more than 400 women whose cancer was found earlier than it would have been had the AI not been present,” said Greg Sorensen MD, chief science officer for RadNet.
 

How RadNet’s AI Program Works

Patients coming to RadNet facilities for screening mammography undergo 3D high-resolution mammography that includes the use of 70-micron resolution detector technology, said Dr. Sorensen. The mammogram is reviewed by a qualified radiologist with assistance from two Food and Drug Administration–cleared AI programs, Saige-Q and Saige-Density. The radiologist then makes an interpretation.

Saige-Q is an AI tool that helps identify more suspicious mammograms by providing a quick signal to radiologists if the AI considers a given mammogram to be in a suspicious category, according to Dr. Sorensen. Saige-Density provides a density rating for each mammogram using one of the four standard categories:

• A. Almost entirely fatty
• B. Scattered areas of fibroglandular density
• C. Heterogeneously dense
• D. Extremely dense

Starting in September 2024, the FDA will require all mammogram reports to indicate density.

For patients who choose the $40 add-on service, called Enhanced Breast Cancer Detection, two other FDA-registered AI programs are also applied: Saige-Dx and Saige-Assure. These AI programs go a step further by placing marks on areas within the images that they find suspicious. Mammograms flagged as “high-suspicion” by the AI are then reviewed by a second human radiologist. The first and second radiologists confer to agree on a final diagnosis, Dr. Sorensen explained.

“Our research shows that approximately 20% more cancers are found when the safeguard review process is in place,” Dr. Sorensen said. “We also have seen [30%] decreases in recall rates” — the percentage of screening cases in which further tests are recommended by the radiologist.

Bethesda radiologist Janet Storella, MD, has used the AI program for about 3 years and said the technology has improved her screening performance.

The AI is linked to her practice’s imaging software, and radiologists have the option of turning the AI on at any time during their reading of screening mammograms, Dr. Storella explained. Some radiologists review the mammogram first and then initiate the AI, while others like Dr. Storella turn it on at the start, she said. Once initiated, the AI draws bounding boxes — or outlines — around areas that it deems suspicious.

The AI helps focus Dr. Storella’s attention on suspicious areas and grades the level of suspicion into one of four categories: high, intermediate, low, and minimal, she said.

“I find it especially useful in patients who have dense breast tissue,” said Dr. Storella, medical director of women’s imaging at Community Radiology Associates, a RadNet practice. “In these situations, the tissue on the mammogram is a field of white, and cancers are also white, so you’re looking for that little white golf ball on a sea of snow. The AI really helps hone that down to specific areas.”

About 35% of RadNet’s screening mammography patients have enrolled in the Enhanced Breast Cancer Detection program, according to RadNet data. In a recent study of nine general radiologists and nine breast imaging specialists, all radiologists improved their interpretation performance of DBT screening mammograms when reading with RadNet’s AI versus without it. (An average AUC [area under the receiver operating characteristic curve] of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI, 0.04-0.08; P < .001)
 

Is Mammography Ready for AI?

RadNet is among a growing number of commercial companies offering AI solutions for mammography. MammoScreen and Hologic, for example, are two other companies that provide AI programs to assist radiologists in reading screening mammograms.

“We are at the start of the AI integration into breast imaging at this point,” said Laura Heacock, MD, a breast imaging radiologist and associate professor of radiology at NYU Langone Health. “There are multiple commercial AI models now available to radiologists to use in their practice [ and] there will likely be more. We’re in the transition stage where people are still deciding: Which is the best model to go with? How do I put it in my system? How do I ensure it works they way it was intended? Every practice and medical system will have a different answer to that question.”

At NYU Langone Health, researchers have been developing and studying optimal AI models for breast imaging for several years, Dr. Heacock said. Researchers thus far, have developed AI models for 2D digital mammography, 3D mammograms, breast ultrasound, and breast MRI. Similar to commercial AI systems, the AI is embedded into the picture archiving and communication (PACS) system used by radiologists to review images. Radiologists press a button to launch the AI, which draws a box around suspicious areas of the image and scores the suspicion.

“I take a look of where it is on the mammogram and decide whether that fits my level of suspicion,” Dr. Heacock said. The AI may not understand things about the mammogram like we do. For example, surgical scars look very suspicious to an AI model. But if I’m looking at a mammogram where [the patient] has had a stable scar that hasn’t changed in 10 years, I’m not concerned that the AI found it suspicious. My clinical judgment is the ultimate decider. This is just an additional piece of information that’s helpful to me.”

Research by New York University (NYU) has shown that when used by an expert radiologist the AI models have improved breast cancer detection in all four modalities, she said.

However, the AI has not yet launched at NYU Langone. More research is needed before deploying the technology, according to Dr. Heacock.

“At NYU, we are still testing the benefits to patients,” she said. “We know it improves cancer detection, but we want to make sure there are no drawbacks. We are still exploring the best ways to put it into effect at our institution.”

Dr. Heacock pointed to recent studies on AI in screening mammography that show promise.

An analysis of more than 80,000 women, for example, published in The Lancet Oncology in August, found that AI-supported screen reading led to a similar cancer detection rate as compared with a two-person reader system. This screening resulted in 244 screen-detected cancers, 861 recalls, and a total of 46,345 screen readings, according to the study. Standard screening resulted in 203 screen-detected cancers, 817 recalls, and a total of 83,231 screen readings.

The AI system also reduced the screen-reading workload for radiologists by 44%, the study found.

Meanwhile, a September 2023 study, published in The Lancet Digital Health, found that replacing one radiologist with AI resulted in more cancer detection without a large increase in false-positive cases. The AI led to a 4% higher, noninferior cancer detection rate, compared with radiologist double reading, the study found.

Dr. Heacock emphasized that both studies were conducted in Europe where the standard is for two radiologists to evaluate mammograms.

“That makes the results exciting, but not directly applicable to US practice just yet,” she said.
 

What Do the Experts Recommend?

Stamatia V. Destounis, MD, FACR, chair of the American College of Radiology (ACR) Breast Imaging Commission, said the college welcomes ongoing research into the efficacy of AI technologies and that AI may prove to be beneficial as an improved workflow tool.

The ACR has not released any guidance about the use of AI for radiologists and have no recommendation about best practices, Dr. Destounis said.

“The decisions regarding which technologies that various health systems and radiology sites choose to use are made by those facilities,” she said.

Dr. Destounis said more research is needed to demonstrate whether or not AI technologies help radiologists produce better results in identifying disease, injury, and illnesses among the general population or in specific groups — whether based on age, physical characteristics, race, ethnicity or risk status for breast cancer.

“Also, a way to measure each AI product is needed so that we can be certain they are relatively equivalent in their efficacy and accuracy — initially and over a prolonged period of time,” she said.

No consensus or concrete recommendation exists about the use of AI in mammography screening, adds Peter P. Yu, MD, FACP, FASCO, physician-in-chief at the Hartford HealthCare Cancer Institute and a member of the newly-created American Society of Clinical Oncology AI task force.

One of the many discussions concerning AI is to what degree patients should be aware that AI is being used in their healthcare and whether they should be required to give consent to its use, Dr. Yu said.

If AI is used to assist radiologists with mammographic interpretation, radiologists should discuss with patients how it’s being used and explain the ultimate reading is in the hands of their physician radiologist, he said.

“In the unlikely situation where there wasn’t a human in the loop and AI was in effect making a medical decision, the patient needs to be aware,” he said. “I’m not aware that any such situation exists today. AI is more likely to be subtly embedded in the software that operates technology, much like it is embedded in manufacturing and transportation.”
 

Who Will Pay for AI?

When it comes to payment, Dr. Yu said shifting the cost of AI to patients creates serious risk.

“It has enormous potential to increase health inequities,” he said. “If we believe health care is a fundamental human right, AI should inure to the benefit of all, not just those who can afford it. Healthcare should not be a luxury item; if it works, it works for all.”

In general, the issue of payment for AI is still pretty “thorny,” Dr. Heacock noted. Currently, there’s no way for physicians to request direct reimbursement for AI reads of mammograms.

While Dr. Heacock says she is sympathetic to the companies that spend significant time and effort on their AI technology, she doesn’t think charging patients is the right solution.

“We know that many women already have difficulty in paying for mammography-related services and this is just one more charge to confuse them or that they can’t pay,” she said.

Dr. Sorensen expects that, similar to 3D mammography, payers will eventually cover RadNet’s AI technology and that patients will no longer need to pay out of pocket. One Blue Cross carrier will start covering the AI in April 2024, he said.

Screening mammograms miss close to one in eight breast cancers. But early research suggests artificial intelligence (AI) could close this detection gap and markedly improve early diagnosis of the disease. Still, questions remain regarding how to best incorporate AI into screenings and whether it’s too soon to deploy the technology.

Already, some radiology clinics are offering AI analysis of mammograms through an add-on cost method.

Mammography patients who visit RadNet facilities, for example, have the option of an additional AI screening of their images. RadNet, the largest national owner and operator of fixed-site diagnostic imaging centers in the United States with more than 370 locations, first launched its AI program in the Northeast. The company has now rolled out its product across all regions in the country.

Because the AI is not reimbursed by insurers, patients must pay a $40 out-of-pocket fee if they want the AI analysis.

“RadNet practices have identified more than 400 women whose cancer was found earlier than it would have been had the AI not been present,” said Greg Sorensen MD, chief science officer for RadNet.
 

How RadNet’s AI Program Works

Patients coming to RadNet facilities for screening mammography undergo 3D high-resolution mammography that includes the use of 70-micron resolution detector technology, said Dr. Sorensen. The mammogram is reviewed by a qualified radiologist with assistance from two Food and Drug Administration–cleared AI programs, Saige-Q and Saige-Density. The radiologist then makes an interpretation.

Saige-Q is an AI tool that helps identify more suspicious mammograms by providing a quick signal to radiologists if the AI considers a given mammogram to be in a suspicious category, according to Dr. Sorensen. Saige-Density provides a density rating for each mammogram using one of the four standard categories:

• A. Almost entirely fatty
• B. Scattered areas of fibroglandular density
• C. Heterogeneously dense
• D. Extremely dense

Starting in September 2024, the FDA will require all mammogram reports to indicate density.

For patients who choose the $40 add-on service, called Enhanced Breast Cancer Detection, two other FDA-registered AI programs are also applied: Saige-Dx and Saige-Assure. These AI programs go a step further by placing marks on areas within the images that they find suspicious. Mammograms flagged as “high-suspicion” by the AI are then reviewed by a second human radiologist. The first and second radiologists confer to agree on a final diagnosis, Dr. Sorensen explained.

“Our research shows that approximately 20% more cancers are found when the safeguard review process is in place,” Dr. Sorensen said. “We also have seen [30%] decreases in recall rates” — the percentage of screening cases in which further tests are recommended by the radiologist.

Bethesda radiologist Janet Storella, MD, has used the AI program for about 3 years and said the technology has improved her screening performance.

The AI is linked to her practice’s imaging software, and radiologists have the option of turning the AI on at any time during their reading of screening mammograms, Dr. Storella explained. Some radiologists review the mammogram first and then initiate the AI, while others like Dr. Storella turn it on at the start, she said. Once initiated, the AI draws bounding boxes — or outlines — around areas that it deems suspicious.

The AI helps focus Dr. Storella’s attention on suspicious areas and grades the level of suspicion into one of four categories: high, intermediate, low, and minimal, she said.

“I find it especially useful in patients who have dense breast tissue,” said Dr. Storella, medical director of women’s imaging at Community Radiology Associates, a RadNet practice. “In these situations, the tissue on the mammogram is a field of white, and cancers are also white, so you’re looking for that little white golf ball on a sea of snow. The AI really helps hone that down to specific areas.”

About 35% of RadNet’s screening mammography patients have enrolled in the Enhanced Breast Cancer Detection program, according to RadNet data. In a recent study of nine general radiologists and nine breast imaging specialists, all radiologists improved their interpretation performance of DBT screening mammograms when reading with RadNet’s AI versus without it. (An average AUC [area under the receiver operating characteristic curve] of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI, 0.04-0.08; P < .001)
 

Is Mammography Ready for AI?

RadNet is among a growing number of commercial companies offering AI solutions for mammography. MammoScreen and Hologic, for example, are two other companies that provide AI programs to assist radiologists in reading screening mammograms.

“We are at the start of the AI integration into breast imaging at this point,” said Laura Heacock, MD, a breast imaging radiologist and associate professor of radiology at NYU Langone Health. “There are multiple commercial AI models now available to radiologists to use in their practice [ and] there will likely be more. We’re in the transition stage where people are still deciding: Which is the best model to go with? How do I put it in my system? How do I ensure it works they way it was intended? Every practice and medical system will have a different answer to that question.”

At NYU Langone Health, researchers have been developing and studying optimal AI models for breast imaging for several years, Dr. Heacock said. Researchers thus far, have developed AI models for 2D digital mammography, 3D mammograms, breast ultrasound, and breast MRI. Similar to commercial AI systems, the AI is embedded into the picture archiving and communication (PACS) system used by radiologists to review images. Radiologists press a button to launch the AI, which draws a box around suspicious areas of the image and scores the suspicion.

“I take a look of where it is on the mammogram and decide whether that fits my level of suspicion,” Dr. Heacock said. The AI may not understand things about the mammogram like we do. For example, surgical scars look very suspicious to an AI model. But if I’m looking at a mammogram where [the patient] has had a stable scar that hasn’t changed in 10 years, I’m not concerned that the AI found it suspicious. My clinical judgment is the ultimate decider. This is just an additional piece of information that’s helpful to me.”

Research by New York University (NYU) has shown that when used by an expert radiologist the AI models have improved breast cancer detection in all four modalities, she said.

However, the AI has not yet launched at NYU Langone. More research is needed before deploying the technology, according to Dr. Heacock.

“At NYU, we are still testing the benefits to patients,” she said. “We know it improves cancer detection, but we want to make sure there are no drawbacks. We are still exploring the best ways to put it into effect at our institution.”

Dr. Heacock pointed to recent studies on AI in screening mammography that show promise.

An analysis of more than 80,000 women, for example, published in The Lancet Oncology in August, found that AI-supported screen reading led to a similar cancer detection rate as compared with a two-person reader system. This screening resulted in 244 screen-detected cancers, 861 recalls, and a total of 46,345 screen readings, according to the study. Standard screening resulted in 203 screen-detected cancers, 817 recalls, and a total of 83,231 screen readings.

The AI system also reduced the screen-reading workload for radiologists by 44%, the study found.

Meanwhile, a September 2023 study, published in The Lancet Digital Health, found that replacing one radiologist with AI resulted in more cancer detection without a large increase in false-positive cases. The AI led to a 4% higher, noninferior cancer detection rate, compared with radiologist double reading, the study found.

Dr. Heacock emphasized that both studies were conducted in Europe where the standard is for two radiologists to evaluate mammograms.

“That makes the results exciting, but not directly applicable to US practice just yet,” she said.
 

What Do the Experts Recommend?

Stamatia V. Destounis, MD, FACR, chair of the American College of Radiology (ACR) Breast Imaging Commission, said the college welcomes ongoing research into the efficacy of AI technologies and that AI may prove to be beneficial as an improved workflow tool.

The ACR has not released any guidance about the use of AI for radiologists and have no recommendation about best practices, Dr. Destounis said.

“The decisions regarding which technologies that various health systems and radiology sites choose to use are made by those facilities,” she said.

Dr. Destounis said more research is needed to demonstrate whether or not AI technologies help radiologists produce better results in identifying disease, injury, and illnesses among the general population or in specific groups — whether based on age, physical characteristics, race, ethnicity or risk status for breast cancer.

“Also, a way to measure each AI product is needed so that we can be certain they are relatively equivalent in their efficacy and accuracy — initially and over a prolonged period of time,” she said.

No consensus or concrete recommendation exists about the use of AI in mammography screening, adds Peter P. Yu, MD, FACP, FASCO, physician-in-chief at the Hartford HealthCare Cancer Institute and a member of the newly-created American Society of Clinical Oncology AI task force.

One of the many discussions concerning AI is to what degree patients should be aware that AI is being used in their healthcare and whether they should be required to give consent to its use, Dr. Yu said.

If AI is used to assist radiologists with mammographic interpretation, radiologists should discuss with patients how it’s being used and explain the ultimate reading is in the hands of their physician radiologist, he said.

“In the unlikely situation where there wasn’t a human in the loop and AI was in effect making a medical decision, the patient needs to be aware,” he said. “I’m not aware that any such situation exists today. AI is more likely to be subtly embedded in the software that operates technology, much like it is embedded in manufacturing and transportation.”
 

Who Will Pay for AI?

When it comes to payment, Dr. Yu said shifting the cost of AI to patients creates serious risk.

“It has enormous potential to increase health inequities,” he said. “If we believe health care is a fundamental human right, AI should inure to the benefit of all, not just those who can afford it. Healthcare should not be a luxury item; if it works, it works for all.”

In general, the issue of payment for AI is still pretty “thorny,” Dr. Heacock noted. Currently, there’s no way for physicians to request direct reimbursement for AI reads of mammograms.

While Dr. Heacock says she is sympathetic to the companies that spend significant time and effort on their AI technology, she doesn’t think charging patients is the right solution.

“We know that many women already have difficulty in paying for mammography-related services and this is just one more charge to confuse them or that they can’t pay,” she said.

Dr. Sorensen expects that, similar to 3D mammography, payers will eventually cover RadNet’s AI technology and that patients will no longer need to pay out of pocket. One Blue Cross carrier will start covering the AI in April 2024, he said.

TOPLINE:

Several female reproductive factors across the life cycle were significantly associated with increased COPD risk, including age at menarche, number of children, infertility, pregnancy outcomes, and age at menopause.

METHODOLOGY:

• The researchers reviewed data from women in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) consortium, which includes 27 observational studies involving more than 850,000 women in 12 countries.
• The current study included 283,070 women, 3.8% of whom developed COPD over a median of 11 years.
• The researchers examined the association between COPD and age at menarche, number of children, infertility, miscarriage, stillbirth, and age at natural menopause.

TAKEAWAY: 

• Higher risk of COPD was significantly associated with menarche at age 11 years or younger (hazard ratio [HR], 1.17), and at 16 years and older (HR, 1.24), as well as having three or more children.
• Higher risk of COPD was significantly associated with a history of infertility, and with miscarriage, or stillbirth compared with no miscarriages or stillbirths; the risk increased with the number of miscarriages or stillbirths (HR, 1.36 for ≥ 3 miscarriages and 1.67 for ≥ 2 stillbirths). 
• COPD risk was significantly increased with earlier age at the time of natural menopause (HR, 1.69 for those aged < 40 years and 1.42 for those aged 40-44 years compared with those aged 50-51 years). 

IN PRACTICE:

“Further research is needed to understand the mechanisms linking multiple female reproductive histories and COPD,” which could include autoimmune components and social/environmental factors, the researchers wrote. 

SOURCE:

The lead author on the study was Chen Liang, MD, of the University of Queensland, Australia. The study was published online in BMJ Thorax). 

LIMITATIONS: 

Study limitations included volunteer bias, underreporting of COPD, potential confounders such as childhood respiratory infections and smoking history, and the inability to assess the effects of medications including contraceptives and hormone replacement therapy on COPD. 

DISCLOSURES:

The InterLACE project is supported by the Australian National Health and Medical Research Council and Centres of Research Excellence. Corresponding author Gita D. Mishra disclosed support from the Australian National Health and Medical Research Council Leadership Fellowship. 

A version of this article appeared on Medscape.com.

TOPLINE:

Several female reproductive factors across the life cycle were significantly associated with increased COPD risk, including age at menarche, number of children, infertility, pregnancy outcomes, and age at menopause.

METHODOLOGY:

• The researchers reviewed data from women in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) consortium, which includes 27 observational studies involving more than 850,000 women in 12 countries.
• The current study included 283,070 women, 3.8% of whom developed COPD over a median of 11 years.
• The researchers examined the association between COPD and age at menarche, number of children, infertility, miscarriage, stillbirth, and age at natural menopause.

TAKEAWAY: 

• Higher risk of COPD was significantly associated with menarche at age 11 years or younger (hazard ratio [HR], 1.17), and at 16 years and older (HR, 1.24), as well as having three or more children.
• Higher risk of COPD was significantly associated with a history of infertility, and with miscarriage, or stillbirth compared with no miscarriages or stillbirths; the risk increased with the number of miscarriages or stillbirths (HR, 1.36 for ≥ 3 miscarriages and 1.67 for ≥ 2 stillbirths). 
• COPD risk was significantly increased with earlier age at the time of natural menopause (HR, 1.69 for those aged < 40 years and 1.42 for those aged 40-44 years compared with those aged 50-51 years). 

IN PRACTICE:

“Further research is needed to understand the mechanisms linking multiple female reproductive histories and COPD,” which could include autoimmune components and social/environmental factors, the researchers wrote. 

SOURCE:

The lead author on the study was Chen Liang, MD, of the University of Queensland, Australia. The study was published online in BMJ Thorax). 

LIMITATIONS: 

Study limitations included volunteer bias, underreporting of COPD, potential confounders such as childhood respiratory infections and smoking history, and the inability to assess the effects of medications including contraceptives and hormone replacement therapy on COPD. 

DISCLOSURES:

The InterLACE project is supported by the Australian National Health and Medical Research Council and Centres of Research Excellence. Corresponding author Gita D. Mishra disclosed support from the Australian National Health and Medical Research Council Leadership Fellowship. 

A version of this article appeared on Medscape.com.

TOPLINE:

Several female reproductive factors across the life cycle were significantly associated with increased COPD risk, including age at menarche, number of children, infertility, pregnancy outcomes, and age at menopause.

METHODOLOGY:

• The researchers reviewed data from women in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) consortium, which includes 27 observational studies involving more than 850,000 women in 12 countries.
• The current study included 283,070 women, 3.8% of whom developed COPD over a median of 11 years.
• The researchers examined the association between COPD and age at menarche, number of children, infertility, miscarriage, stillbirth, and age at natural menopause.

TAKEAWAY: 

• Higher risk of COPD was significantly associated with menarche at age 11 years or younger (hazard ratio [HR], 1.17), and at 16 years and older (HR, 1.24), as well as having three or more children.
• Higher risk of COPD was significantly associated with a history of infertility, and with miscarriage, or stillbirth compared with no miscarriages or stillbirths; the risk increased with the number of miscarriages or stillbirths (HR, 1.36 for ≥ 3 miscarriages and 1.67 for ≥ 2 stillbirths). 
• COPD risk was significantly increased with earlier age at the time of natural menopause (HR, 1.69 for those aged < 40 years and 1.42 for those aged 40-44 years compared with those aged 50-51 years). 

IN PRACTICE:

“Further research is needed to understand the mechanisms linking multiple female reproductive histories and COPD,” which could include autoimmune components and social/environmental factors, the researchers wrote. 

SOURCE:

The lead author on the study was Chen Liang, MD, of the University of Queensland, Australia. The study was published online in BMJ Thorax). 

LIMITATIONS: 

Study limitations included volunteer bias, underreporting of COPD, potential confounders such as childhood respiratory infections and smoking history, and the inability to assess the effects of medications including contraceptives and hormone replacement therapy on COPD. 

DISCLOSURES:

The InterLACE project is supported by the Australian National Health and Medical Research Council and Centres of Research Excellence. Corresponding author Gita D. Mishra disclosed support from the Australian National Health and Medical Research Council Leadership Fellowship. 

A version of this article appeared on Medscape.com.

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Several new clinical trials in gynecologic cancers have started enrolling recently. Perhaps one of your patients is eligible to take part?

Persistent or recurrent endometrial cancer or any advanced solid gynecologic tumor with appropriate ATR mutations. Patients with one of these diagnoses may be eligible to join a phase 2, randomized, open-label study of an experimental drug called ART0380. ART0380 inhibits the ability of cancer cells to repair DNA damage by targeting a DNA repair kinase called ATR (ataxia telangiectasia–mutated and Rad3-related) protein, which is faulty in some tumors. The hope is that ART0380 will overwhelm the inadequate DNA repair processes of these cancer cells while sparing the more robust DNA repair in healthy cells. 

All participants in the trial will take daily oral ART0380 until disease progression, withdrawal of consent, or unacceptable toxicity, whichever happens first. Some individuals will receive the treatment for 3 weeks out of every 4. Sites in California, Illinois, Massachusetts, New York, Oklahoma, Pennsylvania, Rhode Island, and France started recruiting 60 participants with endometrial cancer or any solid tumor in September 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and quality of life (QOL) is not assessed. More details at ClinicalTrials.gov

Maurie Markman, MD, president of medicine and science at City of Hope, Atlanta, who is not involved in this trial, explained that because “ a meaningful proportion of this population may have a defect in this DNA repair mechanism,” this hypothesis seems “worthy of clinical exploration.” 

Cancer of the endometrium, cervix, vagina, or vulva. Women with one of these types of cancer who can read and understand English or Spanish can join a randomized, open-label phase 2 trial to determine whether Reiki therapy can reduce pain and distress associated with brachytherapy. 

Reiki is a complementary therapy that involves a Reiki practitioner holding their hands lightly on or above the patient’s body for several minutes. Some hospitals in the US and the UK offer Reiki as a relaxation aid, although high-quality science is lacking.

In this study, one group of participants will each undergo Reiki in a quiet clinic room during the lengthy waiting period between placement of the vaginal cylinder and infusion of the radiation source, which is a time of anxiety and discomfort for many women. A second group of women will simply lie and wait in a clinic room, if desired accompanied by a friend or family member. 

The Huntsman Cancer Institute, Salt Lake City, Utah, started recruiting its 68 participants in October 2023. The primary outcome is self-reported anxiety. The secondary outcomes are other validated measures of anxiety, pain, and depression. Overall survival and broader measures of QOL will not be assessed. More details at ClinicalTrials.gov

Dr. Markman said that the benefits of Reiki may be “nothing more than a placebo effect.” But he highlighted the novelty of conducting a randomized trial to scientifically test Reiki’s “widely applied (without any real evidence) ‘integrative medicine’ approach to symptom management.”

Unresectable or metastatic endometrial cancer with deficient mismatch repair /high microsatellite instability. People in this clinical situation whose disease has progressed after one or two lines of prior chemotherapy, including platinum-based treatment, may be interested in an open-label nonrandomized, phase 2 investigation of bispecific antibody acasunlimab in combination with pembrolizumab (Keytruda). 

Acasunlimab stimulates T-cell antitumor activity as well as blocking programmed death ligand 1 (PD-L1) and is being tested in several types of solid-tumor cancer. For up to 2 years, all participants will receive intravenous (IV) infusions of the drug combination. Study sites in Florida and Europe opened in January 2024, ready for 80 participants. The primary outcome is objective response rate. Overall survival will not be assessed. More details at ClinicalTrials.gov

“In the absence of a randomized population to compare treatment outcomes, the results of this trial will likely provide limited data upon which to determine the clinical benefits of this novel drug combination strategy,” said Dr. Markman. However, he added, “the results will be helpful in assessing the potential toxicity of this approach.”

Recurrent or metastatic endometrial cancer with proficient mismatch repair. Women with this diagnosis who have progressed after one prior platinum chemotherapy regimen in any setting may wish to consider a randomized, triple-blind, phase 2 trial of pembrolizumab plus favezelimab. Favezelimab, which blocks the lymphocyte activation gene 3 (LAG3), appears to boost the antitumor activity of programmed cell death protein 1 (PD-1) inhibition in other cancers such as classic Hodgkin lymphoma. 

In the trial, participants will be assigned to one of four groups. One group will receive 17 doses of the combination treatment IV every 3 weeks — three doses in the neoadjuvant period and 14 as adjuvant therapy. A second group of individuals will receive IV pembrolizumab monotherapy on the same schedule. A third will be given up to 35 doses of the combo therapy every 3 weeks plus a daily capsule of lenvatinib (Lenvima). The fourth group will receive 35 doses of pembrolizumab plus daily lenvatinib. 

Sites in North Carolina, New Jersey, Pennsylvania, and four countries other than the US started recruiting 60 participants with a solid tumor in September 2023. Pathologic complete response and objective response rate are the primary endpoints. Overall survival over approximately 3.5 years is a secondary endpoint, and QOL will not be measured. More details at ClinicalTrials.gov

Unresectable advanced or metastatic HER2-positive endometrial or ovarian cancer. Adults with one of these diagnoses in whom failed platinum-based therapy has failed may enroll in an open-label, phase 2 study to see whether their disease will respond to the antibody-drug conjugate disitamab vedotin. Everyone in the trial will receive IV disitamab vedotin every 2 weeks for up to approximately 5 years. 

Study sites in California, Connecticut, Michigan, Minnesota, Montana, New York, Ohio, Texas, and Canada began welcoming their 190 participants with one of a range of solid cancers in November 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and QOL will not be tracked. More details at ClinicalTrials.gov

High-risk locally advanced cervical cancer. Girls and women older than 14 years with this cancer that has not progressed after platinum-based chemoradiation are sought for a randomized, quadruple-blind, phase 3 trial to determine whether the investigational immunotherapy volrustomig can slow disease progression. Volrustomig targets PD-1 and cytotoxic T lymphocyte protein 4 (CTLA4) and is being tested in a wide range of solid cancers. 

For approximately 3 years or until disease progression or death, whichever happens first, half of participants will receive IV infusions of volrustomig while the others will receive saline. Asian research sites started seeking the study’s 1000 participants in September 2023, while centers in 12 US states and eight other countries are gearing up for patient enrollment. Progression-free survival in participants with PD-L1 expression is the primary endpoint; overall survival and QOL are secondary endpoints. More details at ClinicalTrials.gov

All trial information is from the National Institutes of Health US National Library of Medicine (online at ClinicalTrials.gov). Dr. Markman declared he is not involved with these trials.

A version of this article appeared on Medscape.com .

Several new clinical trials in gynecologic cancers have started enrolling recently. Perhaps one of your patients is eligible to take part?

Persistent or recurrent endometrial cancer or any advanced solid gynecologic tumor with appropriate ATR mutations. Patients with one of these diagnoses may be eligible to join a phase 2, randomized, open-label study of an experimental drug called ART0380. ART0380 inhibits the ability of cancer cells to repair DNA damage by targeting a DNA repair kinase called ATR (ataxia telangiectasia–mutated and Rad3-related) protein, which is faulty in some tumors. The hope is that ART0380 will overwhelm the inadequate DNA repair processes of these cancer cells while sparing the more robust DNA repair in healthy cells. 

All participants in the trial will take daily oral ART0380 until disease progression, withdrawal of consent, or unacceptable toxicity, whichever happens first. Some individuals will receive the treatment for 3 weeks out of every 4. Sites in California, Illinois, Massachusetts, New York, Oklahoma, Pennsylvania, Rhode Island, and France started recruiting 60 participants with endometrial cancer or any solid tumor in September 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and quality of life (QOL) is not assessed. More details at ClinicalTrials.gov

Maurie Markman, MD, president of medicine and science at City of Hope, Atlanta, who is not involved in this trial, explained that because “ a meaningful proportion of this population may have a defect in this DNA repair mechanism,” this hypothesis seems “worthy of clinical exploration.” 

Cancer of the endometrium, cervix, vagina, or vulva. Women with one of these types of cancer who can read and understand English or Spanish can join a randomized, open-label phase 2 trial to determine whether Reiki therapy can reduce pain and distress associated with brachytherapy. 

Reiki is a complementary therapy that involves a Reiki practitioner holding their hands lightly on or above the patient’s body for several minutes. Some hospitals in the US and the UK offer Reiki as a relaxation aid, although high-quality science is lacking.

In this study, one group of participants will each undergo Reiki in a quiet clinic room during the lengthy waiting period between placement of the vaginal cylinder and infusion of the radiation source, which is a time of anxiety and discomfort for many women. A second group of women will simply lie and wait in a clinic room, if desired accompanied by a friend or family member. 

The Huntsman Cancer Institute, Salt Lake City, Utah, started recruiting its 68 participants in October 2023. The primary outcome is self-reported anxiety. The secondary outcomes are other validated measures of anxiety, pain, and depression. Overall survival and broader measures of QOL will not be assessed. More details at ClinicalTrials.gov

Dr. Markman said that the benefits of Reiki may be “nothing more than a placebo effect.” But he highlighted the novelty of conducting a randomized trial to scientifically test Reiki’s “widely applied (without any real evidence) ‘integrative medicine’ approach to symptom management.”

Unresectable or metastatic endometrial cancer with deficient mismatch repair /high microsatellite instability. People in this clinical situation whose disease has progressed after one or two lines of prior chemotherapy, including platinum-based treatment, may be interested in an open-label nonrandomized, phase 2 investigation of bispecific antibody acasunlimab in combination with pembrolizumab (Keytruda). 

Acasunlimab stimulates T-cell antitumor activity as well as blocking programmed death ligand 1 (PD-L1) and is being tested in several types of solid-tumor cancer. For up to 2 years, all participants will receive intravenous (IV) infusions of the drug combination. Study sites in Florida and Europe opened in January 2024, ready for 80 participants. The primary outcome is objective response rate. Overall survival will not be assessed. More details at ClinicalTrials.gov

“In the absence of a randomized population to compare treatment outcomes, the results of this trial will likely provide limited data upon which to determine the clinical benefits of this novel drug combination strategy,” said Dr. Markman. However, he added, “the results will be helpful in assessing the potential toxicity of this approach.”

Recurrent or metastatic endometrial cancer with proficient mismatch repair. Women with this diagnosis who have progressed after one prior platinum chemotherapy regimen in any setting may wish to consider a randomized, triple-blind, phase 2 trial of pembrolizumab plus favezelimab. Favezelimab, which blocks the lymphocyte activation gene 3 (LAG3), appears to boost the antitumor activity of programmed cell death protein 1 (PD-1) inhibition in other cancers such as classic Hodgkin lymphoma. 

In the trial, participants will be assigned to one of four groups. One group will receive 17 doses of the combination treatment IV every 3 weeks — three doses in the neoadjuvant period and 14 as adjuvant therapy. A second group of individuals will receive IV pembrolizumab monotherapy on the same schedule. A third will be given up to 35 doses of the combo therapy every 3 weeks plus a daily capsule of lenvatinib (Lenvima). The fourth group will receive 35 doses of pembrolizumab plus daily lenvatinib. 

Sites in North Carolina, New Jersey, Pennsylvania, and four countries other than the US started recruiting 60 participants with a solid tumor in September 2023. Pathologic complete response and objective response rate are the primary endpoints. Overall survival over approximately 3.5 years is a secondary endpoint, and QOL will not be measured. More details at ClinicalTrials.gov

Unresectable advanced or metastatic HER2-positive endometrial or ovarian cancer. Adults with one of these diagnoses in whom failed platinum-based therapy has failed may enroll in an open-label, phase 2 study to see whether their disease will respond to the antibody-drug conjugate disitamab vedotin. Everyone in the trial will receive IV disitamab vedotin every 2 weeks for up to approximately 5 years. 

Study sites in California, Connecticut, Michigan, Minnesota, Montana, New York, Ohio, Texas, and Canada began welcoming their 190 participants with one of a range of solid cancers in November 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and QOL will not be tracked. More details at ClinicalTrials.gov

High-risk locally advanced cervical cancer. Girls and women older than 14 years with this cancer that has not progressed after platinum-based chemoradiation are sought for a randomized, quadruple-blind, phase 3 trial to determine whether the investigational immunotherapy volrustomig can slow disease progression. Volrustomig targets PD-1 and cytotoxic T lymphocyte protein 4 (CTLA4) and is being tested in a wide range of solid cancers. 

For approximately 3 years or until disease progression or death, whichever happens first, half of participants will receive IV infusions of volrustomig while the others will receive saline. Asian research sites started seeking the study’s 1000 participants in September 2023, while centers in 12 US states and eight other countries are gearing up for patient enrollment. Progression-free survival in participants with PD-L1 expression is the primary endpoint; overall survival and QOL are secondary endpoints. More details at ClinicalTrials.gov

All trial information is from the National Institutes of Health US National Library of Medicine (online at ClinicalTrials.gov). Dr. Markman declared he is not involved with these trials.

A version of this article appeared on Medscape.com .

Several new clinical trials in gynecologic cancers have started enrolling recently. Perhaps one of your patients is eligible to take part?

Persistent or recurrent endometrial cancer or any advanced solid gynecologic tumor with appropriate ATR mutations. Patients with one of these diagnoses may be eligible to join a phase 2, randomized, open-label study of an experimental drug called ART0380. ART0380 inhibits the ability of cancer cells to repair DNA damage by targeting a DNA repair kinase called ATR (ataxia telangiectasia–mutated and Rad3-related) protein, which is faulty in some tumors. The hope is that ART0380 will overwhelm the inadequate DNA repair processes of these cancer cells while sparing the more robust DNA repair in healthy cells. 

All participants in the trial will take daily oral ART0380 until disease progression, withdrawal of consent, or unacceptable toxicity, whichever happens first. Some individuals will receive the treatment for 3 weeks out of every 4. Sites in California, Illinois, Massachusetts, New York, Oklahoma, Pennsylvania, Rhode Island, and France started recruiting 60 participants with endometrial cancer or any solid tumor in September 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and quality of life (QOL) is not assessed. More details at ClinicalTrials.gov

Maurie Markman, MD, president of medicine and science at City of Hope, Atlanta, who is not involved in this trial, explained that because “ a meaningful proportion of this population may have a defect in this DNA repair mechanism,” this hypothesis seems “worthy of clinical exploration.” 

Cancer of the endometrium, cervix, vagina, or vulva. Women with one of these types of cancer who can read and understand English or Spanish can join a randomized, open-label phase 2 trial to determine whether Reiki therapy can reduce pain and distress associated with brachytherapy. 

Reiki is a complementary therapy that involves a Reiki practitioner holding their hands lightly on or above the patient’s body for several minutes. Some hospitals in the US and the UK offer Reiki as a relaxation aid, although high-quality science is lacking.

In this study, one group of participants will each undergo Reiki in a quiet clinic room during the lengthy waiting period between placement of the vaginal cylinder and infusion of the radiation source, which is a time of anxiety and discomfort for many women. A second group of women will simply lie and wait in a clinic room, if desired accompanied by a friend or family member. 

The Huntsman Cancer Institute, Salt Lake City, Utah, started recruiting its 68 participants in October 2023. The primary outcome is self-reported anxiety. The secondary outcomes are other validated measures of anxiety, pain, and depression. Overall survival and broader measures of QOL will not be assessed. More details at ClinicalTrials.gov

Dr. Markman said that the benefits of Reiki may be “nothing more than a placebo effect.” But he highlighted the novelty of conducting a randomized trial to scientifically test Reiki’s “widely applied (without any real evidence) ‘integrative medicine’ approach to symptom management.”

Unresectable or metastatic endometrial cancer with deficient mismatch repair /high microsatellite instability. People in this clinical situation whose disease has progressed after one or two lines of prior chemotherapy, including platinum-based treatment, may be interested in an open-label nonrandomized, phase 2 investigation of bispecific antibody acasunlimab in combination with pembrolizumab (Keytruda). 

Acasunlimab stimulates T-cell antitumor activity as well as blocking programmed death ligand 1 (PD-L1) and is being tested in several types of solid-tumor cancer. For up to 2 years, all participants will receive intravenous (IV) infusions of the drug combination. Study sites in Florida and Europe opened in January 2024, ready for 80 participants. The primary outcome is objective response rate. Overall survival will not be assessed. More details at ClinicalTrials.gov

“In the absence of a randomized population to compare treatment outcomes, the results of this trial will likely provide limited data upon which to determine the clinical benefits of this novel drug combination strategy,” said Dr. Markman. However, he added, “the results will be helpful in assessing the potential toxicity of this approach.”

Recurrent or metastatic endometrial cancer with proficient mismatch repair. Women with this diagnosis who have progressed after one prior platinum chemotherapy regimen in any setting may wish to consider a randomized, triple-blind, phase 2 trial of pembrolizumab plus favezelimab. Favezelimab, which blocks the lymphocyte activation gene 3 (LAG3), appears to boost the antitumor activity of programmed cell death protein 1 (PD-1) inhibition in other cancers such as classic Hodgkin lymphoma. 

In the trial, participants will be assigned to one of four groups. One group will receive 17 doses of the combination treatment IV every 3 weeks — three doses in the neoadjuvant period and 14 as adjuvant therapy. A second group of individuals will receive IV pembrolizumab monotherapy on the same schedule. A third will be given up to 35 doses of the combo therapy every 3 weeks plus a daily capsule of lenvatinib (Lenvima). The fourth group will receive 35 doses of pembrolizumab plus daily lenvatinib. 

Sites in North Carolina, New Jersey, Pennsylvania, and four countries other than the US started recruiting 60 participants with a solid tumor in September 2023. Pathologic complete response and objective response rate are the primary endpoints. Overall survival over approximately 3.5 years is a secondary endpoint, and QOL will not be measured. More details at ClinicalTrials.gov

Unresectable advanced or metastatic HER2-positive endometrial or ovarian cancer. Adults with one of these diagnoses in whom failed platinum-based therapy has failed may enroll in an open-label, phase 2 study to see whether their disease will respond to the antibody-drug conjugate disitamab vedotin. Everyone in the trial will receive IV disitamab vedotin every 2 weeks for up to approximately 5 years. 

Study sites in California, Connecticut, Michigan, Minnesota, Montana, New York, Ohio, Texas, and Canada began welcoming their 190 participants with one of a range of solid cancers in November 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and QOL will not be tracked. More details at ClinicalTrials.gov

High-risk locally advanced cervical cancer. Girls and women older than 14 years with this cancer that has not progressed after platinum-based chemoradiation are sought for a randomized, quadruple-blind, phase 3 trial to determine whether the investigational immunotherapy volrustomig can slow disease progression. Volrustomig targets PD-1 and cytotoxic T lymphocyte protein 4 (CTLA4) and is being tested in a wide range of solid cancers. 

For approximately 3 years or until disease progression or death, whichever happens first, half of participants will receive IV infusions of volrustomig while the others will receive saline. Asian research sites started seeking the study’s 1000 participants in September 2023, while centers in 12 US states and eight other countries are gearing up for patient enrollment. Progression-free survival in participants with PD-L1 expression is the primary endpoint; overall survival and QOL are secondary endpoints. More details at ClinicalTrials.gov

All trial information is from the National Institutes of Health US National Library of Medicine (online at ClinicalTrials.gov). Dr. Markman declared he is not involved with these trials.

A version of this article appeared on Medscape.com .

NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.

After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).

Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.

In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.

The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.

The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.

The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.

The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.

Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.

Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).

Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.

Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.

Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).

Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
 

Data Support Orals as Effective Gestational Diabetes Option

“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.

The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.

Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.

A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.

Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.

The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.

After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).

Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.

In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.

The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.

The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.

The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.

The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.

Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.

Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).

Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.

Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.

Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).

Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
 

Data Support Orals as Effective Gestational Diabetes Option

“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.

The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.

Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.

A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.

Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.

The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.

After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).

Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.

In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.

The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.

The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.

The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.

The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.

Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.

Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).

Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.

Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.

Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).

Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
 

Data Support Orals as Effective Gestational Diabetes Option

“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.

The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.

Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.

A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.

Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.

The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Women who experience an adverse pregnancy outcome during their first pregnancy are significantly more likely to experience either the same or any adverse pregnancy outcome in a subsequent pregnancy than are those with no adverse pregnancy outcome during a first pregnancy, based on data from more than 4000 individuals.

Adverse pregnancy outcomes (APOs) occur in approximately 20%-30% of pregnancies and contribute to significant perinatal morbidity, William A. Grobman, MD, of The Ohio State University, Columbus, said in a presentation at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine (abstract 17).

Risk factors for APOs include nulliparity and prior APOs, as well as age, body mass index, and blood pressure, he said. However, less is known about factors identified early in a first pregnancy that might predict an APO in a second pregnancy, he explained.

Dr. Grobman and colleagues used data from the nuMoM2b Heart Health Study, a cohort of more than 10,000 nulliparous women at eight sites in the United States.

The current study included a subset of individuals with two pregnancies of at least 20 weeks’ gestation who were followed for up to 7 years after delivery via telephone and in-person visits and for whom APO information was available.

An APO was defined as any of a range of outcomes including hypertensive disorders of pregnancy, preterm birth at less than 37 weeks’ gestation, small-for-gestational age at birth (less than 5th percentile for weight), gestational diabetes, or fetal death.

The goal of the study was to determine patterns of APOs across two pregnancies, and to identify factors in the first pregnancy that might be associated with these patterns, Dr. Grobman said.

The study population included 4253 women from the nuMOM2b; of these, 1332 (31%) experienced an APO during their first pregnancies.

Women with an APO during the first pregnancy were significantly more likely to have a second APO than were those with no initial APO (40% vs. 15%), said Dr. Grobman. Overall, the APO that occurred most frequently in the first pregnancy was the one most likely to occur in the second.

However, “the increased risk for an APO during a second pregnancy was greater for any APO in women with a history of any APO compared to women with no prior APO,” he said.

In this study, the most common APOs were gestational diabetes and hypertensive disorders of pregnancy.

“In general, no risk markers were associated with a particular pattern of APO development,” Dr. Grobman said.

However, some markers from the first trimester of the first pregnancy were significantly associated with an APO in the second pregnancy, including body mass index, age older than 35 years, blood pressure, and cardiometabolic serum analytes. Also, the magnitude of APO recurrence risk was highest among non-Hispanic Black individuals compared with other ethnicities.

The findings were limited by a lack of data on placental pathology, Dr. Grobman noted during the discussion. However, the findings underscored the need to better understand the risk factors for APOs and develop prevention strategies, he said. The results also emphasize the need to account for transitions of care for patients who experience an APO, he added.
 

Data May Inform Patient Guidance

“Patients with an adverse pregnancy outcome in a first pregnancy often experience considerable anxiety when thinking about a second pregnancy,” Joseph R. Biggio Jr., MD, a maternal-fetal medicine specialist at Ochsner Health in New Orleans, said in an interview.

“This study helps to provide insight into factors which may be associated with increased risk in a subsequent pregnancy, and importantly identifies some factors that are potentially modifiable, such as BMI and blood pressure,” said Dr. Biggio, who served as a moderator for the session in which the study was presented.

“Based on the findings from this analysis, we need research to determine whether these findings apply to not only patients having their first pregnancy, but also adverse outcomes in any pregnancy,” Dr. Biggio said in an interview. “In addition, we need to explore whether modification of any of these risk factors can improve pregnancy outcomes, so that all patients can have the birth experience that they desire,” he said.

The study received no outside funding. Dr. Grobman and Dr. Biggio had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Women who experience an adverse pregnancy outcome during their first pregnancy are significantly more likely to experience either the same or any adverse pregnancy outcome in a subsequent pregnancy than are those with no adverse pregnancy outcome during a first pregnancy, based on data from more than 4000 individuals.

Adverse pregnancy outcomes (APOs) occur in approximately 20%-30% of pregnancies and contribute to significant perinatal morbidity, William A. Grobman, MD, of The Ohio State University, Columbus, said in a presentation at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine (abstract 17).

Risk factors for APOs include nulliparity and prior APOs, as well as age, body mass index, and blood pressure, he said. However, less is known about factors identified early in a first pregnancy that might predict an APO in a second pregnancy, he explained.

Dr. Grobman and colleagues used data from the nuMoM2b Heart Health Study, a cohort of more than 10,000 nulliparous women at eight sites in the United States.

The current study included a subset of individuals with two pregnancies of at least 20 weeks’ gestation who were followed for up to 7 years after delivery via telephone and in-person visits and for whom APO information was available.

An APO was defined as any of a range of outcomes including hypertensive disorders of pregnancy, preterm birth at less than 37 weeks’ gestation, small-for-gestational age at birth (less than 5th percentile for weight), gestational diabetes, or fetal death.

The goal of the study was to determine patterns of APOs across two pregnancies, and to identify factors in the first pregnancy that might be associated with these patterns, Dr. Grobman said.

The study population included 4253 women from the nuMOM2b; of these, 1332 (31%) experienced an APO during their first pregnancies.

Women with an APO during the first pregnancy were significantly more likely to have a second APO than were those with no initial APO (40% vs. 15%), said Dr. Grobman. Overall, the APO that occurred most frequently in the first pregnancy was the one most likely to occur in the second.

However, “the increased risk for an APO during a second pregnancy was greater for any APO in women with a history of any APO compared to women with no prior APO,” he said.

In this study, the most common APOs were gestational diabetes and hypertensive disorders of pregnancy.

“In general, no risk markers were associated with a particular pattern of APO development,” Dr. Grobman said.

However, some markers from the first trimester of the first pregnancy were significantly associated with an APO in the second pregnancy, including body mass index, age older than 35 years, blood pressure, and cardiometabolic serum analytes. Also, the magnitude of APO recurrence risk was highest among non-Hispanic Black individuals compared with other ethnicities.

The findings were limited by a lack of data on placental pathology, Dr. Grobman noted during the discussion. However, the findings underscored the need to better understand the risk factors for APOs and develop prevention strategies, he said. The results also emphasize the need to account for transitions of care for patients who experience an APO, he added.
 

Data May Inform Patient Guidance

“Patients with an adverse pregnancy outcome in a first pregnancy often experience considerable anxiety when thinking about a second pregnancy,” Joseph R. Biggio Jr., MD, a maternal-fetal medicine specialist at Ochsner Health in New Orleans, said in an interview.

“This study helps to provide insight into factors which may be associated with increased risk in a subsequent pregnancy, and importantly identifies some factors that are potentially modifiable, such as BMI and blood pressure,” said Dr. Biggio, who served as a moderator for the session in which the study was presented.

“Based on the findings from this analysis, we need research to determine whether these findings apply to not only patients having their first pregnancy, but also adverse outcomes in any pregnancy,” Dr. Biggio said in an interview. “In addition, we need to explore whether modification of any of these risk factors can improve pregnancy outcomes, so that all patients can have the birth experience that they desire,” he said.

The study received no outside funding. Dr. Grobman and Dr. Biggio had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Women who experience an adverse pregnancy outcome during their first pregnancy are significantly more likely to experience either the same or any adverse pregnancy outcome in a subsequent pregnancy than are those with no adverse pregnancy outcome during a first pregnancy, based on data from more than 4000 individuals.

Adverse pregnancy outcomes (APOs) occur in approximately 20%-30% of pregnancies and contribute to significant perinatal morbidity, William A. Grobman, MD, of The Ohio State University, Columbus, said in a presentation at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine (abstract 17).

Risk factors for APOs include nulliparity and prior APOs, as well as age, body mass index, and blood pressure, he said. However, less is known about factors identified early in a first pregnancy that might predict an APO in a second pregnancy, he explained.

Dr. Grobman and colleagues used data from the nuMoM2b Heart Health Study, a cohort of more than 10,000 nulliparous women at eight sites in the United States.

The current study included a subset of individuals with two pregnancies of at least 20 weeks’ gestation who were followed for up to 7 years after delivery via telephone and in-person visits and for whom APO information was available.

An APO was defined as any of a range of outcomes including hypertensive disorders of pregnancy, preterm birth at less than 37 weeks’ gestation, small-for-gestational age at birth (less than 5th percentile for weight), gestational diabetes, or fetal death.

The goal of the study was to determine patterns of APOs across two pregnancies, and to identify factors in the first pregnancy that might be associated with these patterns, Dr. Grobman said.

The study population included 4253 women from the nuMOM2b; of these, 1332 (31%) experienced an APO during their first pregnancies.

Women with an APO during the first pregnancy were significantly more likely to have a second APO than were those with no initial APO (40% vs. 15%), said Dr. Grobman. Overall, the APO that occurred most frequently in the first pregnancy was the one most likely to occur in the second.

However, “the increased risk for an APO during a second pregnancy was greater for any APO in women with a history of any APO compared to women with no prior APO,” he said.

In this study, the most common APOs were gestational diabetes and hypertensive disorders of pregnancy.

“In general, no risk markers were associated with a particular pattern of APO development,” Dr. Grobman said.

However, some markers from the first trimester of the first pregnancy were significantly associated with an APO in the second pregnancy, including body mass index, age older than 35 years, blood pressure, and cardiometabolic serum analytes. Also, the magnitude of APO recurrence risk was highest among non-Hispanic Black individuals compared with other ethnicities.

The findings were limited by a lack of data on placental pathology, Dr. Grobman noted during the discussion. However, the findings underscored the need to better understand the risk factors for APOs and develop prevention strategies, he said. The results also emphasize the need to account for transitions of care for patients who experience an APO, he added.
 

Data May Inform Patient Guidance

“Patients with an adverse pregnancy outcome in a first pregnancy often experience considerable anxiety when thinking about a second pregnancy,” Joseph R. Biggio Jr., MD, a maternal-fetal medicine specialist at Ochsner Health in New Orleans, said in an interview.

“This study helps to provide insight into factors which may be associated with increased risk in a subsequent pregnancy, and importantly identifies some factors that are potentially modifiable, such as BMI and blood pressure,” said Dr. Biggio, who served as a moderator for the session in which the study was presented.

“Based on the findings from this analysis, we need research to determine whether these findings apply to not only patients having their first pregnancy, but also adverse outcomes in any pregnancy,” Dr. Biggio said in an interview. “In addition, we need to explore whether modification of any of these risk factors can improve pregnancy outcomes, so that all patients can have the birth experience that they desire,” he said.

The study received no outside funding. Dr. Grobman and Dr. Biggio had no financial conflicts to disclose.

Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.

“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
 

Papillomavirus and Cancer

One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.

However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.

“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.

In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.

It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
 

Time of Infection

Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.

However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.

It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.

Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.

“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
 

Protecting One’s Partner

Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.

The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”

So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
 

Clearing the Virus

There are treatments for cervical lesions but not for papillomavirus infection.

“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.

“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.

“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
 

Papillomavirus and Cancer

One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.

However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.

“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.

In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.

It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
 

Time of Infection

Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.

However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.

It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.

Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.

“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
 

Protecting One’s Partner

Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.

The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”

So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
 

Clearing the Virus

There are treatments for cervical lesions but not for papillomavirus infection.

“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.

“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.

“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
 

Papillomavirus and Cancer

One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.

However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.

“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.

In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.

It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
 

Time of Infection

Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.

However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.

It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.

Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.

“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
 

Protecting One’s Partner

Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.

The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”

So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
 

Clearing the Virus

There are treatments for cervical lesions but not for papillomavirus infection.

“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.

“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.

Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.

Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”

Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.

A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.

Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.

“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”

The Knowns And Unknowns of CGM in Pregnancy

The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.

The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.

Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.

Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)

More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”

There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”

And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).

Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.

Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).

The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.

CGM in Type 2, GDM

CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”

While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.

Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
 

Is Preventing Maternal Hypoglycemia Possible?

Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.

The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.

Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.

In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.

Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).

The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”

Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.

Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.

Rethinking Intrapartum Care

Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.

A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).

Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).

Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).

Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).

The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.

Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.

The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.

Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.

“I do think we need to rethink our current recommendations,” she said.

Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.

WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.

Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.

Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”

Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.

A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.

Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.

“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”

The Knowns And Unknowns of CGM in Pregnancy

The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.

The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.

Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.

Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)

More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”

There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”

And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).

Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.

Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).

The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.

CGM in Type 2, GDM

CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”

While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.

Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
 

Is Preventing Maternal Hypoglycemia Possible?

Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.

The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.

Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.

In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.

Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).

The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”

Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.

Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.

Rethinking Intrapartum Care

Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.

A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).

Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).

Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).

Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).

The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.

Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.

The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.

Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.

“I do think we need to rethink our current recommendations,” she said.

Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.

WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.

Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.

Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”

Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.

A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.

Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.

“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”

The Knowns And Unknowns of CGM in Pregnancy

The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.

The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.

Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.

Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)

More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”

There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”

And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).

Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.

Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).

The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.

CGM in Type 2, GDM

CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”

While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.

Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
 

Is Preventing Maternal Hypoglycemia Possible?

Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.

The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.

Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.

In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.

Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).

The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”

Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.

Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.

Rethinking Intrapartum Care

Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.

A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).

Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).

Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).

Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).

The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.

Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.

The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.

Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.

“I do think we need to rethink our current recommendations,” she said.

Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.