MDedge ObGyn

Among a sample of younger women with invasive breast cancer and employer-sponsored insurance, outpatient-related out-of-pocket (OOP) costs were greater than drug costs.

For these same patients, prescriptions were largely for nonproprietary anticancer drugs and entailed limited OOP costs. For women with high-deductible health plans (HDHPs) and commercially driven health plans (CDHPs), OOP costs were higher, compared with coverage by more generous plans, according to the Research Letter published in JAMA Network Open.

“You would expect that people undergoing cancer treatment should not have to face very high out-of-pocket costs associated with care regardless of treatment modality because their treatment is largely guideline-indicated, and they have no choices,” stated corresponding author Rena Conti, PhD, associate professor with the school of business, Boston University, in an interview. “If you are diagnosed with cancer and undergoing treatment, you’re following the recommendation of your doctor, and your doctor is following standard protocols for treatment. In that scenario, Economics 101 suggests that people should not have to pay anything or [should pay] very little, especially for things that are cheap and are known to be effective, because there’s no overuse. Where normally we think that out-of-pocket costs are meant to control overuse, people with breast cancer are not opting to get more than indicated chemotherapy or radiation.”

The analysis of 25,224 women with invasive breast cancer diagnosis and claims for 1 or more of 14 oral anticancer drugs revealed that OOP costs for nondrug outpatient claims represented 79.0% of total costs. OOP drug costs were modest, with a 30-day supply ranging from $0.57-$0.60 for tamoxifen to $134.08-$141.07 for palbociclib.

“We were interested in understanding to what extent women who are insured with private insurance are exposed to out-of-pocket costs for standard breast cancer treatment, both in looking at drugs, but also the other aspects of the treatments they undergo.”

High OOP costs for the oral anticancer prescription drugs that are central to breast cancer treatment are associated with treatment nonadherence and discontinuation. Little has been known, however, about OOP costs of treatment associated with invasive breast cancer among employer-insured women younger than 65 years, the paper says.

“This population may face significant financial burdens related to long-term hormonal-based prevention and enrollment in high-deductible health plans and consumer-driven health plans,” the authors state in their paper.

In the cross-sectional study, which used the national 2018 Marative MarketScan database, 23.1% were HDHP- or CDHP-insured. Fifty-one percent had no OOP costs for drugs. The total mean estimated OOP cost, however, was $1,502.23 per patient, with inpatient costs representing only $112.41 (95% confidence interval, $112.40-$112.42); outpatient costs were $1,186.27 (95% CI, $1,185.67-$1,188.16). Pharmaceutical costs were $203.55 (95% CI, $203.34-$203.78).“We were surprised to find that the vast majority were getting breast cancer treatment with older, very effective, very safe, relatively inexpensive drugs and had limited out-of-pocket costs with some variation – higher costs for the few receiving newer, expensive drugs. The backbone of treatment is the older, generic drugs, which are cheap for both the insurers and the patients. But we found also that women are facing high out-of-pocket costs for nondrug-based therapy – specifically for doctor visits, getting check-ups, diagnostic scans, and maybe other types of treatment, as well. ... It’s a very different story than the one typically being told about the preponderance of out-of-pocket costs being drug-related,” Dr. Conti said.

The explanation may be that progress in breast cancer treatment over the last decades has led to effective treatments that are largely now inexpensive. The situation is different with ovarian cancer and many blood cancers such as chronic lymphocytic leukemia and multiple myeloma. For them, the new, innovative, safe, and effective drugs are very expensive, she noted.

“I think that insurers can modulate the out-of-pocket costs associated with drug treatment through formulary design and other tools they have. It’s less easy for them to modulate out-of-pocket costs associated with other modalties of care. Still, for medical care that is obviously necessary, there needs to be a cap on what women should have to pay,” Dr. Conti said.

A further concern raised by Dr. Conti is shrinking Medicaid coverage with the expiration of COVID-specific expanded Medicaid eligibility.

“Policy folks are closely watching the size of uninsured populations and also the growing importance of the high deductible and consumer-driven plans in which patients face high out-of-pocket first dollar coverage for care. With Medicaid rolls shrinking, we’ll see more people in low-premium, not well-insured plans. Americans’ exposure to higher costs for guideline-recommended care might grow, especially as more of them are independent contractors in the gig economy and not working for big corporations.”

“We worry that if and when they get a diagnosis of breast cancer, which is common among younger women, they are going to be faced with costs associated with their care that are going to have to be paid out-of-pocket – and it’s not going to be for the drug, it’s the other types of care. Doctors should know that the younger patient population that they are serving might be facing burdens associated with their care.”

Dr. Conti added, “Among women who are underinsured, there is a clear burden associated with cancer treatment. Reform efforts have largely focused on reducing out-of-pocket costs for seniors and have not focused much on guideline-consistent care for those under 65 who are working. Their burden can be quite onerous and cause financial harm for them and their families, resulting in worse health,” she continued, “Policy attention should go to unburdening people who have a serious diagnosis and who really have to be treated. There’s very good evidence that imposing additional out-of-pocket costs for guideline-consistent care causes people to make really hard decisions about paying rent versus paying for meds, about splitting pills and not doing all the things their physician is recommending, and about staying in jobs they don’t love but are locked into [because of health coverage].”

Dr. Conti concluded, “The good news is that, in breast cancer, the drugs work and are cheap. But the bad news is that there are many people who are underinsured and therefore, their care still has a high out-of-pocket burden. ACA radically changed working age people’s ability to qualify for insurance and be insured, but that didn’t mean that they are really well-covered when they become sick. They are still in peril over high out-of-pocket costs because of the proliferation of plans that are very skimpy. Women think they are insured until they get a diagnosis.”

Noting study limitations, Dr. Conti said that OOP costs cited are an underestimate, because many patients will also be treated for other comorbidities and complications related to treatment.

The authors disclosed no conflicts of interest. The study was funded by the American Cancer Society.

Among a sample of younger women with invasive breast cancer and employer-sponsored insurance, outpatient-related out-of-pocket (OOP) costs were greater than drug costs.

For these same patients, prescriptions were largely for nonproprietary anticancer drugs and entailed limited OOP costs. For women with high-deductible health plans (HDHPs) and commercially driven health plans (CDHPs), OOP costs were higher, compared with coverage by more generous plans, according to the Research Letter published in JAMA Network Open.

“You would expect that people undergoing cancer treatment should not have to face very high out-of-pocket costs associated with care regardless of treatment modality because their treatment is largely guideline-indicated, and they have no choices,” stated corresponding author Rena Conti, PhD, associate professor with the school of business, Boston University, in an interview. “If you are diagnosed with cancer and undergoing treatment, you’re following the recommendation of your doctor, and your doctor is following standard protocols for treatment. In that scenario, Economics 101 suggests that people should not have to pay anything or [should pay] very little, especially for things that are cheap and are known to be effective, because there’s no overuse. Where normally we think that out-of-pocket costs are meant to control overuse, people with breast cancer are not opting to get more than indicated chemotherapy or radiation.”

The analysis of 25,224 women with invasive breast cancer diagnosis and claims for 1 or more of 14 oral anticancer drugs revealed that OOP costs for nondrug outpatient claims represented 79.0% of total costs. OOP drug costs were modest, with a 30-day supply ranging from $0.57-$0.60 for tamoxifen to $134.08-$141.07 for palbociclib.

“We were interested in understanding to what extent women who are insured with private insurance are exposed to out-of-pocket costs for standard breast cancer treatment, both in looking at drugs, but also the other aspects of the treatments they undergo.”

High OOP costs for the oral anticancer prescription drugs that are central to breast cancer treatment are associated with treatment nonadherence and discontinuation. Little has been known, however, about OOP costs of treatment associated with invasive breast cancer among employer-insured women younger than 65 years, the paper says.

“This population may face significant financial burdens related to long-term hormonal-based prevention and enrollment in high-deductible health plans and consumer-driven health plans,” the authors state in their paper.

In the cross-sectional study, which used the national 2018 Marative MarketScan database, 23.1% were HDHP- or CDHP-insured. Fifty-one percent had no OOP costs for drugs. The total mean estimated OOP cost, however, was $1,502.23 per patient, with inpatient costs representing only $112.41 (95% confidence interval, $112.40-$112.42); outpatient costs were $1,186.27 (95% CI, $1,185.67-$1,188.16). Pharmaceutical costs were $203.55 (95% CI, $203.34-$203.78).“We were surprised to find that the vast majority were getting breast cancer treatment with older, very effective, very safe, relatively inexpensive drugs and had limited out-of-pocket costs with some variation – higher costs for the few receiving newer, expensive drugs. The backbone of treatment is the older, generic drugs, which are cheap for both the insurers and the patients. But we found also that women are facing high out-of-pocket costs for nondrug-based therapy – specifically for doctor visits, getting check-ups, diagnostic scans, and maybe other types of treatment, as well. ... It’s a very different story than the one typically being told about the preponderance of out-of-pocket costs being drug-related,” Dr. Conti said.

The explanation may be that progress in breast cancer treatment over the last decades has led to effective treatments that are largely now inexpensive. The situation is different with ovarian cancer and many blood cancers such as chronic lymphocytic leukemia and multiple myeloma. For them, the new, innovative, safe, and effective drugs are very expensive, she noted.

“I think that insurers can modulate the out-of-pocket costs associated with drug treatment through formulary design and other tools they have. It’s less easy for them to modulate out-of-pocket costs associated with other modalties of care. Still, for medical care that is obviously necessary, there needs to be a cap on what women should have to pay,” Dr. Conti said.

A further concern raised by Dr. Conti is shrinking Medicaid coverage with the expiration of COVID-specific expanded Medicaid eligibility.

“Policy folks are closely watching the size of uninsured populations and also the growing importance of the high deductible and consumer-driven plans in which patients face high out-of-pocket first dollar coverage for care. With Medicaid rolls shrinking, we’ll see more people in low-premium, not well-insured plans. Americans’ exposure to higher costs for guideline-recommended care might grow, especially as more of them are independent contractors in the gig economy and not working for big corporations.”

“We worry that if and when they get a diagnosis of breast cancer, which is common among younger women, they are going to be faced with costs associated with their care that are going to have to be paid out-of-pocket – and it’s not going to be for the drug, it’s the other types of care. Doctors should know that the younger patient population that they are serving might be facing burdens associated with their care.”

Dr. Conti added, “Among women who are underinsured, there is a clear burden associated with cancer treatment. Reform efforts have largely focused on reducing out-of-pocket costs for seniors and have not focused much on guideline-consistent care for those under 65 who are working. Their burden can be quite onerous and cause financial harm for them and their families, resulting in worse health,” she continued, “Policy attention should go to unburdening people who have a serious diagnosis and who really have to be treated. There’s very good evidence that imposing additional out-of-pocket costs for guideline-consistent care causes people to make really hard decisions about paying rent versus paying for meds, about splitting pills and not doing all the things their physician is recommending, and about staying in jobs they don’t love but are locked into [because of health coverage].”

Dr. Conti concluded, “The good news is that, in breast cancer, the drugs work and are cheap. But the bad news is that there are many people who are underinsured and therefore, their care still has a high out-of-pocket burden. ACA radically changed working age people’s ability to qualify for insurance and be insured, but that didn’t mean that they are really well-covered when they become sick. They are still in peril over high out-of-pocket costs because of the proliferation of plans that are very skimpy. Women think they are insured until they get a diagnosis.”

Noting study limitations, Dr. Conti said that OOP costs cited are an underestimate, because many patients will also be treated for other comorbidities and complications related to treatment.

The authors disclosed no conflicts of interest. The study was funded by the American Cancer Society.

Among a sample of younger women with invasive breast cancer and employer-sponsored insurance, outpatient-related out-of-pocket (OOP) costs were greater than drug costs.

For these same patients, prescriptions were largely for nonproprietary anticancer drugs and entailed limited OOP costs. For women with high-deductible health plans (HDHPs) and commercially driven health plans (CDHPs), OOP costs were higher, compared with coverage by more generous plans, according to the Research Letter published in JAMA Network Open.

“You would expect that people undergoing cancer treatment should not have to face very high out-of-pocket costs associated with care regardless of treatment modality because their treatment is largely guideline-indicated, and they have no choices,” stated corresponding author Rena Conti, PhD, associate professor with the school of business, Boston University, in an interview. “If you are diagnosed with cancer and undergoing treatment, you’re following the recommendation of your doctor, and your doctor is following standard protocols for treatment. In that scenario, Economics 101 suggests that people should not have to pay anything or [should pay] very little, especially for things that are cheap and are known to be effective, because there’s no overuse. Where normally we think that out-of-pocket costs are meant to control overuse, people with breast cancer are not opting to get more than indicated chemotherapy or radiation.”

The analysis of 25,224 women with invasive breast cancer diagnosis and claims for 1 or more of 14 oral anticancer drugs revealed that OOP costs for nondrug outpatient claims represented 79.0% of total costs. OOP drug costs were modest, with a 30-day supply ranging from $0.57-$0.60 for tamoxifen to $134.08-$141.07 for palbociclib.

“We were interested in understanding to what extent women who are insured with private insurance are exposed to out-of-pocket costs for standard breast cancer treatment, both in looking at drugs, but also the other aspects of the treatments they undergo.”

High OOP costs for the oral anticancer prescription drugs that are central to breast cancer treatment are associated with treatment nonadherence and discontinuation. Little has been known, however, about OOP costs of treatment associated with invasive breast cancer among employer-insured women younger than 65 years, the paper says.

“This population may face significant financial burdens related to long-term hormonal-based prevention and enrollment in high-deductible health plans and consumer-driven health plans,” the authors state in their paper.

In the cross-sectional study, which used the national 2018 Marative MarketScan database, 23.1% were HDHP- or CDHP-insured. Fifty-one percent had no OOP costs for drugs. The total mean estimated OOP cost, however, was $1,502.23 per patient, with inpatient costs representing only $112.41 (95% confidence interval, $112.40-$112.42); outpatient costs were $1,186.27 (95% CI, $1,185.67-$1,188.16). Pharmaceutical costs were $203.55 (95% CI, $203.34-$203.78).“We were surprised to find that the vast majority were getting breast cancer treatment with older, very effective, very safe, relatively inexpensive drugs and had limited out-of-pocket costs with some variation – higher costs for the few receiving newer, expensive drugs. The backbone of treatment is the older, generic drugs, which are cheap for both the insurers and the patients. But we found also that women are facing high out-of-pocket costs for nondrug-based therapy – specifically for doctor visits, getting check-ups, diagnostic scans, and maybe other types of treatment, as well. ... It’s a very different story than the one typically being told about the preponderance of out-of-pocket costs being drug-related,” Dr. Conti said.

The explanation may be that progress in breast cancer treatment over the last decades has led to effective treatments that are largely now inexpensive. The situation is different with ovarian cancer and many blood cancers such as chronic lymphocytic leukemia and multiple myeloma. For them, the new, innovative, safe, and effective drugs are very expensive, she noted.

“I think that insurers can modulate the out-of-pocket costs associated with drug treatment through formulary design and other tools they have. It’s less easy for them to modulate out-of-pocket costs associated with other modalties of care. Still, for medical care that is obviously necessary, there needs to be a cap on what women should have to pay,” Dr. Conti said.

A further concern raised by Dr. Conti is shrinking Medicaid coverage with the expiration of COVID-specific expanded Medicaid eligibility.

“Policy folks are closely watching the size of uninsured populations and also the growing importance of the high deductible and consumer-driven plans in which patients face high out-of-pocket first dollar coverage for care. With Medicaid rolls shrinking, we’ll see more people in low-premium, not well-insured plans. Americans’ exposure to higher costs for guideline-recommended care might grow, especially as more of them are independent contractors in the gig economy and not working for big corporations.”

“We worry that if and when they get a diagnosis of breast cancer, which is common among younger women, they are going to be faced with costs associated with their care that are going to have to be paid out-of-pocket – and it’s not going to be for the drug, it’s the other types of care. Doctors should know that the younger patient population that they are serving might be facing burdens associated with their care.”

Dr. Conti added, “Among women who are underinsured, there is a clear burden associated with cancer treatment. Reform efforts have largely focused on reducing out-of-pocket costs for seniors and have not focused much on guideline-consistent care for those under 65 who are working. Their burden can be quite onerous and cause financial harm for them and their families, resulting in worse health,” she continued, “Policy attention should go to unburdening people who have a serious diagnosis and who really have to be treated. There’s very good evidence that imposing additional out-of-pocket costs for guideline-consistent care causes people to make really hard decisions about paying rent versus paying for meds, about splitting pills and not doing all the things their physician is recommending, and about staying in jobs they don’t love but are locked into [because of health coverage].”

Dr. Conti concluded, “The good news is that, in breast cancer, the drugs work and are cheap. But the bad news is that there are many people who are underinsured and therefore, their care still has a high out-of-pocket burden. ACA radically changed working age people’s ability to qualify for insurance and be insured, but that didn’t mean that they are really well-covered when they become sick. They are still in peril over high out-of-pocket costs because of the proliferation of plans that are very skimpy. Women think they are insured until they get a diagnosis.”

Noting study limitations, Dr. Conti said that OOP costs cited are an underestimate, because many patients will also be treated for other comorbidities and complications related to treatment.

The authors disclosed no conflicts of interest. The study was funded by the American Cancer Society.

Implementing universal ultrasound during the third trimester of pregnancy significantly reduced the number of undiagnosed breech presentations, according to a study published in PLOS Medicine. The effects held if sonographers used a traditional ultrasound machine or if midwives used a handheld ultrasound tool to perform what is known as a point-of-care ultrasound (POCUS) procedure.

“Giving pregnant women a third-trimester scan reduces the rate of undetected breech in labor by over two-thirds, which reduces the chances of harm to the baby,” said Asma Khalil, MBBCh, MD, professor of obstetrics and maternal-fetal medicine at the University of London’s St. George’s Hospital, and a coauthor of the new study.

Routine ultrasounds typically are performed from the 10th to the 13th week of pregnancy, not during the third trimester, when the risk for a breech birth would be most apparent. Breech births occur in 3%-4% of pregnancies, raising the risk that babies will experience broken bones or hemorrhage. Knowing that breech is possible before birth enables physicians to discuss options with the pregnant woman in advance, Dr. Khalil said. These steps include rotating the baby in the uterus or conducting a cesarean delivery. Such counseling is not possible if breech is undetected until spontaneous or induced labor. 

“Breech presentation at term is not very common, but diagnosing it prior to the onset of labor or induction of labor offers patients much more flexibility in terms of options and planning,” said Cecilia B. Leggett, MD, a resident in obstetrics and gynecology at Cedars-Sinai in Los Angeles. Dr. Leggett, who was not involved in the study, has shown that handheld devices are as accurate at assessing fetal weight as are standard ultrasound machines.
 

Two tools, same result

Dr. Khalil and her colleagues compared the rates of undiagnosed breech presentations before and after implementing universal third-semester ultrasound at two hospitals in the United Kingdom. The requirement began in 2020; the study compared the rate of undiagnosed breeches from the period of 2016-2020 with that of 2020-2021.

St. George’s Hospital in London used a traditional ultrasound machine that is read by a sonographer, whereas the Norfolk and Norwich University Hospitals, in Norwich, England, employed midwives to use a handheld ultrasound device.

The rate of undiagnosed breech cases declined from 14.2% at St. George’s before the universal ultrasound requirement (82 missed cases of 578 breech births) to 2.8% after the requirement began (7 missed cases of 251 breech births). The story was similar at Norfolk and Norwich, where 16.2% missed breech cases occurred before the requirement (27 of 167) and 3.5% missed cases were reported after it (5 of 142).

The increased accuracy of breech diagnosis before labor probably led to fewer cases of impaired blood flow to a baby’s brain at birth, Dr. Khalil’s group reported, as well as a probable reduction in the number of stillborn babies or those who die extremely young.

Traditional ultrasound scans read by sonographers are expensive, Dr. Khalil noted, whereas the portable handheld devices are much cheaper and could be used widely to improve detection of breech births. That step would require robust training about how to properly use these devices, Dr. Leggett said.

“As we see more and more studies come out about technology for POCUS, I think it’s important to keep in mind that we need the education about the tools to be as accessible as the tools themselves,” she said.

Dr. Leggett had no relevant financial relationships. Dr. Khalil is a vice president of the Royal College of Obstetricians and Gynaecologists, is a trustee and the treasurer of the International Society of Ultrasound in Obstetrics and Gynecology, and has lectured at and consulted in several ultrasound-based projects, webinars, and educational events.
 

A version of this article first appeared on Medscape.com.

Implementing universal ultrasound during the third trimester of pregnancy significantly reduced the number of undiagnosed breech presentations, according to a study published in PLOS Medicine. The effects held if sonographers used a traditional ultrasound machine or if midwives used a handheld ultrasound tool to perform what is known as a point-of-care ultrasound (POCUS) procedure.

“Giving pregnant women a third-trimester scan reduces the rate of undetected breech in labor by over two-thirds, which reduces the chances of harm to the baby,” said Asma Khalil, MBBCh, MD, professor of obstetrics and maternal-fetal medicine at the University of London’s St. George’s Hospital, and a coauthor of the new study.

Routine ultrasounds typically are performed from the 10th to the 13th week of pregnancy, not during the third trimester, when the risk for a breech birth would be most apparent. Breech births occur in 3%-4% of pregnancies, raising the risk that babies will experience broken bones or hemorrhage. Knowing that breech is possible before birth enables physicians to discuss options with the pregnant woman in advance, Dr. Khalil said. These steps include rotating the baby in the uterus or conducting a cesarean delivery. Such counseling is not possible if breech is undetected until spontaneous or induced labor. 

“Breech presentation at term is not very common, but diagnosing it prior to the onset of labor or induction of labor offers patients much more flexibility in terms of options and planning,” said Cecilia B. Leggett, MD, a resident in obstetrics and gynecology at Cedars-Sinai in Los Angeles. Dr. Leggett, who was not involved in the study, has shown that handheld devices are as accurate at assessing fetal weight as are standard ultrasound machines.
 

Two tools, same result

Dr. Khalil and her colleagues compared the rates of undiagnosed breech presentations before and after implementing universal third-semester ultrasound at two hospitals in the United Kingdom. The requirement began in 2020; the study compared the rate of undiagnosed breeches from the period of 2016-2020 with that of 2020-2021.

St. George’s Hospital in London used a traditional ultrasound machine that is read by a sonographer, whereas the Norfolk and Norwich University Hospitals, in Norwich, England, employed midwives to use a handheld ultrasound device.

The rate of undiagnosed breech cases declined from 14.2% at St. George’s before the universal ultrasound requirement (82 missed cases of 578 breech births) to 2.8% after the requirement began (7 missed cases of 251 breech births). The story was similar at Norfolk and Norwich, where 16.2% missed breech cases occurred before the requirement (27 of 167) and 3.5% missed cases were reported after it (5 of 142).

The increased accuracy of breech diagnosis before labor probably led to fewer cases of impaired blood flow to a baby’s brain at birth, Dr. Khalil’s group reported, as well as a probable reduction in the number of stillborn babies or those who die extremely young.

Traditional ultrasound scans read by sonographers are expensive, Dr. Khalil noted, whereas the portable handheld devices are much cheaper and could be used widely to improve detection of breech births. That step would require robust training about how to properly use these devices, Dr. Leggett said.

“As we see more and more studies come out about technology for POCUS, I think it’s important to keep in mind that we need the education about the tools to be as accessible as the tools themselves,” she said.

Dr. Leggett had no relevant financial relationships. Dr. Khalil is a vice president of the Royal College of Obstetricians and Gynaecologists, is a trustee and the treasurer of the International Society of Ultrasound in Obstetrics and Gynecology, and has lectured at and consulted in several ultrasound-based projects, webinars, and educational events.
 

A version of this article first appeared on Medscape.com.

Implementing universal ultrasound during the third trimester of pregnancy significantly reduced the number of undiagnosed breech presentations, according to a study published in PLOS Medicine. The effects held if sonographers used a traditional ultrasound machine or if midwives used a handheld ultrasound tool to perform what is known as a point-of-care ultrasound (POCUS) procedure.

“Giving pregnant women a third-trimester scan reduces the rate of undetected breech in labor by over two-thirds, which reduces the chances of harm to the baby,” said Asma Khalil, MBBCh, MD, professor of obstetrics and maternal-fetal medicine at the University of London’s St. George’s Hospital, and a coauthor of the new study.

Routine ultrasounds typically are performed from the 10th to the 13th week of pregnancy, not during the third trimester, when the risk for a breech birth would be most apparent. Breech births occur in 3%-4% of pregnancies, raising the risk that babies will experience broken bones or hemorrhage. Knowing that breech is possible before birth enables physicians to discuss options with the pregnant woman in advance, Dr. Khalil said. These steps include rotating the baby in the uterus or conducting a cesarean delivery. Such counseling is not possible if breech is undetected until spontaneous or induced labor. 

“Breech presentation at term is not very common, but diagnosing it prior to the onset of labor or induction of labor offers patients much more flexibility in terms of options and planning,” said Cecilia B. Leggett, MD, a resident in obstetrics and gynecology at Cedars-Sinai in Los Angeles. Dr. Leggett, who was not involved in the study, has shown that handheld devices are as accurate at assessing fetal weight as are standard ultrasound machines.
 

Two tools, same result

Dr. Khalil and her colleagues compared the rates of undiagnosed breech presentations before and after implementing universal third-semester ultrasound at two hospitals in the United Kingdom. The requirement began in 2020; the study compared the rate of undiagnosed breeches from the period of 2016-2020 with that of 2020-2021.

St. George’s Hospital in London used a traditional ultrasound machine that is read by a sonographer, whereas the Norfolk and Norwich University Hospitals, in Norwich, England, employed midwives to use a handheld ultrasound device.

The rate of undiagnosed breech cases declined from 14.2% at St. George’s before the universal ultrasound requirement (82 missed cases of 578 breech births) to 2.8% after the requirement began (7 missed cases of 251 breech births). The story was similar at Norfolk and Norwich, where 16.2% missed breech cases occurred before the requirement (27 of 167) and 3.5% missed cases were reported after it (5 of 142).

The increased accuracy of breech diagnosis before labor probably led to fewer cases of impaired blood flow to a baby’s brain at birth, Dr. Khalil’s group reported, as well as a probable reduction in the number of stillborn babies or those who die extremely young.

Traditional ultrasound scans read by sonographers are expensive, Dr. Khalil noted, whereas the portable handheld devices are much cheaper and could be used widely to improve detection of breech births. That step would require robust training about how to properly use these devices, Dr. Leggett said.

“As we see more and more studies come out about technology for POCUS, I think it’s important to keep in mind that we need the education about the tools to be as accessible as the tools themselves,” she said.

Dr. Leggett had no relevant financial relationships. Dr. Khalil is a vice president of the Royal College of Obstetricians and Gynaecologists, is a trustee and the treasurer of the International Society of Ultrasound in Obstetrics and Gynecology, and has lectured at and consulted in several ultrasound-based projects, webinars, and educational events.
 

A version of this article first appeared on Medscape.com.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

Results of a study recently published in Nature Communications suggests that radiation from ultraviolet nail polish dryers could induce cell death and trigger molecular changes linked to cancer in human cells. According to two experts, these findings raise concerns regarding the safety of frequent use of these nail dryers.

In the study, human and mouse cells were exposed to radiation from UV nail dryers. Exposing human and mice skin cells to UVA light for 20 minutes resulted in the death of 20%-30% of cells; three consecutive 20-minute sessions resulted in the death of 65%-70% of cells. Additionally, surviving cells suffered oxidative damage to their DNA and mitochondria, with mutational patterns similar to those seen in skin cancer, study investigator Maria Zhivagui, PhD, of the University of California, San Diego, and associates reported.  

“This study showed that irradiation of human and mouse cell lines using UV nail polish dryers resulted in DNA damage and genome mutations,” Shari Lipner, MD, PhD, director of the nail division at New York–Presbyterian Hospital/Weill Cornell Medicine, New York, said in an interview. The study “ties together exposure to UV light from nail polish dryers and genetic mutations that are associated with skin cancers,” added Dr. Lipner, who was not involved with the study.

UV nail lamps are commonly used to dry and harden gel nail polish formulas. Often referred to as “mini tanning beds,” these devices emit UVA radiation, classified as a Group 1 Carcinogen by the International Agency for Research on Cancer.

“Both UVA and UVB are main drivers of both melanoma and keratinocyte carcinomas (basal cell carcinoma and squamous cell carcinoma),” said Anthony Rossi, MD, a dermatologic surgeon at Memorial Sloan Kettering Cancer Center, New York, who was also not a study investigator. UV irradiance “produces DNA mutations that are specific to forming types of skin cancer,” he said in an interview.

UVA wavelengths commonly used in nail dryers can penetrate all layers of the epidermis, the top layer of the skin, potentially affecting stem cells in the skin, according to the study.

Dr. Lipner noted that “there have been several case reports of patients with histories of gel manicures using UV nail polish dryers who later developed squamous cell carcinomas on the dorsal hands, fingers, and nails, and articles describing high UV emissions from nail polish dryers, but the direct connection between UV dryers and skin cancer development was tenuous.” The first of its kind, the new study investigated the impact of UV nail drying devices at a cellular level.

The results of this study, in combination with previous case reports suggesting the development of skin cancers following UVA dryer use, raise concern regarding the safety of these commonly used devices. The study, the authors wrote, “does not provide direct evidence for an increased cancer risk in human beings,” but their findings and “prior evidence strongly suggest that radiation emitted by UV nail polish dryers may cause cancers of the hand and that UV nail polish dryers, similar to tanning beds, may increase the risk of early onset skin cancer.”

Courtesy MSKCC

Dr. Rossi said that, “while this study shows that the UV exposure does affect human cells and causes mutations, the study was not done in vivo in human beings, so further studies are needed to know at what dose and frequency gel manicures would be needed to cause detrimental effects.” However, for people who regularly receive gel manicures involving UV nail dryers, both Dr. Lipner and Dr. Rossi recommend applying a broad-spectrum sunscreen to protect the dorsal hands, fingertips, and skin surrounding the nails, or wearing UV-protective gloves.

The study was supported by an Alfred B. Sloan Research Fellowship to one of the authors and grants from the National Institutes of Health to two authors. One author reported being a compensated consultant and having an equity interest in io9. Dr. Lipner and Dr. Rossi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Results of a study recently published in Nature Communications suggests that radiation from ultraviolet nail polish dryers could induce cell death and trigger molecular changes linked to cancer in human cells. According to two experts, these findings raise concerns regarding the safety of frequent use of these nail dryers.

In the study, human and mouse cells were exposed to radiation from UV nail dryers. Exposing human and mice skin cells to UVA light for 20 minutes resulted in the death of 20%-30% of cells; three consecutive 20-minute sessions resulted in the death of 65%-70% of cells. Additionally, surviving cells suffered oxidative damage to their DNA and mitochondria, with mutational patterns similar to those seen in skin cancer, study investigator Maria Zhivagui, PhD, of the University of California, San Diego, and associates reported.  

“This study showed that irradiation of human and mouse cell lines using UV nail polish dryers resulted in DNA damage and genome mutations,” Shari Lipner, MD, PhD, director of the nail division at New York–Presbyterian Hospital/Weill Cornell Medicine, New York, said in an interview. The study “ties together exposure to UV light from nail polish dryers and genetic mutations that are associated with skin cancers,” added Dr. Lipner, who was not involved with the study.

UV nail lamps are commonly used to dry and harden gel nail polish formulas. Often referred to as “mini tanning beds,” these devices emit UVA radiation, classified as a Group 1 Carcinogen by the International Agency for Research on Cancer.

“Both UVA and UVB are main drivers of both melanoma and keratinocyte carcinomas (basal cell carcinoma and squamous cell carcinoma),” said Anthony Rossi, MD, a dermatologic surgeon at Memorial Sloan Kettering Cancer Center, New York, who was also not a study investigator. UV irradiance “produces DNA mutations that are specific to forming types of skin cancer,” he said in an interview.

UVA wavelengths commonly used in nail dryers can penetrate all layers of the epidermis, the top layer of the skin, potentially affecting stem cells in the skin, according to the study.

Dr. Lipner noted that “there have been several case reports of patients with histories of gel manicures using UV nail polish dryers who later developed squamous cell carcinomas on the dorsal hands, fingers, and nails, and articles describing high UV emissions from nail polish dryers, but the direct connection between UV dryers and skin cancer development was tenuous.” The first of its kind, the new study investigated the impact of UV nail drying devices at a cellular level.

The results of this study, in combination with previous case reports suggesting the development of skin cancers following UVA dryer use, raise concern regarding the safety of these commonly used devices. The study, the authors wrote, “does not provide direct evidence for an increased cancer risk in human beings,” but their findings and “prior evidence strongly suggest that radiation emitted by UV nail polish dryers may cause cancers of the hand and that UV nail polish dryers, similar to tanning beds, may increase the risk of early onset skin cancer.”

Courtesy MSKCC

Dr. Rossi said that, “while this study shows that the UV exposure does affect human cells and causes mutations, the study was not done in vivo in human beings, so further studies are needed to know at what dose and frequency gel manicures would be needed to cause detrimental effects.” However, for people who regularly receive gel manicures involving UV nail dryers, both Dr. Lipner and Dr. Rossi recommend applying a broad-spectrum sunscreen to protect the dorsal hands, fingertips, and skin surrounding the nails, or wearing UV-protective gloves.

The study was supported by an Alfred B. Sloan Research Fellowship to one of the authors and grants from the National Institutes of Health to two authors. One author reported being a compensated consultant and having an equity interest in io9. Dr. Lipner and Dr. Rossi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Results of a study recently published in Nature Communications suggests that radiation from ultraviolet nail polish dryers could induce cell death and trigger molecular changes linked to cancer in human cells. According to two experts, these findings raise concerns regarding the safety of frequent use of these nail dryers.

In the study, human and mouse cells were exposed to radiation from UV nail dryers. Exposing human and mice skin cells to UVA light for 20 minutes resulted in the death of 20%-30% of cells; three consecutive 20-minute sessions resulted in the death of 65%-70% of cells. Additionally, surviving cells suffered oxidative damage to their DNA and mitochondria, with mutational patterns similar to those seen in skin cancer, study investigator Maria Zhivagui, PhD, of the University of California, San Diego, and associates reported.  

“This study showed that irradiation of human and mouse cell lines using UV nail polish dryers resulted in DNA damage and genome mutations,” Shari Lipner, MD, PhD, director of the nail division at New York–Presbyterian Hospital/Weill Cornell Medicine, New York, said in an interview. The study “ties together exposure to UV light from nail polish dryers and genetic mutations that are associated with skin cancers,” added Dr. Lipner, who was not involved with the study.

UV nail lamps are commonly used to dry and harden gel nail polish formulas. Often referred to as “mini tanning beds,” these devices emit UVA radiation, classified as a Group 1 Carcinogen by the International Agency for Research on Cancer.

“Both UVA and UVB are main drivers of both melanoma and keratinocyte carcinomas (basal cell carcinoma and squamous cell carcinoma),” said Anthony Rossi, MD, a dermatologic surgeon at Memorial Sloan Kettering Cancer Center, New York, who was also not a study investigator. UV irradiance “produces DNA mutations that are specific to forming types of skin cancer,” he said in an interview.

UVA wavelengths commonly used in nail dryers can penetrate all layers of the epidermis, the top layer of the skin, potentially affecting stem cells in the skin, according to the study.

Dr. Lipner noted that “there have been several case reports of patients with histories of gel manicures using UV nail polish dryers who later developed squamous cell carcinomas on the dorsal hands, fingers, and nails, and articles describing high UV emissions from nail polish dryers, but the direct connection between UV dryers and skin cancer development was tenuous.” The first of its kind, the new study investigated the impact of UV nail drying devices at a cellular level.

The results of this study, in combination with previous case reports suggesting the development of skin cancers following UVA dryer use, raise concern regarding the safety of these commonly used devices. The study, the authors wrote, “does not provide direct evidence for an increased cancer risk in human beings,” but their findings and “prior evidence strongly suggest that radiation emitted by UV nail polish dryers may cause cancers of the hand and that UV nail polish dryers, similar to tanning beds, may increase the risk of early onset skin cancer.”

Courtesy MSKCC

Dr. Rossi said that, “while this study shows that the UV exposure does affect human cells and causes mutations, the study was not done in vivo in human beings, so further studies are needed to know at what dose and frequency gel manicures would be needed to cause detrimental effects.” However, for people who regularly receive gel manicures involving UV nail dryers, both Dr. Lipner and Dr. Rossi recommend applying a broad-spectrum sunscreen to protect the dorsal hands, fingertips, and skin surrounding the nails, or wearing UV-protective gloves.

The study was supported by an Alfred B. Sloan Research Fellowship to one of the authors and grants from the National Institutes of Health to two authors. One author reported being a compensated consultant and having an equity interest in io9. Dr. Lipner and Dr. Rossi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has decided to withdraw approval of Makena and generic versions of the drug, the agency announced April 6.

The medication was approved in 2011 to reduce the risk for preterm birth in women who had previously experienced spontaneous preterm birth. The treatment had been approved under an accelerated pathway that required another trial to confirm clinical benefit.

A postmarketing study did not show clinical benefit, however, and the agency proposed withdrawing the drug, hydroxyprogesterone caproate injection, in 2020. The drug’s sponsor requested a hearing on the decision, and that meeting was held in October 2022.

The FDA commissioner and chief scientist subsequently reviewed submitted reports, comments, and transcripts, and made the decision to withdraw the drug.

“Effective today, Makena and its generics are no longer approved and cannot lawfully be distributed in interstate commerce,” the agency said.

“It is tragic that the scientific research and medical communities have not yet found a treatment shown to be effective in preventing preterm birth and improving neonatal outcomes – particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women,” FDA Commissioner Robert M. Califf, MD, said in a statement.

Risks associated with the drug include thromboembolic disorders, allergic reactions, decreased glucose tolerance, and fluid retention, regulators have noted. The agency acknowledged that some supplies of the product have already been distributed. Patients with questions should talk to their health care provider, the FDA advised.

The Food and Drug Administration has decided to withdraw approval of Makena and generic versions of the drug, the agency announced April 6.

The medication was approved in 2011 to reduce the risk for preterm birth in women who had previously experienced spontaneous preterm birth. The treatment had been approved under an accelerated pathway that required another trial to confirm clinical benefit.

A postmarketing study did not show clinical benefit, however, and the agency proposed withdrawing the drug, hydroxyprogesterone caproate injection, in 2020. The drug’s sponsor requested a hearing on the decision, and that meeting was held in October 2022.

The FDA commissioner and chief scientist subsequently reviewed submitted reports, comments, and transcripts, and made the decision to withdraw the drug.

“Effective today, Makena and its generics are no longer approved and cannot lawfully be distributed in interstate commerce,” the agency said.

“It is tragic that the scientific research and medical communities have not yet found a treatment shown to be effective in preventing preterm birth and improving neonatal outcomes – particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women,” FDA Commissioner Robert M. Califf, MD, said in a statement.

Risks associated with the drug include thromboembolic disorders, allergic reactions, decreased glucose tolerance, and fluid retention, regulators have noted. The agency acknowledged that some supplies of the product have already been distributed. Patients with questions should talk to their health care provider, the FDA advised.

The Food and Drug Administration has decided to withdraw approval of Makena and generic versions of the drug, the agency announced April 6.

The medication was approved in 2011 to reduce the risk for preterm birth in women who had previously experienced spontaneous preterm birth. The treatment had been approved under an accelerated pathway that required another trial to confirm clinical benefit.

A postmarketing study did not show clinical benefit, however, and the agency proposed withdrawing the drug, hydroxyprogesterone caproate injection, in 2020. The drug’s sponsor requested a hearing on the decision, and that meeting was held in October 2022.

The FDA commissioner and chief scientist subsequently reviewed submitted reports, comments, and transcripts, and made the decision to withdraw the drug.

“Effective today, Makena and its generics are no longer approved and cannot lawfully be distributed in interstate commerce,” the agency said.

“It is tragic that the scientific research and medical communities have not yet found a treatment shown to be effective in preventing preterm birth and improving neonatal outcomes – particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women,” FDA Commissioner Robert M. Califf, MD, said in a statement.

Risks associated with the drug include thromboembolic disorders, allergic reactions, decreased glucose tolerance, and fluid retention, regulators have noted. The agency acknowledged that some supplies of the product have already been distributed. Patients with questions should talk to their health care provider, the FDA advised.

Compared with infants who were not exposed to COVID-19 in the womb, those who were exposed had a lower weight and body mass index at birth, but greater weight gain, during the first year of life, in a new analysis.

This “exaggerated growth pattern observed among infants with COVID-19 exposure may in some cases be a catch-up response to a prenatal growth deficit,” Mollie W. Ockene and colleagues wrote in a report published recently in the Journal of Clinical Endocrinology & Metabolism.

But given that lower birth weight and accelerated postnatal weight gain are risk factors for cardiometabolic disease, the findings “raise concern” about whether children born to mothers with prenatal COVID-19 go on to develop obesity, diabetes, or cardiovascular disease, senior coauthors Andrea G. Edlow, MD, and Lindsay T. Fourman, MD, of Massachusetts General Hospital, Boston, told this news organization.

Further studies in larger numbers of patients with longer follow-up and detailed assessments are needed, the researchers said, but this points to “a potentially increased cardiometabolic disease risk for the large global population of children with in utero COVID-19 exposure.”

It will be “important for clinicians caring for children with in utero exposure to maternal COVID-19 to be aware of this history,” Dr. Edlow and Dr. Fourman added, “and to view the child’s growth trajectory and metabolic risk factors in a holistic context that includes this prenatal infection exposure.”
 

COVID-19 vaccination important during and prior to pregnancy

The study also underscores the importance of primary prevention of COVID-19 among women who are contemplating pregnancy or who are already pregnant, the researchers noted, “including the need for widespread implementation of protective measures such as indoor masking and COVID-19 vaccination and boosting during or prior to pregnancy.”

Dr. Edlow and Dr. Fourman added, “Given the disproportionate impact that COVID-19 has had on historically marginalized populations, adverse health outcomes following in utero exposure to maternal COVID-19 may threaten to widen existing disparities in child health.”

On the other hand, although “COVID-19 vaccination rates lagged behind in minority populations following the initial vaccine rollout,” they noted, “these differences have fortunately narrowed over time, particularly for Hispanic individuals, though they do still persist in the Black population,” according to a recent report.
 

BMI trajectories during first year of life

In utero exposure to COVID-19 has been linked to fetal/neonatal morbidity and mortality, including stillbirth, preterm birth, preeclampsia, and gestational hypertension, but less is known about infant outcomes during the first year of life.

The researchers aimed to compare weight, length, and BMI trajectories over the first year of life in infants with, versus without, in utero exposure to COVID-19.

They identified 149 infants with in utero exposure to COVID-19 and 127 unexposed infants; all were born between March 30, 2020, and May 30, 2021, to mothers who participated in the Mass General Brigham COVID-19 Perinatal Biorepository.

The study excluded infants whose mothers received the vaccine (n = 5) or who had unclear vaccination status during pregnancy (n = 4) to reduce sample heterogeneity.

At the time of the study, few women had received the COVID-19 vaccine because vaccines were approved by the Food and Drug Administration for emergency use in December 2020 and the CDC recommended them for all pregnant women much later, in August 2021.

The researchers examined the weight, length, and BMI of the infants at birth, and at 2, 6, and 12 months, standardized using World Health Organization (WHO) growth charts.

Compared with mothers who did not have COVID-19 during pregnancy, those who had COVID-19 were younger (mean age, 32 vs. 34 years) and had a higher earliest BMI during pregnancy (29 vs. 26 kg/m²) and greater parity (previous births, excluding the index pregnancy, 1.2 vs. 0.9), and they were more likely to be Hispanic or Black and less likely to have private insurance.

Compared with infants exposed to COVID-19 in utero, infants who were not exposed were more likely to be male (47% vs. 55%).

Both infant groups were equally likely to be breastfed (90%).

Compared with the unexposed infants, infants born to mothers with prenatal COVID-19 had lower BMI z-scores at birth (effect size, −0.35; P = .03) and greater gain in BMI z-scores from birth to 12 months (effect size, 0.53; P = .03), but they had similar length at birth and over 12 months, after adjustment for maternal age at delivery, ethnicity, parity, insurance status, and earliest BMI during pregnancy, as well as infant sex, date of birth, and if applicable, history of breastfeeding.

The study received funding from the National Institutes of Health, Harvard Nutrition Obesity Research Center, Boston Area Diabetes Endocrinology Research Centers, American Heart Association, and Simons Foundation. Ms. Ockene has reported no relevant financial relationships. Dr. Edlow has reported being a consultant for Mirvie and receiving research funding from Merck outside the study. Dr. Fourman has reported serving as a consultant and receiving grant funding to her institution from Amryt outside the study. Disclosures for the other authors are listed with the article.

Compared with infants who were not exposed to COVID-19 in the womb, those who were exposed had a lower weight and body mass index at birth, but greater weight gain, during the first year of life, in a new analysis.

This “exaggerated growth pattern observed among infants with COVID-19 exposure may in some cases be a catch-up response to a prenatal growth deficit,” Mollie W. Ockene and colleagues wrote in a report published recently in the Journal of Clinical Endocrinology & Metabolism.

But given that lower birth weight and accelerated postnatal weight gain are risk factors for cardiometabolic disease, the findings “raise concern” about whether children born to mothers with prenatal COVID-19 go on to develop obesity, diabetes, or cardiovascular disease, senior coauthors Andrea G. Edlow, MD, and Lindsay T. Fourman, MD, of Massachusetts General Hospital, Boston, told this news organization.

Further studies in larger numbers of patients with longer follow-up and detailed assessments are needed, the researchers said, but this points to “a potentially increased cardiometabolic disease risk for the large global population of children with in utero COVID-19 exposure.”

It will be “important for clinicians caring for children with in utero exposure to maternal COVID-19 to be aware of this history,” Dr. Edlow and Dr. Fourman added, “and to view the child’s growth trajectory and metabolic risk factors in a holistic context that includes this prenatal infection exposure.”
 

COVID-19 vaccination important during and prior to pregnancy

The study also underscores the importance of primary prevention of COVID-19 among women who are contemplating pregnancy or who are already pregnant, the researchers noted, “including the need for widespread implementation of protective measures such as indoor masking and COVID-19 vaccination and boosting during or prior to pregnancy.”

Dr. Edlow and Dr. Fourman added, “Given the disproportionate impact that COVID-19 has had on historically marginalized populations, adverse health outcomes following in utero exposure to maternal COVID-19 may threaten to widen existing disparities in child health.”

On the other hand, although “COVID-19 vaccination rates lagged behind in minority populations following the initial vaccine rollout,” they noted, “these differences have fortunately narrowed over time, particularly for Hispanic individuals, though they do still persist in the Black population,” according to a recent report.
 

BMI trajectories during first year of life

In utero exposure to COVID-19 has been linked to fetal/neonatal morbidity and mortality, including stillbirth, preterm birth, preeclampsia, and gestational hypertension, but less is known about infant outcomes during the first year of life.

The researchers aimed to compare weight, length, and BMI trajectories over the first year of life in infants with, versus without, in utero exposure to COVID-19.

They identified 149 infants with in utero exposure to COVID-19 and 127 unexposed infants; all were born between March 30, 2020, and May 30, 2021, to mothers who participated in the Mass General Brigham COVID-19 Perinatal Biorepository.

The study excluded infants whose mothers received the vaccine (n = 5) or who had unclear vaccination status during pregnancy (n = 4) to reduce sample heterogeneity.

At the time of the study, few women had received the COVID-19 vaccine because vaccines were approved by the Food and Drug Administration for emergency use in December 2020 and the CDC recommended them for all pregnant women much later, in August 2021.

The researchers examined the weight, length, and BMI of the infants at birth, and at 2, 6, and 12 months, standardized using World Health Organization (WHO) growth charts.

Compared with mothers who did not have COVID-19 during pregnancy, those who had COVID-19 were younger (mean age, 32 vs. 34 years) and had a higher earliest BMI during pregnancy (29 vs. 26 kg/m²) and greater parity (previous births, excluding the index pregnancy, 1.2 vs. 0.9), and they were more likely to be Hispanic or Black and less likely to have private insurance.

Compared with infants exposed to COVID-19 in utero, infants who were not exposed were more likely to be male (47% vs. 55%).

Both infant groups were equally likely to be breastfed (90%).

Compared with the unexposed infants, infants born to mothers with prenatal COVID-19 had lower BMI z-scores at birth (effect size, −0.35; P = .03) and greater gain in BMI z-scores from birth to 12 months (effect size, 0.53; P = .03), but they had similar length at birth and over 12 months, after adjustment for maternal age at delivery, ethnicity, parity, insurance status, and earliest BMI during pregnancy, as well as infant sex, date of birth, and if applicable, history of breastfeeding.

The study received funding from the National Institutes of Health, Harvard Nutrition Obesity Research Center, Boston Area Diabetes Endocrinology Research Centers, American Heart Association, and Simons Foundation. Ms. Ockene has reported no relevant financial relationships. Dr. Edlow has reported being a consultant for Mirvie and receiving research funding from Merck outside the study. Dr. Fourman has reported serving as a consultant and receiving grant funding to her institution from Amryt outside the study. Disclosures for the other authors are listed with the article.

Compared with infants who were not exposed to COVID-19 in the womb, those who were exposed had a lower weight and body mass index at birth, but greater weight gain, during the first year of life, in a new analysis.

This “exaggerated growth pattern observed among infants with COVID-19 exposure may in some cases be a catch-up response to a prenatal growth deficit,” Mollie W. Ockene and colleagues wrote in a report published recently in the Journal of Clinical Endocrinology & Metabolism.

But given that lower birth weight and accelerated postnatal weight gain are risk factors for cardiometabolic disease, the findings “raise concern” about whether children born to mothers with prenatal COVID-19 go on to develop obesity, diabetes, or cardiovascular disease, senior coauthors Andrea G. Edlow, MD, and Lindsay T. Fourman, MD, of Massachusetts General Hospital, Boston, told this news organization.

Further studies in larger numbers of patients with longer follow-up and detailed assessments are needed, the researchers said, but this points to “a potentially increased cardiometabolic disease risk for the large global population of children with in utero COVID-19 exposure.”

It will be “important for clinicians caring for children with in utero exposure to maternal COVID-19 to be aware of this history,” Dr. Edlow and Dr. Fourman added, “and to view the child’s growth trajectory and metabolic risk factors in a holistic context that includes this prenatal infection exposure.”
 

COVID-19 vaccination important during and prior to pregnancy

The study also underscores the importance of primary prevention of COVID-19 among women who are contemplating pregnancy or who are already pregnant, the researchers noted, “including the need for widespread implementation of protective measures such as indoor masking and COVID-19 vaccination and boosting during or prior to pregnancy.”

Dr. Edlow and Dr. Fourman added, “Given the disproportionate impact that COVID-19 has had on historically marginalized populations, adverse health outcomes following in utero exposure to maternal COVID-19 may threaten to widen existing disparities in child health.”

On the other hand, although “COVID-19 vaccination rates lagged behind in minority populations following the initial vaccine rollout,” they noted, “these differences have fortunately narrowed over time, particularly for Hispanic individuals, though they do still persist in the Black population,” according to a recent report.
 

BMI trajectories during first year of life

In utero exposure to COVID-19 has been linked to fetal/neonatal morbidity and mortality, including stillbirth, preterm birth, preeclampsia, and gestational hypertension, but less is known about infant outcomes during the first year of life.

The researchers aimed to compare weight, length, and BMI trajectories over the first year of life in infants with, versus without, in utero exposure to COVID-19.

They identified 149 infants with in utero exposure to COVID-19 and 127 unexposed infants; all were born between March 30, 2020, and May 30, 2021, to mothers who participated in the Mass General Brigham COVID-19 Perinatal Biorepository.

The study excluded infants whose mothers received the vaccine (n = 5) or who had unclear vaccination status during pregnancy (n = 4) to reduce sample heterogeneity.

At the time of the study, few women had received the COVID-19 vaccine because vaccines were approved by the Food and Drug Administration for emergency use in December 2020 and the CDC recommended them for all pregnant women much later, in August 2021.

The researchers examined the weight, length, and BMI of the infants at birth, and at 2, 6, and 12 months, standardized using World Health Organization (WHO) growth charts.

Compared with mothers who did not have COVID-19 during pregnancy, those who had COVID-19 were younger (mean age, 32 vs. 34 years) and had a higher earliest BMI during pregnancy (29 vs. 26 kg/m²) and greater parity (previous births, excluding the index pregnancy, 1.2 vs. 0.9), and they were more likely to be Hispanic or Black and less likely to have private insurance.

Compared with infants exposed to COVID-19 in utero, infants who were not exposed were more likely to be male (47% vs. 55%).

Both infant groups were equally likely to be breastfed (90%).

Compared with the unexposed infants, infants born to mothers with prenatal COVID-19 had lower BMI z-scores at birth (effect size, −0.35; P = .03) and greater gain in BMI z-scores from birth to 12 months (effect size, 0.53; P = .03), but they had similar length at birth and over 12 months, after adjustment for maternal age at delivery, ethnicity, parity, insurance status, and earliest BMI during pregnancy, as well as infant sex, date of birth, and if applicable, history of breastfeeding.

The study received funding from the National Institutes of Health, Harvard Nutrition Obesity Research Center, Boston Area Diabetes Endocrinology Research Centers, American Heart Association, and Simons Foundation. Ms. Ockene has reported no relevant financial relationships. Dr. Edlow has reported being a consultant for Mirvie and receiving research funding from Merck outside the study. Dr. Fourman has reported serving as a consultant and receiving grant funding to her institution from Amryt outside the study. Disclosures for the other authors are listed with the article.

Court cases show that physicians continually underestimate their liability in supervising nurse practitioners (NPs) and physician assistants (PAs).

Even in states that have abolished requirements that NPs be physician-supervised, physicians may still be liable by virtue of employing the NP, according to William P. Sullivan, DO, an attorney and emergency physician in Frankfort, Ill.

Indeed, the vast majority of lawsuits against NPs and PAs name the supervising physician. According to a study of claims against NPs from 2011 to 2016, 82% of the cases also named the supervising physician.

Employed or contracted physicians assigned to supervise NPs or PAs are also affected, Dr. Sullivan said. “The employed physicians’ contract with a hospital or staffing company may require them to assist in the selection, supervision, and/or training of NPs or PAs,” he said. He added that supervisory duties may also be assigned through hospital bylaws.

“The physician is usually not paid anything extra for this work and may not be given extra time to perform it,” Dr. Sullivan said. But still, he said, that physician could be named in a lawsuit and wind up bearing some responsibility for an NP’s or PA’s mistake.

In addition to facing medical malpractice suits, Dr. Sullivan said, doctors are often sanctioned by state licensure boards for improperly supervising NPs and PAs. Licensure boards often require extensive protocols for supervision of NPs and PAs.
 

Yet more states are removing supervision requirements

With the addition of Kansas and New York in 2022 and California in 2023, 27 states no longer require supervision for all or most NPs. Sixteen of those states, including New York and California, have instituted progressive practice authority that requires temporary supervision of new NPs but then removes supervision after a period of 6 months to 4 years, depending on the state, for the rest of their career.

“When it comes to NP independence, the horse is already out of the barn,” Dr. Sullivan said. “It’s unlikely that states will repeal laws granting NPs independence, and in fact, more states are likely to pass them.”

*PAs, in contrast, are well behind NPs in achieving independence, but the American Academy of Physician Associates (AAPA) is calling to eliminate a mandated relationship with a specific physician. So far, Utah, North Dakota and Wyoming have ended physician supervision of PAs, while California and Hawaii have eliminated mandated chart review. Other states are considering eliminating physician supervision of PAs, according to the AAPA.

In states that have abolished oversight requirements for NPs, “liability can then shift to the NP when the NP is fully independent,” Cathy Klein, an advanced practice registered nurse who helped found the NP profession 50 years ago, told this news organization. “More NPs are starting their own practices, and in many cases, patients actually prefer to see an NP.”

As more NPs became more autonomous, the average payment that NPs incurred in professional liability lawsuits rose by 10.5% from 2017 to 2022, to $332,187, according to the Nurses Service Organization (NSO), a nursing malpractice insurer.

The number of malpractice judgments against autonomous NPs alone has also been rising. From 2012 to 2017, autonomous NPs’ share of all NP cases rose from 7% to 16.4%, the NSO reported.

The good news for physicians is that states’ removal of restrictions on NPs has reduced physicians’ liability to some extent. A 2017 study found that enacting less restrictive scope-of-practice laws for NPs decreased the number of payments made by physicians in NP cases by as much as 31%.

However, the top location for NP payouts remains the physician’s office, not the autonomous NP’s practice, according to the latter NSO report. Plaintiffs sue NPs’ and PAs’ supervising physicians on the basis of legal concepts, such as vicarious liability and respondeat superior. Even if the physician-employer never saw the patient, he or she can be held liable.

Court cases in which supervising physician was found liable

There are plenty of judgments against supervising or collaborating physicians when the NP or PA made the error. Typically, the doctor was faulted for paying little attention to the NP or PA he or she was supposed to supervise.

Dr. Sullivan points to a 2016 case in which a New York jury held a physician 40% liable for a $7 million judgment in a malpractice case involving a PA’s care of a patient in the emergency department. The case is Shajan v. South Nassau Community Hospital in New York.

“The patient presented with nontraumatic leg pain to his lower leg, was diagnosed by the PA with a muscle strain, and discharged without a physician evaluation,” Dr. Sullivan said. The next day, the patient visited an orthopedist who immediately diagnosed compartment syndrome, an emergent condition in which pressure builds up in an affected extremity, damaging the muscles and nerves. “The patient developed irreversible nerve damage and chronic regional pain syndrome,” he said.

A malpractice lawsuit named the PA and the emergency physician he was supposed to be reporting to. Even though the physician had never seen the patient, he had signed off on the PA’s note from a patient’s ED visit. “Testimony during the trial focused on hospital protocols that the supervising physician was supposed to take,” Dr. Sullivan said.

When doctors share fault, they frequently failed to follow the collaborative agreement with the NP or PA. In Collip v. Ratts, a 2015 Indiana case in which the patient died from a drug interaction, the doctor’s certified public accountant stated that the doctor was required to review at least 5% of the NP’s charts every week to evaluate her prescriptive practices.

The doctor admitted that he never reviewed the NP’s charts on a weekly basis. He did conduct some cursory reviews of some of the NP’s notes, and in them he noted concerns for her prescribing practices and suggested she attend a narcotics-prescribing seminar, but he did not follow up to make sure she had done this.

Sometimes the NP or PA who made the mistake may actually be dropped from the lawsuit, leaving the supervising physician fully liable. In these cases, courts reason that a fully engaged supervisor could have prevented the error. In the 2006 case of  Husak v. Siegal, the Florida Supreme Court dropped the NP from the case, ruling that the NP had provided the supervising doctor all the information he needed in order to tell her what to do for the patient.

The court noted the physician had failed to look at the chart, even though he was required to do so under his supervisory agreement with the NP. The doctor “could have made the correct diagnosis or referral had he been attentive,” the court said. Therefore, there was “no evidence of independent negligence” by the NP, even though she was the one who had made the incorrect diagnosis that harmed the patient.

When states require an autonomous NP to have a supervisory relationship with a doctor, the supervisor may be unavailable and may fail to designate a substitute. In Texas in January 2019, a 7-year-old girl died of pneumonia after being treated by an NP in an urgent care clinic. The NP had told the parents that the child could safely go home and only needed ibuprofen. The parents brought the girl back home, and she died 15 hours later. The Wattenbargers sued the NP, and the doctor’s supervision was a topic in the trial.

The supervising physician for the NP was out of the country at the time. He said that he had found a substitute, but the substitute doctor testified she had no idea she was designated to be the substitute, according to Niran Al-Agba, MD, a family physician in Silverdale, Wash., who has written on the Texas case. Dr. Al-Agba told this news organization the case appears to have been settled confidentially.
 

Different standards for expert witnesses

In many states, courts do not allow physicians to testify as expert witnesses in malpractice cases against NPs, arguing that nurses have a different set of standards than doctors have, Dr. Sullivan reported.

These states include Arkansas, Illinois, North Carolina, and New York, according to a report by SEAK Inc., an expert witness training program. The report said most other states allow physician experts in these cases, but they may still require that they have experience with the nursing standard of care.

Dr. Sullivan said some courts are whittling away at the ban on physician experts, and the ban may eventually disappear. He reported that in Oklahoma, which normally upholds the ban, a judge recently allowed a physician-expert to testify in a case involving the death of a 19-year-old woman, Alexus Ochoa, in an ED staffed by an NP. The judge reasoned that Ms. Ochoa’s parents assumed the ED was staffed by physicians and would adhere to medical standards.
 

Supervision pointers from a physician

Physicians who supervise NPs or PAs say it is important to keep track of their skills and help them sharpen their expertise. Their scope of practice and physicians’ supervisory responsibilities are included in the collaborative agreement.

Arthur Apolinario, MD, a family physician in Clinton, N.C., says his 10-physician practice, which employs six NPs and one PA, works under a collaborative agreement. “The agreement defines each person’s scope of practice. They can’t do certain procedures, such as surgery, and they need extra training before doing certain tasks alone, such as joint injection.

“You have to always figure that if there is a lawsuit against one of them, you as the supervising physician would be named,” said Dr. Apolinario, who is also president of the North Carolina Medical Society. “We try to avert mistakes by meeting regularly with our NPs and PAs and making sure they keep up to date.”
 

Collaborating with autonomous NPs

Even when NPs operate independently in states that have abolished supervision, physicians may still have some liability if they give NPs advice, Dr. Al-Agba said.

At her Washington state practice, Dr. Al-Agba shares an office with an autonomous NP. “We share overhead and a front desk, but we have separate patients,” Dr. Al-Agba said. “This arrangement works very well for both of us.”

The NP sometimes asks her for advice. When this occurs, Dr. Al-Agba said she always makes sure to see the patient first. “If you don’t actually see the patient, there could be a misunderstanding that could lead to an error,” she said.
 

Conclusion

Even though NPs now have autonomy in most states, supervising physicians may still be liable for NP malpractice by virtue of being their employers, and physicians in the remaining states are liable for NPs through state law and for PAs in virtually all the states. To determine the supervising physician’s fault, courts often study whether the physician has met the terms of the collaborative agreement.

Physicians can reduce collaborating NPs’ and PAs’ liability by properly training them, by verifying their scope of practice, by making themselves easily available for consultation, and by occasionally seeing their patients. If their NPs and PAs do commit malpractice, supervising physicians may be able to protect themselves from liability by adhering to all requirements of the collaborative agreement.

*Correction, 4/19/2023: An earlier version of this story misstated the name of the AAPA and the states that have ended physician supervision of PAs.

A version of this article first appeared on Medscape.com.

Court cases show that physicians continually underestimate their liability in supervising nurse practitioners (NPs) and physician assistants (PAs).

Even in states that have abolished requirements that NPs be physician-supervised, physicians may still be liable by virtue of employing the NP, according to William P. Sullivan, DO, an attorney and emergency physician in Frankfort, Ill.

Indeed, the vast majority of lawsuits against NPs and PAs name the supervising physician. According to a study of claims against NPs from 2011 to 2016, 82% of the cases also named the supervising physician.

Employed or contracted physicians assigned to supervise NPs or PAs are also affected, Dr. Sullivan said. “The employed physicians’ contract with a hospital or staffing company may require them to assist in the selection, supervision, and/or training of NPs or PAs,” he said. He added that supervisory duties may also be assigned through hospital bylaws.

“The physician is usually not paid anything extra for this work and may not be given extra time to perform it,” Dr. Sullivan said. But still, he said, that physician could be named in a lawsuit and wind up bearing some responsibility for an NP’s or PA’s mistake.

In addition to facing medical malpractice suits, Dr. Sullivan said, doctors are often sanctioned by state licensure boards for improperly supervising NPs and PAs. Licensure boards often require extensive protocols for supervision of NPs and PAs.
 

Yet more states are removing supervision requirements

With the addition of Kansas and New York in 2022 and California in 2023, 27 states no longer require supervision for all or most NPs. Sixteen of those states, including New York and California, have instituted progressive practice authority that requires temporary supervision of new NPs but then removes supervision after a period of 6 months to 4 years, depending on the state, for the rest of their career.

“When it comes to NP independence, the horse is already out of the barn,” Dr. Sullivan said. “It’s unlikely that states will repeal laws granting NPs independence, and in fact, more states are likely to pass them.”

*PAs, in contrast, are well behind NPs in achieving independence, but the American Academy of Physician Associates (AAPA) is calling to eliminate a mandated relationship with a specific physician. So far, Utah, North Dakota and Wyoming have ended physician supervision of PAs, while California and Hawaii have eliminated mandated chart review. Other states are considering eliminating physician supervision of PAs, according to the AAPA.

In states that have abolished oversight requirements for NPs, “liability can then shift to the NP when the NP is fully independent,” Cathy Klein, an advanced practice registered nurse who helped found the NP profession 50 years ago, told this news organization. “More NPs are starting their own practices, and in many cases, patients actually prefer to see an NP.”

As more NPs became more autonomous, the average payment that NPs incurred in professional liability lawsuits rose by 10.5% from 2017 to 2022, to $332,187, according to the Nurses Service Organization (NSO), a nursing malpractice insurer.

The number of malpractice judgments against autonomous NPs alone has also been rising. From 2012 to 2017, autonomous NPs’ share of all NP cases rose from 7% to 16.4%, the NSO reported.

The good news for physicians is that states’ removal of restrictions on NPs has reduced physicians’ liability to some extent. A 2017 study found that enacting less restrictive scope-of-practice laws for NPs decreased the number of payments made by physicians in NP cases by as much as 31%.

However, the top location for NP payouts remains the physician’s office, not the autonomous NP’s practice, according to the latter NSO report. Plaintiffs sue NPs’ and PAs’ supervising physicians on the basis of legal concepts, such as vicarious liability and respondeat superior. Even if the physician-employer never saw the patient, he or she can be held liable.

Court cases in which supervising physician was found liable

There are plenty of judgments against supervising or collaborating physicians when the NP or PA made the error. Typically, the doctor was faulted for paying little attention to the NP or PA he or she was supposed to supervise.

Dr. Sullivan points to a 2016 case in which a New York jury held a physician 40% liable for a $7 million judgment in a malpractice case involving a PA’s care of a patient in the emergency department. The case is Shajan v. South Nassau Community Hospital in New York.

“The patient presented with nontraumatic leg pain to his lower leg, was diagnosed by the PA with a muscle strain, and discharged without a physician evaluation,” Dr. Sullivan said. The next day, the patient visited an orthopedist who immediately diagnosed compartment syndrome, an emergent condition in which pressure builds up in an affected extremity, damaging the muscles and nerves. “The patient developed irreversible nerve damage and chronic regional pain syndrome,” he said.

A malpractice lawsuit named the PA and the emergency physician he was supposed to be reporting to. Even though the physician had never seen the patient, he had signed off on the PA’s note from a patient’s ED visit. “Testimony during the trial focused on hospital protocols that the supervising physician was supposed to take,” Dr. Sullivan said.

When doctors share fault, they frequently failed to follow the collaborative agreement with the NP or PA. In Collip v. Ratts, a 2015 Indiana case in which the patient died from a drug interaction, the doctor’s certified public accountant stated that the doctor was required to review at least 5% of the NP’s charts every week to evaluate her prescriptive practices.

The doctor admitted that he never reviewed the NP’s charts on a weekly basis. He did conduct some cursory reviews of some of the NP’s notes, and in them he noted concerns for her prescribing practices and suggested she attend a narcotics-prescribing seminar, but he did not follow up to make sure she had done this.

Sometimes the NP or PA who made the mistake may actually be dropped from the lawsuit, leaving the supervising physician fully liable. In these cases, courts reason that a fully engaged supervisor could have prevented the error. In the 2006 case of  Husak v. Siegal, the Florida Supreme Court dropped the NP from the case, ruling that the NP had provided the supervising doctor all the information he needed in order to tell her what to do for the patient.

The court noted the physician had failed to look at the chart, even though he was required to do so under his supervisory agreement with the NP. The doctor “could have made the correct diagnosis or referral had he been attentive,” the court said. Therefore, there was “no evidence of independent negligence” by the NP, even though she was the one who had made the incorrect diagnosis that harmed the patient.

When states require an autonomous NP to have a supervisory relationship with a doctor, the supervisor may be unavailable and may fail to designate a substitute. In Texas in January 2019, a 7-year-old girl died of pneumonia after being treated by an NP in an urgent care clinic. The NP had told the parents that the child could safely go home and only needed ibuprofen. The parents brought the girl back home, and she died 15 hours later. The Wattenbargers sued the NP, and the doctor’s supervision was a topic in the trial.

The supervising physician for the NP was out of the country at the time. He said that he had found a substitute, but the substitute doctor testified she had no idea she was designated to be the substitute, according to Niran Al-Agba, MD, a family physician in Silverdale, Wash., who has written on the Texas case. Dr. Al-Agba told this news organization the case appears to have been settled confidentially.
 

Different standards for expert witnesses

In many states, courts do not allow physicians to testify as expert witnesses in malpractice cases against NPs, arguing that nurses have a different set of standards than doctors have, Dr. Sullivan reported.

These states include Arkansas, Illinois, North Carolina, and New York, according to a report by SEAK Inc., an expert witness training program. The report said most other states allow physician experts in these cases, but they may still require that they have experience with the nursing standard of care.

Dr. Sullivan said some courts are whittling away at the ban on physician experts, and the ban may eventually disappear. He reported that in Oklahoma, which normally upholds the ban, a judge recently allowed a physician-expert to testify in a case involving the death of a 19-year-old woman, Alexus Ochoa, in an ED staffed by an NP. The judge reasoned that Ms. Ochoa’s parents assumed the ED was staffed by physicians and would adhere to medical standards.
 

Supervision pointers from a physician

Physicians who supervise NPs or PAs say it is important to keep track of their skills and help them sharpen their expertise. Their scope of practice and physicians’ supervisory responsibilities are included in the collaborative agreement.

Arthur Apolinario, MD, a family physician in Clinton, N.C., says his 10-physician practice, which employs six NPs and one PA, works under a collaborative agreement. “The agreement defines each person’s scope of practice. They can’t do certain procedures, such as surgery, and they need extra training before doing certain tasks alone, such as joint injection.

“You have to always figure that if there is a lawsuit against one of them, you as the supervising physician would be named,” said Dr. Apolinario, who is also president of the North Carolina Medical Society. “We try to avert mistakes by meeting regularly with our NPs and PAs and making sure they keep up to date.”
 

Collaborating with autonomous NPs

Even when NPs operate independently in states that have abolished supervision, physicians may still have some liability if they give NPs advice, Dr. Al-Agba said.

At her Washington state practice, Dr. Al-Agba shares an office with an autonomous NP. “We share overhead and a front desk, but we have separate patients,” Dr. Al-Agba said. “This arrangement works very well for both of us.”

The NP sometimes asks her for advice. When this occurs, Dr. Al-Agba said she always makes sure to see the patient first. “If you don’t actually see the patient, there could be a misunderstanding that could lead to an error,” she said.
 

Conclusion

Even though NPs now have autonomy in most states, supervising physicians may still be liable for NP malpractice by virtue of being their employers, and physicians in the remaining states are liable for NPs through state law and for PAs in virtually all the states. To determine the supervising physician’s fault, courts often study whether the physician has met the terms of the collaborative agreement.

Physicians can reduce collaborating NPs’ and PAs’ liability by properly training them, by verifying their scope of practice, by making themselves easily available for consultation, and by occasionally seeing their patients. If their NPs and PAs do commit malpractice, supervising physicians may be able to protect themselves from liability by adhering to all requirements of the collaborative agreement.

*Correction, 4/19/2023: An earlier version of this story misstated the name of the AAPA and the states that have ended physician supervision of PAs.

A version of this article first appeared on Medscape.com.

Court cases show that physicians continually underestimate their liability in supervising nurse practitioners (NPs) and physician assistants (PAs).

Even in states that have abolished requirements that NPs be physician-supervised, physicians may still be liable by virtue of employing the NP, according to William P. Sullivan, DO, an attorney and emergency physician in Frankfort, Ill.

Indeed, the vast majority of lawsuits against NPs and PAs name the supervising physician. According to a study of claims against NPs from 2011 to 2016, 82% of the cases also named the supervising physician.

Employed or contracted physicians assigned to supervise NPs or PAs are also affected, Dr. Sullivan said. “The employed physicians’ contract with a hospital or staffing company may require them to assist in the selection, supervision, and/or training of NPs or PAs,” he said. He added that supervisory duties may also be assigned through hospital bylaws.

“The physician is usually not paid anything extra for this work and may not be given extra time to perform it,” Dr. Sullivan said. But still, he said, that physician could be named in a lawsuit and wind up bearing some responsibility for an NP’s or PA’s mistake.

In addition to facing medical malpractice suits, Dr. Sullivan said, doctors are often sanctioned by state licensure boards for improperly supervising NPs and PAs. Licensure boards often require extensive protocols for supervision of NPs and PAs.
 

Yet more states are removing supervision requirements

With the addition of Kansas and New York in 2022 and California in 2023, 27 states no longer require supervision for all or most NPs. Sixteen of those states, including New York and California, have instituted progressive practice authority that requires temporary supervision of new NPs but then removes supervision after a period of 6 months to 4 years, depending on the state, for the rest of their career.

“When it comes to NP independence, the horse is already out of the barn,” Dr. Sullivan said. “It’s unlikely that states will repeal laws granting NPs independence, and in fact, more states are likely to pass them.”

*PAs, in contrast, are well behind NPs in achieving independence, but the American Academy of Physician Associates (AAPA) is calling to eliminate a mandated relationship with a specific physician. So far, Utah, North Dakota and Wyoming have ended physician supervision of PAs, while California and Hawaii have eliminated mandated chart review. Other states are considering eliminating physician supervision of PAs, according to the AAPA.

In states that have abolished oversight requirements for NPs, “liability can then shift to the NP when the NP is fully independent,” Cathy Klein, an advanced practice registered nurse who helped found the NP profession 50 years ago, told this news organization. “More NPs are starting their own practices, and in many cases, patients actually prefer to see an NP.”

As more NPs became more autonomous, the average payment that NPs incurred in professional liability lawsuits rose by 10.5% from 2017 to 2022, to $332,187, according to the Nurses Service Organization (NSO), a nursing malpractice insurer.

The number of malpractice judgments against autonomous NPs alone has also been rising. From 2012 to 2017, autonomous NPs’ share of all NP cases rose from 7% to 16.4%, the NSO reported.

The good news for physicians is that states’ removal of restrictions on NPs has reduced physicians’ liability to some extent. A 2017 study found that enacting less restrictive scope-of-practice laws for NPs decreased the number of payments made by physicians in NP cases by as much as 31%.

However, the top location for NP payouts remains the physician’s office, not the autonomous NP’s practice, according to the latter NSO report. Plaintiffs sue NPs’ and PAs’ supervising physicians on the basis of legal concepts, such as vicarious liability and respondeat superior. Even if the physician-employer never saw the patient, he or she can be held liable.

Court cases in which supervising physician was found liable

There are plenty of judgments against supervising or collaborating physicians when the NP or PA made the error. Typically, the doctor was faulted for paying little attention to the NP or PA he or she was supposed to supervise.

Dr. Sullivan points to a 2016 case in which a New York jury held a physician 40% liable for a $7 million judgment in a malpractice case involving a PA’s care of a patient in the emergency department. The case is Shajan v. South Nassau Community Hospital in New York.

“The patient presented with nontraumatic leg pain to his lower leg, was diagnosed by the PA with a muscle strain, and discharged without a physician evaluation,” Dr. Sullivan said. The next day, the patient visited an orthopedist who immediately diagnosed compartment syndrome, an emergent condition in which pressure builds up in an affected extremity, damaging the muscles and nerves. “The patient developed irreversible nerve damage and chronic regional pain syndrome,” he said.

A malpractice lawsuit named the PA and the emergency physician he was supposed to be reporting to. Even though the physician had never seen the patient, he had signed off on the PA’s note from a patient’s ED visit. “Testimony during the trial focused on hospital protocols that the supervising physician was supposed to take,” Dr. Sullivan said.

When doctors share fault, they frequently failed to follow the collaborative agreement with the NP or PA. In Collip v. Ratts, a 2015 Indiana case in which the patient died from a drug interaction, the doctor’s certified public accountant stated that the doctor was required to review at least 5% of the NP’s charts every week to evaluate her prescriptive practices.

The doctor admitted that he never reviewed the NP’s charts on a weekly basis. He did conduct some cursory reviews of some of the NP’s notes, and in them he noted concerns for her prescribing practices and suggested she attend a narcotics-prescribing seminar, but he did not follow up to make sure she had done this.

Sometimes the NP or PA who made the mistake may actually be dropped from the lawsuit, leaving the supervising physician fully liable. In these cases, courts reason that a fully engaged supervisor could have prevented the error. In the 2006 case of  Husak v. Siegal, the Florida Supreme Court dropped the NP from the case, ruling that the NP had provided the supervising doctor all the information he needed in order to tell her what to do for the patient.

The court noted the physician had failed to look at the chart, even though he was required to do so under his supervisory agreement with the NP. The doctor “could have made the correct diagnosis or referral had he been attentive,” the court said. Therefore, there was “no evidence of independent negligence” by the NP, even though she was the one who had made the incorrect diagnosis that harmed the patient.

When states require an autonomous NP to have a supervisory relationship with a doctor, the supervisor may be unavailable and may fail to designate a substitute. In Texas in January 2019, a 7-year-old girl died of pneumonia after being treated by an NP in an urgent care clinic. The NP had told the parents that the child could safely go home and only needed ibuprofen. The parents brought the girl back home, and she died 15 hours later. The Wattenbargers sued the NP, and the doctor’s supervision was a topic in the trial.

The supervising physician for the NP was out of the country at the time. He said that he had found a substitute, but the substitute doctor testified she had no idea she was designated to be the substitute, according to Niran Al-Agba, MD, a family physician in Silverdale, Wash., who has written on the Texas case. Dr. Al-Agba told this news organization the case appears to have been settled confidentially.
 

Different standards for expert witnesses

In many states, courts do not allow physicians to testify as expert witnesses in malpractice cases against NPs, arguing that nurses have a different set of standards than doctors have, Dr. Sullivan reported.

These states include Arkansas, Illinois, North Carolina, and New York, according to a report by SEAK Inc., an expert witness training program. The report said most other states allow physician experts in these cases, but they may still require that they have experience with the nursing standard of care.

Dr. Sullivan said some courts are whittling away at the ban on physician experts, and the ban may eventually disappear. He reported that in Oklahoma, which normally upholds the ban, a judge recently allowed a physician-expert to testify in a case involving the death of a 19-year-old woman, Alexus Ochoa, in an ED staffed by an NP. The judge reasoned that Ms. Ochoa’s parents assumed the ED was staffed by physicians and would adhere to medical standards.
 

Supervision pointers from a physician

Physicians who supervise NPs or PAs say it is important to keep track of their skills and help them sharpen their expertise. Their scope of practice and physicians’ supervisory responsibilities are included in the collaborative agreement.

Arthur Apolinario, MD, a family physician in Clinton, N.C., says his 10-physician practice, which employs six NPs and one PA, works under a collaborative agreement. “The agreement defines each person’s scope of practice. They can’t do certain procedures, such as surgery, and they need extra training before doing certain tasks alone, such as joint injection.

“You have to always figure that if there is a lawsuit against one of them, you as the supervising physician would be named,” said Dr. Apolinario, who is also president of the North Carolina Medical Society. “We try to avert mistakes by meeting regularly with our NPs and PAs and making sure they keep up to date.”
 

Collaborating with autonomous NPs

Even when NPs operate independently in states that have abolished supervision, physicians may still have some liability if they give NPs advice, Dr. Al-Agba said.

At her Washington state practice, Dr. Al-Agba shares an office with an autonomous NP. “We share overhead and a front desk, but we have separate patients,” Dr. Al-Agba said. “This arrangement works very well for both of us.”

The NP sometimes asks her for advice. When this occurs, Dr. Al-Agba said she always makes sure to see the patient first. “If you don’t actually see the patient, there could be a misunderstanding that could lead to an error,” she said.
 

Conclusion

Even though NPs now have autonomy in most states, supervising physicians may still be liable for NP malpractice by virtue of being their employers, and physicians in the remaining states are liable for NPs through state law and for PAs in virtually all the states. To determine the supervising physician’s fault, courts often study whether the physician has met the terms of the collaborative agreement.

Physicians can reduce collaborating NPs’ and PAs’ liability by properly training them, by verifying their scope of practice, by making themselves easily available for consultation, and by occasionally seeing their patients. If their NPs and PAs do commit malpractice, supervising physicians may be able to protect themselves from liability by adhering to all requirements of the collaborative agreement.

*Correction, 4/19/2023: An earlier version of this story misstated the name of the AAPA and the states that have ended physician supervision of PAs.

A version of this article first appeared on Medscape.com.

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

A version of this article originally appeared on Medscape.com.

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

A version of this article originally appeared on Medscape.com.

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

A version of this article originally appeared on Medscape.com.

A whole new, tiny level of hangry

Ever been so hungry that everything just got on your nerves? Maybe you feel a little snappy right now? Like you’ll just lash out unless you get something to eat? Been there. And so have bacteria.

New research shows that some bacteria go into a full-on Hulk smash if they’re not getting the nutrients they need by releasing toxins into the body. Sounds like a bacterial temper tantrum.

Rosenthal et al.

Even though two cells may be genetically identical, they don’t always behave the same in a bacterial community. Some do their job and stay in line, but some evil twins rage out and make people sick by releasing toxins into the environment, Adam Rosenthal, PhD, of the University of North Carolina and his colleagues discovered.

To figure out why some cells were all business as usual while others were not, the investigators looked at Clostridium perfringens, a bacterium found in the intestines of humans and other vertebrates. When the C. perfringens cells were fed a little acetate to munch on, the hangry cells calmed down faster than a kid with a bag of fruit snacks, reducing toxin levels. Some cells even disappeared, falling in line with their model-citizen counterparts.

So what does this really mean? More research, duh. Now that we know nutrients play a role in toxicity, it may open the door to finding a way to fight against antibiotic resistance in humans and reduce antibiotic use in the food industry.

So think to yourself. Are you bothered for no reason? Getting a little testy with your friends and coworkers? Maybe you just haven’t eaten in a while. You’re literally not alone. Even a single-cell organism can behave based on its hunger levels.

Now go have a snack. Your bacteria are getting restless.
 

The very hangry iguana?

Imagine yourself on a warm, sunny tropical beach. You are enjoying a piece of cake as you take in the slow beat of the waves lapping against the shore. Life is as good as it could be.

Then you feel a presence nearby. Hostility. Hunger. A set of feral, covetous eyes in the nearby jungle. A reptilian beast stalks you, and its all-encompassing sweet tooth desires your cake.

Wait, hold on, what?

As an unfortunate 3-year-old on vacation in Costa Rica found out, there’s at least one iguana in the world out there with a taste for sugar (better than a taste for blood, we suppose).

Ulrike Mai/Pixabay

While out on the beach, the lizard darted out of nowhere, bit the girl on the back of the hand, and stole her cake. Still not the worst party guest ever. The child was taken to a local clinic, where the wound was cleaned and a 5-day antibiotic treatment (lizards carry salmonella) was provided. Things seemed fine, and the girl returned home without incident.

But of course, that’s not the end of the story. Five months later, the girl’s parents noticed a red bump at the wound site. Over the next 3 months, the surrounding skin grew red and painful. A trip to the hospital in California revealed that she had a ganglion cyst and a discharge of pus. Turns out our cake-obsessed lizard friend did give the little girl a gift: the first known human case of Mycobacterium marinum infection following an iguana bite on record.

M. marinum, which causes a disease similar to tuberculosis, typically infects fish but can infect humans if skin wounds are exposed to contaminated water. It’s also resistant to most antibiotics, which is why the first round didn’t clear up the infection. A second round of more-potent antibiotics seems to be working well.

So, to sum up, this poor child got bitten by a lizard, had her cake stolen, and contracted a rare illness in exchange. For a 3-year-old, that’s gotta be in the top-10 worst days ever. Unless, of course, we’re actually living in the Marvel universe (sorry, multiverse at this point). Then we’re totally going to see the emergence of the new superhero Iguana Girl in 15 years or so. Keep your eyes open.
 

No allergies? Let them give up cake

Allergy season is already here – starting earlier every year, it seems – and many people are not happy about it. So unhappy, actually, that there’s a list of things they would be willing to give up for a year to get rid of their of allergies, according to a survey conducted by OnePoll on behalf of Flonase.

nicoletaionescu/Getty Images

Nearly 40% of 2,000 respondents with allergies would go a year without eating cake or chocolate or playing video games in exchange for allergy-free status, the survey results show. Almost as many would forgo coffee (38%) or pizza (37%) for a year, while 36% would stay off social media and 31% would take a pay cut or give up their smartphones, the Independent reported.

More than half of the allergic Americans – 54%, to be exact – who were polled this past winter – Feb. 24 to March 1, to be exact – consider allergy symptoms to be the most frustrating part of the spring. Annoying things that were less frustrating to the group included mosquitoes (41%), filing tax returns (38%), and daylight savings time (37%).

The Trump arraignment circus, of course, occurred too late to make the list, as did the big “We’re going back to the office! No wait, we’re closing the office forever!” email extravaganza and emotional roller coaster. That second one, however, did not get nearly as much media coverage.

A whole new, tiny level of hangry

Ever been so hungry that everything just got on your nerves? Maybe you feel a little snappy right now? Like you’ll just lash out unless you get something to eat? Been there. And so have bacteria.

New research shows that some bacteria go into a full-on Hulk smash if they’re not getting the nutrients they need by releasing toxins into the body. Sounds like a bacterial temper tantrum.

Rosenthal et al.

Even though two cells may be genetically identical, they don’t always behave the same in a bacterial community. Some do their job and stay in line, but some evil twins rage out and make people sick by releasing toxins into the environment, Adam Rosenthal, PhD, of the University of North Carolina and his colleagues discovered.

To figure out why some cells were all business as usual while others were not, the investigators looked at Clostridium perfringens, a bacterium found in the intestines of humans and other vertebrates. When the C. perfringens cells were fed a little acetate to munch on, the hangry cells calmed down faster than a kid with a bag of fruit snacks, reducing toxin levels. Some cells even disappeared, falling in line with their model-citizen counterparts.

So what does this really mean? More research, duh. Now that we know nutrients play a role in toxicity, it may open the door to finding a way to fight against antibiotic resistance in humans and reduce antibiotic use in the food industry.

So think to yourself. Are you bothered for no reason? Getting a little testy with your friends and coworkers? Maybe you just haven’t eaten in a while. You’re literally not alone. Even a single-cell organism can behave based on its hunger levels.

Now go have a snack. Your bacteria are getting restless.
 

The very hangry iguana?

Imagine yourself on a warm, sunny tropical beach. You are enjoying a piece of cake as you take in the slow beat of the waves lapping against the shore. Life is as good as it could be.

Then you feel a presence nearby. Hostility. Hunger. A set of feral, covetous eyes in the nearby jungle. A reptilian beast stalks you, and its all-encompassing sweet tooth desires your cake.

Wait, hold on, what?

As an unfortunate 3-year-old on vacation in Costa Rica found out, there’s at least one iguana in the world out there with a taste for sugar (better than a taste for blood, we suppose).

Ulrike Mai/Pixabay

While out on the beach, the lizard darted out of nowhere, bit the girl on the back of the hand, and stole her cake. Still not the worst party guest ever. The child was taken to a local clinic, where the wound was cleaned and a 5-day antibiotic treatment (lizards carry salmonella) was provided. Things seemed fine, and the girl returned home without incident.

But of course, that’s not the end of the story. Five months later, the girl’s parents noticed a red bump at the wound site. Over the next 3 months, the surrounding skin grew red and painful. A trip to the hospital in California revealed that she had a ganglion cyst and a discharge of pus. Turns out our cake-obsessed lizard friend did give the little girl a gift: the first known human case of Mycobacterium marinum infection following an iguana bite on record.

M. marinum, which causes a disease similar to tuberculosis, typically infects fish but can infect humans if skin wounds are exposed to contaminated water. It’s also resistant to most antibiotics, which is why the first round didn’t clear up the infection. A second round of more-potent antibiotics seems to be working well.

So, to sum up, this poor child got bitten by a lizard, had her cake stolen, and contracted a rare illness in exchange. For a 3-year-old, that’s gotta be in the top-10 worst days ever. Unless, of course, we’re actually living in the Marvel universe (sorry, multiverse at this point). Then we’re totally going to see the emergence of the new superhero Iguana Girl in 15 years or so. Keep your eyes open.
 

No allergies? Let them give up cake

Allergy season is already here – starting earlier every year, it seems – and many people are not happy about it. So unhappy, actually, that there’s a list of things they would be willing to give up for a year to get rid of their of allergies, according to a survey conducted by OnePoll on behalf of Flonase.

nicoletaionescu/Getty Images

Nearly 40% of 2,000 respondents with allergies would go a year without eating cake or chocolate or playing video games in exchange for allergy-free status, the survey results show. Almost as many would forgo coffee (38%) or pizza (37%) for a year, while 36% would stay off social media and 31% would take a pay cut or give up their smartphones, the Independent reported.

More than half of the allergic Americans – 54%, to be exact – who were polled this past winter – Feb. 24 to March 1, to be exact – consider allergy symptoms to be the most frustrating part of the spring. Annoying things that were less frustrating to the group included mosquitoes (41%), filing tax returns (38%), and daylight savings time (37%).

The Trump arraignment circus, of course, occurred too late to make the list, as did the big “We’re going back to the office! No wait, we’re closing the office forever!” email extravaganza and emotional roller coaster. That second one, however, did not get nearly as much media coverage.

A whole new, tiny level of hangry

Ever been so hungry that everything just got on your nerves? Maybe you feel a little snappy right now? Like you’ll just lash out unless you get something to eat? Been there. And so have bacteria.

New research shows that some bacteria go into a full-on Hulk smash if they’re not getting the nutrients they need by releasing toxins into the body. Sounds like a bacterial temper tantrum.

Rosenthal et al.

Even though two cells may be genetically identical, they don’t always behave the same in a bacterial community. Some do their job and stay in line, but some evil twins rage out and make people sick by releasing toxins into the environment, Adam Rosenthal, PhD, of the University of North Carolina and his colleagues discovered.

To figure out why some cells were all business as usual while others were not, the investigators looked at Clostridium perfringens, a bacterium found in the intestines of humans and other vertebrates. When the C. perfringens cells were fed a little acetate to munch on, the hangry cells calmed down faster than a kid with a bag of fruit snacks, reducing toxin levels. Some cells even disappeared, falling in line with their model-citizen counterparts.

So what does this really mean? More research, duh. Now that we know nutrients play a role in toxicity, it may open the door to finding a way to fight against antibiotic resistance in humans and reduce antibiotic use in the food industry.

So think to yourself. Are you bothered for no reason? Getting a little testy with your friends and coworkers? Maybe you just haven’t eaten in a while. You’re literally not alone. Even a single-cell organism can behave based on its hunger levels.

Now go have a snack. Your bacteria are getting restless.
 

The very hangry iguana?

Imagine yourself on a warm, sunny tropical beach. You are enjoying a piece of cake as you take in the slow beat of the waves lapping against the shore. Life is as good as it could be.

Then you feel a presence nearby. Hostility. Hunger. A set of feral, covetous eyes in the nearby jungle. A reptilian beast stalks you, and its all-encompassing sweet tooth desires your cake.

Wait, hold on, what?

As an unfortunate 3-year-old on vacation in Costa Rica found out, there’s at least one iguana in the world out there with a taste for sugar (better than a taste for blood, we suppose).

Ulrike Mai/Pixabay

While out on the beach, the lizard darted out of nowhere, bit the girl on the back of the hand, and stole her cake. Still not the worst party guest ever. The child was taken to a local clinic, where the wound was cleaned and a 5-day antibiotic treatment (lizards carry salmonella) was provided. Things seemed fine, and the girl returned home without incident.

But of course, that’s not the end of the story. Five months later, the girl’s parents noticed a red bump at the wound site. Over the next 3 months, the surrounding skin grew red and painful. A trip to the hospital in California revealed that she had a ganglion cyst and a discharge of pus. Turns out our cake-obsessed lizard friend did give the little girl a gift: the first known human case of Mycobacterium marinum infection following an iguana bite on record.

M. marinum, which causes a disease similar to tuberculosis, typically infects fish but can infect humans if skin wounds are exposed to contaminated water. It’s also resistant to most antibiotics, which is why the first round didn’t clear up the infection. A second round of more-potent antibiotics seems to be working well.

So, to sum up, this poor child got bitten by a lizard, had her cake stolen, and contracted a rare illness in exchange. For a 3-year-old, that’s gotta be in the top-10 worst days ever. Unless, of course, we’re actually living in the Marvel universe (sorry, multiverse at this point). Then we’re totally going to see the emergence of the new superhero Iguana Girl in 15 years or so. Keep your eyes open.
 

No allergies? Let them give up cake

Allergy season is already here – starting earlier every year, it seems – and many people are not happy about it. So unhappy, actually, that there’s a list of things they would be willing to give up for a year to get rid of their of allergies, according to a survey conducted by OnePoll on behalf of Flonase.

nicoletaionescu/Getty Images

Nearly 40% of 2,000 respondents with allergies would go a year without eating cake or chocolate or playing video games in exchange for allergy-free status, the survey results show. Almost as many would forgo coffee (38%) or pizza (37%) for a year, while 36% would stay off social media and 31% would take a pay cut or give up their smartphones, the Independent reported.

More than half of the allergic Americans – 54%, to be exact – who were polled this past winter – Feb. 24 to March 1, to be exact – consider allergy symptoms to be the most frustrating part of the spring. Annoying things that were less frustrating to the group included mosquitoes (41%), filing tax returns (38%), and daylight savings time (37%).

The Trump arraignment circus, of course, occurred too late to make the list, as did the big “We’re going back to the office! No wait, we’re closing the office forever!” email extravaganza and emotional roller coaster. That second one, however, did not get nearly as much media coverage.

Researchers have found for the first time that COVID infection has crossed the placenta and caused brain damage in two newborns, according to a study published online today in Pediatrics .

One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.

Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.

Zelda Calvert

“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
 

Both infants negative for the virus at birth

The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.

Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.

Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.

Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.

“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.

Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.

Seizures started on day 1 of life

The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.

“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.

Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.

Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.

The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.

Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.

Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
 

Mothers had very different presentations

Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.

One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.

In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.

He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
 

Instances are rare

The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.

Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”

Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.

Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.

Researchers have found for the first time that COVID infection has crossed the placenta and caused brain damage in two newborns, according to a study published online today in Pediatrics .

One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.

Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.

Zelda Calvert

“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
 

Both infants negative for the virus at birth

The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.

Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.

Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.

Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.

“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.

Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.

Seizures started on day 1 of life

The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.

“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.

Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.

Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.

The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.

Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.

Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
 

Mothers had very different presentations

Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.

One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.

In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.

He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
 

Instances are rare

The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.

Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”

Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.

Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.

Researchers have found for the first time that COVID infection has crossed the placenta and caused brain damage in two newborns, according to a study published online today in Pediatrics .

One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.

Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.

Zelda Calvert

“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
 

Both infants negative for the virus at birth

The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.

Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.

Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.

Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.

“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.

Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.

Seizures started on day 1 of life

The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.

“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.

Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.

Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.

The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.

Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.

Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
 

Mothers had very different presentations

Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.

One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.

In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.

He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
 

Instances are rare

The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.

Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”

Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.

Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.