Ob.Gyn. News

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.

Rapid weight gain (RWG) in infants and the mother’s prepregnancy overweight have a synergistic effect in increasing the odds that a child will develop overweight or obesity, new research suggests.

Findings were published online in Pediatrics.

Each factor has independently been associated with higher risk of childhood obesity but whether the two factors together exacerbate the risk has not been well studied, according to the authors led by Stephanie Gilley, MD, PhD, department of pediatrics, section of nutrition, University of Colorado at Denver, Aurora.

“Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity,” the authors conclude.

Dr. Gilley’s team studied mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort. RWG was defined as a weight-for-age z score increase of at least 0.67 from birth to 3-7 months.

They found that RWG boosted the link between prepregnancy body mass index (ppBMI) and BMI z score, especially in female infants. Females exposed to both maternal obesity with RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) “nearly at the cutoff for classification of obesity,” compared with those exposed to normal ppBMI with no RWG, who had an average childhood BMI at the 51st percentile.

“Currently, our nutrition recommendations as pediatricians are that all children are fed the same, essentially, after they’re born. We don’t have different growth parameters or different trajectories or targets for children who may have had different in utero exposures,” Dr. Gilley said.

Do some children need more monitoring for RWG?

Though we can’t necessarily draw conclusions from this one study, she says, the findings raise the question of whether children who were exposed in utero to obesity should be monitored for RWG more closely.

Lydia Shook, MD, Mass General Brigham maternal-fetal specialist and codirector of the Diabetes in Pregnancy Program at Massachusetts General Hospital in Boston, said she was struck by the finding in this study that with female infants, but not males, RWG significantly modified the association between ppBMI and early childhood BMI z scores.

“It’s an interesting finding and should be followed up with larger cohorts,” she said, noting that some previous studies have shown males are more vulnerable to maternal obesity and RWG.

“[Often] when we stratify by sex, you really need larger groups to be able to see the differences well,” Dr. Shook said.

She said she also found it interesting that when the researchers adjusted for breastfeeding status or caloric intake in childhood, the findings did not substantially change.

“That’s something that would warrant further investigation in an observational study or controlled trial,” Dr. Shook said.

Preventing rapid weight gain

The authors note that they did not consider possible interventions for preventing RGW in the study, although there are many, Dr. Gilley said.

Dr. Gilley also noted that a limitation of this study is that the population studied was primarily White.

Recent studies have shown the benefits of responsive parenting (RP) interventions, including a large study in 2022 geared toward Black families to teach better infant sleep practices as a way to prevent rapid weight gain.

That study, which tested the SAAF intervention, (Strong African American Families) found that “RP infants were nearly half as likely to experience upward crossing of two major weight-for-age percentile lines (14.1%), compared with control infants (24.2%); P = .09; odds ratio, 0.52; 95% confidence interval, 0.24-1.12.”

Along with sleep interventions, Dr. Gilley said, some researchers are studying the effects on RWG of better paternal engagement, or more involvement with the Women, Infants, and Children program, particularly with lower-income families.

Other studies have looked at breastfeeding vs. formula feeding – “but there have been mixed results there” – and responsive feeding practices, such as teaching families to recognize when a baby is full.

Dr. Gilley said she hopes this work will help broaden the thinking when it comes to infant weight gain.

“We spend a lot of time thinking about babies who are not growing fast enough and very little time thinking about babies who are growing too fast,” she said, “especially in those first 4-6 months of life.”

Dr. Gilley points to a study that illustrates that point. Pesch et al. concluded in a 2021 study based on interviews that pediatricians “are uncertain about the concept, definition, management, and long-term risks of rapid infant weight gain.”

Authors and Dr. Gilley declare no relevant financial relationships.

Rapid weight gain (RWG) in infants and the mother’s prepregnancy overweight have a synergistic effect in increasing the odds that a child will develop overweight or obesity, new research suggests.

Findings were published online in Pediatrics.

Each factor has independently been associated with higher risk of childhood obesity but whether the two factors together exacerbate the risk has not been well studied, according to the authors led by Stephanie Gilley, MD, PhD, department of pediatrics, section of nutrition, University of Colorado at Denver, Aurora.

“Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity,” the authors conclude.

Dr. Gilley’s team studied mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort. RWG was defined as a weight-for-age z score increase of at least 0.67 from birth to 3-7 months.

They found that RWG boosted the link between prepregnancy body mass index (ppBMI) and BMI z score, especially in female infants. Females exposed to both maternal obesity with RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) “nearly at the cutoff for classification of obesity,” compared with those exposed to normal ppBMI with no RWG, who had an average childhood BMI at the 51st percentile.

“Currently, our nutrition recommendations as pediatricians are that all children are fed the same, essentially, after they’re born. We don’t have different growth parameters or different trajectories or targets for children who may have had different in utero exposures,” Dr. Gilley said.

Do some children need more monitoring for RWG?

Though we can’t necessarily draw conclusions from this one study, she says, the findings raise the question of whether children who were exposed in utero to obesity should be monitored for RWG more closely.

Lydia Shook, MD, Mass General Brigham maternal-fetal specialist and codirector of the Diabetes in Pregnancy Program at Massachusetts General Hospital in Boston, said she was struck by the finding in this study that with female infants, but not males, RWG significantly modified the association between ppBMI and early childhood BMI z scores.

“It’s an interesting finding and should be followed up with larger cohorts,” she said, noting that some previous studies have shown males are more vulnerable to maternal obesity and RWG.

“[Often] when we stratify by sex, you really need larger groups to be able to see the differences well,” Dr. Shook said.

She said she also found it interesting that when the researchers adjusted for breastfeeding status or caloric intake in childhood, the findings did not substantially change.

“That’s something that would warrant further investigation in an observational study or controlled trial,” Dr. Shook said.

Preventing rapid weight gain

The authors note that they did not consider possible interventions for preventing RGW in the study, although there are many, Dr. Gilley said.

Dr. Gilley also noted that a limitation of this study is that the population studied was primarily White.

Recent studies have shown the benefits of responsive parenting (RP) interventions, including a large study in 2022 geared toward Black families to teach better infant sleep practices as a way to prevent rapid weight gain.

That study, which tested the SAAF intervention, (Strong African American Families) found that “RP infants were nearly half as likely to experience upward crossing of two major weight-for-age percentile lines (14.1%), compared with control infants (24.2%); P = .09; odds ratio, 0.52; 95% confidence interval, 0.24-1.12.”

Along with sleep interventions, Dr. Gilley said, some researchers are studying the effects on RWG of better paternal engagement, or more involvement with the Women, Infants, and Children program, particularly with lower-income families.

Other studies have looked at breastfeeding vs. formula feeding – “but there have been mixed results there” – and responsive feeding practices, such as teaching families to recognize when a baby is full.

Dr. Gilley said she hopes this work will help broaden the thinking when it comes to infant weight gain.

“We spend a lot of time thinking about babies who are not growing fast enough and very little time thinking about babies who are growing too fast,” she said, “especially in those first 4-6 months of life.”

Dr. Gilley points to a study that illustrates that point. Pesch et al. concluded in a 2021 study based on interviews that pediatricians “are uncertain about the concept, definition, management, and long-term risks of rapid infant weight gain.”

Authors and Dr. Gilley declare no relevant financial relationships.

Rapid weight gain (RWG) in infants and the mother’s prepregnancy overweight have a synergistic effect in increasing the odds that a child will develop overweight or obesity, new research suggests.

Findings were published online in Pediatrics.

Each factor has independently been associated with higher risk of childhood obesity but whether the two factors together exacerbate the risk has not been well studied, according to the authors led by Stephanie Gilley, MD, PhD, department of pediatrics, section of nutrition, University of Colorado at Denver, Aurora.

“Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity,” the authors conclude.

Dr. Gilley’s team studied mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort. RWG was defined as a weight-for-age z score increase of at least 0.67 from birth to 3-7 months.

They found that RWG boosted the link between prepregnancy body mass index (ppBMI) and BMI z score, especially in female infants. Females exposed to both maternal obesity with RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) “nearly at the cutoff for classification of obesity,” compared with those exposed to normal ppBMI with no RWG, who had an average childhood BMI at the 51st percentile.

“Currently, our nutrition recommendations as pediatricians are that all children are fed the same, essentially, after they’re born. We don’t have different growth parameters or different trajectories or targets for children who may have had different in utero exposures,” Dr. Gilley said.

Do some children need more monitoring for RWG?

Though we can’t necessarily draw conclusions from this one study, she says, the findings raise the question of whether children who were exposed in utero to obesity should be monitored for RWG more closely.

Lydia Shook, MD, Mass General Brigham maternal-fetal specialist and codirector of the Diabetes in Pregnancy Program at Massachusetts General Hospital in Boston, said she was struck by the finding in this study that with female infants, but not males, RWG significantly modified the association between ppBMI and early childhood BMI z scores.

“It’s an interesting finding and should be followed up with larger cohorts,” she said, noting that some previous studies have shown males are more vulnerable to maternal obesity and RWG.

“[Often] when we stratify by sex, you really need larger groups to be able to see the differences well,” Dr. Shook said.

She said she also found it interesting that when the researchers adjusted for breastfeeding status or caloric intake in childhood, the findings did not substantially change.

“That’s something that would warrant further investigation in an observational study or controlled trial,” Dr. Shook said.

Preventing rapid weight gain

The authors note that they did not consider possible interventions for preventing RGW in the study, although there are many, Dr. Gilley said.

Dr. Gilley also noted that a limitation of this study is that the population studied was primarily White.

Recent studies have shown the benefits of responsive parenting (RP) interventions, including a large study in 2022 geared toward Black families to teach better infant sleep practices as a way to prevent rapid weight gain.

That study, which tested the SAAF intervention, (Strong African American Families) found that “RP infants were nearly half as likely to experience upward crossing of two major weight-for-age percentile lines (14.1%), compared with control infants (24.2%); P = .09; odds ratio, 0.52; 95% confidence interval, 0.24-1.12.”

Along with sleep interventions, Dr. Gilley said, some researchers are studying the effects on RWG of better paternal engagement, or more involvement with the Women, Infants, and Children program, particularly with lower-income families.

Other studies have looked at breastfeeding vs. formula feeding – “but there have been mixed results there” – and responsive feeding practices, such as teaching families to recognize when a baby is full.

Dr. Gilley said she hopes this work will help broaden the thinking when it comes to infant weight gain.

“We spend a lot of time thinking about babies who are not growing fast enough and very little time thinking about babies who are growing too fast,” she said, “especially in those first 4-6 months of life.”

Dr. Gilley points to a study that illustrates that point. Pesch et al. concluded in a 2021 study based on interviews that pediatricians “are uncertain about the concept, definition, management, and long-term risks of rapid infant weight gain.”

Authors and Dr. Gilley declare no relevant financial relationships.

“Did you love your wife?” asks a character in “Rose,” a book by Martin Cruz Smith.

“No, but she became a fact through perseverance,” the man replied.

Medicine also has such relationships, it seems – tentative ideas that turned into fact simply by existing long enough.

Age 65 as the cutoff for cervical screening may be one such example. It has existed for 27 years with limited science to back it up. That may soon change with the launch of a $3.3 million study that is being funded by the National Institutes of Health (NIH). The study is intended to provide a more solid foundation for the benefits and harms of cervical screening for women older than 65.

It’s an important issue: 20% of all cervical cancer cases are found in women who are older than 65. Most of these patients have late-stage disease, which can be fatal. In the United States, 35% of cervical cancer deaths occur after age 65. But women in this age group are usually no longer screened for cervical cancer.

Back in 1996, the U.S. Preventive Services Task Force recommended that for women at average risk with adequate prior screening, cervical screening should stop at the age of 65. This recommendation has been carried forward year after year and has been incorporated into several other guidelines.

For example, current guidelines from the American Cancer Society, the American College of Obstetricians and Gynecologists, and the USPSTF recommend that cervical screening stop at aged 65 for patients with adequate prior screening.

“Adequate screening” is defined as three consecutive normal Pap tests or two consecutive negative human papillomavirus tests or two consecutive negative co-tests within the prior 10 years, with the most recent screening within 5 years and with no precancerous lesions in the past 25 years.

This all sounds reasonable; however, for most women, medical records aren’t up to the task of providing a clean bill of cervical health over many decades.

Explained Sarah Feldman, MD, an associate professor in obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston: “You know, when a patient says to me at 65, ‘Should I continue screening?’ I say, ‘Do you have all your results?’ And they’ll say, ‘Well, I remember I had a sort of abnormal pap 15 years ago,’ and I say, ‘All right; well, who knows what that was?’ So I’ll continue screening.”

According to George Sawaya, MD, professor of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, up to 60% of women do not meet the criteria to end screening at age 65. This means that each year in the United States, approximately 1.7 million women turn 65 and should, in theory, continue to undergo screening for cervical cancer.

Unfortunately, the evidence base for the harms and benefits of cervical screening after age 65 is almost nonexistent – at least by the current standards of evidence-based medicine.

“We need to be clear that we don’t really know the appropriateness of the screening after 65,” said Dr. Sawaya, “which is ironic, because cervical cancer screening is probably the most commonly implemented cancer screening test in the country because it starts so early and ends so late and it’s applied so frequently.”

Dr. Feldman agrees that the age 65 cutoff is “somewhat arbitrary.” She said, “Why don’t they want to consider it continuing past 65? I don’t really understand, I have to be honest with you.”

So what’s the scientific evidence backing up the 27-year-old recommendation?

In 2018, the USPSTF’s cervical-screening guidelines concluded “with moderate certainty that the benefits of screening in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer do not outweigh the potential harms.”

This recommendation was based on a new decision model commissioned by the USPSTF. The model was needed because, as noted by the guidelines’ authors, “None of the screening trials enrolled women older than 65 years, so direct evidence on when to stop screening is not available.”

In 2020, the ACS carried out a fresh literature review and published its own recommendations. The ACS concluded that “the evidence for the effectiveness of screening beyond age 65 is limited, based solely on observational and modeling studies.”

As a result, the ACS assigned a “qualified recommendation” to the age-65 moratorium (defined as “less certainty about the balance of benefits and harms or about patients’ values and preferences”).

Most recently, the 2021 Updated Cervical Cancer Screening Guidelines, published by the American College of Obstetricians and Gynecologists, endorsed the recommendations of the USPSTF.

Dr. Sawaya said, “The whole issue about screening over 65 is complicated from a lot of perspectives. We don’t know a lot about the safety. We don’t really know a lot about patients’ perceptions of it. But we do know that there has to be an upper age limit after which screening is just simply imprudent.”

Dr. Sawaya acknowledges that there exists a “heck-why-not” attitude toward cervical screening after 65 among some physicians, given that the tests are quick and cheap and could save a life, but he sounds a note of caution.

“It’s like when we used to use old cameras: the film was cheap, but the developing was really expensive,” Dr. Sawaya said. “So it’s not necessarily about the tests being cheap, it’s about the cascade of events [that follow].”

Follow-up for cervical cancer can be more hazardous for a postmenopausal patient than for a younger woman, explained Dr. Sawaya, because the transformation zone of the cervix may be difficult to see on colposcopy. Instead of a straightforward 5-minute procedure in the doctor’s office, the older patient may need the operating room simply to provide the first biopsy.

In addition, treatments such as cone biopsy, loop excision, or ablation are also more worrying for older women, said Dr. Sawaya, “So you start thinking about the risks of anesthesia, you start thinking about the risks of bleeding and infection, etc. And these have not been well described in older people.”

To add to the uncertainty about the merits and risks of hunting out cervical cancer in older women, a lot has changed in women’s health since 1996.

Explained Dr. Sawaya, “This stake was put in the ground in 1996, ... but since that time, life expectancy has gained 5 years. So a logical person would say, ‘Oh, well, let’s just say it should be 70 now, right?’ [But] can we even use old studies to inform the current cohort of women who are entering this 65-year-and-older age group?”

To answer all these questions, a 5-year, $3.3 million study funded by the NIH through the National Cancer Institute is now underway.

The project, named Comparative Effectiveness Research to Validate and Improve Cervical Cancer Screening (CERVICCS 2), will be led by Dr. Sawaya and Michael Silverberg, PhD, associate director of the Behavioral Health, Aging and Infectious Diseases Section of Kaiser Permanente Northern California’s Division of Research.

Dr. Sawaya concluded: “There’s very few things that are packaged away and thought to be just the truth. And this is why we always have to be vigilant. ... And that’s what keeps science so interesting and exciting.”

Dr. Sawaya has disclosed no relevant financial relationships. Dr. Feldman writes for UpToDate and receives several NIH grants.

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

“Did you love your wife?” asks a character in “Rose,” a book by Martin Cruz Smith.

“No, but she became a fact through perseverance,” the man replied.

Medicine also has such relationships, it seems – tentative ideas that turned into fact simply by existing long enough.

Age 65 as the cutoff for cervical screening may be one such example. It has existed for 27 years with limited science to back it up. That may soon change with the launch of a $3.3 million study that is being funded by the National Institutes of Health (NIH). The study is intended to provide a more solid foundation for the benefits and harms of cervical screening for women older than 65.

It’s an important issue: 20% of all cervical cancer cases are found in women who are older than 65. Most of these patients have late-stage disease, which can be fatal. In the United States, 35% of cervical cancer deaths occur after age 65. But women in this age group are usually no longer screened for cervical cancer.

Back in 1996, the U.S. Preventive Services Task Force recommended that for women at average risk with adequate prior screening, cervical screening should stop at the age of 65. This recommendation has been carried forward year after year and has been incorporated into several other guidelines.

For example, current guidelines from the American Cancer Society, the American College of Obstetricians and Gynecologists, and the USPSTF recommend that cervical screening stop at aged 65 for patients with adequate prior screening.

“Adequate screening” is defined as three consecutive normal Pap tests or two consecutive negative human papillomavirus tests or two consecutive negative co-tests within the prior 10 years, with the most recent screening within 5 years and with no precancerous lesions in the past 25 years.

This all sounds reasonable; however, for most women, medical records aren’t up to the task of providing a clean bill of cervical health over many decades.

Explained Sarah Feldman, MD, an associate professor in obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston: “You know, when a patient says to me at 65, ‘Should I continue screening?’ I say, ‘Do you have all your results?’ And they’ll say, ‘Well, I remember I had a sort of abnormal pap 15 years ago,’ and I say, ‘All right; well, who knows what that was?’ So I’ll continue screening.”

According to George Sawaya, MD, professor of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, up to 60% of women do not meet the criteria to end screening at age 65. This means that each year in the United States, approximately 1.7 million women turn 65 and should, in theory, continue to undergo screening for cervical cancer.

Unfortunately, the evidence base for the harms and benefits of cervical screening after age 65 is almost nonexistent – at least by the current standards of evidence-based medicine.

“We need to be clear that we don’t really know the appropriateness of the screening after 65,” said Dr. Sawaya, “which is ironic, because cervical cancer screening is probably the most commonly implemented cancer screening test in the country because it starts so early and ends so late and it’s applied so frequently.”

Dr. Feldman agrees that the age 65 cutoff is “somewhat arbitrary.” She said, “Why don’t they want to consider it continuing past 65? I don’t really understand, I have to be honest with you.”

So what’s the scientific evidence backing up the 27-year-old recommendation?

In 2018, the USPSTF’s cervical-screening guidelines concluded “with moderate certainty that the benefits of screening in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer do not outweigh the potential harms.”

This recommendation was based on a new decision model commissioned by the USPSTF. The model was needed because, as noted by the guidelines’ authors, “None of the screening trials enrolled women older than 65 years, so direct evidence on when to stop screening is not available.”

In 2020, the ACS carried out a fresh literature review and published its own recommendations. The ACS concluded that “the evidence for the effectiveness of screening beyond age 65 is limited, based solely on observational and modeling studies.”

As a result, the ACS assigned a “qualified recommendation” to the age-65 moratorium (defined as “less certainty about the balance of benefits and harms or about patients’ values and preferences”).

Most recently, the 2021 Updated Cervical Cancer Screening Guidelines, published by the American College of Obstetricians and Gynecologists, endorsed the recommendations of the USPSTF.

Dr. Sawaya said, “The whole issue about screening over 65 is complicated from a lot of perspectives. We don’t know a lot about the safety. We don’t really know a lot about patients’ perceptions of it. But we do know that there has to be an upper age limit after which screening is just simply imprudent.”

Dr. Sawaya acknowledges that there exists a “heck-why-not” attitude toward cervical screening after 65 among some physicians, given that the tests are quick and cheap and could save a life, but he sounds a note of caution.

“It’s like when we used to use old cameras: the film was cheap, but the developing was really expensive,” Dr. Sawaya said. “So it’s not necessarily about the tests being cheap, it’s about the cascade of events [that follow].”

Follow-up for cervical cancer can be more hazardous for a postmenopausal patient than for a younger woman, explained Dr. Sawaya, because the transformation zone of the cervix may be difficult to see on colposcopy. Instead of a straightforward 5-minute procedure in the doctor’s office, the older patient may need the operating room simply to provide the first biopsy.

In addition, treatments such as cone biopsy, loop excision, or ablation are also more worrying for older women, said Dr. Sawaya, “So you start thinking about the risks of anesthesia, you start thinking about the risks of bleeding and infection, etc. And these have not been well described in older people.”

To add to the uncertainty about the merits and risks of hunting out cervical cancer in older women, a lot has changed in women’s health since 1996.

Explained Dr. Sawaya, “This stake was put in the ground in 1996, ... but since that time, life expectancy has gained 5 years. So a logical person would say, ‘Oh, well, let’s just say it should be 70 now, right?’ [But] can we even use old studies to inform the current cohort of women who are entering this 65-year-and-older age group?”

To answer all these questions, a 5-year, $3.3 million study funded by the NIH through the National Cancer Institute is now underway.

The project, named Comparative Effectiveness Research to Validate and Improve Cervical Cancer Screening (CERVICCS 2), will be led by Dr. Sawaya and Michael Silverberg, PhD, associate director of the Behavioral Health, Aging and Infectious Diseases Section of Kaiser Permanente Northern California’s Division of Research.

Dr. Sawaya concluded: “There’s very few things that are packaged away and thought to be just the truth. And this is why we always have to be vigilant. ... And that’s what keeps science so interesting and exciting.”

Dr. Sawaya has disclosed no relevant financial relationships. Dr. Feldman writes for UpToDate and receives several NIH grants.

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

“Did you love your wife?” asks a character in “Rose,” a book by Martin Cruz Smith.

“No, but she became a fact through perseverance,” the man replied.

Medicine also has such relationships, it seems – tentative ideas that turned into fact simply by existing long enough.

Age 65 as the cutoff for cervical screening may be one such example. It has existed for 27 years with limited science to back it up. That may soon change with the launch of a $3.3 million study that is being funded by the National Institutes of Health (NIH). The study is intended to provide a more solid foundation for the benefits and harms of cervical screening for women older than 65.

It’s an important issue: 20% of all cervical cancer cases are found in women who are older than 65. Most of these patients have late-stage disease, which can be fatal. In the United States, 35% of cervical cancer deaths occur after age 65. But women in this age group are usually no longer screened for cervical cancer.

Back in 1996, the U.S. Preventive Services Task Force recommended that for women at average risk with adequate prior screening, cervical screening should stop at the age of 65. This recommendation has been carried forward year after year and has been incorporated into several other guidelines.

For example, current guidelines from the American Cancer Society, the American College of Obstetricians and Gynecologists, and the USPSTF recommend that cervical screening stop at aged 65 for patients with adequate prior screening.

“Adequate screening” is defined as three consecutive normal Pap tests or two consecutive negative human papillomavirus tests or two consecutive negative co-tests within the prior 10 years, with the most recent screening within 5 years and with no precancerous lesions in the past 25 years.

This all sounds reasonable; however, for most women, medical records aren’t up to the task of providing a clean bill of cervical health over many decades.

Explained Sarah Feldman, MD, an associate professor in obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston: “You know, when a patient says to me at 65, ‘Should I continue screening?’ I say, ‘Do you have all your results?’ And they’ll say, ‘Well, I remember I had a sort of abnormal pap 15 years ago,’ and I say, ‘All right; well, who knows what that was?’ So I’ll continue screening.”

According to George Sawaya, MD, professor of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, up to 60% of women do not meet the criteria to end screening at age 65. This means that each year in the United States, approximately 1.7 million women turn 65 and should, in theory, continue to undergo screening for cervical cancer.

Unfortunately, the evidence base for the harms and benefits of cervical screening after age 65 is almost nonexistent – at least by the current standards of evidence-based medicine.

“We need to be clear that we don’t really know the appropriateness of the screening after 65,” said Dr. Sawaya, “which is ironic, because cervical cancer screening is probably the most commonly implemented cancer screening test in the country because it starts so early and ends so late and it’s applied so frequently.”

Dr. Feldman agrees that the age 65 cutoff is “somewhat arbitrary.” She said, “Why don’t they want to consider it continuing past 65? I don’t really understand, I have to be honest with you.”

So what’s the scientific evidence backing up the 27-year-old recommendation?

In 2018, the USPSTF’s cervical-screening guidelines concluded “with moderate certainty that the benefits of screening in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer do not outweigh the potential harms.”

This recommendation was based on a new decision model commissioned by the USPSTF. The model was needed because, as noted by the guidelines’ authors, “None of the screening trials enrolled women older than 65 years, so direct evidence on when to stop screening is not available.”

In 2020, the ACS carried out a fresh literature review and published its own recommendations. The ACS concluded that “the evidence for the effectiveness of screening beyond age 65 is limited, based solely on observational and modeling studies.”

As a result, the ACS assigned a “qualified recommendation” to the age-65 moratorium (defined as “less certainty about the balance of benefits and harms or about patients’ values and preferences”).

Most recently, the 2021 Updated Cervical Cancer Screening Guidelines, published by the American College of Obstetricians and Gynecologists, endorsed the recommendations of the USPSTF.

Dr. Sawaya said, “The whole issue about screening over 65 is complicated from a lot of perspectives. We don’t know a lot about the safety. We don’t really know a lot about patients’ perceptions of it. But we do know that there has to be an upper age limit after which screening is just simply imprudent.”

Dr. Sawaya acknowledges that there exists a “heck-why-not” attitude toward cervical screening after 65 among some physicians, given that the tests are quick and cheap and could save a life, but he sounds a note of caution.

“It’s like when we used to use old cameras: the film was cheap, but the developing was really expensive,” Dr. Sawaya said. “So it’s not necessarily about the tests being cheap, it’s about the cascade of events [that follow].”

Follow-up for cervical cancer can be more hazardous for a postmenopausal patient than for a younger woman, explained Dr. Sawaya, because the transformation zone of the cervix may be difficult to see on colposcopy. Instead of a straightforward 5-minute procedure in the doctor’s office, the older patient may need the operating room simply to provide the first biopsy.

In addition, treatments such as cone biopsy, loop excision, or ablation are also more worrying for older women, said Dr. Sawaya, “So you start thinking about the risks of anesthesia, you start thinking about the risks of bleeding and infection, etc. And these have not been well described in older people.”

To add to the uncertainty about the merits and risks of hunting out cervical cancer in older women, a lot has changed in women’s health since 1996.

Explained Dr. Sawaya, “This stake was put in the ground in 1996, ... but since that time, life expectancy has gained 5 years. So a logical person would say, ‘Oh, well, let’s just say it should be 70 now, right?’ [But] can we even use old studies to inform the current cohort of women who are entering this 65-year-and-older age group?”

To answer all these questions, a 5-year, $3.3 million study funded by the NIH through the National Cancer Institute is now underway.

The project, named Comparative Effectiveness Research to Validate and Improve Cervical Cancer Screening (CERVICCS 2), will be led by Dr. Sawaya and Michael Silverberg, PhD, associate director of the Behavioral Health, Aging and Infectious Diseases Section of Kaiser Permanente Northern California’s Division of Research.

Dr. Sawaya concluded: “There’s very few things that are packaged away and thought to be just the truth. And this is why we always have to be vigilant. ... And that’s what keeps science so interesting and exciting.”

Dr. Sawaya has disclosed no relevant financial relationships. Dr. Feldman writes for UpToDate and receives several NIH grants.

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

Cesarean deliveries in women in the United States who were at low risk for the procedure declined overall during the 2 decades from 2000 to 2019, based on data from more than 40 million deliveries.

Although clinically indicated cesarean deliveries may improve outcomes for mothers and infants, “when not clinically indicated, cesarean delivery is a major surgical intervention that increases risk for adverse outcomes,” wrote Anna M. Frappaolo of Columbia University College of Physicians and Surgeons, New York, and colleagues.

The Healthy People 2030 campaign includes the reduction of cesarean deliveries, but trends in these procedures, especially with regard to diagnoses of labor arrest, have not been well studied, the researchers said.

In an analysis published in JAMA Network Open, the researchers reviewed delivery hospitalizations using data from the National Inpatient Sample from 2000 to 2019.

Births deemed low risk for cesarean delivery were identified by using criteria of the Society for Maternal-Fetal Medicine and additional criteria, and joinpoint regression analysis was used to estimate changes.

The researchers examined overall trends in cesarean deliveries as well as trends for three specific diagnoses: nonreassuring fetal status, labor arrest, and obstructed labor.

The final analysis included 40,517,867 deliveries; of these, 4,885,716 (12.1%) were cesarean deliveries.

Overall, cesarean deliveries in patients deemed at low risk increased from 9.7% in 2000 to 13.9% in 2009, then plateaued and decreased from 13.0% in 2012 to 11.1% in 2019. The average annual percentage change (AAPC) for cesarean delivery was 6.4% for the years from 2000 to 2005, 1.2% from 2005 to 2009, and −2.2% from 2009 to 2019.

Cesarean delivery for nonreassuring fetal status increased over the entire study period, from 3.4% in 2000 to 5.1% in 2019. By contrast, overall cesarean delivery for labor arrest increased from 3.6% in 2000 to a high of 4.8% in 2009, then decreased to 2.7% in 2019. Cesarean deliveries with a diagnosis of obstructed labor decreased from 0.9% in 2008 to 0.3% in 2019.

More specifically, cesarean deliveries for labor arrest in the active phase, latent phase, and second stage of labor increased from 1.5% to 2.1%, 1.1% to 1.5%, and 0.9% to 1.3%, respectively, from 2000 to 2009, and decreased from 2.1% to 1.7% for the active phase, from 1.5% to 1.2% for the latent phase, and from 1.2% to 0.9% for the second stage between 2010 and 2019.

Patients with increased odds of cesarean delivery were older (aged 35-39 years vs. 25-29 years, adjusted odds ratio 1.27), delivered in a hospital in the South vs. the Northeast of the United States (aOR 1.11), and were more likely to be non-Hispanic Black vs. non-Hispanic White (OR 1.23).

Notably, changes in nomenclature and interpretation of intrapartum electronic fetal heart monitoring occurred during the study period, with recommendations for the adoption of a three-tiered system for fetal heart rate patterns in 2008. “It is possible that current evidence and nomenclature related to intrapartum FHR interpretation may result in identification of a larger number of fetuses deemed at indeterminate risk for abnormal acid-base status,” the researchers wrote in their discussion.

The study findings were limited by several factors including the use of administrative discharge data rather than clinical records, the exclusion of patients with chronic conditions associated with cesarean delivery, changes in billing codes during the study period, and the inability to account for the effect of health factors, maternal age, and use of assisted reproductive technology, the researchers noted.

However, the results were strengthened by the large sample size and 20-year study period, as well as the stratification of labor arrest by stage, and suggest uptake of newer recommendations, they said. “Future reductions in cesarean deliveries among patients at low risk for cesarean delivery may be dependent on improved assessment of intrapartum fetal status,” they concluded.

Consider populations and outcomes in cesarean risk assessment

The decreasing rates of cesarean deliveries in the current study can be seen as positive, but more research is needed to examine maternal and neonatal outcomes, and to consider other conditions that affect risk for cesarean delivery, Paolo Ivo Cavoretto, MD, and Massimo Candiani, MD, of IRCCS San Raffaele Scientific Institute, and Antonio Farina, MD, of the University of Bologna, Italy, wrote in an accompanying editorial.

Notably, the study authors identified a population aged 15-39 years as low risk, and an increased risk for cesarean delivery within this range increased with age. “Maternal age remains a major risk factor associated with the risk of cesarean delivery, both from results of this study and those of previous analyses assessing its independence from other related risk factors,” the editorialists said.

The study findings also reflect the changes in standards for labor duration during the study period, they noted. The longer duration of labor may reduce cesarean delivery rates, but it is not without maternal and fetal-neonatal risks, they wrote.

“To be sure that the described trend of cesarean delivery rate reduction can be considered positive, there would be the theoretical need to analyze other maternal-fetal-neonatal outcomes (e.g., rates of operative deliveries, neonatal acidemia, intensive care unit use, maternal hemorrhage, pelvic floor trauma and dysfunction, and psychological distress),” the editorialists concluded.
 

More research needed to explore clinical decisions

“Reducing the cesarean delivery rate is a top priority, but evidence is lacking on an optimal rate that improves maternal and neonatal outcomes,” Iris Krishna, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Hospital quality and safety committees have been working to decrease cesarean deliveries amongst low-risk women, and identifying contemporary trends gives us insight on whether some of these efforts have translated to a lower cesarean delivery rate,” she said.

Dr. Krishna said she was not surprised by the higher cesarean section rate in the South. “The decision for cesarean delivery is multifaceted, and although this study was not able to assess clinical indications for cesarean delivery or maternal and fetal outcomes, we cannot ignore that social determinants of health contribute greatly to overall health outcomes,” she said. The trends in the current study further underscore the geographic disparities in access to health care present in the South, she added.

“This study notes that cesarean delivery for nonreassuring fetal status increased; however, nonreassuring fetal status as an indication for cesarean delivery can be subjective,” Dr. Krishna said. “Hospital quality and safety committees should consider reviewing the clinical scenarios that led to this decision to identify opportunities for improvement and further education,” she said.

“Defining contemporary trends in cesarean delivery for low-risk patients has merit, but the study findings should be interpreted with caution,” said Dr. Krishna, who is a member of the Ob.Gyn. News advisory board. More research is needed to define an optimal cesarean section rate that promotes positive maternal and fetal outcomes, and to determine whether identifying an optimal rate should be based on patient risk profiles, she said.

The study received no outside funding. Lead author Ms. Frappaolo had no financial conflicts to disclose; nor did the editorial authors or Dr. Krishna.