As a psychiatrist specializing in eating disorders, Kim Dennis, MD, has seen firsthand the complex relationship between obesity treatment and mental health in adolescents.

Now, with the rising popularity of medications like Ozempic for weight loss, she fears she will care for more teens with eating disorders who are seeking glucagon-like peptide 1 (GLP-1) agonists or who have developed a disorder while taking them.

“We haven’t seen patients yet, but I’m sure they are on their way,” said Dr. Dennis, a clinical assistant professor in the Department of Psychiatry at the University of Illinois College of Medicine in Chicago. She is also the cofounder and chief medical officer of SunCloud Health, an outpatient eating disorder treatment center in Illinois.

Dr. Dennis’ concerns reflect a growing unease among eating disorder specialists as obesity medications gain traction for adolescent use. A recent study published in JAMA Pediatrics showed nearly 80% of teens in treatment for obesity reported symptoms of disordered eating at the outset of an intervention. These included signs of binge eating and loss of control.

The randomized clinical trial, conducted from 2018 to 2023, examined 141 adolescents with obesity undergoing interventions like low-energy diets or intermittent energy restriction. Almost half scored as having risk for an undiagnosed eating disorder, as defined by the Eating Disorder Examination Questionnaire (EDE-Q).

At the end of the intervention, many teens continued to have symptoms of disordered eating, while a smaller group was newly scored as having a risk for an eating disorder.
 

Weight Loss and Eating Disorders: A Balancing Act

The findings illuminate a significant challenge for pediatricians and primary care clinicians: Balancing effective weight management with the risk of exacerbating or triggering eating disorders, said Hiba Jebeile, PhD, a research dietitian at The Children’s Hospital at Westmead in Australia, and the study’s lead author. Adding weight loss medication on top of the equation can further complicate care.

“It is helpful for obesity and eating disorder services to work together, with clear referral pathways, to manage these adolescents,” Dr. Jebeile said.

The US Food and Drug Administration approved semaglutide for weight loss in adolescents aged 12-17 years in December 2020. One study found that the number of adolescents prescribed GLP-1 receptor agonists (GLP-1 RAs) for type 2 diabetes and weight management rose from 8722 to 60,567 between 2020 and 2023 — a nearly sevenfold increase.

“The number of adolescents taking these medications is going up because they work,” said Suzanne Cuda, MD, medical director of Alamo City Healthy Kids and Families, a medical weight management clinic in San Antonio. The medications have been shown to treat type 2 diabetes, lower blood pressure, and reduce the risk for cardiovascular diseases.

“The younger you are, the better the outcome,” Dr. Cuda said.

How GLP-1 agonists may affect adolescents in the long run is not yet clear. Existing studies on GLP-1 medications in patients with eating disorders have shown mixed results. Some studies indicate that the drugs decrease binge episodes for those with binge eating disorder or bulimia nervosa. However, these studies had small sample sizes and measured only short-term effects, leaving long-term outcomes and risks unknown.

Traditional treatments for eating disorders emphasize regular eating patterns, body acceptance, addressing weight stigma, and improving attunement to hunger and fullness cues — approaches that may conflict with the effects of GLP-1 agonists. These drugs suppress appetite, alter metabolic signals, and may unintentionally reinforce weight loss as a primary goal, creating a potential disconnect between the aims of recovery from eating disorders and the biologic effects of the medication, experts said.

Dr. Cuda said she has cared for adolescents with diagnosed eating disorders in her practice who are seeking GLP-1 agonists. She said she first works with patients to treat the underlying disorder before prescribing medication.

“One of the concerns is the extreme reductions in calories that could be induced by GLP-1 RA in children and adolescents,” she said. Unlike adults, adolescents use caloric energy not just for physical activity but also for growing and developing, she said.

“They can’t catch up on that growth and development,” she added.
 

Advice for Screening and Monitoring

The National Eating Disorders Association raised concerns about the potential misuse of these medications and their potential to exacerbate eating disorder behaviors in people who are already at a higher risk of developing one of the conditions, including those with existing mental health disorders, stress, who have already dieted, and who have experienced weight-centric bullying.

Clinicians should be on the lookout for patients seeking GLP-1s who present with symptoms of an eating disorder that may be less apparent, such as picky eating, insomnia or difficulty sleeping, or, for girls, irregular menstrual periods, Dr. Dennis said. These patients may be more likely to go undiagnosed or misdiagnosed. Research also suggests that people of color are less likely to be diagnosed or receive specialty care for eating disorders.

Discussions between patients and clinicians about obesity treatment prior to prescribing provide a crucial opportunity to screen and monitor for disordered eating, which Dr. Dennis said does not universally occur currently.

Dr. Dennis recommended initial assessments using validated screening tools like the EDE-Q and the Center for Epidemiologic Studies Depression Scale Revised, 10-Item Version.

Ongoing monitoring throughout treatment is essential, with initial monthly check-ins that include dietary counseling to detect subtle changes in eating behaviors or attitudes toward food and body image, Dr. Cuda said.

The Obesity Medicine Association (OMA) has stressed the importance of a collaborative approach involving connections with mental health professionals specializing in eating disorders and dietitians.

“If you have a chance to send them to an obesity medicine specialist, you should do that,” said Dr. Cuda, who coauthored the OMA statement. “It’s impractical to expect a primary care physician to do everything: Screen for dietary disorders, do a full dietary counseling, follow up on their activity.”

For patients showing signs of disordered eating, clinicians should avoid recommending restrictive dietary approaches, like cutting out food groups such as carbohydrates or a restricted calorie goal. Instead, they can suggest focusing on healthier lifestyle habits and referring to a psychotherapist, the experts said. Clinicians also should be prepared to adjust or pause GLP-1 agonists if disordered eating disorder symptoms worsen.

“I think a weight-agnostic approach where the focus of care is not weight loss but increase in health protective behaviors and nutritional intake is safest for all kids, especially those with eating disorders or eating disorder risk factors,” Dr. Dennis said.

Various authors of the eating disorder study reported receiving grants, advisory board fees, and speaker fees from entities including the National Health and Medical Research Council of Australia, Eli Lilly, Novo Nordisk, Nu-Mega Ingredients, and the National Institutes of Health, among others.
 

A version of this article appeared on Medscape.com.

As a psychiatrist specializing in eating disorders, Kim Dennis, MD, has seen firsthand the complex relationship between obesity treatment and mental health in adolescents.

Now, with the rising popularity of medications like Ozempic for weight loss, she fears she will care for more teens with eating disorders who are seeking glucagon-like peptide 1 (GLP-1) agonists or who have developed a disorder while taking them.

“We haven’t seen patients yet, but I’m sure they are on their way,” said Dr. Dennis, a clinical assistant professor in the Department of Psychiatry at the University of Illinois College of Medicine in Chicago. She is also the cofounder and chief medical officer of SunCloud Health, an outpatient eating disorder treatment center in Illinois.

Dr. Dennis’ concerns reflect a growing unease among eating disorder specialists as obesity medications gain traction for adolescent use. A recent study published in JAMA Pediatrics showed nearly 80% of teens in treatment for obesity reported symptoms of disordered eating at the outset of an intervention. These included signs of binge eating and loss of control.

The randomized clinical trial, conducted from 2018 to 2023, examined 141 adolescents with obesity undergoing interventions like low-energy diets or intermittent energy restriction. Almost half scored as having risk for an undiagnosed eating disorder, as defined by the Eating Disorder Examination Questionnaire (EDE-Q).

At the end of the intervention, many teens continued to have symptoms of disordered eating, while a smaller group was newly scored as having a risk for an eating disorder.
 

Weight Loss and Eating Disorders: A Balancing Act

The findings illuminate a significant challenge for pediatricians and primary care clinicians: Balancing effective weight management with the risk of exacerbating or triggering eating disorders, said Hiba Jebeile, PhD, a research dietitian at The Children’s Hospital at Westmead in Australia, and the study’s lead author. Adding weight loss medication on top of the equation can further complicate care.

“It is helpful for obesity and eating disorder services to work together, with clear referral pathways, to manage these adolescents,” Dr. Jebeile said.

The US Food and Drug Administration approved semaglutide for weight loss in adolescents aged 12-17 years in December 2020. One study found that the number of adolescents prescribed GLP-1 receptor agonists (GLP-1 RAs) for type 2 diabetes and weight management rose from 8722 to 60,567 between 2020 and 2023 — a nearly sevenfold increase.

“The number of adolescents taking these medications is going up because they work,” said Suzanne Cuda, MD, medical director of Alamo City Healthy Kids and Families, a medical weight management clinic in San Antonio. The medications have been shown to treat type 2 diabetes, lower blood pressure, and reduce the risk for cardiovascular diseases.

“The younger you are, the better the outcome,” Dr. Cuda said.

How GLP-1 agonists may affect adolescents in the long run is not yet clear. Existing studies on GLP-1 medications in patients with eating disorders have shown mixed results. Some studies indicate that the drugs decrease binge episodes for those with binge eating disorder or bulimia nervosa. However, these studies had small sample sizes and measured only short-term effects, leaving long-term outcomes and risks unknown.

Traditional treatments for eating disorders emphasize regular eating patterns, body acceptance, addressing weight stigma, and improving attunement to hunger and fullness cues — approaches that may conflict with the effects of GLP-1 agonists. These drugs suppress appetite, alter metabolic signals, and may unintentionally reinforce weight loss as a primary goal, creating a potential disconnect between the aims of recovery from eating disorders and the biologic effects of the medication, experts said.

Dr. Cuda said she has cared for adolescents with diagnosed eating disorders in her practice who are seeking GLP-1 agonists. She said she first works with patients to treat the underlying disorder before prescribing medication.

“One of the concerns is the extreme reductions in calories that could be induced by GLP-1 RA in children and adolescents,” she said. Unlike adults, adolescents use caloric energy not just for physical activity but also for growing and developing, she said.

“They can’t catch up on that growth and development,” she added.
 

Advice for Screening and Monitoring

The National Eating Disorders Association raised concerns about the potential misuse of these medications and their potential to exacerbate eating disorder behaviors in people who are already at a higher risk of developing one of the conditions, including those with existing mental health disorders, stress, who have already dieted, and who have experienced weight-centric bullying.

Clinicians should be on the lookout for patients seeking GLP-1s who present with symptoms of an eating disorder that may be less apparent, such as picky eating, insomnia or difficulty sleeping, or, for girls, irregular menstrual periods, Dr. Dennis said. These patients may be more likely to go undiagnosed or misdiagnosed. Research also suggests that people of color are less likely to be diagnosed or receive specialty care for eating disorders.

Discussions between patients and clinicians about obesity treatment prior to prescribing provide a crucial opportunity to screen and monitor for disordered eating, which Dr. Dennis said does not universally occur currently.

Dr. Dennis recommended initial assessments using validated screening tools like the EDE-Q and the Center for Epidemiologic Studies Depression Scale Revised, 10-Item Version.

Ongoing monitoring throughout treatment is essential, with initial monthly check-ins that include dietary counseling to detect subtle changes in eating behaviors or attitudes toward food and body image, Dr. Cuda said.

The Obesity Medicine Association (OMA) has stressed the importance of a collaborative approach involving connections with mental health professionals specializing in eating disorders and dietitians.

“If you have a chance to send them to an obesity medicine specialist, you should do that,” said Dr. Cuda, who coauthored the OMA statement. “It’s impractical to expect a primary care physician to do everything: Screen for dietary disorders, do a full dietary counseling, follow up on their activity.”

For patients showing signs of disordered eating, clinicians should avoid recommending restrictive dietary approaches, like cutting out food groups such as carbohydrates or a restricted calorie goal. Instead, they can suggest focusing on healthier lifestyle habits and referring to a psychotherapist, the experts said. Clinicians also should be prepared to adjust or pause GLP-1 agonists if disordered eating disorder symptoms worsen.

“I think a weight-agnostic approach where the focus of care is not weight loss but increase in health protective behaviors and nutritional intake is safest for all kids, especially those with eating disorders or eating disorder risk factors,” Dr. Dennis said.

Various authors of the eating disorder study reported receiving grants, advisory board fees, and speaker fees from entities including the National Health and Medical Research Council of Australia, Eli Lilly, Novo Nordisk, Nu-Mega Ingredients, and the National Institutes of Health, among others.
 

A version of this article appeared on Medscape.com.

As a psychiatrist specializing in eating disorders, Kim Dennis, MD, has seen firsthand the complex relationship between obesity treatment and mental health in adolescents.

Now, with the rising popularity of medications like Ozempic for weight loss, she fears she will care for more teens with eating disorders who are seeking glucagon-like peptide 1 (GLP-1) agonists or who have developed a disorder while taking them.

“We haven’t seen patients yet, but I’m sure they are on their way,” said Dr. Dennis, a clinical assistant professor in the Department of Psychiatry at the University of Illinois College of Medicine in Chicago. She is also the cofounder and chief medical officer of SunCloud Health, an outpatient eating disorder treatment center in Illinois.

Dr. Dennis’ concerns reflect a growing unease among eating disorder specialists as obesity medications gain traction for adolescent use. A recent study published in JAMA Pediatrics showed nearly 80% of teens in treatment for obesity reported symptoms of disordered eating at the outset of an intervention. These included signs of binge eating and loss of control.

The randomized clinical trial, conducted from 2018 to 2023, examined 141 adolescents with obesity undergoing interventions like low-energy diets or intermittent energy restriction. Almost half scored as having risk for an undiagnosed eating disorder, as defined by the Eating Disorder Examination Questionnaire (EDE-Q).

At the end of the intervention, many teens continued to have symptoms of disordered eating, while a smaller group was newly scored as having a risk for an eating disorder.
 

Weight Loss and Eating Disorders: A Balancing Act

The findings illuminate a significant challenge for pediatricians and primary care clinicians: Balancing effective weight management with the risk of exacerbating or triggering eating disorders, said Hiba Jebeile, PhD, a research dietitian at The Children’s Hospital at Westmead in Australia, and the study’s lead author. Adding weight loss medication on top of the equation can further complicate care.

“It is helpful for obesity and eating disorder services to work together, with clear referral pathways, to manage these adolescents,” Dr. Jebeile said.

The US Food and Drug Administration approved semaglutide for weight loss in adolescents aged 12-17 years in December 2020. One study found that the number of adolescents prescribed GLP-1 receptor agonists (GLP-1 RAs) for type 2 diabetes and weight management rose from 8722 to 60,567 between 2020 and 2023 — a nearly sevenfold increase.

“The number of adolescents taking these medications is going up because they work,” said Suzanne Cuda, MD, medical director of Alamo City Healthy Kids and Families, a medical weight management clinic in San Antonio. The medications have been shown to treat type 2 diabetes, lower blood pressure, and reduce the risk for cardiovascular diseases.

“The younger you are, the better the outcome,” Dr. Cuda said.

How GLP-1 agonists may affect adolescents in the long run is not yet clear. Existing studies on GLP-1 medications in patients with eating disorders have shown mixed results. Some studies indicate that the drugs decrease binge episodes for those with binge eating disorder or bulimia nervosa. However, these studies had small sample sizes and measured only short-term effects, leaving long-term outcomes and risks unknown.

Traditional treatments for eating disorders emphasize regular eating patterns, body acceptance, addressing weight stigma, and improving attunement to hunger and fullness cues — approaches that may conflict with the effects of GLP-1 agonists. These drugs suppress appetite, alter metabolic signals, and may unintentionally reinforce weight loss as a primary goal, creating a potential disconnect between the aims of recovery from eating disorders and the biologic effects of the medication, experts said.

Dr. Cuda said she has cared for adolescents with diagnosed eating disorders in her practice who are seeking GLP-1 agonists. She said she first works with patients to treat the underlying disorder before prescribing medication.

“One of the concerns is the extreme reductions in calories that could be induced by GLP-1 RA in children and adolescents,” she said. Unlike adults, adolescents use caloric energy not just for physical activity but also for growing and developing, she said.

“They can’t catch up on that growth and development,” she added.
 

Advice for Screening and Monitoring

The National Eating Disorders Association raised concerns about the potential misuse of these medications and their potential to exacerbate eating disorder behaviors in people who are already at a higher risk of developing one of the conditions, including those with existing mental health disorders, stress, who have already dieted, and who have experienced weight-centric bullying.

Clinicians should be on the lookout for patients seeking GLP-1s who present with symptoms of an eating disorder that may be less apparent, such as picky eating, insomnia or difficulty sleeping, or, for girls, irregular menstrual periods, Dr. Dennis said. These patients may be more likely to go undiagnosed or misdiagnosed. Research also suggests that people of color are less likely to be diagnosed or receive specialty care for eating disorders.

Discussions between patients and clinicians about obesity treatment prior to prescribing provide a crucial opportunity to screen and monitor for disordered eating, which Dr. Dennis said does not universally occur currently.

Dr. Dennis recommended initial assessments using validated screening tools like the EDE-Q and the Center for Epidemiologic Studies Depression Scale Revised, 10-Item Version.

Ongoing monitoring throughout treatment is essential, with initial monthly check-ins that include dietary counseling to detect subtle changes in eating behaviors or attitudes toward food and body image, Dr. Cuda said.

The Obesity Medicine Association (OMA) has stressed the importance of a collaborative approach involving connections with mental health professionals specializing in eating disorders and dietitians.

“If you have a chance to send them to an obesity medicine specialist, you should do that,” said Dr. Cuda, who coauthored the OMA statement. “It’s impractical to expect a primary care physician to do everything: Screen for dietary disorders, do a full dietary counseling, follow up on their activity.”

For patients showing signs of disordered eating, clinicians should avoid recommending restrictive dietary approaches, like cutting out food groups such as carbohydrates or a restricted calorie goal. Instead, they can suggest focusing on healthier lifestyle habits and referring to a psychotherapist, the experts said. Clinicians also should be prepared to adjust or pause GLP-1 agonists if disordered eating disorder symptoms worsen.

“I think a weight-agnostic approach where the focus of care is not weight loss but increase in health protective behaviors and nutritional intake is safest for all kids, especially those with eating disorders or eating disorder risk factors,” Dr. Dennis said.

Various authors of the eating disorder study reported receiving grants, advisory board fees, and speaker fees from entities including the National Health and Medical Research Council of Australia, Eli Lilly, Novo Nordisk, Nu-Mega Ingredients, and the National Institutes of Health, among others.
 

A version of this article appeared on Medscape.com.

In a review of 32 mixed-type human studies, multinational researchers found a growing association between various classes of environmental pollutants and the risk for inflammatory bowel disease (IBD).

The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.

In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.

Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.

“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”

Icahn School of Medicine at Mount Sinai

• Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
• The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
• Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
• Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
• Zinc was linked to an increase in tight junction proteins.

Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.

A version of this article appeared on Medscape.com.

In a review of 32 mixed-type human studies, multinational researchers found a growing association between various classes of environmental pollutants and the risk for inflammatory bowel disease (IBD).

The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.

In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.

Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.

“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”

Icahn School of Medicine at Mount Sinai

• Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
• The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
• Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
• Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
• Zinc was linked to an increase in tight junction proteins.

Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.

A version of this article appeared on Medscape.com.

In a review of 32 mixed-type human studies, multinational researchers found a growing association between various classes of environmental pollutants and the risk for inflammatory bowel disease (IBD).

The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.

In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.

Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.

“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”

Icahn School of Medicine at Mount Sinai

• Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
• The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
• Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
• Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
• Zinc was linked to an increase in tight junction proteins.

Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.

A version of this article appeared on Medscape.com.

COPENHAGEN — Relative to starting on an immunomodulator and then switching to a more potent anti-CD20 monoclonal antibody, the likelihood of long-term accumulation of disability in patients with multiple sclerosis (MS) is significantly lower if the more potent drug is started first, according to extension data out to 6 years.

By the most recent analysis of a phase 3 extension study, there were “fewer disability worsening events and greater likelihood of being progression free among those started on ofatumumab than those started on teriflunomide and switched,” reported Amit Bar-Or, MD, director of the Center of Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia.

Stated differently, if ofatumumab is delayed, it never fully compensates for the advantage of better early MS control in treatment-naïve patients, according to Dr. Bar-Or, who presented these data at the 2024 ECTRIMS annual meeting.
 

Anti-CD20 Disability Protection Already Seen in Pivotal Trial

In two phase 3 trials called ASCLEPIOS I and II that were published together several years ago in The New England Journal of Medicine, the anti-CD20 monoclonal antibody ofatumumab reduced the annualized relapse rate (ARR) by half (0.11 vs. 0.22). While ARR was the primary endpoint, ofatumumab was also associated with a 34% reduction (P = .002) in risk of confirmed disability worsening at 3 months (3mCDW) at a medium follow-up of 1.6 years.

After the completion of ASCLEPIOS I and II, the majority of both arms of the study were enrolled in the ALITHIOS extension study. Patients in ofatumumab arm have remained on their initially assigned drug. Patients in the teriflunomide group were switched. Characterized as the delayed ofatumumab group, they have been receiving the same 20-mg, once-monthly subcutaneous (SQ) dose of ofatumumab as those initially assigned to this drug. ALITHIOS will continue to follow both groups until 2028.

Patients have now been followed for up to 6 years. In the latest results presented at ECTRIMS, data were available for 690 patients on continuous treatment and 677 switch patients. Baseline characteristics of the two groups were similar. About half of each group were treatment naive when enrolled in the ASCLEPIOS trials.

Whether compared for 6-month confirmed disability worsening (6mCDW), 6-month progression independent of relapse activity (6mPIRA) or 6-month relapse-associated worsening (6mRAW), disease progression was consistently worse for those with delayed ofatumumab. The differences were most pronounced in those who were treatment naive when started on therapy.
 

Anti-CD20 MAB sustains Disability Protection for up to Years

For those who were treatment naive, the rates of 6mCDW at the most recent follow-up were 16.61% vs 23.74% (P = .033) for continuous and delayed ofatumumab, respectively. For the entire study, these rates were 21.09% versus 24.77%, respectively, which represented a strong trend (P = .063).

The relative rates for 6mPIRA (11.12% vs 16.75%) and 6mRAW (4.26% vs 4.82%) in treatment-naive patients also favored continuous over delayed ofatumumab, and the numerical advantage was also seen with up to 6 years of follow-up in the overall study population for 6mPIRA (15.45% vs 16.56%) and 6mRAW (5.24% vs 5.81%).

Translating these into freedom from disability, Dr. Bar-Or reported that more than 80% (83.4%) of patients on continuous ofatumumab were progression free for up to 6 years, a figure that exceeded the 76.3% free of progression in the delayed ofatumumab group.

On the basis of 6mPIRA, that absence of disability progression neared 90% (88.9%) on continuous ofatumumab relative to 83.3% for delayed ofatumumab.

An advantage for a reduction in disability accumulation for ofatumumab relative to teriflunomide was established at the end of the ASCLEPIOS I and II trial, but the latest follow-up shows that it is “sustained out to 6 years.” The advantage is achieved with no greater cost in adverse events during the early treatment period, according to Dr. Bar-Or, who noted that ofatumumab and teriflunomide were similarly well tolerated in ASCLEPIOS I and II.
 

No New Gd T1 Lesions Observed Over 12 Months

Although other anti-CD20 monoclonal antibodies have also been shown to be highly effective and often more effective than immunomodulators in the first- and second-line treatment of relapsing remitting MS (RRMS), another set of data presented at ECTRIMS 2024 looked specifically at transitioning from intravenous (IV) anti-CD20 drugs to SQ ofatumumab.

In this study, called OLIKOS, 102 RRMS patients who had received either IV ocrelizumab or IV rituximab were followed after transitioning to ofatumumab administered SQ with an autoinjector pen. The primary endpoint was the proportion of patients with no change or a reduction gadolinium-enhancing (Gd) T1 lesions over 12 months of follow-up.

“At month 12, 84 of 84 evaluable patients with evaluable MRI assessments met the primary endpoint,” reported the principal investigator Le Hua, MD, director of the Multiple Sclerosis Program, Cleveland Clinic in Ohio.

At 12 months, there were also no new or enlarging T2 lesions in 98% of patients receiving SQ ofatumumab following the transition from one of the other anti-CD20 IV drugs, but Dr. Hua characterized this as an exploratory endpoint.

The safety and tolerability data during the OLIKOS study was also reassuring with no new or unexpected safety signals for SQ ofatumumab, which has been well tolerated in the phase 3 development program. IgM and IgG levels remained stable over the course of follow-up.

High-efficacy anti-CD20 drugs were once reserved for RRMS patients with highly active disease, but long-term data, such as those generated by the ALITHIOS extension study, suggest greater efficacy with acceptable safety of these agents relative to conventional first-line RRMS therapies. Based on ALITHIOS data, Dr. Bar-Or suggested that early use of the most effective therapy appears to lead to better long-term protection from increased cumulative disability.

Dr. Bar-Or reported financial relationships with Accure, Atara, Biogen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. Dr. Hua reported financial relationships with Alexion, EMD Serono, Genentech, Horizon, Novartis, and TG Therapeutics.

COPENHAGEN — Relative to starting on an immunomodulator and then switching to a more potent anti-CD20 monoclonal antibody, the likelihood of long-term accumulation of disability in patients with multiple sclerosis (MS) is significantly lower if the more potent drug is started first, according to extension data out to 6 years.

By the most recent analysis of a phase 3 extension study, there were “fewer disability worsening events and greater likelihood of being progression free among those started on ofatumumab than those started on teriflunomide and switched,” reported Amit Bar-Or, MD, director of the Center of Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia.

Stated differently, if ofatumumab is delayed, it never fully compensates for the advantage of better early MS control in treatment-naïve patients, according to Dr. Bar-Or, who presented these data at the 2024 ECTRIMS annual meeting.
 

Anti-CD20 Disability Protection Already Seen in Pivotal Trial

In two phase 3 trials called ASCLEPIOS I and II that were published together several years ago in The New England Journal of Medicine, the anti-CD20 monoclonal antibody ofatumumab reduced the annualized relapse rate (ARR) by half (0.11 vs. 0.22). While ARR was the primary endpoint, ofatumumab was also associated with a 34% reduction (P = .002) in risk of confirmed disability worsening at 3 months (3mCDW) at a medium follow-up of 1.6 years.

After the completion of ASCLEPIOS I and II, the majority of both arms of the study were enrolled in the ALITHIOS extension study. Patients in ofatumumab arm have remained on their initially assigned drug. Patients in the teriflunomide group were switched. Characterized as the delayed ofatumumab group, they have been receiving the same 20-mg, once-monthly subcutaneous (SQ) dose of ofatumumab as those initially assigned to this drug. ALITHIOS will continue to follow both groups until 2028.

Patients have now been followed for up to 6 years. In the latest results presented at ECTRIMS, data were available for 690 patients on continuous treatment and 677 switch patients. Baseline characteristics of the two groups were similar. About half of each group were treatment naive when enrolled in the ASCLEPIOS trials.

Whether compared for 6-month confirmed disability worsening (6mCDW), 6-month progression independent of relapse activity (6mPIRA) or 6-month relapse-associated worsening (6mRAW), disease progression was consistently worse for those with delayed ofatumumab. The differences were most pronounced in those who were treatment naive when started on therapy.
 

Anti-CD20 MAB sustains Disability Protection for up to Years

For those who were treatment naive, the rates of 6mCDW at the most recent follow-up were 16.61% vs 23.74% (P = .033) for continuous and delayed ofatumumab, respectively. For the entire study, these rates were 21.09% versus 24.77%, respectively, which represented a strong trend (P = .063).

The relative rates for 6mPIRA (11.12% vs 16.75%) and 6mRAW (4.26% vs 4.82%) in treatment-naive patients also favored continuous over delayed ofatumumab, and the numerical advantage was also seen with up to 6 years of follow-up in the overall study population for 6mPIRA (15.45% vs 16.56%) and 6mRAW (5.24% vs 5.81%).

Translating these into freedom from disability, Dr. Bar-Or reported that more than 80% (83.4%) of patients on continuous ofatumumab were progression free for up to 6 years, a figure that exceeded the 76.3% free of progression in the delayed ofatumumab group.

On the basis of 6mPIRA, that absence of disability progression neared 90% (88.9%) on continuous ofatumumab relative to 83.3% for delayed ofatumumab.

An advantage for a reduction in disability accumulation for ofatumumab relative to teriflunomide was established at the end of the ASCLEPIOS I and II trial, but the latest follow-up shows that it is “sustained out to 6 years.” The advantage is achieved with no greater cost in adverse events during the early treatment period, according to Dr. Bar-Or, who noted that ofatumumab and teriflunomide were similarly well tolerated in ASCLEPIOS I and II.
 

No New Gd T1 Lesions Observed Over 12 Months

Although other anti-CD20 monoclonal antibodies have also been shown to be highly effective and often more effective than immunomodulators in the first- and second-line treatment of relapsing remitting MS (RRMS), another set of data presented at ECTRIMS 2024 looked specifically at transitioning from intravenous (IV) anti-CD20 drugs to SQ ofatumumab.

In this study, called OLIKOS, 102 RRMS patients who had received either IV ocrelizumab or IV rituximab were followed after transitioning to ofatumumab administered SQ with an autoinjector pen. The primary endpoint was the proportion of patients with no change or a reduction gadolinium-enhancing (Gd) T1 lesions over 12 months of follow-up.

“At month 12, 84 of 84 evaluable patients with evaluable MRI assessments met the primary endpoint,” reported the principal investigator Le Hua, MD, director of the Multiple Sclerosis Program, Cleveland Clinic in Ohio.

At 12 months, there were also no new or enlarging T2 lesions in 98% of patients receiving SQ ofatumumab following the transition from one of the other anti-CD20 IV drugs, but Dr. Hua characterized this as an exploratory endpoint.

The safety and tolerability data during the OLIKOS study was also reassuring with no new or unexpected safety signals for SQ ofatumumab, which has been well tolerated in the phase 3 development program. IgM and IgG levels remained stable over the course of follow-up.

High-efficacy anti-CD20 drugs were once reserved for RRMS patients with highly active disease, but long-term data, such as those generated by the ALITHIOS extension study, suggest greater efficacy with acceptable safety of these agents relative to conventional first-line RRMS therapies. Based on ALITHIOS data, Dr. Bar-Or suggested that early use of the most effective therapy appears to lead to better long-term protection from increased cumulative disability.

Dr. Bar-Or reported financial relationships with Accure, Atara, Biogen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. Dr. Hua reported financial relationships with Alexion, EMD Serono, Genentech, Horizon, Novartis, and TG Therapeutics.

COPENHAGEN — Relative to starting on an immunomodulator and then switching to a more potent anti-CD20 monoclonal antibody, the likelihood of long-term accumulation of disability in patients with multiple sclerosis (MS) is significantly lower if the more potent drug is started first, according to extension data out to 6 years.

By the most recent analysis of a phase 3 extension study, there were “fewer disability worsening events and greater likelihood of being progression free among those started on ofatumumab than those started on teriflunomide and switched,” reported Amit Bar-Or, MD, director of the Center of Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia.

Stated differently, if ofatumumab is delayed, it never fully compensates for the advantage of better early MS control in treatment-naïve patients, according to Dr. Bar-Or, who presented these data at the 2024 ECTRIMS annual meeting.
 

Anti-CD20 Disability Protection Already Seen in Pivotal Trial

In two phase 3 trials called ASCLEPIOS I and II that were published together several years ago in The New England Journal of Medicine, the anti-CD20 monoclonal antibody ofatumumab reduced the annualized relapse rate (ARR) by half (0.11 vs. 0.22). While ARR was the primary endpoint, ofatumumab was also associated with a 34% reduction (P = .002) in risk of confirmed disability worsening at 3 months (3mCDW) at a medium follow-up of 1.6 years.

After the completion of ASCLEPIOS I and II, the majority of both arms of the study were enrolled in the ALITHIOS extension study. Patients in ofatumumab arm have remained on their initially assigned drug. Patients in the teriflunomide group were switched. Characterized as the delayed ofatumumab group, they have been receiving the same 20-mg, once-monthly subcutaneous (SQ) dose of ofatumumab as those initially assigned to this drug. ALITHIOS will continue to follow both groups until 2028.

Patients have now been followed for up to 6 years. In the latest results presented at ECTRIMS, data were available for 690 patients on continuous treatment and 677 switch patients. Baseline characteristics of the two groups were similar. About half of each group were treatment naive when enrolled in the ASCLEPIOS trials.

Whether compared for 6-month confirmed disability worsening (6mCDW), 6-month progression independent of relapse activity (6mPIRA) or 6-month relapse-associated worsening (6mRAW), disease progression was consistently worse for those with delayed ofatumumab. The differences were most pronounced in those who were treatment naive when started on therapy.
 

Anti-CD20 MAB sustains Disability Protection for up to Years

For those who were treatment naive, the rates of 6mCDW at the most recent follow-up were 16.61% vs 23.74% (P = .033) for continuous and delayed ofatumumab, respectively. For the entire study, these rates were 21.09% versus 24.77%, respectively, which represented a strong trend (P = .063).

The relative rates for 6mPIRA (11.12% vs 16.75%) and 6mRAW (4.26% vs 4.82%) in treatment-naive patients also favored continuous over delayed ofatumumab, and the numerical advantage was also seen with up to 6 years of follow-up in the overall study population for 6mPIRA (15.45% vs 16.56%) and 6mRAW (5.24% vs 5.81%).

Translating these into freedom from disability, Dr. Bar-Or reported that more than 80% (83.4%) of patients on continuous ofatumumab were progression free for up to 6 years, a figure that exceeded the 76.3% free of progression in the delayed ofatumumab group.

On the basis of 6mPIRA, that absence of disability progression neared 90% (88.9%) on continuous ofatumumab relative to 83.3% for delayed ofatumumab.

An advantage for a reduction in disability accumulation for ofatumumab relative to teriflunomide was established at the end of the ASCLEPIOS I and II trial, but the latest follow-up shows that it is “sustained out to 6 years.” The advantage is achieved with no greater cost in adverse events during the early treatment period, according to Dr. Bar-Or, who noted that ofatumumab and teriflunomide were similarly well tolerated in ASCLEPIOS I and II.
 

No New Gd T1 Lesions Observed Over 12 Months

Although other anti-CD20 monoclonal antibodies have also been shown to be highly effective and often more effective than immunomodulators in the first- and second-line treatment of relapsing remitting MS (RRMS), another set of data presented at ECTRIMS 2024 looked specifically at transitioning from intravenous (IV) anti-CD20 drugs to SQ ofatumumab.

In this study, called OLIKOS, 102 RRMS patients who had received either IV ocrelizumab or IV rituximab were followed after transitioning to ofatumumab administered SQ with an autoinjector pen. The primary endpoint was the proportion of patients with no change or a reduction gadolinium-enhancing (Gd) T1 lesions over 12 months of follow-up.

“At month 12, 84 of 84 evaluable patients with evaluable MRI assessments met the primary endpoint,” reported the principal investigator Le Hua, MD, director of the Multiple Sclerosis Program, Cleveland Clinic in Ohio.

At 12 months, there were also no new or enlarging T2 lesions in 98% of patients receiving SQ ofatumumab following the transition from one of the other anti-CD20 IV drugs, but Dr. Hua characterized this as an exploratory endpoint.

The safety and tolerability data during the OLIKOS study was also reassuring with no new or unexpected safety signals for SQ ofatumumab, which has been well tolerated in the phase 3 development program. IgM and IgG levels remained stable over the course of follow-up.

High-efficacy anti-CD20 drugs were once reserved for RRMS patients with highly active disease, but long-term data, such as those generated by the ALITHIOS extension study, suggest greater efficacy with acceptable safety of these agents relative to conventional first-line RRMS therapies. Based on ALITHIOS data, Dr. Bar-Or suggested that early use of the most effective therapy appears to lead to better long-term protection from increased cumulative disability.

Dr. Bar-Or reported financial relationships with Accure, Atara, Biogen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. Dr. Hua reported financial relationships with Alexion, EMD Serono, Genentech, Horizon, Novartis, and TG Therapeutics.

It may not have an aesthetic-sounding appeal to most people, but salmon sperm is indeed one of the novel ingredients featured in products for human skin. Used topically after procedures like skin tightening and in fillers, polydeoxyribonucleotides (PDRNs) and purified polynucleotides (PNs) derived from salmon sperm are on the market. These products also reportedly enhance and promote skin regeneration.¹ This column will focus on the innovative approach to skin care involving purified polynucleotides derived from salmon sperm.

The Properties and Activities of PDRNs, PNs

PDRNs contain DNA fragments primarily derived from Pacific or chum salmon (Oncorhynchus keta), and salmon trout (Oncorhynchus mykiss) sperm cells.² Through preclinical and clinical trials, PDRN has demonstrated a wide range of salutary functions, including antiallodynic, antiapoptotic, anti-inflammatory, antimelanogenetic, antiosteonecrotic, antiosteoporotic, antiulcerative, bone-regenerative, tissue damage–preventive, and wound-healing activities through adenosine A2A receptor and salvage pathways activation. Indeed, PDRNs have been shown in vitro to spur the proliferation of preadipocytes and, in vivo, to be effective in treating wounds and ulcers.^3,4 In particular, atrophic, hypertrophic, surgical, and various acne scars have been treated with such injections.^2,5,6 PDRN is thought to affect cutaneous health more directly by facilitating angiogenesis, cellular functions, especially fibroblast stimulation, collagen production, soft-tissue regeneration, and skin revitalization. Further, it has been used successfully to treat hyperpigmentation.⁷

Dave Steers Photo/Moment Open/Getty Images

PNs, derived from the same fish species as PDRNs, have been used effectively to ameliorate skin elasticity, hydration, pore size, thickness, wrinkles, as well as pigmentation and, specifically, in treating periorbital rhytides and postsurgical scars.^5,6,8 Beyond skin rejuvenation, PNs have been recognized for effectiveness in treating stretch marks and achieving vulvovaginal revitalization; guidelines for its use have been established and implemented in recent years.^6,9,10 In South Korea, PNs have become a popular treatment for facial erythema even though preclinical and clinical data are sparse.¹¹ Nevertheless, the use of these novel substances is thought to foster tissue regeneration and a more natural rejuvenation than achieved through more traditional fillers.⁶

Skin Rejuvenation

Park and colleagues conducted a small study with five patients in 2016 in which long-chain polynucleotide filler was used for skin rejuvenation. Over a 2-week period, five Korean women received four injections of the filler (0.05 mL) on one side of the face. No adverse side effects were reported. In the patients in their 30s, pore and skin thickness significantly improved with treatment. For patients in their 40s, observable improvements were noted in melanin, sagging, skin tone, and wrinkles. Despite the small study size, the investigators concluded that this intradermal injection material is a safe and effective product for skin rejuvenation therapy.¹ The product is also available in Europe and reportedly spurs the regeneration of damaged tissues and yields a more natural appearance.¹

A Hybrid HA-PN Filler

Given that the most common filling agent, hyaluronic acid (HA), is associated with multiple side effects, JH Kim and colleagues set out in 2020 to compare HA with a new HA-PN dermal filler that has displayed notable biocompatibility and promoted tissue regeneration. The investigators observed that the combination filler provoked greater cell migration in a wound healing assay and was more effective in promoting collagen production in human and mouse fibroblasts. To their knowledge, this was the first study showing the efficacy, safety, and durability of a hybrid HA-PN filler. They concluded that fillers containing both HA and PN were more effective than HA alone in suppressing cutaneous aging and may represent the next step in the evolution of dermal filling agents.¹²

Most Recent Findings

In August 2023, MJ Kim and colleagues became the first to report on the successful use of PNs derived from fish sperm as a volumizing treatment for fat atrophy in vivo (in the temple in one case, and the cheek in the other). Injections were made into the subcutaneous layer to treat iatrogenic volume loss resulting from lipolysis injections. In one case, a depression in the left temple of a 53-year-old female lipolysis patient was treated with a series of 1 cc PN injections in a 20 mg/mL concentration. At 1 month after the final series of injections (four treatments), significant clinical improvement was observed, with the result (barely visible depression) maintained at 11 months and 21 months after the last treatment. The second patient, a 34-year-old female, presented with two depressed areas on the left cheek 2 months after steroid injections for two acne lesions. A series of PN filler injections also with a concentration of 20 mg/mL was administered (four treatments) at 1-month intervals. Significant improvement was seen 2 months after the last treatment, with maintenance of complete healing noted at 5 months and 12 months after the final treatment. No adverse effects were reported in either case. The investigators concluded that long-chain PN fillers appear to be effective in treating depressions in the skin, but more data, particularly from controlled studies, is necessary to determine the safety and efficacy as a lone therapeutic approach for soft-tissue depression.⁶

Baumann Cosmetic & Research Institute

A month later, Lee and colleagues reported on the results of their survey of clinicians in South Korea who use PNs in clinical practice. The goal was to understand current practices and perceptions of effectiveness in treating facial erythema. Of the 557 physicians who participated, 84.4% used PNs for facial erythema provoked by inflammatory facial dermatosis, 66.4% for facial erythema induced by repeated laser/microneedle radiofrequency, and 47.4% for facial erythema caused by steroid overuse. In these same classifications, 88.1%, 90%, and 83.7%, respectively, found PNs to be “highly effective” or “effective.” Survey respondents also characterized PNs as imparting wound healing/regeneration (95.8%), skin barrier protection (92.2%), hydration (90.5%), vascular stabilization (81.0%), and anti-inflammatory activity (79.5%).¹¹

Conclusion

The use of salmon sperm cells is an example of the recent trend toward a cellular approach in which cutaneous components are activated with the intention of stimulating tissue regeneration. It is commonly used in Brazil and my Brazilian patients seem to know all about it. This innovative outlook is intriguing as are a spate of recently reported results. Nevertheless, much more evidence is required to ascertain safety and effectiveness in large sample sizes and, ideally, to establish maintenance of corrections over longer periods whether these ingredients are used in filling agents or topical formulations.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in office and as a e-commerce solution. Write to her at dermnews@mdedge.com.

References

1. Park KY et al. Dermatol Ther. 2016 Jan;29(1):37-40. .

2. Kim TH et al. Mar Drugs. 2021 May 22;19(6):296.

3. Raposio E et al. Cell Prolif. 2008 Oct;41(5):739-54.

4. Veronesi F et al. J Cell Physiol. 2017 Sep;232(9):2299-2307.

5. Kim JH et al. Lasers Surg Med. 2018 Mar 25.

6. Kim MJ et al. Skin Res Technol. 2023 Aug;29(8):e13439.

7. Khan A et al. Chinese Journal of Plastic and Reconstructive Surgery. 2022 Dec;4(4):187-193.

8. Lee YJ et al. J Dermatolog Treat. 2022 Feb;33(1):254-260.

9. De Caridi G et al. Int Wound J. 2016 Oct;13(5):754-8.

10. Cavallini M et al. J Cosmet Dermatol. 2021 Mar;20(3):922-928.

11. Lee D. Skin Res Technol. 2023 Sep;29(9):e13466. doi: 10.1111/srt.13466.

12. Kim JH et al. Sci Rep. 2020 Mar 20;10(1):5127. .

It may not have an aesthetic-sounding appeal to most people, but salmon sperm is indeed one of the novel ingredients featured in products for human skin. Used topically after procedures like skin tightening and in fillers, polydeoxyribonucleotides (PDRNs) and purified polynucleotides (PNs) derived from salmon sperm are on the market. These products also reportedly enhance and promote skin regeneration.¹ This column will focus on the innovative approach to skin care involving purified polynucleotides derived from salmon sperm.

The Properties and Activities of PDRNs, PNs

PDRNs contain DNA fragments primarily derived from Pacific or chum salmon (Oncorhynchus keta), and salmon trout (Oncorhynchus mykiss) sperm cells.² Through preclinical and clinical trials, PDRN has demonstrated a wide range of salutary functions, including antiallodynic, antiapoptotic, anti-inflammatory, antimelanogenetic, antiosteonecrotic, antiosteoporotic, antiulcerative, bone-regenerative, tissue damage–preventive, and wound-healing activities through adenosine A2A receptor and salvage pathways activation. Indeed, PDRNs have been shown in vitro to spur the proliferation of preadipocytes and, in vivo, to be effective in treating wounds and ulcers.^3,4 In particular, atrophic, hypertrophic, surgical, and various acne scars have been treated with such injections.^2,5,6 PDRN is thought to affect cutaneous health more directly by facilitating angiogenesis, cellular functions, especially fibroblast stimulation, collagen production, soft-tissue regeneration, and skin revitalization. Further, it has been used successfully to treat hyperpigmentation.⁷

Dave Steers Photo/Moment Open/Getty Images

PNs, derived from the same fish species as PDRNs, have been used effectively to ameliorate skin elasticity, hydration, pore size, thickness, wrinkles, as well as pigmentation and, specifically, in treating periorbital rhytides and postsurgical scars.^5,6,8 Beyond skin rejuvenation, PNs have been recognized for effectiveness in treating stretch marks and achieving vulvovaginal revitalization; guidelines for its use have been established and implemented in recent years.^6,9,10 In South Korea, PNs have become a popular treatment for facial erythema even though preclinical and clinical data are sparse.¹¹ Nevertheless, the use of these novel substances is thought to foster tissue regeneration and a more natural rejuvenation than achieved through more traditional fillers.⁶

Skin Rejuvenation

Park and colleagues conducted a small study with five patients in 2016 in which long-chain polynucleotide filler was used for skin rejuvenation. Over a 2-week period, five Korean women received four injections of the filler (0.05 mL) on one side of the face. No adverse side effects were reported. In the patients in their 30s, pore and skin thickness significantly improved with treatment. For patients in their 40s, observable improvements were noted in melanin, sagging, skin tone, and wrinkles. Despite the small study size, the investigators concluded that this intradermal injection material is a safe and effective product for skin rejuvenation therapy.¹ The product is also available in Europe and reportedly spurs the regeneration of damaged tissues and yields a more natural appearance.¹

A Hybrid HA-PN Filler

Given that the most common filling agent, hyaluronic acid (HA), is associated with multiple side effects, JH Kim and colleagues set out in 2020 to compare HA with a new HA-PN dermal filler that has displayed notable biocompatibility and promoted tissue regeneration. The investigators observed that the combination filler provoked greater cell migration in a wound healing assay and was more effective in promoting collagen production in human and mouse fibroblasts. To their knowledge, this was the first study showing the efficacy, safety, and durability of a hybrid HA-PN filler. They concluded that fillers containing both HA and PN were more effective than HA alone in suppressing cutaneous aging and may represent the next step in the evolution of dermal filling agents.¹²

Most Recent Findings

In August 2023, MJ Kim and colleagues became the first to report on the successful use of PNs derived from fish sperm as a volumizing treatment for fat atrophy in vivo (in the temple in one case, and the cheek in the other). Injections were made into the subcutaneous layer to treat iatrogenic volume loss resulting from lipolysis injections. In one case, a depression in the left temple of a 53-year-old female lipolysis patient was treated with a series of 1 cc PN injections in a 20 mg/mL concentration. At 1 month after the final series of injections (four treatments), significant clinical improvement was observed, with the result (barely visible depression) maintained at 11 months and 21 months after the last treatment. The second patient, a 34-year-old female, presented with two depressed areas on the left cheek 2 months after steroid injections for two acne lesions. A series of PN filler injections also with a concentration of 20 mg/mL was administered (four treatments) at 1-month intervals. Significant improvement was seen 2 months after the last treatment, with maintenance of complete healing noted at 5 months and 12 months after the final treatment. No adverse effects were reported in either case. The investigators concluded that long-chain PN fillers appear to be effective in treating depressions in the skin, but more data, particularly from controlled studies, is necessary to determine the safety and efficacy as a lone therapeutic approach for soft-tissue depression.⁶

Baumann Cosmetic & Research Institute

A month later, Lee and colleagues reported on the results of their survey of clinicians in South Korea who use PNs in clinical practice. The goal was to understand current practices and perceptions of effectiveness in treating facial erythema. Of the 557 physicians who participated, 84.4% used PNs for facial erythema provoked by inflammatory facial dermatosis, 66.4% for facial erythema induced by repeated laser/microneedle radiofrequency, and 47.4% for facial erythema caused by steroid overuse. In these same classifications, 88.1%, 90%, and 83.7%, respectively, found PNs to be “highly effective” or “effective.” Survey respondents also characterized PNs as imparting wound healing/regeneration (95.8%), skin barrier protection (92.2%), hydration (90.5%), vascular stabilization (81.0%), and anti-inflammatory activity (79.5%).¹¹

Conclusion

The use of salmon sperm cells is an example of the recent trend toward a cellular approach in which cutaneous components are activated with the intention of stimulating tissue regeneration. It is commonly used in Brazil and my Brazilian patients seem to know all about it. This innovative outlook is intriguing as are a spate of recently reported results. Nevertheless, much more evidence is required to ascertain safety and effectiveness in large sample sizes and, ideally, to establish maintenance of corrections over longer periods whether these ingredients are used in filling agents or topical formulations.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in office and as a e-commerce solution. Write to her at dermnews@mdedge.com.

References

1. Park KY et al. Dermatol Ther. 2016 Jan;29(1):37-40. .

2. Kim TH et al. Mar Drugs. 2021 May 22;19(6):296.

3. Raposio E et al. Cell Prolif. 2008 Oct;41(5):739-54.

4. Veronesi F et al. J Cell Physiol. 2017 Sep;232(9):2299-2307.

5. Kim JH et al. Lasers Surg Med. 2018 Mar 25.

6. Kim MJ et al. Skin Res Technol. 2023 Aug;29(8):e13439.

7. Khan A et al. Chinese Journal of Plastic and Reconstructive Surgery. 2022 Dec;4(4):187-193.

8. Lee YJ et al. J Dermatolog Treat. 2022 Feb;33(1):254-260.

9. De Caridi G et al. Int Wound J. 2016 Oct;13(5):754-8.

10. Cavallini M et al. J Cosmet Dermatol. 2021 Mar;20(3):922-928.

11. Lee D. Skin Res Technol. 2023 Sep;29(9):e13466. doi: 10.1111/srt.13466.

12. Kim JH et al. Sci Rep. 2020 Mar 20;10(1):5127. .

It may not have an aesthetic-sounding appeal to most people, but salmon sperm is indeed one of the novel ingredients featured in products for human skin. Used topically after procedures like skin tightening and in fillers, polydeoxyribonucleotides (PDRNs) and purified polynucleotides (PNs) derived from salmon sperm are on the market. These products also reportedly enhance and promote skin regeneration.¹ This column will focus on the innovative approach to skin care involving purified polynucleotides derived from salmon sperm.

The Properties and Activities of PDRNs, PNs

PDRNs contain DNA fragments primarily derived from Pacific or chum salmon (Oncorhynchus keta), and salmon trout (Oncorhynchus mykiss) sperm cells.² Through preclinical and clinical trials, PDRN has demonstrated a wide range of salutary functions, including antiallodynic, antiapoptotic, anti-inflammatory, antimelanogenetic, antiosteonecrotic, antiosteoporotic, antiulcerative, bone-regenerative, tissue damage–preventive, and wound-healing activities through adenosine A2A receptor and salvage pathways activation. Indeed, PDRNs have been shown in vitro to spur the proliferation of preadipocytes and, in vivo, to be effective in treating wounds and ulcers.^3,4 In particular, atrophic, hypertrophic, surgical, and various acne scars have been treated with such injections.^2,5,6 PDRN is thought to affect cutaneous health more directly by facilitating angiogenesis, cellular functions, especially fibroblast stimulation, collagen production, soft-tissue regeneration, and skin revitalization. Further, it has been used successfully to treat hyperpigmentation.⁷

Dave Steers Photo/Moment Open/Getty Images

PNs, derived from the same fish species as PDRNs, have been used effectively to ameliorate skin elasticity, hydration, pore size, thickness, wrinkles, as well as pigmentation and, specifically, in treating periorbital rhytides and postsurgical scars.^5,6,8 Beyond skin rejuvenation, PNs have been recognized for effectiveness in treating stretch marks and achieving vulvovaginal revitalization; guidelines for its use have been established and implemented in recent years.^6,9,10 In South Korea, PNs have become a popular treatment for facial erythema even though preclinical and clinical data are sparse.¹¹ Nevertheless, the use of these novel substances is thought to foster tissue regeneration and a more natural rejuvenation than achieved through more traditional fillers.⁶

Skin Rejuvenation

Park and colleagues conducted a small study with five patients in 2016 in which long-chain polynucleotide filler was used for skin rejuvenation. Over a 2-week period, five Korean women received four injections of the filler (0.05 mL) on one side of the face. No adverse side effects were reported. In the patients in their 30s, pore and skin thickness significantly improved with treatment. For patients in their 40s, observable improvements were noted in melanin, sagging, skin tone, and wrinkles. Despite the small study size, the investigators concluded that this intradermal injection material is a safe and effective product for skin rejuvenation therapy.¹ The product is also available in Europe and reportedly spurs the regeneration of damaged tissues and yields a more natural appearance.¹

A Hybrid HA-PN Filler

Given that the most common filling agent, hyaluronic acid (HA), is associated with multiple side effects, JH Kim and colleagues set out in 2020 to compare HA with a new HA-PN dermal filler that has displayed notable biocompatibility and promoted tissue regeneration. The investigators observed that the combination filler provoked greater cell migration in a wound healing assay and was more effective in promoting collagen production in human and mouse fibroblasts. To their knowledge, this was the first study showing the efficacy, safety, and durability of a hybrid HA-PN filler. They concluded that fillers containing both HA and PN were more effective than HA alone in suppressing cutaneous aging and may represent the next step in the evolution of dermal filling agents.¹²

Most Recent Findings

In August 2023, MJ Kim and colleagues became the first to report on the successful use of PNs derived from fish sperm as a volumizing treatment for fat atrophy in vivo (in the temple in one case, and the cheek in the other). Injections were made into the subcutaneous layer to treat iatrogenic volume loss resulting from lipolysis injections. In one case, a depression in the left temple of a 53-year-old female lipolysis patient was treated with a series of 1 cc PN injections in a 20 mg/mL concentration. At 1 month after the final series of injections (four treatments), significant clinical improvement was observed, with the result (barely visible depression) maintained at 11 months and 21 months after the last treatment. The second patient, a 34-year-old female, presented with two depressed areas on the left cheek 2 months after steroid injections for two acne lesions. A series of PN filler injections also with a concentration of 20 mg/mL was administered (four treatments) at 1-month intervals. Significant improvement was seen 2 months after the last treatment, with maintenance of complete healing noted at 5 months and 12 months after the final treatment. No adverse effects were reported in either case. The investigators concluded that long-chain PN fillers appear to be effective in treating depressions in the skin, but more data, particularly from controlled studies, is necessary to determine the safety and efficacy as a lone therapeutic approach for soft-tissue depression.⁶

Baumann Cosmetic & Research Institute

A month later, Lee and colleagues reported on the results of their survey of clinicians in South Korea who use PNs in clinical practice. The goal was to understand current practices and perceptions of effectiveness in treating facial erythema. Of the 557 physicians who participated, 84.4% used PNs for facial erythema provoked by inflammatory facial dermatosis, 66.4% for facial erythema induced by repeated laser/microneedle radiofrequency, and 47.4% for facial erythema caused by steroid overuse. In these same classifications, 88.1%, 90%, and 83.7%, respectively, found PNs to be “highly effective” or “effective.” Survey respondents also characterized PNs as imparting wound healing/regeneration (95.8%), skin barrier protection (92.2%), hydration (90.5%), vascular stabilization (81.0%), and anti-inflammatory activity (79.5%).¹¹

Conclusion

The use of salmon sperm cells is an example of the recent trend toward a cellular approach in which cutaneous components are activated with the intention of stimulating tissue regeneration. It is commonly used in Brazil and my Brazilian patients seem to know all about it. This innovative outlook is intriguing as are a spate of recently reported results. Nevertheless, much more evidence is required to ascertain safety and effectiveness in large sample sizes and, ideally, to establish maintenance of corrections over longer periods whether these ingredients are used in filling agents or topical formulations.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in office and as a e-commerce solution. Write to her at dermnews@mdedge.com.

References

1. Park KY et al. Dermatol Ther. 2016 Jan;29(1):37-40. .

2. Kim TH et al. Mar Drugs. 2021 May 22;19(6):296.

3. Raposio E et al. Cell Prolif. 2008 Oct;41(5):739-54.

4. Veronesi F et al. J Cell Physiol. 2017 Sep;232(9):2299-2307.

5. Kim JH et al. Lasers Surg Med. 2018 Mar 25.

6. Kim MJ et al. Skin Res Technol. 2023 Aug;29(8):e13439.

7. Khan A et al. Chinese Journal of Plastic and Reconstructive Surgery. 2022 Dec;4(4):187-193.

8. Lee YJ et al. J Dermatolog Treat. 2022 Feb;33(1):254-260.

9. De Caridi G et al. Int Wound J. 2016 Oct;13(5):754-8.

10. Cavallini M et al. J Cosmet Dermatol. 2021 Mar;20(3):922-928.

11. Lee D. Skin Res Technol. 2023 Sep;29(9):e13466. doi: 10.1111/srt.13466.

12. Kim JH et al. Sci Rep. 2020 Mar 20;10(1):5127. .

The Food and Drug Administration (FDA) plans to scrutinize the safety and efficacy of lab-developed tests — those designed, manufactured, and used in a single laboratory — far more thoroughly in the future.

Under a rule finalized in April, the FDA will treat facilities that develop and use lab tests as manufacturers and regulate tests as medical devices. That means that most lab tests will need an FDA review before going on sale.

The FDA will also impose new quality standards, requiring test manufacturers to report adverse events and create a registry of lab tests under the new rule, which will be phased in over 4 years.

FDA officials have been concerned for years about the reliability of commercial lab tests, which have ballooned into a multibillion-dollar industry.

Consumer groups have long urged the FDA to regulate lab tests more strictly, arguing that the lack of scrutiny allows doctors and patients to be exploited by bad actors such as Theranos, which falsely claimed that its tests could diagnose multiple diseases with a single drop of blood.

“When it comes to some of these tests that doctors are recommending for patients, many doctors are just crossing their fingers and relying on the representation of the company because nobody is checking” to verify a manufacturer’s claims, said Joshua Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
 

Nearly 12,000 Labs Making Medical Tests

Although the FDA estimates there are nearly 12,000 labs manufacturing medical tests, agency officials said they don’t know how many tests are being marketed. The FDA already requires that home test kits marketed directly to consumers, such as those used to detect COVID-19, get clearance from the agency before being sold.

“There’s plenty of time for industry to get its act together to develop the data that it might need to make a premarket application,” said Peter Lurie, MD, PhD, a former associate commissioner at the FDA. In 2015, Dr. Lurie led a report outlining some of the dangers of unregulated lab tests.

For the average physician who orders lab tests, nothing is going to immediately change because of the final rule, said Dr. Lurie, now president of the Center for Science in the Public Interest, a nonprofit consumer watchdog.

“Tomorrow, this will look just the same as it does today,” Dr. Lurie said. “For the next 3 years, the companies will be scurrying behind the scenes to comply with the early stages of implementation. But most of that will be invisible to the average practitioner.”

Dr. Lurie predicted the FDA will focus its scrutiny on tests that pose the greatest potential risk to patients, such as ones used to diagnose serious diseases or guide treatment for life-threatening conditions. “The least significant tests will likely get very limited, if any, scrutiny,” said Dr. Lurie, adding that the FDA will likely issue guidance about how it plans to define low- and high-risk tests. “My suspicion is that it will be probably a small minority of products that are subject to full premarket approval.”
 

Lab Industry Groups Push Back

But imposing new rules with the potential to affect an industry’s bottom line is no easy task.

The American Clinical Laboratory Association, which represents the lab industry, said in a statement that the FDA rule will “limit access to scores of critical tests, increase healthcare costs, and undermine innovation in new diagnostics.” Another industry group, the Association for Molecular Pathology, has warned of “significant and harmful disruption to laboratory medicine.”

The two associations have filed separate lawsuits, charging that the FDA overstepped the authority granted by Congress. In their lawsuits, groups claim that lab tests are professional services, not manufactured products. The groups noted that the Centers for Medicare & Medicaid Services (CMS) already inspects lab facilities. CMS does not assess the tests’ quality or reliability.

A recent Supreme Court decision could make those lawsuits more likely to succeed, said David Simon, JD, LLM, PhD, an assistant professor of law at the Northeastern University School of Law, Boston, Massachusetts.

In the case of Loper Bright Enterprises v. Raimondo, decided in June, justices overturned a long-standing precedent known as Chevron deference, which required courts to defer to federal agencies when interpreting ambiguous laws. That means that courts no longer have to accept the FDA’s definition of a device, Dr. Simon said.

“Because judges may have more active roles in defining agency authority, federal agencies may have correspondingly less robust roles in policymaking,” Dr. Simon wrote in an editorial coauthored with Michael J. Young, MD, MPhil, of Harvard Medical School, Boston.

The Supreme Court ruling could pressure Congress to more clearly define FDA’s ruling in regulating lab tests, Dr. Simon and Dr. Young wrote.

Members of Congress first introduced a bill to clarify the FDA’s role in regulating lab tests, called the VALID Act, in 2020. The bill stalled and, despite efforts to revive it, still hasn’t passed.

FDA officials have said they remain “open to working with Congress,” noting that any future legislation about lab-developed tests would supersede their current policy.

In an interview, Dr. Simon noted the FDA significantly narrowed the scope of the final rule in response to comments from critics who objected to an earlier version of the policy proposed in 2023. The final rule carves out several categories of tests that won’t need to apply for “premarket review.”

Notably, a “grandfather clause” will allow some lab tests already on the market to continue being sold without undergoing FDA’s premarket review process. In explaining the exemption, FDA officials said they did not want doctors and patients to lose access to tests on which they rely. But Dr. Lurie noted that because the FDA views all these tests as under its jurisdiction, the agency could opt to take a closer look “at a very old device that is causing a problem today.”

The FDA also will exempt tests approved by New York State’s Clinical Laboratory Evaluation Program, which conducts its own stringent reviews. And the FDA will continue to allow hospitals to develop tests for patients within their healthcare system without going through the FDA approval process, if no FDA-approved tests are available.

Hospital-based tests play a critical role in treating infectious diseases, said Amesh Adalja, MD, an infectious diseases specialist and senior scholar at the Johns Hopkins Center for Health Security. For example, a large research hospital treating a patient with cytomegalovirus may need to develop its own test to determine whether the infection is resistant to antiviral drugs, Dr. Adalja said.

“With novel infectious disease outbreaks, researchers are able to move quickly to make diagnostic tests months and months before commercial laboratories are able to get through regulatory processes,” Dr. Adalja said.

To help scientists respond quickly to emergencies, the FDA published special guidance for labs that develop unauthorized lab tests for disease outbreaks.

Medical groups such as the American Hospital Association and Infectious Diseases Society of America remain concerned about the burden of complying with new regulations.

“Many vital tests developed in hospitals and health systems may be subjected to unnecessary and costly paperwork,” said Stacey Hughes, executive vice president of the American Hospital Association, in a statement.

Other groups, such as the American Society of Clinical Oncology, praised the new FDA policy. In comments submitted to the FDA in 2023, the cancer group said it “emphatically supports” requiring lab tests to undergo FDA review.

“We appreciate FDA action to modernize oversight of these tests and are hopeful this rule will increase focus on the need to balance rapid diagnostic innovation with patient safety and access” Everett Vokes, MD, the group’s board chair, said in a statement released after the FDA’s final rule was published.

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

The Food and Drug Administration (FDA) plans to scrutinize the safety and efficacy of lab-developed tests — those designed, manufactured, and used in a single laboratory — far more thoroughly in the future.

Under a rule finalized in April, the FDA will treat facilities that develop and use lab tests as manufacturers and regulate tests as medical devices. That means that most lab tests will need an FDA review before going on sale.

The FDA will also impose new quality standards, requiring test manufacturers to report adverse events and create a registry of lab tests under the new rule, which will be phased in over 4 years.

FDA officials have been concerned for years about the reliability of commercial lab tests, which have ballooned into a multibillion-dollar industry.

Consumer groups have long urged the FDA to regulate lab tests more strictly, arguing that the lack of scrutiny allows doctors and patients to be exploited by bad actors such as Theranos, which falsely claimed that its tests could diagnose multiple diseases with a single drop of blood.

“When it comes to some of these tests that doctors are recommending for patients, many doctors are just crossing their fingers and relying on the representation of the company because nobody is checking” to verify a manufacturer’s claims, said Joshua Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
 

Nearly 12,000 Labs Making Medical Tests

Although the FDA estimates there are nearly 12,000 labs manufacturing medical tests, agency officials said they don’t know how many tests are being marketed. The FDA already requires that home test kits marketed directly to consumers, such as those used to detect COVID-19, get clearance from the agency before being sold.

“There’s plenty of time for industry to get its act together to develop the data that it might need to make a premarket application,” said Peter Lurie, MD, PhD, a former associate commissioner at the FDA. In 2015, Dr. Lurie led a report outlining some of the dangers of unregulated lab tests.

For the average physician who orders lab tests, nothing is going to immediately change because of the final rule, said Dr. Lurie, now president of the Center for Science in the Public Interest, a nonprofit consumer watchdog.

“Tomorrow, this will look just the same as it does today,” Dr. Lurie said. “For the next 3 years, the companies will be scurrying behind the scenes to comply with the early stages of implementation. But most of that will be invisible to the average practitioner.”

Dr. Lurie predicted the FDA will focus its scrutiny on tests that pose the greatest potential risk to patients, such as ones used to diagnose serious diseases or guide treatment for life-threatening conditions. “The least significant tests will likely get very limited, if any, scrutiny,” said Dr. Lurie, adding that the FDA will likely issue guidance about how it plans to define low- and high-risk tests. “My suspicion is that it will be probably a small minority of products that are subject to full premarket approval.”
 

Lab Industry Groups Push Back

But imposing new rules with the potential to affect an industry’s bottom line is no easy task.

The American Clinical Laboratory Association, which represents the lab industry, said in a statement that the FDA rule will “limit access to scores of critical tests, increase healthcare costs, and undermine innovation in new diagnostics.” Another industry group, the Association for Molecular Pathology, has warned of “significant and harmful disruption to laboratory medicine.”

The two associations have filed separate lawsuits, charging that the FDA overstepped the authority granted by Congress. In their lawsuits, groups claim that lab tests are professional services, not manufactured products. The groups noted that the Centers for Medicare & Medicaid Services (CMS) already inspects lab facilities. CMS does not assess the tests’ quality or reliability.

A recent Supreme Court decision could make those lawsuits more likely to succeed, said David Simon, JD, LLM, PhD, an assistant professor of law at the Northeastern University School of Law, Boston, Massachusetts.

In the case of Loper Bright Enterprises v. Raimondo, decided in June, justices overturned a long-standing precedent known as Chevron deference, which required courts to defer to federal agencies when interpreting ambiguous laws. That means that courts no longer have to accept the FDA’s definition of a device, Dr. Simon said.

“Because judges may have more active roles in defining agency authority, federal agencies may have correspondingly less robust roles in policymaking,” Dr. Simon wrote in an editorial coauthored with Michael J. Young, MD, MPhil, of Harvard Medical School, Boston.

The Supreme Court ruling could pressure Congress to more clearly define FDA’s ruling in regulating lab tests, Dr. Simon and Dr. Young wrote.

Members of Congress first introduced a bill to clarify the FDA’s role in regulating lab tests, called the VALID Act, in 2020. The bill stalled and, despite efforts to revive it, still hasn’t passed.

FDA officials have said they remain “open to working with Congress,” noting that any future legislation about lab-developed tests would supersede their current policy.

In an interview, Dr. Simon noted the FDA significantly narrowed the scope of the final rule in response to comments from critics who objected to an earlier version of the policy proposed in 2023. The final rule carves out several categories of tests that won’t need to apply for “premarket review.”

Notably, a “grandfather clause” will allow some lab tests already on the market to continue being sold without undergoing FDA’s premarket review process. In explaining the exemption, FDA officials said they did not want doctors and patients to lose access to tests on which they rely. But Dr. Lurie noted that because the FDA views all these tests as under its jurisdiction, the agency could opt to take a closer look “at a very old device that is causing a problem today.”

The FDA also will exempt tests approved by New York State’s Clinical Laboratory Evaluation Program, which conducts its own stringent reviews. And the FDA will continue to allow hospitals to develop tests for patients within their healthcare system without going through the FDA approval process, if no FDA-approved tests are available.

Hospital-based tests play a critical role in treating infectious diseases, said Amesh Adalja, MD, an infectious diseases specialist and senior scholar at the Johns Hopkins Center for Health Security. For example, a large research hospital treating a patient with cytomegalovirus may need to develop its own test to determine whether the infection is resistant to antiviral drugs, Dr. Adalja said.

“With novel infectious disease outbreaks, researchers are able to move quickly to make diagnostic tests months and months before commercial laboratories are able to get through regulatory processes,” Dr. Adalja said.

To help scientists respond quickly to emergencies, the FDA published special guidance for labs that develop unauthorized lab tests for disease outbreaks.

Medical groups such as the American Hospital Association and Infectious Diseases Society of America remain concerned about the burden of complying with new regulations.

“Many vital tests developed in hospitals and health systems may be subjected to unnecessary and costly paperwork,” said Stacey Hughes, executive vice president of the American Hospital Association, in a statement.

Other groups, such as the American Society of Clinical Oncology, praised the new FDA policy. In comments submitted to the FDA in 2023, the cancer group said it “emphatically supports” requiring lab tests to undergo FDA review.

“We appreciate FDA action to modernize oversight of these tests and are hopeful this rule will increase focus on the need to balance rapid diagnostic innovation with patient safety and access” Everett Vokes, MD, the group’s board chair, said in a statement released after the FDA’s final rule was published.

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

The Food and Drug Administration (FDA) plans to scrutinize the safety and efficacy of lab-developed tests — those designed, manufactured, and used in a single laboratory — far more thoroughly in the future.

Under a rule finalized in April, the FDA will treat facilities that develop and use lab tests as manufacturers and regulate tests as medical devices. That means that most lab tests will need an FDA review before going on sale.

The FDA will also impose new quality standards, requiring test manufacturers to report adverse events and create a registry of lab tests under the new rule, which will be phased in over 4 years.

FDA officials have been concerned for years about the reliability of commercial lab tests, which have ballooned into a multibillion-dollar industry.

Consumer groups have long urged the FDA to regulate lab tests more strictly, arguing that the lack of scrutiny allows doctors and patients to be exploited by bad actors such as Theranos, which falsely claimed that its tests could diagnose multiple diseases with a single drop of blood.

“When it comes to some of these tests that doctors are recommending for patients, many doctors are just crossing their fingers and relying on the representation of the company because nobody is checking” to verify a manufacturer’s claims, said Joshua Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
 

Nearly 12,000 Labs Making Medical Tests

Although the FDA estimates there are nearly 12,000 labs manufacturing medical tests, agency officials said they don’t know how many tests are being marketed. The FDA already requires that home test kits marketed directly to consumers, such as those used to detect COVID-19, get clearance from the agency before being sold.

“There’s plenty of time for industry to get its act together to develop the data that it might need to make a premarket application,” said Peter Lurie, MD, PhD, a former associate commissioner at the FDA. In 2015, Dr. Lurie led a report outlining some of the dangers of unregulated lab tests.

For the average physician who orders lab tests, nothing is going to immediately change because of the final rule, said Dr. Lurie, now president of the Center for Science in the Public Interest, a nonprofit consumer watchdog.

“Tomorrow, this will look just the same as it does today,” Dr. Lurie said. “For the next 3 years, the companies will be scurrying behind the scenes to comply with the early stages of implementation. But most of that will be invisible to the average practitioner.”

Dr. Lurie predicted the FDA will focus its scrutiny on tests that pose the greatest potential risk to patients, such as ones used to diagnose serious diseases or guide treatment for life-threatening conditions. “The least significant tests will likely get very limited, if any, scrutiny,” said Dr. Lurie, adding that the FDA will likely issue guidance about how it plans to define low- and high-risk tests. “My suspicion is that it will be probably a small minority of products that are subject to full premarket approval.”
 

Lab Industry Groups Push Back

But imposing new rules with the potential to affect an industry’s bottom line is no easy task.

The American Clinical Laboratory Association, which represents the lab industry, said in a statement that the FDA rule will “limit access to scores of critical tests, increase healthcare costs, and undermine innovation in new diagnostics.” Another industry group, the Association for Molecular Pathology, has warned of “significant and harmful disruption to laboratory medicine.”

The two associations have filed separate lawsuits, charging that the FDA overstepped the authority granted by Congress. In their lawsuits, groups claim that lab tests are professional services, not manufactured products. The groups noted that the Centers for Medicare & Medicaid Services (CMS) already inspects lab facilities. CMS does not assess the tests’ quality or reliability.

A recent Supreme Court decision could make those lawsuits more likely to succeed, said David Simon, JD, LLM, PhD, an assistant professor of law at the Northeastern University School of Law, Boston, Massachusetts.

In the case of Loper Bright Enterprises v. Raimondo, decided in June, justices overturned a long-standing precedent known as Chevron deference, which required courts to defer to federal agencies when interpreting ambiguous laws. That means that courts no longer have to accept the FDA’s definition of a device, Dr. Simon said.

“Because judges may have more active roles in defining agency authority, federal agencies may have correspondingly less robust roles in policymaking,” Dr. Simon wrote in an editorial coauthored with Michael J. Young, MD, MPhil, of Harvard Medical School, Boston.

The Supreme Court ruling could pressure Congress to more clearly define FDA’s ruling in regulating lab tests, Dr. Simon and Dr. Young wrote.

Members of Congress first introduced a bill to clarify the FDA’s role in regulating lab tests, called the VALID Act, in 2020. The bill stalled and, despite efforts to revive it, still hasn’t passed.

FDA officials have said they remain “open to working with Congress,” noting that any future legislation about lab-developed tests would supersede their current policy.

In an interview, Dr. Simon noted the FDA significantly narrowed the scope of the final rule in response to comments from critics who objected to an earlier version of the policy proposed in 2023. The final rule carves out several categories of tests that won’t need to apply for “premarket review.”

Notably, a “grandfather clause” will allow some lab tests already on the market to continue being sold without undergoing FDA’s premarket review process. In explaining the exemption, FDA officials said they did not want doctors and patients to lose access to tests on which they rely. But Dr. Lurie noted that because the FDA views all these tests as under its jurisdiction, the agency could opt to take a closer look “at a very old device that is causing a problem today.”

The FDA also will exempt tests approved by New York State’s Clinical Laboratory Evaluation Program, which conducts its own stringent reviews. And the FDA will continue to allow hospitals to develop tests for patients within their healthcare system without going through the FDA approval process, if no FDA-approved tests are available.

Hospital-based tests play a critical role in treating infectious diseases, said Amesh Adalja, MD, an infectious diseases specialist and senior scholar at the Johns Hopkins Center for Health Security. For example, a large research hospital treating a patient with cytomegalovirus may need to develop its own test to determine whether the infection is resistant to antiviral drugs, Dr. Adalja said.

“With novel infectious disease outbreaks, researchers are able to move quickly to make diagnostic tests months and months before commercial laboratories are able to get through regulatory processes,” Dr. Adalja said.

To help scientists respond quickly to emergencies, the FDA published special guidance for labs that develop unauthorized lab tests for disease outbreaks.

Medical groups such as the American Hospital Association and Infectious Diseases Society of America remain concerned about the burden of complying with new regulations.

“Many vital tests developed in hospitals and health systems may be subjected to unnecessary and costly paperwork,” said Stacey Hughes, executive vice president of the American Hospital Association, in a statement.

Other groups, such as the American Society of Clinical Oncology, praised the new FDA policy. In comments submitted to the FDA in 2023, the cancer group said it “emphatically supports” requiring lab tests to undergo FDA review.

“We appreciate FDA action to modernize oversight of these tests and are hopeful this rule will increase focus on the need to balance rapid diagnostic innovation with patient safety and access” Everett Vokes, MD, the group’s board chair, said in a statement released after the FDA’s final rule was published.

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

It’s well known that the United States enjoys the dubious distinction of having the worst maternal morbidity and mortality rates among industrialized nations. Maternal mortality in this country increased by 14% from 2018 to 2020, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics.

But a current trend of engaging birth doulas — nonmedical guides offering continuous one-on-one physical and psychological support in the pre-, peri,- and postnatal periods — may be poised to brighten that dismal statistical landscape.

Recent research has shown that mothers matched with a doula are less likely to have a low birth weight baby, less likely to experience a birth complication, and significantly more likely to initiate breastfeeding.

Doula services — even delivered digitally — are seen to lower healthcare costs, reduce cesarean sections, decrease maternal anxiety and depression, and improve communication between healthcare providers and low-income, racially/ethnically diverse pregnant women. Doulas can be especially helpful for mothers dealing with the psychological fallout of miscarriage or stillbirth. They can guide patients in the postpartum period, when problems can arise and when some mothers are lost to medical follow-up, and provide an ongoing source of patient information for the ob.gyn.

“Research has shown that in addition to better outcomes, doula care can shorten labor time and increase patient satisfaction,” said ob.gyn. Layan Alrahmani, MD, in an interview. A maternal-fetal medicine specialist with a focus on high-risk pregnancies among low-income women at Loyola Medicine in Maywood, Illinois, Dr. Alrahmani welcomes doulas to her patients’ antenatal visits.

“Many of my patients who are looking to avoid an epidural will work with a labor doula, in order to stay home as long as possible and to have one-on-one coaching through the pain as things progress,” said Susan Rothenberg, MD, an assistant professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai and an ob/gyn at Mount Sinai Downtown Union Square in New York City. She added, “When a woman’s partner is squeamish or potentially unavailable, a labor doula can be a great option.”

Another ob.gyn. who enthusiastically embraces doula care is L. Joy Baker, MD, who practices in LaGrange, Georgia, and is affiliated with Wellstar West Georgia Medical Center. “I love it when my patients have a doula. A doula answers a patient’s questions throughout the pregnancy and amplifies the mother’s voice in the medical system and the clinical setting,” Dr. Baker told this news organization.

“They provide important details on patients’ food, housing, and transportation status when the mothers themselves would not bring those up in a short appointment with their doctors,” she said. Dr. Baker called for more recognition of their merit, especially for first-time and high-risk moms.

Efua B. Leke, MD, MPH, an assistant professor at Baylor College of Medicine and chief of obstetrics at Ben Taub Hospital in Houston, Texas, also believes a major benefit of doulas is improved flow of information. “We know that having doulas participate in maternal care can ease communication between pregnant and parturient mothers and their clinical team,” Dr. Leke said. “This is especially important for under-resourced pregnant women for whom morbidity tends to be disparately higher.”

Doulas can also take pressure off embattled ob.gyn. clinical staff. “Our volume of patients is huge, so we have to keep appointments brief,” Dr. Baker said. “The US is currently 8000 ob.gyn.s short, and to make matters worse, we’re seeing more and more obstetrical care deserts.”

Still largely underutilized, doula care is seen by its proponents as important in light of the drastic shortage of ob.gyn.s and the shrinking presence of maternity care in many US counties.

According to a recent March of Dimes report, access to maternity care is waning, with more than 35% of US counties offering no community obstetrical care and 52% providing no maternity care in local hospitals. That translates to long distances and extended travel time for mothers seeking care.
 

Growth Remains Slow

Although many believe doulas could become part of the solution to the lack of access to maternity care, their acceptance seems to be slow growing. In a 2012 national survey by Declercq and associates, about 6% of mothers used a doula during childbirth, up from 3% in a 2006 national survey. Of those who were familiar with but lacking doula care, just 27% would have chosen to have this service.

“I’d estimate that doulas are still involved in only about 6%-8% of births,” said Shaconna Haley, MA, a certified holistic doula and doula trainer in Atlanta, Georgia.

And are there enough practicing doulas in the United States to put a dent in the current shortfall in pregnancy care? Although no reliable estimate of their numbers exists, a centralized online doula registration service listed 9000 registered practitioners in 2018. Contrast that with the approximately 3.6 million live births in 2023.
 

Potential for Friction?

Although generally seen as benign and helpful, the presence of a doula can add another layer of people for hard-pressed medical staff to deal with. Can their attendance occasionally lead to an adversarial encounter? Yes, said Dr. Baker, especially in the case of assertive questioning or suggestions directed at medical staff. “There can be some mistrust on the part of clinicians when nonmedical persons start raising concerns and asking questions. Staff can get a little prickly at this.”

In the view of Melissa A. Simon, MD, MPH, a professor of obstetrics and gynecology, preventive medicine, and medical social sciences at Northwestern University Feinberg School of Medicine in Chicago, Illinois, simple, preventable communication breakdown is often the cause of occasional antagonism. “As in all team care approaches, it’s helpful to have upfront conversations with the birthing person, the doula, and any care team members or support people who will be present in the birthing room. These conversations should be about expectations.”

According to Ms. Haley, “As long as the focus stays firmly on the client/patient and not on the other team members, there should be no friction. Medical staff should be aware there will be a doula in attendance and ideally there should be a collaborative team and plan in place before the birth.” 

In Dr. Leke’s experience, doulas do not hinder the medical team as long as clinical roles are well clarified and the patient is engaged in her care plan. “Friction can occur when doulas are functioning outside of their scope of practice, such as speaking to the healthcare team on behalf of the mother instead empowering the mother to speak up herself,” she said. “Or, when the healthcare team doesn’t understand the doula’s scope of practice or recognize the doula as a member of the team.” 

Added Dr. Rothenberg, “I’ve occasionally run into doulas who imagine I have an ulterior motive when making recommendations to patients when that’s completely untrue. It’s common for women to decide to become doulas because they didn’t feel listened to during their own birthing experience, and for a few of them, it’s hard to not project that onto their clients’ labor situations, creating conflict where it doesn’t need to exist.”
 

Barriers and Challenges 

Unfortunately, the barriers of cost and access remain high for pregnant and birthing mothers from lower socioeconomic echelons who have no or limited insurance. “There also are very few multilingual doulas or doulas from diverse racial-ethnic backgrounds and identities,” Dr. Simon pointed out.
Yet by all indications, Medicaid members who receive doula services experience positive maternal outcomes, even those at higher risk for pregnancy complications.

As for Medicaid coverage of doula services, in a recent Centers for Medicare & Medicaid Services report, just 11 state Medicaid programs were reimbursing doula services, whereas an additional five were in the process of implementing reimbursement.

Doula care is not covered by all private insurance plans either, Dr. Simon said. “Although there are maternity care bundles with payment models that help integrate doula care, and there are ways to use your flexible spending account to cover it.”

Some hospitals may undertake independent initiatives. Dr. Baker’s center is offering antenatal and peripartum doula support for under-resourced mothers thanks to a Health Resources and Services Administration grant.* 

But for now, doula services are largely limited to middle- and high-income women able to afford the associated out-of-pocket costs. These mothers are disproportionately White, and the doulas serving them tend to be of the same race and socioeconomic class.

The Future

Dr. Simon foresees an optimal scenario in which a team of doulas works with all birthing persons on a hospital labor floor as well as with a team of clinicians. “It takes a true team approach to ensure an optimal birthing experience and optimal birth outcomes,” she said.

Despite the many challenges ahead, doulas will probably become a permanent fixture in pregnancy, birth, and postpartum care, said Dr. Baker. “Doula care is going to be a game changer, and obstetricians welcome doulas to the obstetrical care team.” 

Dr. Alrahmani, Dr. Baker, Ms. Haley, Dr. Leke, Dr. Rothenberg, and Dr. Simon declared no conflicts of interest relevant to their comments.

*This story was updated on October 1, 2024.

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

It’s well known that the United States enjoys the dubious distinction of having the worst maternal morbidity and mortality rates among industrialized nations. Maternal mortality in this country increased by 14% from 2018 to 2020, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics.

But a current trend of engaging birth doulas — nonmedical guides offering continuous one-on-one physical and psychological support in the pre-, peri,- and postnatal periods — may be poised to brighten that dismal statistical landscape.

Recent research has shown that mothers matched with a doula are less likely to have a low birth weight baby, less likely to experience a birth complication, and significantly more likely to initiate breastfeeding.

Doula services — even delivered digitally — are seen to lower healthcare costs, reduce cesarean sections, decrease maternal anxiety and depression, and improve communication between healthcare providers and low-income, racially/ethnically diverse pregnant women. Doulas can be especially helpful for mothers dealing with the psychological fallout of miscarriage or stillbirth. They can guide patients in the postpartum period, when problems can arise and when some mothers are lost to medical follow-up, and provide an ongoing source of patient information for the ob.gyn.

“Research has shown that in addition to better outcomes, doula care can shorten labor time and increase patient satisfaction,” said ob.gyn. Layan Alrahmani, MD, in an interview. A maternal-fetal medicine specialist with a focus on high-risk pregnancies among low-income women at Loyola Medicine in Maywood, Illinois, Dr. Alrahmani welcomes doulas to her patients’ antenatal visits.

“Many of my patients who are looking to avoid an epidural will work with a labor doula, in order to stay home as long as possible and to have one-on-one coaching through the pain as things progress,” said Susan Rothenberg, MD, an assistant professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai and an ob/gyn at Mount Sinai Downtown Union Square in New York City. She added, “When a woman’s partner is squeamish or potentially unavailable, a labor doula can be a great option.”

Another ob.gyn. who enthusiastically embraces doula care is L. Joy Baker, MD, who practices in LaGrange, Georgia, and is affiliated with Wellstar West Georgia Medical Center. “I love it when my patients have a doula. A doula answers a patient’s questions throughout the pregnancy and amplifies the mother’s voice in the medical system and the clinical setting,” Dr. Baker told this news organization.

“They provide important details on patients’ food, housing, and transportation status when the mothers themselves would not bring those up in a short appointment with their doctors,” she said. Dr. Baker called for more recognition of their merit, especially for first-time and high-risk moms.

Efua B. Leke, MD, MPH, an assistant professor at Baylor College of Medicine and chief of obstetrics at Ben Taub Hospital in Houston, Texas, also believes a major benefit of doulas is improved flow of information. “We know that having doulas participate in maternal care can ease communication between pregnant and parturient mothers and their clinical team,” Dr. Leke said. “This is especially important for under-resourced pregnant women for whom morbidity tends to be disparately higher.”

Doulas can also take pressure off embattled ob.gyn. clinical staff. “Our volume of patients is huge, so we have to keep appointments brief,” Dr. Baker said. “The US is currently 8000 ob.gyn.s short, and to make matters worse, we’re seeing more and more obstetrical care deserts.”

Still largely underutilized, doula care is seen by its proponents as important in light of the drastic shortage of ob.gyn.s and the shrinking presence of maternity care in many US counties.

According to a recent March of Dimes report, access to maternity care is waning, with more than 35% of US counties offering no community obstetrical care and 52% providing no maternity care in local hospitals. That translates to long distances and extended travel time for mothers seeking care.
 

Growth Remains Slow

Although many believe doulas could become part of the solution to the lack of access to maternity care, their acceptance seems to be slow growing. In a 2012 national survey by Declercq and associates, about 6% of mothers used a doula during childbirth, up from 3% in a 2006 national survey. Of those who were familiar with but lacking doula care, just 27% would have chosen to have this service.

“I’d estimate that doulas are still involved in only about 6%-8% of births,” said Shaconna Haley, MA, a certified holistic doula and doula trainer in Atlanta, Georgia.

And are there enough practicing doulas in the United States to put a dent in the current shortfall in pregnancy care? Although no reliable estimate of their numbers exists, a centralized online doula registration service listed 9000 registered practitioners in 2018. Contrast that with the approximately 3.6 million live births in 2023.
 

Potential for Friction?

Although generally seen as benign and helpful, the presence of a doula can add another layer of people for hard-pressed medical staff to deal with. Can their attendance occasionally lead to an adversarial encounter? Yes, said Dr. Baker, especially in the case of assertive questioning or suggestions directed at medical staff. “There can be some mistrust on the part of clinicians when nonmedical persons start raising concerns and asking questions. Staff can get a little prickly at this.”

In the view of Melissa A. Simon, MD, MPH, a professor of obstetrics and gynecology, preventive medicine, and medical social sciences at Northwestern University Feinberg School of Medicine in Chicago, Illinois, simple, preventable communication breakdown is often the cause of occasional antagonism. “As in all team care approaches, it’s helpful to have upfront conversations with the birthing person, the doula, and any care team members or support people who will be present in the birthing room. These conversations should be about expectations.”

According to Ms. Haley, “As long as the focus stays firmly on the client/patient and not on the other team members, there should be no friction. Medical staff should be aware there will be a doula in attendance and ideally there should be a collaborative team and plan in place before the birth.” 

In Dr. Leke’s experience, doulas do not hinder the medical team as long as clinical roles are well clarified and the patient is engaged in her care plan. “Friction can occur when doulas are functioning outside of their scope of practice, such as speaking to the healthcare team on behalf of the mother instead empowering the mother to speak up herself,” she said. “Or, when the healthcare team doesn’t understand the doula’s scope of practice or recognize the doula as a member of the team.” 

Added Dr. Rothenberg, “I’ve occasionally run into doulas who imagine I have an ulterior motive when making recommendations to patients when that’s completely untrue. It’s common for women to decide to become doulas because they didn’t feel listened to during their own birthing experience, and for a few of them, it’s hard to not project that onto their clients’ labor situations, creating conflict where it doesn’t need to exist.”
 

Barriers and Challenges 

Unfortunately, the barriers of cost and access remain high for pregnant and birthing mothers from lower socioeconomic echelons who have no or limited insurance. “There also are very few multilingual doulas or doulas from diverse racial-ethnic backgrounds and identities,” Dr. Simon pointed out.
Yet by all indications, Medicaid members who receive doula services experience positive maternal outcomes, even those at higher risk for pregnancy complications.

As for Medicaid coverage of doula services, in a recent Centers for Medicare & Medicaid Services report, just 11 state Medicaid programs were reimbursing doula services, whereas an additional five were in the process of implementing reimbursement.

Doula care is not covered by all private insurance plans either, Dr. Simon said. “Although there are maternity care bundles with payment models that help integrate doula care, and there are ways to use your flexible spending account to cover it.”

Some hospitals may undertake independent initiatives. Dr. Baker’s center is offering antenatal and peripartum doula support for under-resourced mothers thanks to a Health Resources and Services Administration grant.* 

But for now, doula services are largely limited to middle- and high-income women able to afford the associated out-of-pocket costs. These mothers are disproportionately White, and the doulas serving them tend to be of the same race and socioeconomic class.

The Future

Dr. Simon foresees an optimal scenario in which a team of doulas works with all birthing persons on a hospital labor floor as well as with a team of clinicians. “It takes a true team approach to ensure an optimal birthing experience and optimal birth outcomes,” she said.

Despite the many challenges ahead, doulas will probably become a permanent fixture in pregnancy, birth, and postpartum care, said Dr. Baker. “Doula care is going to be a game changer, and obstetricians welcome doulas to the obstetrical care team.” 

Dr. Alrahmani, Dr. Baker, Ms. Haley, Dr. Leke, Dr. Rothenberg, and Dr. Simon declared no conflicts of interest relevant to their comments.

*This story was updated on October 1, 2024.

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

It’s well known that the United States enjoys the dubious distinction of having the worst maternal morbidity and mortality rates among industrialized nations. Maternal mortality in this country increased by 14% from 2018 to 2020, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics.

But a current trend of engaging birth doulas — nonmedical guides offering continuous one-on-one physical and psychological support in the pre-, peri,- and postnatal periods — may be poised to brighten that dismal statistical landscape.

Recent research has shown that mothers matched with a doula are less likely to have a low birth weight baby, less likely to experience a birth complication, and significantly more likely to initiate breastfeeding.

Doula services — even delivered digitally — are seen to lower healthcare costs, reduce cesarean sections, decrease maternal anxiety and depression, and improve communication between healthcare providers and low-income, racially/ethnically diverse pregnant women. Doulas can be especially helpful for mothers dealing with the psychological fallout of miscarriage or stillbirth. They can guide patients in the postpartum period, when problems can arise and when some mothers are lost to medical follow-up, and provide an ongoing source of patient information for the ob.gyn.

“Research has shown that in addition to better outcomes, doula care can shorten labor time and increase patient satisfaction,” said ob.gyn. Layan Alrahmani, MD, in an interview. A maternal-fetal medicine specialist with a focus on high-risk pregnancies among low-income women at Loyola Medicine in Maywood, Illinois, Dr. Alrahmani welcomes doulas to her patients’ antenatal visits.

“Many of my patients who are looking to avoid an epidural will work with a labor doula, in order to stay home as long as possible and to have one-on-one coaching through the pain as things progress,” said Susan Rothenberg, MD, an assistant professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai and an ob/gyn at Mount Sinai Downtown Union Square in New York City. She added, “When a woman’s partner is squeamish or potentially unavailable, a labor doula can be a great option.”

Another ob.gyn. who enthusiastically embraces doula care is L. Joy Baker, MD, who practices in LaGrange, Georgia, and is affiliated with Wellstar West Georgia Medical Center. “I love it when my patients have a doula. A doula answers a patient’s questions throughout the pregnancy and amplifies the mother’s voice in the medical system and the clinical setting,” Dr. Baker told this news organization.

“They provide important details on patients’ food, housing, and transportation status when the mothers themselves would not bring those up in a short appointment with their doctors,” she said. Dr. Baker called for more recognition of their merit, especially for first-time and high-risk moms.

Efua B. Leke, MD, MPH, an assistant professor at Baylor College of Medicine and chief of obstetrics at Ben Taub Hospital in Houston, Texas, also believes a major benefit of doulas is improved flow of information. “We know that having doulas participate in maternal care can ease communication between pregnant and parturient mothers and their clinical team,” Dr. Leke said. “This is especially important for under-resourced pregnant women for whom morbidity tends to be disparately higher.”

Doulas can also take pressure off embattled ob.gyn. clinical staff. “Our volume of patients is huge, so we have to keep appointments brief,” Dr. Baker said. “The US is currently 8000 ob.gyn.s short, and to make matters worse, we’re seeing more and more obstetrical care deserts.”

Still largely underutilized, doula care is seen by its proponents as important in light of the drastic shortage of ob.gyn.s and the shrinking presence of maternity care in many US counties.

According to a recent March of Dimes report, access to maternity care is waning, with more than 35% of US counties offering no community obstetrical care and 52% providing no maternity care in local hospitals. That translates to long distances and extended travel time for mothers seeking care.
 

Growth Remains Slow

Although many believe doulas could become part of the solution to the lack of access to maternity care, their acceptance seems to be slow growing. In a 2012 national survey by Declercq and associates, about 6% of mothers used a doula during childbirth, up from 3% in a 2006 national survey. Of those who were familiar with but lacking doula care, just 27% would have chosen to have this service.

“I’d estimate that doulas are still involved in only about 6%-8% of births,” said Shaconna Haley, MA, a certified holistic doula and doula trainer in Atlanta, Georgia.

And are there enough practicing doulas in the United States to put a dent in the current shortfall in pregnancy care? Although no reliable estimate of their numbers exists, a centralized online doula registration service listed 9000 registered practitioners in 2018. Contrast that with the approximately 3.6 million live births in 2023.
 

Potential for Friction?

Although generally seen as benign and helpful, the presence of a doula can add another layer of people for hard-pressed medical staff to deal with. Can their attendance occasionally lead to an adversarial encounter? Yes, said Dr. Baker, especially in the case of assertive questioning or suggestions directed at medical staff. “There can be some mistrust on the part of clinicians when nonmedical persons start raising concerns and asking questions. Staff can get a little prickly at this.”

In the view of Melissa A. Simon, MD, MPH, a professor of obstetrics and gynecology, preventive medicine, and medical social sciences at Northwestern University Feinberg School of Medicine in Chicago, Illinois, simple, preventable communication breakdown is often the cause of occasional antagonism. “As in all team care approaches, it’s helpful to have upfront conversations with the birthing person, the doula, and any care team members or support people who will be present in the birthing room. These conversations should be about expectations.”

According to Ms. Haley, “As long as the focus stays firmly on the client/patient and not on the other team members, there should be no friction. Medical staff should be aware there will be a doula in attendance and ideally there should be a collaborative team and plan in place before the birth.” 

In Dr. Leke’s experience, doulas do not hinder the medical team as long as clinical roles are well clarified and the patient is engaged in her care plan. “Friction can occur when doulas are functioning outside of their scope of practice, such as speaking to the healthcare team on behalf of the mother instead empowering the mother to speak up herself,” she said. “Or, when the healthcare team doesn’t understand the doula’s scope of practice or recognize the doula as a member of the team.” 

Added Dr. Rothenberg, “I’ve occasionally run into doulas who imagine I have an ulterior motive when making recommendations to patients when that’s completely untrue. It’s common for women to decide to become doulas because they didn’t feel listened to during their own birthing experience, and for a few of them, it’s hard to not project that onto their clients’ labor situations, creating conflict where it doesn’t need to exist.”
 

Barriers and Challenges 

Unfortunately, the barriers of cost and access remain high for pregnant and birthing mothers from lower socioeconomic echelons who have no or limited insurance. “There also are very few multilingual doulas or doulas from diverse racial-ethnic backgrounds and identities,” Dr. Simon pointed out.
Yet by all indications, Medicaid members who receive doula services experience positive maternal outcomes, even those at higher risk for pregnancy complications.

As for Medicaid coverage of doula services, in a recent Centers for Medicare & Medicaid Services report, just 11 state Medicaid programs were reimbursing doula services, whereas an additional five were in the process of implementing reimbursement.

Doula care is not covered by all private insurance plans either, Dr. Simon said. “Although there are maternity care bundles with payment models that help integrate doula care, and there are ways to use your flexible spending account to cover it.”

Some hospitals may undertake independent initiatives. Dr. Baker’s center is offering antenatal and peripartum doula support for under-resourced mothers thanks to a Health Resources and Services Administration grant.* 

But for now, doula services are largely limited to middle- and high-income women able to afford the associated out-of-pocket costs. These mothers are disproportionately White, and the doulas serving them tend to be of the same race and socioeconomic class.

The Future

Dr. Simon foresees an optimal scenario in which a team of doulas works with all birthing persons on a hospital labor floor as well as with a team of clinicians. “It takes a true team approach to ensure an optimal birthing experience and optimal birth outcomes,” she said.

Despite the many challenges ahead, doulas will probably become a permanent fixture in pregnancy, birth, and postpartum care, said Dr. Baker. “Doula care is going to be a game changer, and obstetricians welcome doulas to the obstetrical care team.” 

Dr. Alrahmani, Dr. Baker, Ms. Haley, Dr. Leke, Dr. Rothenberg, and Dr. Simon declared no conflicts of interest relevant to their comments.

*This story was updated on October 1, 2024.

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

TOPLINE:

Diabetes and prediabetes are associated with accelerated brain aging with brain age gaps of 2.29 and 0.50 years, respectively. This association is more pronounced in men and those with poor cardiometabolic health but may be mitigated by a healthy lifestyle.

METHODOLOGY:

• Diabetes is a known risk factor for cognitive impairment, dementia, and global brain atrophy but conflicting results have been reported for prediabetes, and it’s unknown whether a healthy lifestyle can counteract the negative impact of prediabetes.
• Researchers examined the cross-sectional and longitudinal relationship between hyperglycemia and brain aging, as well as the potential mitigating effect of a healthy lifestyle in 31,229 dementia-free adults (mean age, 54.8 years; 53% women) from the UK Biobank, including 13,518 participants with prediabetes and 1149 with diabetes.
• The glycemic status of the participants was determined by their medical history, medication use, and A1c levels.
• The brain age gap was calculated as a difference between chronologic age and brain age estimated from MRI data from six modalities vs several hundred brain MRI phenotypes that were modeled from a subset of healthy individuals.
• The role of sex, cardiometabolic risk factors, and a healthy lifestyle and their association with brain age was also explored, with a healthy lifestyle defined as never smoking, no or light or moderate alcohol consumption, and high physical activity.

TAKEAWAY:

• Prediabetes and diabetes were associated with a higher brain age gap than normoglycemia (beta-coefficient, 0.22 and 2.01; 95% CI, 0.10-0.34 and 1.70-2.32, respectively), and diabetes was more pronounced in men vs women and those with a higher vs lower burden of cardiometabolic risk factors.
• The brain ages of those with prediabetes and diabetes were 0.50 years and 2.29 years older on average than their respective chronologic ages.
• In an exploratory longitudinal analysis of the 2414 participants with two brain MRI scans, diabetes was linked to a 0.27-year annual increase in the brain age gap, and higher A1c, but not prediabetes, was associated with a significant increase in brain age gap.
• A healthy lifestyle attenuated the association between diabetes and a higher brain age gap (P = .003), reducing it by 1.68 years, also with a significant interaction between glycemic status and lifestyle.

IN PRACTICE:

“Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health,” the authors wrote.

SOURCE:

This study, led by Abigail Dove, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, was published online in Diabetes Care.

LIMITATIONS:

The generalizability of the findings was limited due to a healthy volunteer bias in the UK Biobank. A high proportion of missing data prevented the inclusion of diet in the healthy lifestyle construct. Reverse causality may be possible as an older brain may contribute to the development of prediabetes by making it more difficult to manage medical conditions and adhere to a healthy lifestyle. A1c levels were measured only at baseline, preventing the assessment of changes in glycemic control over time.

DISCLOSURES:

The authors reported receiving funding from the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Karolinska Institutet Board of Research; Riksbankens Jubileumsfond; Marianne and Marcus Wallenberg Foundation; Alzheimerfonden; and Demensfonden. They declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Diabetes and prediabetes are associated with accelerated brain aging with brain age gaps of 2.29 and 0.50 years, respectively. This association is more pronounced in men and those with poor cardiometabolic health but may be mitigated by a healthy lifestyle.

METHODOLOGY:

• Diabetes is a known risk factor for cognitive impairment, dementia, and global brain atrophy but conflicting results have been reported for prediabetes, and it’s unknown whether a healthy lifestyle can counteract the negative impact of prediabetes.
• Researchers examined the cross-sectional and longitudinal relationship between hyperglycemia and brain aging, as well as the potential mitigating effect of a healthy lifestyle in 31,229 dementia-free adults (mean age, 54.8 years; 53% women) from the UK Biobank, including 13,518 participants with prediabetes and 1149 with diabetes.
• The glycemic status of the participants was determined by their medical history, medication use, and A1c levels.
• The brain age gap was calculated as a difference between chronologic age and brain age estimated from MRI data from six modalities vs several hundred brain MRI phenotypes that were modeled from a subset of healthy individuals.
• The role of sex, cardiometabolic risk factors, and a healthy lifestyle and their association with brain age was also explored, with a healthy lifestyle defined as never smoking, no or light or moderate alcohol consumption, and high physical activity.

TAKEAWAY:

• Prediabetes and diabetes were associated with a higher brain age gap than normoglycemia (beta-coefficient, 0.22 and 2.01; 95% CI, 0.10-0.34 and 1.70-2.32, respectively), and diabetes was more pronounced in men vs women and those with a higher vs lower burden of cardiometabolic risk factors.
• The brain ages of those with prediabetes and diabetes were 0.50 years and 2.29 years older on average than their respective chronologic ages.
• In an exploratory longitudinal analysis of the 2414 participants with two brain MRI scans, diabetes was linked to a 0.27-year annual increase in the brain age gap, and higher A1c, but not prediabetes, was associated with a significant increase in brain age gap.
• A healthy lifestyle attenuated the association between diabetes and a higher brain age gap (P = .003), reducing it by 1.68 years, also with a significant interaction between glycemic status and lifestyle.

IN PRACTICE:

“Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health,” the authors wrote.

SOURCE:

This study, led by Abigail Dove, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, was published online in Diabetes Care.

LIMITATIONS:

The generalizability of the findings was limited due to a healthy volunteer bias in the UK Biobank. A high proportion of missing data prevented the inclusion of diet in the healthy lifestyle construct. Reverse causality may be possible as an older brain may contribute to the development of prediabetes by making it more difficult to manage medical conditions and adhere to a healthy lifestyle. A1c levels were measured only at baseline, preventing the assessment of changes in glycemic control over time.

DISCLOSURES:

The authors reported receiving funding from the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Karolinska Institutet Board of Research; Riksbankens Jubileumsfond; Marianne and Marcus Wallenberg Foundation; Alzheimerfonden; and Demensfonden. They declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Diabetes and prediabetes are associated with accelerated brain aging with brain age gaps of 2.29 and 0.50 years, respectively. This association is more pronounced in men and those with poor cardiometabolic health but may be mitigated by a healthy lifestyle.

METHODOLOGY:

• Diabetes is a known risk factor for cognitive impairment, dementia, and global brain atrophy but conflicting results have been reported for prediabetes, and it’s unknown whether a healthy lifestyle can counteract the negative impact of prediabetes.
• Researchers examined the cross-sectional and longitudinal relationship between hyperglycemia and brain aging, as well as the potential mitigating effect of a healthy lifestyle in 31,229 dementia-free adults (mean age, 54.8 years; 53% women) from the UK Biobank, including 13,518 participants with prediabetes and 1149 with diabetes.
• The glycemic status of the participants was determined by their medical history, medication use, and A1c levels.
• The brain age gap was calculated as a difference between chronologic age and brain age estimated from MRI data from six modalities vs several hundred brain MRI phenotypes that were modeled from a subset of healthy individuals.
• The role of sex, cardiometabolic risk factors, and a healthy lifestyle and their association with brain age was also explored, with a healthy lifestyle defined as never smoking, no or light or moderate alcohol consumption, and high physical activity.

TAKEAWAY:

• Prediabetes and diabetes were associated with a higher brain age gap than normoglycemia (beta-coefficient, 0.22 and 2.01; 95% CI, 0.10-0.34 and 1.70-2.32, respectively), and diabetes was more pronounced in men vs women and those with a higher vs lower burden of cardiometabolic risk factors.
• The brain ages of those with prediabetes and diabetes were 0.50 years and 2.29 years older on average than their respective chronologic ages.
• In an exploratory longitudinal analysis of the 2414 participants with two brain MRI scans, diabetes was linked to a 0.27-year annual increase in the brain age gap, and higher A1c, but not prediabetes, was associated with a significant increase in brain age gap.
• A healthy lifestyle attenuated the association between diabetes and a higher brain age gap (P = .003), reducing it by 1.68 years, also with a significant interaction between glycemic status and lifestyle.

IN PRACTICE:

“Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health,” the authors wrote.

SOURCE:

This study, led by Abigail Dove, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, was published online in Diabetes Care.

LIMITATIONS:

The generalizability of the findings was limited due to a healthy volunteer bias in the UK Biobank. A high proportion of missing data prevented the inclusion of diet in the healthy lifestyle construct. Reverse causality may be possible as an older brain may contribute to the development of prediabetes by making it more difficult to manage medical conditions and adhere to a healthy lifestyle. A1c levels were measured only at baseline, preventing the assessment of changes in glycemic control over time.

DISCLOSURES:

The authors reported receiving funding from the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Karolinska Institutet Board of Research; Riksbankens Jubileumsfond; Marianne and Marcus Wallenberg Foundation; Alzheimerfonden; and Demensfonden. They declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Higher body mass index (BMI) in both partners is linked to lower fecundability and increased subfertility. Overweight and obesity in women are associated with higher odds of miscarriage.

METHODOLOGY:

• Researchers conducted a population-based prospective cohort study in Rotterdam, the Netherlands, from August 9, 2017, to July 1, 2021.
• A total of 3604 women and their partners were included, with follow-up until birth.
• BMI was measured in preconception or early pregnancy, and outcomes included fecundability, subfertility, and miscarriage.
• Fecundability was defined as the probability of conceiving within 1 month and subfertility as time to pregnancy or duration of actively pursuing pregnancy of more than 12 months or use of assisted reproductive technology.
• Miscarriage was defined as pregnancy loss before 22 weeks of gestation.

TAKEAWAY:

• Higher BMI in women and men was associated with lower fecundability: For every unit increase in BMI, fecundability decreased (women, 0.98; 95% CI, 0.97-0.99; men, 0.99; 95% CI, 0.98-1.00).
• Women with overweight (0.88; 95% CI, 0.80-0.98) and obesity (0.72; 95% CI, 0.63-0.82) had lower fecundability than women with normal weight.
• Overweight (1.35; 95% CI, 1.11-1.63) and obesity (1.67; 95% CI, 1.30-2.13) in women were associated with increased odds of subfertility.
• Obesity in men was associated with increased odds of subfertility (1.69; 95% CI, 1.24-2.31).

IN PRACTICE:

“We observed in this cohort study that BMI outside of the normal category in women and men was associated with lower fecundability, subfertility, and increased odds of miscarriage. Optimizing BMI from the preconception period onward in women and men might be an important strategy to improve fertility and pregnancy outcomes,” wrote the authors of the study.

SOURCE:

The study was led by Aline J. Boxem, MD, and Vincent W. V. Jaddoe, MD, PhD, The Generation R Study Group, Erasmus University Medical Centre in Rotterdam, the Netherlands. It was published online in JAMA Network Open.

LIMITATIONS:

The study’s generalizability may be affected by differences between included and excluded participants, who were younger and had a higher BMI. The accuracy of time-to-pregnancy duration may have been impacted by retrospectively answered questionnaires. Residual confounding might still be an issue due to the observational nature of the study.

DISCLOSURES:

Dr. Boxem and Dr. Jaddoe disclosed receiving grants from the Erasmus University Medical Centre, the Erasmus University Rotterdam, and the Netherlands Organisation for Health Research and Development. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Higher body mass index (BMI) in both partners is linked to lower fecundability and increased subfertility. Overweight and obesity in women are associated with higher odds of miscarriage.

METHODOLOGY:

• Researchers conducted a population-based prospective cohort study in Rotterdam, the Netherlands, from August 9, 2017, to July 1, 2021.
• A total of 3604 women and their partners were included, with follow-up until birth.
• BMI was measured in preconception or early pregnancy, and outcomes included fecundability, subfertility, and miscarriage.
• Fecundability was defined as the probability of conceiving within 1 month and subfertility as time to pregnancy or duration of actively pursuing pregnancy of more than 12 months or use of assisted reproductive technology.
• Miscarriage was defined as pregnancy loss before 22 weeks of gestation.

TAKEAWAY:

• Higher BMI in women and men was associated with lower fecundability: For every unit increase in BMI, fecundability decreased (women, 0.98; 95% CI, 0.97-0.99; men, 0.99; 95% CI, 0.98-1.00).
• Women with overweight (0.88; 95% CI, 0.80-0.98) and obesity (0.72; 95% CI, 0.63-0.82) had lower fecundability than women with normal weight.
• Overweight (1.35; 95% CI, 1.11-1.63) and obesity (1.67; 95% CI, 1.30-2.13) in women were associated with increased odds of subfertility.
• Obesity in men was associated with increased odds of subfertility (1.69; 95% CI, 1.24-2.31).

IN PRACTICE:

“We observed in this cohort study that BMI outside of the normal category in women and men was associated with lower fecundability, subfertility, and increased odds of miscarriage. Optimizing BMI from the preconception period onward in women and men might be an important strategy to improve fertility and pregnancy outcomes,” wrote the authors of the study.

SOURCE:

The study was led by Aline J. Boxem, MD, and Vincent W. V. Jaddoe, MD, PhD, The Generation R Study Group, Erasmus University Medical Centre in Rotterdam, the Netherlands. It was published online in JAMA Network Open.

LIMITATIONS:

The study’s generalizability may be affected by differences between included and excluded participants, who were younger and had a higher BMI. The accuracy of time-to-pregnancy duration may have been impacted by retrospectively answered questionnaires. Residual confounding might still be an issue due to the observational nature of the study.

DISCLOSURES:

Dr. Boxem and Dr. Jaddoe disclosed receiving grants from the Erasmus University Medical Centre, the Erasmus University Rotterdam, and the Netherlands Organisation for Health Research and Development. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Higher body mass index (BMI) in both partners is linked to lower fecundability and increased subfertility. Overweight and obesity in women are associated with higher odds of miscarriage.

METHODOLOGY:

• Researchers conducted a population-based prospective cohort study in Rotterdam, the Netherlands, from August 9, 2017, to July 1, 2021.
• A total of 3604 women and their partners were included, with follow-up until birth.
• BMI was measured in preconception or early pregnancy, and outcomes included fecundability, subfertility, and miscarriage.
• Fecundability was defined as the probability of conceiving within 1 month and subfertility as time to pregnancy or duration of actively pursuing pregnancy of more than 12 months or use of assisted reproductive technology.
• Miscarriage was defined as pregnancy loss before 22 weeks of gestation.

TAKEAWAY:

• Higher BMI in women and men was associated with lower fecundability: For every unit increase in BMI, fecundability decreased (women, 0.98; 95% CI, 0.97-0.99; men, 0.99; 95% CI, 0.98-1.00).
• Women with overweight (0.88; 95% CI, 0.80-0.98) and obesity (0.72; 95% CI, 0.63-0.82) had lower fecundability than women with normal weight.
• Overweight (1.35; 95% CI, 1.11-1.63) and obesity (1.67; 95% CI, 1.30-2.13) in women were associated with increased odds of subfertility.
• Obesity in men was associated with increased odds of subfertility (1.69; 95% CI, 1.24-2.31).

IN PRACTICE:

“We observed in this cohort study that BMI outside of the normal category in women and men was associated with lower fecundability, subfertility, and increased odds of miscarriage. Optimizing BMI from the preconception period onward in women and men might be an important strategy to improve fertility and pregnancy outcomes,” wrote the authors of the study.

SOURCE:

The study was led by Aline J. Boxem, MD, and Vincent W. V. Jaddoe, MD, PhD, The Generation R Study Group, Erasmus University Medical Centre in Rotterdam, the Netherlands. It was published online in JAMA Network Open.

LIMITATIONS:

The study’s generalizability may be affected by differences between included and excluded participants, who were younger and had a higher BMI. The accuracy of time-to-pregnancy duration may have been impacted by retrospectively answered questionnaires. Residual confounding might still be an issue due to the observational nature of the study.

DISCLOSURES:

Dr. Boxem and Dr. Jaddoe disclosed receiving grants from the Erasmus University Medical Centre, the Erasmus University Rotterdam, and the Netherlands Organisation for Health Research and Development. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Pertussis cases in the United States have increased fourfold compared with the same time period last year, according to data from the Centers for Disease Control and Prevention (CDC). Reports from several states illustrate this trend, thought to be due to reduced immunity across the country.

The Alaska Department of Health issued a statement on its website about the significant increase in pertussis cases in the state during the summer, with 90 cases in July and 61 in August, compared with 24 in June and a total of 26 cases in 2023.

Similarly, the Florida Department of Health reported a pertussis increase in July 2024 that was higher than the June 2024 case count and also above the previous 5-year average.

Experts in these and other states suggest that several factors are driving the nationwide increase, including the fact that fewer people are consistently wearing masks. The mass masking during the COVID-19 pandemic caused a significant drop in pertussis, but the latest data suggest a return to prepandemic levels, and waning immunity likely plays a role as well.

Pertussis, also known as whooping cough, typically begins with symptoms similar to those of the common cold, including runny nose, sneezing, mild fever, and cough, according to the CDC. However, babies with whooping cough may experience trouble breathing rather than a cough. The coughing fits often associated with pertussis may not start until 2 weeks after the onset of other symptoms, according to the CDC.

Those who have been vaccinated against pertussis can still become infected, but the risk is lower, and the illness, if it occurs, is likely to be milder. Complications such as apnea, pneumonia, and convulsions can occur in babies younger than 1 year, especially if they have not been vaccinated, according to the CDC.
 

Beyond Easing Pandemic Precautions

Many respiratory-based infections dipped during the COVID-19 pandemic, almost certainly from the multifactorial interventions of masking, distancing, and the general lack of comingling, said David J. Cennimo, MD, associate professor of medicine & pediatrics in the Division of Infectious Diseases at Rutgers New Jersey Medical School, Newark, New Jersey, in an interview.

The number of cases of many of these diseases returned to previous levels after COVID-19 restrictions were lifted, he said.

“However, we know pertussis immunity wanes over time. Children get DTaP at 2, 4, 6, and 15 months, and a Tdap booster at 11-12 years old gets them to adulthood,” Dr. Cennimo said. Adults should be getting a Tdap every 10 years, he added.

The latest available CDC data indicate that Tdap vaccine coverage in adults is approximately 40%, which means that there may be a large number of susceptible people who can become infected and propagate to others, said Dr. Cennimo.
 

Not Just the Young Ones

A recent pertussis outbreak among college students in Virginia highlighted the fact that the infection can affect all ages, and that the effectiveness of childhood vaccines may decrease over time. The majority of the recently diagnosed cases occurred in individuals who had been previously vaccinated, according to a press release from the Virginia Department of Health.

Clinical Clues

The initial stage of pertussis infection looks like a common cold with symptoms of upper respiratory infection, Dr. Cennimo told this news organization. “Unless there is reason to suspect pertussis exposure, it would almost certainly be missed,” he noted.

The characteristic barking/seal-like cough is mostly seen in children, said Dr. Cennimo. Adults and children can experience coughing fits that can lead to shortness of breath and/or vomiting, which would raise suspicion for pertussis, but is not universally present, he said. The convalescent stage of pertussis can be prolonged and is characterized by chronic coughing. “In the past, pertussis had been called the 100-day cough,” and at that point, treatment is ineffective, Dr. Cennimo said.

In clinical practice, “I advise everyone to get the Tdap vaccine every 10 years,” and remember that the “Td” is the every 10-year tetanus shot as well, Dr. Cennimo told this news organization. Reassure patients that the Tdap can be given with other vaccines, he said, and remind patients that, as with any of the respiratory illnesses, they should stay home if sick, cover a cough, consider wearing a mask in public, and wash hands frequently, he said. 

Dr. Cennimo had no financial conflicts to disclose.

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

Pertussis cases in the United States have increased fourfold compared with the same time period last year, according to data from the Centers for Disease Control and Prevention (CDC). Reports from several states illustrate this trend, thought to be due to reduced immunity across the country.

The Alaska Department of Health issued a statement on its website about the significant increase in pertussis cases in the state during the summer, with 90 cases in July and 61 in August, compared with 24 in June and a total of 26 cases in 2023.

Similarly, the Florida Department of Health reported a pertussis increase in July 2024 that was higher than the June 2024 case count and also above the previous 5-year average.

Experts in these and other states suggest that several factors are driving the nationwide increase, including the fact that fewer people are consistently wearing masks. The mass masking during the COVID-19 pandemic caused a significant drop in pertussis, but the latest data suggest a return to prepandemic levels, and waning immunity likely plays a role as well.

Pertussis, also known as whooping cough, typically begins with symptoms similar to those of the common cold, including runny nose, sneezing, mild fever, and cough, according to the CDC. However, babies with whooping cough may experience trouble breathing rather than a cough. The coughing fits often associated with pertussis may not start until 2 weeks after the onset of other symptoms, according to the CDC.

Those who have been vaccinated against pertussis can still become infected, but the risk is lower, and the illness, if it occurs, is likely to be milder. Complications such as apnea, pneumonia, and convulsions can occur in babies younger than 1 year, especially if they have not been vaccinated, according to the CDC.
 

Beyond Easing Pandemic Precautions

Many respiratory-based infections dipped during the COVID-19 pandemic, almost certainly from the multifactorial interventions of masking, distancing, and the general lack of comingling, said David J. Cennimo, MD, associate professor of medicine & pediatrics in the Division of Infectious Diseases at Rutgers New Jersey Medical School, Newark, New Jersey, in an interview.

The number of cases of many of these diseases returned to previous levels after COVID-19 restrictions were lifted, he said.

“However, we know pertussis immunity wanes over time. Children get DTaP at 2, 4, 6, and 15 months, and a Tdap booster at 11-12 years old gets them to adulthood,” Dr. Cennimo said. Adults should be getting a Tdap every 10 years, he added.

The latest available CDC data indicate that Tdap vaccine coverage in adults is approximately 40%, which means that there may be a large number of susceptible people who can become infected and propagate to others, said Dr. Cennimo.
 

Not Just the Young Ones

A recent pertussis outbreak among college students in Virginia highlighted the fact that the infection can affect all ages, and that the effectiveness of childhood vaccines may decrease over time. The majority of the recently diagnosed cases occurred in individuals who had been previously vaccinated, according to a press release from the Virginia Department of Health.

Clinical Clues

The initial stage of pertussis infection looks like a common cold with symptoms of upper respiratory infection, Dr. Cennimo told this news organization. “Unless there is reason to suspect pertussis exposure, it would almost certainly be missed,” he noted.

The characteristic barking/seal-like cough is mostly seen in children, said Dr. Cennimo. Adults and children can experience coughing fits that can lead to shortness of breath and/or vomiting, which would raise suspicion for pertussis, but is not universally present, he said. The convalescent stage of pertussis can be prolonged and is characterized by chronic coughing. “In the past, pertussis had been called the 100-day cough,” and at that point, treatment is ineffective, Dr. Cennimo said.

In clinical practice, “I advise everyone to get the Tdap vaccine every 10 years,” and remember that the “Td” is the every 10-year tetanus shot as well, Dr. Cennimo told this news organization. Reassure patients that the Tdap can be given with other vaccines, he said, and remind patients that, as with any of the respiratory illnesses, they should stay home if sick, cover a cough, consider wearing a mask in public, and wash hands frequently, he said. 

Dr. Cennimo had no financial conflicts to disclose.

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

Pertussis cases in the United States have increased fourfold compared with the same time period last year, according to data from the Centers for Disease Control and Prevention (CDC). Reports from several states illustrate this trend, thought to be due to reduced immunity across the country.

The Alaska Department of Health issued a statement on its website about the significant increase in pertussis cases in the state during the summer, with 90 cases in July and 61 in August, compared with 24 in June and a total of 26 cases in 2023.

Similarly, the Florida Department of Health reported a pertussis increase in July 2024 that was higher than the June 2024 case count and also above the previous 5-year average.

Experts in these and other states suggest that several factors are driving the nationwide increase, including the fact that fewer people are consistently wearing masks. The mass masking during the COVID-19 pandemic caused a significant drop in pertussis, but the latest data suggest a return to prepandemic levels, and waning immunity likely plays a role as well.

Pertussis, also known as whooping cough, typically begins with symptoms similar to those of the common cold, including runny nose, sneezing, mild fever, and cough, according to the CDC. However, babies with whooping cough may experience trouble breathing rather than a cough. The coughing fits often associated with pertussis may not start until 2 weeks after the onset of other symptoms, according to the CDC.

Those who have been vaccinated against pertussis can still become infected, but the risk is lower, and the illness, if it occurs, is likely to be milder. Complications such as apnea, pneumonia, and convulsions can occur in babies younger than 1 year, especially if they have not been vaccinated, according to the CDC.
 

Beyond Easing Pandemic Precautions

Many respiratory-based infections dipped during the COVID-19 pandemic, almost certainly from the multifactorial interventions of masking, distancing, and the general lack of comingling, said David J. Cennimo, MD, associate professor of medicine & pediatrics in the Division of Infectious Diseases at Rutgers New Jersey Medical School, Newark, New Jersey, in an interview.

The number of cases of many of these diseases returned to previous levels after COVID-19 restrictions were lifted, he said.

“However, we know pertussis immunity wanes over time. Children get DTaP at 2, 4, 6, and 15 months, and a Tdap booster at 11-12 years old gets them to adulthood,” Dr. Cennimo said. Adults should be getting a Tdap every 10 years, he added.

The latest available CDC data indicate that Tdap vaccine coverage in adults is approximately 40%, which means that there may be a large number of susceptible people who can become infected and propagate to others, said Dr. Cennimo.
 

Not Just the Young Ones

A recent pertussis outbreak among college students in Virginia highlighted the fact that the infection can affect all ages, and that the effectiveness of childhood vaccines may decrease over time. The majority of the recently diagnosed cases occurred in individuals who had been previously vaccinated, according to a press release from the Virginia Department of Health.

Clinical Clues

The initial stage of pertussis infection looks like a common cold with symptoms of upper respiratory infection, Dr. Cennimo told this news organization. “Unless there is reason to suspect pertussis exposure, it would almost certainly be missed,” he noted.

The characteristic barking/seal-like cough is mostly seen in children, said Dr. Cennimo. Adults and children can experience coughing fits that can lead to shortness of breath and/or vomiting, which would raise suspicion for pertussis, but is not universally present, he said. The convalescent stage of pertussis can be prolonged and is characterized by chronic coughing. “In the past, pertussis had been called the 100-day cough,” and at that point, treatment is ineffective, Dr. Cennimo said.

In clinical practice, “I advise everyone to get the Tdap vaccine every 10 years,” and remember that the “Td” is the every 10-year tetanus shot as well, Dr. Cennimo told this news organization. Reassure patients that the Tdap can be given with other vaccines, he said, and remind patients that, as with any of the respiratory illnesses, they should stay home if sick, cover a cough, consider wearing a mask in public, and wash hands frequently, he said. 

Dr. Cennimo had no financial conflicts to disclose.

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

The patient had been diagnosed with pemphigus vulgaris (PV) 1 year prior to presentation with erosions on the axilla. Biopsy at that time revealed intraepithelial acantholytic blistering with areas of suprabasilar and subcorneal clefting. Direct immunofluorescence was positive for linear/granular IgG deposition throughout the epithelial cell surfaces, as well as linear/granular C3 deposits of the lower two thirds of the epithelial strata, consistent for pemphigus vulgaris.

PV is a rare autoimmune bullous disease in which antibodies are directed against desmoglein 1 and 3 and less commonly, plakoglobin. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.

Clinically, PV presents with flaccid blistering lesions that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions can involve the lips, esophagus, conjunctiva, and genitals.

Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.

There are numerous reports in the literature of PV occurring in previous surgical scars, and areas of friction or trauma. This so-called Koebner’s phenomenon is seen more commonly in several dermatologic conditions, such as psoriasis, lichen planus, verruca vulgaris, and vitiligo.

Treatment for PV is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid sparing agent such as mycophenolate mofetil. Other steroid sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Cerottini JP et al. Eur J Dermatol. 2000 Oct-Nov;10(7):546-7.

Reichert-Penetrat S et al. Eur J Dermatol. 1998 Jan-Feb;8(1):60-2.

Saini P et al. Skinmed. 2020 Aug 1;18(4):252-253.

The patient had been diagnosed with pemphigus vulgaris (PV) 1 year prior to presentation with erosions on the axilla. Biopsy at that time revealed intraepithelial acantholytic blistering with areas of suprabasilar and subcorneal clefting. Direct immunofluorescence was positive for linear/granular IgG deposition throughout the epithelial cell surfaces, as well as linear/granular C3 deposits of the lower two thirds of the epithelial strata, consistent for pemphigus vulgaris.

PV is a rare autoimmune bullous disease in which antibodies are directed against desmoglein 1 and 3 and less commonly, plakoglobin. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.

Clinically, PV presents with flaccid blistering lesions that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions can involve the lips, esophagus, conjunctiva, and genitals.

Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.

There are numerous reports in the literature of PV occurring in previous surgical scars, and areas of friction or trauma. This so-called Koebner’s phenomenon is seen more commonly in several dermatologic conditions, such as psoriasis, lichen planus, verruca vulgaris, and vitiligo.

Treatment for PV is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid sparing agent such as mycophenolate mofetil. Other steroid sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Cerottini JP et al. Eur J Dermatol. 2000 Oct-Nov;10(7):546-7.

Reichert-Penetrat S et al. Eur J Dermatol. 1998 Jan-Feb;8(1):60-2.

Saini P et al. Skinmed. 2020 Aug 1;18(4):252-253.

The patient had been diagnosed with pemphigus vulgaris (PV) 1 year prior to presentation with erosions on the axilla. Biopsy at that time revealed intraepithelial acantholytic blistering with areas of suprabasilar and subcorneal clefting. Direct immunofluorescence was positive for linear/granular IgG deposition throughout the epithelial cell surfaces, as well as linear/granular C3 deposits of the lower two thirds of the epithelial strata, consistent for pemphigus vulgaris.

PV is a rare autoimmune bullous disease in which antibodies are directed against desmoglein 1 and 3 and less commonly, plakoglobin. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.

Clinically, PV presents with flaccid blistering lesions that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions can involve the lips, esophagus, conjunctiva, and genitals.

Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.

There are numerous reports in the literature of PV occurring in previous surgical scars, and areas of friction or trauma. This so-called Koebner’s phenomenon is seen more commonly in several dermatologic conditions, such as psoriasis, lichen planus, verruca vulgaris, and vitiligo.

Treatment for PV is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid sparing agent such as mycophenolate mofetil. Other steroid sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Cerottini JP et al. Eur J Dermatol. 2000 Oct-Nov;10(7):546-7.

Reichert-Penetrat S et al. Eur J Dermatol. 1998 Jan-Feb;8(1):60-2.

Saini P et al. Skinmed. 2020 Aug 1;18(4):252-253.