The annual production of plastic worldwide has increased exponentially from about 2 million tons in 1950 to 460 million tons in 2019, and current levels are expected to triple by 2060.

Plastic contains more than 10,000 chemicals, including carcinogenic substances and endocrine disruptors. Plastic and associated chemicals are responsible for widespread pollution, contaminating aquatic (marine and freshwater), terrestrial, and atmospheric environments globally.

Atmospheric concentrations of plastic particles are on the rise, to the extent that in a remote station in the Eastern Alps in Austria, the contribution of micro- and nanoplastics (MNPs) to organic matter was comparable to data collected at an urban site.

The ocean is the ultimate destination for much of the plastic. All oceans, on the surface and in the depths, contain plastic, which is even found in polar sea ice. Many plastics seem to resist decomposition in the ocean and could persist in the environment for decades. Macro- and microplastic (MP) particles have been identified in hundreds of marine species, including species consumed by humans.

The quantity and fate of MP particles (> 10 µm) and smaller nanoplastics (< 10 µm) in aquatic environments are poorly understood, but what is most concerning is their ability to cross biologic barriers and the potential harm associated with their mobility in biologic systems.
 

MNP Exposure

MNPs can originate from a wide variety of sources, including food, beverages, and food product packaging. Water bottles represent a significant source of ingestible MNPs for people in their daily lives. Recent estimates, using stimulated Raman scattering imaging, documented a concentration of MNP of approximately 2.4 ± 1.3 × 10⁵ particles per liter of bottled water. Around 90% are nanoplastics, which is two to three orders of magnitude higher than previously reported results for larger MPs.

MNPs enter the body primarily through ingestion or inhalation. For example, MNPs can be ingested by drinking liquids or eating food that has been stored or heated in plastic containers from which they have leaked or by using toothpaste that contains them. Infants are exposed to MPs from artificial milk preparation in polypropylene baby bottles, with higher levels than previously detected and ranging from 14,600 to 4,550,000 particles per capita per day.
 

MNP and Biologic Systems

The possible formation of hetero-aggregates between nanoplastics and natural organic matter has long been recognized as a potential challenge in the analysis of nanoplastics and can influence toxicologic results in biologic exposure. The direct visualization of such hetero-aggregates in real-world samples supports these concerns, but the analysis of MNPs with traditional techniques remains challenging. Unlike engineered nanoparticles (prepared in the laboratory as model systems), the nanoplastics in the environment are label-free and exhibit significant heterogeneity in chemical composition and morphology.

A systematic analysis of evidence on the toxic effects of MNPs on murine models, however, showed that 52.78% of biologic endpoints (related to glucose metabolism, reproduction, oxidative stress, and lipid metabolism) were significantly affected by MNP exposure.
 

Between Risk and Toxicity

MNP can enter the body in vivo through the digestive tract, respiratory tract, and skin contact. On average, humans could ingest from 0.1 to 5 g of MNP per week through various exposure routes.

MNPs are a potential risk factor for cardiovascular diseases, as suggested by a recent study on 257 patients with carotid atheromatous plaques. In 58.4% of cases, polyvinyl chloride was detected in the carotid artery plaque, with an average level of 5.2 ± 2.4 μg/mg of plaque. Patients with MNPs inside the atheroma had a higher risk (relative risk, 4.53) for a composite cardiovascular event of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than participants where MNPs were not detectable inside the atheromatous plaque.

The potential link between inflammatory bowel disease (IBD) and MPs has been hypothesized by a study that reported a higher fecal MP concentration in patients with IBD than in healthy individuals. Fecal MP level was correlated with disease severity.

However, these studies have not demonstrated a causal relationship between MNPs and disease, and the way MNPs may influence cellular functions and induce stress responses is not yet well understood.
 

Future Scenarios

Current evidence confirms the fragmentation of plastic beyond the micrometer level and has unequivocally detected nanoplastics in real samples. As with many other particle distributions of the same size in the natural world, there are substantially more nanoplastics, despite their invisibility with conventional imaging techniques, than particles larger than the micron size.

The initial results of studies on MNPs in humans will stimulate future research on the amounts of MNPs that accumulate in tissue over a person’s lifetime. Researchers also will examine how the particles’ characteristics, including their chemical composition, size, and shape, can influence organs and tissues.

The way MNPs can cause harm, including through effects on the immune system and microbiome, will need to be clarified by investigating possible direct cytotoxic effects, consistent with the introductory statement of the Organization for Economic Cooperation and Development global policy forum on plastics, which states, “Plastic pollution is one of the great environmental challenges of the 21st century, causing wide-ranging damage to ecosystems and human health.”

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The annual production of plastic worldwide has increased exponentially from about 2 million tons in 1950 to 460 million tons in 2019, and current levels are expected to triple by 2060.

Plastic contains more than 10,000 chemicals, including carcinogenic substances and endocrine disruptors. Plastic and associated chemicals are responsible for widespread pollution, contaminating aquatic (marine and freshwater), terrestrial, and atmospheric environments globally.

Atmospheric concentrations of plastic particles are on the rise, to the extent that in a remote station in the Eastern Alps in Austria, the contribution of micro- and nanoplastics (MNPs) to organic matter was comparable to data collected at an urban site.

The ocean is the ultimate destination for much of the plastic. All oceans, on the surface and in the depths, contain plastic, which is even found in polar sea ice. Many plastics seem to resist decomposition in the ocean and could persist in the environment for decades. Macro- and microplastic (MP) particles have been identified in hundreds of marine species, including species consumed by humans.

The quantity and fate of MP particles (> 10 µm) and smaller nanoplastics (< 10 µm) in aquatic environments are poorly understood, but what is most concerning is their ability to cross biologic barriers and the potential harm associated with their mobility in biologic systems.
 

MNP Exposure

MNPs can originate from a wide variety of sources, including food, beverages, and food product packaging. Water bottles represent a significant source of ingestible MNPs for people in their daily lives. Recent estimates, using stimulated Raman scattering imaging, documented a concentration of MNP of approximately 2.4 ± 1.3 × 10⁵ particles per liter of bottled water. Around 90% are nanoplastics, which is two to three orders of magnitude higher than previously reported results for larger MPs.

MNPs enter the body primarily through ingestion or inhalation. For example, MNPs can be ingested by drinking liquids or eating food that has been stored or heated in plastic containers from which they have leaked or by using toothpaste that contains them. Infants are exposed to MPs from artificial milk preparation in polypropylene baby bottles, with higher levels than previously detected and ranging from 14,600 to 4,550,000 particles per capita per day.
 

MNP and Biologic Systems

The possible formation of hetero-aggregates between nanoplastics and natural organic matter has long been recognized as a potential challenge in the analysis of nanoplastics and can influence toxicologic results in biologic exposure. The direct visualization of such hetero-aggregates in real-world samples supports these concerns, but the analysis of MNPs with traditional techniques remains challenging. Unlike engineered nanoparticles (prepared in the laboratory as model systems), the nanoplastics in the environment are label-free and exhibit significant heterogeneity in chemical composition and morphology.

A systematic analysis of evidence on the toxic effects of MNPs on murine models, however, showed that 52.78% of biologic endpoints (related to glucose metabolism, reproduction, oxidative stress, and lipid metabolism) were significantly affected by MNP exposure.
 

Between Risk and Toxicity

MNP can enter the body in vivo through the digestive tract, respiratory tract, and skin contact. On average, humans could ingest from 0.1 to 5 g of MNP per week through various exposure routes.

MNPs are a potential risk factor for cardiovascular diseases, as suggested by a recent study on 257 patients with carotid atheromatous plaques. In 58.4% of cases, polyvinyl chloride was detected in the carotid artery plaque, with an average level of 5.2 ± 2.4 μg/mg of plaque. Patients with MNPs inside the atheroma had a higher risk (relative risk, 4.53) for a composite cardiovascular event of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than participants where MNPs were not detectable inside the atheromatous plaque.

The potential link between inflammatory bowel disease (IBD) and MPs has been hypothesized by a study that reported a higher fecal MP concentration in patients with IBD than in healthy individuals. Fecal MP level was correlated with disease severity.

However, these studies have not demonstrated a causal relationship between MNPs and disease, and the way MNPs may influence cellular functions and induce stress responses is not yet well understood.
 

Future Scenarios

Current evidence confirms the fragmentation of plastic beyond the micrometer level and has unequivocally detected nanoplastics in real samples. As with many other particle distributions of the same size in the natural world, there are substantially more nanoplastics, despite their invisibility with conventional imaging techniques, than particles larger than the micron size.

The initial results of studies on MNPs in humans will stimulate future research on the amounts of MNPs that accumulate in tissue over a person’s lifetime. Researchers also will examine how the particles’ characteristics, including their chemical composition, size, and shape, can influence organs and tissues.

The way MNPs can cause harm, including through effects on the immune system and microbiome, will need to be clarified by investigating possible direct cytotoxic effects, consistent with the introductory statement of the Organization for Economic Cooperation and Development global policy forum on plastics, which states, “Plastic pollution is one of the great environmental challenges of the 21st century, causing wide-ranging damage to ecosystems and human health.”

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The annual production of plastic worldwide has increased exponentially from about 2 million tons in 1950 to 460 million tons in 2019, and current levels are expected to triple by 2060.

Plastic contains more than 10,000 chemicals, including carcinogenic substances and endocrine disruptors. Plastic and associated chemicals are responsible for widespread pollution, contaminating aquatic (marine and freshwater), terrestrial, and atmospheric environments globally.

Atmospheric concentrations of plastic particles are on the rise, to the extent that in a remote station in the Eastern Alps in Austria, the contribution of micro- and nanoplastics (MNPs) to organic matter was comparable to data collected at an urban site.

The ocean is the ultimate destination for much of the plastic. All oceans, on the surface and in the depths, contain plastic, which is even found in polar sea ice. Many plastics seem to resist decomposition in the ocean and could persist in the environment for decades. Macro- and microplastic (MP) particles have been identified in hundreds of marine species, including species consumed by humans.

The quantity and fate of MP particles (> 10 µm) and smaller nanoplastics (< 10 µm) in aquatic environments are poorly understood, but what is most concerning is their ability to cross biologic barriers and the potential harm associated with their mobility in biologic systems.
 

MNP Exposure

MNPs can originate from a wide variety of sources, including food, beverages, and food product packaging. Water bottles represent a significant source of ingestible MNPs for people in their daily lives. Recent estimates, using stimulated Raman scattering imaging, documented a concentration of MNP of approximately 2.4 ± 1.3 × 10⁵ particles per liter of bottled water. Around 90% are nanoplastics, which is two to three orders of magnitude higher than previously reported results for larger MPs.

MNPs enter the body primarily through ingestion or inhalation. For example, MNPs can be ingested by drinking liquids or eating food that has been stored or heated in plastic containers from which they have leaked or by using toothpaste that contains them. Infants are exposed to MPs from artificial milk preparation in polypropylene baby bottles, with higher levels than previously detected and ranging from 14,600 to 4,550,000 particles per capita per day.
 

MNP and Biologic Systems

The possible formation of hetero-aggregates between nanoplastics and natural organic matter has long been recognized as a potential challenge in the analysis of nanoplastics and can influence toxicologic results in biologic exposure. The direct visualization of such hetero-aggregates in real-world samples supports these concerns, but the analysis of MNPs with traditional techniques remains challenging. Unlike engineered nanoparticles (prepared in the laboratory as model systems), the nanoplastics in the environment are label-free and exhibit significant heterogeneity in chemical composition and morphology.

A systematic analysis of evidence on the toxic effects of MNPs on murine models, however, showed that 52.78% of biologic endpoints (related to glucose metabolism, reproduction, oxidative stress, and lipid metabolism) were significantly affected by MNP exposure.
 

Between Risk and Toxicity

MNP can enter the body in vivo through the digestive tract, respiratory tract, and skin contact. On average, humans could ingest from 0.1 to 5 g of MNP per week through various exposure routes.

MNPs are a potential risk factor for cardiovascular diseases, as suggested by a recent study on 257 patients with carotid atheromatous plaques. In 58.4% of cases, polyvinyl chloride was detected in the carotid artery plaque, with an average level of 5.2 ± 2.4 μg/mg of plaque. Patients with MNPs inside the atheroma had a higher risk (relative risk, 4.53) for a composite cardiovascular event of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than participants where MNPs were not detectable inside the atheromatous plaque.

The potential link between inflammatory bowel disease (IBD) and MPs has been hypothesized by a study that reported a higher fecal MP concentration in patients with IBD than in healthy individuals. Fecal MP level was correlated with disease severity.

However, these studies have not demonstrated a causal relationship between MNPs and disease, and the way MNPs may influence cellular functions and induce stress responses is not yet well understood.
 

Future Scenarios

Current evidence confirms the fragmentation of plastic beyond the micrometer level and has unequivocally detected nanoplastics in real samples. As with many other particle distributions of the same size in the natural world, there are substantially more nanoplastics, despite their invisibility with conventional imaging techniques, than particles larger than the micron size.

The initial results of studies on MNPs in humans will stimulate future research on the amounts of MNPs that accumulate in tissue over a person’s lifetime. Researchers also will examine how the particles’ characteristics, including their chemical composition, size, and shape, can influence organs and tissues.

The way MNPs can cause harm, including through effects on the immune system and microbiome, will need to be clarified by investigating possible direct cytotoxic effects, consistent with the introductory statement of the Organization for Economic Cooperation and Development global policy forum on plastics, which states, “Plastic pollution is one of the great environmental challenges of the 21st century, causing wide-ranging damage to ecosystems and human health.”

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

People with HIV who wish to breastfeed their infants should have sustained viral suppression, with a viral load below 50 copies per mL, to have the least risk of transmitting HIV to their baby aside from avoiding breastfeeding altogether, according to a new clinical report from the American Academy of Pediatrics (AAP).

“The risk of HIV transmission via breastfeeding from a parent with HIV who is receiving antiretroviral treatment (ART) and is virally suppressed is estimated to be less than 1%,” Lisa Abuogi, MD, an associate professor of pediatric infectious disease at the University of Colorado Anschutz Medical Campus, and her colleagues wrote in Pediatrics. For people living with HIV in the United States, however, the AAP recommends that “avoidance of breastfeeding is the only infant feeding option with 0% risk of HIV transmission.”

The authors go on to suggest that pediatricians “be prepared to offer a family-centered, nonjudgmental, harm reduction approach” to support people with HIV who do want to breastfeed and have sustained viral suppression. Parents with HIV who are not on ART or who do not have adequate viral suppression should be advised against breastfeeding, the report states. Members of the AAP Committee on Pediatric and Adolescent HIV and of the AAP Section on Breastfeeding coauthored the clinical report.

“The new guidelines emphasize the importance of patient-centered counseling as the foundation for shared decision-making, allowing patients and pediatric providers to make feeding decisions together and for the first time really giving support to people with HIV in the U.S. who want to breastfeed,” Danna Biala, MD, MS, an attending pediatrician at Children’s Hospital at Montefiore and an assistant professor at Albert Einstein College of Medicine, told MDedge News.

Dr. Biala was not involved in the development of the report, but she said the AAP’s guidance reflects the recent shift in the stance of the Centers for Disease Control and Prevention (CDC) regarding breastfeeding among people who are HIV+. Recommendations from the CDC and the U.S. Department of Health and Human Services (HHS) were updated in 2023.

“I’m glad that the AAP is putting out guidelines on infant feeding for people with HIV,” Dr. Biala said. “For so long in the U.S., pediatricians have been advising all mothers with HIV to avoid breastfeeding, believing that the risk of transmission outweighed the benefits of breastfeeding.”

The updated guidance from HHS in 2023 “was revolutionary in supporting people with HIV in low-risk situations who want to breastfeed,” Dr. Biala said, but “clear protocols for monitoring and follow-up were not in place,” which these AAP guidelines help address.
 

Prior Discordance Between Global, U.S. Guidance

An estimated 5,000 people with HIV give birth each year in the United States, and up to one third of pregnant people with HIV may be unaware of their HIV status, the AAP report notes. Pediatric healthcare professionals in the United States therefore need to be aware of recommendations related to HIV testing of pregnant people and of counseling the feeding of infants exposed to HIV. The report recommends opt-out HIV testing at the first prenatal visit and then possibly retesting in the third trimester in areas with high HIV incidence or for people at high risk for HIV or with signs or symptoms of acute HIV infection.

The report also highlights the health benefits of breastfeeding to both the infant and the breastfeeding parent, but notes the CDC’s historical recommendation against breastfeeding for people who are HIV+. The WHO, meanwhile, began recommending in 2016 that infants be breastfed through 12 to 24 months old if the parent was on ART and/or the infant was receiving antiretroviral (ARV) prophylaxis, since research showed those treatments were effective in reducing transmission risk.

Still, an estimated 30% of perinatal HIV transmission occurs via breastfeeding worldwide, primarily from people with HIV who are not on ART or are not adequately virally suppressed. Without parental ART or infant ARV prophylaxis, HIV transmission risk to infants via breastfeeding is highest, about 5%-6%, in the first 4-6 weeks of life. Risk then declines to about 0.9% a month thereafter. The AAP report goes on to describe factors that increase or decrease the likelihood of transmission during breastfeeding, but it notes that neither ART in the breastfeeding person nor ARV prophylaxis in the infant completely eliminates the risk of HIV transmission during breastfeeding. There have been rare cases where transmission occurred despite viral suppression in the person with HIV.

Among the reasons people with HIV have expressed a desire to breastfeed are wanting to bond with their infant, wanting to provide optimal nutrition and health benefits to their baby, and meeting cultural expectations, including the desire not to disclose their HIV infection status to family or friends by virtue of not breastfeeding.

“Among immigrant and refugee populations, the discordance between infant feeding guidelines in the United States and their country of birth may result in confusion, especially among parents who breastfed previous infants,” the AAP report also notes. Further, not breastfeeding could compound health disparities already more likely to be present among those living with HIV.

Discussions about infant feeding with parents with HIV should therefore “begin as early as possible and involve a multidisciplinary team that might include the pediatric primary care provider (once identified), a pediatric HIV expert, the breastfeeding parent’s HIV care and obstetric providers, and lactation consultants,” the report states. ”The parent’s motivations for breastfeeding should be explored and counseling provided on the risks and benefits of each feeding option, including breastfeeding, formula feeding, or certified, banked donor human milk.” The statement emphasizes the need for providing counseling in a “non-judgmental, respectful way, recognizing potential drivers for their decisions such as avoidance of stigma, prior experience with breastfeeding, and cultural contributors.”
 

Clear Recommendations Can Help Providers

The AAP’s statement that “replacement feeding (with formula or certified, banked donor human milk) is the only option that is 100% certain to prevent postnatal transmission of HIV” feels like it takes a “more conservative or discouraging approach” to breastfeeding than the CDC or WHO guidelines, Alissa Parker-Smith, APRN, DNP, CPNP-PC, IBCLC, a nurse practitioner and lactation consultant at PrimaryPlus, a Federally Qualified Health Clinic in Ashland, Kentucky, told MDedge. But she said they do clearly align with the CDC guidelines, and their differences from the WHO guidelines make sense in light of the different populations served by the WHO versus the U.S. agencies.

“Unclean water for formula preparation and a reduced or lack of access to formula in general can lead to many other risks of death for the infant other than the very small risk of HIV infection from breastfeeding from an HIV+ parent,” Ms. Parker-Smith said. “In the U.S. we generally have consistent access to clean water and safe formula as well as social structures to help families have access to formula, so the very small risk of HIV being passed to the infant is far greater than an infant in the U.S. dying as a result of unclean water or formula contamination.”

Ms. Parker-Smith also said the AAP recommendations seem thorough in helping pediatric practitioners counsel and support parents with HIV. “If I had a parent who is HIV+ walk in the door today wanting to breastfeed their infant, the AAP guidelines give me specific steps to make me feel confident in helping that parent breastfeed as safely as possible as well as providing education to assist that parent through the decision process,” she said.

Dr. Biala agreed, noting that the clinical report “very clearly delineates recommendations for different groups of people: those in labor or postpartum with undocumented HIV infection status, pregnant and postpartum people with HIV, those without HIV but at high risk of acquiring it, and those with suspected acute HIV infection while breastfeeding.” Dr. Biala said the report “provides concrete, detailed, and easy-to-follow guidance on comprehensive counseling, strategies to minimize risk of transmission, and infant screening timelines.”

How easily the guidelines can be implemented will depend on the existing resources at different institutions in the United States, Dr. Biala added.

“In hospitals and clinics that have, or could easily have, systems in place to ensure follow-up and regular assessment during breastfeeding, the guidelines could be implemented fairly quickly,” she said. “It might be more challenging in areas with inadequate or limited access to multidisciplinary team members, including HIV care providers and lactation consultants.”

The report did not use external funding, and the authors reported no disclosures. Dr. Abuogi and Ms. Parker-Smith have no disclosures.

People with HIV who wish to breastfeed their infants should have sustained viral suppression, with a viral load below 50 copies per mL, to have the least risk of transmitting HIV to their baby aside from avoiding breastfeeding altogether, according to a new clinical report from the American Academy of Pediatrics (AAP).

“The risk of HIV transmission via breastfeeding from a parent with HIV who is receiving antiretroviral treatment (ART) and is virally suppressed is estimated to be less than 1%,” Lisa Abuogi, MD, an associate professor of pediatric infectious disease at the University of Colorado Anschutz Medical Campus, and her colleagues wrote in Pediatrics. For people living with HIV in the United States, however, the AAP recommends that “avoidance of breastfeeding is the only infant feeding option with 0% risk of HIV transmission.”

The authors go on to suggest that pediatricians “be prepared to offer a family-centered, nonjudgmental, harm reduction approach” to support people with HIV who do want to breastfeed and have sustained viral suppression. Parents with HIV who are not on ART or who do not have adequate viral suppression should be advised against breastfeeding, the report states. Members of the AAP Committee on Pediatric and Adolescent HIV and of the AAP Section on Breastfeeding coauthored the clinical report.

“The new guidelines emphasize the importance of patient-centered counseling as the foundation for shared decision-making, allowing patients and pediatric providers to make feeding decisions together and for the first time really giving support to people with HIV in the U.S. who want to breastfeed,” Danna Biala, MD, MS, an attending pediatrician at Children’s Hospital at Montefiore and an assistant professor at Albert Einstein College of Medicine, told MDedge News.

Dr. Biala was not involved in the development of the report, but she said the AAP’s guidance reflects the recent shift in the stance of the Centers for Disease Control and Prevention (CDC) regarding breastfeeding among people who are HIV+. Recommendations from the CDC and the U.S. Department of Health and Human Services (HHS) were updated in 2023.

“I’m glad that the AAP is putting out guidelines on infant feeding for people with HIV,” Dr. Biala said. “For so long in the U.S., pediatricians have been advising all mothers with HIV to avoid breastfeeding, believing that the risk of transmission outweighed the benefits of breastfeeding.”

The updated guidance from HHS in 2023 “was revolutionary in supporting people with HIV in low-risk situations who want to breastfeed,” Dr. Biala said, but “clear protocols for monitoring and follow-up were not in place,” which these AAP guidelines help address.
 

Prior Discordance Between Global, U.S. Guidance

An estimated 5,000 people with HIV give birth each year in the United States, and up to one third of pregnant people with HIV may be unaware of their HIV status, the AAP report notes. Pediatric healthcare professionals in the United States therefore need to be aware of recommendations related to HIV testing of pregnant people and of counseling the feeding of infants exposed to HIV. The report recommends opt-out HIV testing at the first prenatal visit and then possibly retesting in the third trimester in areas with high HIV incidence or for people at high risk for HIV or with signs or symptoms of acute HIV infection.

The report also highlights the health benefits of breastfeeding to both the infant and the breastfeeding parent, but notes the CDC’s historical recommendation against breastfeeding for people who are HIV+. The WHO, meanwhile, began recommending in 2016 that infants be breastfed through 12 to 24 months old if the parent was on ART and/or the infant was receiving antiretroviral (ARV) prophylaxis, since research showed those treatments were effective in reducing transmission risk.

Still, an estimated 30% of perinatal HIV transmission occurs via breastfeeding worldwide, primarily from people with HIV who are not on ART or are not adequately virally suppressed. Without parental ART or infant ARV prophylaxis, HIV transmission risk to infants via breastfeeding is highest, about 5%-6%, in the first 4-6 weeks of life. Risk then declines to about 0.9% a month thereafter. The AAP report goes on to describe factors that increase or decrease the likelihood of transmission during breastfeeding, but it notes that neither ART in the breastfeeding person nor ARV prophylaxis in the infant completely eliminates the risk of HIV transmission during breastfeeding. There have been rare cases where transmission occurred despite viral suppression in the person with HIV.

Among the reasons people with HIV have expressed a desire to breastfeed are wanting to bond with their infant, wanting to provide optimal nutrition and health benefits to their baby, and meeting cultural expectations, including the desire not to disclose their HIV infection status to family or friends by virtue of not breastfeeding.

“Among immigrant and refugee populations, the discordance between infant feeding guidelines in the United States and their country of birth may result in confusion, especially among parents who breastfed previous infants,” the AAP report also notes. Further, not breastfeeding could compound health disparities already more likely to be present among those living with HIV.

Discussions about infant feeding with parents with HIV should therefore “begin as early as possible and involve a multidisciplinary team that might include the pediatric primary care provider (once identified), a pediatric HIV expert, the breastfeeding parent’s HIV care and obstetric providers, and lactation consultants,” the report states. ”The parent’s motivations for breastfeeding should be explored and counseling provided on the risks and benefits of each feeding option, including breastfeeding, formula feeding, or certified, banked donor human milk.” The statement emphasizes the need for providing counseling in a “non-judgmental, respectful way, recognizing potential drivers for their decisions such as avoidance of stigma, prior experience with breastfeeding, and cultural contributors.”
 

Clear Recommendations Can Help Providers

The AAP’s statement that “replacement feeding (with formula or certified, banked donor human milk) is the only option that is 100% certain to prevent postnatal transmission of HIV” feels like it takes a “more conservative or discouraging approach” to breastfeeding than the CDC or WHO guidelines, Alissa Parker-Smith, APRN, DNP, CPNP-PC, IBCLC, a nurse practitioner and lactation consultant at PrimaryPlus, a Federally Qualified Health Clinic in Ashland, Kentucky, told MDedge. But she said they do clearly align with the CDC guidelines, and their differences from the WHO guidelines make sense in light of the different populations served by the WHO versus the U.S. agencies.

“Unclean water for formula preparation and a reduced or lack of access to formula in general can lead to many other risks of death for the infant other than the very small risk of HIV infection from breastfeeding from an HIV+ parent,” Ms. Parker-Smith said. “In the U.S. we generally have consistent access to clean water and safe formula as well as social structures to help families have access to formula, so the very small risk of HIV being passed to the infant is far greater than an infant in the U.S. dying as a result of unclean water or formula contamination.”

Ms. Parker-Smith also said the AAP recommendations seem thorough in helping pediatric practitioners counsel and support parents with HIV. “If I had a parent who is HIV+ walk in the door today wanting to breastfeed their infant, the AAP guidelines give me specific steps to make me feel confident in helping that parent breastfeed as safely as possible as well as providing education to assist that parent through the decision process,” she said.

Dr. Biala agreed, noting that the clinical report “very clearly delineates recommendations for different groups of people: those in labor or postpartum with undocumented HIV infection status, pregnant and postpartum people with HIV, those without HIV but at high risk of acquiring it, and those with suspected acute HIV infection while breastfeeding.” Dr. Biala said the report “provides concrete, detailed, and easy-to-follow guidance on comprehensive counseling, strategies to minimize risk of transmission, and infant screening timelines.”

How easily the guidelines can be implemented will depend on the existing resources at different institutions in the United States, Dr. Biala added.

“In hospitals and clinics that have, or could easily have, systems in place to ensure follow-up and regular assessment during breastfeeding, the guidelines could be implemented fairly quickly,” she said. “It might be more challenging in areas with inadequate or limited access to multidisciplinary team members, including HIV care providers and lactation consultants.”

The report did not use external funding, and the authors reported no disclosures. Dr. Abuogi and Ms. Parker-Smith have no disclosures.

People with HIV who wish to breastfeed their infants should have sustained viral suppression, with a viral load below 50 copies per mL, to have the least risk of transmitting HIV to their baby aside from avoiding breastfeeding altogether, according to a new clinical report from the American Academy of Pediatrics (AAP).

“The risk of HIV transmission via breastfeeding from a parent with HIV who is receiving antiretroviral treatment (ART) and is virally suppressed is estimated to be less than 1%,” Lisa Abuogi, MD, an associate professor of pediatric infectious disease at the University of Colorado Anschutz Medical Campus, and her colleagues wrote in Pediatrics. For people living with HIV in the United States, however, the AAP recommends that “avoidance of breastfeeding is the only infant feeding option with 0% risk of HIV transmission.”

The authors go on to suggest that pediatricians “be prepared to offer a family-centered, nonjudgmental, harm reduction approach” to support people with HIV who do want to breastfeed and have sustained viral suppression. Parents with HIV who are not on ART or who do not have adequate viral suppression should be advised against breastfeeding, the report states. Members of the AAP Committee on Pediatric and Adolescent HIV and of the AAP Section on Breastfeeding coauthored the clinical report.

“The new guidelines emphasize the importance of patient-centered counseling as the foundation for shared decision-making, allowing patients and pediatric providers to make feeding decisions together and for the first time really giving support to people with HIV in the U.S. who want to breastfeed,” Danna Biala, MD, MS, an attending pediatrician at Children’s Hospital at Montefiore and an assistant professor at Albert Einstein College of Medicine, told MDedge News.

Dr. Biala was not involved in the development of the report, but she said the AAP’s guidance reflects the recent shift in the stance of the Centers for Disease Control and Prevention (CDC) regarding breastfeeding among people who are HIV+. Recommendations from the CDC and the U.S. Department of Health and Human Services (HHS) were updated in 2023.

“I’m glad that the AAP is putting out guidelines on infant feeding for people with HIV,” Dr. Biala said. “For so long in the U.S., pediatricians have been advising all mothers with HIV to avoid breastfeeding, believing that the risk of transmission outweighed the benefits of breastfeeding.”

The updated guidance from HHS in 2023 “was revolutionary in supporting people with HIV in low-risk situations who want to breastfeed,” Dr. Biala said, but “clear protocols for monitoring and follow-up were not in place,” which these AAP guidelines help address.
 

Prior Discordance Between Global, U.S. Guidance

An estimated 5,000 people with HIV give birth each year in the United States, and up to one third of pregnant people with HIV may be unaware of their HIV status, the AAP report notes. Pediatric healthcare professionals in the United States therefore need to be aware of recommendations related to HIV testing of pregnant people and of counseling the feeding of infants exposed to HIV. The report recommends opt-out HIV testing at the first prenatal visit and then possibly retesting in the third trimester in areas with high HIV incidence or for people at high risk for HIV or with signs or symptoms of acute HIV infection.

The report also highlights the health benefits of breastfeeding to both the infant and the breastfeeding parent, but notes the CDC’s historical recommendation against breastfeeding for people who are HIV+. The WHO, meanwhile, began recommending in 2016 that infants be breastfed through 12 to 24 months old if the parent was on ART and/or the infant was receiving antiretroviral (ARV) prophylaxis, since research showed those treatments were effective in reducing transmission risk.

Still, an estimated 30% of perinatal HIV transmission occurs via breastfeeding worldwide, primarily from people with HIV who are not on ART or are not adequately virally suppressed. Without parental ART or infant ARV prophylaxis, HIV transmission risk to infants via breastfeeding is highest, about 5%-6%, in the first 4-6 weeks of life. Risk then declines to about 0.9% a month thereafter. The AAP report goes on to describe factors that increase or decrease the likelihood of transmission during breastfeeding, but it notes that neither ART in the breastfeeding person nor ARV prophylaxis in the infant completely eliminates the risk of HIV transmission during breastfeeding. There have been rare cases where transmission occurred despite viral suppression in the person with HIV.

Among the reasons people with HIV have expressed a desire to breastfeed are wanting to bond with their infant, wanting to provide optimal nutrition and health benefits to their baby, and meeting cultural expectations, including the desire not to disclose their HIV infection status to family or friends by virtue of not breastfeeding.

“Among immigrant and refugee populations, the discordance between infant feeding guidelines in the United States and their country of birth may result in confusion, especially among parents who breastfed previous infants,” the AAP report also notes. Further, not breastfeeding could compound health disparities already more likely to be present among those living with HIV.

Discussions about infant feeding with parents with HIV should therefore “begin as early as possible and involve a multidisciplinary team that might include the pediatric primary care provider (once identified), a pediatric HIV expert, the breastfeeding parent’s HIV care and obstetric providers, and lactation consultants,” the report states. ”The parent’s motivations for breastfeeding should be explored and counseling provided on the risks and benefits of each feeding option, including breastfeeding, formula feeding, or certified, banked donor human milk.” The statement emphasizes the need for providing counseling in a “non-judgmental, respectful way, recognizing potential drivers for their decisions such as avoidance of stigma, prior experience with breastfeeding, and cultural contributors.”
 

Clear Recommendations Can Help Providers

The AAP’s statement that “replacement feeding (with formula or certified, banked donor human milk) is the only option that is 100% certain to prevent postnatal transmission of HIV” feels like it takes a “more conservative or discouraging approach” to breastfeeding than the CDC or WHO guidelines, Alissa Parker-Smith, APRN, DNP, CPNP-PC, IBCLC, a nurse practitioner and lactation consultant at PrimaryPlus, a Federally Qualified Health Clinic in Ashland, Kentucky, told MDedge. But she said they do clearly align with the CDC guidelines, and their differences from the WHO guidelines make sense in light of the different populations served by the WHO versus the U.S. agencies.

“Unclean water for formula preparation and a reduced or lack of access to formula in general can lead to many other risks of death for the infant other than the very small risk of HIV infection from breastfeeding from an HIV+ parent,” Ms. Parker-Smith said. “In the U.S. we generally have consistent access to clean water and safe formula as well as social structures to help families have access to formula, so the very small risk of HIV being passed to the infant is far greater than an infant in the U.S. dying as a result of unclean water or formula contamination.”

Ms. Parker-Smith also said the AAP recommendations seem thorough in helping pediatric practitioners counsel and support parents with HIV. “If I had a parent who is HIV+ walk in the door today wanting to breastfeed their infant, the AAP guidelines give me specific steps to make me feel confident in helping that parent breastfeed as safely as possible as well as providing education to assist that parent through the decision process,” she said.

Dr. Biala agreed, noting that the clinical report “very clearly delineates recommendations for different groups of people: those in labor or postpartum with undocumented HIV infection status, pregnant and postpartum people with HIV, those without HIV but at high risk of acquiring it, and those with suspected acute HIV infection while breastfeeding.” Dr. Biala said the report “provides concrete, detailed, and easy-to-follow guidance on comprehensive counseling, strategies to minimize risk of transmission, and infant screening timelines.”

How easily the guidelines can be implemented will depend on the existing resources at different institutions in the United States, Dr. Biala added.

“In hospitals and clinics that have, or could easily have, systems in place to ensure follow-up and regular assessment during breastfeeding, the guidelines could be implemented fairly quickly,” she said. “It might be more challenging in areas with inadequate or limited access to multidisciplinary team members, including HIV care providers and lactation consultants.”

The report did not use external funding, and the authors reported no disclosures. Dr. Abuogi and Ms. Parker-Smith have no disclosures.

The combination of atezolizumab plus sacituzumab govitecan as first-line treatment showed encouraging anti-tumor activity in previously untreated patients with triple-negative breast cancer (TNBC), in an ongoing phase 1b/2 trial.

MORPHEUS-pan BC (NCT03424005) is evaluating multiple treatment combinations in patients with locally advanced or metastatic TNBC.

The trial’s interim clinical data was presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Rationale for Combining Antibody-Drug Conjugates with Immunotherapy

Peter Schmid, MD, PhD, professor at the Centre for Experimental Cancer Medicine in London, England, presented interim findings from one study arm of MORPHEUS-pan BC at the meeting. The arm consisted of patients with TNBC who were treated with a combination of atezolizumab, a PD-L1 inhibitor, and sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein commonly expressed in TNBC.

TNBC is one of the most challenging subtypes of breast cancer to treat because of its aggressive characteristics and innate resistance to hormonal therapy and HER2-targeted treatments. However, the recent approval of immunotherapy for TNBC has provided renewed hope for patients, according to Dr. Schmid.

Atezolizumab, in combination with nab-paclitaxel, has already been approved as a first-line treatment for PD-L1–positive, unresectable locally advanced or metastatic TNBC; however, not all patients respond to this combination treatment. Sacituzumab govitecan is approved for second-line and subsequent-line treatment of metastatic TNBC.

“Cancer immunotherapy in combination with chemotherapy has transformed the TNBC treatment landscape, but new combinations are needed to further improve survival outcomes,” Dr. Schmid said during his presentation. “We hoped that combining immunotherapy with an antibody-drug conjugate would not only improve safety but also increase efficacy through enhanced immune activation.”
 

Study Design

The MORPHEUS-pan BC trial enrolled patients with previously untreated, PD-L1–positive, inoperable, locally advanced or metastatic TNBC. Patients were randomized to receive experimental treatment consisting of atezolizumab plus the antibody-drug conjugate sacituzumab govitecan. Patients in the second arm received a control regimen of atezolizumab plus nab-paclitaxel chemotherapy.

“The control regimen is part of the current standard of care for patients with PD-L1–positive TNBC,” Dr. Schmid explained in his presentation. As of the data cut-off, 11 patients were enrolled in the control arm and 31 in the atezolizumab plus sacituzumab govitecan arm.

During the discussion session after his talk, Dr. Schmid commented on the use of PD-L1 expression to select patients for enrollment, acknowledging that PD-L1 is not the best biomarker.

“Its expression is very dynamic and can change rapidly,” he said. He added, however, that it is currently the most suitable biomarker for patient selection for treatment with anti–PD-1/PD-L1 agents.

Sara M. Tolaney, MD, MPH, added that, because patients were selected based on PD-L1 expression, it is unclear whether this combination therapy would show anti-tumor activity in patients with PD-L1–negative tumors. Dr. Tolaney, a medical oncologist at the Dana-Farber Cancer Institute who was not involved in the study, served as a discussant, providing her expert opinion on the findings presented by Dr. Schmid.
 

Promising Anti-tumor Activity

The combination of atezolizumab and sacituzumab govitecan demonstrated promising anti-tumor activity as initial treatment for this patient population. The interim analysis at 18 weeks showed an objective response rate of 76.7% (95% CI, 57.7-90.1; n = 23, including five complete responses) in the atezolizumab plus sacituzumab govitecan arm, versus 66.7% (95% CI, 29.9-92.5; n = 6, all of which were partial responses) in the control arm.

“The 66% response rate in the control arm aligns with what we see in historical data from patients treated with immunotherapy plus chemotherapy,” noted Dr. Schmid during his talk.

The clinical benefit rate, which includes complete and partial responses as well as stable disease, was also encouraging at 83.3% (95% CI, 65.3-94.4) with the dual immunotherapy regimen versus 66.7% (95% CI, 29.9-92.5) with standard therapy.

Commenting on the potential mechanisms of the synergistic effect of this combination therapy, Dr. Tolaney said, “In addition to delivering chemotherapy payloads to cancer cells, antibody-drug conjugates can lead to dendritic cell activation, T-cell activation, and immune cell infiltration.”

She added that antibody-drug conjugates can cause Fc activation in NK cells, thereby enhancing antibody-dependent cytotoxicity.
 

Encouraging survival trends

Interim survival data showed trends favoring atezolizumab plus sacituzumab govitecan over the control arm of atezolizumab plus nab-paclitaxel chemotherapy. The median progression-free survival (PFS) was 12.2 months (95% CI, 7.4-not estimable) in the immunotherapy combination group versus 5.9 months (95% CI, 4.1-8.7) in the control group, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.70). The overall survival data are still immature.

During the discussion session, Dr. Schmid cautioned that, although the benefit of this combination therapy in terms of PFS seems promising, the validity of the hazard ratio is limited because of the small cohort size. He added, “The survival data is still immature, and longer follow-up is needed.”

These encouraging response and PFS rates need to be confirmed in larger studies of this immunotherapy combination as a potential new first-line standard for PD-L1–positive TNBC, according to Dr. Schmid.
 

Relationship between biomarker expression and response

The MORPHEUS-pan BC trial enrolled only patients with PD-L1–positive tumors at baseline, defined as PD-L1 expression in at least 1% of immune cells infiltrating the tumor. Tumors at baseline were also tested for Trop-2 expression, CD8 immune phenotype, and stromal tumor-infiltrating lymphocytes (TILs).

“We wanted to get an idea of whether these biomarkers are associated with treatment response,” Dr. Schmid explained during his talk.

Although the benefit of sacituzumab govitecan treatment was observed across all Trop-2 expression levels, preliminary analyses suggest that high Trop-2 expression, CD8 immune phenotype, and stromal TILs may be associated with response to atezolizumab plus sacituzumab govitecan. However, Dr. Schmid noted that validation of these associations in larger cohorts is required.
 

Safety of combination treatment

The side effect profile of atezolizumab plus sacituzumab govitecan appeared consistent with that expected from the two individual drugs, with no new toxicity signals.

All patients in both treatment arms experienced at least one adverse event; however, there were no fatal adverse events. Grade 3-4 adverse events were more common in the experimental arm (70.0%) than in the control arm (44.4%), while serious adverse events were more common in the control group (44.4% versus 23.3%). Immune-related adverse events were considerably more common in the atezolizumab plus sacituzumab govitecan group than in the control group (80.0% versus 55.6%).

The most common adverse events in patients treated with atezolizumab plus sacituzumab govitecan were nausea, alopecia, diarrhea, and neutropenia. Dr. Schmid emphasized in his presentation that this toxicity profile was dominated by adverse events that are common in patients treated with chemotherapy.

“These safety data are significant as they suggest that the combination therapy does not introduce additional risks beyond those already associated with each drug,” he added.
 

Looking Ahead

Dr. Tolaney highlighted that the cohort size of this study was small and the follow-up time was insufficient to draw conclusions about survival outcomes. Larger studies with long-term follow-up are needed to confirm the efficacy of first-line atezolizumab plus sacituzumab govitecan, she said.

“While this was a small study, the response data is very intriguing, with 17% of patients experiencing complete responses. The PFS data are also impressive, and there seems to be an interesting trend towards better response in patients with high Trop-2 expression and those with high levels of stromal TILs,” she added.

Dr. Tolaney also noted that the response rates and PFS data presented are similar to those of one of the treatment arms in the BEGONIA trial (NCT03742102), which investigated different combinations of immunotherapy in patients with metastatic TNBC. Like MORPHEUS-pan BC (NCT03424005), this study evaluated the efficacy of a different antibody-drug conjugate with chemotherapy. Patients in the study arm of the BEGONIA trial she was referring to received durvalumab (an anti-PD-L1 agent) and datopotamab deruxtecan (an antibody-drug conjugate).

Dr. Schmid said that biomarker analyses are ongoing to assess whether there is a correlation between Trop-2 expression levels and the benefits of sacituzumab govitecan. Studies are also needed to determine whether this combination can improve pathologic complete response rates in early-stage TNBC.

Dr. Tolaney echoed the importance of evaluating the efficacy of antibody-drug conjugates plus immune checkpoint inhibitors in different settings, including patients with PD-L1–negative or immunologically cold tumors and those with early-stage disease. “Ultimately, we want this combination treatment to move forward to early-stage TNBC to see if we could cure more patients,” she said, during the discussion.

Dr. Schmid reported financial relationships with Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (consulting or advisory roles); Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (honoraria); and AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas, and Medivation (research funding). Dr. Tolaney reported financial relationships with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., Beyond Spring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, and Jazz Pharmaceuticals (consulting or advisory roles); Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics (research funding).

The combination of atezolizumab plus sacituzumab govitecan as first-line treatment showed encouraging anti-tumor activity in previously untreated patients with triple-negative breast cancer (TNBC), in an ongoing phase 1b/2 trial.

MORPHEUS-pan BC (NCT03424005) is evaluating multiple treatment combinations in patients with locally advanced or metastatic TNBC.

The trial’s interim clinical data was presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Rationale for Combining Antibody-Drug Conjugates with Immunotherapy

Peter Schmid, MD, PhD, professor at the Centre for Experimental Cancer Medicine in London, England, presented interim findings from one study arm of MORPHEUS-pan BC at the meeting. The arm consisted of patients with TNBC who were treated with a combination of atezolizumab, a PD-L1 inhibitor, and sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein commonly expressed in TNBC.

TNBC is one of the most challenging subtypes of breast cancer to treat because of its aggressive characteristics and innate resistance to hormonal therapy and HER2-targeted treatments. However, the recent approval of immunotherapy for TNBC has provided renewed hope for patients, according to Dr. Schmid.

Atezolizumab, in combination with nab-paclitaxel, has already been approved as a first-line treatment for PD-L1–positive, unresectable locally advanced or metastatic TNBC; however, not all patients respond to this combination treatment. Sacituzumab govitecan is approved for second-line and subsequent-line treatment of metastatic TNBC.

“Cancer immunotherapy in combination with chemotherapy has transformed the TNBC treatment landscape, but new combinations are needed to further improve survival outcomes,” Dr. Schmid said during his presentation. “We hoped that combining immunotherapy with an antibody-drug conjugate would not only improve safety but also increase efficacy through enhanced immune activation.”
 

Study Design

The MORPHEUS-pan BC trial enrolled patients with previously untreated, PD-L1–positive, inoperable, locally advanced or metastatic TNBC. Patients were randomized to receive experimental treatment consisting of atezolizumab plus the antibody-drug conjugate sacituzumab govitecan. Patients in the second arm received a control regimen of atezolizumab plus nab-paclitaxel chemotherapy.

“The control regimen is part of the current standard of care for patients with PD-L1–positive TNBC,” Dr. Schmid explained in his presentation. As of the data cut-off, 11 patients were enrolled in the control arm and 31 in the atezolizumab plus sacituzumab govitecan arm.

During the discussion session after his talk, Dr. Schmid commented on the use of PD-L1 expression to select patients for enrollment, acknowledging that PD-L1 is not the best biomarker.

“Its expression is very dynamic and can change rapidly,” he said. He added, however, that it is currently the most suitable biomarker for patient selection for treatment with anti–PD-1/PD-L1 agents.

Sara M. Tolaney, MD, MPH, added that, because patients were selected based on PD-L1 expression, it is unclear whether this combination therapy would show anti-tumor activity in patients with PD-L1–negative tumors. Dr. Tolaney, a medical oncologist at the Dana-Farber Cancer Institute who was not involved in the study, served as a discussant, providing her expert opinion on the findings presented by Dr. Schmid.
 

Promising Anti-tumor Activity

The combination of atezolizumab and sacituzumab govitecan demonstrated promising anti-tumor activity as initial treatment for this patient population. The interim analysis at 18 weeks showed an objective response rate of 76.7% (95% CI, 57.7-90.1; n = 23, including five complete responses) in the atezolizumab plus sacituzumab govitecan arm, versus 66.7% (95% CI, 29.9-92.5; n = 6, all of which were partial responses) in the control arm.

“The 66% response rate in the control arm aligns with what we see in historical data from patients treated with immunotherapy plus chemotherapy,” noted Dr. Schmid during his talk.

The clinical benefit rate, which includes complete and partial responses as well as stable disease, was also encouraging at 83.3% (95% CI, 65.3-94.4) with the dual immunotherapy regimen versus 66.7% (95% CI, 29.9-92.5) with standard therapy.

Commenting on the potential mechanisms of the synergistic effect of this combination therapy, Dr. Tolaney said, “In addition to delivering chemotherapy payloads to cancer cells, antibody-drug conjugates can lead to dendritic cell activation, T-cell activation, and immune cell infiltration.”

She added that antibody-drug conjugates can cause Fc activation in NK cells, thereby enhancing antibody-dependent cytotoxicity.
 

Encouraging survival trends

Interim survival data showed trends favoring atezolizumab plus sacituzumab govitecan over the control arm of atezolizumab plus nab-paclitaxel chemotherapy. The median progression-free survival (PFS) was 12.2 months (95% CI, 7.4-not estimable) in the immunotherapy combination group versus 5.9 months (95% CI, 4.1-8.7) in the control group, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.70). The overall survival data are still immature.

During the discussion session, Dr. Schmid cautioned that, although the benefit of this combination therapy in terms of PFS seems promising, the validity of the hazard ratio is limited because of the small cohort size. He added, “The survival data is still immature, and longer follow-up is needed.”

These encouraging response and PFS rates need to be confirmed in larger studies of this immunotherapy combination as a potential new first-line standard for PD-L1–positive TNBC, according to Dr. Schmid.
 

Relationship between biomarker expression and response

The MORPHEUS-pan BC trial enrolled only patients with PD-L1–positive tumors at baseline, defined as PD-L1 expression in at least 1% of immune cells infiltrating the tumor. Tumors at baseline were also tested for Trop-2 expression, CD8 immune phenotype, and stromal tumor-infiltrating lymphocytes (TILs).

“We wanted to get an idea of whether these biomarkers are associated with treatment response,” Dr. Schmid explained during his talk.

Although the benefit of sacituzumab govitecan treatment was observed across all Trop-2 expression levels, preliminary analyses suggest that high Trop-2 expression, CD8 immune phenotype, and stromal TILs may be associated with response to atezolizumab plus sacituzumab govitecan. However, Dr. Schmid noted that validation of these associations in larger cohorts is required.
 

Safety of combination treatment

The side effect profile of atezolizumab plus sacituzumab govitecan appeared consistent with that expected from the two individual drugs, with no new toxicity signals.

All patients in both treatment arms experienced at least one adverse event; however, there were no fatal adverse events. Grade 3-4 adverse events were more common in the experimental arm (70.0%) than in the control arm (44.4%), while serious adverse events were more common in the control group (44.4% versus 23.3%). Immune-related adverse events were considerably more common in the atezolizumab plus sacituzumab govitecan group than in the control group (80.0% versus 55.6%).

The most common adverse events in patients treated with atezolizumab plus sacituzumab govitecan were nausea, alopecia, diarrhea, and neutropenia. Dr. Schmid emphasized in his presentation that this toxicity profile was dominated by adverse events that are common in patients treated with chemotherapy.

“These safety data are significant as they suggest that the combination therapy does not introduce additional risks beyond those already associated with each drug,” he added.
 

Looking Ahead

Dr. Tolaney highlighted that the cohort size of this study was small and the follow-up time was insufficient to draw conclusions about survival outcomes. Larger studies with long-term follow-up are needed to confirm the efficacy of first-line atezolizumab plus sacituzumab govitecan, she said.

“While this was a small study, the response data is very intriguing, with 17% of patients experiencing complete responses. The PFS data are also impressive, and there seems to be an interesting trend towards better response in patients with high Trop-2 expression and those with high levels of stromal TILs,” she added.

Dr. Tolaney also noted that the response rates and PFS data presented are similar to those of one of the treatment arms in the BEGONIA trial (NCT03742102), which investigated different combinations of immunotherapy in patients with metastatic TNBC. Like MORPHEUS-pan BC (NCT03424005), this study evaluated the efficacy of a different antibody-drug conjugate with chemotherapy. Patients in the study arm of the BEGONIA trial she was referring to received durvalumab (an anti-PD-L1 agent) and datopotamab deruxtecan (an antibody-drug conjugate).

Dr. Schmid said that biomarker analyses are ongoing to assess whether there is a correlation between Trop-2 expression levels and the benefits of sacituzumab govitecan. Studies are also needed to determine whether this combination can improve pathologic complete response rates in early-stage TNBC.

Dr. Tolaney echoed the importance of evaluating the efficacy of antibody-drug conjugates plus immune checkpoint inhibitors in different settings, including patients with PD-L1–negative or immunologically cold tumors and those with early-stage disease. “Ultimately, we want this combination treatment to move forward to early-stage TNBC to see if we could cure more patients,” she said, during the discussion.

Dr. Schmid reported financial relationships with Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (consulting or advisory roles); Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (honoraria); and AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas, and Medivation (research funding). Dr. Tolaney reported financial relationships with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., Beyond Spring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, and Jazz Pharmaceuticals (consulting or advisory roles); Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics (research funding).

The combination of atezolizumab plus sacituzumab govitecan as first-line treatment showed encouraging anti-tumor activity in previously untreated patients with triple-negative breast cancer (TNBC), in an ongoing phase 1b/2 trial.

MORPHEUS-pan BC (NCT03424005) is evaluating multiple treatment combinations in patients with locally advanced or metastatic TNBC.

The trial’s interim clinical data was presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Rationale for Combining Antibody-Drug Conjugates with Immunotherapy

Peter Schmid, MD, PhD, professor at the Centre for Experimental Cancer Medicine in London, England, presented interim findings from one study arm of MORPHEUS-pan BC at the meeting. The arm consisted of patients with TNBC who were treated with a combination of atezolizumab, a PD-L1 inhibitor, and sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein commonly expressed in TNBC.

TNBC is one of the most challenging subtypes of breast cancer to treat because of its aggressive characteristics and innate resistance to hormonal therapy and HER2-targeted treatments. However, the recent approval of immunotherapy for TNBC has provided renewed hope for patients, according to Dr. Schmid.

Atezolizumab, in combination with nab-paclitaxel, has already been approved as a first-line treatment for PD-L1–positive, unresectable locally advanced or metastatic TNBC; however, not all patients respond to this combination treatment. Sacituzumab govitecan is approved for second-line and subsequent-line treatment of metastatic TNBC.

“Cancer immunotherapy in combination with chemotherapy has transformed the TNBC treatment landscape, but new combinations are needed to further improve survival outcomes,” Dr. Schmid said during his presentation. “We hoped that combining immunotherapy with an antibody-drug conjugate would not only improve safety but also increase efficacy through enhanced immune activation.”
 

Study Design

The MORPHEUS-pan BC trial enrolled patients with previously untreated, PD-L1–positive, inoperable, locally advanced or metastatic TNBC. Patients were randomized to receive experimental treatment consisting of atezolizumab plus the antibody-drug conjugate sacituzumab govitecan. Patients in the second arm received a control regimen of atezolizumab plus nab-paclitaxel chemotherapy.

“The control regimen is part of the current standard of care for patients with PD-L1–positive TNBC,” Dr. Schmid explained in his presentation. As of the data cut-off, 11 patients were enrolled in the control arm and 31 in the atezolizumab plus sacituzumab govitecan arm.

During the discussion session after his talk, Dr. Schmid commented on the use of PD-L1 expression to select patients for enrollment, acknowledging that PD-L1 is not the best biomarker.

“Its expression is very dynamic and can change rapidly,” he said. He added, however, that it is currently the most suitable biomarker for patient selection for treatment with anti–PD-1/PD-L1 agents.

Sara M. Tolaney, MD, MPH, added that, because patients were selected based on PD-L1 expression, it is unclear whether this combination therapy would show anti-tumor activity in patients with PD-L1–negative tumors. Dr. Tolaney, a medical oncologist at the Dana-Farber Cancer Institute who was not involved in the study, served as a discussant, providing her expert opinion on the findings presented by Dr. Schmid.
 

Promising Anti-tumor Activity

The combination of atezolizumab and sacituzumab govitecan demonstrated promising anti-tumor activity as initial treatment for this patient population. The interim analysis at 18 weeks showed an objective response rate of 76.7% (95% CI, 57.7-90.1; n = 23, including five complete responses) in the atezolizumab plus sacituzumab govitecan arm, versus 66.7% (95% CI, 29.9-92.5; n = 6, all of which were partial responses) in the control arm.

“The 66% response rate in the control arm aligns with what we see in historical data from patients treated with immunotherapy plus chemotherapy,” noted Dr. Schmid during his talk.

The clinical benefit rate, which includes complete and partial responses as well as stable disease, was also encouraging at 83.3% (95% CI, 65.3-94.4) with the dual immunotherapy regimen versus 66.7% (95% CI, 29.9-92.5) with standard therapy.

Commenting on the potential mechanisms of the synergistic effect of this combination therapy, Dr. Tolaney said, “In addition to delivering chemotherapy payloads to cancer cells, antibody-drug conjugates can lead to dendritic cell activation, T-cell activation, and immune cell infiltration.”

She added that antibody-drug conjugates can cause Fc activation in NK cells, thereby enhancing antibody-dependent cytotoxicity.
 

Encouraging survival trends

Interim survival data showed trends favoring atezolizumab plus sacituzumab govitecan over the control arm of atezolizumab plus nab-paclitaxel chemotherapy. The median progression-free survival (PFS) was 12.2 months (95% CI, 7.4-not estimable) in the immunotherapy combination group versus 5.9 months (95% CI, 4.1-8.7) in the control group, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.70). The overall survival data are still immature.

During the discussion session, Dr. Schmid cautioned that, although the benefit of this combination therapy in terms of PFS seems promising, the validity of the hazard ratio is limited because of the small cohort size. He added, “The survival data is still immature, and longer follow-up is needed.”

These encouraging response and PFS rates need to be confirmed in larger studies of this immunotherapy combination as a potential new first-line standard for PD-L1–positive TNBC, according to Dr. Schmid.
 

Relationship between biomarker expression and response

The MORPHEUS-pan BC trial enrolled only patients with PD-L1–positive tumors at baseline, defined as PD-L1 expression in at least 1% of immune cells infiltrating the tumor. Tumors at baseline were also tested for Trop-2 expression, CD8 immune phenotype, and stromal tumor-infiltrating lymphocytes (TILs).

“We wanted to get an idea of whether these biomarkers are associated with treatment response,” Dr. Schmid explained during his talk.

Although the benefit of sacituzumab govitecan treatment was observed across all Trop-2 expression levels, preliminary analyses suggest that high Trop-2 expression, CD8 immune phenotype, and stromal TILs may be associated with response to atezolizumab plus sacituzumab govitecan. However, Dr. Schmid noted that validation of these associations in larger cohorts is required.
 

Safety of combination treatment

The side effect profile of atezolizumab plus sacituzumab govitecan appeared consistent with that expected from the two individual drugs, with no new toxicity signals.

All patients in both treatment arms experienced at least one adverse event; however, there were no fatal adverse events. Grade 3-4 adverse events were more common in the experimental arm (70.0%) than in the control arm (44.4%), while serious adverse events were more common in the control group (44.4% versus 23.3%). Immune-related adverse events were considerably more common in the atezolizumab plus sacituzumab govitecan group than in the control group (80.0% versus 55.6%).

The most common adverse events in patients treated with atezolizumab plus sacituzumab govitecan were nausea, alopecia, diarrhea, and neutropenia. Dr. Schmid emphasized in his presentation that this toxicity profile was dominated by adverse events that are common in patients treated with chemotherapy.

“These safety data are significant as they suggest that the combination therapy does not introduce additional risks beyond those already associated with each drug,” he added.
 

Looking Ahead

Dr. Tolaney highlighted that the cohort size of this study was small and the follow-up time was insufficient to draw conclusions about survival outcomes. Larger studies with long-term follow-up are needed to confirm the efficacy of first-line atezolizumab plus sacituzumab govitecan, she said.

“While this was a small study, the response data is very intriguing, with 17% of patients experiencing complete responses. The PFS data are also impressive, and there seems to be an interesting trend towards better response in patients with high Trop-2 expression and those with high levels of stromal TILs,” she added.

Dr. Tolaney also noted that the response rates and PFS data presented are similar to those of one of the treatment arms in the BEGONIA trial (NCT03742102), which investigated different combinations of immunotherapy in patients with metastatic TNBC. Like MORPHEUS-pan BC (NCT03424005), this study evaluated the efficacy of a different antibody-drug conjugate with chemotherapy. Patients in the study arm of the BEGONIA trial she was referring to received durvalumab (an anti-PD-L1 agent) and datopotamab deruxtecan (an antibody-drug conjugate).

Dr. Schmid said that biomarker analyses are ongoing to assess whether there is a correlation between Trop-2 expression levels and the benefits of sacituzumab govitecan. Studies are also needed to determine whether this combination can improve pathologic complete response rates in early-stage TNBC.

Dr. Tolaney echoed the importance of evaluating the efficacy of antibody-drug conjugates plus immune checkpoint inhibitors in different settings, including patients with PD-L1–negative or immunologically cold tumors and those with early-stage disease. “Ultimately, we want this combination treatment to move forward to early-stage TNBC to see if we could cure more patients,” she said, during the discussion.

Dr. Schmid reported financial relationships with Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (consulting or advisory roles); Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (honoraria); and AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas, and Medivation (research funding). Dr. Tolaney reported financial relationships with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., Beyond Spring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, and Jazz Pharmaceuticals (consulting or advisory roles); Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics (research funding).

Lipoid proteinosis, or Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis with a global prevalence of less than 500 reported cases, with an equal distribution across genders and ethnicities.¹ It is caused by mutations in the ECM1 gene² on chromosome 1q21. This leads to the abnormal deposition of hyaline material in various tissues across different organ systems, with the classic manifestations known as the “string of pearls” sign and a hoarse cry or voice.

The rarity of lipoid proteinosis often leads to challenges in diagnosis. Particularly when deviating from the common association with consanguinity, the potential for de novo mutations or a broader genetic variability in disease expression is highlighted. Our patient presents with symptoms that are pathognomonic to LP with moniliform blepharosis and hoarseness of the voice, in addition to scarring of the extremities. 

Other common clinical manifestations in patients with LP include cobblestoning of the mucosa; hyperkeratosis of the elbows, knees, and hands; and calcification of the amygdala with neuroimaging.³

Genetic testing that identifies a loss-of-function mutation in ECM1 offers diagnostic confirmation. Patients often need multidisciplinary care involving dermatology; ear, nose, throat; neurology; and genetics. Treatment of LP is mostly symptomatic with unsatisfactory resolution of cutaneous changes, with retinoids such as acitretin used as the first-line option and surgery as a consideration for laryngeal hyaline deposits.² Although LP can affect different organ systems, patients tend to have a normal lifespan.

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 [email protected].

References

1. Mcgrath JA. Handb Clin Neurol. 2015:132:317-22. doi: 10.1016/B978-0-444-62702-5.00023-8.

2. Hamada Tet al. Hum Mol Genet. 2002 Apr 1;11(7):833-40. doi: 10.1093/hmg/11.7.833.

3. Frenkel B et al. Clin Oral Investig. 2017 Sep;21(7):2245-51 doi: 10.1007/s00784-016-2017-7.

Lipoid proteinosis, or Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis with a global prevalence of less than 500 reported cases, with an equal distribution across genders and ethnicities.¹ It is caused by mutations in the ECM1 gene² on chromosome 1q21. This leads to the abnormal deposition of hyaline material in various tissues across different organ systems, with the classic manifestations known as the “string of pearls” sign and a hoarse cry or voice.

The rarity of lipoid proteinosis often leads to challenges in diagnosis. Particularly when deviating from the common association with consanguinity, the potential for de novo mutations or a broader genetic variability in disease expression is highlighted. Our patient presents with symptoms that are pathognomonic to LP with moniliform blepharosis and hoarseness of the voice, in addition to scarring of the extremities. 

Other common clinical manifestations in patients with LP include cobblestoning of the mucosa; hyperkeratosis of the elbows, knees, and hands; and calcification of the amygdala with neuroimaging.³

Genetic testing that identifies a loss-of-function mutation in ECM1 offers diagnostic confirmation. Patients often need multidisciplinary care involving dermatology; ear, nose, throat; neurology; and genetics. Treatment of LP is mostly symptomatic with unsatisfactory resolution of cutaneous changes, with retinoids such as acitretin used as the first-line option and surgery as a consideration for laryngeal hyaline deposits.² Although LP can affect different organ systems, patients tend to have a normal lifespan.

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 [email protected].

References

1. Mcgrath JA. Handb Clin Neurol. 2015:132:317-22. doi: 10.1016/B978-0-444-62702-5.00023-8.

2. Hamada Tet al. Hum Mol Genet. 2002 Apr 1;11(7):833-40. doi: 10.1093/hmg/11.7.833.

3. Frenkel B et al. Clin Oral Investig. 2017 Sep;21(7):2245-51 doi: 10.1007/s00784-016-2017-7.

Lipoid proteinosis, or Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis with a global prevalence of less than 500 reported cases, with an equal distribution across genders and ethnicities.¹ It is caused by mutations in the ECM1 gene² on chromosome 1q21. This leads to the abnormal deposition of hyaline material in various tissues across different organ systems, with the classic manifestations known as the “string of pearls” sign and a hoarse cry or voice.

The rarity of lipoid proteinosis often leads to challenges in diagnosis. Particularly when deviating from the common association with consanguinity, the potential for de novo mutations or a broader genetic variability in disease expression is highlighted. Our patient presents with symptoms that are pathognomonic to LP with moniliform blepharosis and hoarseness of the voice, in addition to scarring of the extremities. 

Other common clinical manifestations in patients with LP include cobblestoning of the mucosa; hyperkeratosis of the elbows, knees, and hands; and calcification of the amygdala with neuroimaging.³

Genetic testing that identifies a loss-of-function mutation in ECM1 offers diagnostic confirmation. Patients often need multidisciplinary care involving dermatology; ear, nose, throat; neurology; and genetics. Treatment of LP is mostly symptomatic with unsatisfactory resolution of cutaneous changes, with retinoids such as acitretin used as the first-line option and surgery as a consideration for laryngeal hyaline deposits.² Although LP can affect different organ systems, patients tend to have a normal lifespan.

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 [email protected].

References

1. Mcgrath JA. Handb Clin Neurol. 2015:132:317-22. doi: 10.1016/B978-0-444-62702-5.00023-8.

2. Hamada Tet al. Hum Mol Genet. 2002 Apr 1;11(7):833-40. doi: 10.1093/hmg/11.7.833.

3. Frenkel B et al. Clin Oral Investig. 2017 Sep;21(7):2245-51 doi: 10.1007/s00784-016-2017-7.

Seniors are increasingly targeted in ever-sophisticated online financial cybercrimes, but mental health clinicians can play a key role in protecting their patients.

Elizabeth J. Santos, MD, clinical chief, Division of Geriatric Mental Health & Memory Care, and associate professor of psychiatry, neurology & medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, provided tips to attendees of the American Psychiatric Association (APA) 2024 Annual Meeting, and elaborated on these for this news organization.

Cybercrimes targeting seniors are common. A 2023 University of Michigan National Poll on Healthy Aging found 75% of adults aged 50-80 years experienced a fraud attempt either online or by phone, text, email, or mail in the past 2 years.

The poll found about 30% of respondents reported experiencing financial fraud, which could involve compromising credit cards, hacking bank accounts, or identity theft.

Older age is a risk factor for cybercrime. Seniors may have lower cognitive functioning and/or impaired decision-making. In addition, they are often socially isolated, dependent on others, and have poor health and financial literacy.
 

Romance Scams Common

Romance scams are another common financial fraud. Stephanie Garayalde, MD, a geriatric psychiatrist at the University of Florida, Gainesville, Florida, and another presenter at the APA session, used the example of Mr. L, a 74-year-old outpatient under treatment for depression who was unable to pay his rent.

Mr. L was giving money to his “girlfriend” he met online. Their relationship was totally virtual; she always had constant excuses for not meeting in person. He was funneling increasing funds to pay what he believed were medical bills and to bail her out of various other emergencies.

Once the fraud was discovered, Mr. L not only felt the loneliness of a lost romantic connection but also grappled with feelings of embarrassment and guilt.

“I see older patients who have been scammed who feel ashamed that they haven’t left enough money for their families,” said Dr. Santos.

Another well-known scam targets grandparents. Fraudsters sometimes use an artificial intelligence–generated voice mimicking a young family member and pretend to need money right away for bail or another problem.

In such situations, Dr. Santos advises patients to “hang up and call your family” to verify the call “no matter what the person says or who they sound like.”

Scammers may impersonate government officials to try to get social insurance information. Dr. Santos stresses the importance of never giving out this information. “If someone says they’re from your bank or a government agency like the IRS, hang up and call the bank or agency yourself.”

Evidence suggests this and other cybercrimes are on the rise. The Federal Bureau of Investigation’s Internet Crime Complaint Center received 888,000 complaints in 2023, a 10% increase from 2022, and losses of about $12.5 billion, which is a 22% increase over 2022.

It’s not that uncommon for the same older person to be scammed by numerous people and fall for it again and again, said Dr. Santos.

To mitigate the risk to this vulnerable group, researchers at the University of Central Florida, Orlando, Florida, are developing a scam screener for the elderly that will provide tools to help doctors screen older adults. The screen will focus on identifying factors that make victims most vulnerable, including seniors’ ability to think critically, a necessary skill for guarding against cybercrime.
 

Red Flags

In the meantime, Dr. Santos identified red flags for clinicians. Patients may show deviations in their typical behaviors; for example, they may seem sadder, more subdued, or more withdrawn than usual.

As loneliness and isolation can be a signal of victimization, “ask patients about their connectedness and be suspicious if the connectedness is all virtual,” she said.

Learning about the quality of their relationships is also important. “Instead of asking the superficial question of ‘Do you have friends’, ask ‘How do you talk to your friends? Are you actually getting out and meeting them?’”

If patients report they have never actually seen these so-called friends in-person, it should raise a red flag.

Another clue something may be amiss is “needing to be on their device or be home to get a call at a certain time.” Dr. Santos recalled a patient whose cell phone rang constantly during an evaluation, even after she had changed her phone number several times. “The scammers kept tracking her down,” she said.

Patients who are victims of cybercrime may stop taking their medications, fail to follow up on ordered tests, or miss paying for medical services.

Dr. Santos recommended screening for conditions known to be linked to cybercrime victimization such as depression. One of her patients was attending her memory clinic, but their cognitive issues were due to depression, not dementia.

It is important to identify subtle cognitive impairments. Dr. Santos recommended using the Saint Louis University Mental Status Examination, which she says is easier to use than the Montreal Cognitive Assessment.
 

Avoid Shaming

When managing patients who are potential cybercrime victims, she also suggests doctors be careful about their tone and their attitude. “Don’t shame someone for becoming a victim because it happens to everyone.”

When patients show signs of victimization, physicians could consider asking about their Internet use, social media practices, and general safety surrounding their finances.

They should emphasize the importance of protecting accounts through strong passwords, multifactor authentication when possible, and avoidance of sharing personal information with anyone who calls, emails, or texts.

Clinicians might also consider asking patients to review bills for new or unusual charges, check their bank account statements for withdrawals they didn’t make, and review credit reports for accounts in their name they don’t recognize.

Clinicians should also encourage patients to have a healthcare proxy, power of attorney, and advanced directives and recommend resources that can help victims. These include:

Federal Trade Commission (to report identity theft): https://reportfraud.ftc.gov;  https://www.identitytheft.gov

Federal Bureau of Investigation – Internet Crime and Complaint Center https://www.ic3.gov

National Elder Fraud Hotline (1-833-372-8311) or 1-833-FRAUD-11

http://ovc.ojp.gov/program/stop-elder-fraud/providing-help-restoring-hope

A version of this article appeared on Medscape.com.

Seniors are increasingly targeted in ever-sophisticated online financial cybercrimes, but mental health clinicians can play a key role in protecting their patients.

Elizabeth J. Santos, MD, clinical chief, Division of Geriatric Mental Health & Memory Care, and associate professor of psychiatry, neurology & medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, provided tips to attendees of the American Psychiatric Association (APA) 2024 Annual Meeting, and elaborated on these for this news organization.

Cybercrimes targeting seniors are common. A 2023 University of Michigan National Poll on Healthy Aging found 75% of adults aged 50-80 years experienced a fraud attempt either online or by phone, text, email, or mail in the past 2 years.

The poll found about 30% of respondents reported experiencing financial fraud, which could involve compromising credit cards, hacking bank accounts, or identity theft.

Older age is a risk factor for cybercrime. Seniors may have lower cognitive functioning and/or impaired decision-making. In addition, they are often socially isolated, dependent on others, and have poor health and financial literacy.
 

Romance Scams Common

Romance scams are another common financial fraud. Stephanie Garayalde, MD, a geriatric psychiatrist at the University of Florida, Gainesville, Florida, and another presenter at the APA session, used the example of Mr. L, a 74-year-old outpatient under treatment for depression who was unable to pay his rent.

Mr. L was giving money to his “girlfriend” he met online. Their relationship was totally virtual; she always had constant excuses for not meeting in person. He was funneling increasing funds to pay what he believed were medical bills and to bail her out of various other emergencies.

Once the fraud was discovered, Mr. L not only felt the loneliness of a lost romantic connection but also grappled with feelings of embarrassment and guilt.

“I see older patients who have been scammed who feel ashamed that they haven’t left enough money for their families,” said Dr. Santos.

Another well-known scam targets grandparents. Fraudsters sometimes use an artificial intelligence–generated voice mimicking a young family member and pretend to need money right away for bail or another problem.

In such situations, Dr. Santos advises patients to “hang up and call your family” to verify the call “no matter what the person says or who they sound like.”

Scammers may impersonate government officials to try to get social insurance information. Dr. Santos stresses the importance of never giving out this information. “If someone says they’re from your bank or a government agency like the IRS, hang up and call the bank or agency yourself.”

Evidence suggests this and other cybercrimes are on the rise. The Federal Bureau of Investigation’s Internet Crime Complaint Center received 888,000 complaints in 2023, a 10% increase from 2022, and losses of about $12.5 billion, which is a 22% increase over 2022.

It’s not that uncommon for the same older person to be scammed by numerous people and fall for it again and again, said Dr. Santos.

To mitigate the risk to this vulnerable group, researchers at the University of Central Florida, Orlando, Florida, are developing a scam screener for the elderly that will provide tools to help doctors screen older adults. The screen will focus on identifying factors that make victims most vulnerable, including seniors’ ability to think critically, a necessary skill for guarding against cybercrime.
 

Red Flags

In the meantime, Dr. Santos identified red flags for clinicians. Patients may show deviations in their typical behaviors; for example, they may seem sadder, more subdued, or more withdrawn than usual.

As loneliness and isolation can be a signal of victimization, “ask patients about their connectedness and be suspicious if the connectedness is all virtual,” she said.

Learning about the quality of their relationships is also important. “Instead of asking the superficial question of ‘Do you have friends’, ask ‘How do you talk to your friends? Are you actually getting out and meeting them?’”

If patients report they have never actually seen these so-called friends in-person, it should raise a red flag.

Another clue something may be amiss is “needing to be on their device or be home to get a call at a certain time.” Dr. Santos recalled a patient whose cell phone rang constantly during an evaluation, even after she had changed her phone number several times. “The scammers kept tracking her down,” she said.

Patients who are victims of cybercrime may stop taking their medications, fail to follow up on ordered tests, or miss paying for medical services.

Dr. Santos recommended screening for conditions known to be linked to cybercrime victimization such as depression. One of her patients was attending her memory clinic, but their cognitive issues were due to depression, not dementia.

It is important to identify subtle cognitive impairments. Dr. Santos recommended using the Saint Louis University Mental Status Examination, which she says is easier to use than the Montreal Cognitive Assessment.
 

Avoid Shaming

When managing patients who are potential cybercrime victims, she also suggests doctors be careful about their tone and their attitude. “Don’t shame someone for becoming a victim because it happens to everyone.”

When patients show signs of victimization, physicians could consider asking about their Internet use, social media practices, and general safety surrounding their finances.

They should emphasize the importance of protecting accounts through strong passwords, multifactor authentication when possible, and avoidance of sharing personal information with anyone who calls, emails, or texts.

Clinicians might also consider asking patients to review bills for new or unusual charges, check their bank account statements for withdrawals they didn’t make, and review credit reports for accounts in their name they don’t recognize.

Clinicians should also encourage patients to have a healthcare proxy, power of attorney, and advanced directives and recommend resources that can help victims. These include:

Federal Trade Commission (to report identity theft): https://reportfraud.ftc.gov;  https://www.identitytheft.gov

Federal Bureau of Investigation – Internet Crime and Complaint Center https://www.ic3.gov

National Elder Fraud Hotline (1-833-372-8311) or 1-833-FRAUD-11

http://ovc.ojp.gov/program/stop-elder-fraud/providing-help-restoring-hope

A version of this article appeared on Medscape.com.

Seniors are increasingly targeted in ever-sophisticated online financial cybercrimes, but mental health clinicians can play a key role in protecting their patients.

Elizabeth J. Santos, MD, clinical chief, Division of Geriatric Mental Health & Memory Care, and associate professor of psychiatry, neurology & medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, provided tips to attendees of the American Psychiatric Association (APA) 2024 Annual Meeting, and elaborated on these for this news organization.

Cybercrimes targeting seniors are common. A 2023 University of Michigan National Poll on Healthy Aging found 75% of adults aged 50-80 years experienced a fraud attempt either online or by phone, text, email, or mail in the past 2 years.

The poll found about 30% of respondents reported experiencing financial fraud, which could involve compromising credit cards, hacking bank accounts, or identity theft.

Older age is a risk factor for cybercrime. Seniors may have lower cognitive functioning and/or impaired decision-making. In addition, they are often socially isolated, dependent on others, and have poor health and financial literacy.
 

Romance Scams Common

Romance scams are another common financial fraud. Stephanie Garayalde, MD, a geriatric psychiatrist at the University of Florida, Gainesville, Florida, and another presenter at the APA session, used the example of Mr. L, a 74-year-old outpatient under treatment for depression who was unable to pay his rent.

Mr. L was giving money to his “girlfriend” he met online. Their relationship was totally virtual; she always had constant excuses for not meeting in person. He was funneling increasing funds to pay what he believed were medical bills and to bail her out of various other emergencies.

Once the fraud was discovered, Mr. L not only felt the loneliness of a lost romantic connection but also grappled with feelings of embarrassment and guilt.

“I see older patients who have been scammed who feel ashamed that they haven’t left enough money for their families,” said Dr. Santos.

Another well-known scam targets grandparents. Fraudsters sometimes use an artificial intelligence–generated voice mimicking a young family member and pretend to need money right away for bail or another problem.

In such situations, Dr. Santos advises patients to “hang up and call your family” to verify the call “no matter what the person says or who they sound like.”

Scammers may impersonate government officials to try to get social insurance information. Dr. Santos stresses the importance of never giving out this information. “If someone says they’re from your bank or a government agency like the IRS, hang up and call the bank or agency yourself.”

Evidence suggests this and other cybercrimes are on the rise. The Federal Bureau of Investigation’s Internet Crime Complaint Center received 888,000 complaints in 2023, a 10% increase from 2022, and losses of about $12.5 billion, which is a 22% increase over 2022.

It’s not that uncommon for the same older person to be scammed by numerous people and fall for it again and again, said Dr. Santos.

To mitigate the risk to this vulnerable group, researchers at the University of Central Florida, Orlando, Florida, are developing a scam screener for the elderly that will provide tools to help doctors screen older adults. The screen will focus on identifying factors that make victims most vulnerable, including seniors’ ability to think critically, a necessary skill for guarding against cybercrime.
 

Red Flags

In the meantime, Dr. Santos identified red flags for clinicians. Patients may show deviations in their typical behaviors; for example, they may seem sadder, more subdued, or more withdrawn than usual.

As loneliness and isolation can be a signal of victimization, “ask patients about their connectedness and be suspicious if the connectedness is all virtual,” she said.

Learning about the quality of their relationships is also important. “Instead of asking the superficial question of ‘Do you have friends’, ask ‘How do you talk to your friends? Are you actually getting out and meeting them?’”

If patients report they have never actually seen these so-called friends in-person, it should raise a red flag.

Another clue something may be amiss is “needing to be on their device or be home to get a call at a certain time.” Dr. Santos recalled a patient whose cell phone rang constantly during an evaluation, even after she had changed her phone number several times. “The scammers kept tracking her down,” she said.

Patients who are victims of cybercrime may stop taking their medications, fail to follow up on ordered tests, or miss paying for medical services.

Dr. Santos recommended screening for conditions known to be linked to cybercrime victimization such as depression. One of her patients was attending her memory clinic, but their cognitive issues were due to depression, not dementia.

It is important to identify subtle cognitive impairments. Dr. Santos recommended using the Saint Louis University Mental Status Examination, which she says is easier to use than the Montreal Cognitive Assessment.
 

Avoid Shaming

When managing patients who are potential cybercrime victims, she also suggests doctors be careful about their tone and their attitude. “Don’t shame someone for becoming a victim because it happens to everyone.”

When patients show signs of victimization, physicians could consider asking about their Internet use, social media practices, and general safety surrounding their finances.

They should emphasize the importance of protecting accounts through strong passwords, multifactor authentication when possible, and avoidance of sharing personal information with anyone who calls, emails, or texts.

Clinicians might also consider asking patients to review bills for new or unusual charges, check their bank account statements for withdrawals they didn’t make, and review credit reports for accounts in their name they don’t recognize.

Clinicians should also encourage patients to have a healthcare proxy, power of attorney, and advanced directives and recommend resources that can help victims. These include:

Federal Trade Commission (to report identity theft): https://reportfraud.ftc.gov;  https://www.identitytheft.gov

Federal Bureau of Investigation – Internet Crime and Complaint Center https://www.ic3.gov

National Elder Fraud Hotline (1-833-372-8311) or 1-833-FRAUD-11

http://ovc.ojp.gov/program/stop-elder-fraud/providing-help-restoring-hope

A version of this article appeared on Medscape.com.

New expert guidance to help clinicians manage the treatment of patients with epilepsy during pregnancy has been released.

Issued by the American Academy of Neurology, the American Epilepsy Society, and the Society for Maternal-Fetal Medicine, the new practice guideline covers the use of antiseizure medications (ASMs) and folic acid supplementation before conception and during pregnancy.

“Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications,” the guidelines’ lead author Alison M. Pack, MD, MPH, professor of neurology and chief of the Epilepsy and Sleep Division, Columbia University, New York City, said in a news release.

“This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy, so that doctors and people with epilepsy can determine which treatments may be best for them,” she added. 

The guideline was published online in Neurology.
 

Why Now? 

The new guideline updates the 2009 guidance on epilepsy management during pregnancy. Since then, Dr. Pack told this news organization, there has been a wealth of new data on differential effects of different ASMs — notably, lamotrigine and levetiracetam — the most commonly prescribed medications in this population.

“In this guideline, we were able to assess differential effects of different ASMs on outcomes of interest, including major congenital malformations [MCMs], perinatal outcomes, and neurodevelopmental outcomes. In addition, we looked at the effect of folic acid supplementation on each of these outcomes,” she said.

The overarching goals of care for patients are to “optimize health outcomes both for individuals and their future offspring,” the authors wrote. Shared decision-making, they add, leads to better decision-making by providing a better understanding of the available treatment options and their potential risks, resulting in enhanced decision-making that aligns with personal values.

Clinicians should recommend ASMs that optimize seizure control and fetal outcomes, in the event of a pregnancy, at the earliest possible preconception time, the guideline authors note.

“Overall, treating clinicians need to balance treating the person with epilepsy to control convulsive seizures (generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures) to minimize potential risks to the birth parent and the possible risks of certain ASMs on the fetus if pregnancy occurs,” they wrote.

If a patient is already pregnant, the experts recommend that clinicians “exercise caution” in removing or replacing an ASM that controls convulsive seizures, even if it’s “not an optimal choice” for the fetus. 

In addition, they advise that ASM levels should be monitored throughout the pregnancy, guided by individual ASM pharmacokinetics and an individual patient’s clinical presentation. ASM dose, they note, should be adjusted during pregnancy in response to decreasing serum ASM levels or worsening seizure control.

The authors point out that there are limited data on “pregnancy-related outcomes with respect to acetazolamide, eslicarbazepine, ethosuximide, lacosamide, nitrazepam, perampanel, piracetam, pregabalin, rufinamide, stiripentol, tiagabine, and vigabatrin.”

Patients should be informed that the birth prevalence of any major congenital malformation in the general population ranges between 2.4% and 2.9%.
 

If Feasible, Avoid Valproic Acid 

“One of the most important take-home messages is that valproic acid has the highest unadjusted birth prevalence of all major congenital malformations — 9.7% — and the highest unadjusted birth prevalence of neural tube defects at 1.4%,” Dr. Pack said. As a result, the guideline authors advise against using valproic acid, if clinically feasible.

Valproic acid also has the highest prevalence of negative neurodevelopmental outcomes, including a reduction in global IQ and an increased prevalence of autism spectrum disorder (ASD). Patients should be counseled accordingly and advised of the increased risk for ASD and decreased IQ resulting from valproic acid.

Clinicians should consider using lamotrigine, levetiracetam, or oxcarbazepine when appropriate. Serum concentrations of most ASMs have a “defined therapeutic window” for effective seizure control and that concentration may decrease during pregnancy, particularly with lamotrigine and levetiracetam, the authors note.

Phenobarbital, topiramate, and valproic acid should because of the increased risk for cardiac malformations, oral clefts, and urogenital and renal malformations.

Fetal screening for major congenital malformations is recommended to enable early detection and timely intervention in patients treated with any ASM during pregnancy Patients receiving phenobarbital during pregnancy should also undergo fetal cardiac screenings.

Valproic acid and topiramate are also associated with children who are small for their gestational age. To enable early identification of fetal growth restriction, patients taking valproic acid or topiramate should be monitored. In addition, children exposed to these medications in utero should be monitored during childhood to ensure they are meeting age-appropriate developmental milestones. 

Folic acid taken during pregnancy can reduce the prevalence of negative neurodevelopment outcomes, but not major congenital malformations, Dr. Pack noted. 

“Due to limited available data, we were unable to define an optimal dose of folic acid supplementation beyond at least 0.4 mg/d,” Dr. Pack said. “Future studies, preferably randomized clinical trials, are needed to better define the optimal dose.”

She emphasized that epilepsy is one of the most common neurologic disorders, and 1 in 5 of those affected are people of childbearing potential. Understanding the effects of ASMs on pregnancy outcomes is critical for physicians who manage these patients.
 

Uncertainty Remains 

Commenting for this news organization, Kimford Meador, MD, a professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine , Stanford Neuroscience Health Center, Palo Alto, California, noted that the new guidelines reflect the gains in knowledge since 2009 and that the recommendations are “reasonable, based on available data.”

However, “one very important point is how much remains unknown,” said Dr. Meador, who was not involved in writing the current guideline. “Many ASMs have no data, and several have estimates based on small samples or a single observational study.” Thus, “the risks for the majority of ASMs are uncertain.”

Given that randomized trials “are not possible in this population, and that all observational studies are subject to residual confounding, a reliable signal across multiple studies in humans is required to be certain of findings,” he stated.

This practice guideline was developed with financial support from the American Academy of Neurology. Dr. Pack serves on the editorial board for the journal Epilepsy Currents, receives royalties from UpToDate, receives funding from the National Institutes of Health for serving as coinvestigator and site principal investigator for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, and receives funding from Bayer for serving as a co-investigator on a study on women with epilepsy initiating a progestin intrauterine device. One of Dr. Pack’s immediate family members has received personal compensation for serving as an employee of REGENEXBIO. The other authors’ disclosures are listed on the original paper. Dr. Meador has received research support from the National Institutes of Health, Veterans Administration, Eisai, Inc, and Suno Medtronic Navigation, Inc, and the Epilepsy Study Consortium pays Dr. Meador’s university for his research on the Human Epilepsy Project and consultant time related to Eisai, UCB Pharma, and Xenon.

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

New expert guidance to help clinicians manage the treatment of patients with epilepsy during pregnancy has been released.

Issued by the American Academy of Neurology, the American Epilepsy Society, and the Society for Maternal-Fetal Medicine, the new practice guideline covers the use of antiseizure medications (ASMs) and folic acid supplementation before conception and during pregnancy.

“Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications,” the guidelines’ lead author Alison M. Pack, MD, MPH, professor of neurology and chief of the Epilepsy and Sleep Division, Columbia University, New York City, said in a news release.

“This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy, so that doctors and people with epilepsy can determine which treatments may be best for them,” she added. 

The guideline was published online in Neurology.
 

Why Now? 

The new guideline updates the 2009 guidance on epilepsy management during pregnancy. Since then, Dr. Pack told this news organization, there has been a wealth of new data on differential effects of different ASMs — notably, lamotrigine and levetiracetam — the most commonly prescribed medications in this population.

“In this guideline, we were able to assess differential effects of different ASMs on outcomes of interest, including major congenital malformations [MCMs], perinatal outcomes, and neurodevelopmental outcomes. In addition, we looked at the effect of folic acid supplementation on each of these outcomes,” she said.

The overarching goals of care for patients are to “optimize health outcomes both for individuals and their future offspring,” the authors wrote. Shared decision-making, they add, leads to better decision-making by providing a better understanding of the available treatment options and their potential risks, resulting in enhanced decision-making that aligns with personal values.

Clinicians should recommend ASMs that optimize seizure control and fetal outcomes, in the event of a pregnancy, at the earliest possible preconception time, the guideline authors note.

“Overall, treating clinicians need to balance treating the person with epilepsy to control convulsive seizures (generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures) to minimize potential risks to the birth parent and the possible risks of certain ASMs on the fetus if pregnancy occurs,” they wrote.

If a patient is already pregnant, the experts recommend that clinicians “exercise caution” in removing or replacing an ASM that controls convulsive seizures, even if it’s “not an optimal choice” for the fetus. 

In addition, they advise that ASM levels should be monitored throughout the pregnancy, guided by individual ASM pharmacokinetics and an individual patient’s clinical presentation. ASM dose, they note, should be adjusted during pregnancy in response to decreasing serum ASM levels or worsening seizure control.

The authors point out that there are limited data on “pregnancy-related outcomes with respect to acetazolamide, eslicarbazepine, ethosuximide, lacosamide, nitrazepam, perampanel, piracetam, pregabalin, rufinamide, stiripentol, tiagabine, and vigabatrin.”

Patients should be informed that the birth prevalence of any major congenital malformation in the general population ranges between 2.4% and 2.9%.
 

If Feasible, Avoid Valproic Acid 

“One of the most important take-home messages is that valproic acid has the highest unadjusted birth prevalence of all major congenital malformations — 9.7% — and the highest unadjusted birth prevalence of neural tube defects at 1.4%,” Dr. Pack said. As a result, the guideline authors advise against using valproic acid, if clinically feasible.

Valproic acid also has the highest prevalence of negative neurodevelopmental outcomes, including a reduction in global IQ and an increased prevalence of autism spectrum disorder (ASD). Patients should be counseled accordingly and advised of the increased risk for ASD and decreased IQ resulting from valproic acid.

Clinicians should consider using lamotrigine, levetiracetam, or oxcarbazepine when appropriate. Serum concentrations of most ASMs have a “defined therapeutic window” for effective seizure control and that concentration may decrease during pregnancy, particularly with lamotrigine and levetiracetam, the authors note.

Phenobarbital, topiramate, and valproic acid should because of the increased risk for cardiac malformations, oral clefts, and urogenital and renal malformations.

Fetal screening for major congenital malformations is recommended to enable early detection and timely intervention in patients treated with any ASM during pregnancy Patients receiving phenobarbital during pregnancy should also undergo fetal cardiac screenings.

Valproic acid and topiramate are also associated with children who are small for their gestational age. To enable early identification of fetal growth restriction, patients taking valproic acid or topiramate should be monitored. In addition, children exposed to these medications in utero should be monitored during childhood to ensure they are meeting age-appropriate developmental milestones. 

Folic acid taken during pregnancy can reduce the prevalence of negative neurodevelopment outcomes, but not major congenital malformations, Dr. Pack noted. 

“Due to limited available data, we were unable to define an optimal dose of folic acid supplementation beyond at least 0.4 mg/d,” Dr. Pack said. “Future studies, preferably randomized clinical trials, are needed to better define the optimal dose.”

She emphasized that epilepsy is one of the most common neurologic disorders, and 1 in 5 of those affected are people of childbearing potential. Understanding the effects of ASMs on pregnancy outcomes is critical for physicians who manage these patients.
 

Uncertainty Remains 

Commenting for this news organization, Kimford Meador, MD, a professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine , Stanford Neuroscience Health Center, Palo Alto, California, noted that the new guidelines reflect the gains in knowledge since 2009 and that the recommendations are “reasonable, based on available data.”

However, “one very important point is how much remains unknown,” said Dr. Meador, who was not involved in writing the current guideline. “Many ASMs have no data, and several have estimates based on small samples or a single observational study.” Thus, “the risks for the majority of ASMs are uncertain.”

Given that randomized trials “are not possible in this population, and that all observational studies are subject to residual confounding, a reliable signal across multiple studies in humans is required to be certain of findings,” he stated.

This practice guideline was developed with financial support from the American Academy of Neurology. Dr. Pack serves on the editorial board for the journal Epilepsy Currents, receives royalties from UpToDate, receives funding from the National Institutes of Health for serving as coinvestigator and site principal investigator for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, and receives funding from Bayer for serving as a co-investigator on a study on women with epilepsy initiating a progestin intrauterine device. One of Dr. Pack’s immediate family members has received personal compensation for serving as an employee of REGENEXBIO. The other authors’ disclosures are listed on the original paper. Dr. Meador has received research support from the National Institutes of Health, Veterans Administration, Eisai, Inc, and Suno Medtronic Navigation, Inc, and the Epilepsy Study Consortium pays Dr. Meador’s university for his research on the Human Epilepsy Project and consultant time related to Eisai, UCB Pharma, and Xenon.

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

New expert guidance to help clinicians manage the treatment of patients with epilepsy during pregnancy has been released.

Issued by the American Academy of Neurology, the American Epilepsy Society, and the Society for Maternal-Fetal Medicine, the new practice guideline covers the use of antiseizure medications (ASMs) and folic acid supplementation before conception and during pregnancy.

“Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications,” the guidelines’ lead author Alison M. Pack, MD, MPH, professor of neurology and chief of the Epilepsy and Sleep Division, Columbia University, New York City, said in a news release.

“This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy, so that doctors and people with epilepsy can determine which treatments may be best for them,” she added. 

The guideline was published online in Neurology.
 

Why Now? 

The new guideline updates the 2009 guidance on epilepsy management during pregnancy. Since then, Dr. Pack told this news organization, there has been a wealth of new data on differential effects of different ASMs — notably, lamotrigine and levetiracetam — the most commonly prescribed medications in this population.

“In this guideline, we were able to assess differential effects of different ASMs on outcomes of interest, including major congenital malformations [MCMs], perinatal outcomes, and neurodevelopmental outcomes. In addition, we looked at the effect of folic acid supplementation on each of these outcomes,” she said.

The overarching goals of care for patients are to “optimize health outcomes both for individuals and their future offspring,” the authors wrote. Shared decision-making, they add, leads to better decision-making by providing a better understanding of the available treatment options and their potential risks, resulting in enhanced decision-making that aligns with personal values.

Clinicians should recommend ASMs that optimize seizure control and fetal outcomes, in the event of a pregnancy, at the earliest possible preconception time, the guideline authors note.

“Overall, treating clinicians need to balance treating the person with epilepsy to control convulsive seizures (generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures) to minimize potential risks to the birth parent and the possible risks of certain ASMs on the fetus if pregnancy occurs,” they wrote.

If a patient is already pregnant, the experts recommend that clinicians “exercise caution” in removing or replacing an ASM that controls convulsive seizures, even if it’s “not an optimal choice” for the fetus. 

In addition, they advise that ASM levels should be monitored throughout the pregnancy, guided by individual ASM pharmacokinetics and an individual patient’s clinical presentation. ASM dose, they note, should be adjusted during pregnancy in response to decreasing serum ASM levels or worsening seizure control.

The authors point out that there are limited data on “pregnancy-related outcomes with respect to acetazolamide, eslicarbazepine, ethosuximide, lacosamide, nitrazepam, perampanel, piracetam, pregabalin, rufinamide, stiripentol, tiagabine, and vigabatrin.”

Patients should be informed that the birth prevalence of any major congenital malformation in the general population ranges between 2.4% and 2.9%.
 

If Feasible, Avoid Valproic Acid 

“One of the most important take-home messages is that valproic acid has the highest unadjusted birth prevalence of all major congenital malformations — 9.7% — and the highest unadjusted birth prevalence of neural tube defects at 1.4%,” Dr. Pack said. As a result, the guideline authors advise against using valproic acid, if clinically feasible.

Valproic acid also has the highest prevalence of negative neurodevelopmental outcomes, including a reduction in global IQ and an increased prevalence of autism spectrum disorder (ASD). Patients should be counseled accordingly and advised of the increased risk for ASD and decreased IQ resulting from valproic acid.

Clinicians should consider using lamotrigine, levetiracetam, or oxcarbazepine when appropriate. Serum concentrations of most ASMs have a “defined therapeutic window” for effective seizure control and that concentration may decrease during pregnancy, particularly with lamotrigine and levetiracetam, the authors note.

Phenobarbital, topiramate, and valproic acid should because of the increased risk for cardiac malformations, oral clefts, and urogenital and renal malformations.

Fetal screening for major congenital malformations is recommended to enable early detection and timely intervention in patients treated with any ASM during pregnancy Patients receiving phenobarbital during pregnancy should also undergo fetal cardiac screenings.

Valproic acid and topiramate are also associated with children who are small for their gestational age. To enable early identification of fetal growth restriction, patients taking valproic acid or topiramate should be monitored. In addition, children exposed to these medications in utero should be monitored during childhood to ensure they are meeting age-appropriate developmental milestones. 

Folic acid taken during pregnancy can reduce the prevalence of negative neurodevelopment outcomes, but not major congenital malformations, Dr. Pack noted. 

“Due to limited available data, we were unable to define an optimal dose of folic acid supplementation beyond at least 0.4 mg/d,” Dr. Pack said. “Future studies, preferably randomized clinical trials, are needed to better define the optimal dose.”

She emphasized that epilepsy is one of the most common neurologic disorders, and 1 in 5 of those affected are people of childbearing potential. Understanding the effects of ASMs on pregnancy outcomes is critical for physicians who manage these patients.
 

Uncertainty Remains 

Commenting for this news organization, Kimford Meador, MD, a professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine , Stanford Neuroscience Health Center, Palo Alto, California, noted that the new guidelines reflect the gains in knowledge since 2009 and that the recommendations are “reasonable, based on available data.”

However, “one very important point is how much remains unknown,” said Dr. Meador, who was not involved in writing the current guideline. “Many ASMs have no data, and several have estimates based on small samples or a single observational study.” Thus, “the risks for the majority of ASMs are uncertain.”

Given that randomized trials “are not possible in this population, and that all observational studies are subject to residual confounding, a reliable signal across multiple studies in humans is required to be certain of findings,” he stated.

This practice guideline was developed with financial support from the American Academy of Neurology. Dr. Pack serves on the editorial board for the journal Epilepsy Currents, receives royalties from UpToDate, receives funding from the National Institutes of Health for serving as coinvestigator and site principal investigator for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, and receives funding from Bayer for serving as a co-investigator on a study on women with epilepsy initiating a progestin intrauterine device. One of Dr. Pack’s immediate family members has received personal compensation for serving as an employee of REGENEXBIO. The other authors’ disclosures are listed on the original paper. Dr. Meador has received research support from the National Institutes of Health, Veterans Administration, Eisai, Inc, and Suno Medtronic Navigation, Inc, and the Epilepsy Study Consortium pays Dr. Meador’s university for his research on the Human Epilepsy Project and consultant time related to Eisai, UCB Pharma, and Xenon.

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

SAN FRANCISCO — Discussion of gestational weight gain occurred in only half of first-time obstetric visits, most often brought up by the provider, according to data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Weight can be a challenging and sensitive topic at a healthcare visit,” Malini Harinath, an undergraduate research assistant at Magee-Women’s Research Institute at University of Pittsburgh Medical Center, told attendees. “Providers discussed weight gain recommendations in less than half of conversations.”

The researchers analyzed an existing dataset of audio-recorded first obstetric visits to find out how often gestational weight gain was brought up, who initiated the discussion, whether ACOG guidelines were discussed, and what the provider’s comments were.

Among 150 visits, half (50%) involved discussion of weight, with patients bringing it up 24% of the time and providers bringing it up 72% of the time. In the other 3% of visits, it was brought up by a third party, such as a partner or other family member with the patient.

Only two of those visits mentioned body mass index (BMI) specifically, and ACOG guidelines on gestational weight gain were brought up in only six visits (8% of the visits where weight was mentioned). However, mention of recommendations on gestational weight gain was more frequent, coming up in nearly half (46.7%) of the visits where weight was mentioned, though that was still just 23% of all visits.

Concern about weight was brought up in 25.3% of visits where weight was discussed, and the provider’s reassurance to the patient occurred in about a third (32%) of those visits. General comments about the patient’s body occurred in 16% of visits, such as a clinician saying, “Usually we start trying [to find the heartbeat] at about 15 weeks, but you are so skinny we might be able to find it now.”

Ms. Harinath intends to look in future research at whether patient race or BMI are associated with the frequency and content of gestational weight gain conversations and to explore how patients react to different ways that discussion of weight is brought up.

Katherine Kaak, MD, a second-year resident at the University of Tennessee Graduate School of Medicine in Knoxville, was surprised that weight was brought up in only half of the visits. “The clinical takeaway is just how important counseling in the prenatal time is and how a lot of this discussion is preventive medicine,” Dr. Kaak said. “Even though we think of those visits as being quick, it’s good to keep in mind that we need to really take our time and make sure we counsel the patient as best we can.”

There’s a fair amount of research suggesting that existing recommendations on gestational weight gain are not very good because they’re very generic, Jill Maples, PhD, associate professor of ob.gyn. research at the University of Tennessee Graduate School of Medicine, said in an interview. For example, the guidelines are generally the same for everyone with a BMI over 30, but a person with a BMI of 30 is very different from someone with a BMI of 50, she said.

“There’s not even a lot of clarity on what is appropriate weight gain for that group because some people have seen good outcomes on the lower end of gestational weight gain,” Dr. Maples said. She said it’s important that clinicians not forget about the importance of these discussions, however, because lifestyle habits and gestational weight gain are related to maternal and neonatal outcomes.

The authors, Dr. Kaak, and Dr. Maples had no disclosures. The research was funded by the National Institute on Drug Abuse.

SAN FRANCISCO — Discussion of gestational weight gain occurred in only half of first-time obstetric visits, most often brought up by the provider, according to data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Weight can be a challenging and sensitive topic at a healthcare visit,” Malini Harinath, an undergraduate research assistant at Magee-Women’s Research Institute at University of Pittsburgh Medical Center, told attendees. “Providers discussed weight gain recommendations in less than half of conversations.”

The researchers analyzed an existing dataset of audio-recorded first obstetric visits to find out how often gestational weight gain was brought up, who initiated the discussion, whether ACOG guidelines were discussed, and what the provider’s comments were.

Among 150 visits, half (50%) involved discussion of weight, with patients bringing it up 24% of the time and providers bringing it up 72% of the time. In the other 3% of visits, it was brought up by a third party, such as a partner or other family member with the patient.

Only two of those visits mentioned body mass index (BMI) specifically, and ACOG guidelines on gestational weight gain were brought up in only six visits (8% of the visits where weight was mentioned). However, mention of recommendations on gestational weight gain was more frequent, coming up in nearly half (46.7%) of the visits where weight was mentioned, though that was still just 23% of all visits.

Concern about weight was brought up in 25.3% of visits where weight was discussed, and the provider’s reassurance to the patient occurred in about a third (32%) of those visits. General comments about the patient’s body occurred in 16% of visits, such as a clinician saying, “Usually we start trying [to find the heartbeat] at about 15 weeks, but you are so skinny we might be able to find it now.”

Ms. Harinath intends to look in future research at whether patient race or BMI are associated with the frequency and content of gestational weight gain conversations and to explore how patients react to different ways that discussion of weight is brought up.

Katherine Kaak, MD, a second-year resident at the University of Tennessee Graduate School of Medicine in Knoxville, was surprised that weight was brought up in only half of the visits. “The clinical takeaway is just how important counseling in the prenatal time is and how a lot of this discussion is preventive medicine,” Dr. Kaak said. “Even though we think of those visits as being quick, it’s good to keep in mind that we need to really take our time and make sure we counsel the patient as best we can.”

There’s a fair amount of research suggesting that existing recommendations on gestational weight gain are not very good because they’re very generic, Jill Maples, PhD, associate professor of ob.gyn. research at the University of Tennessee Graduate School of Medicine, said in an interview. For example, the guidelines are generally the same for everyone with a BMI over 30, but a person with a BMI of 30 is very different from someone with a BMI of 50, she said.

“There’s not even a lot of clarity on what is appropriate weight gain for that group because some people have seen good outcomes on the lower end of gestational weight gain,” Dr. Maples said. She said it’s important that clinicians not forget about the importance of these discussions, however, because lifestyle habits and gestational weight gain are related to maternal and neonatal outcomes.

The authors, Dr. Kaak, and Dr. Maples had no disclosures. The research was funded by the National Institute on Drug Abuse.

SAN FRANCISCO — Discussion of gestational weight gain occurred in only half of first-time obstetric visits, most often brought up by the provider, according to data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Weight can be a challenging and sensitive topic at a healthcare visit,” Malini Harinath, an undergraduate research assistant at Magee-Women’s Research Institute at University of Pittsburgh Medical Center, told attendees. “Providers discussed weight gain recommendations in less than half of conversations.”

The researchers analyzed an existing dataset of audio-recorded first obstetric visits to find out how often gestational weight gain was brought up, who initiated the discussion, whether ACOG guidelines were discussed, and what the provider’s comments were.

Among 150 visits, half (50%) involved discussion of weight, with patients bringing it up 24% of the time and providers bringing it up 72% of the time. In the other 3% of visits, it was brought up by a third party, such as a partner or other family member with the patient.

Only two of those visits mentioned body mass index (BMI) specifically, and ACOG guidelines on gestational weight gain were brought up in only six visits (8% of the visits where weight was mentioned). However, mention of recommendations on gestational weight gain was more frequent, coming up in nearly half (46.7%) of the visits where weight was mentioned, though that was still just 23% of all visits.

Concern about weight was brought up in 25.3% of visits where weight was discussed, and the provider’s reassurance to the patient occurred in about a third (32%) of those visits. General comments about the patient’s body occurred in 16% of visits, such as a clinician saying, “Usually we start trying [to find the heartbeat] at about 15 weeks, but you are so skinny we might be able to find it now.”

Ms. Harinath intends to look in future research at whether patient race or BMI are associated with the frequency and content of gestational weight gain conversations and to explore how patients react to different ways that discussion of weight is brought up.

Katherine Kaak, MD, a second-year resident at the University of Tennessee Graduate School of Medicine in Knoxville, was surprised that weight was brought up in only half of the visits. “The clinical takeaway is just how important counseling in the prenatal time is and how a lot of this discussion is preventive medicine,” Dr. Kaak said. “Even though we think of those visits as being quick, it’s good to keep in mind that we need to really take our time and make sure we counsel the patient as best we can.”

There’s a fair amount of research suggesting that existing recommendations on gestational weight gain are not very good because they’re very generic, Jill Maples, PhD, associate professor of ob.gyn. research at the University of Tennessee Graduate School of Medicine, said in an interview. For example, the guidelines are generally the same for everyone with a BMI over 30, but a person with a BMI of 30 is very different from someone with a BMI of 50, she said.

“There’s not even a lot of clarity on what is appropriate weight gain for that group because some people have seen good outcomes on the lower end of gestational weight gain,” Dr. Maples said. She said it’s important that clinicians not forget about the importance of these discussions, however, because lifestyle habits and gestational weight gain are related to maternal and neonatal outcomes.

The authors, Dr. Kaak, and Dr. Maples had no disclosures. The research was funded by the National Institute on Drug Abuse.

SAN FRANCISCO — Women who used marijuana during pregnancy were significantly less likely to view it as risky even in a state where it was not legalized, according to prospectively collected data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. But most of those women had not received any counseling about stopping its use, and more than half wanted more information about its effects on pregnancy complications.

“The biggest thing we recognized was that our counseling in prenatal visits was lower than what it really should have been,” Abigail M. Ramseyer, DO, of University of Michigan Health– Sparrow in Lansing, said in an interview. She said doctors really need to be asking their patients about marijuana use and having a conversation about the risks of its use during pregnancy.

An estimated 3%-30% of pregnant women use marijuana, depending on the population, but prevalence has been rising as more states legalize its use. Yet research has shown an association between marijuana use during pregnancy and multiple neonatal complications, including fetal growth restriction and low birth weight.

Pregnant women at a single center in Arkansas were invited during their prenatal visits to complete a 35-question, anonymous survey electronically or on paper. Of the 460 approached, 88.7% completed the survey and 11.8% of those women reported use of marijuana during pregnancy. Among those who used it while pregnant, 50% reported using it 2-3 times a week, 27% reported using it once weekly, and 18.8% reported using it daily.

The women who used it while pregnant were less likely to have a college degree and half (50%) were aged 18-24, with use declining with increasing age. A third of those who use it were White (33.3%), 52.1% were Black, and 6.3% were Hispanic.

More than half of the women (52.7%) who used marijuana during pregnancy reported that there had not been any discussion about substance use during pregnancy at the prenatal visit, and 82.4% said they had not received any counseling about stopping its use during pregnancy. Yet 54% of them wanted more information about pregnancy complications linked to cannabis use.

The other questions asked respondents on a 5-point Likert scale how much they agreed or disagreed with various statements related to perceptions of marijuana, its use during pregnancy, and its risks.

Most respondents strongly agreed that “marijuana isn’t as bad as other drugs like heroin, cocaine or meth,” but average agreement was higher among those who used marijuana (4.88) than who didn’t (4.02, P < .001).

Respondents largely neither agreed nor disagreed with its being okay to use marijuana during pregnancy with a prescription, but agreement was still higher among those who used it (3.68) than didn’t use it (2.82, P < .001). Those who used marijuana were more likely to agree that it’s “a natural substance and not a drug” (4.67 vs. 3.38, P < .001); to believe “marijuana has minimal health risks during and outside of pregnancy” (4.15 vs. 2.96, P < .001); and to believe “marijuana has less risk for treating symptoms in pregnancy than prescription medication from my provider” (4.19 vs. 3.01, P < .001).

It was not surprising that patients using marijuana would have more favorable opinions toward legalizing it, Dr. Ramseyer said, but it was interesting that the respondents’ attitude overall, regardless of use, was positive in a fairly conservative state where it was still illegal. She said her research group has data they are starting to analyze about the perceptions of patients’ partners and family members regarding marijuana use during pregnancy.

Animesh Upadhyay, MD, a resident at Yale–New Haven Medical Center in Connecticut, was also surprised by how positive the attitudes toward marijuana use and legalization were in a state where it’s illegal.

“The thing that disturbs me is that nobody has spoken about the risks of marijuana in pregnancy” to many of the respondents, said Dr. Upadhyay, who was not involved in the study. Based on the findings, Dr. Upadhyay said he would definitely begin asking patients more about their use of marijuana and their beliefs about it.

In a separate poster, Sarah Dzubay, BS, of Oregon Health & Science University, Portland, presented data examining potential associations between cannabis use and fertility. Previous research has suggested an association, but the cross-sectional analysis by Ms. Dzubay identified only a nonsignificant trend toward an association.

The researchers analyzed data from the 2013-2018 National Health and Nutrition Examination Study (NHANES) for woman aged 20-49 based on self-reported use of cannabis. Among 3166 women, 51% reported never using cannabis, 29% reported irregular use, and 20% reported regular use at least monthly.

“Women reporting regular use were younger, of lower income and educational attainment, and more likely to be single,” Ms. Dzubay reported. Those reporting irregular use, meanwhile, were more likely to be college graduates.

More of the women who used cannabis regularly (15.4%) reported an inability to conceive within one year than women who used cannabis irregularly (10.8%) or never (12.6%). The higher odds ratio of infertility among those using cannabis regularly (OR 1.47) compared to never using it was not statistically significant, however, nor was the reduced odds ratio among those using it irregularly (OR 0.83).

Because the results were not significant, the possibility of a link to infertility is “something to keep in mind,” Ms. Dzubay said, but “a lot more data has to be collected about this question before we can definitively say there’s a risk.”

The authors and Dr. Upadhyay had no disclosures. Neither study noted any external funding.

SAN FRANCISCO — Women who used marijuana during pregnancy were significantly less likely to view it as risky even in a state where it was not legalized, according to prospectively collected data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. But most of those women had not received any counseling about stopping its use, and more than half wanted more information about its effects on pregnancy complications.

“The biggest thing we recognized was that our counseling in prenatal visits was lower than what it really should have been,” Abigail M. Ramseyer, DO, of University of Michigan Health– Sparrow in Lansing, said in an interview. She said doctors really need to be asking their patients about marijuana use and having a conversation about the risks of its use during pregnancy.

An estimated 3%-30% of pregnant women use marijuana, depending on the population, but prevalence has been rising as more states legalize its use. Yet research has shown an association between marijuana use during pregnancy and multiple neonatal complications, including fetal growth restriction and low birth weight.

Pregnant women at a single center in Arkansas were invited during their prenatal visits to complete a 35-question, anonymous survey electronically or on paper. Of the 460 approached, 88.7% completed the survey and 11.8% of those women reported use of marijuana during pregnancy. Among those who used it while pregnant, 50% reported using it 2-3 times a week, 27% reported using it once weekly, and 18.8% reported using it daily.

The women who used it while pregnant were less likely to have a college degree and half (50%) were aged 18-24, with use declining with increasing age. A third of those who use it were White (33.3%), 52.1% were Black, and 6.3% were Hispanic.

More than half of the women (52.7%) who used marijuana during pregnancy reported that there had not been any discussion about substance use during pregnancy at the prenatal visit, and 82.4% said they had not received any counseling about stopping its use during pregnancy. Yet 54% of them wanted more information about pregnancy complications linked to cannabis use.

The other questions asked respondents on a 5-point Likert scale how much they agreed or disagreed with various statements related to perceptions of marijuana, its use during pregnancy, and its risks.

Most respondents strongly agreed that “marijuana isn’t as bad as other drugs like heroin, cocaine or meth,” but average agreement was higher among those who used marijuana (4.88) than who didn’t (4.02, P < .001).

Respondents largely neither agreed nor disagreed with its being okay to use marijuana during pregnancy with a prescription, but agreement was still higher among those who used it (3.68) than didn’t use it (2.82, P < .001). Those who used marijuana were more likely to agree that it’s “a natural substance and not a drug” (4.67 vs. 3.38, P < .001); to believe “marijuana has minimal health risks during and outside of pregnancy” (4.15 vs. 2.96, P < .001); and to believe “marijuana has less risk for treating symptoms in pregnancy than prescription medication from my provider” (4.19 vs. 3.01, P < .001).

It was not surprising that patients using marijuana would have more favorable opinions toward legalizing it, Dr. Ramseyer said, but it was interesting that the respondents’ attitude overall, regardless of use, was positive in a fairly conservative state where it was still illegal. She said her research group has data they are starting to analyze about the perceptions of patients’ partners and family members regarding marijuana use during pregnancy.

Animesh Upadhyay, MD, a resident at Yale–New Haven Medical Center in Connecticut, was also surprised by how positive the attitudes toward marijuana use and legalization were in a state where it’s illegal.

“The thing that disturbs me is that nobody has spoken about the risks of marijuana in pregnancy” to many of the respondents, said Dr. Upadhyay, who was not involved in the study. Based on the findings, Dr. Upadhyay said he would definitely begin asking patients more about their use of marijuana and their beliefs about it.

In a separate poster, Sarah Dzubay, BS, of Oregon Health & Science University, Portland, presented data examining potential associations between cannabis use and fertility. Previous research has suggested an association, but the cross-sectional analysis by Ms. Dzubay identified only a nonsignificant trend toward an association.

The researchers analyzed data from the 2013-2018 National Health and Nutrition Examination Study (NHANES) for woman aged 20-49 based on self-reported use of cannabis. Among 3166 women, 51% reported never using cannabis, 29% reported irregular use, and 20% reported regular use at least monthly.

“Women reporting regular use were younger, of lower income and educational attainment, and more likely to be single,” Ms. Dzubay reported. Those reporting irregular use, meanwhile, were more likely to be college graduates.

More of the women who used cannabis regularly (15.4%) reported an inability to conceive within one year than women who used cannabis irregularly (10.8%) or never (12.6%). The higher odds ratio of infertility among those using cannabis regularly (OR 1.47) compared to never using it was not statistically significant, however, nor was the reduced odds ratio among those using it irregularly (OR 0.83).

Because the results were not significant, the possibility of a link to infertility is “something to keep in mind,” Ms. Dzubay said, but “a lot more data has to be collected about this question before we can definitively say there’s a risk.”

The authors and Dr. Upadhyay had no disclosures. Neither study noted any external funding.

SAN FRANCISCO — Women who used marijuana during pregnancy were significantly less likely to view it as risky even in a state where it was not legalized, according to prospectively collected data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. But most of those women had not received any counseling about stopping its use, and more than half wanted more information about its effects on pregnancy complications.

“The biggest thing we recognized was that our counseling in prenatal visits was lower than what it really should have been,” Abigail M. Ramseyer, DO, of University of Michigan Health– Sparrow in Lansing, said in an interview. She said doctors really need to be asking their patients about marijuana use and having a conversation about the risks of its use during pregnancy.

An estimated 3%-30% of pregnant women use marijuana, depending on the population, but prevalence has been rising as more states legalize its use. Yet research has shown an association between marijuana use during pregnancy and multiple neonatal complications, including fetal growth restriction and low birth weight.

Pregnant women at a single center in Arkansas were invited during their prenatal visits to complete a 35-question, anonymous survey electronically or on paper. Of the 460 approached, 88.7% completed the survey and 11.8% of those women reported use of marijuana during pregnancy. Among those who used it while pregnant, 50% reported using it 2-3 times a week, 27% reported using it once weekly, and 18.8% reported using it daily.

The women who used it while pregnant were less likely to have a college degree and half (50%) were aged 18-24, with use declining with increasing age. A third of those who use it were White (33.3%), 52.1% were Black, and 6.3% were Hispanic.

More than half of the women (52.7%) who used marijuana during pregnancy reported that there had not been any discussion about substance use during pregnancy at the prenatal visit, and 82.4% said they had not received any counseling about stopping its use during pregnancy. Yet 54% of them wanted more information about pregnancy complications linked to cannabis use.

The other questions asked respondents on a 5-point Likert scale how much they agreed or disagreed with various statements related to perceptions of marijuana, its use during pregnancy, and its risks.

Most respondents strongly agreed that “marijuana isn’t as bad as other drugs like heroin, cocaine or meth,” but average agreement was higher among those who used marijuana (4.88) than who didn’t (4.02, P < .001).

Respondents largely neither agreed nor disagreed with its being okay to use marijuana during pregnancy with a prescription, but agreement was still higher among those who used it (3.68) than didn’t use it (2.82, P < .001). Those who used marijuana were more likely to agree that it’s “a natural substance and not a drug” (4.67 vs. 3.38, P < .001); to believe “marijuana has minimal health risks during and outside of pregnancy” (4.15 vs. 2.96, P < .001); and to believe “marijuana has less risk for treating symptoms in pregnancy than prescription medication from my provider” (4.19 vs. 3.01, P < .001).

It was not surprising that patients using marijuana would have more favorable opinions toward legalizing it, Dr. Ramseyer said, but it was interesting that the respondents’ attitude overall, regardless of use, was positive in a fairly conservative state where it was still illegal. She said her research group has data they are starting to analyze about the perceptions of patients’ partners and family members regarding marijuana use during pregnancy.

Animesh Upadhyay, MD, a resident at Yale–New Haven Medical Center in Connecticut, was also surprised by how positive the attitudes toward marijuana use and legalization were in a state where it’s illegal.

“The thing that disturbs me is that nobody has spoken about the risks of marijuana in pregnancy” to many of the respondents, said Dr. Upadhyay, who was not involved in the study. Based on the findings, Dr. Upadhyay said he would definitely begin asking patients more about their use of marijuana and their beliefs about it.

In a separate poster, Sarah Dzubay, BS, of Oregon Health & Science University, Portland, presented data examining potential associations between cannabis use and fertility. Previous research has suggested an association, but the cross-sectional analysis by Ms. Dzubay identified only a nonsignificant trend toward an association.

The researchers analyzed data from the 2013-2018 National Health and Nutrition Examination Study (NHANES) for woman aged 20-49 based on self-reported use of cannabis. Among 3166 women, 51% reported never using cannabis, 29% reported irregular use, and 20% reported regular use at least monthly.

“Women reporting regular use were younger, of lower income and educational attainment, and more likely to be single,” Ms. Dzubay reported. Those reporting irregular use, meanwhile, were more likely to be college graduates.

More of the women who used cannabis regularly (15.4%) reported an inability to conceive within one year than women who used cannabis irregularly (10.8%) or never (12.6%). The higher odds ratio of infertility among those using cannabis regularly (OR 1.47) compared to never using it was not statistically significant, however, nor was the reduced odds ratio among those using it irregularly (OR 0.83).

Because the results were not significant, the possibility of a link to infertility is “something to keep in mind,” Ms. Dzubay said, but “a lot more data has to be collected about this question before we can definitively say there’s a risk.”

The authors and Dr. Upadhyay had no disclosures. Neither study noted any external funding.

On February 11, 2024, the American Academy of Ophthalmology (AAO) issued new guidelines regarding dry eye syndrome or keratoconjunctivitis sicca. According to the National Eye Institute, dry eye affects approximately 16 million Americans. Dry eye is a multifactorial disease with causes including excessive screen time and refractive surgery. While it may seem that dry eye is a nuisance disease, it can actually damage the cornea if not treated appropriately.

The guidelines state that dry eye can affect the quality of life as well as the outcomes of ocular surgeries such as cataract surgery. It is imperative that we discuss this potential complication before our patients undergo these procedures. As primary care physicians, we have seen that patients may not be well educated on their health conditions by other doctors. We may not be the one performing the surgery but it is likely the patient will seek our advice if any complication arises.

The guidelines say that clinical examination is the gold standard for diagnosing this disease. We need to be proficient at doing eye exams and refer to a specialist when appropriate. The treatment can likely be undertaken in the primary care office unless there are other symptoms such as loss of visual acuity. The guidelines suggest several diagnostic tests, such as the Schirmer test and tear osmolarity test, which may be outside the scope of the primary care setting. Often, clinical history will guide the diagnosis.

Treatments include several Food and Drug Administration–approved eye drops. We need to know what they are and when to prescribe them. We know they will not cure the disease but can keep it under control and improve the patient’s quality of life.

Dry eye may seem a trivial complaint in the sea of diseases we treat on a daily basis. However, it is not trivial to the patient. It can affect their vision and make their life miserable. We need to pay attention when our patients bring this to our attention. We are not just making them comfortable but protecting their corneas. This can be done in conjunction with routine ophthalmologic visits.

According to the authors of these guidelines, approximately 10% of patients with significantly dry eyes and mouth will have Sjögren’s syndrome. Autoimmune testing should be undertaken in these patients.

These guidelines also suggest a classification for dry eye including mild, moderate, and severe. Since the treatment varies depending on classification, we need to learn this classification system. They also stress follow-up visits. It is not enough just to diagnose the disease and start treatment, we need to see the patients back for follow-up.

Currently, most people work and play on electronic devices. Dry eye syndrome can make this more difficult and vice versa. While it is typically not a vision-threatening disease, it can be a life-altering one. Ocular symptoms are something we see frequently in our practices, from allergic conjunctivitis to glaucoma. Often, the patient starts seeking help in our office.

Yes, our patients may have more life-threatening diseases. Our job is not just to save lives but to help our patients live healthy lives. If their lives are being affected by any disease, we must step in and do something. Dry eye is not just an inconvenience but something that causes great suffering. Eventually we may end up referring the patient to the ophthalmologist, but if we can do something to ease their discomfort while they are waiting, we would be changing their lives. We must educate ourselves on this disease and appropriate treatments to be prescribed depending on the classification of disease.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, NJ. She has no conflicts of interest.

On February 11, 2024, the American Academy of Ophthalmology (AAO) issued new guidelines regarding dry eye syndrome or keratoconjunctivitis sicca. According to the National Eye Institute, dry eye affects approximately 16 million Americans. Dry eye is a multifactorial disease with causes including excessive screen time and refractive surgery. While it may seem that dry eye is a nuisance disease, it can actually damage the cornea if not treated appropriately.

The guidelines state that dry eye can affect the quality of life as well as the outcomes of ocular surgeries such as cataract surgery. It is imperative that we discuss this potential complication before our patients undergo these procedures. As primary care physicians, we have seen that patients may not be well educated on their health conditions by other doctors. We may not be the one performing the surgery but it is likely the patient will seek our advice if any complication arises.

The guidelines say that clinical examination is the gold standard for diagnosing this disease. We need to be proficient at doing eye exams and refer to a specialist when appropriate. The treatment can likely be undertaken in the primary care office unless there are other symptoms such as loss of visual acuity. The guidelines suggest several diagnostic tests, such as the Schirmer test and tear osmolarity test, which may be outside the scope of the primary care setting. Often, clinical history will guide the diagnosis.

Treatments include several Food and Drug Administration–approved eye drops. We need to know what they are and when to prescribe them. We know they will not cure the disease but can keep it under control and improve the patient’s quality of life.

Dry eye may seem a trivial complaint in the sea of diseases we treat on a daily basis. However, it is not trivial to the patient. It can affect their vision and make their life miserable. We need to pay attention when our patients bring this to our attention. We are not just making them comfortable but protecting their corneas. This can be done in conjunction with routine ophthalmologic visits.

According to the authors of these guidelines, approximately 10% of patients with significantly dry eyes and mouth will have Sjögren’s syndrome. Autoimmune testing should be undertaken in these patients.

These guidelines also suggest a classification for dry eye including mild, moderate, and severe. Since the treatment varies depending on classification, we need to learn this classification system. They also stress follow-up visits. It is not enough just to diagnose the disease and start treatment, we need to see the patients back for follow-up.

Currently, most people work and play on electronic devices. Dry eye syndrome can make this more difficult and vice versa. While it is typically not a vision-threatening disease, it can be a life-altering one. Ocular symptoms are something we see frequently in our practices, from allergic conjunctivitis to glaucoma. Often, the patient starts seeking help in our office.

Yes, our patients may have more life-threatening diseases. Our job is not just to save lives but to help our patients live healthy lives. If their lives are being affected by any disease, we must step in and do something. Dry eye is not just an inconvenience but something that causes great suffering. Eventually we may end up referring the patient to the ophthalmologist, but if we can do something to ease their discomfort while they are waiting, we would be changing their lives. We must educate ourselves on this disease and appropriate treatments to be prescribed depending on the classification of disease.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, NJ. She has no conflicts of interest.

On February 11, 2024, the American Academy of Ophthalmology (AAO) issued new guidelines regarding dry eye syndrome or keratoconjunctivitis sicca. According to the National Eye Institute, dry eye affects approximately 16 million Americans. Dry eye is a multifactorial disease with causes including excessive screen time and refractive surgery. While it may seem that dry eye is a nuisance disease, it can actually damage the cornea if not treated appropriately.

The guidelines state that dry eye can affect the quality of life as well as the outcomes of ocular surgeries such as cataract surgery. It is imperative that we discuss this potential complication before our patients undergo these procedures. As primary care physicians, we have seen that patients may not be well educated on their health conditions by other doctors. We may not be the one performing the surgery but it is likely the patient will seek our advice if any complication arises.

The guidelines say that clinical examination is the gold standard for diagnosing this disease. We need to be proficient at doing eye exams and refer to a specialist when appropriate. The treatment can likely be undertaken in the primary care office unless there are other symptoms such as loss of visual acuity. The guidelines suggest several diagnostic tests, such as the Schirmer test and tear osmolarity test, which may be outside the scope of the primary care setting. Often, clinical history will guide the diagnosis.

Treatments include several Food and Drug Administration–approved eye drops. We need to know what they are and when to prescribe them. We know they will not cure the disease but can keep it under control and improve the patient’s quality of life.

Dry eye may seem a trivial complaint in the sea of diseases we treat on a daily basis. However, it is not trivial to the patient. It can affect their vision and make their life miserable. We need to pay attention when our patients bring this to our attention. We are not just making them comfortable but protecting their corneas. This can be done in conjunction with routine ophthalmologic visits.

According to the authors of these guidelines, approximately 10% of patients with significantly dry eyes and mouth will have Sjögren’s syndrome. Autoimmune testing should be undertaken in these patients.

These guidelines also suggest a classification for dry eye including mild, moderate, and severe. Since the treatment varies depending on classification, we need to learn this classification system. They also stress follow-up visits. It is not enough just to diagnose the disease and start treatment, we need to see the patients back for follow-up.

Currently, most people work and play on electronic devices. Dry eye syndrome can make this more difficult and vice versa. While it is typically not a vision-threatening disease, it can be a life-altering one. Ocular symptoms are something we see frequently in our practices, from allergic conjunctivitis to glaucoma. Often, the patient starts seeking help in our office.

Yes, our patients may have more life-threatening diseases. Our job is not just to save lives but to help our patients live healthy lives. If their lives are being affected by any disease, we must step in and do something. Dry eye is not just an inconvenience but something that causes great suffering. Eventually we may end up referring the patient to the ophthalmologist, but if we can do something to ease their discomfort while they are waiting, we would be changing their lives. We must educate ourselves on this disease and appropriate treatments to be prescribed depending on the classification of disease.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, NJ. She has no conflicts of interest.

Macadamia (Macadamia tetraphylla) is endemic to Australia and is now commercially cultivated worldwide.¹ It is closely related genetically to the other macadamia plants, including the other main one, M. integrifolia, cultivated for macadamia nuts. Known in Brazil as sapucaia or castanha-de-sapucaia, Lecythis pisonis (also referred to as “cream nut” or “monkey pot”) is a large, deciduous tropical tree and member of the Brazil nut family, Lecythidaceae.² Various parts of both of these plants have been associated with medicinal properties, including the potential for dermatologic activity. Notably, the leaves of L. pisonis have been used in traditional medicine to treat pruritus.²This column focuses on the studies suggesting the possible benefits of macadamia and sapucaia components for skin care.

Macadamia

Extraction to Harness Antioxidant Activity

In 2015, Dailey and Vuong developed an aqueous extraction process to recover the phenolic content and antioxidant functionality from the skin waste of M. tetraphylla using response surface methodology. As an environmentally suitable solvent that is also cheap and safe, water was chosen to maximize the extraction scenario. They identified the proper conditions (90° C, a time of 20 min, and a sample-to-solvent ratio of 5 g/100 mL) to obtain sufficient phenolic compounds, proanthocyanidins, and flavonoids to render robust antioxidant function.¹

Baumann Cosmetic &amp; Research Institute

Early in 2023, Somwongin et al. investigated various green extraction methods for viability in harnessing the cosmetic/cosmeceutical ingredients of M. integrifolia pericarps. Extracts were assessed for total phenolic content as well as antioxidant and anti–skin aging functions. They found that among the green extraction methods (ultrasound, micellar, microwave, and pulsed electric field extraction with water used as a clean solvent), the ultrasound-assisted extraction method netted the greatest yield and total phenolic content. It was also associated with the most robust antioxidant and anti–skin aging activities. Indeed, the researchers reported that its antioxidant activities were comparable to ascorbic acid and Trolox and its anti–skin aging potency on a par with epigallocatechin-3-gallate and oleanolic acid. The ultrasound-assisted extract was also deemed safe as it did not provoke irritation. The authors concluded that this environmentally suitable extraction method for M. integrifolia is appropriate for obtaining effective macadamia extracts for use in cosmetics and cosmeceuticals.³

Anti-Aging Activity

In 2017, Addy et al. set out to characterize skin surface lipid composition and differences in an age- and sex-controlled population as a foundation for developing a botanically derived skin surface lipid mimetic agent. They noted that fatty acids, triglycerides, cholesterol, steryl esters, wax esters, and squalene are the main constituents of skin surface lipids. The investigators obtained skin surface lipid samples from the foreheads of 59 healthy 22-year-old women, analyzed them, and used the raw components of M. integrifolia, Simmondsia chinensis, and Olea europaea to engineer a mimetic product. They reported that the esterification reactions of jojoba, macadamia, and tall oils, combined with squalene derived from O. europaea, yielded an appropriate skin surface lipid mimetic, which, when applied to delipidized skin, assisted in recovering barrier function, enhancing skin hydration, and improving elasticity as well as firmness in aged skin. The researchers concluded that this skin surface lipid mimetic could serve as an effective supplement to human skin surface lipids in aged skin and for conditions in which the stratum corneum is impaired.⁴

Two years later, Hanum et al. compared the effects of macadamia nut oil nanocream and conventional cream for treating cutaneous aging over a 4-week period. The macadamia nut oil nanocream, which contained macadamia nut oil 10%, tween 80, propylene glycol, cetyl alcohol, methylparaben, propylparaben, and distilled water, was compared with the conventional cream based on effects on moisture, evenness, pore size, melanin, and wrinkling. The macadamia nut oil was found to yield superior anti-aging activity along each parameter as compared with the conventional cream. The researchers concluded that the macadamia nut oil in nanocream can be an effective formulation for providing benefits in addressing cutaneous aging.⁵

Matthieu Sontag/Wikimedia Commons/CC-BY-SA

Antifungal Activity

In 2015, Vieira et al. characterized 12 fractions enriched in peptides derived from L. pisonis seeds to determine inhibitory activity against Candida albicans. The fraction that exerted the strongest activity at 10 μg/mL, suppressing C. albicans growth by 38.5% and inducing a 69.3% loss of viability, was identified as similar to plant defensins and thus dubbed “L. pisonis defensin 1 (Lp-Def1).” The investigators concluded that Lp-Def1 acts on C. albicans by slightly elevating the induction of reactive oxygen species and causing a significant reduction in mitochondrial activity. They suggested that their findings support the use of plant defensins, particularly Lp-Def1, in the formulation of antifungal products, especially to address C. albicans.¹⁰

Pruritus

In 2012, Silva et al. studied the antipruritic impact of L. pisonis leaf extracts in mice and rats. Pretreatment with the various fractions of L. pisonis as well as constituent mixed triterpenes (ursolic and oleanolic acids) significantly blocked scratching behavior provoked by compound 48/80. The degranulation of rat peritoneal mast cells caused by compound 48/80 was also substantially decreased from pretreatment with the ethanol extract of L. pisonis, ether-L. pisonis fraction, and mixed triterpenes. The L. pisonis ether fraction suppressed edema induced by carrageenan administration and the ethanol extract displayed no toxicity up to an oral dose of 2g/kg. The investigators concluded that their results strongly support the antipruritic effects of L. pisonis leaves as well as the traditional use of the plant to treat pruritus.²

Stability for Cosmetic Creams

In 2020, Rampazzo et al. assessed the stability and cytotoxicity of a cosmetic cream containing sapucaia nut oil. All three tested concentrations (1%, 5%, and 10%) of the cream were found to be stable, with an effective preservative system, and deemed safe for use on human skin. To maintain a pH appropriate for a body cream, the formulation requires a stabilizing agent. The cream with 5% nut oil was identified as the most stable and satisfying for use on the skin.⁷

More recently, Hertel Pereira et al. investigated the benefits of using L. pisonis pericarp extract, known to exhibit abundant antioxidants, in an all-natural skin cream. They found that formulation instability increased proportionally with the concentration of the extract, but the use of the outer pericarp of L. pisonis was well suited for the cream formulation, with physical-chemical and organoleptic qualities unchanged after the stability test.¹¹

Conclusion

The available literature on the medical applications of macadamia and sapucaia plants is sparse. Some recent findings are promising regarding possible uses in skin health. However, much more research is necessary before considering macadamia and sapucaia as viable sources of botanical agents capable of delivering significant cutaneous benefits.

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 Inc., an SaaS company used to generate skin care routines in office and as an e-commerce solution. Write to her at [email protected].

References

1. Dailey A and Vuong QV. Antioxidants (Basel). 2015 Nov 12;4(4):699-718.

2. Silva LL et al. J Ethnopharmacol. 2012 Jan 6;139(1):90-97.

3. Somwongin S et al. Ultrason Sonochem. 2023 Jan;92:106266.

4. Addy J et al. J Cosmet Sci. 2017 Jan/Feb;68(1):59-67.

5. Hanum TI et al. Open Access Maced J Med Sci. 2019 Nov 14;7(22):3917-3920.

6. Akhtar N and Yazan Y. Pak J Pharm Sci. 2008 Jan;21(1):45-50.

7. Rampazzo APS et al. J Cosmet Sci. 2020 Sep/Oct;71(5):239-250.

8. Rosa TLM et al. Food Res Int. 2020 Nov;137:109383.

9. Demoliner F et al. Food Res Int. 2018 Oct;112:434-442.

10. Vieira ME et al. Acta Biochim Biophys Sin (Shanghai). 2015 Sep;47(9):716-729.

11. Hertel Pereira AC et al. J Cosmet Sci. 2021 Mar-Apr;72(2):155-162.

Macadamia (Macadamia tetraphylla) is endemic to Australia and is now commercially cultivated worldwide.¹ It is closely related genetically to the other macadamia plants, including the other main one, M. integrifolia, cultivated for macadamia nuts. Known in Brazil as sapucaia or castanha-de-sapucaia, Lecythis pisonis (also referred to as “cream nut” or “monkey pot”) is a large, deciduous tropical tree and member of the Brazil nut family, Lecythidaceae.² Various parts of both of these plants have been associated with medicinal properties, including the potential for dermatologic activity. Notably, the leaves of L. pisonis have been used in traditional medicine to treat pruritus.²This column focuses on the studies suggesting the possible benefits of macadamia and sapucaia components for skin care.

Macadamia

Extraction to Harness Antioxidant Activity

In 2015, Dailey and Vuong developed an aqueous extraction process to recover the phenolic content and antioxidant functionality from the skin waste of M. tetraphylla using response surface methodology. As an environmentally suitable solvent that is also cheap and safe, water was chosen to maximize the extraction scenario. They identified the proper conditions (90° C, a time of 20 min, and a sample-to-solvent ratio of 5 g/100 mL) to obtain sufficient phenolic compounds, proanthocyanidins, and flavonoids to render robust antioxidant function.¹

Baumann Cosmetic &amp; Research Institute

Early in 2023, Somwongin et al. investigated various green extraction methods for viability in harnessing the cosmetic/cosmeceutical ingredients of M. integrifolia pericarps. Extracts were assessed for total phenolic content as well as antioxidant and anti–skin aging functions. They found that among the green extraction methods (ultrasound, micellar, microwave, and pulsed electric field extraction with water used as a clean solvent), the ultrasound-assisted extraction method netted the greatest yield and total phenolic content. It was also associated with the most robust antioxidant and anti–skin aging activities. Indeed, the researchers reported that its antioxidant activities were comparable to ascorbic acid and Trolox and its anti–skin aging potency on a par with epigallocatechin-3-gallate and oleanolic acid. The ultrasound-assisted extract was also deemed safe as it did not provoke irritation. The authors concluded that this environmentally suitable extraction method for M. integrifolia is appropriate for obtaining effective macadamia extracts for use in cosmetics and cosmeceuticals.³

Anti-Aging Activity

In 2017, Addy et al. set out to characterize skin surface lipid composition and differences in an age- and sex-controlled population as a foundation for developing a botanically derived skin surface lipid mimetic agent. They noted that fatty acids, triglycerides, cholesterol, steryl esters, wax esters, and squalene are the main constituents of skin surface lipids. The investigators obtained skin surface lipid samples from the foreheads of 59 healthy 22-year-old women, analyzed them, and used the raw components of M. integrifolia, Simmondsia chinensis, and Olea europaea to engineer a mimetic product. They reported that the esterification reactions of jojoba, macadamia, and tall oils, combined with squalene derived from O. europaea, yielded an appropriate skin surface lipid mimetic, which, when applied to delipidized skin, assisted in recovering barrier function, enhancing skin hydration, and improving elasticity as well as firmness in aged skin. The researchers concluded that this skin surface lipid mimetic could serve as an effective supplement to human skin surface lipids in aged skin and for conditions in which the stratum corneum is impaired.⁴

Two years later, Hanum et al. compared the effects of macadamia nut oil nanocream and conventional cream for treating cutaneous aging over a 4-week period. The macadamia nut oil nanocream, which contained macadamia nut oil 10%, tween 80, propylene glycol, cetyl alcohol, methylparaben, propylparaben, and distilled water, was compared with the conventional cream based on effects on moisture, evenness, pore size, melanin, and wrinkling. The macadamia nut oil was found to yield superior anti-aging activity along each parameter as compared with the conventional cream. The researchers concluded that the macadamia nut oil in nanocream can be an effective formulation for providing benefits in addressing cutaneous aging.⁵

Matthieu Sontag/Wikimedia Commons/CC-BY-SA

Antifungal Activity

In 2015, Vieira et al. characterized 12 fractions enriched in peptides derived from L. pisonis seeds to determine inhibitory activity against Candida albicans. The fraction that exerted the strongest activity at 10 μg/mL, suppressing C. albicans growth by 38.5% and inducing a 69.3% loss of viability, was identified as similar to plant defensins and thus dubbed “L. pisonis defensin 1 (Lp-Def1).” The investigators concluded that Lp-Def1 acts on C. albicans by slightly elevating the induction of reactive oxygen species and causing a significant reduction in mitochondrial activity. They suggested that their findings support the use of plant defensins, particularly Lp-Def1, in the formulation of antifungal products, especially to address C. albicans.¹⁰

Pruritus

In 2012, Silva et al. studied the antipruritic impact of L. pisonis leaf extracts in mice and rats. Pretreatment with the various fractions of L. pisonis as well as constituent mixed triterpenes (ursolic and oleanolic acids) significantly blocked scratching behavior provoked by compound 48/80. The degranulation of rat peritoneal mast cells caused by compound 48/80 was also substantially decreased from pretreatment with the ethanol extract of L. pisonis, ether-L. pisonis fraction, and mixed triterpenes. The L. pisonis ether fraction suppressed edema induced by carrageenan administration and the ethanol extract displayed no toxicity up to an oral dose of 2g/kg. The investigators concluded that their results strongly support the antipruritic effects of L. pisonis leaves as well as the traditional use of the plant to treat pruritus.²

Stability for Cosmetic Creams

In 2020, Rampazzo et al. assessed the stability and cytotoxicity of a cosmetic cream containing sapucaia nut oil. All three tested concentrations (1%, 5%, and 10%) of the cream were found to be stable, with an effective preservative system, and deemed safe for use on human skin. To maintain a pH appropriate for a body cream, the formulation requires a stabilizing agent. The cream with 5% nut oil was identified as the most stable and satisfying for use on the skin.⁷

More recently, Hertel Pereira et al. investigated the benefits of using L. pisonis pericarp extract, known to exhibit abundant antioxidants, in an all-natural skin cream. They found that formulation instability increased proportionally with the concentration of the extract, but the use of the outer pericarp of L. pisonis was well suited for the cream formulation, with physical-chemical and organoleptic qualities unchanged after the stability test.¹¹

Conclusion

The available literature on the medical applications of macadamia and sapucaia plants is sparse. Some recent findings are promising regarding possible uses in skin health. However, much more research is necessary before considering macadamia and sapucaia as viable sources of botanical agents capable of delivering significant cutaneous benefits.

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 Inc., an SaaS company used to generate skin care routines in office and as an e-commerce solution. Write to her at [email protected].

References

1. Dailey A and Vuong QV. Antioxidants (Basel). 2015 Nov 12;4(4):699-718.

2. Silva LL et al. J Ethnopharmacol. 2012 Jan 6;139(1):90-97.

3. Somwongin S et al. Ultrason Sonochem. 2023 Jan;92:106266.

4. Addy J et al. J Cosmet Sci. 2017 Jan/Feb;68(1):59-67.

5. Hanum TI et al. Open Access Maced J Med Sci. 2019 Nov 14;7(22):3917-3920.

6. Akhtar N and Yazan Y. Pak J Pharm Sci. 2008 Jan;21(1):45-50.

7. Rampazzo APS et al. J Cosmet Sci. 2020 Sep/Oct;71(5):239-250.

8. Rosa TLM et al. Food Res Int. 2020 Nov;137:109383.

9. Demoliner F et al. Food Res Int. 2018 Oct;112:434-442.

10. Vieira ME et al. Acta Biochim Biophys Sin (Shanghai). 2015 Sep;47(9):716-729.

11. Hertel Pereira AC et al. J Cosmet Sci. 2021 Mar-Apr;72(2):155-162.

Macadamia (Macadamia tetraphylla) is endemic to Australia and is now commercially cultivated worldwide.¹ It is closely related genetically to the other macadamia plants, including the other main one, M. integrifolia, cultivated for macadamia nuts. Known in Brazil as sapucaia or castanha-de-sapucaia, Lecythis pisonis (also referred to as “cream nut” or “monkey pot”) is a large, deciduous tropical tree and member of the Brazil nut family, Lecythidaceae.² Various parts of both of these plants have been associated with medicinal properties, including the potential for dermatologic activity. Notably, the leaves of L. pisonis have been used in traditional medicine to treat pruritus.²This column focuses on the studies suggesting the possible benefits of macadamia and sapucaia components for skin care.

Macadamia

Extraction to Harness Antioxidant Activity

In 2015, Dailey and Vuong developed an aqueous extraction process to recover the phenolic content and antioxidant functionality from the skin waste of M. tetraphylla using response surface methodology. As an environmentally suitable solvent that is also cheap and safe, water was chosen to maximize the extraction scenario. They identified the proper conditions (90° C, a time of 20 min, and a sample-to-solvent ratio of 5 g/100 mL) to obtain sufficient phenolic compounds, proanthocyanidins, and flavonoids to render robust antioxidant function.¹

Baumann Cosmetic &amp; Research Institute

Early in 2023, Somwongin et al. investigated various green extraction methods for viability in harnessing the cosmetic/cosmeceutical ingredients of M. integrifolia pericarps. Extracts were assessed for total phenolic content as well as antioxidant and anti–skin aging functions. They found that among the green extraction methods (ultrasound, micellar, microwave, and pulsed electric field extraction with water used as a clean solvent), the ultrasound-assisted extraction method netted the greatest yield and total phenolic content. It was also associated with the most robust antioxidant and anti–skin aging activities. Indeed, the researchers reported that its antioxidant activities were comparable to ascorbic acid and Trolox and its anti–skin aging potency on a par with epigallocatechin-3-gallate and oleanolic acid. The ultrasound-assisted extract was also deemed safe as it did not provoke irritation. The authors concluded that this environmentally suitable extraction method for M. integrifolia is appropriate for obtaining effective macadamia extracts for use in cosmetics and cosmeceuticals.³

Anti-Aging Activity

In 2017, Addy et al. set out to characterize skin surface lipid composition and differences in an age- and sex-controlled population as a foundation for developing a botanically derived skin surface lipid mimetic agent. They noted that fatty acids, triglycerides, cholesterol, steryl esters, wax esters, and squalene are the main constituents of skin surface lipids. The investigators obtained skin surface lipid samples from the foreheads of 59 healthy 22-year-old women, analyzed them, and used the raw components of M. integrifolia, Simmondsia chinensis, and Olea europaea to engineer a mimetic product. They reported that the esterification reactions of jojoba, macadamia, and tall oils, combined with squalene derived from O. europaea, yielded an appropriate skin surface lipid mimetic, which, when applied to delipidized skin, assisted in recovering barrier function, enhancing skin hydration, and improving elasticity as well as firmness in aged skin. The researchers concluded that this skin surface lipid mimetic could serve as an effective supplement to human skin surface lipids in aged skin and for conditions in which the stratum corneum is impaired.⁴

Two years later, Hanum et al. compared the effects of macadamia nut oil nanocream and conventional cream for treating cutaneous aging over a 4-week period. The macadamia nut oil nanocream, which contained macadamia nut oil 10%, tween 80, propylene glycol, cetyl alcohol, methylparaben, propylparaben, and distilled water, was compared with the conventional cream based on effects on moisture, evenness, pore size, melanin, and wrinkling. The macadamia nut oil was found to yield superior anti-aging activity along each parameter as compared with the conventional cream. The researchers concluded that the macadamia nut oil in nanocream can be an effective formulation for providing benefits in addressing cutaneous aging.⁵

Matthieu Sontag/Wikimedia Commons/CC-BY-SA

Antifungal Activity

In 2015, Vieira et al. characterized 12 fractions enriched in peptides derived from L. pisonis seeds to determine inhibitory activity against Candida albicans. The fraction that exerted the strongest activity at 10 μg/mL, suppressing C. albicans growth by 38.5% and inducing a 69.3% loss of viability, was identified as similar to plant defensins and thus dubbed “L. pisonis defensin 1 (Lp-Def1).” The investigators concluded that Lp-Def1 acts on C. albicans by slightly elevating the induction of reactive oxygen species and causing a significant reduction in mitochondrial activity. They suggested that their findings support the use of plant defensins, particularly Lp-Def1, in the formulation of antifungal products, especially to address C. albicans.¹⁰

Pruritus

In 2012, Silva et al. studied the antipruritic impact of L. pisonis leaf extracts in mice and rats. Pretreatment with the various fractions of L. pisonis as well as constituent mixed triterpenes (ursolic and oleanolic acids) significantly blocked scratching behavior provoked by compound 48/80. The degranulation of rat peritoneal mast cells caused by compound 48/80 was also substantially decreased from pretreatment with the ethanol extract of L. pisonis, ether-L. pisonis fraction, and mixed triterpenes. The L. pisonis ether fraction suppressed edema induced by carrageenan administration and the ethanol extract displayed no toxicity up to an oral dose of 2g/kg. The investigators concluded that their results strongly support the antipruritic effects of L. pisonis leaves as well as the traditional use of the plant to treat pruritus.²

Stability for Cosmetic Creams

In 2020, Rampazzo et al. assessed the stability and cytotoxicity of a cosmetic cream containing sapucaia nut oil. All three tested concentrations (1%, 5%, and 10%) of the cream were found to be stable, with an effective preservative system, and deemed safe for use on human skin. To maintain a pH appropriate for a body cream, the formulation requires a stabilizing agent. The cream with 5% nut oil was identified as the most stable and satisfying for use on the skin.⁷

More recently, Hertel Pereira et al. investigated the benefits of using L. pisonis pericarp extract, known to exhibit abundant antioxidants, in an all-natural skin cream. They found that formulation instability increased proportionally with the concentration of the extract, but the use of the outer pericarp of L. pisonis was well suited for the cream formulation, with physical-chemical and organoleptic qualities unchanged after the stability test.¹¹

Conclusion

The available literature on the medical applications of macadamia and sapucaia plants is sparse. Some recent findings are promising regarding possible uses in skin health. However, much more research is necessary before considering macadamia and sapucaia as viable sources of botanical agents capable of delivering significant cutaneous benefits.

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 Inc., an SaaS company used to generate skin care routines in office and as an e-commerce solution. Write to her at [email protected].

References

1. Dailey A and Vuong QV. Antioxidants (Basel). 2015 Nov 12;4(4):699-718.

2. Silva LL et al. J Ethnopharmacol. 2012 Jan 6;139(1):90-97.

3. Somwongin S et al. Ultrason Sonochem. 2023 Jan;92:106266.

4. Addy J et al. J Cosmet Sci. 2017 Jan/Feb;68(1):59-67.

5. Hanum TI et al. Open Access Maced J Med Sci. 2019 Nov 14;7(22):3917-3920.

6. Akhtar N and Yazan Y. Pak J Pharm Sci. 2008 Jan;21(1):45-50.

7. Rampazzo APS et al. J Cosmet Sci. 2020 Sep/Oct;71(5):239-250.

8. Rosa TLM et al. Food Res Int. 2020 Nov;137:109383.

9. Demoliner F et al. Food Res Int. 2018 Oct;112:434-442.

10. Vieira ME et al. Acta Biochim Biophys Sin (Shanghai). 2015 Sep;47(9):716-729.

11. Hertel Pereira AC et al. J Cosmet Sci. 2021 Mar-Apr;72(2):155-162.