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Is Parenthood Losing Its Appeal?

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Changed
Thu, 08/01/2024 - 09:27

A recent survey by the Pew Research Center has found that among adults younger than 50, the percentage who say they are unlikely to have children rose from 37% to 47%. With this trend freshly etched in my consciousness, I stumbled across an interview with Anastasia Berg, an assistant professor of philosophy at the University of California, Irvine. Professor Berg and Rachel Wiseman have just published What Are Children For? On Ambivalence and Choice. How could a pediatrician with time on his hands ignore a provocative title like that?

I was immediately drawn to Professor Berg’s observations about the “concerns, anxieties, and lines of reasoning people encounter when considering whether or not they should have children.” Prior to the 1960s, motherhood seemed to just be a natural progression from marriage. That’s the way my wife and I approached it when we had our first child while I was in my last year of medical school in 1971. There was no discussion of the pros and cons, except maybe that financially waiting until the eve of my first professional paycheck seemed to make sense.

Dr. William G. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years.
Dr. William G. Wilkoff

However, as Professor Berg points out, from the 1960s up until well into the 1980s, as feminist thought gained a higher profile, there were anti-motherhood factions. There were others who wanted to see motherhood reformed and adapted so it “could once again be a legitimate source of meaning and value in life.” However, both camps agreed that the choice to have children was a decision that “women should make completely on their own.”

Now, well into the new millennium, we are looking at a completely different landscape. In the past, having children was woven into the fabric of human life in which we had a past, a present, and a role in creating the future. Professor Berg observes that currently, having children is often considered a project, not unlike our other projects such as “career choice or travel plans.” What are the pluses and minuses?

The Pew Survey found that 60% of adults younger than 50 who don’t have children said that not having children made it less difficult to be successful and have an active social life. Many felt that being a parent would improve the chances of having someone to care for you as you aged.

When my wife and I considered the financial costs of motherhood more than 50 years ago, our calculation was primarily about the timing. The decision to have a second child focused our concern around our ability to balance our attention between two siblings. A third child just sorta happened without any discussion.

Professor Berg echoes the Pew findings when she observes that currently woman are considering the cost in terms of their identities. Will motherhood transform me? Will there be a cost not only to my career but also to all the associations, interests, and activities I have accumulated? These costs are likely to be greater the longer the decision to have a child is put off. She adds that viewing motherhood as a transformation can make the decision to have children scarier than it needs to be. My wife and I, at age 26 and 27, were still in the early stages of building our identities. My wife had a 2-year college degree and no career plans on the horizon. Having a child was one of those things that was built into who we became.

But to compare our experiences in the 1970s to the realities of the first quarter of the 21st century ignores the concerns facing today’s adults who are facing the cloud of uncertainty hanging over all of us. Despite their claims to fix the situation, both sides of the political spectrum are leveraging fear to gain our support. Even climate change skeptics must have some concern in the spate of natural disasters we are experiencing. Not to mention the pandemic. Anxiety in this country is at an all time high. Optimism doesn’t seem to fit into today’s journalists’ lexicon, as they chose to focus on conflict instead of cooperation. It’s hard to question any adult who harbors serious doubts on taking on the challenge of parenthood and bringing a child into a world that feels unsettled.

However, based on her research and her own experience as a parent, Professor Berg offers some advice. She encourages people to think and discuss the decision to have children earlier in their life trajectory, before they have made decisions that may eventually limit their options. Second, she discourages making a list of pros and cons. Finally, she advises taking a long view and ask yourself whether you “choose to take a direct part in ushering in the next generation.”

Sounds like advice that will optimize the chances of making the good decision about having a child. I’m just thankful to have lived at time and in a situation when having child was just the thing most married couples did.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

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A recent survey by the Pew Research Center has found that among adults younger than 50, the percentage who say they are unlikely to have children rose from 37% to 47%. With this trend freshly etched in my consciousness, I stumbled across an interview with Anastasia Berg, an assistant professor of philosophy at the University of California, Irvine. Professor Berg and Rachel Wiseman have just published What Are Children For? On Ambivalence and Choice. How could a pediatrician with time on his hands ignore a provocative title like that?

I was immediately drawn to Professor Berg’s observations about the “concerns, anxieties, and lines of reasoning people encounter when considering whether or not they should have children.” Prior to the 1960s, motherhood seemed to just be a natural progression from marriage. That’s the way my wife and I approached it when we had our first child while I was in my last year of medical school in 1971. There was no discussion of the pros and cons, except maybe that financially waiting until the eve of my first professional paycheck seemed to make sense.

Dr. William G. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years.
Dr. William G. Wilkoff

However, as Professor Berg points out, from the 1960s up until well into the 1980s, as feminist thought gained a higher profile, there were anti-motherhood factions. There were others who wanted to see motherhood reformed and adapted so it “could once again be a legitimate source of meaning and value in life.” However, both camps agreed that the choice to have children was a decision that “women should make completely on their own.”

Now, well into the new millennium, we are looking at a completely different landscape. In the past, having children was woven into the fabric of human life in which we had a past, a present, and a role in creating the future. Professor Berg observes that currently, having children is often considered a project, not unlike our other projects such as “career choice or travel plans.” What are the pluses and minuses?

The Pew Survey found that 60% of adults younger than 50 who don’t have children said that not having children made it less difficult to be successful and have an active social life. Many felt that being a parent would improve the chances of having someone to care for you as you aged.

When my wife and I considered the financial costs of motherhood more than 50 years ago, our calculation was primarily about the timing. The decision to have a second child focused our concern around our ability to balance our attention between two siblings. A third child just sorta happened without any discussion.

Professor Berg echoes the Pew findings when she observes that currently woman are considering the cost in terms of their identities. Will motherhood transform me? Will there be a cost not only to my career but also to all the associations, interests, and activities I have accumulated? These costs are likely to be greater the longer the decision to have a child is put off. She adds that viewing motherhood as a transformation can make the decision to have children scarier than it needs to be. My wife and I, at age 26 and 27, were still in the early stages of building our identities. My wife had a 2-year college degree and no career plans on the horizon. Having a child was one of those things that was built into who we became.

But to compare our experiences in the 1970s to the realities of the first quarter of the 21st century ignores the concerns facing today’s adults who are facing the cloud of uncertainty hanging over all of us. Despite their claims to fix the situation, both sides of the political spectrum are leveraging fear to gain our support. Even climate change skeptics must have some concern in the spate of natural disasters we are experiencing. Not to mention the pandemic. Anxiety in this country is at an all time high. Optimism doesn’t seem to fit into today’s journalists’ lexicon, as they chose to focus on conflict instead of cooperation. It’s hard to question any adult who harbors serious doubts on taking on the challenge of parenthood and bringing a child into a world that feels unsettled.

However, based on her research and her own experience as a parent, Professor Berg offers some advice. She encourages people to think and discuss the decision to have children earlier in their life trajectory, before they have made decisions that may eventually limit their options. Second, she discourages making a list of pros and cons. Finally, she advises taking a long view and ask yourself whether you “choose to take a direct part in ushering in the next generation.”

Sounds like advice that will optimize the chances of making the good decision about having a child. I’m just thankful to have lived at time and in a situation when having child was just the thing most married couples did.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

A recent survey by the Pew Research Center has found that among adults younger than 50, the percentage who say they are unlikely to have children rose from 37% to 47%. With this trend freshly etched in my consciousness, I stumbled across an interview with Anastasia Berg, an assistant professor of philosophy at the University of California, Irvine. Professor Berg and Rachel Wiseman have just published What Are Children For? On Ambivalence and Choice. How could a pediatrician with time on his hands ignore a provocative title like that?

I was immediately drawn to Professor Berg’s observations about the “concerns, anxieties, and lines of reasoning people encounter when considering whether or not they should have children.” Prior to the 1960s, motherhood seemed to just be a natural progression from marriage. That’s the way my wife and I approached it when we had our first child while I was in my last year of medical school in 1971. There was no discussion of the pros and cons, except maybe that financially waiting until the eve of my first professional paycheck seemed to make sense.

Dr. William G. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years.
Dr. William G. Wilkoff

However, as Professor Berg points out, from the 1960s up until well into the 1980s, as feminist thought gained a higher profile, there were anti-motherhood factions. There were others who wanted to see motherhood reformed and adapted so it “could once again be a legitimate source of meaning and value in life.” However, both camps agreed that the choice to have children was a decision that “women should make completely on their own.”

Now, well into the new millennium, we are looking at a completely different landscape. In the past, having children was woven into the fabric of human life in which we had a past, a present, and a role in creating the future. Professor Berg observes that currently, having children is often considered a project, not unlike our other projects such as “career choice or travel plans.” What are the pluses and minuses?

The Pew Survey found that 60% of adults younger than 50 who don’t have children said that not having children made it less difficult to be successful and have an active social life. Many felt that being a parent would improve the chances of having someone to care for you as you aged.

When my wife and I considered the financial costs of motherhood more than 50 years ago, our calculation was primarily about the timing. The decision to have a second child focused our concern around our ability to balance our attention between two siblings. A third child just sorta happened without any discussion.

Professor Berg echoes the Pew findings when she observes that currently woman are considering the cost in terms of their identities. Will motherhood transform me? Will there be a cost not only to my career but also to all the associations, interests, and activities I have accumulated? These costs are likely to be greater the longer the decision to have a child is put off. She adds that viewing motherhood as a transformation can make the decision to have children scarier than it needs to be. My wife and I, at age 26 and 27, were still in the early stages of building our identities. My wife had a 2-year college degree and no career plans on the horizon. Having a child was one of those things that was built into who we became.

But to compare our experiences in the 1970s to the realities of the first quarter of the 21st century ignores the concerns facing today’s adults who are facing the cloud of uncertainty hanging over all of us. Despite their claims to fix the situation, both sides of the political spectrum are leveraging fear to gain our support. Even climate change skeptics must have some concern in the spate of natural disasters we are experiencing. Not to mention the pandemic. Anxiety in this country is at an all time high. Optimism doesn’t seem to fit into today’s journalists’ lexicon, as they chose to focus on conflict instead of cooperation. It’s hard to question any adult who harbors serious doubts on taking on the challenge of parenthood and bringing a child into a world that feels unsettled.

However, based on her research and her own experience as a parent, Professor Berg offers some advice. She encourages people to think and discuss the decision to have children earlier in their life trajectory, before they have made decisions that may eventually limit their options. Second, she discourages making a list of pros and cons. Finally, she advises taking a long view and ask yourself whether you “choose to take a direct part in ushering in the next generation.”

Sounds like advice that will optimize the chances of making the good decision about having a child. I’m just thankful to have lived at time and in a situation when having child was just the thing most married couples did.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

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Study Quantifies Benefit of Newborn Screening for Vitamin B12 Deficiency

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Changed
Wed, 07/31/2024 - 15:34

Newborn screening for neonatal vitamin B12 deficiency may lead to a fourfold reduction in chances of developing symptomatic vitamin B12 in the first year of life compared with infants without newborn screening, a hospital-based surveillance study in Germany indicates.

Vitamin B12 deficiency can impede development in infants, but the true impact of newborn screening versus no screening had not been known in Germany. Early treatment had been shown to be linked with normal development in infants who got newborn screening, but left unclear was how many who had newborn screening would have progressed to symptomatic vitamin B12 deficiency without treatment. Thus formal evidence for the benefit of the screening was lacking.

The nationwide surveillance study, led by Ulrike Mütze, MD, with the Heidelberg University Center for Child and Adolescent Medicine, was published online in Pediatrics. It used prospectively collected data from incident cases of infants under 12 months of age with vitamin B12 deficiency from 2021 to 2022.

The researchers analyzed 61 cases of vitamin B12 deficiency reported to the German Pediatric Surveillance Unit. They were either identified by newborn screening (n = 31) or diagnosed after the onset of suggestive symptoms (non-newborn screening; n = 30).

At a median 4 months of age, the great majority (90%) of the infants identified by newborn screening were still asymptomatic, while the non-newborn screening cohort presented with muscular hypotonia (68%), anemia (58%), developmental delay (44%), microcephalia (30%), and seizures (12%).

Symptomatically diagnosed vitamin B12 deficiency in the baby’s first year was reported four times more frequently in infants who did not receive newborn screening for neonatal vitamin B12 deficiency compared with those screened for vitamin B12 as newborns (Fisher’s Exact Test; odds ratio, 4.12 [95% confidence interval, 1.29-17.18], P = .008).

Clinical presentation of vitamin B12 deficiency in infants usually starts in the first months and reportedly includes, in addition to developmental delay, feeding difficulties, muscular hypotonia and weakness, severe failure to thrive, irritability, lethargy, and (as late symptoms) megaloblastic anemia and brain atrophy.

The current study confirmed these reports and highlighted that the most common presentations in symptomatic infantile vitamin B12 deficiency were muscular hypotonia, anemia, developmental delay, malnutrition or failure to thrive, and microcephalia, brain atrophy, or delayed myelination.

Stephen Walker, MD, a pediatric neurologist at University of Alabama, Birmingham, who was not involved with the study, said newborn screening for vitamin B12 deficiency is routine in the United States.

“In Alabama, we’re generally the last to adopt any of these newborn screenings ... and we’ve been doing it for several years,” he said. Vitamin B12 deficiency is one of 59 conditions included in the state’s newborn blood spot screening. In the United States, he added, when deficiencies are identified, cases are quickly referred to genetic or nutritional specialists.

In the Mütze et al. study, the authors conclude, “The incidence of symptomatic vitamin B12 deficiency accounts for about half of the estimated incidence of the vitamin B12 deficiency identified by newborn screening [NBS]. This supports the notion that not all newborns identified will develop a symptomatic infantile vitamin B12 deficiency but at the same time [this study demonstrates] the high beneficial potential of NBS for vitamin B12 deficiency.”

Dr. Mütze received a research grant from the Medical Faculty of Heidelberg University, Germany. Dr. Kölker, Dr. Hoffmann, and Dr. Mütze received research grants for their work on newborn screening from the Dietmar Hopp Foundation, St. Leon-Rot, Germany. Dr. Hoffmann, Dr. Janzen, and Dr. Röschinger are principal investigators for newborn screening pilot studies including neonatal vitamin B12 deficiency. The other authors have no relevant disclosures. Dr. Walker reports no relevant financial relationships.

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Newborn screening for neonatal vitamin B12 deficiency may lead to a fourfold reduction in chances of developing symptomatic vitamin B12 in the first year of life compared with infants without newborn screening, a hospital-based surveillance study in Germany indicates.

Vitamin B12 deficiency can impede development in infants, but the true impact of newborn screening versus no screening had not been known in Germany. Early treatment had been shown to be linked with normal development in infants who got newborn screening, but left unclear was how many who had newborn screening would have progressed to symptomatic vitamin B12 deficiency without treatment. Thus formal evidence for the benefit of the screening was lacking.

The nationwide surveillance study, led by Ulrike Mütze, MD, with the Heidelberg University Center for Child and Adolescent Medicine, was published online in Pediatrics. It used prospectively collected data from incident cases of infants under 12 months of age with vitamin B12 deficiency from 2021 to 2022.

The researchers analyzed 61 cases of vitamin B12 deficiency reported to the German Pediatric Surveillance Unit. They were either identified by newborn screening (n = 31) or diagnosed after the onset of suggestive symptoms (non-newborn screening; n = 30).

At a median 4 months of age, the great majority (90%) of the infants identified by newborn screening were still asymptomatic, while the non-newborn screening cohort presented with muscular hypotonia (68%), anemia (58%), developmental delay (44%), microcephalia (30%), and seizures (12%).

Symptomatically diagnosed vitamin B12 deficiency in the baby’s first year was reported four times more frequently in infants who did not receive newborn screening for neonatal vitamin B12 deficiency compared with those screened for vitamin B12 as newborns (Fisher’s Exact Test; odds ratio, 4.12 [95% confidence interval, 1.29-17.18], P = .008).

Clinical presentation of vitamin B12 deficiency in infants usually starts in the first months and reportedly includes, in addition to developmental delay, feeding difficulties, muscular hypotonia and weakness, severe failure to thrive, irritability, lethargy, and (as late symptoms) megaloblastic anemia and brain atrophy.

The current study confirmed these reports and highlighted that the most common presentations in symptomatic infantile vitamin B12 deficiency were muscular hypotonia, anemia, developmental delay, malnutrition or failure to thrive, and microcephalia, brain atrophy, or delayed myelination.

Stephen Walker, MD, a pediatric neurologist at University of Alabama, Birmingham, who was not involved with the study, said newborn screening for vitamin B12 deficiency is routine in the United States.

“In Alabama, we’re generally the last to adopt any of these newborn screenings ... and we’ve been doing it for several years,” he said. Vitamin B12 deficiency is one of 59 conditions included in the state’s newborn blood spot screening. In the United States, he added, when deficiencies are identified, cases are quickly referred to genetic or nutritional specialists.

In the Mütze et al. study, the authors conclude, “The incidence of symptomatic vitamin B12 deficiency accounts for about half of the estimated incidence of the vitamin B12 deficiency identified by newborn screening [NBS]. This supports the notion that not all newborns identified will develop a symptomatic infantile vitamin B12 deficiency but at the same time [this study demonstrates] the high beneficial potential of NBS for vitamin B12 deficiency.”

Dr. Mütze received a research grant from the Medical Faculty of Heidelberg University, Germany. Dr. Kölker, Dr. Hoffmann, and Dr. Mütze received research grants for their work on newborn screening from the Dietmar Hopp Foundation, St. Leon-Rot, Germany. Dr. Hoffmann, Dr. Janzen, and Dr. Röschinger are principal investigators for newborn screening pilot studies including neonatal vitamin B12 deficiency. The other authors have no relevant disclosures. Dr. Walker reports no relevant financial relationships.

Newborn screening for neonatal vitamin B12 deficiency may lead to a fourfold reduction in chances of developing symptomatic vitamin B12 in the first year of life compared with infants without newborn screening, a hospital-based surveillance study in Germany indicates.

Vitamin B12 deficiency can impede development in infants, but the true impact of newborn screening versus no screening had not been known in Germany. Early treatment had been shown to be linked with normal development in infants who got newborn screening, but left unclear was how many who had newborn screening would have progressed to symptomatic vitamin B12 deficiency without treatment. Thus formal evidence for the benefit of the screening was lacking.

The nationwide surveillance study, led by Ulrike Mütze, MD, with the Heidelberg University Center for Child and Adolescent Medicine, was published online in Pediatrics. It used prospectively collected data from incident cases of infants under 12 months of age with vitamin B12 deficiency from 2021 to 2022.

The researchers analyzed 61 cases of vitamin B12 deficiency reported to the German Pediatric Surveillance Unit. They were either identified by newborn screening (n = 31) or diagnosed after the onset of suggestive symptoms (non-newborn screening; n = 30).

At a median 4 months of age, the great majority (90%) of the infants identified by newborn screening were still asymptomatic, while the non-newborn screening cohort presented with muscular hypotonia (68%), anemia (58%), developmental delay (44%), microcephalia (30%), and seizures (12%).

Symptomatically diagnosed vitamin B12 deficiency in the baby’s first year was reported four times more frequently in infants who did not receive newborn screening for neonatal vitamin B12 deficiency compared with those screened for vitamin B12 as newborns (Fisher’s Exact Test; odds ratio, 4.12 [95% confidence interval, 1.29-17.18], P = .008).

Clinical presentation of vitamin B12 deficiency in infants usually starts in the first months and reportedly includes, in addition to developmental delay, feeding difficulties, muscular hypotonia and weakness, severe failure to thrive, irritability, lethargy, and (as late symptoms) megaloblastic anemia and brain atrophy.

The current study confirmed these reports and highlighted that the most common presentations in symptomatic infantile vitamin B12 deficiency were muscular hypotonia, anemia, developmental delay, malnutrition or failure to thrive, and microcephalia, brain atrophy, or delayed myelination.

Stephen Walker, MD, a pediatric neurologist at University of Alabama, Birmingham, who was not involved with the study, said newborn screening for vitamin B12 deficiency is routine in the United States.

“In Alabama, we’re generally the last to adopt any of these newborn screenings ... and we’ve been doing it for several years,” he said. Vitamin B12 deficiency is one of 59 conditions included in the state’s newborn blood spot screening. In the United States, he added, when deficiencies are identified, cases are quickly referred to genetic or nutritional specialists.

In the Mütze et al. study, the authors conclude, “The incidence of symptomatic vitamin B12 deficiency accounts for about half of the estimated incidence of the vitamin B12 deficiency identified by newborn screening [NBS]. This supports the notion that not all newborns identified will develop a symptomatic infantile vitamin B12 deficiency but at the same time [this study demonstrates] the high beneficial potential of NBS for vitamin B12 deficiency.”

Dr. Mütze received a research grant from the Medical Faculty of Heidelberg University, Germany. Dr. Kölker, Dr. Hoffmann, and Dr. Mütze received research grants for their work on newborn screening from the Dietmar Hopp Foundation, St. Leon-Rot, Germany. Dr. Hoffmann, Dr. Janzen, and Dr. Röschinger are principal investigators for newborn screening pilot studies including neonatal vitamin B12 deficiency. The other authors have no relevant disclosures. Dr. Walker reports no relevant financial relationships.

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How Common Are Life-Threatening Infections In Infants with Pustules, Vesicles?

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Changed
Wed, 07/17/2024 - 09:37

 

TOPLINE:

Full-term afebrile infants with pustules and vesicles have a low likelihood of life-threatening infections once herpes simplex virus (HSV) is ruled out, according to the findings from a retrospective study.

METHODOLOGY:

  • Researchers reviewed the electronic medical records of infants aged ≤ 60 days who received a pediatric dermatology consultation at six US academic institutions between September 2013 and August 2019.
  • Among 879 consults, 183 afebrile infants were identified as having presented with pustules, vesicles, and/or bullae.
  • Infectious disease workups included blood cultures, urine cultures, lumbar punctures, and HSV testing using viral skin culture, direct immunofluorescence assay, and/or polymerase chain reaction.
  • Patients were categorized by gestational age as preterm (< 37 weeks), full-term (37-42 weeks), and post-term (≥ 42 weeks).
  • Overall, 67.8% of infants had pustules, 31.1% had vesicles, and 10.4% had bullae.

TAKEAWAY:

  • None of the cases showed positive cerebrospinal fluid or pathogenic blood cultures. In 122 of the cases (66.6%), a noninfectious cause was diagnosed, and an infectious cause was diagnosed in 71 cases (38.8%; some patients had more than one diagnosis).
  • Of the 127 newborns evaluated for HSV infection, nine (7.1%) tested positive, of whom seven (5.5%) had disease affecting the skin, eye, and mouth and were full- term infants, and two (1.6%) had disseminated HSV and were preterm infants.
  • Angioinvasive fungal infection was diagnosed in five infants (2.7%), all of whom were preterm infants (< 28 weeks gestational age).
  • The risk for life-threatening disease was higher in preterm infants born before 32 weeks of gestational age (P < .01) compared with those born after 32 weeks.

IN PRACTICE:

“Full-term, well-appearing, afebrile infants ≤ 60 days of age presenting with pustules or vesicles may not require full SBI [serious bacterial infection] work-up, although larger studies are needed,” the authors concluded. Testing for HSV, they added, “is recommended in all infants with vesicles, grouped pustules, or pustules accompanied by punched out or grouped erosions,” and preterm infants “should be assessed for disseminated fungal infection and HSV in the setting of fluid-filled skin lesions.”

SOURCE:

The study was led by Sonora Yun, BA, Columbia University, New York City, and was published online in Pediatrics.

LIMITATIONS:

The data were limited by the sample size and very low incidence of serious infections. Infants probably had atypical or severe presentations that warranted pediatric dermatology consultation, which may have led to overrepresentation of infectious disease rates. The study inclusion was restricted to those who received a dermatology consult; therefore, the findings may not be generalizable to outpatient primary care.

DISCLOSURES:

This study did not receive any external funding. The authors declared that they had no relevant conflicts of interest.

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

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TOPLINE:

Full-term afebrile infants with pustules and vesicles have a low likelihood of life-threatening infections once herpes simplex virus (HSV) is ruled out, according to the findings from a retrospective study.

METHODOLOGY:

  • Researchers reviewed the electronic medical records of infants aged ≤ 60 days who received a pediatric dermatology consultation at six US academic institutions between September 2013 and August 2019.
  • Among 879 consults, 183 afebrile infants were identified as having presented with pustules, vesicles, and/or bullae.
  • Infectious disease workups included blood cultures, urine cultures, lumbar punctures, and HSV testing using viral skin culture, direct immunofluorescence assay, and/or polymerase chain reaction.
  • Patients were categorized by gestational age as preterm (< 37 weeks), full-term (37-42 weeks), and post-term (≥ 42 weeks).
  • Overall, 67.8% of infants had pustules, 31.1% had vesicles, and 10.4% had bullae.

TAKEAWAY:

  • None of the cases showed positive cerebrospinal fluid or pathogenic blood cultures. In 122 of the cases (66.6%), a noninfectious cause was diagnosed, and an infectious cause was diagnosed in 71 cases (38.8%; some patients had more than one diagnosis).
  • Of the 127 newborns evaluated for HSV infection, nine (7.1%) tested positive, of whom seven (5.5%) had disease affecting the skin, eye, and mouth and were full- term infants, and two (1.6%) had disseminated HSV and were preterm infants.
  • Angioinvasive fungal infection was diagnosed in five infants (2.7%), all of whom were preterm infants (< 28 weeks gestational age).
  • The risk for life-threatening disease was higher in preterm infants born before 32 weeks of gestational age (P < .01) compared with those born after 32 weeks.

IN PRACTICE:

“Full-term, well-appearing, afebrile infants ≤ 60 days of age presenting with pustules or vesicles may not require full SBI [serious bacterial infection] work-up, although larger studies are needed,” the authors concluded. Testing for HSV, they added, “is recommended in all infants with vesicles, grouped pustules, or pustules accompanied by punched out or grouped erosions,” and preterm infants “should be assessed for disseminated fungal infection and HSV in the setting of fluid-filled skin lesions.”

SOURCE:

The study was led by Sonora Yun, BA, Columbia University, New York City, and was published online in Pediatrics.

LIMITATIONS:

The data were limited by the sample size and very low incidence of serious infections. Infants probably had atypical or severe presentations that warranted pediatric dermatology consultation, which may have led to overrepresentation of infectious disease rates. The study inclusion was restricted to those who received a dermatology consult; therefore, the findings may not be generalizable to outpatient primary care.

DISCLOSURES:

This study did not receive any external funding. The authors declared that they had no relevant conflicts of interest.

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

 

TOPLINE:

Full-term afebrile infants with pustules and vesicles have a low likelihood of life-threatening infections once herpes simplex virus (HSV) is ruled out, according to the findings from a retrospective study.

METHODOLOGY:

  • Researchers reviewed the electronic medical records of infants aged ≤ 60 days who received a pediatric dermatology consultation at six US academic institutions between September 2013 and August 2019.
  • Among 879 consults, 183 afebrile infants were identified as having presented with pustules, vesicles, and/or bullae.
  • Infectious disease workups included blood cultures, urine cultures, lumbar punctures, and HSV testing using viral skin culture, direct immunofluorescence assay, and/or polymerase chain reaction.
  • Patients were categorized by gestational age as preterm (< 37 weeks), full-term (37-42 weeks), and post-term (≥ 42 weeks).
  • Overall, 67.8% of infants had pustules, 31.1% had vesicles, and 10.4% had bullae.

TAKEAWAY:

  • None of the cases showed positive cerebrospinal fluid or pathogenic blood cultures. In 122 of the cases (66.6%), a noninfectious cause was diagnosed, and an infectious cause was diagnosed in 71 cases (38.8%; some patients had more than one diagnosis).
  • Of the 127 newborns evaluated for HSV infection, nine (7.1%) tested positive, of whom seven (5.5%) had disease affecting the skin, eye, and mouth and were full- term infants, and two (1.6%) had disseminated HSV and were preterm infants.
  • Angioinvasive fungal infection was diagnosed in five infants (2.7%), all of whom were preterm infants (< 28 weeks gestational age).
  • The risk for life-threatening disease was higher in preterm infants born before 32 weeks of gestational age (P < .01) compared with those born after 32 weeks.

IN PRACTICE:

“Full-term, well-appearing, afebrile infants ≤ 60 days of age presenting with pustules or vesicles may not require full SBI [serious bacterial infection] work-up, although larger studies are needed,” the authors concluded. Testing for HSV, they added, “is recommended in all infants with vesicles, grouped pustules, or pustules accompanied by punched out or grouped erosions,” and preterm infants “should be assessed for disseminated fungal infection and HSV in the setting of fluid-filled skin lesions.”

SOURCE:

The study was led by Sonora Yun, BA, Columbia University, New York City, and was published online in Pediatrics.

LIMITATIONS:

The data were limited by the sample size and very low incidence of serious infections. Infants probably had atypical or severe presentations that warranted pediatric dermatology consultation, which may have led to overrepresentation of infectious disease rates. The study inclusion was restricted to those who received a dermatology consult; therefore, the findings may not be generalizable to outpatient primary care.

DISCLOSURES:

This study did not receive any external funding. The authors declared that they had no relevant conflicts of interest.

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

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Research Highlights From ESMO Breast Cancer

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Five experts discussed research that they considered to be highlights of the European Society of Medical Oncology (ESMO) Breast Cancer annual congress during a “Key Takeaways” session at the meeting.

Among the topics the speakers addressed were breast cancer prevention, early breast cancer, advanced breast cancer, and supportive care.

In recent years, the way clinicians look at carcinogenesis in breast cancer has changed, and many new targets for potential early detection and prevention have emerged, said Suzette Delaloge, MD, of Gustave Roussy, Paris, France, in her presentation at the meeting.

Instant risk assessment at different time points could potentially intercept cancer among high-risk individuals, she said.

A study by Mikael Eriksson, PhD, and colleagues focused on external validation of the Profound AI tool to identify breast cancer risk in the general population. The researchers showed an area under the curve of 0.72 in their AI risk model, which has the potential to be clinically meaningful, although it must be prospectively validated, Dr. Delaloge said in her presentation.

She also reviewed two studies on the use of genes to further refine breast cancer risk among carriers. One of these, a prospective study presented in a session by Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Center, Melbourne, Australia, used the CANRISK online risk assessment tool and validated increased breast cancer risk in BRCA1 and BRCA2 carriers, with AUCs of 0.79 and 0.78, respectively. The other study, which was by Maria Rezqallah Aron, MD, and colleagues examined polygenic scores as a way to refine breast cancer risk stratification among carriers of the ALM and PALB2 genes as well. These genes might be useful in identifying individuals who could benefit from early intervention, including surgery, Dr. Delaloge said.
 

Translational Research

“Preparing my talk, I felt like a kid in a candy store,” because of the amount of new translational research presented, including several studies of endocrine treatment–based approaches to therapy, said Marleen Kok, MD, of the Netherlands Cancer Institute, Amsterdam.

In her presentation, Dr. Kok highlighted findings from an analysis of patients in the monarchE study (a trial of high-risk patients) showing a consistent improvement in invasive disease-free survival for the subset of patients with germline BRCA1 and BRCA2 mutations who received abemaciclib plus endocrine therapy.

The value of tumor-infiltrating lymphocytes (TILs) on patients who are not receiving chemotherapy is important because of the focus on prognosis, and prospective trials are underway, she said.

A poster on the impact of chemotherapy and stromal tumor-infiltrating lymphocytes (sTILs) in stage I triple-negative breast cancer showed no association between chemotherapy and better outcomes regardless of sTILs in patients who did and did not receive chemotherapy, which has implications for potential treatment sparing in this population, Dr. Kok noted.

Artificial Intelligence (AI) was the subject of several posters at the meeting, and Dr. Kok identified a multisite European study of an automated HER2 scoring system as notable for its size and accuracy. In the study, the accuracy among pathologists was much higher with the assistance of AI, she said. Using AI for more complex analysis has shown success, she said.

Dr. Kok ended her talk with a poster that surveyed breast cancer patients about their understanding of their disease. The results showed that less than half (44%) of patients reported that their healthcare providers had given them enough information to learn about their breast cancer type, and less than one third could recall terminology about biomarkers; the study is important because it shows that clinicians need to do better in explaining these terms to patients, Dr. Kok said.
 

 

 

Early Breast Cancer

Right-sizing therapy, meaning identifying the right treatment for every patient, is a key element of new research in early breast cancer, said Erika Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, Tenn.

She highlighted safety and treatment duration updates from the NATALEE study, which compared adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) to NSAI alone for ER+/HER2- breast cancer. The current analysis presented at the meeting showed significant benefits with the addition of ribociclib and no evidence of new safety signals or adverse event exacerbations at 3 years, she said. Dose modifications had no significant impact on efficacy, she added.

The findings of no impact of dose reduction on efficacy in both the NATALEE and monarchE studies provide important information on whether dosage can be reduced in patients, which will increase the odds that patients will tolerate extended therapy with good outcomes and stay on their prescribed therapies, Dr. Hamilton emphasized.

The CARABELA study, a phase 2 trial of neoadjuvant letrozole plus abemaciclib vs adriamycin and cyclophosphamide (AC), showed clinically similar response rates but did not meet its endpoint for residual cancer burden (RCB) scores. These data add to results from other studies and show that it is too soon to universally replace neoadjuvant chemotherapy as first-line treatment for highly proliferative ER+ breast cancer, Dr. Hamilton said in her presentation.
 

Advanced Breast Cancer

Take-home messages about advanced breast cancer include growing evidence for the potential benefits of antibody drug conjugates (ADCs), said Eva Ciruelos, MD, of University Hospital, Madrid, Spain. The TROPION-BREAST01 study, a phase 3 randomized trial, showed significant and clinically meaningful improvement in progression-free survival in patients with previously treated, inoperable, or metastatic HR+/HER2- breast cancer who received datopotamab deruxtecan (Dato-DXd) compared with those who received chemotherapy.

Data from an additional safety analysis were presented at the meeting; although Dato-DXd, a trophoblast cell-surface antigen 2 (TROP2)–directed antibody-drug conjugate, was well-tolerated, it is important to remain aware of toxicities, notably oral mucositis, which occurred in 55.6% of the patients in the study across all grades, and ocular surface toxicity, which occurred in 40% of patients across all grades, Dr. Ciruelos emphasized.

Key research in the area of advanced triple-negative breast cancer included data from the IMPASSION 132 study. This study is “specifically centered on early relapsers,” a population often excluded from other trials, Dr. Ciruelos said. In this study, patients with advanced triple-negative breast cancer were randomized to chemotherapy with or without atezolizumab, and the study showed no benefits with atezolizumab for overall survival, progression-free survival, or overall response rate, she said. “This is something to work with, because this is a very refractory population,” Dr. Ciruelos noted.

New immunotherapy combinations are needed to improve survival in advanced breast cancer patients, Dr. Ciruelos said. At the meeting, researchers presented interim data from a subset of patients in the MORPHEUS-pan breast cancer trial, a phase 1B/2 study involving multiple treatment combinations in locally advanced/metastatic breast cancer patients.

The interim analysis included 18-week data from triple-negative breast cancer patients and compared outcomes for patients randomized to atezolizumab with or without sacituzumab govitecan (SG).

 

 

The study was small, with only 31 patients in the combination arm and 11 controls, but the results were promising, with an overall response rate of 76.7% in the combination arm vs 66.7% in the control arm, Dr. Ciruelos said.

Supportive Care

Key supportive care takeaways included data on pregnancy in young breast cancer survivors and the safety of vaginal estrogen therapy in breast cancer patients with genitourinary symptoms, said Anne May, MD, of the University Medical Center Utrecht, Utrecht, Netherlands.

A study previously published in JAMA including nearly 5000 BRCA carriers who were diagnosed with invasive breast cancer at age 40 years or younger showed no association between pregnancy after breast cancer and adverse maternal or fetal outcomes, and pregnancy had no significant impact on overall survival. The authors presented new data on the safety of assisted reproductive techniques (ART) based on the 543 pregnancies in the original study, at the meeting. Of these, 436 conceived naturally, and 107 used ART. After a median of 9.1 years, ART had no effect on disease-free survival compared to natural conception (hazard ratio [HR], 0.64). Based on these findings, fertility preservation should be offered to all women who receive a breast cancer diagnosis and are interested in future fertility, Dr. May said.

Conceiving after breast cancer treatment and follow-up should not be contraindicated for young BRCA carriers, she added.No trial data are available for the effects of vaginal estrogen therapy (VET) on disease-free survival in breast cancer survivors with genitourinary symptoms caused by declining estrogen levels, Dr. May said. However, researchers in France and Switzerland conducted an emulation of a hypothetical target trial using data from the French National social security system for more than 130,000 individuals. Although VET therapy had no impact on disease-free survival in most breast cancer survivors overall, it did have a negative impact in a subset of patients with HR-positive and HR-negative tumors who were treated with aromatase inhibitors. The study was hypothetical, but important because the results suggest that clinicians can safely propose VTE to patients who report genitourinary symptoms after treatment for early-stage breast cancer with tamoxifen, but VTE should be avoided in patients treated with aromatase inhibitors, Dr. May said.

Dr. Delaloge disclosed research support to her institution from AstraZeneca, MSD, Bristol Myers Squibb, Sanofi, Taiho, Novartis, European Commission, INCa, Banque des Territoires, and Fondation Philanthropia. She also disclosed honoraria to her institution from AstraZeneca, Gilead, Novartis, Elsan, Besins, Sanofi, Exact Sciences, and Lilly, as well as travel support from Novartis.

Dr. Kok disclosed research funding from AstraZeneca, Bristol Myers Squibb, Daichi, and Roche, and advisory board membership/speaker’s fees from Alderaan Biotechnology, BIONTECH, Domain Therapeutics, AstraZeneca, Daichi, Bristol Myers Squibb, Gilead, Medscape, MSD, and Roche.

Dr. Hamilton disclosed a consulting advisory role (to her institution) for Accutar Biotechology, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Entos, Forsum Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Roche/Genentech, Stemline Therapeutics, ands others. She also disclosed contracted research/grant support to her institution only from Abbvie, Acerta Pharma, Accutar Biotechnology , ADC Therapeutics, AKESOBIO Australia , Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond and others.

Dr. Ciruelos disclosed serving as an external advisor for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, and Lilly, as well as serving as a speaker for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, Lilly, and Pierre Fabre. She also disclosed travel grants from Roche, Pfizer, and AstraZeneca, and research grants from Seagen and Roche.

Dr. May had no financial conflicts to disclose.

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Five experts discussed research that they considered to be highlights of the European Society of Medical Oncology (ESMO) Breast Cancer annual congress during a “Key Takeaways” session at the meeting.

Among the topics the speakers addressed were breast cancer prevention, early breast cancer, advanced breast cancer, and supportive care.

In recent years, the way clinicians look at carcinogenesis in breast cancer has changed, and many new targets for potential early detection and prevention have emerged, said Suzette Delaloge, MD, of Gustave Roussy, Paris, France, in her presentation at the meeting.

Instant risk assessment at different time points could potentially intercept cancer among high-risk individuals, she said.

A study by Mikael Eriksson, PhD, and colleagues focused on external validation of the Profound AI tool to identify breast cancer risk in the general population. The researchers showed an area under the curve of 0.72 in their AI risk model, which has the potential to be clinically meaningful, although it must be prospectively validated, Dr. Delaloge said in her presentation.

She also reviewed two studies on the use of genes to further refine breast cancer risk among carriers. One of these, a prospective study presented in a session by Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Center, Melbourne, Australia, used the CANRISK online risk assessment tool and validated increased breast cancer risk in BRCA1 and BRCA2 carriers, with AUCs of 0.79 and 0.78, respectively. The other study, which was by Maria Rezqallah Aron, MD, and colleagues examined polygenic scores as a way to refine breast cancer risk stratification among carriers of the ALM and PALB2 genes as well. These genes might be useful in identifying individuals who could benefit from early intervention, including surgery, Dr. Delaloge said.
 

Translational Research

“Preparing my talk, I felt like a kid in a candy store,” because of the amount of new translational research presented, including several studies of endocrine treatment–based approaches to therapy, said Marleen Kok, MD, of the Netherlands Cancer Institute, Amsterdam.

In her presentation, Dr. Kok highlighted findings from an analysis of patients in the monarchE study (a trial of high-risk patients) showing a consistent improvement in invasive disease-free survival for the subset of patients with germline BRCA1 and BRCA2 mutations who received abemaciclib plus endocrine therapy.

The value of tumor-infiltrating lymphocytes (TILs) on patients who are not receiving chemotherapy is important because of the focus on prognosis, and prospective trials are underway, she said.

A poster on the impact of chemotherapy and stromal tumor-infiltrating lymphocytes (sTILs) in stage I triple-negative breast cancer showed no association between chemotherapy and better outcomes regardless of sTILs in patients who did and did not receive chemotherapy, which has implications for potential treatment sparing in this population, Dr. Kok noted.

Artificial Intelligence (AI) was the subject of several posters at the meeting, and Dr. Kok identified a multisite European study of an automated HER2 scoring system as notable for its size and accuracy. In the study, the accuracy among pathologists was much higher with the assistance of AI, she said. Using AI for more complex analysis has shown success, she said.

Dr. Kok ended her talk with a poster that surveyed breast cancer patients about their understanding of their disease. The results showed that less than half (44%) of patients reported that their healthcare providers had given them enough information to learn about their breast cancer type, and less than one third could recall terminology about biomarkers; the study is important because it shows that clinicians need to do better in explaining these terms to patients, Dr. Kok said.
 

 

 

Early Breast Cancer

Right-sizing therapy, meaning identifying the right treatment for every patient, is a key element of new research in early breast cancer, said Erika Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, Tenn.

She highlighted safety and treatment duration updates from the NATALEE study, which compared adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) to NSAI alone for ER+/HER2- breast cancer. The current analysis presented at the meeting showed significant benefits with the addition of ribociclib and no evidence of new safety signals or adverse event exacerbations at 3 years, she said. Dose modifications had no significant impact on efficacy, she added.

The findings of no impact of dose reduction on efficacy in both the NATALEE and monarchE studies provide important information on whether dosage can be reduced in patients, which will increase the odds that patients will tolerate extended therapy with good outcomes and stay on their prescribed therapies, Dr. Hamilton emphasized.

The CARABELA study, a phase 2 trial of neoadjuvant letrozole plus abemaciclib vs adriamycin and cyclophosphamide (AC), showed clinically similar response rates but did not meet its endpoint for residual cancer burden (RCB) scores. These data add to results from other studies and show that it is too soon to universally replace neoadjuvant chemotherapy as first-line treatment for highly proliferative ER+ breast cancer, Dr. Hamilton said in her presentation.
 

Advanced Breast Cancer

Take-home messages about advanced breast cancer include growing evidence for the potential benefits of antibody drug conjugates (ADCs), said Eva Ciruelos, MD, of University Hospital, Madrid, Spain. The TROPION-BREAST01 study, a phase 3 randomized trial, showed significant and clinically meaningful improvement in progression-free survival in patients with previously treated, inoperable, or metastatic HR+/HER2- breast cancer who received datopotamab deruxtecan (Dato-DXd) compared with those who received chemotherapy.

Data from an additional safety analysis were presented at the meeting; although Dato-DXd, a trophoblast cell-surface antigen 2 (TROP2)–directed antibody-drug conjugate, was well-tolerated, it is important to remain aware of toxicities, notably oral mucositis, which occurred in 55.6% of the patients in the study across all grades, and ocular surface toxicity, which occurred in 40% of patients across all grades, Dr. Ciruelos emphasized.

Key research in the area of advanced triple-negative breast cancer included data from the IMPASSION 132 study. This study is “specifically centered on early relapsers,” a population often excluded from other trials, Dr. Ciruelos said. In this study, patients with advanced triple-negative breast cancer were randomized to chemotherapy with or without atezolizumab, and the study showed no benefits with atezolizumab for overall survival, progression-free survival, or overall response rate, she said. “This is something to work with, because this is a very refractory population,” Dr. Ciruelos noted.

New immunotherapy combinations are needed to improve survival in advanced breast cancer patients, Dr. Ciruelos said. At the meeting, researchers presented interim data from a subset of patients in the MORPHEUS-pan breast cancer trial, a phase 1B/2 study involving multiple treatment combinations in locally advanced/metastatic breast cancer patients.

The interim analysis included 18-week data from triple-negative breast cancer patients and compared outcomes for patients randomized to atezolizumab with or without sacituzumab govitecan (SG).

 

 

The study was small, with only 31 patients in the combination arm and 11 controls, but the results were promising, with an overall response rate of 76.7% in the combination arm vs 66.7% in the control arm, Dr. Ciruelos said.

Supportive Care

Key supportive care takeaways included data on pregnancy in young breast cancer survivors and the safety of vaginal estrogen therapy in breast cancer patients with genitourinary symptoms, said Anne May, MD, of the University Medical Center Utrecht, Utrecht, Netherlands.

A study previously published in JAMA including nearly 5000 BRCA carriers who were diagnosed with invasive breast cancer at age 40 years or younger showed no association between pregnancy after breast cancer and adverse maternal or fetal outcomes, and pregnancy had no significant impact on overall survival. The authors presented new data on the safety of assisted reproductive techniques (ART) based on the 543 pregnancies in the original study, at the meeting. Of these, 436 conceived naturally, and 107 used ART. After a median of 9.1 years, ART had no effect on disease-free survival compared to natural conception (hazard ratio [HR], 0.64). Based on these findings, fertility preservation should be offered to all women who receive a breast cancer diagnosis and are interested in future fertility, Dr. May said.

Conceiving after breast cancer treatment and follow-up should not be contraindicated for young BRCA carriers, she added.No trial data are available for the effects of vaginal estrogen therapy (VET) on disease-free survival in breast cancer survivors with genitourinary symptoms caused by declining estrogen levels, Dr. May said. However, researchers in France and Switzerland conducted an emulation of a hypothetical target trial using data from the French National social security system for more than 130,000 individuals. Although VET therapy had no impact on disease-free survival in most breast cancer survivors overall, it did have a negative impact in a subset of patients with HR-positive and HR-negative tumors who were treated with aromatase inhibitors. The study was hypothetical, but important because the results suggest that clinicians can safely propose VTE to patients who report genitourinary symptoms after treatment for early-stage breast cancer with tamoxifen, but VTE should be avoided in patients treated with aromatase inhibitors, Dr. May said.

Dr. Delaloge disclosed research support to her institution from AstraZeneca, MSD, Bristol Myers Squibb, Sanofi, Taiho, Novartis, European Commission, INCa, Banque des Territoires, and Fondation Philanthropia. She also disclosed honoraria to her institution from AstraZeneca, Gilead, Novartis, Elsan, Besins, Sanofi, Exact Sciences, and Lilly, as well as travel support from Novartis.

Dr. Kok disclosed research funding from AstraZeneca, Bristol Myers Squibb, Daichi, and Roche, and advisory board membership/speaker’s fees from Alderaan Biotechnology, BIONTECH, Domain Therapeutics, AstraZeneca, Daichi, Bristol Myers Squibb, Gilead, Medscape, MSD, and Roche.

Dr. Hamilton disclosed a consulting advisory role (to her institution) for Accutar Biotechology, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Entos, Forsum Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Roche/Genentech, Stemline Therapeutics, ands others. She also disclosed contracted research/grant support to her institution only from Abbvie, Acerta Pharma, Accutar Biotechnology , ADC Therapeutics, AKESOBIO Australia , Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond and others.

Dr. Ciruelos disclosed serving as an external advisor for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, and Lilly, as well as serving as a speaker for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, Lilly, and Pierre Fabre. She also disclosed travel grants from Roche, Pfizer, and AstraZeneca, and research grants from Seagen and Roche.

Dr. May had no financial conflicts to disclose.

 

Five experts discussed research that they considered to be highlights of the European Society of Medical Oncology (ESMO) Breast Cancer annual congress during a “Key Takeaways” session at the meeting.

Among the topics the speakers addressed were breast cancer prevention, early breast cancer, advanced breast cancer, and supportive care.

In recent years, the way clinicians look at carcinogenesis in breast cancer has changed, and many new targets for potential early detection and prevention have emerged, said Suzette Delaloge, MD, of Gustave Roussy, Paris, France, in her presentation at the meeting.

Instant risk assessment at different time points could potentially intercept cancer among high-risk individuals, she said.

A study by Mikael Eriksson, PhD, and colleagues focused on external validation of the Profound AI tool to identify breast cancer risk in the general population. The researchers showed an area under the curve of 0.72 in their AI risk model, which has the potential to be clinically meaningful, although it must be prospectively validated, Dr. Delaloge said in her presentation.

She also reviewed two studies on the use of genes to further refine breast cancer risk among carriers. One of these, a prospective study presented in a session by Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Center, Melbourne, Australia, used the CANRISK online risk assessment tool and validated increased breast cancer risk in BRCA1 and BRCA2 carriers, with AUCs of 0.79 and 0.78, respectively. The other study, which was by Maria Rezqallah Aron, MD, and colleagues examined polygenic scores as a way to refine breast cancer risk stratification among carriers of the ALM and PALB2 genes as well. These genes might be useful in identifying individuals who could benefit from early intervention, including surgery, Dr. Delaloge said.
 

Translational Research

“Preparing my talk, I felt like a kid in a candy store,” because of the amount of new translational research presented, including several studies of endocrine treatment–based approaches to therapy, said Marleen Kok, MD, of the Netherlands Cancer Institute, Amsterdam.

In her presentation, Dr. Kok highlighted findings from an analysis of patients in the monarchE study (a trial of high-risk patients) showing a consistent improvement in invasive disease-free survival for the subset of patients with germline BRCA1 and BRCA2 mutations who received abemaciclib plus endocrine therapy.

The value of tumor-infiltrating lymphocytes (TILs) on patients who are not receiving chemotherapy is important because of the focus on prognosis, and prospective trials are underway, she said.

A poster on the impact of chemotherapy and stromal tumor-infiltrating lymphocytes (sTILs) in stage I triple-negative breast cancer showed no association between chemotherapy and better outcomes regardless of sTILs in patients who did and did not receive chemotherapy, which has implications for potential treatment sparing in this population, Dr. Kok noted.

Artificial Intelligence (AI) was the subject of several posters at the meeting, and Dr. Kok identified a multisite European study of an automated HER2 scoring system as notable for its size and accuracy. In the study, the accuracy among pathologists was much higher with the assistance of AI, she said. Using AI for more complex analysis has shown success, she said.

Dr. Kok ended her talk with a poster that surveyed breast cancer patients about their understanding of their disease. The results showed that less than half (44%) of patients reported that their healthcare providers had given them enough information to learn about their breast cancer type, and less than one third could recall terminology about biomarkers; the study is important because it shows that clinicians need to do better in explaining these terms to patients, Dr. Kok said.
 

 

 

Early Breast Cancer

Right-sizing therapy, meaning identifying the right treatment for every patient, is a key element of new research in early breast cancer, said Erika Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, Tenn.

She highlighted safety and treatment duration updates from the NATALEE study, which compared adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) to NSAI alone for ER+/HER2- breast cancer. The current analysis presented at the meeting showed significant benefits with the addition of ribociclib and no evidence of new safety signals or adverse event exacerbations at 3 years, she said. Dose modifications had no significant impact on efficacy, she added.

The findings of no impact of dose reduction on efficacy in both the NATALEE and monarchE studies provide important information on whether dosage can be reduced in patients, which will increase the odds that patients will tolerate extended therapy with good outcomes and stay on their prescribed therapies, Dr. Hamilton emphasized.

The CARABELA study, a phase 2 trial of neoadjuvant letrozole plus abemaciclib vs adriamycin and cyclophosphamide (AC), showed clinically similar response rates but did not meet its endpoint for residual cancer burden (RCB) scores. These data add to results from other studies and show that it is too soon to universally replace neoadjuvant chemotherapy as first-line treatment for highly proliferative ER+ breast cancer, Dr. Hamilton said in her presentation.
 

Advanced Breast Cancer

Take-home messages about advanced breast cancer include growing evidence for the potential benefits of antibody drug conjugates (ADCs), said Eva Ciruelos, MD, of University Hospital, Madrid, Spain. The TROPION-BREAST01 study, a phase 3 randomized trial, showed significant and clinically meaningful improvement in progression-free survival in patients with previously treated, inoperable, or metastatic HR+/HER2- breast cancer who received datopotamab deruxtecan (Dato-DXd) compared with those who received chemotherapy.

Data from an additional safety analysis were presented at the meeting; although Dato-DXd, a trophoblast cell-surface antigen 2 (TROP2)–directed antibody-drug conjugate, was well-tolerated, it is important to remain aware of toxicities, notably oral mucositis, which occurred in 55.6% of the patients in the study across all grades, and ocular surface toxicity, which occurred in 40% of patients across all grades, Dr. Ciruelos emphasized.

Key research in the area of advanced triple-negative breast cancer included data from the IMPASSION 132 study. This study is “specifically centered on early relapsers,” a population often excluded from other trials, Dr. Ciruelos said. In this study, patients with advanced triple-negative breast cancer were randomized to chemotherapy with or without atezolizumab, and the study showed no benefits with atezolizumab for overall survival, progression-free survival, or overall response rate, she said. “This is something to work with, because this is a very refractory population,” Dr. Ciruelos noted.

New immunotherapy combinations are needed to improve survival in advanced breast cancer patients, Dr. Ciruelos said. At the meeting, researchers presented interim data from a subset of patients in the MORPHEUS-pan breast cancer trial, a phase 1B/2 study involving multiple treatment combinations in locally advanced/metastatic breast cancer patients.

The interim analysis included 18-week data from triple-negative breast cancer patients and compared outcomes for patients randomized to atezolizumab with or without sacituzumab govitecan (SG).

 

 

The study was small, with only 31 patients in the combination arm and 11 controls, but the results were promising, with an overall response rate of 76.7% in the combination arm vs 66.7% in the control arm, Dr. Ciruelos said.

Supportive Care

Key supportive care takeaways included data on pregnancy in young breast cancer survivors and the safety of vaginal estrogen therapy in breast cancer patients with genitourinary symptoms, said Anne May, MD, of the University Medical Center Utrecht, Utrecht, Netherlands.

A study previously published in JAMA including nearly 5000 BRCA carriers who were diagnosed with invasive breast cancer at age 40 years or younger showed no association between pregnancy after breast cancer and adverse maternal or fetal outcomes, and pregnancy had no significant impact on overall survival. The authors presented new data on the safety of assisted reproductive techniques (ART) based on the 543 pregnancies in the original study, at the meeting. Of these, 436 conceived naturally, and 107 used ART. After a median of 9.1 years, ART had no effect on disease-free survival compared to natural conception (hazard ratio [HR], 0.64). Based on these findings, fertility preservation should be offered to all women who receive a breast cancer diagnosis and are interested in future fertility, Dr. May said.

Conceiving after breast cancer treatment and follow-up should not be contraindicated for young BRCA carriers, she added.No trial data are available for the effects of vaginal estrogen therapy (VET) on disease-free survival in breast cancer survivors with genitourinary symptoms caused by declining estrogen levels, Dr. May said. However, researchers in France and Switzerland conducted an emulation of a hypothetical target trial using data from the French National social security system for more than 130,000 individuals. Although VET therapy had no impact on disease-free survival in most breast cancer survivors overall, it did have a negative impact in a subset of patients with HR-positive and HR-negative tumors who were treated with aromatase inhibitors. The study was hypothetical, but important because the results suggest that clinicians can safely propose VTE to patients who report genitourinary symptoms after treatment for early-stage breast cancer with tamoxifen, but VTE should be avoided in patients treated with aromatase inhibitors, Dr. May said.

Dr. Delaloge disclosed research support to her institution from AstraZeneca, MSD, Bristol Myers Squibb, Sanofi, Taiho, Novartis, European Commission, INCa, Banque des Territoires, and Fondation Philanthropia. She also disclosed honoraria to her institution from AstraZeneca, Gilead, Novartis, Elsan, Besins, Sanofi, Exact Sciences, and Lilly, as well as travel support from Novartis.

Dr. Kok disclosed research funding from AstraZeneca, Bristol Myers Squibb, Daichi, and Roche, and advisory board membership/speaker’s fees from Alderaan Biotechnology, BIONTECH, Domain Therapeutics, AstraZeneca, Daichi, Bristol Myers Squibb, Gilead, Medscape, MSD, and Roche.

Dr. Hamilton disclosed a consulting advisory role (to her institution) for Accutar Biotechology, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Entos, Forsum Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Roche/Genentech, Stemline Therapeutics, ands others. She also disclosed contracted research/grant support to her institution only from Abbvie, Acerta Pharma, Accutar Biotechnology , ADC Therapeutics, AKESOBIO Australia , Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond and others.

Dr. Ciruelos disclosed serving as an external advisor for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, and Lilly, as well as serving as a speaker for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, Lilly, and Pierre Fabre. She also disclosed travel grants from Roche, Pfizer, and AstraZeneca, and research grants from Seagen and Roche.

Dr. May had no financial conflicts to disclose.

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AAP Shifts Stance, Updates Guidance on Breastfeeding With HIV

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Mon, 05/20/2024 - 13:47

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.

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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.

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Port-Wine Birthmarks: Shorter Interval Laser Treatments Show Promise in Infants

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Thu, 04/18/2024 - 17:29

 

TOPLINE:

Infants with port-wine birthmarks (PWB) achieved near-total or total clearance with weekly pulsed dye laser (PDL) treatments in a case-series of 10 infants.

METHODOLOGY:

  • Early intervention of PWB in infants can significantly improve outcomes, and some studies suggest shorter intervals between laser treatments may be more effective. While laser treatment with PDL is the gold standard, the optimal treatment interval has not been determined.
  • Researchers evaluated the records of 10 infants with PWB who received weekly PDL treatments from 2022 to 2023 at a single center. Treatment was initiated when the infants were 6 months old or younger, with the median age at the first treatment being 4 weeks. Of the 10 infants, eight had Fitzpatrick skin types I-III and two had skin type IV.
  • Two dermatologists assessed photographs taken before and after laser treatment, and the primary outcome was the percentage improvement of PWB.

TAKEAWAY:

  • Of the 10 patients, six achieved near-total (76%-95%) clearance, and one achieved total (96%-100%) clearance of PWB at a mean of 2 months after the first treatment.
  • Marked improvement (51%-75%) in PWB was observed in the remaining three patients, who achieved near-total clearance with additional treatments.
  • The median duration of treatment was 2 months (range, 0.2-5.1), and a median of eight treatments (range, 2-20) were needed to achieve near total or total clearance.
  • No adverse events were reported, including pigmentary changes, scarring, burns, erosions, or infections.

IN PRACTICE:

The outcomes in the case series, the authors concluded, “are compelling and warrant attention and further investigation into the possibility that this novel and decreased treatment interval of 1 week ... is associated with potential improvement in outcomes and shorter overall treatment duration.”

SOURCE:

This study was led by Shirin Bajaj, MD, of the Laser & Skin Surgery Center of New York, where the infants were treated, and was published online on April 17, 2024, in JAMA Dermatology.

LIMITATIONS:

A small sample size and the lack of a comparison arm limited the ability to draw any conclusions or make treatment recommendations based on the results.

DISCLOSURES:

The authors disclosed no conflicts of interest.
 

A version of this article appeared on Medscape.com.

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TOPLINE:

Infants with port-wine birthmarks (PWB) achieved near-total or total clearance with weekly pulsed dye laser (PDL) treatments in a case-series of 10 infants.

METHODOLOGY:

  • Early intervention of PWB in infants can significantly improve outcomes, and some studies suggest shorter intervals between laser treatments may be more effective. While laser treatment with PDL is the gold standard, the optimal treatment interval has not been determined.
  • Researchers evaluated the records of 10 infants with PWB who received weekly PDL treatments from 2022 to 2023 at a single center. Treatment was initiated when the infants were 6 months old or younger, with the median age at the first treatment being 4 weeks. Of the 10 infants, eight had Fitzpatrick skin types I-III and two had skin type IV.
  • Two dermatologists assessed photographs taken before and after laser treatment, and the primary outcome was the percentage improvement of PWB.

TAKEAWAY:

  • Of the 10 patients, six achieved near-total (76%-95%) clearance, and one achieved total (96%-100%) clearance of PWB at a mean of 2 months after the first treatment.
  • Marked improvement (51%-75%) in PWB was observed in the remaining three patients, who achieved near-total clearance with additional treatments.
  • The median duration of treatment was 2 months (range, 0.2-5.1), and a median of eight treatments (range, 2-20) were needed to achieve near total or total clearance.
  • No adverse events were reported, including pigmentary changes, scarring, burns, erosions, or infections.

IN PRACTICE:

The outcomes in the case series, the authors concluded, “are compelling and warrant attention and further investigation into the possibility that this novel and decreased treatment interval of 1 week ... is associated with potential improvement in outcomes and shorter overall treatment duration.”

SOURCE:

This study was led by Shirin Bajaj, MD, of the Laser & Skin Surgery Center of New York, where the infants were treated, and was published online on April 17, 2024, in JAMA Dermatology.

LIMITATIONS:

A small sample size and the lack of a comparison arm limited the ability to draw any conclusions or make treatment recommendations based on the results.

DISCLOSURES:

The authors disclosed no conflicts of interest.
 

A version of this article appeared on Medscape.com.

 

TOPLINE:

Infants with port-wine birthmarks (PWB) achieved near-total or total clearance with weekly pulsed dye laser (PDL) treatments in a case-series of 10 infants.

METHODOLOGY:

  • Early intervention of PWB in infants can significantly improve outcomes, and some studies suggest shorter intervals between laser treatments may be more effective. While laser treatment with PDL is the gold standard, the optimal treatment interval has not been determined.
  • Researchers evaluated the records of 10 infants with PWB who received weekly PDL treatments from 2022 to 2023 at a single center. Treatment was initiated when the infants were 6 months old or younger, with the median age at the first treatment being 4 weeks. Of the 10 infants, eight had Fitzpatrick skin types I-III and two had skin type IV.
  • Two dermatologists assessed photographs taken before and after laser treatment, and the primary outcome was the percentage improvement of PWB.

TAKEAWAY:

  • Of the 10 patients, six achieved near-total (76%-95%) clearance, and one achieved total (96%-100%) clearance of PWB at a mean of 2 months after the first treatment.
  • Marked improvement (51%-75%) in PWB was observed in the remaining three patients, who achieved near-total clearance with additional treatments.
  • The median duration of treatment was 2 months (range, 0.2-5.1), and a median of eight treatments (range, 2-20) were needed to achieve near total or total clearance.
  • No adverse events were reported, including pigmentary changes, scarring, burns, erosions, or infections.

IN PRACTICE:

The outcomes in the case series, the authors concluded, “are compelling and warrant attention and further investigation into the possibility that this novel and decreased treatment interval of 1 week ... is associated with potential improvement in outcomes and shorter overall treatment duration.”

SOURCE:

This study was led by Shirin Bajaj, MD, of the Laser & Skin Surgery Center of New York, where the infants were treated, and was published online on April 17, 2024, in JAMA Dermatology.

LIMITATIONS:

A small sample size and the lack of a comparison arm limited the ability to draw any conclusions or make treatment recommendations based on the results.

DISCLOSURES:

The authors disclosed no conflicts of interest.
 

A version of this article appeared on Medscape.com.

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New Trial Deepens Debate Over Late-Preterm Steroids

Article Type
Changed
Mon, 04/15/2024 - 17:28

 

The early cancellation of a trial in southern India suggests that the use of antenatal steroids to prevent respiratory complications after late-preterm birth — a recommended practice in the United States — may not be effective in the developing world.

As reported in Obstetrics & Gynecology, researchers led by Hilda Yenuberi, MD, of Christian Medical College, Vellore, Tamil Nadu, India, stopped the randomized, triple-blinded, placebo-controlled CLAP (Corticosteroids in Late Pregnancy) study at 70% enrollment. An interim analysis found no benefit from prescribing betamethasone vs placebo to women at risk of late-preterm delivery between 34 and 36 and 6/7 weeks of gestation (primary outcome of respiratory distress: 4.9% vs 4.8%, respectively, relative risk [RR], 1.03; 95% CI, 0.57-1.84; number needed to treat = 786).

“These findings may suggest differing efficacy of antenatal corticosteroids in developing countries compared with developed countries ... that should be considered when late-preterm antenatal corticosteroids are administered,” the researchers wrote.

The use of steroids in patients at risk of delivery before 34 weeks is widely accepted as a way to prevent neonatal respiratory distress, a common and potentially deadly condition in premature infants whose lungs are not fully developed. However, there’s debate over steroid treatment in women who are expected to deliver later than 34 weeks but still preterm.

As the study notes, “the American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant individuals at risk of delivering between 34 and 36 6/7 weeks of gestation on the basis of the ALPS (Antenatal Late Preterm Steroid) trial.”

But other randomized trials have reached different conclusions, and steroids are not without risks. Studies have linked prenatal steroids to neurosensory disorders in babies, meaning they’re more likely to need hearing aids and eyeglasses, said Kellie Murphy, MD, MSc, professor of obstetrics and gynecology, University of Toronto, Toronto, Ontario, Canada, in an interview. Dr. Murphy, who was not involved in the new trial, added that there are links between steroids and greater likelihood of poorer performance in school,

For the new study, conducted from 2020 to 2022 at Christian Medical College and Hospital in Vellore, India, researchers randomly assigned 423 patients to betamethasone (410 in the interim analysis; average age, 26.8 years) and 424 to placebo (415 in the interim analysis; average age, 26.2 years).

The average age of participants was 26.8 years. All were between 34 and 36 6/7 weeks of gestation and expected to give birth within the next week. A quarter of participants delivered at term, which the authors wrote “may have influenced the primary outcome.” The total number of neonates was 883, including 58 twin pregnancies.

There was no significant difference in respiratory distress between groups, “defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life.” There also were no significant differences in maternal outcomes such as chorioamnionitis or length of hospitalization or neonatal secondary outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, stillbirth, and early neonatal death.

Serious adverse events occurred in four neonates but none were linked to the intervention.

The study doesn’t discuss cost, but a 2019 report suggests that use of betamethasone to prevent neonatal respiratory distress is cost-effective.

“Our findings are contradictory to those of a systematic review, the major contributor of which was the ALPS trial,” the authors of the new study reported. “The primary outcome of the ALPS trial, the composite of neonatal treatment in the first 72 hours, was significantly less in the group who received betamethasone (11.6%), compared with the placebo group (14.4%; relative risk [RR], 0.80; 95% CI, 0.66-0.97).”

The study authors, who didn’t respond to requests for comment, noted that their trial included twin pregnancies and patients with gestational diabetes; the ALPS trial did not.

Perinatologist Cynthia Gyamfi-Bannerman, MD, MS, chair and professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California,San Diego, and principal investigator of the ALPS study, said in an interview that the inclusion of twins in the new trial is “a fundamental flaw.”

“Because antenatal corticosteroids have not been shown to be useful in twins at any gestational age, it is not surprising that including twins likely moved the findings to the null in this study,” she said. “Twins were purposefully excluded from the ALPS trial for this reason.”

According to the new study, “the primary outcome among singleton neonates occurred in 4.8% (18/374) who received betamethasone and 5.1% (20/393) who received placebo (RR, 0.94; 95% CI, 0.51-1.75)

What should clinicians take from the study findings? In an accompanying commentary, Blair J. Wylie, MD, MPH, of Columbia University Medical Center, New York, NY, and Syed Asad Ali, MBBS, MPH, of Aga Khan University, Karachi, Pakistan, wrote that, “in settings similar to the US-based ALPS trial, the practice of administering a course of late-preterm antenatal corticosteroids should be continued, as espoused by our professional organizations.”

However, the new study suggests that “research in high-resource environments may not be generalizable to low-resource settings,” they write.

Neonatologist Elizabeth Asztalos, MD, MSc, an associate scientist with Sunnybrook Health Sciences Center in Toronto, Canada, said in an interview that she doesn’t worry about pregnant mothers not getting steroids later than 34 weeks. “We have tools in our armamentarium in the NICU setting to help babies if they need it,” said Dr. Asztalos, who didn’t take part in the new trial. “We can put them on CPAP if they have wet lung. If they have an element of respiratory distress, we can give them surfactants. These bigger babies have more ability to recover from all this compared to a baby who was born at 24, 25, 26 weeks.”

For her part, the University of Toronto’s Dr. Murphy said decision-making about late-preterm steroids is complicated. “You don’t want to miss the opportunity to give to provide benefits for the patients” via steroids, she said. “But on the flip side, it’s a double-edged sword. It’s not easy. It’s not straightforward.”

In the big picture, she said, “people need to be really clear why they’re giving an intervention and what they hope to achieve.”

Christian Medical College supported the study. The authors, Dr. Murphy, Dr. Asztalos, and commentary co-author Dr. Ali have no disclosures. Dr. Gyamfi-Bannerman discloses being principal investigator of the ALPS trial. Commentary co-author Dr. Wylie serves on the ultrasound quality assurance committee of a trial discussed in the commentary.

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The early cancellation of a trial in southern India suggests that the use of antenatal steroids to prevent respiratory complications after late-preterm birth — a recommended practice in the United States — may not be effective in the developing world.

As reported in Obstetrics & Gynecology, researchers led by Hilda Yenuberi, MD, of Christian Medical College, Vellore, Tamil Nadu, India, stopped the randomized, triple-blinded, placebo-controlled CLAP (Corticosteroids in Late Pregnancy) study at 70% enrollment. An interim analysis found no benefit from prescribing betamethasone vs placebo to women at risk of late-preterm delivery between 34 and 36 and 6/7 weeks of gestation (primary outcome of respiratory distress: 4.9% vs 4.8%, respectively, relative risk [RR], 1.03; 95% CI, 0.57-1.84; number needed to treat = 786).

“These findings may suggest differing efficacy of antenatal corticosteroids in developing countries compared with developed countries ... that should be considered when late-preterm antenatal corticosteroids are administered,” the researchers wrote.

The use of steroids in patients at risk of delivery before 34 weeks is widely accepted as a way to prevent neonatal respiratory distress, a common and potentially deadly condition in premature infants whose lungs are not fully developed. However, there’s debate over steroid treatment in women who are expected to deliver later than 34 weeks but still preterm.

As the study notes, “the American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant individuals at risk of delivering between 34 and 36 6/7 weeks of gestation on the basis of the ALPS (Antenatal Late Preterm Steroid) trial.”

But other randomized trials have reached different conclusions, and steroids are not without risks. Studies have linked prenatal steroids to neurosensory disorders in babies, meaning they’re more likely to need hearing aids and eyeglasses, said Kellie Murphy, MD, MSc, professor of obstetrics and gynecology, University of Toronto, Toronto, Ontario, Canada, in an interview. Dr. Murphy, who was not involved in the new trial, added that there are links between steroids and greater likelihood of poorer performance in school,

For the new study, conducted from 2020 to 2022 at Christian Medical College and Hospital in Vellore, India, researchers randomly assigned 423 patients to betamethasone (410 in the interim analysis; average age, 26.8 years) and 424 to placebo (415 in the interim analysis; average age, 26.2 years).

The average age of participants was 26.8 years. All were between 34 and 36 6/7 weeks of gestation and expected to give birth within the next week. A quarter of participants delivered at term, which the authors wrote “may have influenced the primary outcome.” The total number of neonates was 883, including 58 twin pregnancies.

There was no significant difference in respiratory distress between groups, “defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life.” There also were no significant differences in maternal outcomes such as chorioamnionitis or length of hospitalization or neonatal secondary outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, stillbirth, and early neonatal death.

Serious adverse events occurred in four neonates but none were linked to the intervention.

The study doesn’t discuss cost, but a 2019 report suggests that use of betamethasone to prevent neonatal respiratory distress is cost-effective.

“Our findings are contradictory to those of a systematic review, the major contributor of which was the ALPS trial,” the authors of the new study reported. “The primary outcome of the ALPS trial, the composite of neonatal treatment in the first 72 hours, was significantly less in the group who received betamethasone (11.6%), compared with the placebo group (14.4%; relative risk [RR], 0.80; 95% CI, 0.66-0.97).”

The study authors, who didn’t respond to requests for comment, noted that their trial included twin pregnancies and patients with gestational diabetes; the ALPS trial did not.

Perinatologist Cynthia Gyamfi-Bannerman, MD, MS, chair and professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California,San Diego, and principal investigator of the ALPS study, said in an interview that the inclusion of twins in the new trial is “a fundamental flaw.”

“Because antenatal corticosteroids have not been shown to be useful in twins at any gestational age, it is not surprising that including twins likely moved the findings to the null in this study,” she said. “Twins were purposefully excluded from the ALPS trial for this reason.”

According to the new study, “the primary outcome among singleton neonates occurred in 4.8% (18/374) who received betamethasone and 5.1% (20/393) who received placebo (RR, 0.94; 95% CI, 0.51-1.75)

What should clinicians take from the study findings? In an accompanying commentary, Blair J. Wylie, MD, MPH, of Columbia University Medical Center, New York, NY, and Syed Asad Ali, MBBS, MPH, of Aga Khan University, Karachi, Pakistan, wrote that, “in settings similar to the US-based ALPS trial, the practice of administering a course of late-preterm antenatal corticosteroids should be continued, as espoused by our professional organizations.”

However, the new study suggests that “research in high-resource environments may not be generalizable to low-resource settings,” they write.

Neonatologist Elizabeth Asztalos, MD, MSc, an associate scientist with Sunnybrook Health Sciences Center in Toronto, Canada, said in an interview that she doesn’t worry about pregnant mothers not getting steroids later than 34 weeks. “We have tools in our armamentarium in the NICU setting to help babies if they need it,” said Dr. Asztalos, who didn’t take part in the new trial. “We can put them on CPAP if they have wet lung. If they have an element of respiratory distress, we can give them surfactants. These bigger babies have more ability to recover from all this compared to a baby who was born at 24, 25, 26 weeks.”

For her part, the University of Toronto’s Dr. Murphy said decision-making about late-preterm steroids is complicated. “You don’t want to miss the opportunity to give to provide benefits for the patients” via steroids, she said. “But on the flip side, it’s a double-edged sword. It’s not easy. It’s not straightforward.”

In the big picture, she said, “people need to be really clear why they’re giving an intervention and what they hope to achieve.”

Christian Medical College supported the study. The authors, Dr. Murphy, Dr. Asztalos, and commentary co-author Dr. Ali have no disclosures. Dr. Gyamfi-Bannerman discloses being principal investigator of the ALPS trial. Commentary co-author Dr. Wylie serves on the ultrasound quality assurance committee of a trial discussed in the commentary.

 

The early cancellation of a trial in southern India suggests that the use of antenatal steroids to prevent respiratory complications after late-preterm birth — a recommended practice in the United States — may not be effective in the developing world.

As reported in Obstetrics & Gynecology, researchers led by Hilda Yenuberi, MD, of Christian Medical College, Vellore, Tamil Nadu, India, stopped the randomized, triple-blinded, placebo-controlled CLAP (Corticosteroids in Late Pregnancy) study at 70% enrollment. An interim analysis found no benefit from prescribing betamethasone vs placebo to women at risk of late-preterm delivery between 34 and 36 and 6/7 weeks of gestation (primary outcome of respiratory distress: 4.9% vs 4.8%, respectively, relative risk [RR], 1.03; 95% CI, 0.57-1.84; number needed to treat = 786).

“These findings may suggest differing efficacy of antenatal corticosteroids in developing countries compared with developed countries ... that should be considered when late-preterm antenatal corticosteroids are administered,” the researchers wrote.

The use of steroids in patients at risk of delivery before 34 weeks is widely accepted as a way to prevent neonatal respiratory distress, a common and potentially deadly condition in premature infants whose lungs are not fully developed. However, there’s debate over steroid treatment in women who are expected to deliver later than 34 weeks but still preterm.

As the study notes, “the American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant individuals at risk of delivering between 34 and 36 6/7 weeks of gestation on the basis of the ALPS (Antenatal Late Preterm Steroid) trial.”

But other randomized trials have reached different conclusions, and steroids are not without risks. Studies have linked prenatal steroids to neurosensory disorders in babies, meaning they’re more likely to need hearing aids and eyeglasses, said Kellie Murphy, MD, MSc, professor of obstetrics and gynecology, University of Toronto, Toronto, Ontario, Canada, in an interview. Dr. Murphy, who was not involved in the new trial, added that there are links between steroids and greater likelihood of poorer performance in school,

For the new study, conducted from 2020 to 2022 at Christian Medical College and Hospital in Vellore, India, researchers randomly assigned 423 patients to betamethasone (410 in the interim analysis; average age, 26.8 years) and 424 to placebo (415 in the interim analysis; average age, 26.2 years).

The average age of participants was 26.8 years. All were between 34 and 36 6/7 weeks of gestation and expected to give birth within the next week. A quarter of participants delivered at term, which the authors wrote “may have influenced the primary outcome.” The total number of neonates was 883, including 58 twin pregnancies.

There was no significant difference in respiratory distress between groups, “defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life.” There also were no significant differences in maternal outcomes such as chorioamnionitis or length of hospitalization or neonatal secondary outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, stillbirth, and early neonatal death.

Serious adverse events occurred in four neonates but none were linked to the intervention.

The study doesn’t discuss cost, but a 2019 report suggests that use of betamethasone to prevent neonatal respiratory distress is cost-effective.

“Our findings are contradictory to those of a systematic review, the major contributor of which was the ALPS trial,” the authors of the new study reported. “The primary outcome of the ALPS trial, the composite of neonatal treatment in the first 72 hours, was significantly less in the group who received betamethasone (11.6%), compared with the placebo group (14.4%; relative risk [RR], 0.80; 95% CI, 0.66-0.97).”

The study authors, who didn’t respond to requests for comment, noted that their trial included twin pregnancies and patients with gestational diabetes; the ALPS trial did not.

Perinatologist Cynthia Gyamfi-Bannerman, MD, MS, chair and professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California,San Diego, and principal investigator of the ALPS study, said in an interview that the inclusion of twins in the new trial is “a fundamental flaw.”

“Because antenatal corticosteroids have not been shown to be useful in twins at any gestational age, it is not surprising that including twins likely moved the findings to the null in this study,” she said. “Twins were purposefully excluded from the ALPS trial for this reason.”

According to the new study, “the primary outcome among singleton neonates occurred in 4.8% (18/374) who received betamethasone and 5.1% (20/393) who received placebo (RR, 0.94; 95% CI, 0.51-1.75)

What should clinicians take from the study findings? In an accompanying commentary, Blair J. Wylie, MD, MPH, of Columbia University Medical Center, New York, NY, and Syed Asad Ali, MBBS, MPH, of Aga Khan University, Karachi, Pakistan, wrote that, “in settings similar to the US-based ALPS trial, the practice of administering a course of late-preterm antenatal corticosteroids should be continued, as espoused by our professional organizations.”

However, the new study suggests that “research in high-resource environments may not be generalizable to low-resource settings,” they write.

Neonatologist Elizabeth Asztalos, MD, MSc, an associate scientist with Sunnybrook Health Sciences Center in Toronto, Canada, said in an interview that she doesn’t worry about pregnant mothers not getting steroids later than 34 weeks. “We have tools in our armamentarium in the NICU setting to help babies if they need it,” said Dr. Asztalos, who didn’t take part in the new trial. “We can put them on CPAP if they have wet lung. If they have an element of respiratory distress, we can give them surfactants. These bigger babies have more ability to recover from all this compared to a baby who was born at 24, 25, 26 weeks.”

For her part, the University of Toronto’s Dr. Murphy said decision-making about late-preterm steroids is complicated. “You don’t want to miss the opportunity to give to provide benefits for the patients” via steroids, she said. “But on the flip side, it’s a double-edged sword. It’s not easy. It’s not straightforward.”

In the big picture, she said, “people need to be really clear why they’re giving an intervention and what they hope to achieve.”

Christian Medical College supported the study. The authors, Dr. Murphy, Dr. Asztalos, and commentary co-author Dr. Ali have no disclosures. Dr. Gyamfi-Bannerman discloses being principal investigator of the ALPS trial. Commentary co-author Dr. Wylie serves on the ultrasound quality assurance committee of a trial discussed in the commentary.

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Infant Microbiome Development Minimally Affected by Diet, but Metabolite Profiles Differ

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Mon, 04/15/2024 - 12:11

 

TOPLINE:

Diet has only a marginal impact on microbiome development in infancy, although metabolite profiles differ between breast- and formula-fed infants; circadian rhythm of the gut microbiome is detectable as early as 2 weeks after birth.

METHODOLOGY:

  • A randomized, controlled interventional trial compared microbiota development in 210 newborns who were exclusively breastfed or received one of four formulas: Un-supplemented formula, Bifidobacterium-supplemented formula, galacto-oligosaccharide (GOS)-supplemented, or formula containing GOSs and bifidobacteria. Exclusively breastfed infants served as a reference group to evaluate the impact of infant formula feeding.
  • Researchers tracked the infants’ microbiota and metabolite profiles in response to the different feeding modes via stool samples collected periodically during the first 1-2 years of life.
  • They also made note of the time of day that the stool sample was collected to assess 24-hour oscillations of the microbiome in relation to dietary exposure.

TAKEAWAY:

  • Global microbiota assembly of infants is primarily affected by age and less so by diet. All infants showed a gradual increase in gut microbe diversity, and at 24 months, there was no observable difference between the groups.
  • However, gut metabolite profiles differed significantly between exclusively formula-fed and exclusively breastfed infants. None of the supplemented formulas were able to fully recreate the breast milk-related microbial environment.
  • GOS-supplemented formula was more effective at promoting sustained levels of bifidobacteria than formula containing bifidobacteria.
  • Metabolic and bacterial profiling revealed 24-hour fluctuations and circadian networks as early as 2 weeks after birth. Infant microbes maintained circadian rhythms when grown in continuous culture, even in the absence of external light or host cues, suggesting an intrinsic clock mechanism in bacteria.

IN PRACTICE:

“Our findings warrant the need for further analysis of circadian fluctuations of both bacteria and metabolites and their functional role in contributing to the benefits of infant nutrition,” the study authors wrote.

SOURCE:

The study was published online April 2 in Cell Host & Microbe.

LIMITATIONS:

The group size for exclusively formula-fed infants was limited, and the explicit contribution of breast milk, relative to infant formula, to bacterial rhythms remains unclear. A possible limitation of the circadian analysis is that the number of fecal samples collected during the night was lower than during the daytime and decreased with age.

DISCLOSURES:

This research was supported by Töpfer GmbH, the German Research Foundation, the Joint Programming Initiative of the European Union, and the German Ministry of Education and Research. The authors had disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

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TOPLINE:

Diet has only a marginal impact on microbiome development in infancy, although metabolite profiles differ between breast- and formula-fed infants; circadian rhythm of the gut microbiome is detectable as early as 2 weeks after birth.

METHODOLOGY:

  • A randomized, controlled interventional trial compared microbiota development in 210 newborns who were exclusively breastfed or received one of four formulas: Un-supplemented formula, Bifidobacterium-supplemented formula, galacto-oligosaccharide (GOS)-supplemented, or formula containing GOSs and bifidobacteria. Exclusively breastfed infants served as a reference group to evaluate the impact of infant formula feeding.
  • Researchers tracked the infants’ microbiota and metabolite profiles in response to the different feeding modes via stool samples collected periodically during the first 1-2 years of life.
  • They also made note of the time of day that the stool sample was collected to assess 24-hour oscillations of the microbiome in relation to dietary exposure.

TAKEAWAY:

  • Global microbiota assembly of infants is primarily affected by age and less so by diet. All infants showed a gradual increase in gut microbe diversity, and at 24 months, there was no observable difference between the groups.
  • However, gut metabolite profiles differed significantly between exclusively formula-fed and exclusively breastfed infants. None of the supplemented formulas were able to fully recreate the breast milk-related microbial environment.
  • GOS-supplemented formula was more effective at promoting sustained levels of bifidobacteria than formula containing bifidobacteria.
  • Metabolic and bacterial profiling revealed 24-hour fluctuations and circadian networks as early as 2 weeks after birth. Infant microbes maintained circadian rhythms when grown in continuous culture, even in the absence of external light or host cues, suggesting an intrinsic clock mechanism in bacteria.

IN PRACTICE:

“Our findings warrant the need for further analysis of circadian fluctuations of both bacteria and metabolites and their functional role in contributing to the benefits of infant nutrition,” the study authors wrote.

SOURCE:

The study was published online April 2 in Cell Host & Microbe.

LIMITATIONS:

The group size for exclusively formula-fed infants was limited, and the explicit contribution of breast milk, relative to infant formula, to bacterial rhythms remains unclear. A possible limitation of the circadian analysis is that the number of fecal samples collected during the night was lower than during the daytime and decreased with age.

DISCLOSURES:

This research was supported by Töpfer GmbH, the German Research Foundation, the Joint Programming Initiative of the European Union, and the German Ministry of Education and Research. The authors had disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

 

TOPLINE:

Diet has only a marginal impact on microbiome development in infancy, although metabolite profiles differ between breast- and formula-fed infants; circadian rhythm of the gut microbiome is detectable as early as 2 weeks after birth.

METHODOLOGY:

  • A randomized, controlled interventional trial compared microbiota development in 210 newborns who were exclusively breastfed or received one of four formulas: Un-supplemented formula, Bifidobacterium-supplemented formula, galacto-oligosaccharide (GOS)-supplemented, or formula containing GOSs and bifidobacteria. Exclusively breastfed infants served as a reference group to evaluate the impact of infant formula feeding.
  • Researchers tracked the infants’ microbiota and metabolite profiles in response to the different feeding modes via stool samples collected periodically during the first 1-2 years of life.
  • They also made note of the time of day that the stool sample was collected to assess 24-hour oscillations of the microbiome in relation to dietary exposure.

TAKEAWAY:

  • Global microbiota assembly of infants is primarily affected by age and less so by diet. All infants showed a gradual increase in gut microbe diversity, and at 24 months, there was no observable difference between the groups.
  • However, gut metabolite profiles differed significantly between exclusively formula-fed and exclusively breastfed infants. None of the supplemented formulas were able to fully recreate the breast milk-related microbial environment.
  • GOS-supplemented formula was more effective at promoting sustained levels of bifidobacteria than formula containing bifidobacteria.
  • Metabolic and bacterial profiling revealed 24-hour fluctuations and circadian networks as early as 2 weeks after birth. Infant microbes maintained circadian rhythms when grown in continuous culture, even in the absence of external light or host cues, suggesting an intrinsic clock mechanism in bacteria.

IN PRACTICE:

“Our findings warrant the need for further analysis of circadian fluctuations of both bacteria and metabolites and their functional role in contributing to the benefits of infant nutrition,” the study authors wrote.

SOURCE:

The study was published online April 2 in Cell Host & Microbe.

LIMITATIONS:

The group size for exclusively formula-fed infants was limited, and the explicit contribution of breast milk, relative to infant formula, to bacterial rhythms remains unclear. A possible limitation of the circadian analysis is that the number of fecal samples collected during the night was lower than during the daytime and decreased with age.

DISCLOSURES:

This research was supported by Töpfer GmbH, the German Research Foundation, the Joint Programming Initiative of the European Union, and the German Ministry of Education and Research. The authors had disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

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Infant Exposure to MS Drugs via Breastfeeding: New Data

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Changed
Wed, 03/27/2024 - 12:36

Breastfeeding by women with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) who are taking monoclonal antibodies (mAbs) appears to be safe for infants, new research confirmed.

Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.

“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.

“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Registry Data and Analysis

Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).

Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).

Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.

The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.

In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.

A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
 

‘Reassuring’ Data

Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”

Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”

“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.

“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”

In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.

The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.

A version of this article appeared on Medscape.com.

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Breastfeeding by women with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) who are taking monoclonal antibodies (mAbs) appears to be safe for infants, new research confirmed.

Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.

“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.

“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Registry Data and Analysis

Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).

Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).

Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.

The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.

In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.

A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
 

‘Reassuring’ Data

Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”

Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”

“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.

“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”

In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.

The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.

A version of this article appeared on Medscape.com.

Breastfeeding by women with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) who are taking monoclonal antibodies (mAbs) appears to be safe for infants, new research confirmed.

Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.

“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.

“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Registry Data and Analysis

Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).

Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).

Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.

The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.

In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.

A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
 

‘Reassuring’ Data

Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”

Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”

“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.

“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”

In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.

The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.

A version of this article appeared on Medscape.com.

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Delaying Inguinal Hernia Repair Is Beneficial for Preterm Infants

Article Type
Changed
Wed, 03/27/2024 - 12:06

 

TOPLINE:

A clinical trial of preterm infants with inguinal hernia found that performing repair after discharge from the neonatal intensive care unit (NICU) resulted in fewer adverse events than procedures prior to discharge.

METHODOLOGY:

  • The study compared the safety of repair before discharge from the NICU with repair after discharge and post-55 weeks gestational plus chronological age (postmenstrual age).
  • The study randomized 338 infants from 39 US hospitals to early or late repair; of the 320 infants who had the surgery, 86% were male, 30% were Black, and 59% were White.
  • The primary outcome was the occurrence of at least one serious adverse event over the 10-month observation period, including apnea requiring respiratory intervention, intubation for more than 2 days, bradycardia requiring pharmacological intervention, or death.
  • Secondary outcomes included a total number of days in the hospital, including the initial NICU stay after randomization, postoperative hospitalization, and any inpatient days due to hospital readmission over the course of the following 10-month period.

TAKEAWAY:

  • Infants who underwent late repair had a lower probability of having at least one serious adverse event: 28% had at least one adverse event in the early group vs 18% in the late group.
  • Infants in the late repair group had shorter stays in the NICU after randomization, as well as fewer hospital days following surgery.
  • Late repair provided the greatest benefit to infants with a gestational age younger than 28 weeks and those who had bronchopulmonary dysplasia.
  • Hernias resolved spontaneously in 4% of infants in the early repair group and 11% in the late group, which the authors said supports delaying hernia repair.

IN PRACTICE:

“The decision to treat the inguinal hernia with an early or late repair strategy likely does not influence the overall duration of the neonatal intensive care unit stay but may hasten the discharge by several days if later repair is chosen, which is likely important to parents and neonatologists.”

SOURCE:

The study was published online in JAMA. It was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Martin L. Blakely, MD, MS, from the Department of Surgery at the University of Texas Health Science Center, Houston, Texas, is the corresponding author.

LIMITATIONS:

This study had a modest sample size, an issue compounded by some subjects withdrawing from the trial. The randomization rate was lower than expected. The trial was also discontinued early due to meeting a prespecified stopping rule for effectiveness.

DISCLOSURES:

Study authors report grant support from the US Department of Defense, personal fees, author royalties, and institutional contracts with various companies including Medicem, Fresenius Kabi, Baxter, and Mead Johnson.

A version of this article appeared on Medscape.com.

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TOPLINE:

A clinical trial of preterm infants with inguinal hernia found that performing repair after discharge from the neonatal intensive care unit (NICU) resulted in fewer adverse events than procedures prior to discharge.

METHODOLOGY:

  • The study compared the safety of repair before discharge from the NICU with repair after discharge and post-55 weeks gestational plus chronological age (postmenstrual age).
  • The study randomized 338 infants from 39 US hospitals to early or late repair; of the 320 infants who had the surgery, 86% were male, 30% were Black, and 59% were White.
  • The primary outcome was the occurrence of at least one serious adverse event over the 10-month observation period, including apnea requiring respiratory intervention, intubation for more than 2 days, bradycardia requiring pharmacological intervention, or death.
  • Secondary outcomes included a total number of days in the hospital, including the initial NICU stay after randomization, postoperative hospitalization, and any inpatient days due to hospital readmission over the course of the following 10-month period.

TAKEAWAY:

  • Infants who underwent late repair had a lower probability of having at least one serious adverse event: 28% had at least one adverse event in the early group vs 18% in the late group.
  • Infants in the late repair group had shorter stays in the NICU after randomization, as well as fewer hospital days following surgery.
  • Late repair provided the greatest benefit to infants with a gestational age younger than 28 weeks and those who had bronchopulmonary dysplasia.
  • Hernias resolved spontaneously in 4% of infants in the early repair group and 11% in the late group, which the authors said supports delaying hernia repair.

IN PRACTICE:

“The decision to treat the inguinal hernia with an early or late repair strategy likely does not influence the overall duration of the neonatal intensive care unit stay but may hasten the discharge by several days if later repair is chosen, which is likely important to parents and neonatologists.”

SOURCE:

The study was published online in JAMA. It was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Martin L. Blakely, MD, MS, from the Department of Surgery at the University of Texas Health Science Center, Houston, Texas, is the corresponding author.

LIMITATIONS:

This study had a modest sample size, an issue compounded by some subjects withdrawing from the trial. The randomization rate was lower than expected. The trial was also discontinued early due to meeting a prespecified stopping rule for effectiveness.

DISCLOSURES:

Study authors report grant support from the US Department of Defense, personal fees, author royalties, and institutional contracts with various companies including Medicem, Fresenius Kabi, Baxter, and Mead Johnson.

A version of this article appeared on Medscape.com.

 

TOPLINE:

A clinical trial of preterm infants with inguinal hernia found that performing repair after discharge from the neonatal intensive care unit (NICU) resulted in fewer adverse events than procedures prior to discharge.

METHODOLOGY:

  • The study compared the safety of repair before discharge from the NICU with repair after discharge and post-55 weeks gestational plus chronological age (postmenstrual age).
  • The study randomized 338 infants from 39 US hospitals to early or late repair; of the 320 infants who had the surgery, 86% were male, 30% were Black, and 59% were White.
  • The primary outcome was the occurrence of at least one serious adverse event over the 10-month observation period, including apnea requiring respiratory intervention, intubation for more than 2 days, bradycardia requiring pharmacological intervention, or death.
  • Secondary outcomes included a total number of days in the hospital, including the initial NICU stay after randomization, postoperative hospitalization, and any inpatient days due to hospital readmission over the course of the following 10-month period.

TAKEAWAY:

  • Infants who underwent late repair had a lower probability of having at least one serious adverse event: 28% had at least one adverse event in the early group vs 18% in the late group.
  • Infants in the late repair group had shorter stays in the NICU after randomization, as well as fewer hospital days following surgery.
  • Late repair provided the greatest benefit to infants with a gestational age younger than 28 weeks and those who had bronchopulmonary dysplasia.
  • Hernias resolved spontaneously in 4% of infants in the early repair group and 11% in the late group, which the authors said supports delaying hernia repair.

IN PRACTICE:

“The decision to treat the inguinal hernia with an early or late repair strategy likely does not influence the overall duration of the neonatal intensive care unit stay but may hasten the discharge by several days if later repair is chosen, which is likely important to parents and neonatologists.”

SOURCE:

The study was published online in JAMA. It was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Martin L. Blakely, MD, MS, from the Department of Surgery at the University of Texas Health Science Center, Houston, Texas, is the corresponding author.

LIMITATIONS:

This study had a modest sample size, an issue compounded by some subjects withdrawing from the trial. The randomization rate was lower than expected. The trial was also discontinued early due to meeting a prespecified stopping rule for effectiveness.

DISCLOSURES:

Study authors report grant support from the US Department of Defense, personal fees, author royalties, and institutional contracts with various companies including Medicem, Fresenius Kabi, Baxter, and Mead Johnson.

A version of this article appeared on Medscape.com.

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