Pediatrics

TOPLINE:

Cognitive function in children aged 18 months to 10 years is associated with the enrichment or depletion of specific species of gut microbes, new research reveals.

METHODOLOGY: 

• Researchers analyzed the relationship between the microbiome, neuroanatomy, and cognition (ie, the microbiome-gut-brain axis) in stool samples from 381 neurotypically developing children aged 40 days to 10 years (mean age, 2 years and 2 months).
• Stool samples were taken within a week of age-appropriate cognitive and behavioral assessments.
• Shotgun metagenomic sequencing was used to analyze the DNA of the organisms present in each sample.
• MRI data were obtained, with machine models then used to predict whether participants’ brain region volume was influenced by microbial profiles.

TAKEAWAY: 

• Researchers found increasing variation in microbial species and microbial gene functions in children older than 18 months, and the overall variation was significantly associated with variation in cognitive function scores.
• Several microbial species were significantly enriched in children with higher cognitive function scores (eg, Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii), with Sutterella wadsworthensis being the only species significantly negatively associated with these scores.
• Machine models indicated that taxa key in predicting cognitive function were similarly important for predicting individual brain regions and subscales of cognitive function.

IN PRACTICE:

“Understanding the gut-brain-microbiome axis in early life is particularly important since differences or interventions in early life can have outsized and longer-term consequences than those at later ages,” the authors wrote.

SOURCE:

The study, led by Kevin S. Bonham, PhD, Wellesley College, Wellesley, Massachusetts, was published online on December 22, 2023, in Science Advances.

LIMITATIONS:

Use of multiple age-appropriate cognitive assessments enabled analysis across multiple developmental periods, but test-retest reliability and differences between test administrators may have introduced noise into these observations, particularly in the youngest children. The study period overlapped with the beginning of the pandemic, and score reductions due to the lockdowns were more pronounced in some age groups than during the recruitment period. 

DISCLOSURES:

The study was funded by the US National Institutes of Health and Wellcome: LEAP 1kD. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Cognitive function in children aged 18 months to 10 years is associated with the enrichment or depletion of specific species of gut microbes, new research reveals.

METHODOLOGY: 

• Researchers analyzed the relationship between the microbiome, neuroanatomy, and cognition (ie, the microbiome-gut-brain axis) in stool samples from 381 neurotypically developing children aged 40 days to 10 years (mean age, 2 years and 2 months).
• Stool samples were taken within a week of age-appropriate cognitive and behavioral assessments.
• Shotgun metagenomic sequencing was used to analyze the DNA of the organisms present in each sample.
• MRI data were obtained, with machine models then used to predict whether participants’ brain region volume was influenced by microbial profiles.

TAKEAWAY: 

• Researchers found increasing variation in microbial species and microbial gene functions in children older than 18 months, and the overall variation was significantly associated with variation in cognitive function scores.
• Several microbial species were significantly enriched in children with higher cognitive function scores (eg, Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii), with Sutterella wadsworthensis being the only species significantly negatively associated with these scores.
• Machine models indicated that taxa key in predicting cognitive function were similarly important for predicting individual brain regions and subscales of cognitive function.

IN PRACTICE:

“Understanding the gut-brain-microbiome axis in early life is particularly important since differences or interventions in early life can have outsized and longer-term consequences than those at later ages,” the authors wrote.

SOURCE:

The study, led by Kevin S. Bonham, PhD, Wellesley College, Wellesley, Massachusetts, was published online on December 22, 2023, in Science Advances.

LIMITATIONS:

Use of multiple age-appropriate cognitive assessments enabled analysis across multiple developmental periods, but test-retest reliability and differences between test administrators may have introduced noise into these observations, particularly in the youngest children. The study period overlapped with the beginning of the pandemic, and score reductions due to the lockdowns were more pronounced in some age groups than during the recruitment period. 

DISCLOSURES:

The study was funded by the US National Institutes of Health and Wellcome: LEAP 1kD. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Cognitive function in children aged 18 months to 10 years is associated with the enrichment or depletion of specific species of gut microbes, new research reveals.

METHODOLOGY: 

• Researchers analyzed the relationship between the microbiome, neuroanatomy, and cognition (ie, the microbiome-gut-brain axis) in stool samples from 381 neurotypically developing children aged 40 days to 10 years (mean age, 2 years and 2 months).
• Stool samples were taken within a week of age-appropriate cognitive and behavioral assessments.
• Shotgun metagenomic sequencing was used to analyze the DNA of the organisms present in each sample.
• MRI data were obtained, with machine models then used to predict whether participants’ brain region volume was influenced by microbial profiles.

TAKEAWAY: 

• Researchers found increasing variation in microbial species and microbial gene functions in children older than 18 months, and the overall variation was significantly associated with variation in cognitive function scores.
• Several microbial species were significantly enriched in children with higher cognitive function scores (eg, Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii), with Sutterella wadsworthensis being the only species significantly negatively associated with these scores.
• Machine models indicated that taxa key in predicting cognitive function were similarly important for predicting individual brain regions and subscales of cognitive function.

IN PRACTICE:

“Understanding the gut-brain-microbiome axis in early life is particularly important since differences or interventions in early life can have outsized and longer-term consequences than those at later ages,” the authors wrote.

SOURCE:

The study, led by Kevin S. Bonham, PhD, Wellesley College, Wellesley, Massachusetts, was published online on December 22, 2023, in Science Advances.

LIMITATIONS:

Use of multiple age-appropriate cognitive assessments enabled analysis across multiple developmental periods, but test-retest reliability and differences between test administrators may have introduced noise into these observations, particularly in the youngest children. The study period overlapped with the beginning of the pandemic, and score reductions due to the lockdowns were more pronounced in some age groups than during the recruitment period. 

DISCLOSURES:

The study was funded by the US National Institutes of Health and Wellcome: LEAP 1kD. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — There are subtleties and nuances to diagnosing, treating, and monitoring the progress of treatment of hair loss in children. Moreover, hair loss in children can be challenging because it can be caused by a range of conditions, some common and others relatively rare.

Michelle Oboite, MD, shared tips on how to distinguish types of hair loss, when to treat with medications such as topical corticosteroids or Janus kinase (JAK) inhibitors, and why shared decision-making is important, at the ODAC Dermatology, Aesthetic & Surgical Conference.

What these conditions share is that they can negatively affect the quality of life for a child or teenager when the condition leads to anxiety, teasing, or bullying. “It is very isolating to have this condition that everyone in the world can see that you have and judge you for it,” said Dr. Oboite, an attending physician in the dermatology section of Children’s Hospital of Philadelphia.

While alopecia areata, tinea capitis, and trichotillomania are more common, other causes of hair loss in children include androgenetic alopecia, primary scarring alopecias, such as central centrifugal cicatricial alopecia, and dissecting cellulitis. Others are lichen planopilaris and genetic conditions, including loose anagen syndrome, uncombable hair syndrome, and “something so rare” — it has no acronym — autosomal recessive hypotrichosis with recurrent skin vesicles, Dr. Oboite said.
 

Alopecia Areata

Alopecia areata can differ from child to child and can appear in different stages: A localized patch stage, a diffuse patchy stage, or alopecia universalis. In this last stage, the child has already lost most or all the hair on the scalp and eyebrows, as well as the eyelashes.

The decision to treat or not to treat, particularly in younger children, should be on the basis of shared decision-making between a healthcare provider and caregiver, said Dr. Oboite, who is also an assistant professor of clinical dermatology at the University of Pennsylvania, Philadelphia.

Some younger children may not experience any negative impact from the condition, so waiting until they are older is an option.

Also, consider the impact of treatment on a child. Some therapies require frequent blood draws for monitoring, and some topical therapies that are applied multiple times a day “can be very overwhelming” for young children, Dr. Oboite said.

Most children with alopecia areata are healthy and do not need extensive screening laboratory testing. However, one exception is if thyroid dysfunction, commonly associated with alopecia areata, is suspected.

For alopecia areata, Dr. Oboite recommends starting with topical therapies, either topical corticosteroids (as first line) or topical JAK inhibitors (either topical ruxolitinib or compounded topical tofacitinib, both off-label for this indication).

Topical corticosteroids can be effective, but “you want to be thoughtful of the strength you’re using, the application frequency, and then the total amount of surface area that you’re treating,” Dr. Oboite said. Too potent or too much of a topical corticosteroid increases the risk for atrophy and systemic absorption, respectively. To reduce the risk, she reserves the use of ultrahigh-potency topical corticosteroids, such as clobetasol, for children ages 10 years or older. For children younger than 10 years, she recommends using mid-high-potency topical corticosteroids instead.

She recommends once-a-day application around bedtime 5 days a week, generally Monday through Friday to make it easier to remember.

“For children who have over 50% of the scalp involved, I do consider systemic therapy,” Dr. Oboite said. This can include oral steroids such as dexamethasone, prednisone, or prednisolone. For children with recalcitrant disease, she is more likely to use the oral JAK inhibitor ritlecitinib because it was recently approved by the Food and Drug Administration for treating severe alopecia areata in children 12 years and older and in adults.

Another strategy Dr. Oboite uses is to add low-dose oral minoxidil as an adjuvant to other systemic therapy. “I find that it helps with faster hair regrowth,” she said.
 

Tinea Capitis

Oral treatment is indicated for tinea capitis. “Topicals just don’t really clear this,” Dr. Oboite said. Also, talk to patients and families about preventing reinfection with the dermatophyte that causes this condition. “Make sure we’re cleaning hats, combs, brushes, and pillowcases. That is really important.”

Some patients can develop a widespread rash while on treatment. But in most cases, it’s not an adverse reaction to the medication but rather an indication that the body’s response is revving up, she noted.

Griseofulvin 20 mg/kg/d is one treatment option. Another is terbinafine (using weight-based dosing). A tip with terbinafine is that because the tablet needs to be crushed for a young child, “you can put it in anything, besides applesauce or yogurt with fruit on the bottom, which can be acidic and reduce the effectiveness of the medication,” Dr. Oboite said.

For cases of severe, inflammatory tinea capitis such as a kerion, “I will say you have to hold the hands of these patients, the journey can be long,” she added.
 

Trichotillomania

Trichotillomania occurs when someone cannot stop pulling their own hair, and in the early phases, it can be confused with alopecia areata. A thorough history and examination of the patient can help distinguish the two conditions. Sometimes a child or teen has a history of anxiety-related behaviors like nail biting that points to trichotillomania. Another tip is to use a dermatoscope to help distinguish hair loss conditions because it avoids having to do as many biopsies in children.

Redirection therapy can work for younger children, and cognitive behavioral therapy (CBT) can help older children with trichotillomania. In response to a question during the Q&A period, Dr. Oboite said psychiatrists or psychologists can perform CBT. If it takes time to get an appointment, there are some CBT apps that can help in the meantime, she said.

“One thing really important is to not blame the child,” Dr. Oboite said. “Most children don’t even know that they’re doing this. This is often not a behavior that is being done on purpose.”

Androgenetic Alopecia

Rarely, children and teenagers can also present with androgenetic alopecia, which Dr. Oboite has successfully treated with topical minoxidil, applied once a day before increasing to twice a day if tolerated. “I will tell them that when they pick it up, it will say ‘you should not use in children.’ But it actually can be used in children safely.”

Low-dose oral minoxidil is another option. Both treatments require a commitment by patients and parents because they are “taking this for a long time.”
 

Loose Anagen and Uncombable Hair Syndromes

A rare genetic form of hair loss is called loose anagen syndrome. Children with this disorder will have thin hair that is easily pulled out without a lot of force. Their hair appears to typically only grow to a certain length (such as to the nape of the neck) and then stops.

Another genetic hair loss condition is uncombable hair syndrome. It can cause hair to grow out of the scalp in all directions, and as the name suggests, it is almost impossible to comb or brush down. Along with loose anagen syndrome, uncombable hair syndrome tends to improve as the child gets older. “The key point here is telling parents that it can get better with time,” Dr. Oboite said.
 

A Condition With No Well-Known Acronym

She described a child she treated who had hair that never grew and was easily broken. The patient’s skin was prone to bruising, and her fingernails would easily fall off after trauma; her dentist noted that she had no buds for adult teeth on x-rays. These different presentations are important because hair, teeth, and nails all come from the same ectoderm germ line in embryo development, Dr. Oboite said.

Exome sequencing revealed the girl had a very rare diagnosis called autosomal recessive hypotrichosis with recurrent skin vesicles. “So, it is really important to recognize that children who are presenting with hair issues can have a genetic, underlying condition,” she said. Examining the skin, nails, and teeth, in addition to the hair, can be clues to these very rare diagnoses.

Some of these hair loss conditions in children can be challenging to diagnose and manage, Dr. Oboite said. “So don’t be afraid to ask for help on complex or rare cases.” Pediatric dermatologists “are always happy to help you. Hair loss is daunting, and hair loss in children can be even more daunting,” but the rewards of accurate diagnosis and successful treatment can be great, she said.

Dr. Oboite reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — There are subtleties and nuances to diagnosing, treating, and monitoring the progress of treatment of hair loss in children. Moreover, hair loss in children can be challenging because it can be caused by a range of conditions, some common and others relatively rare.

Michelle Oboite, MD, shared tips on how to distinguish types of hair loss, when to treat with medications such as topical corticosteroids or Janus kinase (JAK) inhibitors, and why shared decision-making is important, at the ODAC Dermatology, Aesthetic & Surgical Conference.

What these conditions share is that they can negatively affect the quality of life for a child or teenager when the condition leads to anxiety, teasing, or bullying. “It is very isolating to have this condition that everyone in the world can see that you have and judge you for it,” said Dr. Oboite, an attending physician in the dermatology section of Children’s Hospital of Philadelphia.

While alopecia areata, tinea capitis, and trichotillomania are more common, other causes of hair loss in children include androgenetic alopecia, primary scarring alopecias, such as central centrifugal cicatricial alopecia, and dissecting cellulitis. Others are lichen planopilaris and genetic conditions, including loose anagen syndrome, uncombable hair syndrome, and “something so rare” — it has no acronym — autosomal recessive hypotrichosis with recurrent skin vesicles, Dr. Oboite said.
 

Alopecia Areata

Alopecia areata can differ from child to child and can appear in different stages: A localized patch stage, a diffuse patchy stage, or alopecia universalis. In this last stage, the child has already lost most or all the hair on the scalp and eyebrows, as well as the eyelashes.

The decision to treat or not to treat, particularly in younger children, should be on the basis of shared decision-making between a healthcare provider and caregiver, said Dr. Oboite, who is also an assistant professor of clinical dermatology at the University of Pennsylvania, Philadelphia.

Some younger children may not experience any negative impact from the condition, so waiting until they are older is an option.

Also, consider the impact of treatment on a child. Some therapies require frequent blood draws for monitoring, and some topical therapies that are applied multiple times a day “can be very overwhelming” for young children, Dr. Oboite said.

Most children with alopecia areata are healthy and do not need extensive screening laboratory testing. However, one exception is if thyroid dysfunction, commonly associated with alopecia areata, is suspected.

For alopecia areata, Dr. Oboite recommends starting with topical therapies, either topical corticosteroids (as first line) or topical JAK inhibitors (either topical ruxolitinib or compounded topical tofacitinib, both off-label for this indication).

Topical corticosteroids can be effective, but “you want to be thoughtful of the strength you’re using, the application frequency, and then the total amount of surface area that you’re treating,” Dr. Oboite said. Too potent or too much of a topical corticosteroid increases the risk for atrophy and systemic absorption, respectively. To reduce the risk, she reserves the use of ultrahigh-potency topical corticosteroids, such as clobetasol, for children ages 10 years or older. For children younger than 10 years, she recommends using mid-high-potency topical corticosteroids instead.

She recommends once-a-day application around bedtime 5 days a week, generally Monday through Friday to make it easier to remember.

“For children who have over 50% of the scalp involved, I do consider systemic therapy,” Dr. Oboite said. This can include oral steroids such as dexamethasone, prednisone, or prednisolone. For children with recalcitrant disease, she is more likely to use the oral JAK inhibitor ritlecitinib because it was recently approved by the Food and Drug Administration for treating severe alopecia areata in children 12 years and older and in adults.

Another strategy Dr. Oboite uses is to add low-dose oral minoxidil as an adjuvant to other systemic therapy. “I find that it helps with faster hair regrowth,” she said.
 

Tinea Capitis

Oral treatment is indicated for tinea capitis. “Topicals just don’t really clear this,” Dr. Oboite said. Also, talk to patients and families about preventing reinfection with the dermatophyte that causes this condition. “Make sure we’re cleaning hats, combs, brushes, and pillowcases. That is really important.”

Some patients can develop a widespread rash while on treatment. But in most cases, it’s not an adverse reaction to the medication but rather an indication that the body’s response is revving up, she noted.

Griseofulvin 20 mg/kg/d is one treatment option. Another is terbinafine (using weight-based dosing). A tip with terbinafine is that because the tablet needs to be crushed for a young child, “you can put it in anything, besides applesauce or yogurt with fruit on the bottom, which can be acidic and reduce the effectiveness of the medication,” Dr. Oboite said.

For cases of severe, inflammatory tinea capitis such as a kerion, “I will say you have to hold the hands of these patients, the journey can be long,” she added.
 

Trichotillomania

Trichotillomania occurs when someone cannot stop pulling their own hair, and in the early phases, it can be confused with alopecia areata. A thorough history and examination of the patient can help distinguish the two conditions. Sometimes a child or teen has a history of anxiety-related behaviors like nail biting that points to trichotillomania. Another tip is to use a dermatoscope to help distinguish hair loss conditions because it avoids having to do as many biopsies in children.

Redirection therapy can work for younger children, and cognitive behavioral therapy (CBT) can help older children with trichotillomania. In response to a question during the Q&A period, Dr. Oboite said psychiatrists or psychologists can perform CBT. If it takes time to get an appointment, there are some CBT apps that can help in the meantime, she said.

“One thing really important is to not blame the child,” Dr. Oboite said. “Most children don’t even know that they’re doing this. This is often not a behavior that is being done on purpose.”

Androgenetic Alopecia

Rarely, children and teenagers can also present with androgenetic alopecia, which Dr. Oboite has successfully treated with topical minoxidil, applied once a day before increasing to twice a day if tolerated. “I will tell them that when they pick it up, it will say ‘you should not use in children.’ But it actually can be used in children safely.”

Low-dose oral minoxidil is another option. Both treatments require a commitment by patients and parents because they are “taking this for a long time.”
 

Loose Anagen and Uncombable Hair Syndromes

A rare genetic form of hair loss is called loose anagen syndrome. Children with this disorder will have thin hair that is easily pulled out without a lot of force. Their hair appears to typically only grow to a certain length (such as to the nape of the neck) and then stops.

Another genetic hair loss condition is uncombable hair syndrome. It can cause hair to grow out of the scalp in all directions, and as the name suggests, it is almost impossible to comb or brush down. Along with loose anagen syndrome, uncombable hair syndrome tends to improve as the child gets older. “The key point here is telling parents that it can get better with time,” Dr. Oboite said.
 

A Condition With No Well-Known Acronym

She described a child she treated who had hair that never grew and was easily broken. The patient’s skin was prone to bruising, and her fingernails would easily fall off after trauma; her dentist noted that she had no buds for adult teeth on x-rays. These different presentations are important because hair, teeth, and nails all come from the same ectoderm germ line in embryo development, Dr. Oboite said.

Exome sequencing revealed the girl had a very rare diagnosis called autosomal recessive hypotrichosis with recurrent skin vesicles. “So, it is really important to recognize that children who are presenting with hair issues can have a genetic, underlying condition,” she said. Examining the skin, nails, and teeth, in addition to the hair, can be clues to these very rare diagnoses.

Some of these hair loss conditions in children can be challenging to diagnose and manage, Dr. Oboite said. “So don’t be afraid to ask for help on complex or rare cases.” Pediatric dermatologists “are always happy to help you. Hair loss is daunting, and hair loss in children can be even more daunting,” but the rewards of accurate diagnosis and successful treatment can be great, she said.

Dr. Oboite reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — There are subtleties and nuances to diagnosing, treating, and monitoring the progress of treatment of hair loss in children. Moreover, hair loss in children can be challenging because it can be caused by a range of conditions, some common and others relatively rare.

Michelle Oboite, MD, shared tips on how to distinguish types of hair loss, when to treat with medications such as topical corticosteroids or Janus kinase (JAK) inhibitors, and why shared decision-making is important, at the ODAC Dermatology, Aesthetic & Surgical Conference.

What these conditions share is that they can negatively affect the quality of life for a child or teenager when the condition leads to anxiety, teasing, or bullying. “It is very isolating to have this condition that everyone in the world can see that you have and judge you for it,” said Dr. Oboite, an attending physician in the dermatology section of Children’s Hospital of Philadelphia.

While alopecia areata, tinea capitis, and trichotillomania are more common, other causes of hair loss in children include androgenetic alopecia, primary scarring alopecias, such as central centrifugal cicatricial alopecia, and dissecting cellulitis. Others are lichen planopilaris and genetic conditions, including loose anagen syndrome, uncombable hair syndrome, and “something so rare” — it has no acronym — autosomal recessive hypotrichosis with recurrent skin vesicles, Dr. Oboite said.
 

Alopecia Areata

Alopecia areata can differ from child to child and can appear in different stages: A localized patch stage, a diffuse patchy stage, or alopecia universalis. In this last stage, the child has already lost most or all the hair on the scalp and eyebrows, as well as the eyelashes.

The decision to treat or not to treat, particularly in younger children, should be on the basis of shared decision-making between a healthcare provider and caregiver, said Dr. Oboite, who is also an assistant professor of clinical dermatology at the University of Pennsylvania, Philadelphia.

Some younger children may not experience any negative impact from the condition, so waiting until they are older is an option.

Also, consider the impact of treatment on a child. Some therapies require frequent blood draws for monitoring, and some topical therapies that are applied multiple times a day “can be very overwhelming” for young children, Dr. Oboite said.

Most children with alopecia areata are healthy and do not need extensive screening laboratory testing. However, one exception is if thyroid dysfunction, commonly associated with alopecia areata, is suspected.

For alopecia areata, Dr. Oboite recommends starting with topical therapies, either topical corticosteroids (as first line) or topical JAK inhibitors (either topical ruxolitinib or compounded topical tofacitinib, both off-label for this indication).

Topical corticosteroids can be effective, but “you want to be thoughtful of the strength you’re using, the application frequency, and then the total amount of surface area that you’re treating,” Dr. Oboite said. Too potent or too much of a topical corticosteroid increases the risk for atrophy and systemic absorption, respectively. To reduce the risk, she reserves the use of ultrahigh-potency topical corticosteroids, such as clobetasol, for children ages 10 years or older. For children younger than 10 years, she recommends using mid-high-potency topical corticosteroids instead.

She recommends once-a-day application around bedtime 5 days a week, generally Monday through Friday to make it easier to remember.

“For children who have over 50% of the scalp involved, I do consider systemic therapy,” Dr. Oboite said. This can include oral steroids such as dexamethasone, prednisone, or prednisolone. For children with recalcitrant disease, she is more likely to use the oral JAK inhibitor ritlecitinib because it was recently approved by the Food and Drug Administration for treating severe alopecia areata in children 12 years and older and in adults.

Another strategy Dr. Oboite uses is to add low-dose oral minoxidil as an adjuvant to other systemic therapy. “I find that it helps with faster hair regrowth,” she said.
 

Tinea Capitis

Oral treatment is indicated for tinea capitis. “Topicals just don’t really clear this,” Dr. Oboite said. Also, talk to patients and families about preventing reinfection with the dermatophyte that causes this condition. “Make sure we’re cleaning hats, combs, brushes, and pillowcases. That is really important.”

Some patients can develop a widespread rash while on treatment. But in most cases, it’s not an adverse reaction to the medication but rather an indication that the body’s response is revving up, she noted.

Griseofulvin 20 mg/kg/d is one treatment option. Another is terbinafine (using weight-based dosing). A tip with terbinafine is that because the tablet needs to be crushed for a young child, “you can put it in anything, besides applesauce or yogurt with fruit on the bottom, which can be acidic and reduce the effectiveness of the medication,” Dr. Oboite said.

For cases of severe, inflammatory tinea capitis such as a kerion, “I will say you have to hold the hands of these patients, the journey can be long,” she added.
 

Trichotillomania

Trichotillomania occurs when someone cannot stop pulling their own hair, and in the early phases, it can be confused with alopecia areata. A thorough history and examination of the patient can help distinguish the two conditions. Sometimes a child or teen has a history of anxiety-related behaviors like nail biting that points to trichotillomania. Another tip is to use a dermatoscope to help distinguish hair loss conditions because it avoids having to do as many biopsies in children.

Redirection therapy can work for younger children, and cognitive behavioral therapy (CBT) can help older children with trichotillomania. In response to a question during the Q&A period, Dr. Oboite said psychiatrists or psychologists can perform CBT. If it takes time to get an appointment, there are some CBT apps that can help in the meantime, she said.

“One thing really important is to not blame the child,” Dr. Oboite said. “Most children don’t even know that they’re doing this. This is often not a behavior that is being done on purpose.”

Androgenetic Alopecia

Rarely, children and teenagers can also present with androgenetic alopecia, which Dr. Oboite has successfully treated with topical minoxidil, applied once a day before increasing to twice a day if tolerated. “I will tell them that when they pick it up, it will say ‘you should not use in children.’ But it actually can be used in children safely.”

Low-dose oral minoxidil is another option. Both treatments require a commitment by patients and parents because they are “taking this for a long time.”
 

Loose Anagen and Uncombable Hair Syndromes

A rare genetic form of hair loss is called loose anagen syndrome. Children with this disorder will have thin hair that is easily pulled out without a lot of force. Their hair appears to typically only grow to a certain length (such as to the nape of the neck) and then stops.

Another genetic hair loss condition is uncombable hair syndrome. It can cause hair to grow out of the scalp in all directions, and as the name suggests, it is almost impossible to comb or brush down. Along with loose anagen syndrome, uncombable hair syndrome tends to improve as the child gets older. “The key point here is telling parents that it can get better with time,” Dr. Oboite said.
 

A Condition With No Well-Known Acronym

She described a child she treated who had hair that never grew and was easily broken. The patient’s skin was prone to bruising, and her fingernails would easily fall off after trauma; her dentist noted that she had no buds for adult teeth on x-rays. These different presentations are important because hair, teeth, and nails all come from the same ectoderm germ line in embryo development, Dr. Oboite said.

Exome sequencing revealed the girl had a very rare diagnosis called autosomal recessive hypotrichosis with recurrent skin vesicles. “So, it is really important to recognize that children who are presenting with hair issues can have a genetic, underlying condition,” she said. Examining the skin, nails, and teeth, in addition to the hair, can be clues to these very rare diagnoses.

Some of these hair loss conditions in children can be challenging to diagnose and manage, Dr. Oboite said. “So don’t be afraid to ask for help on complex or rare cases.” Pediatric dermatologists “are always happy to help you. Hair loss is daunting, and hair loss in children can be even more daunting,” but the rewards of accurate diagnosis and successful treatment can be great, she said.

Dr. Oboite reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?

Acne

One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes. 
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added. 
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.

Psoriasis

A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis. 
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said. 
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.

Atopic Dermatitis

Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up. 

Rosacea

Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said. 
Dr. Shi reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?

Acne

One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes. 
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added. 
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.

Psoriasis

A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis. 
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said. 
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.

Atopic Dermatitis

Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up. 

Rosacea

Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said. 
Dr. Shi reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?

Acne

One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes. 
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added. 
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.

Psoriasis

A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis. 
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said. 
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.

Atopic Dermatitis

Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up. 

Rosacea

Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said. 
Dr. Shi reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Buprenorphine use, compared with methadone use, in pregnancy has been linked with a slightly lower risk of major congenital malformations in a new study of medications for opioid use disorder (OUD).

Elizabeth A. Suarez, PhD, MPH, with the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published the findings in JAMA Internal Medicine.

The lower risk for buprenorphine was small (risk ratio, 0.82; 95% confidence interval [CI], 0.69-0.97), and methadone use should not be ruled out on that basis, the authors wrote. For some women, particularly those on stable treatment before pregnancy or women who do not respond well to buprenorphine, methadone may be the better choice, they explained.
 

Either Medication Better Than Not Treating

The authors noted that either medication “is strongly recommended over untreated OUD during pregnancy.”

JAMA Internal Medicine Deputy Editor Deborah Grady, MD, MPH, with the Department of Medicine, University of California, San Francisco, emphasized that recommendation in an editor’s note, highlighting that treatment for OUD is critical to prevent infections, overdose, and death in pregnant women as well as neonatal opioid withdrawal syndrome and fetal death.

She stressed that internists and other primary care physicians have a key role in ensuring pregnant women with OUD receive appropriate treatment.

Given the importance of the issue, she wrote, “we have taken the unusual step of publishing two accompanying invited commentaries.”

Two developments may help increase use of buprenorphine, the study authors wrote. One is a recent study showing lower risk of adverse neonatal outcomes when buprenorphine is used during pregnancy compared with methadone. Another is the removal last year of the prescribing waiver for buprenorphine.
 

Study Included Medicaid Data Over 18 Years

The population-based cohort study used data from publicly insured Medicaid beneficiaries from 2000 to 2018. Pregnancies with enrollment from 90 days before pregnancy through 1 month after delivery and first-trimester use of buprenorphine or methadone were included (n = 13,360). The data were linked with infants’ health data.

The study group included 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone.

Major malformations were any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, oral clefts, and clubfoot.
 

Two Invited Commentaries Urge Caution in Interpretation

The two invited commentaries Dr. Grady mentioned in her editor’s note point both to the importance of the team’s findings and the need for better understanding of factors that may affect the choice of which OUD medication to use.

A commentary by Max Jordan Nguemeni Tiako, MD, MS, with the Department of Medicine, Brigham and Women’s Hospital, and colleagues, said that while the Suarez et al. data are important to share with patients, “the ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

They urge putting the findings in context given the study population, which comprises a relatively stable group of women with OUD, most of whom were taking OUD medications before they got pregnant. The study sample excludes a substantial number of women who are chronically underinsured or uninsured, Dr. Tiako’s team wrote, because those included were enrolled in Medicaid for 3 consecutive months before pregnancy.

“We urge caution when extrapolating these findings to newly pregnant individuals with untreated OUD,” they wrote.
 

Both Medications are Safe

Cara Poland, MD, MEd, with the Henry Ford Health + Michigan State University Health Sciences in Grand Rapids, and coauthors, added in another commentary that Suarez et al. didn’t include a comparison between the population-level congenital defect rate and the defect rate for people using medications for OUD in pregnancy.

That comparison, they wrote, would have better illustrated the safety of medications for OUD “instead of simply comparing two medications with long-standing safety data.”

When a clinician starts a woman on medication for OUD in pregnancy, it’s important to understand several factors, including individual access to and comfort with different treatment approaches, they noted. It’s also important to weigh whether changing medications is worth the potential drawbacks of disrupting their well-managed care.

They wrote that the paper by Suarez et al. does not make the case for switching medications based on their findings.

Internists, they added, are ideal experts to explain risk of fetal abnormalities in the wider context of supporting engagement with continuous medication for OUD.

“In the absence of other concerns, switching medications (methadone to buprenorphine) or — worse — discontinuing [medication for] OUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy,” Dr. Poland’s team wrote. “No treatment is without risk in pregnancy.”

This study was supported by the National Institute on Drug Abuse. In the Suarez et al. study, coauthors Dr. Hernández-Díaz, Dr. Gray, Dr. Connery, Dr. Zhu, and Dr. Huybrechts reported grants, personal fees and consulting payments from several pharmaceutical companies. Dr. Grady reports no relevant financial relationships in her editor’s note. No relevant financial relationships were reported by authors of the Tiako et al. commentary.

Regarding the commentary by Poland et al., grants were reported from the Michigan Health Endowment Fund, the Michigan Department of Health and Human Services, the National Institute on Drug Abuse and Blue Cross Blue Shield of Michigan outside the submitted work. No other disclosures were reported.

Buprenorphine use, compared with methadone use, in pregnancy has been linked with a slightly lower risk of major congenital malformations in a new study of medications for opioid use disorder (OUD).

Elizabeth A. Suarez, PhD, MPH, with the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published the findings in JAMA Internal Medicine.

The lower risk for buprenorphine was small (risk ratio, 0.82; 95% confidence interval [CI], 0.69-0.97), and methadone use should not be ruled out on that basis, the authors wrote. For some women, particularly those on stable treatment before pregnancy or women who do not respond well to buprenorphine, methadone may be the better choice, they explained.
 

Either Medication Better Than Not Treating

The authors noted that either medication “is strongly recommended over untreated OUD during pregnancy.”

JAMA Internal Medicine Deputy Editor Deborah Grady, MD, MPH, with the Department of Medicine, University of California, San Francisco, emphasized that recommendation in an editor’s note, highlighting that treatment for OUD is critical to prevent infections, overdose, and death in pregnant women as well as neonatal opioid withdrawal syndrome and fetal death.

She stressed that internists and other primary care physicians have a key role in ensuring pregnant women with OUD receive appropriate treatment.

Given the importance of the issue, she wrote, “we have taken the unusual step of publishing two accompanying invited commentaries.”

Two developments may help increase use of buprenorphine, the study authors wrote. One is a recent study showing lower risk of adverse neonatal outcomes when buprenorphine is used during pregnancy compared with methadone. Another is the removal last year of the prescribing waiver for buprenorphine.
 

Study Included Medicaid Data Over 18 Years

The population-based cohort study used data from publicly insured Medicaid beneficiaries from 2000 to 2018. Pregnancies with enrollment from 90 days before pregnancy through 1 month after delivery and first-trimester use of buprenorphine or methadone were included (n = 13,360). The data were linked with infants’ health data.

The study group included 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone.

Major malformations were any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, oral clefts, and clubfoot.
 

Two Invited Commentaries Urge Caution in Interpretation

The two invited commentaries Dr. Grady mentioned in her editor’s note point both to the importance of the team’s findings and the need for better understanding of factors that may affect the choice of which OUD medication to use.

A commentary by Max Jordan Nguemeni Tiako, MD, MS, with the Department of Medicine, Brigham and Women’s Hospital, and colleagues, said that while the Suarez et al. data are important to share with patients, “the ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

They urge putting the findings in context given the study population, which comprises a relatively stable group of women with OUD, most of whom were taking OUD medications before they got pregnant. The study sample excludes a substantial number of women who are chronically underinsured or uninsured, Dr. Tiako’s team wrote, because those included were enrolled in Medicaid for 3 consecutive months before pregnancy.

“We urge caution when extrapolating these findings to newly pregnant individuals with untreated OUD,” they wrote.
 

Both Medications are Safe

Cara Poland, MD, MEd, with the Henry Ford Health + Michigan State University Health Sciences in Grand Rapids, and coauthors, added in another commentary that Suarez et al. didn’t include a comparison between the population-level congenital defect rate and the defect rate for people using medications for OUD in pregnancy.

That comparison, they wrote, would have better illustrated the safety of medications for OUD “instead of simply comparing two medications with long-standing safety data.”

When a clinician starts a woman on medication for OUD in pregnancy, it’s important to understand several factors, including individual access to and comfort with different treatment approaches, they noted. It’s also important to weigh whether changing medications is worth the potential drawbacks of disrupting their well-managed care.

They wrote that the paper by Suarez et al. does not make the case for switching medications based on their findings.

Internists, they added, are ideal experts to explain risk of fetal abnormalities in the wider context of supporting engagement with continuous medication for OUD.

“In the absence of other concerns, switching medications (methadone to buprenorphine) or — worse — discontinuing [medication for] OUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy,” Dr. Poland’s team wrote. “No treatment is without risk in pregnancy.”

This study was supported by the National Institute on Drug Abuse. In the Suarez et al. study, coauthors Dr. Hernández-Díaz, Dr. Gray, Dr. Connery, Dr. Zhu, and Dr. Huybrechts reported grants, personal fees and consulting payments from several pharmaceutical companies. Dr. Grady reports no relevant financial relationships in her editor’s note. No relevant financial relationships were reported by authors of the Tiako et al. commentary.

Regarding the commentary by Poland et al., grants were reported from the Michigan Health Endowment Fund, the Michigan Department of Health and Human Services, the National Institute on Drug Abuse and Blue Cross Blue Shield of Michigan outside the submitted work. No other disclosures were reported.

Buprenorphine use, compared with methadone use, in pregnancy has been linked with a slightly lower risk of major congenital malformations in a new study of medications for opioid use disorder (OUD).

Elizabeth A. Suarez, PhD, MPH, with the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published the findings in JAMA Internal Medicine.

The lower risk for buprenorphine was small (risk ratio, 0.82; 95% confidence interval [CI], 0.69-0.97), and methadone use should not be ruled out on that basis, the authors wrote. For some women, particularly those on stable treatment before pregnancy or women who do not respond well to buprenorphine, methadone may be the better choice, they explained.
 

Either Medication Better Than Not Treating

The authors noted that either medication “is strongly recommended over untreated OUD during pregnancy.”

JAMA Internal Medicine Deputy Editor Deborah Grady, MD, MPH, with the Department of Medicine, University of California, San Francisco, emphasized that recommendation in an editor’s note, highlighting that treatment for OUD is critical to prevent infections, overdose, and death in pregnant women as well as neonatal opioid withdrawal syndrome and fetal death.

She stressed that internists and other primary care physicians have a key role in ensuring pregnant women with OUD receive appropriate treatment.

Given the importance of the issue, she wrote, “we have taken the unusual step of publishing two accompanying invited commentaries.”

Two developments may help increase use of buprenorphine, the study authors wrote. One is a recent study showing lower risk of adverse neonatal outcomes when buprenorphine is used during pregnancy compared with methadone. Another is the removal last year of the prescribing waiver for buprenorphine.
 

Study Included Medicaid Data Over 18 Years

The population-based cohort study used data from publicly insured Medicaid beneficiaries from 2000 to 2018. Pregnancies with enrollment from 90 days before pregnancy through 1 month after delivery and first-trimester use of buprenorphine or methadone were included (n = 13,360). The data were linked with infants’ health data.

The study group included 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone.

Major malformations were any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, oral clefts, and clubfoot.
 

Two Invited Commentaries Urge Caution in Interpretation

The two invited commentaries Dr. Grady mentioned in her editor’s note point both to the importance of the team’s findings and the need for better understanding of factors that may affect the choice of which OUD medication to use.

A commentary by Max Jordan Nguemeni Tiako, MD, MS, with the Department of Medicine, Brigham and Women’s Hospital, and colleagues, said that while the Suarez et al. data are important to share with patients, “the ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

They urge putting the findings in context given the study population, which comprises a relatively stable group of women with OUD, most of whom were taking OUD medications before they got pregnant. The study sample excludes a substantial number of women who are chronically underinsured or uninsured, Dr. Tiako’s team wrote, because those included were enrolled in Medicaid for 3 consecutive months before pregnancy.

“We urge caution when extrapolating these findings to newly pregnant individuals with untreated OUD,” they wrote.
 

Both Medications are Safe

Cara Poland, MD, MEd, with the Henry Ford Health + Michigan State University Health Sciences in Grand Rapids, and coauthors, added in another commentary that Suarez et al. didn’t include a comparison between the population-level congenital defect rate and the defect rate for people using medications for OUD in pregnancy.

That comparison, they wrote, would have better illustrated the safety of medications for OUD “instead of simply comparing two medications with long-standing safety data.”

When a clinician starts a woman on medication for OUD in pregnancy, it’s important to understand several factors, including individual access to and comfort with different treatment approaches, they noted. It’s also important to weigh whether changing medications is worth the potential drawbacks of disrupting their well-managed care.

They wrote that the paper by Suarez et al. does not make the case for switching medications based on their findings.

Internists, they added, are ideal experts to explain risk of fetal abnormalities in the wider context of supporting engagement with continuous medication for OUD.

“In the absence of other concerns, switching medications (methadone to buprenorphine) or — worse — discontinuing [medication for] OUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy,” Dr. Poland’s team wrote. “No treatment is without risk in pregnancy.”

This study was supported by the National Institute on Drug Abuse. In the Suarez et al. study, coauthors Dr. Hernández-Díaz, Dr. Gray, Dr. Connery, Dr. Zhu, and Dr. Huybrechts reported grants, personal fees and consulting payments from several pharmaceutical companies. Dr. Grady reports no relevant financial relationships in her editor’s note. No relevant financial relationships were reported by authors of the Tiako et al. commentary.

Regarding the commentary by Poland et al., grants were reported from the Michigan Health Endowment Fund, the Michigan Department of Health and Human Services, the National Institute on Drug Abuse and Blue Cross Blue Shield of Michigan outside the submitted work. No other disclosures were reported.

A clinic aimed at managing patients with difficult-to-control atopic dermatitis (AD) by involving assessments from a team of clinicians from different disciplines led to significant improvements in severity of the disease, results from a single-center study showed.

“A significant challenge in caring for patients with atopic dermatitis is lack of collaboration between healthcare providers, leading to disjointed care, inconsistent treatment plans, and conflicting dialogue with patients,” first author Alexis Tracy, MD, a combined allergy and dermatology research fellow at Rady Children’s Hospital, San Diego, and colleagues wrote in the study, which was published online January 14, 2024, in Pediatric Dermatology.

Launched in 2019, the clinic, which is called the Multidisciplinary Atopic Dermatitis Program (MADP), is a collaborative effort between with Rady Children’s Hospital and the University of California San Diego Health division of dermatology, division of allergy & immunology, and the hospital’s clinical pharmacy. Patients referred to the MADP undergo a concurrent, comprehensive evaluation by a dermatologist, allergist, clinical pharmacist, and others who help to assess AD severity, provide family education about the disease, and form a care plan using the model of shared decision-making (SDM). Visits take about two hours, and the frequency of follow-up visits varies.

Courtesy Rady Children's Hospital

In the dermatology realm, tools used to compare the extent and severity of AD between visits include the Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), the Children’s Dermatology Life Quality Index (CDLQI), Validated Investigator Global Assessment (vIGA), Body Surface Area (BSA), and the Numerical Rating Scale (NRS).To investigate the MADP’s success to date, Dr. Tracy and colleagues evaluated 44 patients with a history of moderate to severe, persistent AD who were referred to the clinic between April 3, 2019, and October 22, 2022, and had between one and three follow-up visits. The patients ranged from age 4 months to 18 years (mean, 7.74 years).

Compared with baseline, EASI scores of patients decreased significantly, with an average mean improvement of 9.61 by the second visit, 15.12 by the third visit, and 17.42 by the fourth visit (P <.001 for all three). These represent an average decreases of 44.20%, 63.26%, 74.35%, respectively.

At the seventh visit, the EASI score decreased by a mean of 33.48 (P = .008), which represents an average decrease of 91.52% from baseline. Of the 44 patients, 32 achieved an EASI 50 and 21 achieved an EASI 75.

In other findings, the mean vIGA improved with each visit, with the largest observed improvement at the seventh visit (a mean of 2.25 points; P = .009) and the greatest mean improvement in the POEM score was seen at the sixth visit (a mean of 11.13 points; P < .001). The mean difference in CDLQI scores also increased with each visit, with the largest improvement seen at the sixth visit (an increase of 12 points; P < .001).

Similarly, BSA progressively improved at each clinic visit, from a mean decrease of 16.02% at the second visit to a mean decrease of 56.04% at the seventh visit (P < .001 for both). Meanwhile, the largest mean improvement in pruritus was seen at the sixth visit (a mean of 4.10 points; P = .001).

In an interview, MADP’s codirector, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, said that the consistency of data showing rapid, consistent improvement with a varied set of physician assessed scores and patient-reported outcomes “was very impressive, especially given the variation in severity, extent and difficult course of many of the patients we saw, and spectrum of interventions – from topical regimens to advanced systemic therapies,” he said. “As clinicians we tend to remember the ‘tough cases,’ and it was tremendous to see the impact and utility of the clinic.”

Courtesy University of California, San Diego

Important model of care

Asked to comment on the results, pediatric dermatologist Moise L. Levy, MD, professor of internal medicine and pediatrics at the University of Texas at Austin, who was not involved with the study, characterized the MADP as an important model of care. “Multi-interdisciplinary care of such conditions is well-known to be of great help for patients and their families,” he told this news organization.

“A key part of the ‘team’ is the family/patient engagement and shared decision-making. The use of visual aides to highlight components of care was likely of great use, as well,” he said. “All such interventions impact the disease, as well as associated problems, such as itch, sleep, and mental health. Importantly, such interventions, while known to be useful as demonstrated by the authors, take time, and relate to improved outcomes as noted by the date outlined by the authors.”

The study authors acknowledged certain limitations of the study, including the lack of a control group with single-specialty visits. “The real take-away is that taking the time to do more holistic assessments of health — with skin and allergy issues being discussed, and consistent education and messaging — helps make our medical interventions more successful, with both objective disease improvement and patient/family satisfaction,” Dr. Eichenfield said in the interview.

Pfizer and Sanofi provided financial support to MADP, and for the study. Dr. Eichenfield disclosed that he serves as a scientific adviser, consultant, and/or clinical trial investigator for AbbVie, Amgen, Aslan, Castle Biosciences, Dermavant, Eli Lilly and Company, Forté, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron Pharmaceuticals, Sanofi-Genzyme, Trialspark, and UCB. Dr. Geng disclosed ties with Sanofi, Regeneron, Pfizer, and AbbVie, and is an adviser to Incyte, Galderma, Eli-Lilly, and LEO. The other authors reported having no disclosures. Dr. Levy disclosed ties with Abeona, Amgen, Arcutis, Castle Creek, Dusa Pharma, Krystal Bio, Novan, Regeneron, and Sanofi Genzyme. He is also an investigator for Janssen.

A clinic aimed at managing patients with difficult-to-control atopic dermatitis (AD) by involving assessments from a team of clinicians from different disciplines led to significant improvements in severity of the disease, results from a single-center study showed.

“A significant challenge in caring for patients with atopic dermatitis is lack of collaboration between healthcare providers, leading to disjointed care, inconsistent treatment plans, and conflicting dialogue with patients,” first author Alexis Tracy, MD, a combined allergy and dermatology research fellow at Rady Children’s Hospital, San Diego, and colleagues wrote in the study, which was published online January 14, 2024, in Pediatric Dermatology.

Launched in 2019, the clinic, which is called the Multidisciplinary Atopic Dermatitis Program (MADP), is a collaborative effort between with Rady Children’s Hospital and the University of California San Diego Health division of dermatology, division of allergy & immunology, and the hospital’s clinical pharmacy. Patients referred to the MADP undergo a concurrent, comprehensive evaluation by a dermatologist, allergist, clinical pharmacist, and others who help to assess AD severity, provide family education about the disease, and form a care plan using the model of shared decision-making (SDM). Visits take about two hours, and the frequency of follow-up visits varies.

Courtesy Rady Children&#039;s Hospital

In the dermatology realm, tools used to compare the extent and severity of AD between visits include the Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), the Children’s Dermatology Life Quality Index (CDLQI), Validated Investigator Global Assessment (vIGA), Body Surface Area (BSA), and the Numerical Rating Scale (NRS).To investigate the MADP’s success to date, Dr. Tracy and colleagues evaluated 44 patients with a history of moderate to severe, persistent AD who were referred to the clinic between April 3, 2019, and October 22, 2022, and had between one and three follow-up visits. The patients ranged from age 4 months to 18 years (mean, 7.74 years).

Compared with baseline, EASI scores of patients decreased significantly, with an average mean improvement of 9.61 by the second visit, 15.12 by the third visit, and 17.42 by the fourth visit (P <.001 for all three). These represent an average decreases of 44.20%, 63.26%, 74.35%, respectively.

At the seventh visit, the EASI score decreased by a mean of 33.48 (P = .008), which represents an average decrease of 91.52% from baseline. Of the 44 patients, 32 achieved an EASI 50 and 21 achieved an EASI 75.

In other findings, the mean vIGA improved with each visit, with the largest observed improvement at the seventh visit (a mean of 2.25 points; P = .009) and the greatest mean improvement in the POEM score was seen at the sixth visit (a mean of 11.13 points; P < .001). The mean difference in CDLQI scores also increased with each visit, with the largest improvement seen at the sixth visit (an increase of 12 points; P < .001).

Similarly, BSA progressively improved at each clinic visit, from a mean decrease of 16.02% at the second visit to a mean decrease of 56.04% at the seventh visit (P < .001 for both). Meanwhile, the largest mean improvement in pruritus was seen at the sixth visit (a mean of 4.10 points; P = .001).

In an interview, MADP’s codirector, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, said that the consistency of data showing rapid, consistent improvement with a varied set of physician assessed scores and patient-reported outcomes “was very impressive, especially given the variation in severity, extent and difficult course of many of the patients we saw, and spectrum of interventions – from topical regimens to advanced systemic therapies,” he said. “As clinicians we tend to remember the ‘tough cases,’ and it was tremendous to see the impact and utility of the clinic.”

Courtesy University of California, San Diego

Important model of care

Asked to comment on the results, pediatric dermatologist Moise L. Levy, MD, professor of internal medicine and pediatrics at the University of Texas at Austin, who was not involved with the study, characterized the MADP as an important model of care. “Multi-interdisciplinary care of such conditions is well-known to be of great help for patients and their families,” he told this news organization.

“A key part of the ‘team’ is the family/patient engagement and shared decision-making. The use of visual aides to highlight components of care was likely of great use, as well,” he said. “All such interventions impact the disease, as well as associated problems, such as itch, sleep, and mental health. Importantly, such interventions, while known to be useful as demonstrated by the authors, take time, and relate to improved outcomes as noted by the date outlined by the authors.”

The study authors acknowledged certain limitations of the study, including the lack of a control group with single-specialty visits. “The real take-away is that taking the time to do more holistic assessments of health — with skin and allergy issues being discussed, and consistent education and messaging — helps make our medical interventions more successful, with both objective disease improvement and patient/family satisfaction,” Dr. Eichenfield said in the interview.

Pfizer and Sanofi provided financial support to MADP, and for the study. Dr. Eichenfield disclosed that he serves as a scientific adviser, consultant, and/or clinical trial investigator for AbbVie, Amgen, Aslan, Castle Biosciences, Dermavant, Eli Lilly and Company, Forté, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron Pharmaceuticals, Sanofi-Genzyme, Trialspark, and UCB. Dr. Geng disclosed ties with Sanofi, Regeneron, Pfizer, and AbbVie, and is an adviser to Incyte, Galderma, Eli-Lilly, and LEO. The other authors reported having no disclosures. Dr. Levy disclosed ties with Abeona, Amgen, Arcutis, Castle Creek, Dusa Pharma, Krystal Bio, Novan, Regeneron, and Sanofi Genzyme. He is also an investigator for Janssen.

A clinic aimed at managing patients with difficult-to-control atopic dermatitis (AD) by involving assessments from a team of clinicians from different disciplines led to significant improvements in severity of the disease, results from a single-center study showed.

“A significant challenge in caring for patients with atopic dermatitis is lack of collaboration between healthcare providers, leading to disjointed care, inconsistent treatment plans, and conflicting dialogue with patients,” first author Alexis Tracy, MD, a combined allergy and dermatology research fellow at Rady Children’s Hospital, San Diego, and colleagues wrote in the study, which was published online January 14, 2024, in Pediatric Dermatology.

Launched in 2019, the clinic, which is called the Multidisciplinary Atopic Dermatitis Program (MADP), is a collaborative effort between with Rady Children’s Hospital and the University of California San Diego Health division of dermatology, division of allergy & immunology, and the hospital’s clinical pharmacy. Patients referred to the MADP undergo a concurrent, comprehensive evaluation by a dermatologist, allergist, clinical pharmacist, and others who help to assess AD severity, provide family education about the disease, and form a care plan using the model of shared decision-making (SDM). Visits take about two hours, and the frequency of follow-up visits varies.

Courtesy Rady Children&#039;s Hospital

In the dermatology realm, tools used to compare the extent and severity of AD between visits include the Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), the Children’s Dermatology Life Quality Index (CDLQI), Validated Investigator Global Assessment (vIGA), Body Surface Area (BSA), and the Numerical Rating Scale (NRS).To investigate the MADP’s success to date, Dr. Tracy and colleagues evaluated 44 patients with a history of moderate to severe, persistent AD who were referred to the clinic between April 3, 2019, and October 22, 2022, and had between one and three follow-up visits. The patients ranged from age 4 months to 18 years (mean, 7.74 years).

Compared with baseline, EASI scores of patients decreased significantly, with an average mean improvement of 9.61 by the second visit, 15.12 by the third visit, and 17.42 by the fourth visit (P <.001 for all three). These represent an average decreases of 44.20%, 63.26%, 74.35%, respectively.

At the seventh visit, the EASI score decreased by a mean of 33.48 (P = .008), which represents an average decrease of 91.52% from baseline. Of the 44 patients, 32 achieved an EASI 50 and 21 achieved an EASI 75.

In other findings, the mean vIGA improved with each visit, with the largest observed improvement at the seventh visit (a mean of 2.25 points; P = .009) and the greatest mean improvement in the POEM score was seen at the sixth visit (a mean of 11.13 points; P < .001). The mean difference in CDLQI scores also increased with each visit, with the largest improvement seen at the sixth visit (an increase of 12 points; P < .001).

Similarly, BSA progressively improved at each clinic visit, from a mean decrease of 16.02% at the second visit to a mean decrease of 56.04% at the seventh visit (P < .001 for both). Meanwhile, the largest mean improvement in pruritus was seen at the sixth visit (a mean of 4.10 points; P = .001).

In an interview, MADP’s codirector, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, said that the consistency of data showing rapid, consistent improvement with a varied set of physician assessed scores and patient-reported outcomes “was very impressive, especially given the variation in severity, extent and difficult course of many of the patients we saw, and spectrum of interventions – from topical regimens to advanced systemic therapies,” he said. “As clinicians we tend to remember the ‘tough cases,’ and it was tremendous to see the impact and utility of the clinic.”

Courtesy University of California, San Diego

Important model of care

Asked to comment on the results, pediatric dermatologist Moise L. Levy, MD, professor of internal medicine and pediatrics at the University of Texas at Austin, who was not involved with the study, characterized the MADP as an important model of care. “Multi-interdisciplinary care of such conditions is well-known to be of great help for patients and their families,” he told this news organization.

“A key part of the ‘team’ is the family/patient engagement and shared decision-making. The use of visual aides to highlight components of care was likely of great use, as well,” he said. “All such interventions impact the disease, as well as associated problems, such as itch, sleep, and mental health. Importantly, such interventions, while known to be useful as demonstrated by the authors, take time, and relate to improved outcomes as noted by the date outlined by the authors.”

The study authors acknowledged certain limitations of the study, including the lack of a control group with single-specialty visits. “The real take-away is that taking the time to do more holistic assessments of health — with skin and allergy issues being discussed, and consistent education and messaging — helps make our medical interventions more successful, with both objective disease improvement and patient/family satisfaction,” Dr. Eichenfield said in the interview.

Pfizer and Sanofi provided financial support to MADP, and for the study. Dr. Eichenfield disclosed that he serves as a scientific adviser, consultant, and/or clinical trial investigator for AbbVie, Amgen, Aslan, Castle Biosciences, Dermavant, Eli Lilly and Company, Forté, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron Pharmaceuticals, Sanofi-Genzyme, Trialspark, and UCB. Dr. Geng disclosed ties with Sanofi, Regeneron, Pfizer, and AbbVie, and is an adviser to Incyte, Galderma, Eli-Lilly, and LEO. The other authors reported having no disclosures. Dr. Levy disclosed ties with Abeona, Amgen, Arcutis, Castle Creek, Dusa Pharma, Krystal Bio, Novan, Regeneron, and Sanofi Genzyme. He is also an investigator for Janssen.

The US Preventive Services Task Force (USPSTF) has published draft recommendations that 6-year-olds with obesity be lectured to about diet and exercise.

Never mind that there are no reproducible or scalable studies demonstrating durable and clinically meaningful benefits of this for adults let alone children. Never mind that children are not household decision-makers on matters of grocery shopping, cooking, or exercise. Never mind the corollary that many children so lectured who fail to see an impact on their weight will perceive that as their own personal failures. And of course, never mind that we’re privileged to be in an era with safe, effective, pharmacotherapeutic options for obesity. No. We must teach children it’s their fault if they’re fat. Because ultimately that’s what many of them will learn.

That’s not to say there’s no room for counseling. But with children as young as 6, that counseling should be delivered exclusively to their parents and caregivers. That counseling should focus as much if not more so on the impact of weight bias and the biological basis of obesity rather than diet and exercise, while explicitly teaching parents the means to discuss nutrition without risking their children feeling worse about themselves, increasing the risk for conflict over changes, or heightening their children’s chance of developing eating disorders or maladaptive relationships with food.

But back to the USPSTF’s actual recommendation for those 6 years old and up. They’re recommending “at least” 26 hours of lectures over a year-long interprofessional intervention. Putting aside the reality that this isn’t scalable time-wise or cost-wise to reach even a fraction of the roughly 15 million US children with obesity, there is also the issue of service provision. Because when it comes to obesity, if the intervention is purely educational, even if you want to believe there is a syllabus out there that would have a dramatic impact, its impact will vary wildly depending on the skill and approach of the service providers. This inconvenient truth is also the one that makes it impossible to meaningfully compare program outcomes even when they share the same content.

The USPSTF’s draft recommendations also explicitly avoid what the American Academy of Pediatrics has rightly embraced: the use where appropriate of medications or surgery. While opponents of the use of pharmacotherapy for childhood obesity tend to point to a lack of long-term data as rationale for its denial, something that the USPSTF has done, again, we have long-term data demonstrating a lack of scalable, clinically meaningful efficacy for service only based programs.

Childhood obesity is a flood and its ongoing current is relentless. Given its tremendous impact, especially at its extremes, on both physical and mental health, this is yet another example of systemic weight bias in action — it’s as if the USPSTF is recommending a swimming lesson–only approach while actively fearmongering, despite an absence of plausible mechanistic risk, about the long-term use of life jackets.

Dr. Freedhoff is associate professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. Dr. Freedhoff has disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.

A version of this article appeared on Medscape.com.

The US Preventive Services Task Force (USPSTF) has published draft recommendations that 6-year-olds with obesity be lectured to about diet and exercise.

Never mind that there are no reproducible or scalable studies demonstrating durable and clinically meaningful benefits of this for adults let alone children. Never mind that children are not household decision-makers on matters of grocery shopping, cooking, or exercise. Never mind the corollary that many children so lectured who fail to see an impact on their weight will perceive that as their own personal failures. And of course, never mind that we’re privileged to be in an era with safe, effective, pharmacotherapeutic options for obesity. No. We must teach children it’s their fault if they’re fat. Because ultimately that’s what many of them will learn.

That’s not to say there’s no room for counseling. But with children as young as 6, that counseling should be delivered exclusively to their parents and caregivers. That counseling should focus as much if not more so on the impact of weight bias and the biological basis of obesity rather than diet and exercise, while explicitly teaching parents the means to discuss nutrition without risking their children feeling worse about themselves, increasing the risk for conflict over changes, or heightening their children’s chance of developing eating disorders or maladaptive relationships with food.

But back to the USPSTF’s actual recommendation for those 6 years old and up. They’re recommending “at least” 26 hours of lectures over a year-long interprofessional intervention. Putting aside the reality that this isn’t scalable time-wise or cost-wise to reach even a fraction of the roughly 15 million US children with obesity, there is also the issue of service provision. Because when it comes to obesity, if the intervention is purely educational, even if you want to believe there is a syllabus out there that would have a dramatic impact, its impact will vary wildly depending on the skill and approach of the service providers. This inconvenient truth is also the one that makes it impossible to meaningfully compare program outcomes even when they share the same content.

The USPSTF’s draft recommendations also explicitly avoid what the American Academy of Pediatrics has rightly embraced: the use where appropriate of medications or surgery. While opponents of the use of pharmacotherapy for childhood obesity tend to point to a lack of long-term data as rationale for its denial, something that the USPSTF has done, again, we have long-term data demonstrating a lack of scalable, clinically meaningful efficacy for service only based programs.

Childhood obesity is a flood and its ongoing current is relentless. Given its tremendous impact, especially at its extremes, on both physical and mental health, this is yet another example of systemic weight bias in action — it’s as if the USPSTF is recommending a swimming lesson–only approach while actively fearmongering, despite an absence of plausible mechanistic risk, about the long-term use of life jackets.

Dr. Freedhoff is associate professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. Dr. Freedhoff has disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.

A version of this article appeared on Medscape.com.

The US Preventive Services Task Force (USPSTF) has published draft recommendations that 6-year-olds with obesity be lectured to about diet and exercise.

Never mind that there are no reproducible or scalable studies demonstrating durable and clinically meaningful benefits of this for adults let alone children. Never mind that children are not household decision-makers on matters of grocery shopping, cooking, or exercise. Never mind the corollary that many children so lectured who fail to see an impact on their weight will perceive that as their own personal failures. And of course, never mind that we’re privileged to be in an era with safe, effective, pharmacotherapeutic options for obesity. No. We must teach children it’s their fault if they’re fat. Because ultimately that’s what many of them will learn.

That’s not to say there’s no room for counseling. But with children as young as 6, that counseling should be delivered exclusively to their parents and caregivers. That counseling should focus as much if not more so on the impact of weight bias and the biological basis of obesity rather than diet and exercise, while explicitly teaching parents the means to discuss nutrition without risking their children feeling worse about themselves, increasing the risk for conflict over changes, or heightening their children’s chance of developing eating disorders or maladaptive relationships with food.

But back to the USPSTF’s actual recommendation for those 6 years old and up. They’re recommending “at least” 26 hours of lectures over a year-long interprofessional intervention. Putting aside the reality that this isn’t scalable time-wise or cost-wise to reach even a fraction of the roughly 15 million US children with obesity, there is also the issue of service provision. Because when it comes to obesity, if the intervention is purely educational, even if you want to believe there is a syllabus out there that would have a dramatic impact, its impact will vary wildly depending on the skill and approach of the service providers. This inconvenient truth is also the one that makes it impossible to meaningfully compare program outcomes even when they share the same content.

The USPSTF’s draft recommendations also explicitly avoid what the American Academy of Pediatrics has rightly embraced: the use where appropriate of medications or surgery. While opponents of the use of pharmacotherapy for childhood obesity tend to point to a lack of long-term data as rationale for its denial, something that the USPSTF has done, again, we have long-term data demonstrating a lack of scalable, clinically meaningful efficacy for service only based programs.

Childhood obesity is a flood and its ongoing current is relentless. Given its tremendous impact, especially at its extremes, on both physical and mental health, this is yet another example of systemic weight bias in action — it’s as if the USPSTF is recommending a swimming lesson–only approach while actively fearmongering, despite an absence of plausible mechanistic risk, about the long-term use of life jackets.

Dr. Freedhoff is associate professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. Dr. Freedhoff has disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.

A version of this article appeared on Medscape.com.

France did it 5 years ago and now, from January 1, the Dutch have followed suit, banning devices such as mobile phones and tablets in classrooms unless needed during lessons, for medical reasons, or by students with disabilities. The ban aims to limit distractions during the school day. 

We could all surely do with some device detox, but the question remains whether too much screen time has an impact on child development. Karen Mansfield, PhD, a postdoctoral researcher on adolescent well-being in the digital age at Oxford University, told this news organization, “The evidence is definitely not set in stone. There have been some recent reviews of screen time effects on children, demonstrating very mixed findings.”

The latest research, said Dr. Mansfield, is still young, lacking consistency in findings, and rife with misinterpretation.

Tiziana Metitieri, a cognitive neuropsychologist at the Meyer Hospital in Florence, Italy, echoed these sentiments, suggesting that the sheer quantity of screen time is an insufficient metric for understanding its impact on cognitive and psychological development. “There are two main reasons for this,” she explained to this news organization. “Firstly, because the current measurements of screen time rely on self-report data, which can be affected by an overestimation or underestimation of objective usage due to social desirability bias. Secondly, because digital experiences differ in terms of content, device used, context, location, and individuals involved.”
 

Are Politicians in Too Much of a Rush?

UNESCO’s most recent report on technology in education highlighted a correlation between excessive mobile phone use and reduced educational performance and emotional stability.

The OECD report “Empowering Young Children in the Digital Age,” rightly suggested there is a need to improve protection in digital environments, bridge the digital divide, and educate parents and teachers on safe digital practices.

But Dr. Mansfield said, “Currently, policy implementation is racing far ahead of the evidence, with similar suggestions to ban smartphones in schools in the United Kingdom and Canada. However, there is no available evidence on the long-term benefits of banning smartphones. Much of the research behind the OECD and UNESCO policies is observational in nature, which limits causal interpretation more than with interventions.”

While most governments are not pursuing restrictive practices, Dr. Metitieri said that “their approaches are based on their political ideology, often using moral panic as a means to rally support, showing their heartfelt commitment to defending against the invasions of digital technology ruining human civilizations.” 

Sakshi Ghai, PhD, Dr. Mansfield’s fellow postdoctoral researcher at Oxford University, reiterated Dr. Metitieri’s concerns, “Screen time as a concept has limitations, and policy guidance needs to be careful when drawing insights from such limited evidence. What do we mean by screen time? How can time spent on different activities be clearly delineated? An oversimplistic focus on screen time may overlook the nuances and complexity of digital media use.”
 

The Key Is the What and Where

Digital screens can be productive for children, such as when used for educational purposes, be it to join a class over Zoom or partake in extracurricular educational activities. However, Dr. Ghai emphasized the importance of identifying what constitutes reasonable consumption of digital media. “Screens can help disadvantaged children achieve positive educational outcomes, particularly those with learning difficulties,” said Dr. Ghai. “Using media to interact with other children can also bring positive social connections to racially diverse children or those from the LGBTQ community, which reiterates why finding the balance that allows children to reap the benefits of digital technology while safeguarding their mental, physical, and social health, is crucial.”

On the other hand, Dr. Metitieri explained that there is evidence that passive exposure to educational content does not necessarily lead to growth benefits. “The key is the relational environment in which these digital experiences occur,” she said. 

Dr. Mansfield said a lot of research describes excessive use of digital media as a form of addiction. “Some studies have attempted to validate and test ‘smartphone addiction’ scales for adolescent. Besides pathologizing an increasingly common activity, such self-report scales are highly subjective, implying serious limitations when attempting to define ‘cut offs’ or diagnostic thresholds.”

Previous efforts to determine benchmarks for screen time usage, focusing on the relationship between historical screen usage and present mental well-being, have overlooked the nature of the digital interaction and the social and technological backdrop. “Effects of screen time on children is a continuously changing, rapidly developing research field, and other contextual factors have been shown to play a greater role on mental health,” explained Dr. Mansfield.
 

Are School Bans Too Restrictive?

Implementing nationwide policies that warrant a dramatic shift in how we approach activities that have become second nature, such as using a mobile phone, is profoundly difficult, particularly as evidence is inconclusive and inconsistent. “The long-term effects of different types of digital content on children’s learning are yet to be clear, and most education-related research so far has been carried out with college students,” said Dr. Mansfield.

For concerned parents and schools, Dr. Metitieri advised against overly restrictive approaches. “Children and adolescents can find ways around restrictions at home and school, meaning that an overly restrictive approach is limited in its effectiveness,” she said. “The best way to adapt to the changes happening in education, relationships, work, and leisure is through a combination of experiences offline and digital education.”

Mirroring Dr. Metitieri’s outlook, Dr. Mansfield suggested, “Restricting the use of smartphones and other personal devices is one method to reduce distraction, but ultimately, children will need to learn to optimize their use of digital devices.”

Recent Dutch media reports cited government ministers’ consultations with neuropsychiatrist Theo Compernolle, MD, PhD, who compared children’s current smartphone usage patterns to addiction and suggested that such habits may hinder the development of the prefrontal cortex. However, Dr. Mansfield said, “There is no evidence to back up this claim.” Although she acknowledged the potential short-term benefits of a screen time ban in enhancing classroom concentration, she said, “One study directly tested this hypothesis and found no association between social media use and brain development, meaning that any claims of long-term effects remain purely speculative.”

The issue of children’s screen time is complex. Understanding the content and context of screen time, educating parents and teachers, and integrating digital experiences with offline activities seem to be the way forward. While governments contend with the complexities of managing this rather modern challenge, the balance between digital engagement and cognitive development remains a critical topic for continued research and thoughtful policymaking. Dr. Metitieri summed it up, “As adult members of the digital society, it is important for us to educate ourselves on how to effectively use online platforms before sharing our experiences and concerns about the online world with children and adolescents.”

A version of this article appeared on Medscape.com.

France did it 5 years ago and now, from January 1, the Dutch have followed suit, banning devices such as mobile phones and tablets in classrooms unless needed during lessons, for medical reasons, or by students with disabilities. The ban aims to limit distractions during the school day. 

We could all surely do with some device detox, but the question remains whether too much screen time has an impact on child development. Karen Mansfield, PhD, a postdoctoral researcher on adolescent well-being in the digital age at Oxford University, told this news organization, “The evidence is definitely not set in stone. There have been some recent reviews of screen time effects on children, demonstrating very mixed findings.”

The latest research, said Dr. Mansfield, is still young, lacking consistency in findings, and rife with misinterpretation.

Tiziana Metitieri, a cognitive neuropsychologist at the Meyer Hospital in Florence, Italy, echoed these sentiments, suggesting that the sheer quantity of screen time is an insufficient metric for understanding its impact on cognitive and psychological development. “There are two main reasons for this,” she explained to this news organization. “Firstly, because the current measurements of screen time rely on self-report data, which can be affected by an overestimation or underestimation of objective usage due to social desirability bias. Secondly, because digital experiences differ in terms of content, device used, context, location, and individuals involved.”
 

Are Politicians in Too Much of a Rush?

UNESCO’s most recent report on technology in education highlighted a correlation between excessive mobile phone use and reduced educational performance and emotional stability.

The OECD report “Empowering Young Children in the Digital Age,” rightly suggested there is a need to improve protection in digital environments, bridge the digital divide, and educate parents and teachers on safe digital practices.

But Dr. Mansfield said, “Currently, policy implementation is racing far ahead of the evidence, with similar suggestions to ban smartphones in schools in the United Kingdom and Canada. However, there is no available evidence on the long-term benefits of banning smartphones. Much of the research behind the OECD and UNESCO policies is observational in nature, which limits causal interpretation more than with interventions.”

While most governments are not pursuing restrictive practices, Dr. Metitieri said that “their approaches are based on their political ideology, often using moral panic as a means to rally support, showing their heartfelt commitment to defending against the invasions of digital technology ruining human civilizations.” 

Sakshi Ghai, PhD, Dr. Mansfield’s fellow postdoctoral researcher at Oxford University, reiterated Dr. Metitieri’s concerns, “Screen time as a concept has limitations, and policy guidance needs to be careful when drawing insights from such limited evidence. What do we mean by screen time? How can time spent on different activities be clearly delineated? An oversimplistic focus on screen time may overlook the nuances and complexity of digital media use.”
 

The Key Is the What and Where

Digital screens can be productive for children, such as when used for educational purposes, be it to join a class over Zoom or partake in extracurricular educational activities. However, Dr. Ghai emphasized the importance of identifying what constitutes reasonable consumption of digital media. “Screens can help disadvantaged children achieve positive educational outcomes, particularly those with learning difficulties,” said Dr. Ghai. “Using media to interact with other children can also bring positive social connections to racially diverse children or those from the LGBTQ community, which reiterates why finding the balance that allows children to reap the benefits of digital technology while safeguarding their mental, physical, and social health, is crucial.”

On the other hand, Dr. Metitieri explained that there is evidence that passive exposure to educational content does not necessarily lead to growth benefits. “The key is the relational environment in which these digital experiences occur,” she said. 

Dr. Mansfield said a lot of research describes excessive use of digital media as a form of addiction. “Some studies have attempted to validate and test ‘smartphone addiction’ scales for adolescent. Besides pathologizing an increasingly common activity, such self-report scales are highly subjective, implying serious limitations when attempting to define ‘cut offs’ or diagnostic thresholds.”

Previous efforts to determine benchmarks for screen time usage, focusing on the relationship between historical screen usage and present mental well-being, have overlooked the nature of the digital interaction and the social and technological backdrop. “Effects of screen time on children is a continuously changing, rapidly developing research field, and other contextual factors have been shown to play a greater role on mental health,” explained Dr. Mansfield.
 

Are School Bans Too Restrictive?

Implementing nationwide policies that warrant a dramatic shift in how we approach activities that have become second nature, such as using a mobile phone, is profoundly difficult, particularly as evidence is inconclusive and inconsistent. “The long-term effects of different types of digital content on children’s learning are yet to be clear, and most education-related research so far has been carried out with college students,” said Dr. Mansfield.

For concerned parents and schools, Dr. Metitieri advised against overly restrictive approaches. “Children and adolescents can find ways around restrictions at home and school, meaning that an overly restrictive approach is limited in its effectiveness,” she said. “The best way to adapt to the changes happening in education, relationships, work, and leisure is through a combination of experiences offline and digital education.”

Mirroring Dr. Metitieri’s outlook, Dr. Mansfield suggested, “Restricting the use of smartphones and other personal devices is one method to reduce distraction, but ultimately, children will need to learn to optimize their use of digital devices.”

Recent Dutch media reports cited government ministers’ consultations with neuropsychiatrist Theo Compernolle, MD, PhD, who compared children’s current smartphone usage patterns to addiction and suggested that such habits may hinder the development of the prefrontal cortex. However, Dr. Mansfield said, “There is no evidence to back up this claim.” Although she acknowledged the potential short-term benefits of a screen time ban in enhancing classroom concentration, she said, “One study directly tested this hypothesis and found no association between social media use and brain development, meaning that any claims of long-term effects remain purely speculative.”

The issue of children’s screen time is complex. Understanding the content and context of screen time, educating parents and teachers, and integrating digital experiences with offline activities seem to be the way forward. While governments contend with the complexities of managing this rather modern challenge, the balance between digital engagement and cognitive development remains a critical topic for continued research and thoughtful policymaking. Dr. Metitieri summed it up, “As adult members of the digital society, it is important for us to educate ourselves on how to effectively use online platforms before sharing our experiences and concerns about the online world with children and adolescents.”

A version of this article appeared on Medscape.com.

France did it 5 years ago and now, from January 1, the Dutch have followed suit, banning devices such as mobile phones and tablets in classrooms unless needed during lessons, for medical reasons, or by students with disabilities. The ban aims to limit distractions during the school day. 

We could all surely do with some device detox, but the question remains whether too much screen time has an impact on child development. Karen Mansfield, PhD, a postdoctoral researcher on adolescent well-being in the digital age at Oxford University, told this news organization, “The evidence is definitely not set in stone. There have been some recent reviews of screen time effects on children, demonstrating very mixed findings.”

The latest research, said Dr. Mansfield, is still young, lacking consistency in findings, and rife with misinterpretation.

Tiziana Metitieri, a cognitive neuropsychologist at the Meyer Hospital in Florence, Italy, echoed these sentiments, suggesting that the sheer quantity of screen time is an insufficient metric for understanding its impact on cognitive and psychological development. “There are two main reasons for this,” she explained to this news organization. “Firstly, because the current measurements of screen time rely on self-report data, which can be affected by an overestimation or underestimation of objective usage due to social desirability bias. Secondly, because digital experiences differ in terms of content, device used, context, location, and individuals involved.”
 

Are Politicians in Too Much of a Rush?

UNESCO’s most recent report on technology in education highlighted a correlation between excessive mobile phone use and reduced educational performance and emotional stability.

The OECD report “Empowering Young Children in the Digital Age,” rightly suggested there is a need to improve protection in digital environments, bridge the digital divide, and educate parents and teachers on safe digital practices.

But Dr. Mansfield said, “Currently, policy implementation is racing far ahead of the evidence, with similar suggestions to ban smartphones in schools in the United Kingdom and Canada. However, there is no available evidence on the long-term benefits of banning smartphones. Much of the research behind the OECD and UNESCO policies is observational in nature, which limits causal interpretation more than with interventions.”

While most governments are not pursuing restrictive practices, Dr. Metitieri said that “their approaches are based on their political ideology, often using moral panic as a means to rally support, showing their heartfelt commitment to defending against the invasions of digital technology ruining human civilizations.” 

Sakshi Ghai, PhD, Dr. Mansfield’s fellow postdoctoral researcher at Oxford University, reiterated Dr. Metitieri’s concerns, “Screen time as a concept has limitations, and policy guidance needs to be careful when drawing insights from such limited evidence. What do we mean by screen time? How can time spent on different activities be clearly delineated? An oversimplistic focus on screen time may overlook the nuances and complexity of digital media use.”
 

The Key Is the What and Where

Digital screens can be productive for children, such as when used for educational purposes, be it to join a class over Zoom or partake in extracurricular educational activities. However, Dr. Ghai emphasized the importance of identifying what constitutes reasonable consumption of digital media. “Screens can help disadvantaged children achieve positive educational outcomes, particularly those with learning difficulties,” said Dr. Ghai. “Using media to interact with other children can also bring positive social connections to racially diverse children or those from the LGBTQ community, which reiterates why finding the balance that allows children to reap the benefits of digital technology while safeguarding their mental, physical, and social health, is crucial.”

On the other hand, Dr. Metitieri explained that there is evidence that passive exposure to educational content does not necessarily lead to growth benefits. “The key is the relational environment in which these digital experiences occur,” she said. 

Dr. Mansfield said a lot of research describes excessive use of digital media as a form of addiction. “Some studies have attempted to validate and test ‘smartphone addiction’ scales for adolescent. Besides pathologizing an increasingly common activity, such self-report scales are highly subjective, implying serious limitations when attempting to define ‘cut offs’ or diagnostic thresholds.”

Previous efforts to determine benchmarks for screen time usage, focusing on the relationship between historical screen usage and present mental well-being, have overlooked the nature of the digital interaction and the social and technological backdrop. “Effects of screen time on children is a continuously changing, rapidly developing research field, and other contextual factors have been shown to play a greater role on mental health,” explained Dr. Mansfield.
 

Are School Bans Too Restrictive?

Implementing nationwide policies that warrant a dramatic shift in how we approach activities that have become second nature, such as using a mobile phone, is profoundly difficult, particularly as evidence is inconclusive and inconsistent. “The long-term effects of different types of digital content on children’s learning are yet to be clear, and most education-related research so far has been carried out with college students,” said Dr. Mansfield.

For concerned parents and schools, Dr. Metitieri advised against overly restrictive approaches. “Children and adolescents can find ways around restrictions at home and school, meaning that an overly restrictive approach is limited in its effectiveness,” she said. “The best way to adapt to the changes happening in education, relationships, work, and leisure is through a combination of experiences offline and digital education.”

Mirroring Dr. Metitieri’s outlook, Dr. Mansfield suggested, “Restricting the use of smartphones and other personal devices is one method to reduce distraction, but ultimately, children will need to learn to optimize their use of digital devices.”

Recent Dutch media reports cited government ministers’ consultations with neuropsychiatrist Theo Compernolle, MD, PhD, who compared children’s current smartphone usage patterns to addiction and suggested that such habits may hinder the development of the prefrontal cortex. However, Dr. Mansfield said, “There is no evidence to back up this claim.” Although she acknowledged the potential short-term benefits of a screen time ban in enhancing classroom concentration, she said, “One study directly tested this hypothesis and found no association between social media use and brain development, meaning that any claims of long-term effects remain purely speculative.”

The issue of children’s screen time is complex. Understanding the content and context of screen time, educating parents and teachers, and integrating digital experiences with offline activities seem to be the way forward. While governments contend with the complexities of managing this rather modern challenge, the balance between digital engagement and cognitive development remains a critical topic for continued research and thoughtful policymaking. Dr. Metitieri summed it up, “As adult members of the digital society, it is important for us to educate ourselves on how to effectively use online platforms before sharing our experiences and concerns about the online world with children and adolescents.”

A version of this article appeared on Medscape.com.

A1c level strongly predicts the risk of developing type 2 diabetes among adolescents with overweight or obesity, new data suggested.

In a large California healthcare database over a 10-year period, the incidence of type 2 diabetes was relatively low overall among adolescents with overweight and obesity. However, the risk increased with baseline A1c levels above 6.0% as well as in those with more severe obesity, women, and Asian or Pacific Islanders.

The new findings were published online in JAMA Network Open by pediatric endocrinologist Francis M. Hoe, MD, of Kaiser Permanente Roseville Medical Center, Roseville, California, and colleagues.

Previous studies have examined the incidence of type 2 diabetes among all youth, regardless of weight class. This is one of the first large population studies to examine the incidence and risk for type 2 diabetes by incremental level of A1c in a racially and ethnically diverse group of youth with overweight and obesity, Dr. Hoe told this news organization in an interview.

“This study was only possible to do because Kaiser Permanente Northern California has nearly 1 million pediatric members. The biggest thing we learned is that risk for type 2 diabetes is low in overweight and obese youth, especially those with an HbA1c less than 5.9%,” he said.
 

Zeroing in on Those at Greatest Risk for Type 2 Diabetes

Currently, the American Diabetes Association (ADA) recommends screening for type 2 diabetes in adolescents with overweight (body mass index [BMI], 85th percentile or greater) or obesity (≥ 95th) who have at least one additional risk factor, including family history of type 2 diabetes and Native American, Black, or Hispanic ethnicity. About one in four US adolescents qualify by those criteria, the authors noted in the paper.

And, as for adults, ADA recommends subsequent annual diabetes screening in youth identified as having “prediabetes,” that is, a A1c level between 5.7% and 6.5%.

The new study confirmed that adolescents with A1c in the upper end of the prediabetes range were at a greater risk for type 2 diabetes. But those individuals were the minority. Adolescents with overweight/obesity who had baseline A1c levels in the lower end of the prediabetes range, 5.7%-5.8%, accounted for two thirds of those with prediabetes in the study population and had a very low incidence of type 2 diabetes compared with those with higher A1c levels.

“Specifically, we found an annual type 2 diabetes incidence of 0.2% for HbA1c of 5.7%-5.8%, which is much lower than adults. These adolescents will likely benefit from lifestyle intervention. But because their risk of developing type 2 diabetes is lower, they probably don’t need to be screened annually, as currently recommended by the ADA,” Dr. Hoe said.

Similarly, he added, “since obesity severity was associated with a higher risk for type 2 diabetes, increases in BMI percentile should also prompt consideration of repeat diabetes screening.”
 

Large Database Allows for Detailed Findings

The study population was 74,552 adolescents aged 10-17 years with overweight or obesity, of whom 49.4% were male, 64.6% were younger than 15 years, and 73.1% had obesity. Only 21.6% were White, while 43.6% were Hispanic, 11.1% Black, and 17.6% Asian or Pacific Islander.

Nearly a quarter, 22.9%, had baseline A1c in the prediabetes range of 5.7%-6.4%. Mean A1c rose with BMI category from overweight to moderate to severe obesity (P < .001 for each comparison). Baseline A1c was highest (5.53%) in Black adolescents and lowest in White teens (5.38%), also significant differences by group (P < .001).

Of the total 698 who developed diabetes during the follow-up, 89.7% were classified as having type 2 diabetes, with a median 3.8 years from baseline to diagnosis.

The overall incidence rate of type 2 diabetes during the follow-up was 2.1 per 1000 person-years. As the baseline A1c rose from less than 5.5% to 6.0%, from 6.1% to 6.2%, and from 6.3% to 6.4%, those incidence rates were 0.8, 8.1, 21.8, and 68.9 per 1000 person-years, respectively.

In a multivariate analysis, compared to baseline A1c below 5.5%, increased risk was ninefold for A1c 5.9%-6.0%, 23-fold for 6.1%-6.2%, and 72-fold for 6.3%-6.4%.

The incidence rates were higher in female than in male adolescents (2.4 vs 1.8 per 1000 person-years) and increased by BMI category from 0.6 to 1.3 to 4.3 for those with overweight, moderate obesity, and severe obesity, respectively.

Type 2 diabetes incidence per 1000 person-years also varied by race and ethnicity, ranging from 1.3 for White adolescents to 3.0 for Asian or Pacific Islanders.

“We plan on further exploring the effect of the weight and BMI change over time and how that may affect type 2 diabetes risk,” Dr. Hoe told this news organization.

This study was supported by a grant from the Kaiser Permanente Northern California Community Health program. Dr. Hoe and his coauthors had no further disclosures.

A version of this article appeared on Medscape.com.

A1c level strongly predicts the risk of developing type 2 diabetes among adolescents with overweight or obesity, new data suggested.

In a large California healthcare database over a 10-year period, the incidence of type 2 diabetes was relatively low overall among adolescents with overweight and obesity. However, the risk increased with baseline A1c levels above 6.0% as well as in those with more severe obesity, women, and Asian or Pacific Islanders.

The new findings were published online in JAMA Network Open by pediatric endocrinologist Francis M. Hoe, MD, of Kaiser Permanente Roseville Medical Center, Roseville, California, and colleagues.

Previous studies have examined the incidence of type 2 diabetes among all youth, regardless of weight class. This is one of the first large population studies to examine the incidence and risk for type 2 diabetes by incremental level of A1c in a racially and ethnically diverse group of youth with overweight and obesity, Dr. Hoe told this news organization in an interview.

“This study was only possible to do because Kaiser Permanente Northern California has nearly 1 million pediatric members. The biggest thing we learned is that risk for type 2 diabetes is low in overweight and obese youth, especially those with an HbA1c less than 5.9%,” he said.
 

Zeroing in on Those at Greatest Risk for Type 2 Diabetes

Currently, the American Diabetes Association (ADA) recommends screening for type 2 diabetes in adolescents with overweight (body mass index [BMI], 85th percentile or greater) or obesity (≥ 95th) who have at least one additional risk factor, including family history of type 2 diabetes and Native American, Black, or Hispanic ethnicity. About one in four US adolescents qualify by those criteria, the authors noted in the paper.

And, as for adults, ADA recommends subsequent annual diabetes screening in youth identified as having “prediabetes,” that is, a A1c level between 5.7% and 6.5%.

The new study confirmed that adolescents with A1c in the upper end of the prediabetes range were at a greater risk for type 2 diabetes. But those individuals were the minority. Adolescents with overweight/obesity who had baseline A1c levels in the lower end of the prediabetes range, 5.7%-5.8%, accounted for two thirds of those with prediabetes in the study population and had a very low incidence of type 2 diabetes compared with those with higher A1c levels.

“Specifically, we found an annual type 2 diabetes incidence of 0.2% for HbA1c of 5.7%-5.8%, which is much lower than adults. These adolescents will likely benefit from lifestyle intervention. But because their risk of developing type 2 diabetes is lower, they probably don’t need to be screened annually, as currently recommended by the ADA,” Dr. Hoe said.

Similarly, he added, “since obesity severity was associated with a higher risk for type 2 diabetes, increases in BMI percentile should also prompt consideration of repeat diabetes screening.”
 

Large Database Allows for Detailed Findings

The study population was 74,552 adolescents aged 10-17 years with overweight or obesity, of whom 49.4% were male, 64.6% were younger than 15 years, and 73.1% had obesity. Only 21.6% were White, while 43.6% were Hispanic, 11.1% Black, and 17.6% Asian or Pacific Islander.

Nearly a quarter, 22.9%, had baseline A1c in the prediabetes range of 5.7%-6.4%. Mean A1c rose with BMI category from overweight to moderate to severe obesity (P < .001 for each comparison). Baseline A1c was highest (5.53%) in Black adolescents and lowest in White teens (5.38%), also significant differences by group (P < .001).

Of the total 698 who developed diabetes during the follow-up, 89.7% were classified as having type 2 diabetes, with a median 3.8 years from baseline to diagnosis.

The overall incidence rate of type 2 diabetes during the follow-up was 2.1 per 1000 person-years. As the baseline A1c rose from less than 5.5% to 6.0%, from 6.1% to 6.2%, and from 6.3% to 6.4%, those incidence rates were 0.8, 8.1, 21.8, and 68.9 per 1000 person-years, respectively.

In a multivariate analysis, compared to baseline A1c below 5.5%, increased risk was ninefold for A1c 5.9%-6.0%, 23-fold for 6.1%-6.2%, and 72-fold for 6.3%-6.4%.

The incidence rates were higher in female than in male adolescents (2.4 vs 1.8 per 1000 person-years) and increased by BMI category from 0.6 to 1.3 to 4.3 for those with overweight, moderate obesity, and severe obesity, respectively.

Type 2 diabetes incidence per 1000 person-years also varied by race and ethnicity, ranging from 1.3 for White adolescents to 3.0 for Asian or Pacific Islanders.

“We plan on further exploring the effect of the weight and BMI change over time and how that may affect type 2 diabetes risk,” Dr. Hoe told this news organization.

This study was supported by a grant from the Kaiser Permanente Northern California Community Health program. Dr. Hoe and his coauthors had no further disclosures.

A version of this article appeared on Medscape.com.

A1c level strongly predicts the risk of developing type 2 diabetes among adolescents with overweight or obesity, new data suggested.

In a large California healthcare database over a 10-year period, the incidence of type 2 diabetes was relatively low overall among adolescents with overweight and obesity. However, the risk increased with baseline A1c levels above 6.0% as well as in those with more severe obesity, women, and Asian or Pacific Islanders.

The new findings were published online in JAMA Network Open by pediatric endocrinologist Francis M. Hoe, MD, of Kaiser Permanente Roseville Medical Center, Roseville, California, and colleagues.

Previous studies have examined the incidence of type 2 diabetes among all youth, regardless of weight class. This is one of the first large population studies to examine the incidence and risk for type 2 diabetes by incremental level of A1c in a racially and ethnically diverse group of youth with overweight and obesity, Dr. Hoe told this news organization in an interview.

“This study was only possible to do because Kaiser Permanente Northern California has nearly 1 million pediatric members. The biggest thing we learned is that risk for type 2 diabetes is low in overweight and obese youth, especially those with an HbA1c less than 5.9%,” he said.
 

Zeroing in on Those at Greatest Risk for Type 2 Diabetes

Currently, the American Diabetes Association (ADA) recommends screening for type 2 diabetes in adolescents with overweight (body mass index [BMI], 85th percentile or greater) or obesity (≥ 95th) who have at least one additional risk factor, including family history of type 2 diabetes and Native American, Black, or Hispanic ethnicity. About one in four US adolescents qualify by those criteria, the authors noted in the paper.

And, as for adults, ADA recommends subsequent annual diabetes screening in youth identified as having “prediabetes,” that is, a A1c level between 5.7% and 6.5%.

The new study confirmed that adolescents with A1c in the upper end of the prediabetes range were at a greater risk for type 2 diabetes. But those individuals were the minority. Adolescents with overweight/obesity who had baseline A1c levels in the lower end of the prediabetes range, 5.7%-5.8%, accounted for two thirds of those with prediabetes in the study population and had a very low incidence of type 2 diabetes compared with those with higher A1c levels.

“Specifically, we found an annual type 2 diabetes incidence of 0.2% for HbA1c of 5.7%-5.8%, which is much lower than adults. These adolescents will likely benefit from lifestyle intervention. But because their risk of developing type 2 diabetes is lower, they probably don’t need to be screened annually, as currently recommended by the ADA,” Dr. Hoe said.

Similarly, he added, “since obesity severity was associated with a higher risk for type 2 diabetes, increases in BMI percentile should also prompt consideration of repeat diabetes screening.”
 

Large Database Allows for Detailed Findings

The study population was 74,552 adolescents aged 10-17 years with overweight or obesity, of whom 49.4% were male, 64.6% were younger than 15 years, and 73.1% had obesity. Only 21.6% were White, while 43.6% were Hispanic, 11.1% Black, and 17.6% Asian or Pacific Islander.

Nearly a quarter, 22.9%, had baseline A1c in the prediabetes range of 5.7%-6.4%. Mean A1c rose with BMI category from overweight to moderate to severe obesity (P < .001 for each comparison). Baseline A1c was highest (5.53%) in Black adolescents and lowest in White teens (5.38%), also significant differences by group (P < .001).

Of the total 698 who developed diabetes during the follow-up, 89.7% were classified as having type 2 diabetes, with a median 3.8 years from baseline to diagnosis.

The overall incidence rate of type 2 diabetes during the follow-up was 2.1 per 1000 person-years. As the baseline A1c rose from less than 5.5% to 6.0%, from 6.1% to 6.2%, and from 6.3% to 6.4%, those incidence rates were 0.8, 8.1, 21.8, and 68.9 per 1000 person-years, respectively.

In a multivariate analysis, compared to baseline A1c below 5.5%, increased risk was ninefold for A1c 5.9%-6.0%, 23-fold for 6.1%-6.2%, and 72-fold for 6.3%-6.4%.

The incidence rates were higher in female than in male adolescents (2.4 vs 1.8 per 1000 person-years) and increased by BMI category from 0.6 to 1.3 to 4.3 for those with overweight, moderate obesity, and severe obesity, respectively.

Type 2 diabetes incidence per 1000 person-years also varied by race and ethnicity, ranging from 1.3 for White adolescents to 3.0 for Asian or Pacific Islanders.

“We plan on further exploring the effect of the weight and BMI change over time and how that may affect type 2 diabetes risk,” Dr. Hoe told this news organization.

This study was supported by a grant from the Kaiser Permanente Northern California Community Health program. Dr. Hoe and his coauthors had no further disclosures.

A version of this article appeared on Medscape.com.

Investigators from the French Health and Medical Research Institute (INSERM), University of Bordeaux, and Charles Perrens Hospital, alongside their Canadian, British, and Swedish counterparts, have shown that attention-deficit/hyperactivity disorder (ADHD) or attention-deficit disorder without hyperactivity is linked with physical health problems. Cédric Galéra, MD, PhD, child and adolescent psychiatrist and epidemiologist at the Bordeaux Population Health Research Center (INSERM/University of Bordeaux) and the Charles Perrens Hospital, explained these findings to this news organization.
 

A Bilateral Association 

ADHD is a neurodevelopmental condition that develops in childhood and is characterized by high levels of inattention or agitation and impulsiveness. Some studies have revealed a link between ADHD and medical comorbidities, but these studies were carried out on small patient samples and were cross-sectional.

A new longitudinal study published in Lancet Child and Adolescent Health has shown a reciprocal link between ADHD and physical health problems. The researchers conducted statistical analyses to measure the links between ADHD symptoms and subsequent development of certain physical conditions and, conversely, between physical problems during childhood and subsequent development of ADHD symptoms.
 

Children From Quebec

The study was conducted by a team headed by Dr. Galéra in collaboration with teams from Britain, Sweden, and Canada. “We studied a Quebec-based cohort of 2000 children aged between 5 months and 17 years,” said Dr. Galéra.

“The researchers in Quebec sent interviewers to question parents at home. And once the children were able to answer for themselves, from adolescence, they were asked to answer the questions directly,” he added.

The children were assessed on the severity of their ADHD symptoms as well as their physical condition (general well-being, any conditions diagnosed, etc.).
 

Dental Caries, Excess Weight

“We were able to show links between ADHD in childhood and physical health problems in adolescence. There is a greater risk for dental caries, infections, injuries, wounds, sleep disorders, and excess weight.

“Accounting for socioeconomic status and mental health problems such as anxiety and depression or medical treatments, we observed that dental caries, wounds, excess weight, and restless legs syndrome were the conditions that cropped up time and time again,” said Dr. Galéra.

On the other hand, the researchers noted that certain physical health issues in childhood were linked with the onset of ADHD at a later stage. “We discovered that asthma in early childhood, injuries, sleep disturbances, epilepsy, and excess weight were associated with ADHD. Taking all above-referenced features into account, we were left with just wounds and injuries as well as restless legs syndrome as being linked to ADHD,” Dr. Galéra concluded.

For Dr. Galéra, the study illustrates the direction and timing of the links between physical problems and ADHD. “This reflects the link between physical and mental health. It’s important that all healthcare professionals be alert to this. Psychiatrists and mental health professionals must be vigilant about the physical health risks, and pediatricians and family physicians must be aware of the fact that children can present with physical conditions that will later be linked with ADHD. Each of them must be able to refer their young patients to their medical colleagues to ensure that these people receive the best care,” he emphasized.

The team will continue to study this cohort to see which problems emerge in adulthood. They also wish to study the Elfe cohort, a French longitudinal study of children.

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Investigators from the French Health and Medical Research Institute (INSERM), University of Bordeaux, and Charles Perrens Hospital, alongside their Canadian, British, and Swedish counterparts, have shown that attention-deficit/hyperactivity disorder (ADHD) or attention-deficit disorder without hyperactivity is linked with physical health problems. Cédric Galéra, MD, PhD, child and adolescent psychiatrist and epidemiologist at the Bordeaux Population Health Research Center (INSERM/University of Bordeaux) and the Charles Perrens Hospital, explained these findings to this news organization.
 

A Bilateral Association 

ADHD is a neurodevelopmental condition that develops in childhood and is characterized by high levels of inattention or agitation and impulsiveness. Some studies have revealed a link between ADHD and medical comorbidities, but these studies were carried out on small patient samples and were cross-sectional.

A new longitudinal study published in Lancet Child and Adolescent Health has shown a reciprocal link between ADHD and physical health problems. The researchers conducted statistical analyses to measure the links between ADHD symptoms and subsequent development of certain physical conditions and, conversely, between physical problems during childhood and subsequent development of ADHD symptoms.
 

Children From Quebec

The study was conducted by a team headed by Dr. Galéra in collaboration with teams from Britain, Sweden, and Canada. “We studied a Quebec-based cohort of 2000 children aged between 5 months and 17 years,” said Dr. Galéra.

“The researchers in Quebec sent interviewers to question parents at home. And once the children were able to answer for themselves, from adolescence, they were asked to answer the questions directly,” he added.

The children were assessed on the severity of their ADHD symptoms as well as their physical condition (general well-being, any conditions diagnosed, etc.).
 

Dental Caries, Excess Weight

“We were able to show links between ADHD in childhood and physical health problems in adolescence. There is a greater risk for dental caries, infections, injuries, wounds, sleep disorders, and excess weight.

“Accounting for socioeconomic status and mental health problems such as anxiety and depression or medical treatments, we observed that dental caries, wounds, excess weight, and restless legs syndrome were the conditions that cropped up time and time again,” said Dr. Galéra.

On the other hand, the researchers noted that certain physical health issues in childhood were linked with the onset of ADHD at a later stage. “We discovered that asthma in early childhood, injuries, sleep disturbances, epilepsy, and excess weight were associated with ADHD. Taking all above-referenced features into account, we were left with just wounds and injuries as well as restless legs syndrome as being linked to ADHD,” Dr. Galéra concluded.

For Dr. Galéra, the study illustrates the direction and timing of the links between physical problems and ADHD. “This reflects the link between physical and mental health. It’s important that all healthcare professionals be alert to this. Psychiatrists and mental health professionals must be vigilant about the physical health risks, and pediatricians and family physicians must be aware of the fact that children can present with physical conditions that will later be linked with ADHD. Each of them must be able to refer their young patients to their medical colleagues to ensure that these people receive the best care,” he emphasized.

The team will continue to study this cohort to see which problems emerge in adulthood. They also wish to study the Elfe cohort, a French longitudinal study of children.

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Investigators from the French Health and Medical Research Institute (INSERM), University of Bordeaux, and Charles Perrens Hospital, alongside their Canadian, British, and Swedish counterparts, have shown that attention-deficit/hyperactivity disorder (ADHD) or attention-deficit disorder without hyperactivity is linked with physical health problems. Cédric Galéra, MD, PhD, child and adolescent psychiatrist and epidemiologist at the Bordeaux Population Health Research Center (INSERM/University of Bordeaux) and the Charles Perrens Hospital, explained these findings to this news organization.
 

A Bilateral Association 

ADHD is a neurodevelopmental condition that develops in childhood and is characterized by high levels of inattention or agitation and impulsiveness. Some studies have revealed a link between ADHD and medical comorbidities, but these studies were carried out on small patient samples and were cross-sectional.

A new longitudinal study published in Lancet Child and Adolescent Health has shown a reciprocal link between ADHD and physical health problems. The researchers conducted statistical analyses to measure the links between ADHD symptoms and subsequent development of certain physical conditions and, conversely, between physical problems during childhood and subsequent development of ADHD symptoms.
 

Children From Quebec

The study was conducted by a team headed by Dr. Galéra in collaboration with teams from Britain, Sweden, and Canada. “We studied a Quebec-based cohort of 2000 children aged between 5 months and 17 years,” said Dr. Galéra.

“The researchers in Quebec sent interviewers to question parents at home. And once the children were able to answer for themselves, from adolescence, they were asked to answer the questions directly,” he added.

The children were assessed on the severity of their ADHD symptoms as well as their physical condition (general well-being, any conditions diagnosed, etc.).
 

Dental Caries, Excess Weight

“We were able to show links between ADHD in childhood and physical health problems in adolescence. There is a greater risk for dental caries, infections, injuries, wounds, sleep disorders, and excess weight.

“Accounting for socioeconomic status and mental health problems such as anxiety and depression or medical treatments, we observed that dental caries, wounds, excess weight, and restless legs syndrome were the conditions that cropped up time and time again,” said Dr. Galéra.

On the other hand, the researchers noted that certain physical health issues in childhood were linked with the onset of ADHD at a later stage. “We discovered that asthma in early childhood, injuries, sleep disturbances, epilepsy, and excess weight were associated with ADHD. Taking all above-referenced features into account, we were left with just wounds and injuries as well as restless legs syndrome as being linked to ADHD,” Dr. Galéra concluded.

For Dr. Galéra, the study illustrates the direction and timing of the links between physical problems and ADHD. “This reflects the link between physical and mental health. It’s important that all healthcare professionals be alert to this. Psychiatrists and mental health professionals must be vigilant about the physical health risks, and pediatricians and family physicians must be aware of the fact that children can present with physical conditions that will later be linked with ADHD. Each of them must be able to refer their young patients to their medical colleagues to ensure that these people receive the best care,” he emphasized.

The team will continue to study this cohort to see which problems emerge in adulthood. They also wish to study the Elfe cohort, a French longitudinal study of children.

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Introduction: The Many Lanes of Research on Magnesium Sulfate

The research that improves human health in the most expedient and most impactful ways is multitiered, with basic or fundamental research, translational research, interventional studies, and retrospective research often occurring simultaneously. There should be no “single lane” of research and one type of research does not preclude the other.

Too often, we fall short in one of these lanes. While we have achieved many moonshots in obstetrics and maternal-fetal medicine, we have tended not to place a high priority on basic research, which can provide a strong understanding of the biology of major diseases and conditions affecting women and their offspring. When conducted with proper commitment and funding, such research can lead to biologically directed therapy.

Within our specialty, research on how we can effectively prevent preterm birth, prematurity, and preeclampsia has taken a long road, with various types of therapies being tried, but none being overwhelmingly effective — with an ongoing need for more basic or fundamental research. Nevertheless, we can benefit and gain great insights from retrospective and interventional studies associated with clinical therapies used to treat premature labor and preeclampsia when these therapies have an unanticipated and important secondary benefit.

This month our Master Class is focused on the neuroprotection of prematurity. Magnesium sulfate is a valuable tool for the treatment of both premature labor and preeclampsia, and more recently, also for neuroprotection of the fetus. Interestingly, this use stemmed from researchers looking retrospectively at outcomes in women who received the compound for other reasons. It took many years for researchers to prove its neuroprotective value through interventional trials, while researchers simultaneously strove to understand on a basic biologic level how magnesium sulfate works to prevent outcomes such as cerebral palsy.

Basic research underway today continues to improve our understanding of its precise mechanisms of action. Combined with other tiers of research — including more interventional studies and more translational research — we can improve its utility for the neuroprotection of prematurity. Alternatively, ongoing research may lead to different, even more effective treatments.

Our guest author is Irina Burd, MD, PhD, Sylvan Freiman, MD Endowed Professor and Chair of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine.* Dr. Burd is also a physician-scientist. She recounts the important story of magnesium sulfate and what is currently known about its biologic plausibility in neuroprotection — including through her own studies – as well as what may be coming in the future.

E. Albert Reece, MD, PhD, MBA, a maternal-fetal medicine specialist, is dean emeritus of the University of Maryland School of Medicine, former university executive vice president; currently the endowed professor and director of the Center for Advanced Research Training and Innovation (CARTI), and senior scientist in the Center for Birth Defects Research. Dr. Reece reported no relevant disclosures. He is the medical editor of this column. Contact him at [email protected].
 

Magnesium Sulfate for Fetal Neuroprotection in Preterm Birth

Without a doubt, magnesium sulfate (MgSO₄) given before anticipated preterm birth reduces the risk of cerebral palsy. It is a valuable tool for fetal neuroprotection at a time when there are no proven alternatives. Yet without the persistent research that occurred over more than 20 years, it may not have won the endorsement of the American College of Obstetrics and Gynecologists in 2010 and worked its way into routine practice.

Its history is worthy of reflection. It took years of observational trials (not all of which showed neuroprotective effects), six randomized controlled trials (none of which met their primary endpoint), three meta-analyses, and a Cochrane Database Systematic Review to arrive at the conclusion that antenatal magnesium sulfate therapy given to women at risk of preterm birth has definitive neuroprotective benefit.

Origins and Biologic Plausibility

The MgSO₄ story is rooted in the late seventeenth century discovery by physician Nehemiah Grew that the compound was the key component of the then-famous medicinal spring waters in Epsom, England.¹ MgSO₄ was first used for eclampsia in 1906,² and was first reported in the American literature for eclampsia in 1925.³ In 1959, its effect as a tocolytic agent was reported.⁴

More than 30 years later, in 1995, an observational study coauthored by Karin B. Nelson, MD, and Judith K. Grether, PhD of the National Institutes of Health, showed a reduced risk of cerebral palsy in very-low-birth-weight infants (VLBW).⁵ The report marked a turning point in research interest on neuroprotection for anticipated preterm birth.

The precise molecular mechanisms of action of MgSO₄ for neuroprotection are still not well understood. However, research findings from the University of Maryland and other institutions have provided biologic plausibility for its use to prevent cerebral palsy. Our current thinking is that it involves the prevention of periventricular white matter injury and/or the prevention of oxidative stress and a neuronal injury mechanism called excitotoxicity.

Periventricular white matter injury involving injury to preoligodendrocytes before 32 weeks’ gestation is the most prevalent injury seen in cerebral palsy; preoligodendrocytes are precursors of myelinating oligodendrocytes, which constitute a major glial population in the white matter. Our research in a mouse model demonstrated that the intrauterine inflammation frequently associated with preterm birth can lead to neuronal injury as well as white matter damage, and that MgSO₄ may ameliorate both.^6,7

Excitotoxicity results from excessive stimulation of N-methyl-D-aspartate (NMDA) glutamatergic receptors on preoligodendrocytes and a rush of calcium through the voltage-gated channels. This calcium influx leads to the production of nitric oxide, oxidative stress, and subsequent mitochondrial damage and cell death. As a bivalent ion, MgSO₄ sits in the voltage-gated channels of the NMDA receptors and reduces glutamatergic signaling, thus serving as a calcium antagonist and modulating calcium influx (See Figure).

The Long Route of Research

The 1995 Nelson-Grether study compared VLBW (< 1500 g) infants who survived and developed moderate/severe cerebral palsy within 3 years to randomly selected VLBW controls with respect to whether their mothers had received MgSO₄ to prevent seizures in preeclampsia or as a tocolytic agent.⁵ In a population of more than 155,000 children born between 1983 and 1985, in utero exposure to MgSO₄ was reported in 7.1% of 42 VLBW infants with cerebral palsy and 36% of 75 VLBW controls (odds ratio [OR], 0.14; 95% CI, 0.05-0.51). In women without preeclampsia the OR increased to 0.25.

This motivating study had been preceded by several observational studies showing that infants born to women with preeclampsia who received MgSO₄ had significantly lower risks of developing intraventricular hemorrhage (IVH) and germinal matrix hemorrhage (GMH). In one of these studies, published in 1992, Karl C. Kuban, MD, and coauthors reported that “maternal receipt of magnesium sulfate was associated with diminished risk of GMH-IVH even in those babies born to mothers who apparently did not have preeclampsia.”⁹

In the several years following the 1995 Nelson-Grether study, several other case-control/observational studies were reported, with conflicting conclusions, and investigators around the world began designing and conducting needed randomized controlled trials.

The six published randomized controlled trials looking at MgSO₄ and neuroprotection varied in their inclusion and exclusion criteria, their recruitment and enrollment style, the gestational ages for MgSO₄ administration, loading and maintenance doses, how cerebral palsy or neuroprotection was assessed, and other factors (See Table for RCT characteristics and main outcomes).^10-14 One of the trials aimed primarily at evaluating the efficacy of MgSO₄ for preventing preeclampsia.

Moving Forward

The NNTs calculated in these reviews — ranging from 44 to 63 — are convincing, and are comparable with evidence-based medicine data for prevention of other common diseases.¹⁹ For instance, the NNT for a life saved when aspirin is given immediately after a heart attack is 42. Statins given for 5 years in people with known heart disease have an NNT of 83 to save one life, an NNT of 39 to prevent one nonfatal heart attack, and an NNT of 125 to prevent one stroke. For oral anticoagulants used in nonvalvular atrial fibrillation for primary stroke prevention, the NNTs to prevent one stroke, and one death, are 22 and 42, respectively.¹⁹

In its 2010 Committee Opinion on Magnesium Sulfate Before Anticipated Preterm Birth for Neuroprotection (reaffirmed in 2020), the American College of Obstetricians and Gynecologists left it to institutions to develop their own guidelines “regarding inclusion criteria, treatment regimens, concurrent tocolysis, and monitoring in accordance with one of the larger trials.”²⁰

Not surprisingly, most if not all hospitals have chosen a higher dose of MgSO₄ administered up to 31 weeks’ gestation in keeping with the protocols employed in the NICHD-sponsored BEAM trial (See Table).

The hope moving forward is to expand treatment options for neuroprotection in cases of imminent preterm birth. Researchers have been assessing the ability of melatonin to provide neuroprotection in cases of growth restriction and neonatal asphyxia. Melatonin has anti-inflammatory and antioxidant properties and is known to mediate neuronal generation and synaptic plasticity.²¹

N-acetyl-L-cysteine is another potential neuroprotective agent. It acts as an antioxidant, a precursor to glutathione, and a modulator of the glutamate system and has been studied as a neuroprotective agent in cases of maternal chorioamnionitis.²¹ Both melatonin and N-acetyl-L-cysteine are regarded as safe in pregnancy, but much more clinical study is needed to prove their neuroprotective potential when given shortly before birth or earlier.

Dr. Burd is the Sylvan Freiman, MD Endowed Professor and Chair of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. She has no conflicts of interest.  
 

References

1. Clio Med. 1984;19(1-2):1-21.

2. Medicinsk Rev. (Bergen) 1906;32:264-272.

3. Am J Obstet Gynecol. 1996;174(4):1390-1391.

4. Am J Obstet Gynecol. 1959;78(1):27-32.

5. Pediatrics. 1995;95(2):263-269.

6. Am J Obstet Gynecol. 2009;201(3):279.e1-279.e8.

7. Am J Obstet Gynecol. 2010;202(3):292.e1-292.e9.

8. Pediatr Res. 2020;87(3):463-471.

9. J Child Neurol. 1992;7(1):70-76.

10. Lancet. 1997;350:1517-1518.

11. JAMA. 2003;290:2669-2676.

12. BJOG. 2007;114(3):310-318.

13. Lancet. 2002;359(9321):1877-1890.

14. N Engl J Med. 2008;359:895-905.

15. Obstet Gynecol. 2009;113(6):1327-1333.

16. Am J Obstet Gynecol. 2009;200(6):595-609.

17. Obstet Gynecol 2009;114:354-364.

18. Cochrane Database Syst Rev. 2009 Jan 21:(1):CD004661.

19. www.thennt.com.

20. Obstet Gynecol. 2010;115:669-671.

21. Front Synaptic Neurosci. 2012;13:680899.

*This story was corrected on June 10, 2024.

Introduction: The Many Lanes of Research on Magnesium Sulfate

The research that improves human health in the most expedient and most impactful ways is multitiered, with basic or fundamental research, translational research, interventional studies, and retrospective research often occurring simultaneously. There should be no “single lane” of research and one type of research does not preclude the other.

Too often, we fall short in one of these lanes. While we have achieved many moonshots in obstetrics and maternal-fetal medicine, we have tended not to place a high priority on basic research, which can provide a strong understanding of the biology of major diseases and conditions affecting women and their offspring. When conducted with proper commitment and funding, such research can lead to biologically directed therapy.

Within our specialty, research on how we can effectively prevent preterm birth, prematurity, and preeclampsia has taken a long road, with various types of therapies being tried, but none being overwhelmingly effective — with an ongoing need for more basic or fundamental research. Nevertheless, we can benefit and gain great insights from retrospective and interventional studies associated with clinical therapies used to treat premature labor and preeclampsia when these therapies have an unanticipated and important secondary benefit.

This month our Master Class is focused on the neuroprotection of prematurity. Magnesium sulfate is a valuable tool for the treatment of both premature labor and preeclampsia, and more recently, also for neuroprotection of the fetus. Interestingly, this use stemmed from researchers looking retrospectively at outcomes in women who received the compound for other reasons. It took many years for researchers to prove its neuroprotective value through interventional trials, while researchers simultaneously strove to understand on a basic biologic level how magnesium sulfate works to prevent outcomes such as cerebral palsy.

Basic research underway today continues to improve our understanding of its precise mechanisms of action. Combined with other tiers of research — including more interventional studies and more translational research — we can improve its utility for the neuroprotection of prematurity. Alternatively, ongoing research may lead to different, even more effective treatments.

Our guest author is Irina Burd, MD, PhD, Sylvan Freiman, MD Endowed Professor and Chair of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine.* Dr. Burd is also a physician-scientist. She recounts the important story of magnesium sulfate and what is currently known about its biologic plausibility in neuroprotection — including through her own studies – as well as what may be coming in the future.

E. Albert Reece, MD, PhD, MBA, a maternal-fetal medicine specialist, is dean emeritus of the University of Maryland School of Medicine, former university executive vice president; currently the endowed professor and director of the Center for Advanced Research Training and Innovation (CARTI), and senior scientist in the Center for Birth Defects Research. Dr. Reece reported no relevant disclosures. He is the medical editor of this column. Contact him at [email protected].
 

Magnesium Sulfate for Fetal Neuroprotection in Preterm Birth

Without a doubt, magnesium sulfate (MgSO₄) given before anticipated preterm birth reduces the risk of cerebral palsy. It is a valuable tool for fetal neuroprotection at a time when there are no proven alternatives. Yet without the persistent research that occurred over more than 20 years, it may not have won the endorsement of the American College of Obstetrics and Gynecologists in 2010 and worked its way into routine practice.

Its history is worthy of reflection. It took years of observational trials (not all of which showed neuroprotective effects), six randomized controlled trials (none of which met their primary endpoint), three meta-analyses, and a Cochrane Database Systematic Review to arrive at the conclusion that antenatal magnesium sulfate therapy given to women at risk of preterm birth has definitive neuroprotective benefit.

Origins and Biologic Plausibility

The MgSO₄ story is rooted in the late seventeenth century discovery by physician Nehemiah Grew that the compound was the key component of the then-famous medicinal spring waters in Epsom, England.¹ MgSO₄ was first used for eclampsia in 1906,² and was first reported in the American literature for eclampsia in 1925.³ In 1959, its effect as a tocolytic agent was reported.⁴

More than 30 years later, in 1995, an observational study coauthored by Karin B. Nelson, MD, and Judith K. Grether, PhD of the National Institutes of Health, showed a reduced risk of cerebral palsy in very-low-birth-weight infants (VLBW).⁵ The report marked a turning point in research interest on neuroprotection for anticipated preterm birth.

The precise molecular mechanisms of action of MgSO₄ for neuroprotection are still not well understood. However, research findings from the University of Maryland and other institutions have provided biologic plausibility for its use to prevent cerebral palsy. Our current thinking is that it involves the prevention of periventricular white matter injury and/or the prevention of oxidative stress and a neuronal injury mechanism called excitotoxicity.

Periventricular white matter injury involving injury to preoligodendrocytes before 32 weeks’ gestation is the most prevalent injury seen in cerebral palsy; preoligodendrocytes are precursors of myelinating oligodendrocytes, which constitute a major glial population in the white matter. Our research in a mouse model demonstrated that the intrauterine inflammation frequently associated with preterm birth can lead to neuronal injury as well as white matter damage, and that MgSO₄ may ameliorate both.^6,7

Excitotoxicity results from excessive stimulation of N-methyl-D-aspartate (NMDA) glutamatergic receptors on preoligodendrocytes and a rush of calcium through the voltage-gated channels. This calcium influx leads to the production of nitric oxide, oxidative stress, and subsequent mitochondrial damage and cell death. As a bivalent ion, MgSO₄ sits in the voltage-gated channels of the NMDA receptors and reduces glutamatergic signaling, thus serving as a calcium antagonist and modulating calcium influx (See Figure).

The Long Route of Research

The 1995 Nelson-Grether study compared VLBW (< 1500 g) infants who survived and developed moderate/severe cerebral palsy within 3 years to randomly selected VLBW controls with respect to whether their mothers had received MgSO₄ to prevent seizures in preeclampsia or as a tocolytic agent.⁵ In a population of more than 155,000 children born between 1983 and 1985, in utero exposure to MgSO₄ was reported in 7.1% of 42 VLBW infants with cerebral palsy and 36% of 75 VLBW controls (odds ratio [OR], 0.14; 95% CI, 0.05-0.51). In women without preeclampsia the OR increased to 0.25.

This motivating study had been preceded by several observational studies showing that infants born to women with preeclampsia who received MgSO₄ had significantly lower risks of developing intraventricular hemorrhage (IVH) and germinal matrix hemorrhage (GMH). In one of these studies, published in 1992, Karl C. Kuban, MD, and coauthors reported that “maternal receipt of magnesium sulfate was associated with diminished risk of GMH-IVH even in those babies born to mothers who apparently did not have preeclampsia.”⁹

In the several years following the 1995 Nelson-Grether study, several other case-control/observational studies were reported, with conflicting conclusions, and investigators around the world began designing and conducting needed randomized controlled trials.

The six published randomized controlled trials looking at MgSO₄ and neuroprotection varied in their inclusion and exclusion criteria, their recruitment and enrollment style, the gestational ages for MgSO₄ administration, loading and maintenance doses, how cerebral palsy or neuroprotection was assessed, and other factors (See Table for RCT characteristics and main outcomes).^10-14 One of the trials aimed primarily at evaluating the efficacy of MgSO₄ for preventing preeclampsia.

Moving Forward

The NNTs calculated in these reviews — ranging from 44 to 63 — are convincing, and are comparable with evidence-based medicine data for prevention of other common diseases.¹⁹ For instance, the NNT for a life saved when aspirin is given immediately after a heart attack is 42. Statins given for 5 years in people with known heart disease have an NNT of 83 to save one life, an NNT of 39 to prevent one nonfatal heart attack, and an NNT of 125 to prevent one stroke. For oral anticoagulants used in nonvalvular atrial fibrillation for primary stroke prevention, the NNTs to prevent one stroke, and one death, are 22 and 42, respectively.¹⁹

In its 2010 Committee Opinion on Magnesium Sulfate Before Anticipated Preterm Birth for Neuroprotection (reaffirmed in 2020), the American College of Obstetricians and Gynecologists left it to institutions to develop their own guidelines “regarding inclusion criteria, treatment regimens, concurrent tocolysis, and monitoring in accordance with one of the larger trials.”²⁰

Not surprisingly, most if not all hospitals have chosen a higher dose of MgSO₄ administered up to 31 weeks’ gestation in keeping with the protocols employed in the NICHD-sponsored BEAM trial (See Table).

The hope moving forward is to expand treatment options for neuroprotection in cases of imminent preterm birth. Researchers have been assessing the ability of melatonin to provide neuroprotection in cases of growth restriction and neonatal asphyxia. Melatonin has anti-inflammatory and antioxidant properties and is known to mediate neuronal generation and synaptic plasticity.²¹

N-acetyl-L-cysteine is another potential neuroprotective agent. It acts as an antioxidant, a precursor to glutathione, and a modulator of the glutamate system and has been studied as a neuroprotective agent in cases of maternal chorioamnionitis.²¹ Both melatonin and N-acetyl-L-cysteine are regarded as safe in pregnancy, but much more clinical study is needed to prove their neuroprotective potential when given shortly before birth or earlier.

Dr. Burd is the Sylvan Freiman, MD Endowed Professor and Chair of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. She has no conflicts of interest.  
 

References

1. Clio Med. 1984;19(1-2):1-21.

2. Medicinsk Rev. (Bergen) 1906;32:264-272.

3. Am J Obstet Gynecol. 1996;174(4):1390-1391.

4. Am J Obstet Gynecol. 1959;78(1):27-32.

5. Pediatrics. 1995;95(2):263-269.

6. Am J Obstet Gynecol. 2009;201(3):279.e1-279.e8.

7. Am J Obstet Gynecol. 2010;202(3):292.e1-292.e9.

8. Pediatr Res. 2020;87(3):463-471.

9. J Child Neurol. 1992;7(1):70-76.

10. Lancet. 1997;350:1517-1518.

11. JAMA. 2003;290:2669-2676.

12. BJOG. 2007;114(3):310-318.

13. Lancet. 2002;359(9321):1877-1890.

14. N Engl J Med. 2008;359:895-905.

15. Obstet Gynecol. 2009;113(6):1327-1333.

16. Am J Obstet Gynecol. 2009;200(6):595-609.

17. Obstet Gynecol 2009;114:354-364.

18. Cochrane Database Syst Rev. 2009 Jan 21:(1):CD004661.

19. www.thennt.com.

20. Obstet Gynecol. 2010;115:669-671.

21. Front Synaptic Neurosci. 2012;13:680899.

*This story was corrected on June 10, 2024.

Introduction: The Many Lanes of Research on Magnesium Sulfate

The research that improves human health in the most expedient and most impactful ways is multitiered, with basic or fundamental research, translational research, interventional studies, and retrospective research often occurring simultaneously. There should be no “single lane” of research and one type of research does not preclude the other.

Too often, we fall short in one of these lanes. While we have achieved many moonshots in obstetrics and maternal-fetal medicine, we have tended not to place a high priority on basic research, which can provide a strong understanding of the biology of major diseases and conditions affecting women and their offspring. When conducted with proper commitment and funding, such research can lead to biologically directed therapy.

Within our specialty, research on how we can effectively prevent preterm birth, prematurity, and preeclampsia has taken a long road, with various types of therapies being tried, but none being overwhelmingly effective — with an ongoing need for more basic or fundamental research. Nevertheless, we can benefit and gain great insights from retrospective and interventional studies associated with clinical therapies used to treat premature labor and preeclampsia when these therapies have an unanticipated and important secondary benefit.

This month our Master Class is focused on the neuroprotection of prematurity. Magnesium sulfate is a valuable tool for the treatment of both premature labor and preeclampsia, and more recently, also for neuroprotection of the fetus. Interestingly, this use stemmed from researchers looking retrospectively at outcomes in women who received the compound for other reasons. It took many years for researchers to prove its neuroprotective value through interventional trials, while researchers simultaneously strove to understand on a basic biologic level how magnesium sulfate works to prevent outcomes such as cerebral palsy.

Basic research underway today continues to improve our understanding of its precise mechanisms of action. Combined with other tiers of research — including more interventional studies and more translational research — we can improve its utility for the neuroprotection of prematurity. Alternatively, ongoing research may lead to different, even more effective treatments.

Our guest author is Irina Burd, MD, PhD, Sylvan Freiman, MD Endowed Professor and Chair of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine.* Dr. Burd is also a physician-scientist. She recounts the important story of magnesium sulfate and what is currently known about its biologic plausibility in neuroprotection — including through her own studies – as well as what may be coming in the future.

E. Albert Reece, MD, PhD, MBA, a maternal-fetal medicine specialist, is dean emeritus of the University of Maryland School of Medicine, former university executive vice president; currently the endowed professor and director of the Center for Advanced Research Training and Innovation (CARTI), and senior scientist in the Center for Birth Defects Research. Dr. Reece reported no relevant disclosures. He is the medical editor of this column. Contact him at [email protected].
 

Magnesium Sulfate for Fetal Neuroprotection in Preterm Birth

Without a doubt, magnesium sulfate (MgSO₄) given before anticipated preterm birth reduces the risk of cerebral palsy. It is a valuable tool for fetal neuroprotection at a time when there are no proven alternatives. Yet without the persistent research that occurred over more than 20 years, it may not have won the endorsement of the American College of Obstetrics and Gynecologists in 2010 and worked its way into routine practice.

Its history is worthy of reflection. It took years of observational trials (not all of which showed neuroprotective effects), six randomized controlled trials (none of which met their primary endpoint), three meta-analyses, and a Cochrane Database Systematic Review to arrive at the conclusion that antenatal magnesium sulfate therapy given to women at risk of preterm birth has definitive neuroprotective benefit.

Origins and Biologic Plausibility

The MgSO₄ story is rooted in the late seventeenth century discovery by physician Nehemiah Grew that the compound was the key component of the then-famous medicinal spring waters in Epsom, England.¹ MgSO₄ was first used for eclampsia in 1906,² and was first reported in the American literature for eclampsia in 1925.³ In 1959, its effect as a tocolytic agent was reported.⁴

More than 30 years later, in 1995, an observational study coauthored by Karin B. Nelson, MD, and Judith K. Grether, PhD of the National Institutes of Health, showed a reduced risk of cerebral palsy in very-low-birth-weight infants (VLBW).⁵ The report marked a turning point in research interest on neuroprotection for anticipated preterm birth.

The precise molecular mechanisms of action of MgSO₄ for neuroprotection are still not well understood. However, research findings from the University of Maryland and other institutions have provided biologic plausibility for its use to prevent cerebral palsy. Our current thinking is that it involves the prevention of periventricular white matter injury and/or the prevention of oxidative stress and a neuronal injury mechanism called excitotoxicity.

Periventricular white matter injury involving injury to preoligodendrocytes before 32 weeks’ gestation is the most prevalent injury seen in cerebral palsy; preoligodendrocytes are precursors of myelinating oligodendrocytes, which constitute a major glial population in the white matter. Our research in a mouse model demonstrated that the intrauterine inflammation frequently associated with preterm birth can lead to neuronal injury as well as white matter damage, and that MgSO₄ may ameliorate both.^6,7

Excitotoxicity results from excessive stimulation of N-methyl-D-aspartate (NMDA) glutamatergic receptors on preoligodendrocytes and a rush of calcium through the voltage-gated channels. This calcium influx leads to the production of nitric oxide, oxidative stress, and subsequent mitochondrial damage and cell death. As a bivalent ion, MgSO₄ sits in the voltage-gated channels of the NMDA receptors and reduces glutamatergic signaling, thus serving as a calcium antagonist and modulating calcium influx (See Figure).

The Long Route of Research

The 1995 Nelson-Grether study compared VLBW (< 1500 g) infants who survived and developed moderate/severe cerebral palsy within 3 years to randomly selected VLBW controls with respect to whether their mothers had received MgSO₄ to prevent seizures in preeclampsia or as a tocolytic agent.⁵ In a population of more than 155,000 children born between 1983 and 1985, in utero exposure to MgSO₄ was reported in 7.1% of 42 VLBW infants with cerebral palsy and 36% of 75 VLBW controls (odds ratio [OR], 0.14; 95% CI, 0.05-0.51). In women without preeclampsia the OR increased to 0.25.

This motivating study had been preceded by several observational studies showing that infants born to women with preeclampsia who received MgSO₄ had significantly lower risks of developing intraventricular hemorrhage (IVH) and germinal matrix hemorrhage (GMH). In one of these studies, published in 1992, Karl C. Kuban, MD, and coauthors reported that “maternal receipt of magnesium sulfate was associated with diminished risk of GMH-IVH even in those babies born to mothers who apparently did not have preeclampsia.”⁹

In the several years following the 1995 Nelson-Grether study, several other case-control/observational studies were reported, with conflicting conclusions, and investigators around the world began designing and conducting needed randomized controlled trials.

The six published randomized controlled trials looking at MgSO₄ and neuroprotection varied in their inclusion and exclusion criteria, their recruitment and enrollment style, the gestational ages for MgSO₄ administration, loading and maintenance doses, how cerebral palsy or neuroprotection was assessed, and other factors (See Table for RCT characteristics and main outcomes).^10-14 One of the trials aimed primarily at evaluating the efficacy of MgSO₄ for preventing preeclampsia.

Moving Forward

The NNTs calculated in these reviews — ranging from 44 to 63 — are convincing, and are comparable with evidence-based medicine data for prevention of other common diseases.¹⁹ For instance, the NNT for a life saved when aspirin is given immediately after a heart attack is 42. Statins given for 5 years in people with known heart disease have an NNT of 83 to save one life, an NNT of 39 to prevent one nonfatal heart attack, and an NNT of 125 to prevent one stroke. For oral anticoagulants used in nonvalvular atrial fibrillation for primary stroke prevention, the NNTs to prevent one stroke, and one death, are 22 and 42, respectively.¹⁹

In its 2010 Committee Opinion on Magnesium Sulfate Before Anticipated Preterm Birth for Neuroprotection (reaffirmed in 2020), the American College of Obstetricians and Gynecologists left it to institutions to develop their own guidelines “regarding inclusion criteria, treatment regimens, concurrent tocolysis, and monitoring in accordance with one of the larger trials.”²⁰

Not surprisingly, most if not all hospitals have chosen a higher dose of MgSO₄ administered up to 31 weeks’ gestation in keeping with the protocols employed in the NICHD-sponsored BEAM trial (See Table).

The hope moving forward is to expand treatment options for neuroprotection in cases of imminent preterm birth. Researchers have been assessing the ability of melatonin to provide neuroprotection in cases of growth restriction and neonatal asphyxia. Melatonin has anti-inflammatory and antioxidant properties and is known to mediate neuronal generation and synaptic plasticity.²¹

N-acetyl-L-cysteine is another potential neuroprotective agent. It acts as an antioxidant, a precursor to glutathione, and a modulator of the glutamate system and has been studied as a neuroprotective agent in cases of maternal chorioamnionitis.²¹ Both melatonin and N-acetyl-L-cysteine are regarded as safe in pregnancy, but much more clinical study is needed to prove their neuroprotective potential when given shortly before birth or earlier.

Dr. Burd is the Sylvan Freiman, MD Endowed Professor and Chair of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. She has no conflicts of interest.  
 

References

1. Clio Med. 1984;19(1-2):1-21.

2. Medicinsk Rev. (Bergen) 1906;32:264-272.

3. Am J Obstet Gynecol. 1996;174(4):1390-1391.

4. Am J Obstet Gynecol. 1959;78(1):27-32.

5. Pediatrics. 1995;95(2):263-269.

6. Am J Obstet Gynecol. 2009;201(3):279.e1-279.e8.

7. Am J Obstet Gynecol. 2010;202(3):292.e1-292.e9.

8. Pediatr Res. 2020;87(3):463-471.

9. J Child Neurol. 1992;7(1):70-76.

10. Lancet. 1997;350:1517-1518.

11. JAMA. 2003;290:2669-2676.

12. BJOG. 2007;114(3):310-318.

13. Lancet. 2002;359(9321):1877-1890.

14. N Engl J Med. 2008;359:895-905.

15. Obstet Gynecol. 2009;113(6):1327-1333.

16. Am J Obstet Gynecol. 2009;200(6):595-609.

17. Obstet Gynecol 2009;114:354-364.

18. Cochrane Database Syst Rev. 2009 Jan 21:(1):CD004661.

19. www.thennt.com.

20. Obstet Gynecol. 2010;115:669-671.

21. Front Synaptic Neurosci. 2012;13:680899.

*This story was corrected on June 10, 2024.