Pediatrics

Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.

Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).

Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.

In addition to screening, timely diagnosis, effective treatment, and follow-up are important.

Tests don’t always tell the full story with congenital hypothyroidism.

“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.

They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.

Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.

Following are highlights of the guidance:
 

Clinical signs

Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.

Newborn screening in first days

Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.

Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.

The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.

That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.

“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.

If a newborn infant is transferred to another hospital, communication about the screening is critical.
 

Testing strategies

Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.

“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.

Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
 

Multiple births, same-sex twins

The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.

“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
 

Down syndrome

Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.

Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).

“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
 

Communication with primary care provider

Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.

Serum confirmation after abnormal screening

The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.

For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
 

Interpreting serum confirmation

Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.

But there are various other outcomes with more controversy.

Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.

In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.

“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.

Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.

“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
 

Imaging

Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.

Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.

“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.

Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
 

Treatment

Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.

L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.

An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.

“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.

The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.

Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.

“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
 

Monitoring

In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.

In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
 

Developmental outcomes

When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.

In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.

“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”

If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.

The authors report no relevant financial relationships.

Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.

Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).

Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.

In addition to screening, timely diagnosis, effective treatment, and follow-up are important.

Tests don’t always tell the full story with congenital hypothyroidism.

“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.

They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.

Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.

Following are highlights of the guidance:
 

Clinical signs

Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.

Newborn screening in first days

Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.

Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.

The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.

That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.

“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.

If a newborn infant is transferred to another hospital, communication about the screening is critical.
 

Testing strategies

Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.

“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.

Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
 

Multiple births, same-sex twins

The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.

“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
 

Down syndrome

Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.

Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).

“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
 

Communication with primary care provider

Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.

Serum confirmation after abnormal screening

The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.

For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
 

Interpreting serum confirmation

Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.

But there are various other outcomes with more controversy.

Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.

In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.

“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.

Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.

“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
 

Imaging

Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.

Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.

“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.

Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
 

Treatment

Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.

L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.

An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.

“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.

The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.

Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.

“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
 

Monitoring

In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.

In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
 

Developmental outcomes

When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.

In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.

“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”

If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.

The authors report no relevant financial relationships.

Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.

Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).

Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.

In addition to screening, timely diagnosis, effective treatment, and follow-up are important.

Tests don’t always tell the full story with congenital hypothyroidism.

“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.

They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.

Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.

Following are highlights of the guidance:
 

Clinical signs

Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.

Newborn screening in first days

Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.

Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.

The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.

That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.

“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.

If a newborn infant is transferred to another hospital, communication about the screening is critical.
 

Testing strategies

Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.

“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.

Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
 

Multiple births, same-sex twins

The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.

“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
 

Down syndrome

Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.

Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).

“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
 

Communication with primary care provider

Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.

Serum confirmation after abnormal screening

The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.

For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
 

Interpreting serum confirmation

Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.

But there are various other outcomes with more controversy.

Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.

In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.

“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.

Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.

“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
 

Imaging

Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.

Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.

“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.

Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
 

Treatment

Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.

L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.

An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.

“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.

The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.

Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.

“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
 

Monitoring

In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.

In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
 

Developmental outcomes

When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.

In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.

“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”

If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.

The authors report no relevant financial relationships.

The U.S. Centers for Disease Control and Prevention has issued extended growth charts to help doctors and researchers better understand patterns of development for the most overweight children and adolescents.

In 2017-2018, more than 4.5 million U.S. youth met the criteria for severe obesity – defined as 120% of the 95th percentile, or 35 kg/m² or greater – according to the CDC.

The new growth charts will not replace the current charts but extend beyond the 97th percentile for body mass index. Formerly, data were extrapolated for anything over the 95th percentile based on evidence from 1963 to 1980, when obesity rates were lower.

The extended growth charts are based on data collected between 1988 and 2015 from young children and adolescents with obesity.

Experts said the expanded charts will allow researchers and clinicians to track the effects of interventions for obesity whether they involve an increase in physical activity, a decrease in consumption, or other interventions. The corresponding z-score charts also are provided.

Physicians should still use the CDC’s BMI-for-age growth charts from 2000 for pediatric patients with BMIs under the 95th percentile. The agency said it does not intend to update those charts.

The definitions of overweight, obesity, and severe obesity remain unchanged.
 

The U.S. Centers for Disease Control and Prevention has issued extended growth charts to help doctors and researchers better understand patterns of development for the most overweight children and adolescents.

In 2017-2018, more than 4.5 million U.S. youth met the criteria for severe obesity – defined as 120% of the 95th percentile, or 35 kg/m² or greater – according to the CDC.

The new growth charts will not replace the current charts but extend beyond the 97th percentile for body mass index. Formerly, data were extrapolated for anything over the 95th percentile based on evidence from 1963 to 1980, when obesity rates were lower.

The extended growth charts are based on data collected between 1988 and 2015 from young children and adolescents with obesity.

Experts said the expanded charts will allow researchers and clinicians to track the effects of interventions for obesity whether they involve an increase in physical activity, a decrease in consumption, or other interventions. The corresponding z-score charts also are provided.

Physicians should still use the CDC’s BMI-for-age growth charts from 2000 for pediatric patients with BMIs under the 95th percentile. The agency said it does not intend to update those charts.

The definitions of overweight, obesity, and severe obesity remain unchanged.
 

The U.S. Centers for Disease Control and Prevention has issued extended growth charts to help doctors and researchers better understand patterns of development for the most overweight children and adolescents.

In 2017-2018, more than 4.5 million U.S. youth met the criteria for severe obesity – defined as 120% of the 95th percentile, or 35 kg/m² or greater – according to the CDC.

The new growth charts will not replace the current charts but extend beyond the 97th percentile for body mass index. Formerly, data were extrapolated for anything over the 95th percentile based on evidence from 1963 to 1980, when obesity rates were lower.

The extended growth charts are based on data collected between 1988 and 2015 from young children and adolescents with obesity.

Experts said the expanded charts will allow researchers and clinicians to track the effects of interventions for obesity whether they involve an increase in physical activity, a decrease in consumption, or other interventions. The corresponding z-score charts also are provided.

Physicians should still use the CDC’s BMI-for-age growth charts from 2000 for pediatric patients with BMIs under the 95th percentile. The agency said it does not intend to update those charts.

The definitions of overweight, obesity, and severe obesity remain unchanged.
 

Several adverse infant outcomes were significantly more likely for infants whose mothers had diagnoses of sleep apnea or insomnia, based on data from approximately 5,000 infants.

Sleep disturbance is common during pregnancy, and “sleep disorders during pregnancy can have significant consequences for both the pregnant person and their infant,” write Jennifer N. Felder, PhD, of the University of California, San Francisco, and colleagues.

However, data on the impact of maternal insomnia on specific infant outcomes are limited, they said.

In a study published recently in the journal Sleep Health, the researchers reviewed data from 3,371 pregnant women diagnosed with sleep apnea and 3,213 with insomnia. Of these, 2,357 and 2,212 were matched with controls in a propensity-score analysis. The referent controls were matched for maternal characteristics, obstetric factors, and infant factors among individuals without a sleep disorder. All were singleton pregnancies.

Adverse infant outcomes included the following:

• One- and 5-minute Apgar scores less than 7.
• Respiratory distress syndrome.
• Neonatal intensive care unit admission.
• Hypoglycemia.
• Infant death.
• Hospital stay of longer than 2 days for vaginal delivery or longer than 4 days for cesarean delivery.
• Emergency department visit before 3 months of age.
• Emergency department visit in the first year of life.
• Composite measure of adverse infant outcomes.

Compared with matched controls, the infants born to mothers with sleep apnea had a significantly increased risk for any adverse outcome (50.1% vs. 53.5%) and of the specific outcomes of low 1-minute Apgar scores (6.3% vs. 9.6%), neonatal ICU stays (6.3% vs. 8.4%), and an emergency department visit in the first year of life (33.6% vs. 36.9%).

For infants born to mothers with insomnia, the only significant difference in outcomes compared with controls was an increased likelihood of an emergency department visit (37.2% vs. 32.3%).

“Research on possible mechanisms of the relation between maternal prenatal sleep apnea and poorer birth and infant outcomes associations is small but growing, implicating systemic inflammation and late or prolonged fetal heart rate decelerations,” the researchers write in their discussion.

Research on insomnia during pregnancy and adverse infant outcomes is limited, and the largest studies have been complicated by the effects of insomnia medication; therefore, “our finding that infants born to mothers with an insomnia diagnosis were at increased risk of only emergency room visit, but no other analyzed infant outcomes, is important and novel,” they note.

The findings were limited by several factors, including the reliance on medical records, which may lack details on how routinely health care professionals assessed sleep disorders, the researchers noted. “Consequently, the findings presented here may reflect more severe cases of insomnia and sleep apnea, and may not represent the population of individuals with diagnosed sleep apnea or insomnia during pregnancy generally,” the authors say. Other limitations included a lack of information on treatment of sleep disorders and on the timing of diagnosis (before pregnancy or during pregnancy).

However, the results were strengthened by the large, population-based sample and use of codes to highlight research questions, the researchers said.

In light of the health consequences of sleep disorders in pregnancy, the data suggest that sleep apnea and insomnia in pregnant women may serve as targets for risk assessment of adverse infant outcomes, and more research is needed to determine whether addressing sleep issues reduces these outcomes, they concluded.

The study was supported by the University of California, San Francisco, Preterm Birth Initiative and by grants to lead author Dr. Felder from the National Center for Complementary and Integrative Health and to a coauthor from the National Heart, Lung, and Blood Institute. The researchers reported no relevant financial relationships.

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

Several adverse infant outcomes were significantly more likely for infants whose mothers had diagnoses of sleep apnea or insomnia, based on data from approximately 5,000 infants.

Sleep disturbance is common during pregnancy, and “sleep disorders during pregnancy can have significant consequences for both the pregnant person and their infant,” write Jennifer N. Felder, PhD, of the University of California, San Francisco, and colleagues.

However, data on the impact of maternal insomnia on specific infant outcomes are limited, they said.

In a study published recently in the journal Sleep Health, the researchers reviewed data from 3,371 pregnant women diagnosed with sleep apnea and 3,213 with insomnia. Of these, 2,357 and 2,212 were matched with controls in a propensity-score analysis. The referent controls were matched for maternal characteristics, obstetric factors, and infant factors among individuals without a sleep disorder. All were singleton pregnancies.

Adverse infant outcomes included the following:

• One- and 5-minute Apgar scores less than 7.
• Respiratory distress syndrome.
• Neonatal intensive care unit admission.
• Hypoglycemia.
• Infant death.
• Hospital stay of longer than 2 days for vaginal delivery or longer than 4 days for cesarean delivery.
• Emergency department visit before 3 months of age.
• Emergency department visit in the first year of life.
• Composite measure of adverse infant outcomes.

Compared with matched controls, the infants born to mothers with sleep apnea had a significantly increased risk for any adverse outcome (50.1% vs. 53.5%) and of the specific outcomes of low 1-minute Apgar scores (6.3% vs. 9.6%), neonatal ICU stays (6.3% vs. 8.4%), and an emergency department visit in the first year of life (33.6% vs. 36.9%).

For infants born to mothers with insomnia, the only significant difference in outcomes compared with controls was an increased likelihood of an emergency department visit (37.2% vs. 32.3%).

“Research on possible mechanisms of the relation between maternal prenatal sleep apnea and poorer birth and infant outcomes associations is small but growing, implicating systemic inflammation and late or prolonged fetal heart rate decelerations,” the researchers write in their discussion.

Research on insomnia during pregnancy and adverse infant outcomes is limited, and the largest studies have been complicated by the effects of insomnia medication; therefore, “our finding that infants born to mothers with an insomnia diagnosis were at increased risk of only emergency room visit, but no other analyzed infant outcomes, is important and novel,” they note.

The findings were limited by several factors, including the reliance on medical records, which may lack details on how routinely health care professionals assessed sleep disorders, the researchers noted. “Consequently, the findings presented here may reflect more severe cases of insomnia and sleep apnea, and may not represent the population of individuals with diagnosed sleep apnea or insomnia during pregnancy generally,” the authors say. Other limitations included a lack of information on treatment of sleep disorders and on the timing of diagnosis (before pregnancy or during pregnancy).

However, the results were strengthened by the large, population-based sample and use of codes to highlight research questions, the researchers said.

In light of the health consequences of sleep disorders in pregnancy, the data suggest that sleep apnea and insomnia in pregnant women may serve as targets for risk assessment of adverse infant outcomes, and more research is needed to determine whether addressing sleep issues reduces these outcomes, they concluded.

The study was supported by the University of California, San Francisco, Preterm Birth Initiative and by grants to lead author Dr. Felder from the National Center for Complementary and Integrative Health and to a coauthor from the National Heart, Lung, and Blood Institute. The researchers reported no relevant financial relationships.

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

Several adverse infant outcomes were significantly more likely for infants whose mothers had diagnoses of sleep apnea or insomnia, based on data from approximately 5,000 infants.

Sleep disturbance is common during pregnancy, and “sleep disorders during pregnancy can have significant consequences for both the pregnant person and their infant,” write Jennifer N. Felder, PhD, of the University of California, San Francisco, and colleagues.

However, data on the impact of maternal insomnia on specific infant outcomes are limited, they said.

In a study published recently in the journal Sleep Health, the researchers reviewed data from 3,371 pregnant women diagnosed with sleep apnea and 3,213 with insomnia. Of these, 2,357 and 2,212 were matched with controls in a propensity-score analysis. The referent controls were matched for maternal characteristics, obstetric factors, and infant factors among individuals without a sleep disorder. All were singleton pregnancies.

Adverse infant outcomes included the following:

• One- and 5-minute Apgar scores less than 7.
• Respiratory distress syndrome.
• Neonatal intensive care unit admission.
• Hypoglycemia.
• Infant death.
• Hospital stay of longer than 2 days for vaginal delivery or longer than 4 days for cesarean delivery.
• Emergency department visit before 3 months of age.
• Emergency department visit in the first year of life.
• Composite measure of adverse infant outcomes.

Compared with matched controls, the infants born to mothers with sleep apnea had a significantly increased risk for any adverse outcome (50.1% vs. 53.5%) and of the specific outcomes of low 1-minute Apgar scores (6.3% vs. 9.6%), neonatal ICU stays (6.3% vs. 8.4%), and an emergency department visit in the first year of life (33.6% vs. 36.9%).

For infants born to mothers with insomnia, the only significant difference in outcomes compared with controls was an increased likelihood of an emergency department visit (37.2% vs. 32.3%).

“Research on possible mechanisms of the relation between maternal prenatal sleep apnea and poorer birth and infant outcomes associations is small but growing, implicating systemic inflammation and late or prolonged fetal heart rate decelerations,” the researchers write in their discussion.

Research on insomnia during pregnancy and adverse infant outcomes is limited, and the largest studies have been complicated by the effects of insomnia medication; therefore, “our finding that infants born to mothers with an insomnia diagnosis were at increased risk of only emergency room visit, but no other analyzed infant outcomes, is important and novel,” they note.

The findings were limited by several factors, including the reliance on medical records, which may lack details on how routinely health care professionals assessed sleep disorders, the researchers noted. “Consequently, the findings presented here may reflect more severe cases of insomnia and sleep apnea, and may not represent the population of individuals with diagnosed sleep apnea or insomnia during pregnancy generally,” the authors say. Other limitations included a lack of information on treatment of sleep disorders and on the timing of diagnosis (before pregnancy or during pregnancy).

However, the results were strengthened by the large, population-based sample and use of codes to highlight research questions, the researchers said.

In light of the health consequences of sleep disorders in pregnancy, the data suggest that sleep apnea and insomnia in pregnant women may serve as targets for risk assessment of adverse infant outcomes, and more research is needed to determine whether addressing sleep issues reduces these outcomes, they concluded.

The study was supported by the University of California, San Francisco, Preterm Birth Initiative and by grants to lead author Dr. Felder from the National Center for Complementary and Integrative Health and to a coauthor from the National Heart, Lung, and Blood Institute. The researchers reported no relevant financial relationships.

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

Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.

“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”

Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.

“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”

Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.

“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”

NEW ORLEANS – Researchers are calling for a revision of neonatal guidelines in light of new study results from Canada showing that most extremely premature infants fed with formula failed to absorb enough iron.

“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.

courtesy of ASH

According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.

“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”

For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.

The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”

Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.

The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.

“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.

As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.

In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.

Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.

Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.

 


 

NEW ORLEANS – Researchers are calling for a revision of neonatal guidelines in light of new study results from Canada showing that most extremely premature infants fed with formula failed to absorb enough iron.

“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.

courtesy of ASH

According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.

“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”

For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.

The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”

Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.

The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.

“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.

As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.

In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.

Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.

Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.

 


 

NEW ORLEANS – Researchers are calling for a revision of neonatal guidelines in light of new study results from Canada showing that most extremely premature infants fed with formula failed to absorb enough iron.

“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.

courtesy of ASH

According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.

“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”

For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.

The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”

Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.

The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.

“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.

As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.

In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.

Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.

Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.

 


 

A biosimilar drug to the tumor necrosis factor inhibitor adalimumab, marketed as Idacio (adalimumab-aacf), has been approved by the Food and Drug Administration for use in the United States, according to a press release from manufacturer Fresenius Kabi.

Idacio is a citrate-free, low-concentration formulation of adalimumab and is now approved for use for all but three of the indications that currently apply to the reference adalimumab product (Humira): rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis in adults, ankylosing spondylitis, Crohn’s disease in adults and children aged 6 years or older, ulcerative colitis in adults, and plaque psoriasis in adults. It does not apply to Humira’s indications for hidradenitis suppurativa, uveitis, or ulcerative colitis in pediatric patients aged 5 years and older.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Idacio is the eighth adalimumab biosimilar to be approved in the United States. Its approval was based on evidence of a similar profile of pharmacokinetics, safety, efficacy, and immunogenicity to Humira.

Idacio was first launched in 2019 and has been marketed in more than 37 countries worldwide, according to Fresenius Kabi. The U.S. launch is scheduled for July, and Idacio will be available as a self-administered prefilled syringe or prefilled pen.

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

A biosimilar drug to the tumor necrosis factor inhibitor adalimumab, marketed as Idacio (adalimumab-aacf), has been approved by the Food and Drug Administration for use in the United States, according to a press release from manufacturer Fresenius Kabi.

Idacio is a citrate-free, low-concentration formulation of adalimumab and is now approved for use for all but three of the indications that currently apply to the reference adalimumab product (Humira): rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis in adults, ankylosing spondylitis, Crohn’s disease in adults and children aged 6 years or older, ulcerative colitis in adults, and plaque psoriasis in adults. It does not apply to Humira’s indications for hidradenitis suppurativa, uveitis, or ulcerative colitis in pediatric patients aged 5 years and older.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Idacio is the eighth adalimumab biosimilar to be approved in the United States. Its approval was based on evidence of a similar profile of pharmacokinetics, safety, efficacy, and immunogenicity to Humira.

Idacio was first launched in 2019 and has been marketed in more than 37 countries worldwide, according to Fresenius Kabi. The U.S. launch is scheduled for July, and Idacio will be available as a self-administered prefilled syringe or prefilled pen.

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

A biosimilar drug to the tumor necrosis factor inhibitor adalimumab, marketed as Idacio (adalimumab-aacf), has been approved by the Food and Drug Administration for use in the United States, according to a press release from manufacturer Fresenius Kabi.

Idacio is a citrate-free, low-concentration formulation of adalimumab and is now approved for use for all but three of the indications that currently apply to the reference adalimumab product (Humira): rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis in adults, ankylosing spondylitis, Crohn’s disease in adults and children aged 6 years or older, ulcerative colitis in adults, and plaque psoriasis in adults. It does not apply to Humira’s indications for hidradenitis suppurativa, uveitis, or ulcerative colitis in pediatric patients aged 5 years and older.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Idacio is the eighth adalimumab biosimilar to be approved in the United States. Its approval was based on evidence of a similar profile of pharmacokinetics, safety, efficacy, and immunogenicity to Humira.

Idacio was first launched in 2019 and has been marketed in more than 37 countries worldwide, according to Fresenius Kabi. The U.S. launch is scheduled for July, and Idacio will be available as a self-administered prefilled syringe or prefilled pen.

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

A registry-based study provides further evidence that treatment with dupilumab significantly reduces severity and symptoms of atopic dermatitis (AD) in clinical practice.

Dupilumab also decreased severity-associated biomarkers in pediatric patients with moderate to severe AD, researchers in the Netherlands reported.

Obtaining serum biomarkers is not the current standard in everyday practice, but studying them may improve understanding of who might respond best to dupilumab, said Jessica Hui, MD, a pediatric allergist and immunologist at National Jewish Health in Denver, in an email comment to this news organization.

“AD is heterogeneous, as each patient may have different presentations and underlying biology,” said Dr. Hui, who wasn’t involved in the research. “Studying biomarkers can eventually assist us in providing targeted therapy to each individual patient.”

Dr. Hui added, “As blood biomarkers can inform us of severity and treatment response, we can be hopeful that this will assist us in the management of AD patients in the future.”
 

Examining effect on disease severity

Dupilumab, a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, is approved in Europe and the United States to treat moderate to severe AD in patients 6 months of age or older, and to treat certain other inflammatory conditions.

Phase 3 studies show that dupilumab is effective for improving AD symptoms and quality of life in pediatric patients, but few clinical practice studies have researched the effect of the therapy on severity- and disease-related biomarkers in this population, the study authors write.

The study was published online in Pediatric Allergy Immunology.

In a new study, a team led by Esmé Kamphuis, MD, of the University of Groningen, the Netherlands, and colleagues evaluated the efficacy and safety of a 28-week dupilumab treatment course in 61 pediatric patients with moderate to severe AD. Additionally, the investigators examined the effect of this treatment regimen on serum biomarkers associated with disease severity.

Patients in the study were registered in the multicenter BioDay registry, which includes patients with moderate to severe AD receiving biologics or small-molecule agents. The AD cohort included children between 6 and 12 years of age (n = 16) and adolescents between 12 and less than 18 years of age (n = 45), all of whom received dupilumab on a dosing regimen indicated by age and body weight.

Over one-third (36.1%) of dupilumab-treated patients achieved an Investigator Global Assessment score of “almost clear” by 28 weeks of treatment. Approximately 75.4% of patients reached an Eczema Area and Severity Index (EASI) of 50, 49.2% reached EASI-75, and 24.6% reached EASI-90 at the 7-month follow-up.

Among patient-reported outcomes, 84.7% experienced improvements of 4 or more points on the Patient-Oriented Eczema Measure after the 28-week dupilumab treatment. In addition, improvements of 4 or more points on the Numeric Rating Scale for pruritus and pain were achieved by 45.3% and 77.4% of patients, respectively.

The most frequently reported side effects included conjunctivitis (n = 10) and headache (n = 4).

Of the 19 severity-associated serum biomarkers measured at baseline, week 4, and week 16, markers related to AD severity and treatment response significantly decreased during treatment (thymus- and activation-regulated chemokine, pulmonary and activation-regulated chemokine, periostin, soluble IL-2 receptor alpha).

A predicted EASI, calculated from selected biomarkers, demonstrated a significant association with disease severity in the cohort.
 

Implications for practice

When asked to comment on the study findings, Raegan Hunt, MD, the division chief of pediatric dermatology at Texas Children’s Hospital in Houston, said it is important to validate the changes in AD serum biomarkers in pediatric patients on dupilumab therapy, given that this treatment has historically been better studied in adults.

“This study adds to daily practice outcomes data, which in many cases is more relevant to the everyday care of patients than structured clinical trial data,” said Dr. Hunt, an associate professor at the Baylor College of Medicine, Houston.

Dr. Hunt, who didn’t participate in the study, noted that more research is needed on the adverse effects of dupilumab in the pediatric AD population.

Dr. Hui added that there is a lack of clear understanding of the exact underlying mechanisms for certain side effects, such as conjunctivitis, warranting further study.

The study’s BioDay registry is funded by Sanofi/Regeneron, AbbVie, Leo Pharma, Pfizer, and Eli Lilly. Several study coauthors report relationships with several pharmaceutical companies. Dr. Hunt and Dr. Hui report no relevant financial relationships.

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

A registry-based study provides further evidence that treatment with dupilumab significantly reduces severity and symptoms of atopic dermatitis (AD) in clinical practice.

Dupilumab also decreased severity-associated biomarkers in pediatric patients with moderate to severe AD, researchers in the Netherlands reported.

Obtaining serum biomarkers is not the current standard in everyday practice, but studying them may improve understanding of who might respond best to dupilumab, said Jessica Hui, MD, a pediatric allergist and immunologist at National Jewish Health in Denver, in an email comment to this news organization.

“AD is heterogeneous, as each patient may have different presentations and underlying biology,” said Dr. Hui, who wasn’t involved in the research. “Studying biomarkers can eventually assist us in providing targeted therapy to each individual patient.”

Dr. Hui added, “As blood biomarkers can inform us of severity and treatment response, we can be hopeful that this will assist us in the management of AD patients in the future.”
 

Examining effect on disease severity

Dupilumab, a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, is approved in Europe and the United States to treat moderate to severe AD in patients 6 months of age or older, and to treat certain other inflammatory conditions.

Phase 3 studies show that dupilumab is effective for improving AD symptoms and quality of life in pediatric patients, but few clinical practice studies have researched the effect of the therapy on severity- and disease-related biomarkers in this population, the study authors write.

The study was published online in Pediatric Allergy Immunology.

In a new study, a team led by Esmé Kamphuis, MD, of the University of Groningen, the Netherlands, and colleagues evaluated the efficacy and safety of a 28-week dupilumab treatment course in 61 pediatric patients with moderate to severe AD. Additionally, the investigators examined the effect of this treatment regimen on serum biomarkers associated with disease severity.

Patients in the study were registered in the multicenter BioDay registry, which includes patients with moderate to severe AD receiving biologics or small-molecule agents. The AD cohort included children between 6 and 12 years of age (n = 16) and adolescents between 12 and less than 18 years of age (n = 45), all of whom received dupilumab on a dosing regimen indicated by age and body weight.

Over one-third (36.1%) of dupilumab-treated patients achieved an Investigator Global Assessment score of “almost clear” by 28 weeks of treatment. Approximately 75.4% of patients reached an Eczema Area and Severity Index (EASI) of 50, 49.2% reached EASI-75, and 24.6% reached EASI-90 at the 7-month follow-up.

Among patient-reported outcomes, 84.7% experienced improvements of 4 or more points on the Patient-Oriented Eczema Measure after the 28-week dupilumab treatment. In addition, improvements of 4 or more points on the Numeric Rating Scale for pruritus and pain were achieved by 45.3% and 77.4% of patients, respectively.

The most frequently reported side effects included conjunctivitis (n = 10) and headache (n = 4).

Of the 19 severity-associated serum biomarkers measured at baseline, week 4, and week 16, markers related to AD severity and treatment response significantly decreased during treatment (thymus- and activation-regulated chemokine, pulmonary and activation-regulated chemokine, periostin, soluble IL-2 receptor alpha).

A predicted EASI, calculated from selected biomarkers, demonstrated a significant association with disease severity in the cohort.
 

Implications for practice

When asked to comment on the study findings, Raegan Hunt, MD, the division chief of pediatric dermatology at Texas Children’s Hospital in Houston, said it is important to validate the changes in AD serum biomarkers in pediatric patients on dupilumab therapy, given that this treatment has historically been better studied in adults.

“This study adds to daily practice outcomes data, which in many cases is more relevant to the everyday care of patients than structured clinical trial data,” said Dr. Hunt, an associate professor at the Baylor College of Medicine, Houston.

Dr. Hunt, who didn’t participate in the study, noted that more research is needed on the adverse effects of dupilumab in the pediatric AD population.

Dr. Hui added that there is a lack of clear understanding of the exact underlying mechanisms for certain side effects, such as conjunctivitis, warranting further study.

The study’s BioDay registry is funded by Sanofi/Regeneron, AbbVie, Leo Pharma, Pfizer, and Eli Lilly. Several study coauthors report relationships with several pharmaceutical companies. Dr. Hunt and Dr. Hui report no relevant financial relationships.

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

A registry-based study provides further evidence that treatment with dupilumab significantly reduces severity and symptoms of atopic dermatitis (AD) in clinical practice.

Dupilumab also decreased severity-associated biomarkers in pediatric patients with moderate to severe AD, researchers in the Netherlands reported.

Obtaining serum biomarkers is not the current standard in everyday practice, but studying them may improve understanding of who might respond best to dupilumab, said Jessica Hui, MD, a pediatric allergist and immunologist at National Jewish Health in Denver, in an email comment to this news organization.

“AD is heterogeneous, as each patient may have different presentations and underlying biology,” said Dr. Hui, who wasn’t involved in the research. “Studying biomarkers can eventually assist us in providing targeted therapy to each individual patient.”

Dr. Hui added, “As blood biomarkers can inform us of severity and treatment response, we can be hopeful that this will assist us in the management of AD patients in the future.”
 

Examining effect on disease severity

Dupilumab, a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, is approved in Europe and the United States to treat moderate to severe AD in patients 6 months of age or older, and to treat certain other inflammatory conditions.

Phase 3 studies show that dupilumab is effective for improving AD symptoms and quality of life in pediatric patients, but few clinical practice studies have researched the effect of the therapy on severity- and disease-related biomarkers in this population, the study authors write.

The study was published online in Pediatric Allergy Immunology.

In a new study, a team led by Esmé Kamphuis, MD, of the University of Groningen, the Netherlands, and colleagues evaluated the efficacy and safety of a 28-week dupilumab treatment course in 61 pediatric patients with moderate to severe AD. Additionally, the investigators examined the effect of this treatment regimen on serum biomarkers associated with disease severity.

Patients in the study were registered in the multicenter BioDay registry, which includes patients with moderate to severe AD receiving biologics or small-molecule agents. The AD cohort included children between 6 and 12 years of age (n = 16) and adolescents between 12 and less than 18 years of age (n = 45), all of whom received dupilumab on a dosing regimen indicated by age and body weight.

Over one-third (36.1%) of dupilumab-treated patients achieved an Investigator Global Assessment score of “almost clear” by 28 weeks of treatment. Approximately 75.4% of patients reached an Eczema Area and Severity Index (EASI) of 50, 49.2% reached EASI-75, and 24.6% reached EASI-90 at the 7-month follow-up.

Among patient-reported outcomes, 84.7% experienced improvements of 4 or more points on the Patient-Oriented Eczema Measure after the 28-week dupilumab treatment. In addition, improvements of 4 or more points on the Numeric Rating Scale for pruritus and pain were achieved by 45.3% and 77.4% of patients, respectively.

The most frequently reported side effects included conjunctivitis (n = 10) and headache (n = 4).

Of the 19 severity-associated serum biomarkers measured at baseline, week 4, and week 16, markers related to AD severity and treatment response significantly decreased during treatment (thymus- and activation-regulated chemokine, pulmonary and activation-regulated chemokine, periostin, soluble IL-2 receptor alpha).

A predicted EASI, calculated from selected biomarkers, demonstrated a significant association with disease severity in the cohort.
 

Implications for practice

When asked to comment on the study findings, Raegan Hunt, MD, the division chief of pediatric dermatology at Texas Children’s Hospital in Houston, said it is important to validate the changes in AD serum biomarkers in pediatric patients on dupilumab therapy, given that this treatment has historically been better studied in adults.

“This study adds to daily practice outcomes data, which in many cases is more relevant to the everyday care of patients than structured clinical trial data,” said Dr. Hunt, an associate professor at the Baylor College of Medicine, Houston.

Dr. Hunt, who didn’t participate in the study, noted that more research is needed on the adverse effects of dupilumab in the pediatric AD population.

Dr. Hui added that there is a lack of clear understanding of the exact underlying mechanisms for certain side effects, such as conjunctivitis, warranting further study.

The study’s BioDay registry is funded by Sanofi/Regeneron, AbbVie, Leo Pharma, Pfizer, and Eli Lilly. Several study coauthors report relationships with several pharmaceutical companies. Dr. Hunt and Dr. Hui report no relevant financial relationships.

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

We are all seeing more children on the autism spectrum than we ever expected. With a Centers for Disease Control–estimated prevalence of 1 in 44, the average pediatrician will be caring for 45 children with autism. It may feel like even more as parents bring in their children with related concerns or fears. Early entry into services has been shown to improve functioning, making early identification important. However, screening at the youngest ages has important limitations.

Sharing a concern about possible autism with parents is a painful aspect of primary care practice. We want to get it right, not frighten parents unnecessarily, nor miss children and delay intervention.

Autism screening is recommended by the American Academy of Pediatrics at 18- and 24-month pediatric well-child visits. There are several reasons for screening repeatedly: Autism symptoms emerge gradually in the toddler period; about 32% of children later found to have autism were developing in a typical pattern and appeared normal at 18 months only to regress by age 24 months; children may miss the 18 month screen; and all screens have false negatives as well as false positives. But even screening at these two ages is not enough.

One criticism of current screening tests pointed out by the U.S. Preventive Services Task Force has been a problem with the sample used to develop or validate the tool. Many test development studies included only children at risk by being in early intervention, siblings of children with diagnosed autism, or children only failing the screening tests rather than a community sample that the screen in actually used for.

Another obstacle to prediction of autism diagnoses made years later is that some children may not have had any clinical manifestations at the younger age even as judged by the best gold standard testing and, thus, negative screens were ambiguous. Additionally, data from prospective studies of high-risk infant siblings reveal that only 18% of children diagnosed with autism at 36 months were given that diagnosis at 18 months of age despite use of comprehensive diagnostic assessments.

Prevalence is also reported as 30% higher at age 8-12 years as at 3-7 years on gold-standard tests. Children identified later with autism tend to have milder symptoms and higher cognitive functioning. Therefore, we need some humility in thinking we can identify children as early as 18 months; rather, we need to use the best available methods at all ages and remain vigilant to symptoms as they evolve as well as to new screening and testing measures.

The most commonly used parent report screen is the 20-item Modified Checklist for Autism in Toddlers–Revised (M-CHAT-R), a modification of the original CHAT screen. To have reasonable positive predictive value, the M-CHAT-R authors recommend a clinician or trained staff member conduct a structured follow-up interview with the parent when the M-CHAT-R has a score of 3-7. Scores of 8 or more reflect enough symptoms to more strongly predict an autism diagnosis and thus the interview may be skipped in those cases. The recommended two-step process is called M-CHAT-R/F. At 18 months without the R/F, a positive M-CHAT-R only is associated with an autism diagnosis 27% of the time (PPV, 0.27); which is unacceptable for primary care use.

Unfortunately, the M-CHAT-R/F appears to be less accurate for 18-month-olds than 24-month-olds, in part because its yes/no response options are harder for a caregiver to answer, especially for behaviors just developing, or because of lack of experience with toddlers.

An alternative modification of the original CHAT called the Quantitative CHAT or Q-CHAT-10 has a range of response options for the caregiver; for example, always/usually/sometimes/rarely/never or many times a day/a few times a day/a few times a week/less than once a week/never. The authors of the Q-CHAT-10, however, recommend a summary pass/fail result for ease of use rather than using the range of response option values in the score. We recently published a study testing accuracy using add-up scoring that utilized the entire range of response option values, called Q-CHAT-10-O (O for ordinal), for children 16-20 months old as well as cartoon depictions of the behaviors. Our study also included diagnostic testing of screen-negative as well as screen-positive children to accurately calculate sensitivity and specificity for this method. In our study, Q-CHAT-10-O with a cutoff score greater than 11 showed higher sensitivity (0.63) than either M-CHAT-R/F (0.34) or Q-CHAT-10 (0.31) for this age range although the PPV (0.35) and negative predictive value (0.92) were comparable with M-CHAT R/F. Although Q-CHAT-10-O sensitivity (0.63) is less than M-CHAT-R (without follow-up; 0.73) and specificity (0.79) is less than the two-stage R/F procedure (0.90), on balance, it is more accurate and more practical for a primary care population. After 20 months of age, the M-CHAT-R/F has adequate accuracy to rescreen, if indicated, and for the subsequent 24 month screening. Language items are often of highest value in predicting outcomes in several tools including in the screen we are now validating for 18 month olds.

The Q-CHAT-10-O with ordinal scoring and pictures can also be recommended because it shows advantages over M-CHAT-R/F with half the number of items (10 vs. 20), no requirement for a follow-up interview, and improved sensitivity. Unlike M-CHAT-R, it also contributes to equity in screening because results did not differ depending on race or socioeconomic background.

Is there an even better way to detect autism in primary care? In 2022 an article was published regarding an exciting method of early autism detection called the Social Attention and Communication Surveillance–Revised (SACS-R), an eight-item observation checklist completed at public health nurse check-ups in Australia. The observers had 4 years of nursing degree education and a 3.5-hour training session.

The SACS-R and the preschool version (for older children) had significant associations with diagnostic testing at 12, 18, 24, and 42 months. The SACS-R had excellent PPV (82.6%), NPV (98.7%), and specificity (99.6%) and moderate sensitivity (61.5%) when used between 12 and 24 months of age. Pointing, eye contact, waving “bye, bye,” social communication by showing, and pretend play were the key indicators for observations at 18 months, with absence of three or more indicating risk for autism. Different key indicators were used at the other ages, reflecting the evolution of autism symptoms. This hybrid (observation and scoring) surveillance method by professionals shows hopeful data for the critical ability to identify children at risk for autism in primary care very early but requires more than parent report, that is, new levels of autism-specific clinician training and direct observations at multiple visits over time.

The takeaway is to remember that we should all watch closely for early signs of autism, informed by research on the key findings that a professional might observe, as well as by using the best screens available. We should remember that both false positives and false negatives are inherent in screening, especially at the youngest ages. We need to combine our concern with the parent’s concern as well as screen results and be sure to follow-up closely as symptoms can change in even a few months. Many factors may prevent a family from returning to see us or following our advice to go for testing or intervention, so tracking the child and their service use is an important part of the good care we strive to provide children with autism.

Other screening tools

You may have heard of other parent-report screens for autism. It is important to compare their accuracy specifically for 18-month-olds in a community setting.

• The Infant Toddler Checklist (https://psychology-tools.com/test/infant-toddler-checklist) has moderate overall psychometrics with sensitivity ranging from 0.55 to 0.77; specificity from 0.42 to 0.85; PPV from 0.20 to 0.55; and NPV from 0.83 to 0.94. However, the data were based on a sample including both community-dwelling toddlers and those with a family history of autism.
• The Brief Infant-Toddler Social and Emotional Assessment (https://eprovide.mapi-trust.org/instruments/brief-infant-toddler-social-emotional-assessment/) – the screen’s four autism-specific scales had high specificity (84%-90%) but low sensitivity (40%-52%).
• Canvas Dx (https://canvasdx.com/) from the Cognoa company is not a parent-report measure but rather a three-part evaluation including an app-based parent questionnaire, parent uploads of home videos analyzed by a specialist, and a 13- to 15-item primary care physician observational checklist. There were 56 diagnosed of the 426 children in the 18- to 24-month-old range from a sample of children presenting with parent or clinician concerns rather than from a community sample.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at [email protected].

References

Sturner R et al. Autism screening at 18 months of age: A comparison of the Q-CHAT-10 and M-CHAT screeners. Molecular Autism. Jan 3;13(1):2.

Barbaro J et al. Diagnostic accuracy of the Social Attention and Communication Surveillance–Revised with preschool tool for early autism detection in very young children. JAMA Netw Open. 2022;5(3):e2146415.

We are all seeing more children on the autism spectrum than we ever expected. With a Centers for Disease Control–estimated prevalence of 1 in 44, the average pediatrician will be caring for 45 children with autism. It may feel like even more as parents bring in their children with related concerns or fears. Early entry into services has been shown to improve functioning, making early identification important. However, screening at the youngest ages has important limitations.

Sharing a concern about possible autism with parents is a painful aspect of primary care practice. We want to get it right, not frighten parents unnecessarily, nor miss children and delay intervention.

Autism screening is recommended by the American Academy of Pediatrics at 18- and 24-month pediatric well-child visits. There are several reasons for screening repeatedly: Autism symptoms emerge gradually in the toddler period; about 32% of children later found to have autism were developing in a typical pattern and appeared normal at 18 months only to regress by age 24 months; children may miss the 18 month screen; and all screens have false negatives as well as false positives. But even screening at these two ages is not enough.

One criticism of current screening tests pointed out by the U.S. Preventive Services Task Force has been a problem with the sample used to develop or validate the tool. Many test development studies included only children at risk by being in early intervention, siblings of children with diagnosed autism, or children only failing the screening tests rather than a community sample that the screen in actually used for.

Another obstacle to prediction of autism diagnoses made years later is that some children may not have had any clinical manifestations at the younger age even as judged by the best gold standard testing and, thus, negative screens were ambiguous. Additionally, data from prospective studies of high-risk infant siblings reveal that only 18% of children diagnosed with autism at 36 months were given that diagnosis at 18 months of age despite use of comprehensive diagnostic assessments.

Prevalence is also reported as 30% higher at age 8-12 years as at 3-7 years on gold-standard tests. Children identified later with autism tend to have milder symptoms and higher cognitive functioning. Therefore, we need some humility in thinking we can identify children as early as 18 months; rather, we need to use the best available methods at all ages and remain vigilant to symptoms as they evolve as well as to new screening and testing measures.

The most commonly used parent report screen is the 20-item Modified Checklist for Autism in Toddlers–Revised (M-CHAT-R), a modification of the original CHAT screen. To have reasonable positive predictive value, the M-CHAT-R authors recommend a clinician or trained staff member conduct a structured follow-up interview with the parent when the M-CHAT-R has a score of 3-7. Scores of 8 or more reflect enough symptoms to more strongly predict an autism diagnosis and thus the interview may be skipped in those cases. The recommended two-step process is called M-CHAT-R/F. At 18 months without the R/F, a positive M-CHAT-R only is associated with an autism diagnosis 27% of the time (PPV, 0.27); which is unacceptable for primary care use.

Unfortunately, the M-CHAT-R/F appears to be less accurate for 18-month-olds than 24-month-olds, in part because its yes/no response options are harder for a caregiver to answer, especially for behaviors just developing, or because of lack of experience with toddlers.

An alternative modification of the original CHAT called the Quantitative CHAT or Q-CHAT-10 has a range of response options for the caregiver; for example, always/usually/sometimes/rarely/never or many times a day/a few times a day/a few times a week/less than once a week/never. The authors of the Q-CHAT-10, however, recommend a summary pass/fail result for ease of use rather than using the range of response option values in the score. We recently published a study testing accuracy using add-up scoring that utilized the entire range of response option values, called Q-CHAT-10-O (O for ordinal), for children 16-20 months old as well as cartoon depictions of the behaviors. Our study also included diagnostic testing of screen-negative as well as screen-positive children to accurately calculate sensitivity and specificity for this method. In our study, Q-CHAT-10-O with a cutoff score greater than 11 showed higher sensitivity (0.63) than either M-CHAT-R/F (0.34) or Q-CHAT-10 (0.31) for this age range although the PPV (0.35) and negative predictive value (0.92) were comparable with M-CHAT R/F. Although Q-CHAT-10-O sensitivity (0.63) is less than M-CHAT-R (without follow-up; 0.73) and specificity (0.79) is less than the two-stage R/F procedure (0.90), on balance, it is more accurate and more practical for a primary care population. After 20 months of age, the M-CHAT-R/F has adequate accuracy to rescreen, if indicated, and for the subsequent 24 month screening. Language items are often of highest value in predicting outcomes in several tools including in the screen we are now validating for 18 month olds.

The Q-CHAT-10-O with ordinal scoring and pictures can also be recommended because it shows advantages over M-CHAT-R/F with half the number of items (10 vs. 20), no requirement for a follow-up interview, and improved sensitivity. Unlike M-CHAT-R, it also contributes to equity in screening because results did not differ depending on race or socioeconomic background.

Is there an even better way to detect autism in primary care? In 2022 an article was published regarding an exciting method of early autism detection called the Social Attention and Communication Surveillance–Revised (SACS-R), an eight-item observation checklist completed at public health nurse check-ups in Australia. The observers had 4 years of nursing degree education and a 3.5-hour training session.

The SACS-R and the preschool version (for older children) had significant associations with diagnostic testing at 12, 18, 24, and 42 months. The SACS-R had excellent PPV (82.6%), NPV (98.7%), and specificity (99.6%) and moderate sensitivity (61.5%) when used between 12 and 24 months of age. Pointing, eye contact, waving “bye, bye,” social communication by showing, and pretend play were the key indicators for observations at 18 months, with absence of three or more indicating risk for autism. Different key indicators were used at the other ages, reflecting the evolution of autism symptoms. This hybrid (observation and scoring) surveillance method by professionals shows hopeful data for the critical ability to identify children at risk for autism in primary care very early but requires more than parent report, that is, new levels of autism-specific clinician training and direct observations at multiple visits over time.

The takeaway is to remember that we should all watch closely for early signs of autism, informed by research on the key findings that a professional might observe, as well as by using the best screens available. We should remember that both false positives and false negatives are inherent in screening, especially at the youngest ages. We need to combine our concern with the parent’s concern as well as screen results and be sure to follow-up closely as symptoms can change in even a few months. Many factors may prevent a family from returning to see us or following our advice to go for testing or intervention, so tracking the child and their service use is an important part of the good care we strive to provide children with autism.

Other screening tools

You may have heard of other parent-report screens for autism. It is important to compare their accuracy specifically for 18-month-olds in a community setting.

• The Infant Toddler Checklist (https://psychology-tools.com/test/infant-toddler-checklist) has moderate overall psychometrics with sensitivity ranging from 0.55 to 0.77; specificity from 0.42 to 0.85; PPV from 0.20 to 0.55; and NPV from 0.83 to 0.94. However, the data were based on a sample including both community-dwelling toddlers and those with a family history of autism.
• The Brief Infant-Toddler Social and Emotional Assessment (https://eprovide.mapi-trust.org/instruments/brief-infant-toddler-social-emotional-assessment/) – the screen’s four autism-specific scales had high specificity (84%-90%) but low sensitivity (40%-52%).
• Canvas Dx (https://canvasdx.com/) from the Cognoa company is not a parent-report measure but rather a three-part evaluation including an app-based parent questionnaire, parent uploads of home videos analyzed by a specialist, and a 13- to 15-item primary care physician observational checklist. There were 56 diagnosed of the 426 children in the 18- to 24-month-old range from a sample of children presenting with parent or clinician concerns rather than from a community sample.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at [email protected].

References

Sturner R et al. Autism screening at 18 months of age: A comparison of the Q-CHAT-10 and M-CHAT screeners. Molecular Autism. Jan 3;13(1):2.

Barbaro J et al. Diagnostic accuracy of the Social Attention and Communication Surveillance–Revised with preschool tool for early autism detection in very young children. JAMA Netw Open. 2022;5(3):e2146415.

We are all seeing more children on the autism spectrum than we ever expected. With a Centers for Disease Control–estimated prevalence of 1 in 44, the average pediatrician will be caring for 45 children with autism. It may feel like even more as parents bring in their children with related concerns or fears. Early entry into services has been shown to improve functioning, making early identification important. However, screening at the youngest ages has important limitations.

Sharing a concern about possible autism with parents is a painful aspect of primary care practice. We want to get it right, not frighten parents unnecessarily, nor miss children and delay intervention.

Autism screening is recommended by the American Academy of Pediatrics at 18- and 24-month pediatric well-child visits. There are several reasons for screening repeatedly: Autism symptoms emerge gradually in the toddler period; about 32% of children later found to have autism were developing in a typical pattern and appeared normal at 18 months only to regress by age 24 months; children may miss the 18 month screen; and all screens have false negatives as well as false positives. But even screening at these two ages is not enough.

One criticism of current screening tests pointed out by the U.S. Preventive Services Task Force has been a problem with the sample used to develop or validate the tool. Many test development studies included only children at risk by being in early intervention, siblings of children with diagnosed autism, or children only failing the screening tests rather than a community sample that the screen in actually used for.

Another obstacle to prediction of autism diagnoses made years later is that some children may not have had any clinical manifestations at the younger age even as judged by the best gold standard testing and, thus, negative screens were ambiguous. Additionally, data from prospective studies of high-risk infant siblings reveal that only 18% of children diagnosed with autism at 36 months were given that diagnosis at 18 months of age despite use of comprehensive diagnostic assessments.

Prevalence is also reported as 30% higher at age 8-12 years as at 3-7 years on gold-standard tests. Children identified later with autism tend to have milder symptoms and higher cognitive functioning. Therefore, we need some humility in thinking we can identify children as early as 18 months; rather, we need to use the best available methods at all ages and remain vigilant to symptoms as they evolve as well as to new screening and testing measures.

The most commonly used parent report screen is the 20-item Modified Checklist for Autism in Toddlers–Revised (M-CHAT-R), a modification of the original CHAT screen. To have reasonable positive predictive value, the M-CHAT-R authors recommend a clinician or trained staff member conduct a structured follow-up interview with the parent when the M-CHAT-R has a score of 3-7. Scores of 8 or more reflect enough symptoms to more strongly predict an autism diagnosis and thus the interview may be skipped in those cases. The recommended two-step process is called M-CHAT-R/F. At 18 months without the R/F, a positive M-CHAT-R only is associated with an autism diagnosis 27% of the time (PPV, 0.27); which is unacceptable for primary care use.

Unfortunately, the M-CHAT-R/F appears to be less accurate for 18-month-olds than 24-month-olds, in part because its yes/no response options are harder for a caregiver to answer, especially for behaviors just developing, or because of lack of experience with toddlers.

An alternative modification of the original CHAT called the Quantitative CHAT or Q-CHAT-10 has a range of response options for the caregiver; for example, always/usually/sometimes/rarely/never or many times a day/a few times a day/a few times a week/less than once a week/never. The authors of the Q-CHAT-10, however, recommend a summary pass/fail result for ease of use rather than using the range of response option values in the score. We recently published a study testing accuracy using add-up scoring that utilized the entire range of response option values, called Q-CHAT-10-O (O for ordinal), for children 16-20 months old as well as cartoon depictions of the behaviors. Our study also included diagnostic testing of screen-negative as well as screen-positive children to accurately calculate sensitivity and specificity for this method. In our study, Q-CHAT-10-O with a cutoff score greater than 11 showed higher sensitivity (0.63) than either M-CHAT-R/F (0.34) or Q-CHAT-10 (0.31) for this age range although the PPV (0.35) and negative predictive value (0.92) were comparable with M-CHAT R/F. Although Q-CHAT-10-O sensitivity (0.63) is less than M-CHAT-R (without follow-up; 0.73) and specificity (0.79) is less than the two-stage R/F procedure (0.90), on balance, it is more accurate and more practical for a primary care population. After 20 months of age, the M-CHAT-R/F has adequate accuracy to rescreen, if indicated, and for the subsequent 24 month screening. Language items are often of highest value in predicting outcomes in several tools including in the screen we are now validating for 18 month olds.

The Q-CHAT-10-O with ordinal scoring and pictures can also be recommended because it shows advantages over M-CHAT-R/F with half the number of items (10 vs. 20), no requirement for a follow-up interview, and improved sensitivity. Unlike M-CHAT-R, it also contributes to equity in screening because results did not differ depending on race or socioeconomic background.

Is there an even better way to detect autism in primary care? In 2022 an article was published regarding an exciting method of early autism detection called the Social Attention and Communication Surveillance–Revised (SACS-R), an eight-item observation checklist completed at public health nurse check-ups in Australia. The observers had 4 years of nursing degree education and a 3.5-hour training session.

The SACS-R and the preschool version (for older children) had significant associations with diagnostic testing at 12, 18, 24, and 42 months. The SACS-R had excellent PPV (82.6%), NPV (98.7%), and specificity (99.6%) and moderate sensitivity (61.5%) when used between 12 and 24 months of age. Pointing, eye contact, waving “bye, bye,” social communication by showing, and pretend play were the key indicators for observations at 18 months, with absence of three or more indicating risk for autism. Different key indicators were used at the other ages, reflecting the evolution of autism symptoms. This hybrid (observation and scoring) surveillance method by professionals shows hopeful data for the critical ability to identify children at risk for autism in primary care very early but requires more than parent report, that is, new levels of autism-specific clinician training and direct observations at multiple visits over time.

The takeaway is to remember that we should all watch closely for early signs of autism, informed by research on the key findings that a professional might observe, as well as by using the best screens available. We should remember that both false positives and false negatives are inherent in screening, especially at the youngest ages. We need to combine our concern with the parent’s concern as well as screen results and be sure to follow-up closely as symptoms can change in even a few months. Many factors may prevent a family from returning to see us or following our advice to go for testing or intervention, so tracking the child and their service use is an important part of the good care we strive to provide children with autism.

Other screening tools

You may have heard of other parent-report screens for autism. It is important to compare their accuracy specifically for 18-month-olds in a community setting.

• The Infant Toddler Checklist (https://psychology-tools.com/test/infant-toddler-checklist) has moderate overall psychometrics with sensitivity ranging from 0.55 to 0.77; specificity from 0.42 to 0.85; PPV from 0.20 to 0.55; and NPV from 0.83 to 0.94. However, the data were based on a sample including both community-dwelling toddlers and those with a family history of autism.
• The Brief Infant-Toddler Social and Emotional Assessment (https://eprovide.mapi-trust.org/instruments/brief-infant-toddler-social-emotional-assessment/) – the screen’s four autism-specific scales had high specificity (84%-90%) but low sensitivity (40%-52%).
• Canvas Dx (https://canvasdx.com/) from the Cognoa company is not a parent-report measure but rather a three-part evaluation including an app-based parent questionnaire, parent uploads of home videos analyzed by a specialist, and a 13- to 15-item primary care physician observational checklist. There were 56 diagnosed of the 426 children in the 18- to 24-month-old range from a sample of children presenting with parent or clinician concerns rather than from a community sample.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at [email protected].

References

Sturner R et al. Autism screening at 18 months of age: A comparison of the Q-CHAT-10 and M-CHAT screeners. Molecular Autism. Jan 3;13(1):2.

Barbaro J et al. Diagnostic accuracy of the Social Attention and Communication Surveillance–Revised with preschool tool for early autism detection in very young children. JAMA Netw Open. 2022;5(3):e2146415.

When I was growing up, I can remember experiencing “duck and cover” drills at school. If a flash appeared in our peripheral vision, we were told we should not look at it but crawl under our desks. My classmates and I were being taught how to protect ourselves in case of a nuclear attack.

Clearly, had there been such an attack, ducking under our desks would not have saved us. Thankfully, such a conflict never occurred – and hopefully never will. Still, the warning did penetrate our psyches. In those days, families and children in schools were worried, and some were scared.

The situation is quite different today. Our children and grandchildren are being taught to protect themselves not from actions overseas – that never happened – but from what someone living in their community might do that has been occurring in real time. According to my daughter-in-law, her young children are taught during “lockdowns” to hide in their classrooms’ closets. During these drills, some children are directed to line up against a wall that would be out of sight of a shooter, and to stay as still as possible.

Since 2017, the number of intentional shootings in U.S. kindergarten through grade 12 schools increased precipitously (Prev Med. 2022 Dec. doi: 10.1016/j.ypmed.2022.107280). Imagine the psychological impact that the vigilance required to deal with such impending threats must be having on our children, as they learn to fear injury and possible death every day they go to school. I’ve talked with numerous parents about this, including my own adult children, and this is clearly a new dimension of life that is on everyone’s minds. Schools, once bastions of safety, are no longer that safe.

For many years, I’ve written about the need to destigmatize mental illness so that it is treated on a par with physical illness. As we look at the challenges faced by young people, reframing mental illness is more important now than ever. This means finding ways to increase the funding of studies that help us understand young people with mental health issues. It also means encouraging patients to pursue treatment from psychiatrists, psychologists, or mental health counselors who specialize in short-term therapy.

The emphasis here on short-term therapy is not to discourage longer-term care when needed, but clearly short-term care strategies, such as cognitive-behavioral therapies, not only work for problem resolution, they also help in the destigmatization of mental health care – as the circumscribed treatment with a clear beginning, middle, and end is consistent with CBT and consistent with much of medical care for physical disorders.

Furthermore, as we aim to destigmatize mental health care, it’s important to equate it with physical care. For example, taking a day or two from school or work for a sprained ankle, seeing a dentist, or an eye exam, plus a myriad of physical issues is quite acceptable. Why is it not also acceptable for a mental health issue and evaluation, such as for anxiety or PTSD, plus being able to talk about it without stigma? Seeing the “shrink” needs to be removed as a negative but viewed as a very positive move toward care for oneself.

In addition, children and adolescents are battling countless other health challenges that could have implications for mental health professionals, for example:

• During the height of the coronavirus pandemic, pediatric endocrinologists reportedly saw a surge of referrals for girls experiencing early puberty. Puberty should never be medicalized, but early maturation has been linked to numerous psychiatric disorders such as depression, anxiety, and eating disorders (J Pediatr Adolec Gynecol. 2022 Oct. doi: 10.1016/j.jpag.2022.05.005).
• A global epidemiologic study of children estimates that nearly 8 million youth lost a parent or caregiver because of a pandemic-related cause between Jan. 1, 2020, and May 1, 2022. An additional 2.5 million children were affected by the loss of secondary caregivers such as grandparents (JAMA Pediatr. 2022 Sept. doi: 10.1001/jamapediatrics.2022.3157).
• The inpatient and outpatient volume of adolescents and young adults receiving care for eating disorders skyrocketed before and after the pandemic, according to the results of case study series (JAMA Pediatrics. 2022 Nov 7. doi: 10.1001/jamapediatrics.2022.4346).
• Children and adolescents who developed COVID-19 suffered tremendously during the height of the pandemic. A nationwide analysis shows that COVID-19 nearly tripled children’s risks of developing new mental health illnesses, such as attention-deficit/hyperactivity disorder, anxiety, trauma, or stress disorder (Psychiatric Services. 2022 Jun 2. doi: 10.1176/appi.ps.202100646).

In addition to those challenges, young children are facing an increase in respiratory syncytial virus (RSV) infection. We were told the “flu” would be quite bad this year and to beware of monkeypox. However, very little mention is made of the equally distressing “epidemic” of mental health issues, PTSD, anxiety, and depression as we are still in the midst of the COVID pandemic in the United States with almost 400 deaths a day – a very unacceptable number.

Interestingly, we seem to have abandoned the use of masks as protection against COVID and other respiratory diseases, despite their effectiveness. A study in Boston that looked at children in two school districts that did not lift mask mandates demonstrated that mask wearing does indeed lead to significant reductions in the number of pediatric COVID cases. In addition to societal violence and school shootings – which certainly exacerbate anxiety – the fear of dying or the death of a loved one, tied to COVID, may lead to epidemic proportions of PTSD in children. As an article in WebMD noted, “pediatricians are imploring the federal government to declare a national emergency as cases of pediatric respiratory illnesses continue to soar.”

In light of the acknowledged mental health crisis in children, which appears epidemic, I would hope the psychiatric and psychological associations would publicly sound an alarm so that resources could be brought to bear to address this critical issue. I believe doing so would also aid in destigmatizing mental disorders, and increase education and treatment.

Layered on top of those issues are natural disasters, such as the fallout from Tropical Storm Nicole when it recently caused devastation across western Florida. The mental health trauma caused by recent tropical storms seems all but forgotten – except for those who are still suffering. All of this adds up to a society-wide mental health crisis, which seems far more expansive than monkeypox, for example. Yet monkeypox, which did lead to thousands of cases and approximately 29 deaths in the United States, was declared a national public health emergency.

Additionally, RSV killed 100-500 U.S. children under age 5 each year before the pandemic, according to the Centers for Disease Control and Prevention, and currently it appears even worse. Yet despite the seriousness of RSV, it nowhere matches the emotional toll COVID has taken on children globally.

Let’s make it standard practice for children – and of course, adults – to be taught that anxiety is a normal response at times. We should teach that, in some cases, feeling “down” or in despair and even experiencing symptoms of PTSD based on what’s going on personally and within our environment (i.e., COVID, school shootings, etc.) are triggers and responses that can be addressed and often quickly treated by talking with a mental health professional.

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

When I was growing up, I can remember experiencing “duck and cover” drills at school. If a flash appeared in our peripheral vision, we were told we should not look at it but crawl under our desks. My classmates and I were being taught how to protect ourselves in case of a nuclear attack.

Clearly, had there been such an attack, ducking under our desks would not have saved us. Thankfully, such a conflict never occurred – and hopefully never will. Still, the warning did penetrate our psyches. In those days, families and children in schools were worried, and some were scared.

The situation is quite different today. Our children and grandchildren are being taught to protect themselves not from actions overseas – that never happened – but from what someone living in their community might do that has been occurring in real time. According to my daughter-in-law, her young children are taught during “lockdowns” to hide in their classrooms’ closets. During these drills, some children are directed to line up against a wall that would be out of sight of a shooter, and to stay as still as possible.

Since 2017, the number of intentional shootings in U.S. kindergarten through grade 12 schools increased precipitously (Prev Med. 2022 Dec. doi: 10.1016/j.ypmed.2022.107280). Imagine the psychological impact that the vigilance required to deal with such impending threats must be having on our children, as they learn to fear injury and possible death every day they go to school. I’ve talked with numerous parents about this, including my own adult children, and this is clearly a new dimension of life that is on everyone’s minds. Schools, once bastions of safety, are no longer that safe.

For many years, I’ve written about the need to destigmatize mental illness so that it is treated on a par with physical illness. As we look at the challenges faced by young people, reframing mental illness is more important now than ever. This means finding ways to increase the funding of studies that help us understand young people with mental health issues. It also means encouraging patients to pursue treatment from psychiatrists, psychologists, or mental health counselors who specialize in short-term therapy.

The emphasis here on short-term therapy is not to discourage longer-term care when needed, but clearly short-term care strategies, such as cognitive-behavioral therapies, not only work for problem resolution, they also help in the destigmatization of mental health care – as the circumscribed treatment with a clear beginning, middle, and end is consistent with CBT and consistent with much of medical care for physical disorders.

Furthermore, as we aim to destigmatize mental health care, it’s important to equate it with physical care. For example, taking a day or two from school or work for a sprained ankle, seeing a dentist, or an eye exam, plus a myriad of physical issues is quite acceptable. Why is it not also acceptable for a mental health issue and evaluation, such as for anxiety or PTSD, plus being able to talk about it without stigma? Seeing the “shrink” needs to be removed as a negative but viewed as a very positive move toward care for oneself.

In addition, children and adolescents are battling countless other health challenges that could have implications for mental health professionals, for example:

• During the height of the coronavirus pandemic, pediatric endocrinologists reportedly saw a surge of referrals for girls experiencing early puberty. Puberty should never be medicalized, but early maturation has been linked to numerous psychiatric disorders such as depression, anxiety, and eating disorders (J Pediatr Adolec Gynecol. 2022 Oct. doi: 10.1016/j.jpag.2022.05.005).
• A global epidemiologic study of children estimates that nearly 8 million youth lost a parent or caregiver because of a pandemic-related cause between Jan. 1, 2020, and May 1, 2022. An additional 2.5 million children were affected by the loss of secondary caregivers such as grandparents (JAMA Pediatr. 2022 Sept. doi: 10.1001/jamapediatrics.2022.3157).
• The inpatient and outpatient volume of adolescents and young adults receiving care for eating disorders skyrocketed before and after the pandemic, according to the results of case study series (JAMA Pediatrics. 2022 Nov 7. doi: 10.1001/jamapediatrics.2022.4346).
• Children and adolescents who developed COVID-19 suffered tremendously during the height of the pandemic. A nationwide analysis shows that COVID-19 nearly tripled children’s risks of developing new mental health illnesses, such as attention-deficit/hyperactivity disorder, anxiety, trauma, or stress disorder (Psychiatric Services. 2022 Jun 2. doi: 10.1176/appi.ps.202100646).

In addition to those challenges, young children are facing an increase in respiratory syncytial virus (RSV) infection. We were told the “flu” would be quite bad this year and to beware of monkeypox. However, very little mention is made of the equally distressing “epidemic” of mental health issues, PTSD, anxiety, and depression as we are still in the midst of the COVID pandemic in the United States with almost 400 deaths a day – a very unacceptable number.

Interestingly, we seem to have abandoned the use of masks as protection against COVID and other respiratory diseases, despite their effectiveness. A study in Boston that looked at children in two school districts that did not lift mask mandates demonstrated that mask wearing does indeed lead to significant reductions in the number of pediatric COVID cases. In addition to societal violence and school shootings – which certainly exacerbate anxiety – the fear of dying or the death of a loved one, tied to COVID, may lead to epidemic proportions of PTSD in children. As an article in WebMD noted, “pediatricians are imploring the federal government to declare a national emergency as cases of pediatric respiratory illnesses continue to soar.”

In light of the acknowledged mental health crisis in children, which appears epidemic, I would hope the psychiatric and psychological associations would publicly sound an alarm so that resources could be brought to bear to address this critical issue. I believe doing so would also aid in destigmatizing mental disorders, and increase education and treatment.

Layered on top of those issues are natural disasters, such as the fallout from Tropical Storm Nicole when it recently caused devastation across western Florida. The mental health trauma caused by recent tropical storms seems all but forgotten – except for those who are still suffering. All of this adds up to a society-wide mental health crisis, which seems far more expansive than monkeypox, for example. Yet monkeypox, which did lead to thousands of cases and approximately 29 deaths in the United States, was declared a national public health emergency.

Additionally, RSV killed 100-500 U.S. children under age 5 each year before the pandemic, according to the Centers for Disease Control and Prevention, and currently it appears even worse. Yet despite the seriousness of RSV, it nowhere matches the emotional toll COVID has taken on children globally.

Let’s make it standard practice for children – and of course, adults – to be taught that anxiety is a normal response at times. We should teach that, in some cases, feeling “down” or in despair and even experiencing symptoms of PTSD based on what’s going on personally and within our environment (i.e., COVID, school shootings, etc.) are triggers and responses that can be addressed and often quickly treated by talking with a mental health professional.

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

When I was growing up, I can remember experiencing “duck and cover” drills at school. If a flash appeared in our peripheral vision, we were told we should not look at it but crawl under our desks. My classmates and I were being taught how to protect ourselves in case of a nuclear attack.

Clearly, had there been such an attack, ducking under our desks would not have saved us. Thankfully, such a conflict never occurred – and hopefully never will. Still, the warning did penetrate our psyches. In those days, families and children in schools were worried, and some were scared.

The situation is quite different today. Our children and grandchildren are being taught to protect themselves not from actions overseas – that never happened – but from what someone living in their community might do that has been occurring in real time. According to my daughter-in-law, her young children are taught during “lockdowns” to hide in their classrooms’ closets. During these drills, some children are directed to line up against a wall that would be out of sight of a shooter, and to stay as still as possible.

Since 2017, the number of intentional shootings in U.S. kindergarten through grade 12 schools increased precipitously (Prev Med. 2022 Dec. doi: 10.1016/j.ypmed.2022.107280). Imagine the psychological impact that the vigilance required to deal with such impending threats must be having on our children, as they learn to fear injury and possible death every day they go to school. I’ve talked with numerous parents about this, including my own adult children, and this is clearly a new dimension of life that is on everyone’s minds. Schools, once bastions of safety, are no longer that safe.

For many years, I’ve written about the need to destigmatize mental illness so that it is treated on a par with physical illness. As we look at the challenges faced by young people, reframing mental illness is more important now than ever. This means finding ways to increase the funding of studies that help us understand young people with mental health issues. It also means encouraging patients to pursue treatment from psychiatrists, psychologists, or mental health counselors who specialize in short-term therapy.

The emphasis here on short-term therapy is not to discourage longer-term care when needed, but clearly short-term care strategies, such as cognitive-behavioral therapies, not only work for problem resolution, they also help in the destigmatization of mental health care – as the circumscribed treatment with a clear beginning, middle, and end is consistent with CBT and consistent with much of medical care for physical disorders.

Furthermore, as we aim to destigmatize mental health care, it’s important to equate it with physical care. For example, taking a day or two from school or work for a sprained ankle, seeing a dentist, or an eye exam, plus a myriad of physical issues is quite acceptable. Why is it not also acceptable for a mental health issue and evaluation, such as for anxiety or PTSD, plus being able to talk about it without stigma? Seeing the “shrink” needs to be removed as a negative but viewed as a very positive move toward care for oneself.

In addition, children and adolescents are battling countless other health challenges that could have implications for mental health professionals, for example:

• During the height of the coronavirus pandemic, pediatric endocrinologists reportedly saw a surge of referrals for girls experiencing early puberty. Puberty should never be medicalized, but early maturation has been linked to numerous psychiatric disorders such as depression, anxiety, and eating disorders (J Pediatr Adolec Gynecol. 2022 Oct. doi: 10.1016/j.jpag.2022.05.005).
• A global epidemiologic study of children estimates that nearly 8 million youth lost a parent or caregiver because of a pandemic-related cause between Jan. 1, 2020, and May 1, 2022. An additional 2.5 million children were affected by the loss of secondary caregivers such as grandparents (JAMA Pediatr. 2022 Sept. doi: 10.1001/jamapediatrics.2022.3157).
• The inpatient and outpatient volume of adolescents and young adults receiving care for eating disorders skyrocketed before and after the pandemic, according to the results of case study series (JAMA Pediatrics. 2022 Nov 7. doi: 10.1001/jamapediatrics.2022.4346).
• Children and adolescents who developed COVID-19 suffered tremendously during the height of the pandemic. A nationwide analysis shows that COVID-19 nearly tripled children’s risks of developing new mental health illnesses, such as attention-deficit/hyperactivity disorder, anxiety, trauma, or stress disorder (Psychiatric Services. 2022 Jun 2. doi: 10.1176/appi.ps.202100646).

In addition to those challenges, young children are facing an increase in respiratory syncytial virus (RSV) infection. We were told the “flu” would be quite bad this year and to beware of monkeypox. However, very little mention is made of the equally distressing “epidemic” of mental health issues, PTSD, anxiety, and depression as we are still in the midst of the COVID pandemic in the United States with almost 400 deaths a day – a very unacceptable number.

Interestingly, we seem to have abandoned the use of masks as protection against COVID and other respiratory diseases, despite their effectiveness. A study in Boston that looked at children in two school districts that did not lift mask mandates demonstrated that mask wearing does indeed lead to significant reductions in the number of pediatric COVID cases. In addition to societal violence and school shootings – which certainly exacerbate anxiety – the fear of dying or the death of a loved one, tied to COVID, may lead to epidemic proportions of PTSD in children. As an article in WebMD noted, “pediatricians are imploring the federal government to declare a national emergency as cases of pediatric respiratory illnesses continue to soar.”

In light of the acknowledged mental health crisis in children, which appears epidemic, I would hope the psychiatric and psychological associations would publicly sound an alarm so that resources could be brought to bear to address this critical issue. I believe doing so would also aid in destigmatizing mental disorders, and increase education and treatment.

Layered on top of those issues are natural disasters, such as the fallout from Tropical Storm Nicole when it recently caused devastation across western Florida. The mental health trauma caused by recent tropical storms seems all but forgotten – except for those who are still suffering. All of this adds up to a society-wide mental health crisis, which seems far more expansive than monkeypox, for example. Yet monkeypox, which did lead to thousands of cases and approximately 29 deaths in the United States, was declared a national public health emergency.

Additionally, RSV killed 100-500 U.S. children under age 5 each year before the pandemic, according to the Centers for Disease Control and Prevention, and currently it appears even worse. Yet despite the seriousness of RSV, it nowhere matches the emotional toll COVID has taken on children globally.

Let’s make it standard practice for children – and of course, adults – to be taught that anxiety is a normal response at times. We should teach that, in some cases, feeling “down” or in despair and even experiencing symptoms of PTSD based on what’s going on personally and within our environment (i.e., COVID, school shootings, etc.) are triggers and responses that can be addressed and often quickly treated by talking with a mental health professional.

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

AT ASH 2022 NEW ORLEANS – Children with Hodgkin lymphoma can be cured with intensive chemotherapy, radiation, and other modalities, but a large majority of those who survive into adulthood then pay a high price in terms of accelerated aging and neurocognitive impairment.

The research findings emerged from a study of nearly 500 individuals in their late 30s, of whom 215 were adult survivors of pediatric Hodgkin lymphoma (HL) and 282 were community controls.

The results showed that HL survivors had a higher epigenetic age relative to their chronological age, compared with controls, translating into epigenetic age acceleration over chronological age equivalent to a mean of 7.7 years.

In addition, this accelerated epigenetic aging in HL survivors was accompanied by neurocognitive deficits, including declines in visual-motor processing, short-term memory, verbal learning and recall, and executive function.

“We found that biologic aging is associated with long-term neurocognitive impairment in Hodgkin lymphoma survivors,” commented lead author AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester (N.Y.) “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”

Dr. Williams presented the findings at the annual meeting of the American Society of Hematology.

“Our hope is that this biomarker may help us identify those survivors most at risk for early-onset cognitive aging and might actually help us gauge a preclinical response to interventions, so that we can see efficacy sooner than some other endpoints,” she said in a media briefing prior to presenting the data.

“This is an area that is very near and dear to my heart,” commented ASH President Jane N. Winter, MD, from Northwestern University, Chicago.

“Pediatricians have been very much wedded to very intensive therapies and intend to incorporate radiation more frequently in their treatment strategies for children than we do in adults,” she said. In addition, “we are very much focused on the long-term consequences of mediastinal radiation causing breast cancer in adults who were treated as young adults or children for Hodgkin lymphoma, but now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated.”

Such HL therapies may exert a significant long-term impact on a patient population “that we otherwise cure,” Dr. Winter commented, pointing to a study by investigators in Germany that showed high unemployment levels among adult survivors of childhood HL, compared with the general population.

Also reacting to Dr. Williams’ findings, Catherine Bollard, MD, of the Center for Cancer and Immunology Research at Children’s National Research Institute in Washington, D.C., said: “My concern actually is that even today, in pediatrics, we’re still giving combined chemotherapy and radiation to the majority of the children with the more advanced disease, and that is not what is happening for the treatment of adult Hodgkin disease.”

She noted that there are now many immune-based therapies available for Hodgkin lymphoma that could soon obviate the need for chemotherapy.
 

Long-term complications

Dr. Williams and colleagues had previously reported that, compared with their healthy siblings, long-term survivors of HL had significantly higher risk (P < .05 for all comparisons) of neurocognitive impairment, anxiety, depression, unemployment, and impaired physical/mental quality of life.

In the current study, they looked specifically at epigenetic aging, and asked all participants to complete a comprehensive neuropsychological battery of tests.

The 215 trial participants who were survivors of pediatric HL came from the St Jude Lifetime Cohort. The mean patient age was 39, and the survivors were an average of 25 years out from their initial diagnosis.

The mean age of the 282 community controls was 36 years. Both the cohort and the controls were all European ancestry.

All participants provided a blood sample. The investigators performed genome-wide methylation studies on DNA derived from peripheral blood mononuclear cells (PBMC), and used the data to calculate epigenetic age according to a biomarker called DNAm PhenoAge. Also known as “Levine’s Clock,” this epigenetic biomarker of aging for life span and health span was developed by Morgan E. Levine, PhD, and colleagues at the University of California, Los Angeles, and other centers.

Dr. Williams and her team determined epigenetic age acceleration by calculating the difference between epigenetic and chronological age, with a higher epigenetic accelerated age suggesting an older biological age relative to the patient’s actual age.

As noted above, they found that HL survivors had a significantly higher epigenetic accelerated age, compared with controls, equivalent to a mean difference of 7.7 years (P < .001).

More than 80% of the survivors had some degree of accelerated aging, compared with only 23% of controls.

HL survivors with higher degrees (second and third tertiles) of accelerated aging had significantly worse visual-motor processing speed compared with survivors in the first (lowest) tertile, with survivors in the second tertile performing on average 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 SD worse (P < .001).

In addition, relative to first tertile survivors, those in the second and third tertiles performed worse on short-term memory, with a decrease of –0.42 SD (P = .011) and 0.59 SD (P < .001), respectively.

HL survivors in the third tertile performed worse than those in the other tertiles on measures of verbal learning (P =.007) and long-term verbal recall (P = .005), and those in the second or third tertiles had an average decline of 0.4 SD, compared with those in first tertile on verbal fluency, a measure of executive function.

The declines in neurocognitive measures among survivors were relatively small but clinically significant, Dr. Williams said, and were likely to prove troublesome for patients.

Dr. Williams added that she and her colleagues are currently compiling data on a comparison of neurocognitive scores between cohort members and control, for future publication, “but I can say that, in the majority of measures that are reported on, survivors do worse.”

The investigators are planning expansion of DNA methylation profiling in the St. Jude Lifetime Cohort and will follow survivors prospectively to look for changes in epigenetic acceleration and how those changes might predict who is most at risk for neurocognitive decline.

The study was supported by grants from the National Cancer Institute. Dr. Williams, Dr. Winter, and Dr. Bollard all reported no relevant financial relationships.

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

AT ASH 2022 NEW ORLEANS – Children with Hodgkin lymphoma can be cured with intensive chemotherapy, radiation, and other modalities, but a large majority of those who survive into adulthood then pay a high price in terms of accelerated aging and neurocognitive impairment.

The research findings emerged from a study of nearly 500 individuals in their late 30s, of whom 215 were adult survivors of pediatric Hodgkin lymphoma (HL) and 282 were community controls.

The results showed that HL survivors had a higher epigenetic age relative to their chronological age, compared with controls, translating into epigenetic age acceleration over chronological age equivalent to a mean of 7.7 years.

In addition, this accelerated epigenetic aging in HL survivors was accompanied by neurocognitive deficits, including declines in visual-motor processing, short-term memory, verbal learning and recall, and executive function.

“We found that biologic aging is associated with long-term neurocognitive impairment in Hodgkin lymphoma survivors,” commented lead author AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester (N.Y.) “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”

Dr. Williams presented the findings at the annual meeting of the American Society of Hematology.

“Our hope is that this biomarker may help us identify those survivors most at risk for early-onset cognitive aging and might actually help us gauge a preclinical response to interventions, so that we can see efficacy sooner than some other endpoints,” she said in a media briefing prior to presenting the data.

“This is an area that is very near and dear to my heart,” commented ASH President Jane N. Winter, MD, from Northwestern University, Chicago.

“Pediatricians have been very much wedded to very intensive therapies and intend to incorporate radiation more frequently in their treatment strategies for children than we do in adults,” she said. In addition, “we are very much focused on the long-term consequences of mediastinal radiation causing breast cancer in adults who were treated as young adults or children for Hodgkin lymphoma, but now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated.”

Such HL therapies may exert a significant long-term impact on a patient population “that we otherwise cure,” Dr. Winter commented, pointing to a study by investigators in Germany that showed high unemployment levels among adult survivors of childhood HL, compared with the general population.

Also reacting to Dr. Williams’ findings, Catherine Bollard, MD, of the Center for Cancer and Immunology Research at Children’s National Research Institute in Washington, D.C., said: “My concern actually is that even today, in pediatrics, we’re still giving combined chemotherapy and radiation to the majority of the children with the more advanced disease, and that is not what is happening for the treatment of adult Hodgkin disease.”

She noted that there are now many immune-based therapies available for Hodgkin lymphoma that could soon obviate the need for chemotherapy.
 

Long-term complications

Dr. Williams and colleagues had previously reported that, compared with their healthy siblings, long-term survivors of HL had significantly higher risk (P < .05 for all comparisons) of neurocognitive impairment, anxiety, depression, unemployment, and impaired physical/mental quality of life.

In the current study, they looked specifically at epigenetic aging, and asked all participants to complete a comprehensive neuropsychological battery of tests.

The 215 trial participants who were survivors of pediatric HL came from the St Jude Lifetime Cohort. The mean patient age was 39, and the survivors were an average of 25 years out from their initial diagnosis.

The mean age of the 282 community controls was 36 years. Both the cohort and the controls were all European ancestry.

All participants provided a blood sample. The investigators performed genome-wide methylation studies on DNA derived from peripheral blood mononuclear cells (PBMC), and used the data to calculate epigenetic age according to a biomarker called DNAm PhenoAge. Also known as “Levine’s Clock,” this epigenetic biomarker of aging for life span and health span was developed by Morgan E. Levine, PhD, and colleagues at the University of California, Los Angeles, and other centers.

Dr. Williams and her team determined epigenetic age acceleration by calculating the difference between epigenetic and chronological age, with a higher epigenetic accelerated age suggesting an older biological age relative to the patient’s actual age.

As noted above, they found that HL survivors had a significantly higher epigenetic accelerated age, compared with controls, equivalent to a mean difference of 7.7 years (P < .001).

More than 80% of the survivors had some degree of accelerated aging, compared with only 23% of controls.

HL survivors with higher degrees (second and third tertiles) of accelerated aging had significantly worse visual-motor processing speed compared with survivors in the first (lowest) tertile, with survivors in the second tertile performing on average 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 SD worse (P < .001).

In addition, relative to first tertile survivors, those in the second and third tertiles performed worse on short-term memory, with a decrease of –0.42 SD (P = .011) and 0.59 SD (P < .001), respectively.

HL survivors in the third tertile performed worse than those in the other tertiles on measures of verbal learning (P =.007) and long-term verbal recall (P = .005), and those in the second or third tertiles had an average decline of 0.4 SD, compared with those in first tertile on verbal fluency, a measure of executive function.

The declines in neurocognitive measures among survivors were relatively small but clinically significant, Dr. Williams said, and were likely to prove troublesome for patients.

Dr. Williams added that she and her colleagues are currently compiling data on a comparison of neurocognitive scores between cohort members and control, for future publication, “but I can say that, in the majority of measures that are reported on, survivors do worse.”

The investigators are planning expansion of DNA methylation profiling in the St. Jude Lifetime Cohort and will follow survivors prospectively to look for changes in epigenetic acceleration and how those changes might predict who is most at risk for neurocognitive decline.

The study was supported by grants from the National Cancer Institute. Dr. Williams, Dr. Winter, and Dr. Bollard all reported no relevant financial relationships.

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

AT ASH 2022 NEW ORLEANS – Children with Hodgkin lymphoma can be cured with intensive chemotherapy, radiation, and other modalities, but a large majority of those who survive into adulthood then pay a high price in terms of accelerated aging and neurocognitive impairment.

The research findings emerged from a study of nearly 500 individuals in their late 30s, of whom 215 were adult survivors of pediatric Hodgkin lymphoma (HL) and 282 were community controls.

The results showed that HL survivors had a higher epigenetic age relative to their chronological age, compared with controls, translating into epigenetic age acceleration over chronological age equivalent to a mean of 7.7 years.

In addition, this accelerated epigenetic aging in HL survivors was accompanied by neurocognitive deficits, including declines in visual-motor processing, short-term memory, verbal learning and recall, and executive function.

“We found that biologic aging is associated with long-term neurocognitive impairment in Hodgkin lymphoma survivors,” commented lead author AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester (N.Y.) “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”

Dr. Williams presented the findings at the annual meeting of the American Society of Hematology.

“Our hope is that this biomarker may help us identify those survivors most at risk for early-onset cognitive aging and might actually help us gauge a preclinical response to interventions, so that we can see efficacy sooner than some other endpoints,” she said in a media briefing prior to presenting the data.

“This is an area that is very near and dear to my heart,” commented ASH President Jane N. Winter, MD, from Northwestern University, Chicago.

“Pediatricians have been very much wedded to very intensive therapies and intend to incorporate radiation more frequently in their treatment strategies for children than we do in adults,” she said. In addition, “we are very much focused on the long-term consequences of mediastinal radiation causing breast cancer in adults who were treated as young adults or children for Hodgkin lymphoma, but now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated.”

Such HL therapies may exert a significant long-term impact on a patient population “that we otherwise cure,” Dr. Winter commented, pointing to a study by investigators in Germany that showed high unemployment levels among adult survivors of childhood HL, compared with the general population.

Also reacting to Dr. Williams’ findings, Catherine Bollard, MD, of the Center for Cancer and Immunology Research at Children’s National Research Institute in Washington, D.C., said: “My concern actually is that even today, in pediatrics, we’re still giving combined chemotherapy and radiation to the majority of the children with the more advanced disease, and that is not what is happening for the treatment of adult Hodgkin disease.”

She noted that there are now many immune-based therapies available for Hodgkin lymphoma that could soon obviate the need for chemotherapy.
 

Long-term complications

Dr. Williams and colleagues had previously reported that, compared with their healthy siblings, long-term survivors of HL had significantly higher risk (P < .05 for all comparisons) of neurocognitive impairment, anxiety, depression, unemployment, and impaired physical/mental quality of life.

In the current study, they looked specifically at epigenetic aging, and asked all participants to complete a comprehensive neuropsychological battery of tests.

The 215 trial participants who were survivors of pediatric HL came from the St Jude Lifetime Cohort. The mean patient age was 39, and the survivors were an average of 25 years out from their initial diagnosis.

The mean age of the 282 community controls was 36 years. Both the cohort and the controls were all European ancestry.

All participants provided a blood sample. The investigators performed genome-wide methylation studies on DNA derived from peripheral blood mononuclear cells (PBMC), and used the data to calculate epigenetic age according to a biomarker called DNAm PhenoAge. Also known as “Levine’s Clock,” this epigenetic biomarker of aging for life span and health span was developed by Morgan E. Levine, PhD, and colleagues at the University of California, Los Angeles, and other centers.

Dr. Williams and her team determined epigenetic age acceleration by calculating the difference between epigenetic and chronological age, with a higher epigenetic accelerated age suggesting an older biological age relative to the patient’s actual age.

As noted above, they found that HL survivors had a significantly higher epigenetic accelerated age, compared with controls, equivalent to a mean difference of 7.7 years (P < .001).

More than 80% of the survivors had some degree of accelerated aging, compared with only 23% of controls.

HL survivors with higher degrees (second and third tertiles) of accelerated aging had significantly worse visual-motor processing speed compared with survivors in the first (lowest) tertile, with survivors in the second tertile performing on average 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 SD worse (P < .001).

In addition, relative to first tertile survivors, those in the second and third tertiles performed worse on short-term memory, with a decrease of –0.42 SD (P = .011) and 0.59 SD (P < .001), respectively.

HL survivors in the third tertile performed worse than those in the other tertiles on measures of verbal learning (P =.007) and long-term verbal recall (P = .005), and those in the second or third tertiles had an average decline of 0.4 SD, compared with those in first tertile on verbal fluency, a measure of executive function.

The declines in neurocognitive measures among survivors were relatively small but clinically significant, Dr. Williams said, and were likely to prove troublesome for patients.

Dr. Williams added that she and her colleagues are currently compiling data on a comparison of neurocognitive scores between cohort members and control, for future publication, “but I can say that, in the majority of measures that are reported on, survivors do worse.”

The investigators are planning expansion of DNA methylation profiling in the St. Jude Lifetime Cohort and will follow survivors prospectively to look for changes in epigenetic acceleration and how those changes might predict who is most at risk for neurocognitive decline.

The study was supported by grants from the National Cancer Institute. Dr. Williams, Dr. Winter, and Dr. Bollard all reported no relevant financial relationships.

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