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. Food and Drug Administration has approved nadofaragene firadenovec-vncg (Adstiladrin), the first gene therapy for adults with bladder cancer.

The adenovirus vector based gene therapy is indicated for adults with high-risk non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors who are unresponsive to Bacillus Calmette-Guérin (BCG) therapy.

Patients with BCG-unresponsive disease “have historically had limited treatment options other than bladder removal surgery. The approval of Adstiladrin is therefore a significant advance in the current treatment landscape and provides a novel treatment option,” Steven Boorjian, MD, a Mayo Clinic urologist and lead investigator on that agent’s approval trial, said in a press release Dec. 16 from gene therapy developer Ferring Pharmaceuticals.

Nadofaragene firadenovec is instilled into the bladder via urinary catheter once every 3 months for up to a year. The adenovirus vector enters the cells of the bladder wall, releasing a gene that directs the cells to secrete high quantities of interferon alfa-2b, a naturally occurring cancer-fighting protein.

Approval was based on a multicenter clinical study that included 98 evaluable patients with high-risk, BCG-unresponsive disease. Overall, 51% achieved a complete response with a disappearance of all signs of cancer on cystoscopy, biopsied tissue, and urine. The median duration of response was 9.7 months. Overall, 46% of responding patients remained in complete response for at least 1 year.

The most common adverse events were instillation site discharge (33%), fatigue (24%), bladder spasm (20%), micturition urgency (19%), and hematuria (17%). The discontinuation rate due to adverse events was 1.9%.

Ferring expects the gene therapy to be commercially available in the United States in the second half of 2023.

The cost of the gene therapy has not yet been announced, but a cost effectiveness analysis from the Institute for Clinical and Economic Review, published last year, put the range for the annual cost between $158,600 and $262,000.

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

The U.S. Food and Drug Administration has approved nadofaragene firadenovec-vncg (Adstiladrin), the first gene therapy for adults with bladder cancer.

The adenovirus vector based gene therapy is indicated for adults with high-risk non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors who are unresponsive to Bacillus Calmette-Guérin (BCG) therapy.

Patients with BCG-unresponsive disease “have historically had limited treatment options other than bladder removal surgery. The approval of Adstiladrin is therefore a significant advance in the current treatment landscape and provides a novel treatment option,” Steven Boorjian, MD, a Mayo Clinic urologist and lead investigator on that agent’s approval trial, said in a press release Dec. 16 from gene therapy developer Ferring Pharmaceuticals.

Nadofaragene firadenovec is instilled into the bladder via urinary catheter once every 3 months for up to a year. The adenovirus vector enters the cells of the bladder wall, releasing a gene that directs the cells to secrete high quantities of interferon alfa-2b, a naturally occurring cancer-fighting protein.

Approval was based on a multicenter clinical study that included 98 evaluable patients with high-risk, BCG-unresponsive disease. Overall, 51% achieved a complete response with a disappearance of all signs of cancer on cystoscopy, biopsied tissue, and urine. The median duration of response was 9.7 months. Overall, 46% of responding patients remained in complete response for at least 1 year.

The most common adverse events were instillation site discharge (33%), fatigue (24%), bladder spasm (20%), micturition urgency (19%), and hematuria (17%). The discontinuation rate due to adverse events was 1.9%.

Ferring expects the gene therapy to be commercially available in the United States in the second half of 2023.

The cost of the gene therapy has not yet been announced, but a cost effectiveness analysis from the Institute for Clinical and Economic Review, published last year, put the range for the annual cost between $158,600 and $262,000.

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

The U.S. Food and Drug Administration has approved nadofaragene firadenovec-vncg (Adstiladrin), the first gene therapy for adults with bladder cancer.

The adenovirus vector based gene therapy is indicated for adults with high-risk non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors who are unresponsive to Bacillus Calmette-Guérin (BCG) therapy.

Patients with BCG-unresponsive disease “have historically had limited treatment options other than bladder removal surgery. The approval of Adstiladrin is therefore a significant advance in the current treatment landscape and provides a novel treatment option,” Steven Boorjian, MD, a Mayo Clinic urologist and lead investigator on that agent’s approval trial, said in a press release Dec. 16 from gene therapy developer Ferring Pharmaceuticals.

Nadofaragene firadenovec is instilled into the bladder via urinary catheter once every 3 months for up to a year. The adenovirus vector enters the cells of the bladder wall, releasing a gene that directs the cells to secrete high quantities of interferon alfa-2b, a naturally occurring cancer-fighting protein.

Approval was based on a multicenter clinical study that included 98 evaluable patients with high-risk, BCG-unresponsive disease. Overall, 51% achieved a complete response with a disappearance of all signs of cancer on cystoscopy, biopsied tissue, and urine. The median duration of response was 9.7 months. Overall, 46% of responding patients remained in complete response for at least 1 year.

The most common adverse events were instillation site discharge (33%), fatigue (24%), bladder spasm (20%), micturition urgency (19%), and hematuria (17%). The discontinuation rate due to adverse events was 1.9%.

Ferring expects the gene therapy to be commercially available in the United States in the second half of 2023.

The cost of the gene therapy has not yet been announced, but a cost effectiveness analysis from the Institute for Clinical and Economic Review, published last year, put the range for the annual cost between $158,600 and $262,000.

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

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.
 

Outpatient behavioral health treatment (OPBHT) for patients newly diagnosed with depression, substance use disorder, or other behavioral health condition (BHC) is cost-effective.

Results of a large retrospective study showed that patients newly diagnosed with a BHC who receive OPBHT following diagnosis incur lower medical and pharmacy costs over roughly the next 1 to 2 years, compared with peers who don’t receive OPBHT.

“Our findings suggest that promoting OPBHT as part of a population health strategy is associated with improved overall medical spending, particularly among adults,” the investigators write.

The study was published online in JAMA Network Open.
 

Common, undertreated

Nearly a quarter of adults in the United States have a BHC, and they incur greater medical costs than those without a BHC. However, diagnosis of a BHC is often delayed, and most affected individuals receive little to no treatment.

In their cost analysis, Johanna Bellon, PhD, and colleagues with Evernorth Health, St. Louis, analyzed commercial insurance claims data for 203,401 U.S. individuals newly diagnosed with one or more BHCs between 2017 and 2018.

About half of participants had depression and/or anxiety, 11% had substance use or alcohol use disorder, and 6% had a higher-acuity diagnosis, such as bipolar disorder, severe depression, eating disorder, psychotic disorder, or autism spectrum disorder.

About 1 in 5 (22%) had at least one chronic medical condition along with their BHC.

The researchers found that having at least one OPBHT visit was associated with lower medical and pharmacy costs during 15- and 27-month follow-up periods.

Over 15 months, the adjusted mean per member per month (PMPM) medical/pharmacy cost was $686 with no OPBHT visit, compared with $571 with one or more OPBHT visits.

Over 27 months, the adjusted mean PMPM was $464 with no OPBHT, versus $391 with one or more OPBHT visits.
 

Dose-response effect

In addition, there was a “dose-response” relationship between OPBHT and medical/pharmacy costs, such that estimated cost savings were significantly lower in the treated versus the untreated groups at almost every level of treatment.

“Our findings were also largely age independent, especially over 15 months, suggesting that OPBHT has favorable effects among children, young adults, and adults,” the researchers report.

“This is promising given that disease etiology and progression, treatment paradigms, presence of comorbid medical conditions, and overall medical and pharmacy costs differ among the three groups,” they say.

Notably, the dataset largely encompassed in-person OPBHT, because the study period preceded the transition into virtual care that occurred in 2020.

However, overall use of OPBHT was low – older adults, adults with lower income, individuals with comorbid medical conditions, and persons of racial and ethnic minorities were less likely to receive OPBHT, they found.

“These findings support the cost-effectiveness of practitioner- and insurance-based interventions to increase OPBHT utilization, which is a critical resource as new BHC diagnoses continue to increase,” the researchers say.

“Future research should validate these findings in other populations, including government-insured individuals, and explore data by chronic disease category, over longer time horizons, by type and quality of OPBHT, by type of medical spending, within subpopulations with BHCs, and including virtual and digital behavioral health services,” they suggest.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Outpatient behavioral health treatment (OPBHT) for patients newly diagnosed with depression, substance use disorder, or other behavioral health condition (BHC) is cost-effective.

Results of a large retrospective study showed that patients newly diagnosed with a BHC who receive OPBHT following diagnosis incur lower medical and pharmacy costs over roughly the next 1 to 2 years, compared with peers who don’t receive OPBHT.

“Our findings suggest that promoting OPBHT as part of a population health strategy is associated with improved overall medical spending, particularly among adults,” the investigators write.

The study was published online in JAMA Network Open.
 

Common, undertreated

Nearly a quarter of adults in the United States have a BHC, and they incur greater medical costs than those without a BHC. However, diagnosis of a BHC is often delayed, and most affected individuals receive little to no treatment.

In their cost analysis, Johanna Bellon, PhD, and colleagues with Evernorth Health, St. Louis, analyzed commercial insurance claims data for 203,401 U.S. individuals newly diagnosed with one or more BHCs between 2017 and 2018.

About half of participants had depression and/or anxiety, 11% had substance use or alcohol use disorder, and 6% had a higher-acuity diagnosis, such as bipolar disorder, severe depression, eating disorder, psychotic disorder, or autism spectrum disorder.

About 1 in 5 (22%) had at least one chronic medical condition along with their BHC.

The researchers found that having at least one OPBHT visit was associated with lower medical and pharmacy costs during 15- and 27-month follow-up periods.

Over 15 months, the adjusted mean per member per month (PMPM) medical/pharmacy cost was $686 with no OPBHT visit, compared with $571 with one or more OPBHT visits.

Over 27 months, the adjusted mean PMPM was $464 with no OPBHT, versus $391 with one or more OPBHT visits.
 

Dose-response effect

In addition, there was a “dose-response” relationship between OPBHT and medical/pharmacy costs, such that estimated cost savings were significantly lower in the treated versus the untreated groups at almost every level of treatment.

“Our findings were also largely age independent, especially over 15 months, suggesting that OPBHT has favorable effects among children, young adults, and adults,” the researchers report.

“This is promising given that disease etiology and progression, treatment paradigms, presence of comorbid medical conditions, and overall medical and pharmacy costs differ among the three groups,” they say.

Notably, the dataset largely encompassed in-person OPBHT, because the study period preceded the transition into virtual care that occurred in 2020.

However, overall use of OPBHT was low – older adults, adults with lower income, individuals with comorbid medical conditions, and persons of racial and ethnic minorities were less likely to receive OPBHT, they found.

“These findings support the cost-effectiveness of practitioner- and insurance-based interventions to increase OPBHT utilization, which is a critical resource as new BHC diagnoses continue to increase,” the researchers say.

“Future research should validate these findings in other populations, including government-insured individuals, and explore data by chronic disease category, over longer time horizons, by type and quality of OPBHT, by type of medical spending, within subpopulations with BHCs, and including virtual and digital behavioral health services,” they suggest.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Outpatient behavioral health treatment (OPBHT) for patients newly diagnosed with depression, substance use disorder, or other behavioral health condition (BHC) is cost-effective.

Results of a large retrospective study showed that patients newly diagnosed with a BHC who receive OPBHT following diagnosis incur lower medical and pharmacy costs over roughly the next 1 to 2 years, compared with peers who don’t receive OPBHT.

“Our findings suggest that promoting OPBHT as part of a population health strategy is associated with improved overall medical spending, particularly among adults,” the investigators write.

The study was published online in JAMA Network Open.
 

Common, undertreated

Nearly a quarter of adults in the United States have a BHC, and they incur greater medical costs than those without a BHC. However, diagnosis of a BHC is often delayed, and most affected individuals receive little to no treatment.

In their cost analysis, Johanna Bellon, PhD, and colleagues with Evernorth Health, St. Louis, analyzed commercial insurance claims data for 203,401 U.S. individuals newly diagnosed with one or more BHCs between 2017 and 2018.

About half of participants had depression and/or anxiety, 11% had substance use or alcohol use disorder, and 6% had a higher-acuity diagnosis, such as bipolar disorder, severe depression, eating disorder, psychotic disorder, or autism spectrum disorder.

About 1 in 5 (22%) had at least one chronic medical condition along with their BHC.

The researchers found that having at least one OPBHT visit was associated with lower medical and pharmacy costs during 15- and 27-month follow-up periods.

Over 15 months, the adjusted mean per member per month (PMPM) medical/pharmacy cost was $686 with no OPBHT visit, compared with $571 with one or more OPBHT visits.

Over 27 months, the adjusted mean PMPM was $464 with no OPBHT, versus $391 with one or more OPBHT visits.
 

Dose-response effect

In addition, there was a “dose-response” relationship between OPBHT and medical/pharmacy costs, such that estimated cost savings were significantly lower in the treated versus the untreated groups at almost every level of treatment.

“Our findings were also largely age independent, especially over 15 months, suggesting that OPBHT has favorable effects among children, young adults, and adults,” the researchers report.

“This is promising given that disease etiology and progression, treatment paradigms, presence of comorbid medical conditions, and overall medical and pharmacy costs differ among the three groups,” they say.

Notably, the dataset largely encompassed in-person OPBHT, because the study period preceded the transition into virtual care that occurred in 2020.

However, overall use of OPBHT was low – older adults, adults with lower income, individuals with comorbid medical conditions, and persons of racial and ethnic minorities were less likely to receive OPBHT, they found.

“These findings support the cost-effectiveness of practitioner- and insurance-based interventions to increase OPBHT utilization, which is a critical resource as new BHC diagnoses continue to increase,” the researchers say.

“Future research should validate these findings in other populations, including government-insured individuals, and explore data by chronic disease category, over longer time horizons, by type and quality of OPBHT, by type of medical spending, within subpopulations with BHCs, and including virtual and digital behavioral health services,” they suggest.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

A brief aerobic exercise intervention can augment the benefits of exposure therapy for PTSD, new research suggests.

Investigators randomly assigned individuals with PTSD to receive either exposure therapy with aerobic exercise or exposure therapy with passive stretching for 9 weeks. At 6 months post intervention, participants in the aerobic exercise group showed greater reductions in PTSD severity, compared with those in the stretching group.

“There is a critical need to improve outcomes for treating people with PTSD, and this finding points to one potentially cheap and ready-to-use strategy that all clinicians could employ with most patients,” lead author Richard Bryant, MPsych, PhD, DSc, director of the Traumatic Stress Clinic and Scientia Professor of Psychology at the University of New South Wales, Sydney, told this news organization.

The study was published online in The Lancet Psychiatry.
 

Promoting BDNF

“Trauma-focused psychotherapy is the recommended treatment for PTSD, but up to half of patients do not respond to this treatment,” Dr. Bryant said.

“We know that brain-derived neurotrophic factors [BDNF] are critical for synaptic plasticity, which underpins the learning that occurs in therapy so that reminders of trauma are no longer fear-provoking,” he continued. “Preclinical animal and human research inform us that brief aerobic exercise can promote BDNF and new learning that inhibits fear responses.”

The researchers “hypothesized that brief exercise after exposure therapy to trauma memories – which is the key ingredient of trauma-focused psychotherapy – would lead to greater reductions in PTSD, relative to standard trauma-focused therapy,” he said.

To investigate the question, the researchers randomly assigned 130 adults with PTSD (mean age, 39 years; 61% female; 76% White) to receive nine 90-minute sessions of exposure therapy with either aerobic exercise or passive stretching (n = 65 in each group).

There were no differences at baseline in sociodemographic characteristics or psychopathology measures, although the mean age of the stretching group was slightly older than that of the aerobic group (40 years vs. 37 years, respectively), and there was a slightly higher proportion of women in the stretching group (68% vs. 54%).

Participants did not differ on weekly exercise either at baseline, immediately post treatment, or at 6-week follow-up.

PTSD severity (the primary outcome) was measured using the clinician-administered PTSD scale CAPS-2, with assessments conducted at baseline, 1 week post treatment, and 6 months post treatment.

The aerobic exercise regimen was tailored to each participant, based on an assessment of his/her aerobic target zone.

The exposure therapy sessions were identical for both groups. Following the exposure sessions, participants engaged in their respective exercises: Those in the passive stretching group engaged in 20 minutes of exercise, while those in the aerobic group participated in a total of 20 minutes of exercise, with 10 conducted at their personal aerobic target heart rate.

“This level of exercise was chosen because BDNF concentration in the serum is increased by two 3-minute bouts of aerobic exercise, and 10 minutes of aerobic exercise can facilitate extinction learning,” the authors explained.

The aerobic activity consisted of running on a stepper exercise platform while having cardiac activity recorded. A small portion (10%) of the therapy sessions were recorded and rated for treatment fidelity.

Change in PTSD was the primary outcome, with secondary outcomes consisting of changes in depression, anxiety, alcohol use disorder, and posttraumatic cognitions.
 

Few barriers

The researchers found no significant differences in PTSD severity, as measured by CAPS-2 score, between treatment groups at 10 weeks – that is, immediately post treatment (mean difference, 7.0; 95% confidence interval, –2.3 to 16.4; P = .14).

However, significantly greater reductions in PTSD severity were found in the aerobic versus the stretching group at 6-month follow-up (mean difference, 12.1;95% CI, 2.4-21.8; P = .023), pointing to a “moderate effect size” (d = 0.6; 95% CI, 0.1-1.1]).

Although there were no differences found at 6-month assessment between rates of PTSD diagnosis (25% of the aerobic vs 27% of the stretching group), more participants in the aerobic group reached a “minimal clinically important difference,” compared to those in the stretching group (96% vs. 84%, respectively, x² = 4.4; P = .036). 

There were also superior benefits found in the aerobic versus the stretching group on depression severity at 6 months (a secondary outcome), with a mean difference in Beck Depression Inventory-2 score of 5.7 (95% CI, 0.5-10.9; P = .022), yielding a “moderate effect size” (d = 0.5; 95% CI, 0.1-1.0]).

There were no adverse events associated with the intervention, and almost all the sessions (88%) complied with the treatment protocol.

The researchers noted several limitations. For example, they did not obtain plasma to measure BDNF concentrations, so they could not “infer whether the mechanism of change involved BDNF.”

In addition, they did not perform sex-specific analyses. “Future studies could increase the sample size to investigate sex differences because females display less BDNF change following exercise than do males,” they wrote.

Nevertheless, the study “provides initial evidence of a simple and accessible strategy that clinicians could readily apply in combination with exposure therapy,” they stated. “Whereas many pharmacologic interventions pose barriers, including cost, requirement for prescriptions, and patient resistance to drugs, exercise offers clinicians a strategy that can be implemented with few barriers.”

Dr. Bryant emphasized that one study “does not represent a body of evidence, and so it is essential that this finding be replicated in other trials before it can be recommended for clinical use.” He noted that other trials are “currently underway.”
 

Easy augmentation

In a comment, Barbara Rothbaum, PhD, professor in psychiatry and director of the Trauma and Anxiety Recovery Program at Emory University, Atlanta, called it a “well-controlled trial augmenting exposure therapy for PTSD with brief aerobic exercise and finding some benefits of the augmented condition at 6 months posttreatment but not immediately posttreatment.”

The study’s methodology – that is, using independent standard assessment of PTSD and rating audio recordings of therapy sessions for treatment fidelity and quality – can lead us to “be confident in their [the researchers’] conclusions,” she said.

Dr. Rothbaum, who was not associated with this study, described research into methods to augment exposure therapy for PTSD as “timely and clinically relevant.”

Exercise “would be an easy augmentation for many clinicians if it is helpful,” she noted.

The study was funded by the Australian National Health and Medical Research Council. The authors and Dr. Rothbaum reported no relevant financial relationships.

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

A brief aerobic exercise intervention can augment the benefits of exposure therapy for PTSD, new research suggests.

Investigators randomly assigned individuals with PTSD to receive either exposure therapy with aerobic exercise or exposure therapy with passive stretching for 9 weeks. At 6 months post intervention, participants in the aerobic exercise group showed greater reductions in PTSD severity, compared with those in the stretching group.

“There is a critical need to improve outcomes for treating people with PTSD, and this finding points to one potentially cheap and ready-to-use strategy that all clinicians could employ with most patients,” lead author Richard Bryant, MPsych, PhD, DSc, director of the Traumatic Stress Clinic and Scientia Professor of Psychology at the University of New South Wales, Sydney, told this news organization.

The study was published online in The Lancet Psychiatry.
 

Promoting BDNF

“Trauma-focused psychotherapy is the recommended treatment for PTSD, but up to half of patients do not respond to this treatment,” Dr. Bryant said.

“We know that brain-derived neurotrophic factors [BDNF] are critical for synaptic plasticity, which underpins the learning that occurs in therapy so that reminders of trauma are no longer fear-provoking,” he continued. “Preclinical animal and human research inform us that brief aerobic exercise can promote BDNF and new learning that inhibits fear responses.”

The researchers “hypothesized that brief exercise after exposure therapy to trauma memories – which is the key ingredient of trauma-focused psychotherapy – would lead to greater reductions in PTSD, relative to standard trauma-focused therapy,” he said.

To investigate the question, the researchers randomly assigned 130 adults with PTSD (mean age, 39 years; 61% female; 76% White) to receive nine 90-minute sessions of exposure therapy with either aerobic exercise or passive stretching (n = 65 in each group).

There were no differences at baseline in sociodemographic characteristics or psychopathology measures, although the mean age of the stretching group was slightly older than that of the aerobic group (40 years vs. 37 years, respectively), and there was a slightly higher proportion of women in the stretching group (68% vs. 54%).

Participants did not differ on weekly exercise either at baseline, immediately post treatment, or at 6-week follow-up.

PTSD severity (the primary outcome) was measured using the clinician-administered PTSD scale CAPS-2, with assessments conducted at baseline, 1 week post treatment, and 6 months post treatment.

The aerobic exercise regimen was tailored to each participant, based on an assessment of his/her aerobic target zone.

The exposure therapy sessions were identical for both groups. Following the exposure sessions, participants engaged in their respective exercises: Those in the passive stretching group engaged in 20 minutes of exercise, while those in the aerobic group participated in a total of 20 minutes of exercise, with 10 conducted at their personal aerobic target heart rate.

“This level of exercise was chosen because BDNF concentration in the serum is increased by two 3-minute bouts of aerobic exercise, and 10 minutes of aerobic exercise can facilitate extinction learning,” the authors explained.

The aerobic activity consisted of running on a stepper exercise platform while having cardiac activity recorded. A small portion (10%) of the therapy sessions were recorded and rated for treatment fidelity.

Change in PTSD was the primary outcome, with secondary outcomes consisting of changes in depression, anxiety, alcohol use disorder, and posttraumatic cognitions.
 

Few barriers

The researchers found no significant differences in PTSD severity, as measured by CAPS-2 score, between treatment groups at 10 weeks – that is, immediately post treatment (mean difference, 7.0; 95% confidence interval, –2.3 to 16.4; P = .14).

However, significantly greater reductions in PTSD severity were found in the aerobic versus the stretching group at 6-month follow-up (mean difference, 12.1;95% CI, 2.4-21.8; P = .023), pointing to a “moderate effect size” (d = 0.6; 95% CI, 0.1-1.1]).

Although there were no differences found at 6-month assessment between rates of PTSD diagnosis (25% of the aerobic vs 27% of the stretching group), more participants in the aerobic group reached a “minimal clinically important difference,” compared to those in the stretching group (96% vs. 84%, respectively, x² = 4.4; P = .036). 

There were also superior benefits found in the aerobic versus the stretching group on depression severity at 6 months (a secondary outcome), with a mean difference in Beck Depression Inventory-2 score of 5.7 (95% CI, 0.5-10.9; P = .022), yielding a “moderate effect size” (d = 0.5; 95% CI, 0.1-1.0]).

There were no adverse events associated with the intervention, and almost all the sessions (88%) complied with the treatment protocol.

The researchers noted several limitations. For example, they did not obtain plasma to measure BDNF concentrations, so they could not “infer whether the mechanism of change involved BDNF.”

In addition, they did not perform sex-specific analyses. “Future studies could increase the sample size to investigate sex differences because females display less BDNF change following exercise than do males,” they wrote.

Nevertheless, the study “provides initial evidence of a simple and accessible strategy that clinicians could readily apply in combination with exposure therapy,” they stated. “Whereas many pharmacologic interventions pose barriers, including cost, requirement for prescriptions, and patient resistance to drugs, exercise offers clinicians a strategy that can be implemented with few barriers.”

Dr. Bryant emphasized that one study “does not represent a body of evidence, and so it is essential that this finding be replicated in other trials before it can be recommended for clinical use.” He noted that other trials are “currently underway.”
 

Easy augmentation

In a comment, Barbara Rothbaum, PhD, professor in psychiatry and director of the Trauma and Anxiety Recovery Program at Emory University, Atlanta, called it a “well-controlled trial augmenting exposure therapy for PTSD with brief aerobic exercise and finding some benefits of the augmented condition at 6 months posttreatment but not immediately posttreatment.”

The study’s methodology – that is, using independent standard assessment of PTSD and rating audio recordings of therapy sessions for treatment fidelity and quality – can lead us to “be confident in their [the researchers’] conclusions,” she said.

Dr. Rothbaum, who was not associated with this study, described research into methods to augment exposure therapy for PTSD as “timely and clinically relevant.”

Exercise “would be an easy augmentation for many clinicians if it is helpful,” she noted.

The study was funded by the Australian National Health and Medical Research Council. The authors and Dr. Rothbaum reported no relevant financial relationships.

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

A brief aerobic exercise intervention can augment the benefits of exposure therapy for PTSD, new research suggests.

Investigators randomly assigned individuals with PTSD to receive either exposure therapy with aerobic exercise or exposure therapy with passive stretching for 9 weeks. At 6 months post intervention, participants in the aerobic exercise group showed greater reductions in PTSD severity, compared with those in the stretching group.

“There is a critical need to improve outcomes for treating people with PTSD, and this finding points to one potentially cheap and ready-to-use strategy that all clinicians could employ with most patients,” lead author Richard Bryant, MPsych, PhD, DSc, director of the Traumatic Stress Clinic and Scientia Professor of Psychology at the University of New South Wales, Sydney, told this news organization.

The study was published online in The Lancet Psychiatry.
 

Promoting BDNF

“Trauma-focused psychotherapy is the recommended treatment for PTSD, but up to half of patients do not respond to this treatment,” Dr. Bryant said.

“We know that brain-derived neurotrophic factors [BDNF] are critical for synaptic plasticity, which underpins the learning that occurs in therapy so that reminders of trauma are no longer fear-provoking,” he continued. “Preclinical animal and human research inform us that brief aerobic exercise can promote BDNF and new learning that inhibits fear responses.”

The researchers “hypothesized that brief exercise after exposure therapy to trauma memories – which is the key ingredient of trauma-focused psychotherapy – would lead to greater reductions in PTSD, relative to standard trauma-focused therapy,” he said.

To investigate the question, the researchers randomly assigned 130 adults with PTSD (mean age, 39 years; 61% female; 76% White) to receive nine 90-minute sessions of exposure therapy with either aerobic exercise or passive stretching (n = 65 in each group).

There were no differences at baseline in sociodemographic characteristics or psychopathology measures, although the mean age of the stretching group was slightly older than that of the aerobic group (40 years vs. 37 years, respectively), and there was a slightly higher proportion of women in the stretching group (68% vs. 54%).

Participants did not differ on weekly exercise either at baseline, immediately post treatment, or at 6-week follow-up.

PTSD severity (the primary outcome) was measured using the clinician-administered PTSD scale CAPS-2, with assessments conducted at baseline, 1 week post treatment, and 6 months post treatment.

The aerobic exercise regimen was tailored to each participant, based on an assessment of his/her aerobic target zone.

The exposure therapy sessions were identical for both groups. Following the exposure sessions, participants engaged in their respective exercises: Those in the passive stretching group engaged in 20 minutes of exercise, while those in the aerobic group participated in a total of 20 minutes of exercise, with 10 conducted at their personal aerobic target heart rate.

“This level of exercise was chosen because BDNF concentration in the serum is increased by two 3-minute bouts of aerobic exercise, and 10 minutes of aerobic exercise can facilitate extinction learning,” the authors explained.

The aerobic activity consisted of running on a stepper exercise platform while having cardiac activity recorded. A small portion (10%) of the therapy sessions were recorded and rated for treatment fidelity.

Change in PTSD was the primary outcome, with secondary outcomes consisting of changes in depression, anxiety, alcohol use disorder, and posttraumatic cognitions.
 

Few barriers

The researchers found no significant differences in PTSD severity, as measured by CAPS-2 score, between treatment groups at 10 weeks – that is, immediately post treatment (mean difference, 7.0; 95% confidence interval, –2.3 to 16.4; P = .14).

However, significantly greater reductions in PTSD severity were found in the aerobic versus the stretching group at 6-month follow-up (mean difference, 12.1;95% CI, 2.4-21.8; P = .023), pointing to a “moderate effect size” (d = 0.6; 95% CI, 0.1-1.1]).

Although there were no differences found at 6-month assessment between rates of PTSD diagnosis (25% of the aerobic vs 27% of the stretching group), more participants in the aerobic group reached a “minimal clinically important difference,” compared to those in the stretching group (96% vs. 84%, respectively, x² = 4.4; P = .036). 

There were also superior benefits found in the aerobic versus the stretching group on depression severity at 6 months (a secondary outcome), with a mean difference in Beck Depression Inventory-2 score of 5.7 (95% CI, 0.5-10.9; P = .022), yielding a “moderate effect size” (d = 0.5; 95% CI, 0.1-1.0]).

There were no adverse events associated with the intervention, and almost all the sessions (88%) complied with the treatment protocol.

The researchers noted several limitations. For example, they did not obtain plasma to measure BDNF concentrations, so they could not “infer whether the mechanism of change involved BDNF.”

In addition, they did not perform sex-specific analyses. “Future studies could increase the sample size to investigate sex differences because females display less BDNF change following exercise than do males,” they wrote.

Nevertheless, the study “provides initial evidence of a simple and accessible strategy that clinicians could readily apply in combination with exposure therapy,” they stated. “Whereas many pharmacologic interventions pose barriers, including cost, requirement for prescriptions, and patient resistance to drugs, exercise offers clinicians a strategy that can be implemented with few barriers.”

Dr. Bryant emphasized that one study “does not represent a body of evidence, and so it is essential that this finding be replicated in other trials before it can be recommended for clinical use.” He noted that other trials are “currently underway.”
 

Easy augmentation

In a comment, Barbara Rothbaum, PhD, professor in psychiatry and director of the Trauma and Anxiety Recovery Program at Emory University, Atlanta, called it a “well-controlled trial augmenting exposure therapy for PTSD with brief aerobic exercise and finding some benefits of the augmented condition at 6 months posttreatment but not immediately posttreatment.”

The study’s methodology – that is, using independent standard assessment of PTSD and rating audio recordings of therapy sessions for treatment fidelity and quality – can lead us to “be confident in their [the researchers’] conclusions,” she said.

Dr. Rothbaum, who was not associated with this study, described research into methods to augment exposure therapy for PTSD as “timely and clinically relevant.”

Exercise “would be an easy augmentation for many clinicians if it is helpful,” she noted.

The study was funded by the Australian National Health and Medical Research Council. The authors and Dr. Rothbaum reported no relevant financial relationships.

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

SAN FRANCISCO – In a widely anticipated report, researchers reported that a phase 3 study showed statistically significant improvements in patients with agitation related to Alzheimer’s disease (AD) who took the atypical antipsychotic brexpiprazole (Rexulti).

Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.

“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”

Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.

In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.

Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
 

Three trials

All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.

Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.

The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”

The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).

In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).

In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.

The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.

The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.

Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.

University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”

But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”

What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.

Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
 

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

SAN FRANCISCO – In a widely anticipated report, researchers reported that a phase 3 study showed statistically significant improvements in patients with agitation related to Alzheimer’s disease (AD) who took the atypical antipsychotic brexpiprazole (Rexulti).

Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.

“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”

Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.

In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.

Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
 

Three trials

All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.

Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.

The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”

The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).

In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).

In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.

The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.

The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.

Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.

University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”

But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”

What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.

Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
 

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

SAN FRANCISCO – In a widely anticipated report, researchers reported that a phase 3 study showed statistically significant improvements in patients with agitation related to Alzheimer’s disease (AD) who took the atypical antipsychotic brexpiprazole (Rexulti).

Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.

“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”

Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.

In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.

Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
 

Three trials

All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.

Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.

The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”

The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).

In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).

In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.

The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.

The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.

Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.

University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”

But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”

What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.

Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
 

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.

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.

Findings from the LymphVAX study recently presented at the San Antonio Breast Cancer Symposium show that relatively few women with breast cancer who are at risk for lymphedema develop lymph node swelling after receiving an mRNA COVID-19 vaccine.

Lymph node swelling can be a particularly troubling side effect, since it could be mistaken for breast cancer progression. In this study, of 621 women who received the first dose of an mRNA COVID-19 vaccine, 9.8% developed lymph node swelling as compared with 12.9% of 621 women who received the second dose, and 11.3% of 469 women who received the third dose. The findings were comparable to those of studies conducted of the general population, said study author Brooke C. Juhel, BS, a clinical research coordinator in the lymphedema research program at Massachusetts General Hospital and a student at Harvard Medical School, both in Boston. In the general population, 10.2% experienced lymph node swelling after the first dose and 14% after the second dose, according to the Centers for Disease Control and studies of the Pfizer and Moderna vaccines.

“This is consistent with the hypothesis that, after repeated vaccine doses, the immune system already has the antigens ready to fight the virus, thus the side effects may worsen as the immune response has increased,” she said. “Having screened over 6,500 women for breast cancer–related lymphedema, and with our patients reaching out with concerns about vaccine side effects, we were in a unique position to conduct this study.”

The study also confirmed that the most common side effects of receiving mRNA COVID-19 vaccines for women treated for breast cancer included injection site soreness, fatigue, muscle soreness, headache and chills lasting an average of 48 hours, which are symptoms comparable with those experienced by the general population.

“The side-effect profiles reported in this study for a cohort of women treated for breast cancer can be used to provide evidence-based patient education regarding future COVID-19 vaccine administration. The effect of the COVID-19 vaccines on breast cancer–related lymphedema risk is currently unknown and more research is required. In the interim, we would recommend vaccination away from the side of lymph node removal, either in the contralateral arm or in the thigh,” Ms. Juhel said.

The median duration of lymph node swelling was less than 1 week. In cases where lymph node swelling occurred after the first dose, 54.1% had swelling in ipsilateral axillary lymph nodes, and 45.9% in contralateral axillary lymph nodes. About 29.5% experienced swelling in ipsilateral supraclavicular lymph nodes, and 18.0% in contralateral supraclavicular lymph nodes.

Injection-site soreness, fatigue, GMS, headache, and chills occurred less often among older individuals (P < .001), and fatigue, muscle soreness, headache, and chills occurred more frequently after the second dose than the first (P < .001). The median duration of all side effects was 48 hours or less.

“The informed education that can be produced based on these results will hopefully ease the fears of women treated for breast cancer and empower them to make informed decisions regarding future vaccine doses,” Ms. Juhel said.

Ms. Juhel has no relevant financial disclosures.

Findings from the LymphVAX study recently presented at the San Antonio Breast Cancer Symposium show that relatively few women with breast cancer who are at risk for lymphedema develop lymph node swelling after receiving an mRNA COVID-19 vaccine.

Lymph node swelling can be a particularly troubling side effect, since it could be mistaken for breast cancer progression. In this study, of 621 women who received the first dose of an mRNA COVID-19 vaccine, 9.8% developed lymph node swelling as compared with 12.9% of 621 women who received the second dose, and 11.3% of 469 women who received the third dose. The findings were comparable to those of studies conducted of the general population, said study author Brooke C. Juhel, BS, a clinical research coordinator in the lymphedema research program at Massachusetts General Hospital and a student at Harvard Medical School, both in Boston. In the general population, 10.2% experienced lymph node swelling after the first dose and 14% after the second dose, according to the Centers for Disease Control and studies of the Pfizer and Moderna vaccines.

“This is consistent with the hypothesis that, after repeated vaccine doses, the immune system already has the antigens ready to fight the virus, thus the side effects may worsen as the immune response has increased,” she said. “Having screened over 6,500 women for breast cancer–related lymphedema, and with our patients reaching out with concerns about vaccine side effects, we were in a unique position to conduct this study.”

The study also confirmed that the most common side effects of receiving mRNA COVID-19 vaccines for women treated for breast cancer included injection site soreness, fatigue, muscle soreness, headache and chills lasting an average of 48 hours, which are symptoms comparable with those experienced by the general population.

“The side-effect profiles reported in this study for a cohort of women treated for breast cancer can be used to provide evidence-based patient education regarding future COVID-19 vaccine administration. The effect of the COVID-19 vaccines on breast cancer–related lymphedema risk is currently unknown and more research is required. In the interim, we would recommend vaccination away from the side of lymph node removal, either in the contralateral arm or in the thigh,” Ms. Juhel said.

The median duration of lymph node swelling was less than 1 week. In cases where lymph node swelling occurred after the first dose, 54.1% had swelling in ipsilateral axillary lymph nodes, and 45.9% in contralateral axillary lymph nodes. About 29.5% experienced swelling in ipsilateral supraclavicular lymph nodes, and 18.0% in contralateral supraclavicular lymph nodes.

Injection-site soreness, fatigue, GMS, headache, and chills occurred less often among older individuals (P < .001), and fatigue, muscle soreness, headache, and chills occurred more frequently after the second dose than the first (P < .001). The median duration of all side effects was 48 hours or less.

“The informed education that can be produced based on these results will hopefully ease the fears of women treated for breast cancer and empower them to make informed decisions regarding future vaccine doses,” Ms. Juhel said.

Ms. Juhel has no relevant financial disclosures.

Findings from the LymphVAX study recently presented at the San Antonio Breast Cancer Symposium show that relatively few women with breast cancer who are at risk for lymphedema develop lymph node swelling after receiving an mRNA COVID-19 vaccine.

Lymph node swelling can be a particularly troubling side effect, since it could be mistaken for breast cancer progression. In this study, of 621 women who received the first dose of an mRNA COVID-19 vaccine, 9.8% developed lymph node swelling as compared with 12.9% of 621 women who received the second dose, and 11.3% of 469 women who received the third dose. The findings were comparable to those of studies conducted of the general population, said study author Brooke C. Juhel, BS, a clinical research coordinator in the lymphedema research program at Massachusetts General Hospital and a student at Harvard Medical School, both in Boston. In the general population, 10.2% experienced lymph node swelling after the first dose and 14% after the second dose, according to the Centers for Disease Control and studies of the Pfizer and Moderna vaccines.

“This is consistent with the hypothesis that, after repeated vaccine doses, the immune system already has the antigens ready to fight the virus, thus the side effects may worsen as the immune response has increased,” she said. “Having screened over 6,500 women for breast cancer–related lymphedema, and with our patients reaching out with concerns about vaccine side effects, we were in a unique position to conduct this study.”

The study also confirmed that the most common side effects of receiving mRNA COVID-19 vaccines for women treated for breast cancer included injection site soreness, fatigue, muscle soreness, headache and chills lasting an average of 48 hours, which are symptoms comparable with those experienced by the general population.

“The side-effect profiles reported in this study for a cohort of women treated for breast cancer can be used to provide evidence-based patient education regarding future COVID-19 vaccine administration. The effect of the COVID-19 vaccines on breast cancer–related lymphedema risk is currently unknown and more research is required. In the interim, we would recommend vaccination away from the side of lymph node removal, either in the contralateral arm or in the thigh,” Ms. Juhel said.

The median duration of lymph node swelling was less than 1 week. In cases where lymph node swelling occurred after the first dose, 54.1% had swelling in ipsilateral axillary lymph nodes, and 45.9% in contralateral axillary lymph nodes. About 29.5% experienced swelling in ipsilateral supraclavicular lymph nodes, and 18.0% in contralateral supraclavicular lymph nodes.

Injection-site soreness, fatigue, GMS, headache, and chills occurred less often among older individuals (P < .001), and fatigue, muscle soreness, headache, and chills occurred more frequently after the second dose than the first (P < .001). The median duration of all side effects was 48 hours or less.

“The informed education that can be produced based on these results will hopefully ease the fears of women treated for breast cancer and empower them to make informed decisions regarding future vaccine doses,” Ms. Juhel said.

Ms. Juhel has no relevant financial disclosures.

In a series of studies recently presented at the San Antonio Breast Cancer Symposium that examine the effects of the COVID-19 pandemic on women with breast cancer, researchers report that ethnicity played a role in later diagnoses, Hispanics presented with more advanced and aggressive disease, and a focus on a single hospital in San Antonio finds a statistical difference between stage at diagnosis prior to the pandemic, compared with the postvaccine era.

Patients treated at the Mays Cancer Center, a cancer hospital of University of Texas Health and MD Anderson Cancer Center in San Antonio, during the pandemic were found to more likely present with advanced disease between March and December 2020, according to Marcela Mazo, MD, an oncologist with UT Health, San Antonio, and an author of each of three studies.

“We learned that Hispanic patients were presenting with more aggressive histologies such as HER2-positive and triple-negative disease. We also confirmed what we were suspecting, which is that Latina women had less access to medical coverage. We had a higher proportion of Hispanic patients presenting to us without medical coverage, which of course made the treatment extremely challenging,” said Dr. Mazo.

Hispanics are one of the fastest-growing minority groups in the United States, and understanding the factors that affect their healthcare is critical to formulating health policies.

“The findings confirmed my suspicion that most patients did not get a mammogram during the lockdown. And I’m sad to say that, even after everything opened up and people could get vaccinated, I still saw some patients who, for whatever reason, did not get a mammogram – which led to [more] clinical presentations of advanced cancer by the time they were seen by us,” she said.

Dr. Mazo said that underscreened women could also be considered victims of the pandemic. “I tell my patients to get their vaccines so they’re protected and they can feel more comfortable going to the doctor where there is a higher proportion of people who could potentially have COVID.”

Other studies have shown that patients in general, regardless of race or ethnicity, have been diagnosed with later-stage breast cancer diagnoses during the pandemic.

The three studies are based on an analysis of 696 patients treated at Mays Cancer Center. Of these, 264 were diagnosed before the pandemic (cohort A), 171 during the lockdown (Apr. 1 to Dec. 31, 2020, cohort B) and 261 after vaccines were introduced (Jan. 1 to Dec. 31, 2021, cohort C). Overall, there was a slight trend toward a higher incidence of HER2-positive disease during the lockdown period (odds ratio, 1.45) and in the postvaccine period (OR, 1.40), though neither relationship was statistically significant (P = .2). No relationships were seen between time period and incidence of triple-negative breast cancer.

The researchers found that Hispanic patients were more likely to be diagnosed with advanced disease in the pandemic years, compared with pre-COVID times. For example, the likelihood of being diagnosed with carcinoma in situ (Tis) versus T1 disease was lower in the postvaccine era than the pre-COVID era (OR, 0.38; P < .001), although there was no significant difference in Tis versus T1 during the lockdown period, compared with the pre-COVID era. The researchers concluded the difference was likely caused by the latency period of breast cancer.

The postvaccine era saw a 15% increase in patients diagnosed with HER2-positive disease, compared with the pre-COVID era. Patients diagnosed in the COVID era (cohorts B and C) were more likely to require neoadjuvant therapy than patients diagnosed in the pre-COVID era (OR, 1.78; P = .009).

They also found significant disparities in health insurance coverage. 91% of non-Hispanic patients were covered by insurance, compared with 70% of Hispanic patients.

Overall, the findings hint at the depth of health care inequities faced by Hispanic women in the region, and should be a call for action, Dr. Mazo said. “I wish that we as physicians would take the lead to do the best we can to support legislative changes that could help all of our patients get treated – independent of where they come from.”

Dr. Mazo has no relevant financial disclosures.

In a series of studies recently presented at the San Antonio Breast Cancer Symposium that examine the effects of the COVID-19 pandemic on women with breast cancer, researchers report that ethnicity played a role in later diagnoses, Hispanics presented with more advanced and aggressive disease, and a focus on a single hospital in San Antonio finds a statistical difference between stage at diagnosis prior to the pandemic, compared with the postvaccine era.

Patients treated at the Mays Cancer Center, a cancer hospital of University of Texas Health and MD Anderson Cancer Center in San Antonio, during the pandemic were found to more likely present with advanced disease between March and December 2020, according to Marcela Mazo, MD, an oncologist with UT Health, San Antonio, and an author of each of three studies.

“We learned that Hispanic patients were presenting with more aggressive histologies such as HER2-positive and triple-negative disease. We also confirmed what we were suspecting, which is that Latina women had less access to medical coverage. We had a higher proportion of Hispanic patients presenting to us without medical coverage, which of course made the treatment extremely challenging,” said Dr. Mazo.

Hispanics are one of the fastest-growing minority groups in the United States, and understanding the factors that affect their healthcare is critical to formulating health policies.

“The findings confirmed my suspicion that most patients did not get a mammogram during the lockdown. And I’m sad to say that, even after everything opened up and people could get vaccinated, I still saw some patients who, for whatever reason, did not get a mammogram – which led to [more] clinical presentations of advanced cancer by the time they were seen by us,” she said.

Dr. Mazo said that underscreened women could also be considered victims of the pandemic. “I tell my patients to get their vaccines so they’re protected and they can feel more comfortable going to the doctor where there is a higher proportion of people who could potentially have COVID.”

Other studies have shown that patients in general, regardless of race or ethnicity, have been diagnosed with later-stage breast cancer diagnoses during the pandemic.

The three studies are based on an analysis of 696 patients treated at Mays Cancer Center. Of these, 264 were diagnosed before the pandemic (cohort A), 171 during the lockdown (Apr. 1 to Dec. 31, 2020, cohort B) and 261 after vaccines were introduced (Jan. 1 to Dec. 31, 2021, cohort C). Overall, there was a slight trend toward a higher incidence of HER2-positive disease during the lockdown period (odds ratio, 1.45) and in the postvaccine period (OR, 1.40), though neither relationship was statistically significant (P = .2). No relationships were seen between time period and incidence of triple-negative breast cancer.

The researchers found that Hispanic patients were more likely to be diagnosed with advanced disease in the pandemic years, compared with pre-COVID times. For example, the likelihood of being diagnosed with carcinoma in situ (Tis) versus T1 disease was lower in the postvaccine era than the pre-COVID era (OR, 0.38; P < .001), although there was no significant difference in Tis versus T1 during the lockdown period, compared with the pre-COVID era. The researchers concluded the difference was likely caused by the latency period of breast cancer.

The postvaccine era saw a 15% increase in patients diagnosed with HER2-positive disease, compared with the pre-COVID era. Patients diagnosed in the COVID era (cohorts B and C) were more likely to require neoadjuvant therapy than patients diagnosed in the pre-COVID era (OR, 1.78; P = .009).

They also found significant disparities in health insurance coverage. 91% of non-Hispanic patients were covered by insurance, compared with 70% of Hispanic patients.

Overall, the findings hint at the depth of health care inequities faced by Hispanic women in the region, and should be a call for action, Dr. Mazo said. “I wish that we as physicians would take the lead to do the best we can to support legislative changes that could help all of our patients get treated – independent of where they come from.”

Dr. Mazo has no relevant financial disclosures.

In a series of studies recently presented at the San Antonio Breast Cancer Symposium that examine the effects of the COVID-19 pandemic on women with breast cancer, researchers report that ethnicity played a role in later diagnoses, Hispanics presented with more advanced and aggressive disease, and a focus on a single hospital in San Antonio finds a statistical difference between stage at diagnosis prior to the pandemic, compared with the postvaccine era.

Patients treated at the Mays Cancer Center, a cancer hospital of University of Texas Health and MD Anderson Cancer Center in San Antonio, during the pandemic were found to more likely present with advanced disease between March and December 2020, according to Marcela Mazo, MD, an oncologist with UT Health, San Antonio, and an author of each of three studies.

“We learned that Hispanic patients were presenting with more aggressive histologies such as HER2-positive and triple-negative disease. We also confirmed what we were suspecting, which is that Latina women had less access to medical coverage. We had a higher proportion of Hispanic patients presenting to us without medical coverage, which of course made the treatment extremely challenging,” said Dr. Mazo.

Hispanics are one of the fastest-growing minority groups in the United States, and understanding the factors that affect their healthcare is critical to formulating health policies.

“The findings confirmed my suspicion that most patients did not get a mammogram during the lockdown. And I’m sad to say that, even after everything opened up and people could get vaccinated, I still saw some patients who, for whatever reason, did not get a mammogram – which led to [more] clinical presentations of advanced cancer by the time they were seen by us,” she said.

Dr. Mazo said that underscreened women could also be considered victims of the pandemic. “I tell my patients to get their vaccines so they’re protected and they can feel more comfortable going to the doctor where there is a higher proportion of people who could potentially have COVID.”

Other studies have shown that patients in general, regardless of race or ethnicity, have been diagnosed with later-stage breast cancer diagnoses during the pandemic.

The three studies are based on an analysis of 696 patients treated at Mays Cancer Center. Of these, 264 were diagnosed before the pandemic (cohort A), 171 during the lockdown (Apr. 1 to Dec. 31, 2020, cohort B) and 261 after vaccines were introduced (Jan. 1 to Dec. 31, 2021, cohort C). Overall, there was a slight trend toward a higher incidence of HER2-positive disease during the lockdown period (odds ratio, 1.45) and in the postvaccine period (OR, 1.40), though neither relationship was statistically significant (P = .2). No relationships were seen between time period and incidence of triple-negative breast cancer.

The researchers found that Hispanic patients were more likely to be diagnosed with advanced disease in the pandemic years, compared with pre-COVID times. For example, the likelihood of being diagnosed with carcinoma in situ (Tis) versus T1 disease was lower in the postvaccine era than the pre-COVID era (OR, 0.38; P < .001), although there was no significant difference in Tis versus T1 during the lockdown period, compared with the pre-COVID era. The researchers concluded the difference was likely caused by the latency period of breast cancer.

The postvaccine era saw a 15% increase in patients diagnosed with HER2-positive disease, compared with the pre-COVID era. Patients diagnosed in the COVID era (cohorts B and C) were more likely to require neoadjuvant therapy than patients diagnosed in the pre-COVID era (OR, 1.78; P = .009).

They also found significant disparities in health insurance coverage. 91% of non-Hispanic patients were covered by insurance, compared with 70% of Hispanic patients.

Overall, the findings hint at the depth of health care inequities faced by Hispanic women in the region, and should be a call for action, Dr. Mazo said. “I wish that we as physicians would take the lead to do the best we can to support legislative changes that could help all of our patients get treated – independent of where they come from.”

Dr. Mazo has no relevant financial disclosures.