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Does COVID-19 During Pregnancy Affect Male Infant Brain Development?

  • Authors: News Author: Jay Croft; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 5/19/2023
  • Valid for credit through: 5/19/2024, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care clinicians, obstetrician gynecologists, infectious disease specialists, pediatricians, nurses, physician assistants, nurse practitioners, pharmacists and other clinicians who treat and manage pregnant women and young children.

The goal of this activity is for learners to be better able to analyze the risk for neurodevelopmental diagnoses early in childhood associated with maternal SARS-CoV-2 infection.

Upon completion of this activity, participants will:

  • Assess how maternal infection might affect the risk for neurocognitive disease among offspring
  • Analyze the risk for neurodevelopmental diagnoses early in childhood associated with maternal SARS-CoV-2 infection
  • Outline implications for the healthcare team


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News Author

  • Jay Croft

    Freelance writer, Medscape


    Jay Croft has no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine
    Irvine, California


    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: Boehringer Ingelheim; GlaxoSmithKline; Johnson & Johnson

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  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC


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  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


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Does COVID-19 During Pregnancy Affect Male Infant Brain Development?

Authors: News Author: Jay Croft; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 5/19/2023

Valid for credit through: 5/19/2024, 11:59 PM EST


Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to the approved COVID-19 vaccines are provided in this activity in an effort to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

Vaccination is an important part of prenatal care to improve the health outcomes of both mothers and infants. The authors of the current study note that previous research has found that maternal infection with viruses such as influenza during pregnancy is associated with negative neurocognitive outcomes in children. A registry-based study found that infection requiring hospitalization during pregnancy was associated with a 30% increase in the risk for autism spectrum disorders (ASD) among offspring. Another study found that any significant maternal infection was associated with higher risks for ASD and depression among offspring, regardless of the severity of the primary infection.

There is limited research into the effects of maternal infection with COVID-19 on neurocognitive outcomes of children. A meta-analysis of 691 children exposed to COVID-19 in utero found no significant impairment in neurocognitive outcomes through 12 months, although fine motor function was impaired in these children compared with in children without COVID-19 exposure.

The authors of the current study further examine the relationship between COVID-19 during pregnancy and cognitive outcomes, with special attention to sex-based differences. Sex-specific differences in the immune response among female and male fetuses have been implicated in the pathogenesis of the gap between boys and girls for outcomes such as ASD and attention-deficit/hyperactivity disorder.

Study Synopsis and Perspective

Boys born to mothers with COVID-19 could face brain development issues at a rate twice that of others, a new study found.

The study involved more than 18,000 children born at 8 hospitals in Massachusetts. Almost 900 of them were born to women who had COVID-19 while pregnant.

The male babies were more prone to a range of developmental disorders in the first 18 months of life, says the study, which was published in JAMA Network Open. It analyzed electronic health records.

The issues included delays in speech and language, psychological development, motor function, and intellectual abilities.

Those issues can be associated with autism among older children, but “it’s way too soon to reliably diagnose autism” in the children studied, Roy Perlis, MD, told NPR. Dr Perlis is a coauthor of the report and a psychiatrist at Massachusetts General Hospital.

“All we can hope to detect at this point are more subtle sorts of things like delays in language and speech, and delays in motor milestones,” he said. “Most children of moms who have COVID during pregnancy won’t have neurodevelopmental consequences even if there is some increase in risk.”

Other studies have shown that maternal infections can affect fetal brain development, especially in boys, NPR reported.

“If a mom had SARS-CoV-2 infection in pregnancy and had a male child, her 12-month-old was 94% more likely to have any neurodevelopmental diagnosis,” said Andrea Edlow, MD, lead author and a maternal-fetal medicine specialist at Massachusetts General Hospital.

The virus that causes COVID-19 usually does not infect a fetus, she said. The risk to a fetus seems to come from the mother’s immune response, not from the infection.

JAMA Netw Open. 2023;6(3):e234415.[1]

Study Highlights

  • Study data were drawn from 6 community hospitals and 2 tertiary care medical centers in Eastern Massachusetts. Children born in these centers between March 1, 2020, and May 31, 2021 (COVID-19 era), were compared primarily with children born in 2018 (pre-COVID-19 era).
  • The primary outcome was the incidence of neurocognitive pathology among offspring by age 12 months, as determined by diagnosis codes in the health record. Researchers also examined the same outcomes at age 18 months.
  • The main study variable was a positive maternal polymerase chain reaction test for SARS-CoV-2. All COVID-19 infections were considered regardless of trimester.  Of note, universal screening for SARS-CoV-2 on admission to labor and delivery was instituted in April 2020 and continued through the study period.
  • The study analysis accounted for maternal age, sociodemographic factors, delivery variables, and health insurance and hospital type.
  • The COVID-19 pandemic cohort included 18,355 live births; 51.2% were boys, and the cohort was heterogenous in terms of race/ethnicity. The mean maternal age was 33.0 years.
  • 4.8% of children were born to mothers with a history of a positive test for SARS-CoV-2. These children were more likely to be Hispanic or Black or to have a listing of other race.  Children born to mothers with a history of SARS-CoV-2 infection were more likely to have public vs private health insurance. 
  • Children born to mothers with a history of a positive test had a significantly higher rate of premature delivery (13.3%) vs children without a positive maternal test (10.0%).
  • Overall, there were 883 children exposed to SARS-CoV-2, and 2.9% received a neurodevelopmental diagnosis. The rate of such diagnoses among children born without exposure to SARS-CoV-2 was 1.8%.
  • In the primary analysis, the adjusted odds ratio (OR) for a neurodevelopmental diagnosis in comparing children exposed to SARS-CoV-2 vs the unexposed cohort was 1.43 (95% CI, 0.92-2.13). This difference was significant when examining boys only (OR, 1.94; 95% CI, 1.12-3.17). However, the respective outcome was similar among girls exposed and unexposed to SARS-CoV-2.
  • A separate analysis that did not adjust for premature delivery did not alter the main study outcomes.
  • None of 13 children delivered to mothers who had a positive test for SARS-CoV-2 after receipt of at least 1 COVID-19 vaccine developed a neurodevelopmental diagnosis.
  • Further adjustment to account for less than 100% sensitivity of SARS-CoV-2 testing on maternal samples strengthened the association between maternal infection and neurodevelopmental diagnoses in offspring.
  • At 18 months, the OR for a neurodevelopmental diagnosis among boys exposed and not unexposed to COVID-19 was 1.42 (95% CI, 0.92-2.11). The respective OR for girls was 0.98 (95% CI, 0.52-1.71).
  • Finally, researchers examined secular trends in the diagnoses of neurodevelopmental disorders among children, and they found a modest but statistically insignificant increase in the rate of these diagnoses during the COVID-19 pandemic.

Implications for the healthcare team

  • Maternal infection with COVID-19 has been associated with a higher risk for ASD and depression among offspring, with a possible predilection among boys. A meta-analysis of 691 children exposed to COVID-19 in utero found no significant impairment in neurocognitive outcomes through 12 months, although fine motor function was impaired in these children compared with in children without COVID-19 exposure.
  • In the current study, neurodevelopmental diagnoses were more common at age 12 months among boys exposed to SARS-CoV-2 in utero, but SARS-CoV-2 did not affect the rate of neurodevelopmental diagnosis among girls.
  • Clinicians should provide evidence-based education on vaccination against COVID-19 and other infections as part of preconception counseling.

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