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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]

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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