- Exposure to SARS-CoV-2 infection during pregnancy was associated with a 29% greater risk of neurodevelopmental diagnosis by age 3 years.
- The largest effects were observed in third-trimester exposures, both overall and among male offspring.
- Preterm birth, maternal public insurance, and Hispanic ethnicity were all associated with a significantly greater risk for neurodevelopmental diagnosis.
Exposure to SARS-CoV-2 infection in utero was associated with an increased risk of neurodevelopmental diagnoses among children by age 3 years, according to a retrospective cohort study.
Among over 800 children exposed to maternal SARS-CoV-2 infection during pregnancy, 16.3% had a neurodevelopmental diagnosis by age 3 compared with 9.7% of unexposed offspring (adjusted OR 1.29, 95% CI 1.05-1.57, P=0.01), reported Lydia Shook, MD, of Massachusetts General Hospital in Boston, and colleagues in Obstetrics & Gynecology.
"We are building on quite a solid foundation of literature looking at the association between maternal infection and neurodevelopmental outcomes," Shook told MedPage Today. "We think of [COVID-19] as one of many potential exposures in pregnancy that could impact offspring neurodevelopment, probably through a common pathway of maternal immune activation."
Nearly two-thirds of maternal COVID infections occurred during the third trimester. In sensitivity analyses, the largest effects were observed in third-trimester exposures, both overall (aOR 1.36, 95% CI 1.07-1.72, P=0.01) and among male offspring (aOR 1.43, 95% CI 1.05-1.91, P=0.02).
Preterm birth, maternal public insurance, Hispanic ethnicity, and delivery in an academic medical center rather than a community hospital were all associated with a significantly greater risk for neurodevelopmental diagnoses (P<0.001 for all).
The most common diagnoses by 36 months were unspecified speech and language disorders, diagnosed in 9.5% of children born to COVID-exposed mothers versus 4.7% of those born to unexposed mothers. Expressive language disorders were diagnosed in 5.3% and 3.7%, respectively, while motor function disorder was diagnosed in 2.7% and 1.6%. Autistic disorder was diagnosed in 2.7% versus 1.1%, respectively.
"We know vaccines are safe and effective at preventing severe maternal infection, hospitalization, and sequelae of severe maternal illness -- including preterm birth, which we know in and of itself is associated with risk of neurodevelopmental disorders in children," Shook said. "Maybe this does add to the story about how protecting against maternal infection may have some small benefit for the overall low absolute risk of neurodevelopmental disorders."
For this study, the researchers used electronic health record data for all singleton and multiple live births at two academic medical centers and six community hospitals from March 2020 through May 2021, a period early in the COVID pandemic when pregnant women were mostly unvaccinated and naive to SARS-CoV-2 infection. All women had at least one SARS-CoV-2 PCR test taken during their pregnancy.
"Part of the strength of this cohort is that we captured a time period when there was robust testing and ascertainment of disease status so that we could reliably say that a patient had an infection in pregnancy," Shook explained.
The study included 18,124 live births. Median maternal age was 33 years, 69.4% were white, 8.9% were Black, 9.9% were Asian, and 14.2% were Hispanic. Nearly all women were unvaccinated (92.7%). Of the women with SARS-CoV-2 exposure during pregnancy, 48% had public insurance compared with 17.8% of women who were unexposed.
Age at first neurodevelopmental diagnosis was similar between the two groups of children. First diagnosis was between ages 18 and 36 months in 60.7% of those born to SARS-CoV-2-exposed moms compared with 58% of those with unexposed moms.
Study limitations included the lack of systematic diagnostic assessment, which might have led to misclassification. Children who were evaluated outside of the study's health network may have received neurodevelopmental diagnoses that weren't included in the study's dataset. Asymptomatic infections during pregnancies also may have been missed.
Disclosures
The study was supported by the National Institute of Mental Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Simons Foundation Autism Research Initiative.
Shook reported no disclosures.
Colleagues reported relationships with Alkermes, Circular Genomics, Genomind, Merck, and Mirvie.
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