SAR-CoV-2 infection during pregnancy may lead to adverse neurodevelopmental outcomes in male offspring

1. In this retrospective cohort study of infants exposed to SARS-CoV-2 in utero, there was a significantly higher risk of neurodevelopmental diagnoses in male offspring but not female offspring at 12 months following birth.

Evidence Rating Level 2: (Good)

Several epidemiologic studies have suggested that maternal infection or immune activation during pregnancy may be associated increased risk of neurodevelopmental disorders among offspring. In light of the COVID-19 pandemic, there is a need to understand whether maternal exposure may have similar effects on offspring as those reported in the literature for other infections. Prior studies have found a potential association between in utero infections and subsequent adverse neurodevelopmental outcomes, though prior literature suffered from small sample sizes and short follow-up periods. To address this, this retrospective cohort study assessed a large cohort of 18 355 live births from electronic health records from 8 hospitals in Eastern Massachusetts, to determine whether there are sex-specific differences in the development of neurodevelopmental disorders with SARS-CoV-2 exposure in utero, compared with unexposed offspring born during or before the COVID-19 pandemic. After adjusting for potential confounders, maternal SARS-Cov-2 positivity was associated with a statistically significant increased risk of neurodevelopmental diagnoses at 12 months among male offspring (adjusted OR, 1.94 [95% CI, 1.12-3.17]; P = .01), but not female offspring (adjusted OR, 0.89 [95% CI, 0.39-1.76]; P = .77). When extending follow-up to 18 months, there was a similar pattern of greater numerical increase in adverse neurodevelopmental outcomes in male offspring but not in female offspring. However, these findings were not statistically significant, with all 95% CIs including 1. This is likely due in part to the smaller cohort size at the 18-month mark, compared to the 12-month mark. Overall these findings suggest that male offspring exposed to SARS-CoV-2 infection in utero may be at a higher risk for adverse neurodevelopmental outcomes. Given that both SARS-CoV-2-positive and uninfected mothers were exposed to pandemic-era stress, these effects are not primarily due to pandemic factors, rather they are likely attributable to infection exposure itself. Further studies with larger cohorts and extended follow-up are required to accurately assess and characterize the risk.

Click to read the study in JAMA Network Open

Image: PD

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