Importance: Prior studies using large registries suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such risk may be sex-specific. Objective: To determine whether in utero exposure to the novel coronavirus SARS-CoV-2 is associated with sex-specific risk for neurodevelopmental disorders up to 18 months after birth, compared to unexposed offspring born during or prior to the pandemic period. Design: Retrospective cohort. Participants: Live offspring of all mothers who delivered between March 2018 and May 2021 at any of eight hospitals across two health systems in Massachusetts. Exposure: PCR evidence of maternal SARS-CoV-2 infection during pregnancy. Main Outcome and Measures: Electronic health record documentation of ICD-10 diagnostic codes corresponding to neurodevelopmental disorders. Results: The pandemic cohort included 18,323 live births, including 877 (4.8%) to individuals with SARS-CoV-2 positivity during pregnancy. The cohort included 1806 (9.9%) Asian individuals, 1634 (8.9%) Black individuals, 1711 (9.3%) individuals of another race, and 12,694 (69%) White individuals; 2614 (14%) were of Hispanic ethnicity. Mean maternal age was 33.0 years (IQR 30.0-36.0). In adjusted regression models accounting for race, ethnicity, insurance status, hospital type (academic center vs. community), maternal age, and preterm status, SARS-CoV-2 positivity was associated with statistically significant elevation in risk for neurodevelopmental diagnoses among male offspring (adjusted OR 1.99, 95% CI 1.19-3.34; p=0.009) but not female offspring (adjusted OR 0.90, 95% CI 0.43-1.88; p=0.8). Similar effects were identified using matched analyses in lieu of regression. Conclusion and Relevance: SARS-CoV-2 exposure in utero was associated with greater magnitude of risk for neurodevelopmental diagnoses among male offspring in the 12 months following birth. As with prior studies of maternal infection, substantially larger cohorts and longer follow-up will be required to reliably estimate or refute risk.

Dr. Perlis has received consulting fees from Burrage Capital, Genomind, Belle Artificial Intelligence, and Takeda. He holds equity in Psy Therapeutics, Belle Artificial Intelligence, and Circular Genomics. Dr. Edlow has received consulting fees from Mirvie, Inc. and research funding from Merck Pharmaceuticals, both outside of the work reported here. The other authors report no disclosures.

This study was supported by the National Institute of Mental Health (RF1MH132336, Dr. Edlow and Dr. Perlis; R01 MH116270, Dr. Perlis; U54 MH118919, Dr. Edlow), the National Institute of Child Health and Human Development (R01 HD100022-02S2, Dr. Edlow), and Simons Foundation SFARI grant 870754 (Dr. Edlow).

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The Massachusetts General Brigham Institutional Review Board approved all aspects of this study, with a waiver of informed consent as no patient contact was required, the study was considered to be minimal risk, and consent could not feasibly be obtained.

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