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Publications

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Epublish 72 citations

PubMed: 36951861 DOI: 10.1001/jamanetworkopen.2023.4415

Sex-Specific Neurodevelopmental Outcomes Among Offspring of Mothers With SARS-CoV-2 Infection During Pregnancy.

JAMA Netw Open 6(3):e234415

Authors: Andrea G Edlow, Victor M Castro, Lydia L Shook, Sebastien Haneuse, Anjali J Kaimal, Roy H Perlis

Affiliations

  • Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston.
  • Center for Quantitative Health, Massachusetts General Hospital, Boston.
  • Research Information Science and Computing, Mass General Brigham, Somerville, Massachusetts.
  • Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa.
  • Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston.

Abstract

Importance

Prior studies using large registries have 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 SARS-CoV-2 is associated with sex-specific risk for neurodevelopmental disorders up to 18 months after birth, compared with unexposed offspring born during or prior to the COVID-19 pandemic period.

Design, Setting, and Participants

This retrospective cohort study included the live offspring of all mothers who delivered between January 1 and December 31, 2018 (born and followed up before the COVID-19 pandemic), between March 1 and December 31, 2019 (born before and followed up during the COVID-19 pandemic), and between March 1, 2020, and May 31, 2021 (born and followed up during the COVID-19 pandemic). Offspring were born at any of 8 hospitals across 2 health systems in Massachusetts.

Exposures

Polymerase chain reaction evidence of maternal SARS-CoV-2 infection during pregnancy.

Main Outcomes and Measures

Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to neurodevelopmental disorders.

Results

The COVID-19 pandemic cohort included 18 355 live births (9399 boys [51.2%]), including 883 (4.8%) with maternal SARS-CoV-2 positivity during pregnancy. The cohort included 1809 Asian individuals (9.9%), 1635 Black individuals (8.9%), 12 718 White individuals (69.3%), and 1714 individuals (9.3%) who were of other race (American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, more than 1 race); 2617 individuals (14.3%) were of Hispanic ethnicity. Mean maternal age was 33.0 (IQR, 30.0-36.0) years. In adjusted regression models accounting for race, ethnicity, insurance status, hospital type (academic center vs community), maternal age, and preterm status, maternal SARS-CoV-2 positivity was associated with a statistically significant elevation in risk for 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). Similar effects were identified using matched analyses in lieu of regression. At 18 months, more modest effects were observed in male offspring (adjusted OR, 1.42 [95% CI, 0.92-2.11]; P = .10).

Conclusions and Relevance

In this cohort study of offspring with SARS-CoV-2 exposure in utero, such exposure was associated with greater magnitude of risk for neurodevelopmental diagnoses among male offspring at 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.

MeSH

Pregnancy, Sars-Cov-2, Mothers, Parturition, Maternal Age, Cohort Studies, Neurodevelopmental Disorders, Clinical Medicine, Covid-19, Sex, Diagnosis, Pandemics, Severe Acute Respiratory Syndrome-Related Coronavirus, Infections, Neurodevelopment

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