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Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is COVID-19 exposure in utero associated with increased risk for neurodevelopmental disorders in the first year of life?

Findings  In this cohort study of 7772 infants delivered during the COVID-19 pandemic, those born to the 222 mothers with a positive SARS-CoV-2 polymerase chain reaction test during pregnancy were more likely to receive a neurodevelopmental diagnosis in the first 12 months after delivery, even after accounting for preterm delivery.

Meaning  These preliminary findings suggest that COVID-19 exposure may be associated with neurodevelopmental changes and highlight the need for prospective investigation of outcomes in children exposed to COVID-19 in utero.


Importance  Epidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring.

Objective  To evaluate whether in utero exposure to SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth.

Design, Setting, and Participants  This retrospective cohort study examined live offspring of all mothers who delivered between March and September 2020 at any of 6 Massachusetts hospitals across 2 health systems. Statistical analysis was performed from October to December 2021.

Exposures  Maternal SARS-CoV-2 infection confirmed by a polymerase chain reaction test during pregnancy.

Main Outcomes and Measures  Neurodevelopmental disorders determined from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes over the first 12 months of life; sociodemographic and clinical features of mothers and offspring; all drawn from the electronic health record.

Results  The cohort included 7772 live births (7466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean (SD) maternal age of 32.9 (5.0) years; offspring were 9.9% Asian (772), 8.4% Black (656), and 69.0% White (5363); 15.1% (1134) were of Hispanic ethnicity. Preterm delivery was more likely among exposed mothers: 14.4% (32) vs 8.7% (654) (P = .003). Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses in unadjusted models (odds ratio [OR], 2.17 [95% CI, 1.24-3.79]; P = .006) as well as those adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (adjusted OR, 1.86 [95% CI, 1.03-3.36]; P = .04). Third-trimester infection was associated with effects of larger magnitude (adjusted OR, 2.34 [95% CI, 1.23-4.44]; P = .01).

Conclusions and Relevance  This cohort study of SARS-CoV-2 exposure in utero found preliminary evidence that maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring. Prospective studies with longer follow-up duration will be required to exclude confounding and confirm these associations.

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Article Information

Accepted for Publication: April 6, 2022.

Published: June 9, 2022. doi:10.1001/jamanetworkopen.2022.15787

Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2022 Edlow AG et al. JAMA Network Open.

Corresponding Author: Roy H. Perlis, MD, MSc, Center for Quantitative Health and Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge St, Simches Research Building, Boston, MA 02114 (rperlis@mgh.harvard.edu).

Author Contributions: Dr Perlis had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Castro, Kaimal, Perlis.

Acquisition, analysis, or interpretation of data: Edlow, Castro, Shook, Perlis.

Drafting of the manuscript: Edlow, Castro, Perlis.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Castro, Perlis.

Administrative, technical, or material support: Edlow, Castro, Kaimal.

Supervision: Perlis.

Conflict of Interest Disclosures: Dr Edlow reported receiving grants from Simons Foundation during the conduct of the study. Dr Perlis reported receiving consulting fees from Burrage Capital, Genomind, RID Ventures, Belle Artificial Intelligence, and Takeda; he reported receiving equity in Psy Therapeutics, Belle Artificial Intelligence, and Circular Genomics; Dr Perlis also reported receiving personal fees from Genomind Scientific Advisory Board and personal fees from Vault Health Scientific Advisory Board outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by the National Institute of Mental Health (R01MH116270 and 1R56MH115187; Dr Perlis) and the National Institute of Child Health and Human Development (R01 HD100022-02S2; Dr Edlow).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: Dr Perlis is an associate editor for JAMA Network Open but was not involved in the editorial review or decision for this manuscript.

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