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. 2024 Oct 1;7(10):e2439792.
doi: 10.1001/jamanetworkopen.2024.39792.

In Utero Exposure to Maternal COVID-19 and Offspring Neurodevelopment Through Age 24 Months

Eleni G Jaswa  1 , Heather G Huddleston  1 , Karla J Lindquist  2 , Alan H B Wu  3 , Somer L Bishop  4 , Young-Shin Kim  4 , Amy Kaing  1 , Mary Prahl  5 , Stephanie L Gaw  6 , Jamie Corley  1 , Elena Hoskin  1 , Yoon Jae Cho  4 , Elizabeth E Rogers  7 , Marcelle I Cedars  1
Affiliations

In Utero Exposure to Maternal COVID-19 and Offspring Neurodevelopment Through Age 24 Months

Eleni G Jaswa et al. JAMA Netw Open. .

Abstract

Importance: In utero exposure to maternal infections has been associated with abnormal neurodevelopment among offspring. The emergence of a new, now endemic infection (SARS-CoV-2) warrants investigating developmental implications for exposed offspring.

Objective: To assess whether in utero exposure to maternal COVID-19 is associated with abnormal neurodevelopmental scores among children ages 12, 18, and 24 months.

Design, setting, and participants: Data were ascertained from the ASPIRE (Assessing the Safety of Pregnancy in the Coronavirus Pandemic) trial, a prospective cohort of pregnant individuals aged 18 years or older who were enrolled before 10 weeks' gestation and their children. Individuals were recruited online from May 14, 2020, to August 23, 2021, using the Society for Assisted Reproductive Technology and BabyCenter, an online media platform. Participants from all 50 states and Puerto Rico completed activities remotely.

Exposure: In utero exposure to COVID-19.

Main outcomes and measures: Birth mothers completed the Ages & Stages Questionnaires, Third Edition, a validated screening tool for developmental delays, at 12, 18, and 24 months' post partum. A score below the cutoff in any domain (communication, gross motor, fine motor, problem-solving, and social skills) was considered an abnormal developmental screen (scores range from 0 to 60 in each domain, with higher scores indicating less risk for neurodevelopmental delay).

Results: The cohort included 2003 pregnant individuals (mean [SD] age, 33.3 [4.2] years) enrolled before 10 weeks' gestation and who completed study activities; 1750 (87.4%) had earned a college degree. Neurodevelopmental outcomes were available for 1757 children at age 12 months, 1522 at age 18 months, and 1523 at age 24 months. The prevalence of abnormal screens for exposed vs unexposed offspring at age 12 months was 64 of 198 (32.3%) vs 458 of 1559 (29.4%); at age 18 months, 36 of 161 (22.4%) vs 279 of 1361 (20.5%); and at age 24 months, 29 of 151 (19.2%) vs 230 of 1372 (16.8%). In an adjusted mixed-effects logistics regression model, no difference in risk of abnormal neurodevelopmental screens was observed at age 12 months (adjusted risk ratio [ARR], 1.07 [95% CI, 0.85-1.34]), age 18 months (ARR, 1.15 [95% CI, 0.84-1.57]), or age 24 months (ARR, 1.01 [95% CI, 0.69-1.48]). Supplemental analyses did not identify differential risk based on trimester of infection, presence vs absence of fever, or breakthrough infection following vaccination vs primary infection.

Conclusions and relevance: In this cohort study of pregnant individuals and offspring, exposure to maternal COVID-19 was not associated with abnormal neurodevelopmental screening results through 24 months' post partum. Continued study of diverse groups of children is needed because, among other factors, evidence suggests sensitivity of the developing fetal brain to maternal immune activation.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Jaswa reported serving on the medical advisory board for Oura Health Oy. Dr Bishop reported receiving royalties from Western Psychological Services for the Autism Diagnostic Observation Schedule, Second Edition outside the submitted work. Dr Prahl reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Allergy and Infectious Diseases, and the Marino Family Foundation outside the submitted work. Dr Gaw reported receiving grants from the National Institutes of Health and The Benioff Center for Microbiome Medicine outside the submitted work. Dr Cedars reported receiving grants from the National Institute on Aging and the NICHD, serving on the presidential chain of the American Society for Reproductive Medicine and on the executive committee of the American Gynecological & Obstetrical Society, and receiving personal fees for editorial and authorship duties from UpToDate outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of the ASPIRE (Assessing the Safety of Pregnancy in the Coronavirus Pandemic) Trial Population Selection
ASQ-3 indicates Ages & Stages Questionnaire, Third Edition; DBS, dried blood spot.
Figure 2.
Figure 2.. Association of Prenatal Infection vs No Prenatal Infection With Time of Developmental Delay Assessment by Model
Model 1: unadjusted mixed-effects model including only the month of the Ages & Stages Questionnaire, Third Edition measurement; infection status; a month-by-infection interaction term; and random intercepts for participants. Model 2: adjusted for covariates measured at baseline (chosen a priori, as shown in Table 1) including maternal age, race, ethnicity, educational level, household income, mild to severe general anxiety (based on the Generalized Anxiety Disorder 7), mild to severe depression (based on the Patient Health Questionnaire), and the duration of time between enrollment and the time at which COVID-19 vaccines became available to all adults (April 19, 2021). Model 3: adjusted for covariates measured at baseline and infant sex and preterm birth (delivered <37 weeks’ gestation). Whiskers correspond to 95% CI ranges. ARRs indicates adjusted risk ratios.
See this image and copyright information in PMC

Comment in

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