Intrauterine SARS-CoV-2 Exposure and Infant Neurodevelopment through 18 Months of Age: Findings from the Researching COVID to Enhance Recovery (RECOVER) Pregnancy Study

OBJECTIVE: To assess associations between exposure to intrauterine SARS-CoV-2 and subsequent child neurodevelopment in a large, diverse cohort with confirmation of maternal SARS-CoV-2 status. STUDY DESIGN: The Researching COVID to Enhance Recovery (RECOVER) Pregnancy Cohort enrolled adults with and without SARS-CoV-2 during pregnancy and their offspring born January 2020 through December 2023 at 23 sites across the US. Neurodevelopment was assessed at 12 months with the Ages & Stages Questionnaire, 3rd edition (ASQ-3) and at 18 months with the ASQ Social-Emotional (ASQ-SE) and the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). We compared exposed and unexposed infants' ASQ-3 total and subdomain scores, ASQ-SE and M-CHAT-R scores, and proportions meeting published referral thresholds, using multivariable linear and logistic regression. RESULTS: Among 1179 participants enrolled, 1008 (85.5%) had exposure, with 806 (80.0%) exposed during Omicron predominance. Of those with known timing, 349 (41.4%) and 295 (35.0%) were exposed in the second and third trimesters of pregnancy, respectively. Exposure was not associated with differences in the ASQ-3 (adjusted difference -0.61, 95% CI -10.03 to 8.81) or ASQ-3 subdomains at 12 months, ASQ-SE at 18 months (adjusted difference 0.19, 95% CI -4.02 to 4.41), or M-CHAT-R scores. Findings were similar for proportions meeting referral thresholds and when stratified by variant or by trimester. CONCLUSIONS: In this multicenter cohort largely exposed since Omicron and in second or third trimester, intrauterine SARS-CoV-2 exposure was not associated with neurodevelopmental screening outcomes through 18 months of age. Further assessments of the impact of intrauterine SARS-CoV-2 on neurodevelopment beyond 18 months of age are needed.