Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy
Authors: Firestein Morgan R. , Shuffrey Lauren C. , Hu Yunzhe , Kyle Margaret , Hussain Maha , Bianco Catherine , Hott Violet , Hyman Sabrina P. , Kyler Mia , Rodriguez Cynthia , Tejeda Romero Melanie , Tzul Lopez Helen , Alcántara Carmela , Amso Dima , Austin Judy , Bain Jennifer M. , Barbosa Jennifer , Battarbee Ashley N. , Bruno Ann , Ettinger Sharon , Factor-Litvak Pam , Gilboa Suzanne , Goldman Sylvie , Gyamfi-Bannerman Cynthia , Maniatis Panagiotis , Marsh Rachel , Morrill Tyler , Mourad Mirella , Muhle Rebecca , Newes-Adeyi Gabriella , Noble Kimberly G. , O’Reilly Kally C. , Penn Anna A. , Reichle Lawrence , Sania Ayesha , Semenova Vera , Silver Wendy G. , Smotrich Grace , Tita Alan T. , Tottenham Nim , Varner Michael , Welch Martha G. , Zork Noelia , Garey Donna , Fifer William P. , Stockwell Melissa S. , Monk Catherine , Dawood Fatimah , Dumitriu Dani 
Published: April 2023

Importance

Associations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding.

Objective

To assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months.

Design, Setting, and Participants

This cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants.

Exposures

Maternal symptomatic or asymptomatic SARS-CoV-2 infection.

Main Outcomes and Measures

Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language.

Results

Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (β = 0.31; 95% CI, −2.97 to 3.58), gross motor (β = 0.82; 95% CI, −1.34 to 2.99), fine motor (β = 0.36; 95% CI, −0.74 to 1.47), expressive language (β = −1.00; 95% CI, −4.02 to 2.02), or receptive language (β = 0.45; 95% CI, −2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores.

Conclusions and Relevance

In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.