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Observational Study
. 2023 Apr 3;6(4):e237396.
doi: 10.1001/jamanetworkopen.2023.7396.

Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy

Morgan R Firestein  1 , Lauren C Shuffrey  1 , Yunzhe Hu  1 , Margaret Kyle  2 , Maha Hussain  2 , Catherine Bianco  3 , Violet Hott  2 , Sabrina P Hyman  2 , Mia Kyler  2 , Cynthia Rodriguez  2 , Melanie Tejeda Romero  2 , Helen Tzul Lopez  2 , Carmela Alcántara  4 , Dima Amso  3 , Judy Austin  5 , Jennifer M Bain  6 , Jennifer Barbosa  1 , Ashley N Battarbee  7 , Ann Bruno  8 , Sharon Ettinger  9 , Pam Factor-Litvak  10 , Suzanne Gilboa  11 , Sylvie Goldman  6 , Cynthia Gyamfi-Bannerman  12 , Panagiotis Maniatis  11 , Rachel Marsh  1   13 , Tyler Morrill  14 , Mirella Mourad  9 , Rebecca Muhle  1 , Gabriella Newes-Adeyi  14 , Kimberly G Noble  15 , Kally C O'Reilly  1   13 , Anna A Penn  2 , Lawrence Reichle  14 , Ayesha Sania  1 , Vera Semenova  11 , Wendy G Silver  6 , Grace Smotrich  2 , Alan T Tita  7 , Nim Tottenham  3 , Michael Varner  8 , Martha G Welch  1   2   16 , Noelia Zork  9 , Donna Garey  17 , William P Fifer  1   2 , Melissa S Stockwell  2   5 , Catherine Monk  1   9   13 , Fatimah Dawood  11 , Dani Dumitriu  1   2
Affiliations
Observational Study

Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy

Morgan R Firestein et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Firestein reported receiving grants from the Society for Research in Child Development during the conduct of the study. Dr Gyamfi-Bannerman reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the conduct of the study and personal fees from Medela outside the submitted work. Dr Tottenham reported receiving grants from the National Institute of Mental Health and the National Science Foundation outside the submitted work. Dr Fifer reported receiving grants from Columbia University during the conduct of the study. Dr Dumitriu reported receiving grants from the W.K. Kellogg Foundation and funding for the Nurture Science Program (for which Dr. Dumitriu serves as director) from Einhorn Collaborative during the conduct of the study and personal fees from Medela and the Society for Neuroscience outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cohort Flowchart
COMBO indicates COVID-19 Mother Baby Outcomes; CUIMC, Columbia University Irving Medical Center; DAYC-2, Developmental Assessment of Young Children, second edition; ESPI COMBO, Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy plus COMBO substudy; UAB, University of Alabama; and Utah, University of Utah.
Figure 2.
Figure 2.. Unadjusted Standard Scores for Each DAYC-2 Subdomain
Horizontal dashed lines represent the normative mean score for each subdomain. DAYC-2 indicates Developmental Assessment of Young Children, second edition.
See this image and copyright information in PMC

Comment in

  • doi: 10.1001/jamanetworkopen.2023.7403

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