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In Utero Exposure to Maternal COVID-19 and Offspring Neurodevelopment Through Age 24 Months
Eleni G Jaswa1, Heather G Huddleston1, Karla J Lindquist2
1Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco.
Insights
Maternal COVID-19 infection during pregnancy was not linked to abnormal neurodevelopmental screening in children up to 24 months old. Further research is needed to understand potential long-term effects on child development.
Area of Science:
- Perinatal Medicine
- Neurodevelopmental Pediatrics
- Infectious Diseases
Background:
- Maternal infections in utero are linked to adverse neurodevelopmental outcomes in offspring.
- The widespread nature of SARS-CoV-2 (COVID-19) necessitates understanding its impact on fetal development.
Purpose of the Study:
- To determine if in utero exposure to maternal COVID-19 is associated with abnormal neurodevelopmental scores in children at 12, 18, and 24 months of age.
Main Methods:
- Prospective cohort study (ASPIRE trial) of pregnant individuals and their children.
- Maternal COVID-19 exposure was the primary exposure variable.
- Child neurodevelopment was assessed using the Ages & Stages Questionnaires, Third Edition, at 12, 18, and 24 months postpartum.
Main Results:
- No significant association was found between maternal COVID-19 exposure and abnormal neurodevelopmental screening at 12, 18, or 24 months.
- Adjusted risk ratios for abnormal screens were 1.07 (12 months), 1.15 (18 months), and 1.01 (24 months).
- Supplemental analyses showed no differential risk based on trimester of infection, fever, or vaccination status.
Conclusions:
- In utero exposure to maternal COVID-19 was not associated with abnormal neurodevelopmental screening in children up to 24 months postpartum.
- Further research on diverse populations is warranted due to the developing fetal brain's sensitivity to maternal immune activation.
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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