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In Utero Exposure to Maternal COVID-19 Vaccination and Offspring Neurodevelopment at 12 and 18 Months
Eleni G Jaswa1, Marcelle I Cedars1, Karla J Lindquist2
1Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, University of California, San Francisco, San Francisco.
Insights
COVID-19 vaccination during pregnancy did not impact infant neurodevelopment. This study found no significant differences in developmental outcomes at 12 and 18 months for infants exposed to COVID-19 vaccines in utero.
Area of Science:
- Obstetrics and Gynecology
- Pediatric Neurodevelopment
- Infectious Disease Epidemiology
Background:
- Maternal COVID-19 vaccination uptake was limited by safety concerns for unborn children.
- Limited data exists on early neurodevelopmental outcomes following in utero exposure to COVID-19 vaccines.
Purpose of the Study:
- To assess the association between maternal COVID-19 vaccination during pregnancy and infant neurodevelopmental outcomes.
- To evaluate neurodevelopmental scores using the Ages and Stages Questionnaire, third edition (ASQ-3) at 12 and 18 months.
Main Methods:
- Prospective cohort study (Assessing the Safety of Pregnancy During the Coronavirus Pandemic - ASPIRE) with remote enrollment.
- Comparison of neurodevelopmental scores between infants with in utero exposure to maternal COVID-19 vaccination and unexposed infants.
- Analysis of ASQ-3 scores at 12 and 18 months, adjusting for maternal and infant factors.
Main Results:
- No significant differences in abnormal ASQ-3 screens for developmental delay were observed at 12 months (aRR, 1.14; 95% CI, 0.97-1.33) or 18 months (aRR, 0.88; 95% CI, 0.72-1.07).
- Crude analyses also showed no significant differences in developmental delay prevalence at either time point.
- Adjustments for maternal demographics, mental health, preterm birth, and infant sex did not alter the findings.
Conclusions:
- COVID-19 vaccination during pregnancy appears safe concerning infant neurodevelopment up to 18 months of age.
- Findings support the safety of maternal COVID-19 vaccination for fetal neurodevelopment.
- Further long-term research is recommended to confirm these findings and inform clinical practice.
Importance:
Uptake of COVID-19 vaccines among pregnant individuals was hampered by safety concerns around potential risks to unborn children. Data clarifying early neurodevelopmental outcomes of offspring exposed to COVID-19 vaccination in utero are lacking.
Objective:
To determine whether in utero exposure to maternal COVID-19 vaccination was associated with differences in scores on the Ages and Stages Questionnaire, third edition (ASQ-3), at 12 and 18 months of age.
Design, Setting, And Participants:
This prospective cohort study, Assessing the Safety of Pregnancy During the Coronavirus Pandemic (ASPIRE), enrolled pregnant participants from May 2020 to August 2021; follow-up of children from these pregnancies is ongoing. Participants, which included pregnant individuals and their offspring from all 50 states, self-enrolled online. Study activities were performed remotely.
Exposure:
In utero exposure of the fetus to maternal COVID-19 vaccination during pregnancy was compared with those unexposed.
Main Outcomes And Measures:
Neurodevelopmental scores on validated ASQ-3, completed by birth mothers at 12 and 18 months. A score below the established cutoff in any of 5 subdomains (communication, gross motor, fine motor, problem solving, social skills) constituted an abnormal screen for developmental delay.
Results:
A total of 2487 pregnant individuals (mean [SD] age, 33.3 [4.2] years) enrolled at less than 10 weeks' gestation and completed research activities, yielding a total of 2261 and 1940 infants aged 12 and 18 months, respectively, with neurodevelopmental assessments. In crude analyses, 471 of 1541 exposed infants (30.6%) screened abnormally for developmental delay at 12 months vs 203 of 720 unexposed infants (28.2%; χ2 = 1.32; P = .25); the corresponding prevalences at 18 months were 262 of 1301 (20.1%) vs 148 of 639 (23.2%), respectively (χ2 = 2.35; P = .13). In multivariable mixed-effects logistic regression models adjusting for maternal age, race, ethnicity, education, income, maternal depression, and anxiety, no difference in risk for abnormal ASQ-3 screens was observed at either time point (12 months: adjusted risk ratio [aRR], 1.14; 95% CI, 0.97-1.33; 18 months: aRR, 0.88; 95% CI, 0.72-1.07). Further adjustment for preterm birth and infant sex did not affect results (12 months: aRR, 1.16; 95% CI, 0.98-1.36; 18 months: aRR, 0.87; 95% CI, 0.71-1.07).
Conclusions And Relevance:
Results of this cohort study suggest that COVID-19 vaccination was safe during pregnancy from the perspective of infant neurodevelopment to 18 months of age. Additional longer-term research should be conducted to corroborate these findings and buttress clinical guidance with a strong evidence base.
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