COVID-19 vaccination during pregnancy and offspring neurodevelopment

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The increase in COVID-19 vaccination in pregnant people has brought on safety concerns for the unborn child and questions of neurodevelopment. Results of a prospective cohort study published in JAMA Pediatrics suggest that in utero vaccination was safe for the infant regarding neurodevelopment up to 18 months of age.

Pregnant individuals were excluded from early, large-scale clinical trials of COVID-19 vaccines, leaving questions about the impact from vaccine exposure that the offspring could face.

Ranging genetic and environmental factors could underline neurodevelopmental disorders, with fetal exposure to maternal inflammation presenting a potential source for risk.

“For example,” the authors wrote. “In utero exposures to other infections including influenza and rubella have been linked to subsequent increases in lifelong neurodevelopmental and psychiatric impairments including autism spectrum disorder, intellectual disability, schizophrenia, anxiety, and depression."

To determine if in utero exposure to maternal COVID-19 vaccination was associated with risk for neurodevelopmental impairment in 12- and 18-month-old infants, investigators designed the prospective cohort Assessing the Safety of Pregnancy During the Coronavirus Pandemic (ASPIRE) study.

From May 2020 to August 2021, the study enrolled pregnant people aged 18 years and older at 10 weeks’ gestation or less. Completing study activities remotely, participants were followed up through pregnancy and for up to 2 years postpartum.

Completion of the baseline demographics questionnaire, the Ages and Stages Questionnaire (3rd edition [ASQ-3]) at 12 and 18 months postpartum, and of the vaccine history questionnaire (monthly) were inclusion criteria.

An abnormal screen on the ASQ-3, which would indicate risk for developmental delay, was the primary outcome of the study. The investigators established that, “An abnormal screen was defined as falling below the established threshold score (<2 SDs below the normative data average) on any of 5 subdomains: communication, gross motor, fine motor, problem solving, and social skills.”

The ASQ-3 featured 30 questions to indicate the frequency in which their child performed expected milestones, as scores ranged from 0 to 60 (worst to best, respectively). According to authors, the screener is “valid, reliable, and ubiquitous in clinical and research settings, with sensitivity of 86%, specificity 85%, and positive and negative predictive values of 54% and 78%, respectively.”

Vaccination for COVID-19 during pregnancy was the primary exposure, which was indicated by self-report and confirmed by investigators using dates of vaccinations compared to estimated dates of conception and delivery. Any dose of a vaccine series qualified as exposure, with the majority being messenger RNA vaccines.

In all, 2487 pregnant individuals were enrolled at less than 10 weeks’ gestation. With completed research activities, a total of 2261 aged 12 months and 1940 aged 18 months with neurodevelopmental assessments were included.

At 12 months, the prevalence of abnormal screens for developmental delay (ASQ-3 scores below established cutoff on at least 1 domain) was 30.6% among exposed. The prevalence of abnormal screens for unexposed at 12 months was 23.2% (χ2= 2.35; P = .13).

No differences were observed in risk of abnormal screen on the ASQ-3 after in utero exposure to vaccination at 12 or 18 months after adjusting for baseline race, ethnicity, maternal age, education, household income, depression, and anxiety (12 months: aRR, 1.14; 95% CI, 0.97-1.33; 18 months: aRR, 0.88; 95% CI, 0.72-1.07).

Without regard to exposure status, investigators observed more abnormal screens for developmental delay among male infants at 12 and 18 months of age compared to female infants, respectively (12 months: 325 of 980 [33.2%] vs 278 of 984 [28.3%]; χ2 = 5.57; P = .02; 18 months: 210 of 872 [24.1%] vs 161 of 836 [19.3%]; χ2 = 5.84; P = .02).

For female infants, a divergent pattern was demonstrated, as at 12 months, there was no difference in risk of abnormal ASQ-3 screen among exposed vs unexposed (aRR, 1.02; 95% CI, 0.81-1.30), though a reduction of risk was observed for exposed female infants at age 18 months (aRR, 0.69; 95% CI, 0.51-0.93).

Findings from the cohort study suggest that, “maternal vaccination against COVID-19 during pregnancy was safe from the perspective of offspring neurodevelopment through 18 months of age,” the study authors concluded.

Reference:

Jaswa EG, Cedars MI, Lindquist KJ, et al. In utero exposure to maternal COVID-19 vaccination and offspring neurodevelopment at 12 and 18 months. JAMA Pediatr. Published online January 22, 2024. doi:10.1001/jamapediatrics.2023.5743