In utero exposure to COVID-19 vaccine does not harm early infant development

Babies born to mothers who were vaccinated against COVID-19 during pregnancy are not at risk of developmental delays, according to a study.

Analyses of neurodevelopmental scores on the Ages and Stages Questionnaire, third edition (ASQ-3), showed no significant difference in the number of babies with developmental delay between the group exposed to COVID-19 vaccine in utero and the unexposed group both at either 12 months (30.6 percent vs 28.2 percent; p=0.25) or 18 months (20.1 percent vs 23.2 percent; p=0.13) of life. [JAMA Pediatr 2024;178:258-265]

In utero exposure to COVID-19 vaccine was not associated with an increased risk of abnormal ASQ-3 screens at either time point (12 months: adjusted risk ratio [aRR], 1.14, 95 percent confidence interval [CI], 0.97–1.33; 18 months: aRR, 0.88, 95 percent CI, 0.72–1.07) in multivariable mixed-effects logistic regression models adjusted for maternal age, race, ethnicity, education, income, maternal depression, and anxiety.

The results remained null after further adjustment for preterm birth and infant sex (12 months: aRR, 1.16, 95 percent CI, 0.98–1.36; 18 months: aRR, 0.87, 95 percent CI, 0.71–1.07).

“To our knowledge, this [study] represents the first meaningful evidence regarding the safety of maternal COVID-19 vaccination from the standpoint of early offspring neurodevelopment,” the investigators said.

Concerns regarding the potential impact of maternal COVID-19 vaccination on offspring have been raised. This concern, according to the investigators, is linked to the maternal immune activation theory, which suggests that triggering a strong inflammatory response during pregnancy may affect the neonatal neurodevelopment of the offspring, possibly due to the direct effects of proinflammatory cytokines on the placenta and developing foetal brain. [Front Neurosci 2023;17:1135559; Trends Mol Med 2022;28:319-330]

“However, current data are limited, and the impact of vaccination on cytokine profiles and the inflammatory response remain to be elucidated,” the investigators noted, adding that the ASQ-3 is a helpful tool for identifying children who might be at risk of developmental delays.

The study included 2,487 women (mean age 33.3 years, 89.3 percent White) who were enrolled at less than 10 weeks of gestation. These women completed at least one vaccination history questionnaire and the ASQ-3 questionnaire for their offspring at 12 months (n=2,261) and/or 18 months (n=1,940) of age. An abnormal ASQ-3 screen was defined as having scores below the established cutoff in any of the following subdomains: communication, gross motor, fine motor, problem solving, or social skills.

Most of the women (68.0 percent) reported having been COVID-19–vaccinated, with the majority receiving mRNA vaccine and few receiving a viral-vector vaccine.

The investigators called for further research to build an evidence base that can support real-time clinical guidance in the setting of novel exposures to mothers and infants.