Limited impact of prenatal COVID-19 exposure on child neurodevelopmental outcomes

New study finds minor differences in infant regulatory behavior but no significant long-term effects on neurodevelopment.

Study: Neurodevelopment in the First 2 Years of Life Following Prenatal Exposure to Maternal SARS-CoV-2 Infection. Image Credit: mojo cp/Shutterstock.com

In a recent study published in the JAMA Network Open, a group of researchers assessed whether prenatal exposure to maternal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection impacts child neurodevelopmental outcomes during the first two years of life.

Background

Prenatal exposure to viral infections like influenza and SARS has been linked to adverse neurodevelopmental outcomes in children, such as lower Intelligence Quotient (IQ) and increased risk of neuropsychiatric disorders. SARS-CoV-2 infection during pregnancy may similarly affect child neurodevelopment due to maternal systemic inflammation.

Previous studies, mostly limited to the first 18 months, have found limited impacts and often lacked appropriate comparison groups or did not assess domains like temperament.

There is a need for longitudinal research into later childhood to fully understand the potential effects of prenatal SARS-CoV-2 exposure. Therefore, further research is essential to determine if neurodevelopmental impacts emerge over time.

About the study

Participants were drawn from the pan-Canadian longitudinal pregnancy During the Coronavirus Disease 2019 (COVID-19) Pandemic Study, a cohort investigating the pandemic's impact on pregnant individuals and their children across Canada.

Eligible participants were pregnant individuals aged 17 or older, up to 35 weeks gestation, able to read and write in English or French, and recruited between April 2020 and July 2022.

The SARS-CoV-2 exposure group consisted of children born to mothers who had a confirmed positive polymerase chain reaction (PCR) test for SARS-CoV-2 during pregnancy.

The negative comparison group included children whose mothers had no flu-like symptoms or positive tests during pregnancy, had not received SARS-CoV-2 vaccination before or during pregnancy, and whose postpartum dried blood spot samples tested negative for SARS-CoV-2 antibodies.

Demographic and socioeconomic data were collected at enrollment. Child temperament was assessed at ages 6 and 24 months using standardized questionnaires. Developmental and socioemotional milestones were measured at 12 and 24 months using the Ages and Stages Questionnaires.

Statistical analyses were performed using SPSS, adjusting for prepregnancy medical conditions and household socioeconomic status as potential confounders. Mixed models were employed to examine developmental changes over time.

Supplemental analyses explored potential moderating effects of child sex, trimester of exposure, and infection severity and accounted for missing data using multiple imputations.

Study results 

In the present study, 96 children whose birthing parents had confirmed positive PCR tests during pregnancy were examined. These children had a mean gestational age at birth of 39.20 weeks (SD 1.50), with 47% being male. The comparison group consisted of 800 healthy children whose birthing parents tested negative for SARS-CoV-2 antibodies in their dried blood spot samples; these children had a mean gestational age at birth of 39.47 weeks (SD 1.54), and 49% were male.

Notably, birthing parents who had a SARS-CoV-2 infection possessed lower levels of education compared to those in the comparison group. Other than educational differences, no significant disparities were found between the groups regarding parent or child sociodemographic or clinical characteristics, including birth weight,  gestational age, or the child's age at assessment.

The mean gestational age at which the birthing parents contracted SARS-CoV-2 was 20.70 weeks (SD 9.30). Additional infection details indicated that most infected participants were symptomatic (99%), and over half experienced lingering symptoms (55%), while a small portion required hospitalization (5%). 

Analyses of covariance, adjusted for prepregnancy medical conditions and household socioeconomic status, revealed that children exposed to SARS-CoV-2 infection in utero had higher regulation scores on the Infant Behavior Questionnaire-Revised Very Short Form at 6 months of age compared to the comparison group.

The mean difference was 0.19 (95% CI, 0.02 to 0.36; P = .03; ηp² = 0.01), suggesting more regulatory behavior in everyday contexts among the exposed children. However, no significant differences were observed between the two groups in terms of any other outcome measures assessed.

Further analyses utilizing mixed models, also adjusted for prepregnancy medical conditions and household socioeconomic status, indicated that group membership (exposed vs. comparison) was not significantly associated with the intercepts or slopes of any neurodevelopmental outcomes.

This suggests that prenatal exposure to SARS-CoV-2 infection did not have a significant impact on the developmental trajectories of the children over time.

Supplemental analyses explored potential interactions and additional factors. The interaction between child sex and infection exposure status was not significant for neurodevelopmental outcomes at any assessed time point, nor did it influence changes in neurodevelopment over time.

Additionally, neither the trimester during which the exposure occurred nor the severity of the maternal infection was significantly associated with any neurodevelopmental outcomes at ages 6, 12, or 24 months.

It was noted that missing data on certain measures were associated with exposure status; however, when analyses were rerun using multiple imputations to account for missing data, the results remained unchanged. 

Conclusions

To summarize, findings showed that prenatal exposure was associated with slightly more regulatory behavior at 6 months, suggesting better attentional ability, but the effect size was minimal. No significant associations were found with other outcomes or developmental changes between 6 and 24 months.

These results indicate that prenatal SARS-CoV-2 exposure has a negligible impact on neurodevelopment in the first two years of life. Adverse outcomes reported during the pandemic may stem from psychosocial factors rather than direct prenatal infection effects.