Limited Prenatal COVID-19 Impact on Child Development

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

Background

Prenatal exposure to viral diseases such as influenza and SARS has been related to poor neurodevelopmental outcomes in offspring, including lower IQ and an increased risk of neuropsychiatric disorders. SARS-CoV-2 infection during pregnancy may have a comparable effect on infant neurodevelopment due to maternal systemic inflammation.

Previous research, largely limited to the first 18 months, demonstrated minimal effects and sometimes lacked proper comparison groups or did not examine dimensions such as temperament.

Longitudinal studies into later life are required to properly evaluate the possible impacts of prenatal SARS-CoV-2 exposure. Further research is needed to evaluate whether neurodevelopmental effects occur over time.

Prenatal COVID-19 – About the study

Participants were chosen from the pan-Canadian longitudinal pregnancy During the Coronavirus Disease 2019 (COVID-19) Pandemic Study, which is looking into the pandemic’s impact on pregnant women and their children across Canada.

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

The SARS-CoV-2 exposure group included children born to moms who had a positive polymerase chain reaction (PCR) test for SARS-CoV-2 while pregnant.

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

Demographic and socioeconomic information were gathered during enrolling. Standardized questionnaires were used to assess the temperament of children aged 6 and 24 months. The Ages and Stages Questionnaire was used to assess developmental and socioemotional milestones at 12 and 24 months of age.

SPSS was used to conduct statistical analysis, with potential confounders such as prenatal medical problems and household socioeconomic status taken into account. Mixed models were used to investigate developmental changes across time.

Supplemental analyses investigated the potential moderating effects of child sex, exposure trimester, and infection severity, and used multiple imputations to account for missing data.

Study results

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

Notably, birthing parents with SARS-CoV-2 infection had lower levels of education than those in the comparator group. Aside from educational differences, no significant variations were detected between the groups for parent or child sociodemographic or clinical factors, such as birth weight, gestational age, or the kid’s age at the assessment.

The average gestational age when the birthing parents contracted SARS-CoV-2 was 20.70 weeks (SD 9.30). Additional infection information revealed that the majority of infected patients (99%) were symptomatic, with more than half experiencing lasting symptoms (55%), and only a tiny proportion requiring hospitalization (5%).

Covariance analyses, after controlling 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 than the control group.

The exposed children demonstrated higher regulating behavior in everyday circumstances, with a mean difference of 0.19 (95% CI, 0.02 to 0.36; P =.03; ηp² = 0.01). There were no significant differences between the two groups in terms of any other outcome measures assessed.

Further studies using mixed models, which further controlled for pre-pregnancy medical problems and household socioeconomic status, revealed that group membership (exposed vs. comparison) had no significant relationship with the intercepts or slopes of any neurodevelopmental outcomes.

This shows that prenatal exposure to SARS-CoV-2 infection had no meaningful effect on the children’s long-term developmental trajectories.

Supplemental analysis investigated possible interactions and other factors. The relationship between child sex and infection exposure status had no significant effect on neurodevelopmental outcomes at any time point studied, nor did it alter changes in neurodevelopment over time.

Furthermore, neither the trimester of exposure nor the severity of the maternal infection were substantially linked with any neurodevelopmental outcomes at 6, 12, or 24 months.

It was discovered that missing data on particular measures was associated with exposure status; however, when analyses were performed with multiple imputations to account for missing data, the results remained the same.

Conclusions

To summarize, the study found that prenatal exposure was related with slightly more regulated behavior at 6 months, implying improved attentional capacity, but the impact size was small. Between 6 and 24 months, there were no significant associations with other outcomes or developmental changes.

These findings suggest that prenatal SARS-CoV-2 exposure has no effect on neurodevelopment in the first two years of life. Adverse outcomes observed during the pandemic may be due to psychological factors rather than direct prenatal infection effects.

For more information: Vrantsidis DM, van de Wouw M, Hall ERM, et al. (2024) Neurodevelopment in the First 2 Years of Life Following Prenatal Exposure to Maternal SARS-CoV-2 Infection. JAMA Netw Open. doi:10.1001/jamanetworkopen.2024.43697.https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825989