Effects of intrauterine exposure to SARS-CoV-2 on infants’ development: A rapid review and meta-analysis

Abstract

Background Potential medium and long-term neurodevelopmental sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy have not been ruled out. Thus, we aimed to systematically review and summarize the evidence concerning the effects of intrauterine exposure to SARS-CoV-2 on infants’ development and behavior. Methods Scopus, PubMed, Web of Science, CINAHL, and PsycNet databases were searched for studies published up to November 04, 2022, investigating the repercussions of gestational SARS-CoV-2 on infants’ development and behavior. We performed a narrative synthesis according to updated protocols. Studies using comparison groups and with the Ages and Stages Questionnaires-Third Edition (ASQ-3) scores available were included in a meta-analysis performed according to Cochrane protocols. We used the Newcastle-Ottawa Quality Assessment Scale to analyze the risk of bias. Heterogeneity was calculated using the I2 statistic. Results The search identified 2,552 studies. After removing duplicates and applying the eligibility criteria, we performed a narrative synthesis on eight included studies and a meta-analysis on three. There was no evidence of higher developmental delay rates in infants exposed to SARS-CoV-2 during pregnancy compared to non-exposed infants. However, the exposed infants scored lower than either of non-exposed children and pre-pandemic cohorts in some domains. Pooled results from the random-effects model indicated that SARS-CoV-2-exposed infants had lower scores on fine motor (mean difference [MD]=-4.70, 95% confidence interval [CI]: -8.76; -0.63), and problem-solving (MD=-3.05, 95% CI: -5.88; -0.22) domains than non-exposed (heterogeneity: I2 = 69% and 88%, respectively). There was no difference between exposed and non-exposed infants in the communication, gross motor, and personal-social ASQ-3 domains. Conclusions We did not find evidence confirming the association between SARS-CoV-2 gestational exposure and neurodevelopmental delay. However, the meta-analysis indicated that gestational exposure negatively affected fine motor and problem-solving skills. Robust evidence on the topic is still incipient, and the available studies present methodological inconsistencies that limit the drawing of clear-cut conclusions.