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Eur J Pediatr . Effects of intrauterine exposure to SARS-CoV-2 on infants' development: a rapid review and meta-analysis

tetano

Editor, Senior Moderator
Eur J Pediatr


. 2023 Mar 11.
doi: 10.1007/s00431-023-04910-8. Online ahead of print.
Effects of intrauterine exposure to SARS-CoV-2 on infants' development: a rapid review and meta-analysis


Gabriela Soutto Mayor Assumpção Pinheiro[SUP] 1 [/SUP], Rayany Cristina de Souza[SUP] 2 [/SUP], Vivian Mara Gonçalves de Oliveira Azevedo[SUP] 3 [/SUP], Nathalia Sernizon Guimarães[SUP] 4 [/SUP], Laura Gregório Pires[SUP] 5 [/SUP], Stela Maris Aguiar Lemos[SUP] 6 [/SUP], Claudia Regina Lindgren Alves[SUP] 7 [/SUP]



Affiliations

Abstract

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. We aimed to systematically review and summarize the evidence regarding the effects of intrauterine exposure to SARS-CoV-2 on infant development and behavior. Scopus, PubMed, Web of Science, CINAHL, and PsycNet databases were searched for studies published up to February 6, 2023, investigating the effects of gestational SARS-CoV-2 on infant development and behavior. We performed 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 I[SUP]2[/SUP] statistic. The search identified 2,782 studies. After removing duplicates and applying the eligibility criteria, we performed a narrative synthesis of 10 included studies and a meta-analysis of 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 the non-exposed children or 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 infants (heterogeneity: I[SUP]2[/SUP] = 69% and 88%, respectively). There was no difference between the exposed and non-exposed infants in the communication, gross motor, and personal-social ASQ-3 domains. Conclusion: We did not find evidence confirming the association between SARS-CoV-2 gestational exposure and neurodevelopmental delays. However, the meta-analysis indicated that gestational exposure negatively affected fine motor and problem-solving skills. Robust evidence on this topic is still incipient, and the available studies present methodological inconsistencies that limit the drawing of clear-cut conclusions. PROSPERO registration: #CRD42022308002; March 14, 2022. What is Known: • COVID-19 is associated with adverse pregnancy outcomes potentially linked to neurodevelopmental delays. • SARS-CoV-2 vertical transmission is rare; however, infections during pregnancy can be deleterious to the fetus, possibly mediated by maternal immune activation and other inflammatory mechanisms. What is New: • No evidence of increased developmental delay rates among SARS-CoV-2 gestational-exposed infants was found. However, a meta-analysis of three studies showed lower scores in fine motor and personal social ASQ-3 domains among exposed infants. • SARS-CoV-2 gestational exposure and the pandemic can affect child development via many mechanisms. Potential neurodevelopmental sequelae of SARS-CoV-2 exposure during gestation have not been ruled out.

Keywords: COVID-19; Child development; Infant; Maternal exposure; Pregnancy; SARS-CoV-2.
 
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