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

• Published in: European journal of pediatrics Vol. 182; no. 5; pp. 2041 - 2055
• Main Authors: Pinheiro, Gabriela Soutto Mayor Assumpção, de Souza, Rayany Cristina, de Oliveira Azevedo, Vivian Mara Gonçalves, Guimarães, Nathalia Sernizon, Pires, Laura Gregório, Lemos, Stela Maris Aguiar, Alves, Claudia Regina Lindgren
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-05-2023; Springer Nature B.V
• Subjects: Child; Child Development; Complications; Coronaviruses; COVID-19; COVID-19 - epidemiology; Female; Fetuses; Humans; Immune response; Infant; Infants; Inflammation; Intrauterine exposure; Medicine; Medicine & Public Health; Meta-analysis; Motor skill; Pandemics; Pediatrics; Pregnancy; Pregnancy Outcome; Problem solving; Quality control; Review; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; COVID-19; Pregnancy; Infant; SARS-CoV-2; Child development; Maternal exposure
• ISSN: 1432-1076; 0340-6199; 1432-1076
• DOI: 10.1007/s00431-023-04910-8

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
2
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
2
 = 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.