Impacto da exposição ao SARS-CoV-2 durante a gravidez no neurodesenvolvimento infantil: revisão sistemática e metanálise

Miquilussi, Paloma Alves; Aguiar, Thalis Vasconcellos de; Cruz, Paula Lima da; Duca, Ana Paula; Ribeiro, Marcos; Araújo, Cristiano Miranda de; Santos, Rosane Sampaio; Schroder, Angela Graciela Deliga; Crippa, Ana Chrystina de Souza

doi:10.1590/1984-0462/2025/43/2025094

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Review Article • Rev. paul. pediatr. 43 • 2025 • https://doi.org/10.1590/1984-0462/2025/43/2025094 linkcopiar

Impacto da exposição ao SARS-CoV-2 durante a gravidez no neurodesenvolvimento infantil: revisão sistemática e metanálise

Autoria SCIMAGO INSTITUTIONS RANKINGS

Objetivo: Investigar o impacto da exposição intrauterina ao SARS-CoV-2 no neurodesenvolvimento de crianças até os dois anos de idade.

Fontes de dados: Foram utilizadas combinações de palavras-chave e truncamentos em cinco bases de dados: Excerpta Medica database (EMBASE), Latin American and Caribbean Literature in Health Sciences (LILACS), United States National Library of Medicine/Medical Literature Analysis and Retrieval System Online (PubMed/Medline), Scopus e Web of Science. Além disso, literaturas cinzentas foram consultadas, incluindo por meio da American Speech-Language-Hearing Association (ASHA), Google Scholar e Proquest Dissertation and Thesis. A qualidade da evidência foi avaliada com o uso da Joanna Briggs Institute's Critical Appraisal Checklist. Uma metanálise de efeito aleatório foi conduzida utilizando a linguagem R no R Studio version 1.2.1335 (Rstudio Inc, Boston, USA). O peso dos estudos foi calculado pelo método Mantel-Haenszel, enquanto a variância (Tau²) foi estimada por DerSimonian-Laird. Para normalizar os dados, aplicou-se o método do arcoseno duplo de Freeman-Tukey. Intervalos de confiança de 95% foram calculados para cada metanálise.

Síntese dos dados: Foram incluídos nove artigos na síntese qualitativa e oito na quantitativa. Não houve diferença estatisticamente significativa no neurodesenvolvimento entre bebês expostos e não expostos ao SARS-CoV-2 na gestação [risco relativo — RR=5,10; intervalo de confiança de 95% — IC95% 0,36–71,85; I²=91%]. No entanto, para o domínio "motricidade fina", o grupo exposto apresentou risco 2,38 vezes maior de déficit [IC95% 1,22–4,68] em comparação ao grupo não exposto, com baixa heterogeneidade na análise (I²=0%).

Conclusões: A exposição ao SARS-CoV-2 na gestação não se mostrou associada a atraso no neurodesenvolvimento, embora tenha sido relacionada a maior risco de atraso no desenvolvimento da motricidade fina. Contudo, essa evidência ainda é incerta em razão da limitação de estudos e da heterogeneidade metodológica.

Palavra-chave:
COVID-19; Transtornos do neurodesenvolvimento; Complicações na Gravidez; Infecciosa

Database	Search (October 2023) Updated
EMBASE	("COVID-19" OR "SARS-CoV-2" OR "Severe Acute Respiratory Syndrome Coronavirus 2" OR "NCOV" OR "2019 NCOV" OR "severe acute respiratory syndrome" OR "severe acute respiratory syndrome-related coronavirus") AND ("Neurodevelopment" OR "neurodevelopmental disorders" OR "developmental disabilities" OR "developmental disorder")
LILACS	("COVID-19" OR "SARS-CoV-2" OR "Severe Acute Respiratory Syndrome Coronavirus 2"OR "NCOV" OR "2019 NCOV" OR "severe acute respiratory syndrome" OR "severe acute respiratory syndrome-related coronavirus" OR "Síndrome Respiratória Aguda Grave Coronavírus 2" OR "Síndrome Respiratorio Agudo Severo Coronavirus 2" OR "síndrome respiratória aguda grave" OR "Síndrome respiratorio agudo severo" OR "coronavírus relacionado à síndrome respiratória aguda grave" OR "coronavirus relacionado con el síndrome respiratorio agudo severo") AND ("Neurodevelopment" OR "neurodevelopmental disorders" OR "developmental disabilities" OR "developmental disorder" OR "Neurodesenvolvimento" OR "Neurodesarrollo" OR "distúrbios do neurodesenvolvimento" OR "trastornos del neurodesarrollo" OR "deficiências de desenvolvimento" OR "discapacidades del desarrollo" OR "transtorno de desenvolvimento" OR "trastorno del desarrollo")
PubMed	("COVID-19"[All Fields] OR "COVID-19"[MeSH Terms] OR "SARS-CoV-2"[All Fields] OR "sars-cov-2"[MeSH Terms] OR "Severe Acute Respiratory Syndrome Coronavirus 2"[All Fields] OR "NCOV"[All Fields] OR "2019 NCOV"[All Fields] OR "severe acute respiratory syndrome"[MeSH Terms] OR "Severe Acute Respiratory Syndrome"[Text Word] OR "severe acute respiratory syndrome-related coronavirus"[MeSH Terms] OR "Severe acute respiratory syndrome-related coronavirus"[Text Word]) AND ("Neurodevelopment"[All Fields] OR "neurodevelopmental"[All Fields] OR "neurodevelopmental disorders"[MeSH Terms] OR "Neurodevelopmental Disorders"[Text Word] OR "developmental disabilities"[MeSH Terms] OR "developmental disorder"[Text Word])
Scopus	TITLE-ABS-KEY ("COVID-19" OR "SARS-CoV-2" OR "Severe Acute Respiratory Syndrome Coronavirus 2" OR "NCOV" OR "2019 NCOV" OR "severe acute respiratory syndrome" OR "severe acute respiratory syndrome-related coronavirus") AND TITLE-ABS-KEY("Neurodevelopment" OR "neurodevelopmental disorders" OR "developmental disabilities" OR "developmental disorder")
Web of Science	TS=("COVID-19" OR "SARS-CoV-2" OR "Severe Acute Respiratory Syndrome Coronavirus 2" OR "NCOV" OR "2019 NCOV" OR "severe acute respiratory syndrome" OR "severe acute respiratory syndrome-related coronavirus") AND TS=("Neurodevelopment" OR "neurodevelopmental disorders" OR "developmental disabilities" OR "developmental disorder")
LIVIVO	("COVID-19" OR "SARS-CoV-2" OR "Severe Acute Respiratory Syndrome Coronavirus 2" OR "NCOV" OR "2019 NCOV" OR "severe acute respiratory syndrome" OR "severe acute respiratory syndrome-related coronavirus") AND ("Neurodevelopment" OR "neurodevelopmental disorders" OR "developmental disabilities" OR "developmental disorder")
ProQuest	NOFT("COVID-19" OR "SARS-CoV-2" OR "Severe Acute Respiratory Syndrome Coronavirus 2" OR "NCOV" OR "2019 NCOV" OR "severe acute respiratory syndrome" OR "severe acute respiratory syndrome-related coronavirus") AND NOFT("Neurodevelopment" OR "neurodevelopmental disorders" OR "developmental disabilities" OR "developmental disorder")

Study, Country	Study design	Sample size	Assessment method	Results
Ayede et al.²⁴ Kuwait	Cross-sectional	298	ASQ-3	A delay in development was identified in 30 (10.1%) of the babies.
Colom et al.²⁵ Spain	Cross-sectional	55	Bayley-III	96% had normal development, 1 had a developmental disorder, and 1 had a mild developmental delay.
Fajardo-Martinez et al.²⁶ EUA	Cohort	300 (172 exposed and 128 unexposed)	Bayley-III e ASQ-3	In the assessment using Bayley-III, 12 children (9.4%) from the exposed group showed signs of severe developmental delay, while 2 (1.6%) from the non-exposed group did. Using the ASQ-3, 80 children scored below the threshold.
Mulkey et al.²⁷ EUA	Cross-sectional	28	ASQ-3	17 babies showed scores close to or below the threshold considered normal.
Namakin et al.²⁸ Irã	Cohort	342 (161 exposed and 181 unexposed)	ASQ-3	This study found no significant differences between babies exposed and unexposed to COVID-19 regarding neurological development. There were no differences in the average scores of developmental tests, except in the communication area.
Santos et al.²⁹ Brasil	Cohort	137 (69 exposed and 68 unexposed)	ASQ-3	The prevalence of atypical development was 35.7% at 4 months, 7% at 6 months, and 32.1% at 12 months. No association was found between the ASQ-3 scores and the severity of maternal infection, nor with the trimester of infection.
Shah et al.³⁰ EUA	Cohort	51	ASQ-3	Of the 51 individuals, twelve (24%) were below the cutoff point, and twenty-seven (53%) were below or close to the cutoff point in at least one developmental domain.
Shuffrey et al.³¹ EUA	Cohort	255 (114 exposed and 141 unexposed)	ASQ-3	In utero exposure to maternal SARS-CoV-2 infection was not associated with significant differences in any subdomain of the ASQ-3, regardless of the timing or severity of the infection.
Wang et al.³² China	Cross-sectional	57	ASQ-3	The overall proportion in the domains: communication, gross motor, fine motor, problem-solving, or personal-social ranged from 13.5 to 23.1%, while in the socioemotional domain, the proportion was 86.4%.

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[TFN1] ASQ-3: Ages and Stages Questionnaires – third edition; Bayley-III: Bayley Scales of Infant and Toddler Development – third edition; ³SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus.