Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects?

Emerging evidence suggests a potential link between maternal SARS-CoV-2 infection during early pregnancy and the development of congenital heart defects (CHD) in offspring. Although vertical transmission of SARS-CoV-2 is rare, the virus has been associated with placental complications and increased...

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Main Authors: Athina Samara, Conrado Milani Coutinho, Paul T. Heath, Asma Khalil
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Pediatrics
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Online Access:https://www.frontiersin.org/articles/10.3389/fped.2025.1643423/full
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author Athina Samara
Athina Samara
Athina Samara
Conrado Milani Coutinho
Paul T. Heath
Asma Khalil
Asma Khalil
Asma Khalil
author_facet Athina Samara
Athina Samara
Athina Samara
Conrado Milani Coutinho
Paul T. Heath
Asma Khalil
Asma Khalil
Asma Khalil
author_sort Athina Samara
collection DOAJ
description Emerging evidence suggests a potential link between maternal SARS-CoV-2 infection during early pregnancy and the development of congenital heart defects (CHD) in offspring. Although vertical transmission of SARS-CoV-2 is rare, the virus has been associated with placental complications and increased maternal morbidity. Recent studies from China report increased rates of CHD and anomalies such as situs inversus when infection occurs during gestational weeks 4–6, a critical window for cardiac development. Additional reports from different parts of the world also highlight post-pandemic increases in specific cardiac anomalies, including ventricular septal defects (VSDs). Multiple mechanisms may underlie these associations. SARS-CoV-2 can induce placental inflammation, compromise the cytotrophoblast barrier, and impair nutrient and gas exchange, potentially leading to fetal hypoxia and disrupted morphogenic signalling. Furthermore, maternal inflammation and elevated cytokines, along with viral effects on ACE2-expressing fetal cardiac progenitors, could further affect proliferation, differentiation, and apoptosis during cardiac development. Co-infections, hormone disruption, and maternal stress could also contribute. There is an urgent need for longitudinal studies with comprehensive maternal-fetal data, including infection timing, vaccine status, and biological sampling. These will be essential to delineate the multifactorial impacts of maternal infection on fetal cardiac development and long-term outcomes. Special focus should be placed on infections during early pregnancy (weeks 4–7), the period of cardiac septation and left-right asymmetry establishment, to determine causality and inform prevention strategies.
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spelling doaj-art-1c588bf87ca84d0ea3e0733440ed976b2025-08-20T03:44:06ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-08-011310.3389/fped.2025.16434231643423Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects?Athina Samara0Athina Samara1Athina Samara2Conrado Milani Coutinho3Paul T. Heath4Asma Khalil5Asma Khalil6Asma Khalil7Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, SwedenAstrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenFUTURE, Center for Functional Tissue Reconstruction, University of Oslo, Oslo, NorwayHospital das Clínicas, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilCentre for Neonatal and Paediatric Infection & Vaccine Institute, Institute of Infection and Immunity, City St George’s University of London, London, United KingdomFetal Medicine Unit, St George’s University Hospitals NHS Foundation Trust, University of London, London, United KingdomVascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, City St George’s University of London, London, United KingdomRoyal College of Obstetricians and Gynaecologists, London, United KingdomEmerging evidence suggests a potential link between maternal SARS-CoV-2 infection during early pregnancy and the development of congenital heart defects (CHD) in offspring. Although vertical transmission of SARS-CoV-2 is rare, the virus has been associated with placental complications and increased maternal morbidity. Recent studies from China report increased rates of CHD and anomalies such as situs inversus when infection occurs during gestational weeks 4–6, a critical window for cardiac development. Additional reports from different parts of the world also highlight post-pandemic increases in specific cardiac anomalies, including ventricular septal defects (VSDs). Multiple mechanisms may underlie these associations. SARS-CoV-2 can induce placental inflammation, compromise the cytotrophoblast barrier, and impair nutrient and gas exchange, potentially leading to fetal hypoxia and disrupted morphogenic signalling. Furthermore, maternal inflammation and elevated cytokines, along with viral effects on ACE2-expressing fetal cardiac progenitors, could further affect proliferation, differentiation, and apoptosis during cardiac development. Co-infections, hormone disruption, and maternal stress could also contribute. There is an urgent need for longitudinal studies with comprehensive maternal-fetal data, including infection timing, vaccine status, and biological sampling. These will be essential to delineate the multifactorial impacts of maternal infection on fetal cardiac development and long-term outcomes. Special focus should be placed on infections during early pregnancy (weeks 4–7), the period of cardiac septation and left-right asymmetry establishment, to determine causality and inform prevention strategies.https://www.frontiersin.org/articles/10.3389/fped.2025.1643423/fullSARS-CoV2congenital heart defectsmaternal infectionCOVID-19CHD
spellingShingle Athina Samara
Athina Samara
Athina Samara
Conrado Milani Coutinho
Paul T. Heath
Asma Khalil
Asma Khalil
Asma Khalil
Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects?
Frontiers in Pediatrics
SARS-CoV2
congenital heart defects
maternal infection
COVID-19
CHD
title Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects?
title_full Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects?
title_fullStr Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects?
title_full_unstemmed Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects?
title_short Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects?
title_sort is maternal sars cov 2 infection in the first trimester associated with congenital heart defects
topic SARS-CoV2
congenital heart defects
maternal infection
COVID-19
CHD
url https://www.frontiersin.org/articles/10.3389/fped.2025.1643423/full
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