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PERSPECTIVE article

Front. Pediatr.

Sec. Pediatric Cardiology

Volume 13 - 2025 | doi: 10.3389/fped.2025.1643423

This article is part of the Research TopicAdvancements in Congenital Heart Disease: Diagnosis and Management InnovationsView all 8 articles

Is Maternal SARS-CoV-2 Infection in the first Trimester Associated with Congenital Heart Defects?

Provisionally accepted
  • 1Department of Physiology, Karolinska Institutet (KI), Solna, Sweden
  • 2Universitetet i Oslo, Oslo, Norway
  • 3Hospital das Clínicas, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
  • 4Centre for Neonatal and Paediatric Infection & Vaccine Institute, Institute of Infection and Immunity, City St George's University of London, London, United Kingdom
  • 5St George's University of London, London, United Kingdom

The final, formatted version of the article will be published soon.

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.

Keywords: SARS-CoV2, congenital heart defects, Maternal infection, COVID-19, CHD

Received: 08 Jun 2025; Accepted: 30 Jul 2025.

Copyright: © 2025 Samara, Coutinho, Heath and Khalil. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Athina Samara, Department of Physiology, Karolinska Institutet (KI), Solna, Sweden

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