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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Frontiers Media S.A.
2025-08-01
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| 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. |
| format | Article |
| id | doaj-art-1c588bf87ca84d0ea3e0733440ed976b |
| institution | Kabale University |
| issn | 2296-2360 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| 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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