Assisted Reproductive Technology and Risk of Congenital Heart Defects in the Offspring: A Systematic Review and Meta‐Analysis
9 affiliations
- 1Infermi Hospital
- 2Medical University of Silesia
- 3University of Catania
- 4Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
- 5Catholic University of the Sacred Heart
- 6Hospital Sant Joan de Deu
- 7Azienda Ospedaliero Universitaria delle Marche
- 8Ospedale Isola Tiberina, Gemelli Isola
- 9Fondazione Policlinico Universitario A. Gemelli IRCCS
Abstract
BACKGROUND: To date, >10 million children have been conceived via assisted reproductive technology (ART) globally. However, there are some concerns about potential adverse outcomes associated with ART-conceived pregnancies, including the risk of congenital heart defects (CHDs). This meta-analysis aimed to evaluate the association between ART and the risk of major CHDs as well as their specific subtypes. METHODS: Major electronic databases were screened for studies comparing the incidence of CHD following ART-conceived pregnancies versus spontaneous conception. The primary end point was study-defined incidence of CHDs. Secondary end points included incidence of tetralogy of Fallot, transposition of the great arteries, aortic coarctation, ventricular septal defect, atrial septal defect, pulmonary valve atresia, tricuspid valve atresia, and hypoplastic left heart. Pairwise meta-analyses were performed using frequentist random-effect models to calculate risk ratios and 95% CIs. RESULTS: Thirteen studies, encompassing a total of 45 916 925 subjects (4986 conceived via ART), were included in the quantitative synthesis. ART was significantly associated with a higher risk of major CHD compared with natural pregnancy (risk ratio, 2.35 [95% CI, 1.68-3.28]), with significant heterogeneity across the studies. An increased risk of tetralogy of Fallot, ventricular septal defect, and atrial septal defect following ART-conceived pregnancies was found, while no difference was found on other CHDs. Prespecified sensitivity analyses were in line with the primary findings of the meta-analysis. CONCLUSIONS: Our meta-analysis shows a potential link between ART and increased risk of major CHDs, particularly on tetralogy of Fallot, ventricular septal defect, and atrial septal defect.
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- Recombinant follicle‐stimulating hormone (rFSH) versus other recombinant or urinary gonadotropins for ovarian stimulation in assisted reproductive technology cycles
BibTeX
@article{rinaldi2026assisted,
title = {{Assisted Reproductive Technology and Risk of Congenital Heart Defects in the Offspring: A Systematic Review and Meta‐Analysis}},
author = {Riccardo Rinaldi and Kamil Bujak and Claudio Laudani and Giovanni Occhipinti and Andrea Caffè and Francesco M. Animati and Vincenzo Scarica and Paweł Łajczak and Eduardo Flores‐Umanzor and Raquel Luna‐Lopez and Elisa Nicolini and Tommaso Piva and Natalia Pawlas and Ander Regueiro and Xavier Freixa and Mariusz Gąsior and Filippo Ottani and Filippo Crea and Rocco A. Montone},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.125.047875},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.125.047875},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Assisted Reproductive Technology and Risk of Congenital Heart Defects in the Offspring: A Systematic Review and Meta‐Analysis
AU - Riccardo Rinaldi
AU - Kamil Bujak
AU - Claudio Laudani
AU - Giovanni Occhipinti
AU - Andrea Caffè
AU - Francesco M. Animati
AU - Vincenzo Scarica
AU - Paweł Łajczak
AU - Eduardo Flores‐Umanzor
AU - Raquel Luna‐Lopez
AU - Elisa Nicolini
AU - Tommaso Piva
AU - Natalia Pawlas
AU - Ander Regueiro
AU - Xavier Freixa
AU - Mariusz Gąsior
AU - Filippo Ottani
AU - Filippo Crea
AU - Rocco A. Montone
PY - 2026
DA - 2026/10/20
JO - Journal of the American Heart Association
DO - 10.1161/jaha.125.047875
UR - https://www.ahajournals.org/doi/10.1161/JAHA.125.047875
AB - BACKGROUND: To date, >10 million children have been conceived via assisted reproductive technology (ART) globally. However, there are some concerns about potential adverse outcomes associated with ART-conceived pregnancies, including the risk of congenital heart defects (CHDs). This meta-analysis aimed to evaluate the association between ART and the risk of major CHDs as well as their specific subtypes. METHODS: Major electronic databases were screened for studies comparing the incidence of CHD following ART-conceived pregnancies versus spontaneous conception. The primary end point was study-defined incidence of CHDs. Secondary end points included incidence of tetralogy of Fallot, transposition of the great arteries, aortic coarctation, ventricular septal defect, atrial septal defect, pulmonary valve atresia, tricuspid valve atresia, and hypoplastic left heart. Pairwise meta-analyses were performed using frequentist random-effect models to calculate risk ratios and 95% CIs. RESULTS: Thirteen studies, encompassing a total of 45 916 925 subjects (4986 conceived via ART), were included in the quantitative synthesis. ART was significantly associated with a higher risk of major CHD compared with natural pregnancy (risk ratio, 2.35 [95% CI, 1.68-3.28]), with significant heterogeneity across the studies. An increased risk of tetralogy of Fallot, ventricular septal defect, and atrial septal defect following ART-conceived pregnancies was found, while no difference was found on other CHDs. Prespecified sensitivity analyses were in line with the primary findings of the meta-analysis. CONCLUSIONS: Our meta-analysis shows a potential link between ART and increased risk of major CHDs, particularly on tetralogy of Fallot, ventricular septal defect, and atrial septal defect.
SN - 2047-9980
ER -