Journal of the American Heart Association · 2026
Assisted Reproductive Technology and Risk of Congenital Heart Defects in the Offspring: A Systematic Review and Meta-Analysis.
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Rinaldi Riccardo, Bujak Kamil, Laudani Claudio, Occhipinti Giovanni, Caffè Andrea, Animati Francesco M, Scarica Vincenzo, Łajczak Paweł, Flores-Umanzor Eduardo, Luna-Lopez Raquel, Nicolini Elisa, Piva Tommaso, Pawlas Natalia, Regueiro Ander, Freixa Xavier, Gąsior Mariusz, Ottani Filippo, Crea Filippo, Montone Rocco A
Аннотация
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.
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.