Risk of minor congenital heart defect in infants conceived via assisted reproductive technology: cohort study from the Copenhagen Baby Heart Study

OBJECTIVE: Infertility affects up to 20% of couples in high-income countries, which has led to an increased use of assisted reproductive technology (ART). While previous studies have linked ART to a higher risk of major congenital heart defects (CHD), less is known about the associated risk of minor CHD. As minor CHD are associated with premature early-onset cardiac morbidity and mortality, this study aimed to evaluate the risk of minor CHD in singleton infants conceived via ART compared with in those conceived spontaneously. METHODS: The Copenhagen Baby Heart Study (CBHS) is a Danish, prospective, multicenter study of neonates delivered between 1 April 2016 and 31 October 2018. Included in this cohort study based on CBHS data were singleton infants who met the inclusion criteria and had undergone neonatal transthoracic echocardiography (TTE) within 60 days after birth. Infants conceived via ART, defined as either in-vitro fertilization or intracytoplasmic sperm injection, were matched randomly, based on sex and maternal age, in a 1:4 ratio with spontaneously conceived singleton infants, who formed the control group. The primary outcome was the diagnosis of minor CHD, defined as a ventricular septal defect (VSD), bicuspid aortic valve (BAV) and/or atrial septal defect (ASD), detected on neonatal TTE. For analysis of ASD, we assessed a subgroup of the matched infants included within the overall cohort who were evaluated using TTE from 15 May 2017 onwards using an algorithm for the TTE classification of interatrial communications implemented in the CBHS. Using multiple logistic regression analysis, we compared the risk of minor CHD in infants conceived via ART vs those conceived spontaneously, adjusting for maternal age, parental CHD, pregestational diabetes mellitus and maternal body mass index. RESULTS: Of 23 493 infants who met the inclusion criteria, 1630 singletons were conceived by ART. These were matched with 6520 controls who were conceived spontaneously. The subgroup of infants evaluated using the algorithm for TTE classification of interatrial communications comprised 862 infants conceived by ART and 3448 matched infants who were conceived spontaneously. The risk of minor CHD overall (VSD, BAV and/or ASD) in the subcohort evaluated using this algorithm was not significantly different between singleton infants conceived via ART and those conceived spontaneously (adjusted odds ratio, 1.07 (95% CI, 0.83-1.38)). Furthermore, we observed no significant differences in the risk of specific minor CHD subtypes (VSD, BAV and/or ASD) between singleton infants conceived via ART and those conceived spontaneously. Similarly, no significant differences in the risk of minor CHD were observed between ART subtypes, including conception via fresh in-vitro fertilization, fresh intracytoplasmic sperm injection and fresh- and frozen-embryo transfer, or between each ART subtype and infants conceived spontaneously. CONCLUSION: There was no increased risk of minor CHD in singleton infants conceived via ART compared with singleton infants conceived spontaneously. These findings provide reassuring evidence that ART is unlikely to impose an increased long-term cardiovascular risk attributable to subclinical minor CHD that would otherwise remain undiagnosed in the absence of screening. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.