Pregnancies conceived through assisted reproduction linked to higher risk of major heart defects

Pregnancies conceived through assisted reproductive technology (ART) were associated with a 2.35-fold higher risk of major congenital heart defects (CHDs) compared with naturally conceived pregnancies, according to a study published Oct. 10, 2026, in the Journal of the American Heart Association (JAHA).

CHDs are the most common group of birth defects, affecting about 1% to 2% of live births worldwide, and they remain a leading cause of death related to congenital abnormalities, according to the CDC. The authors of the study noted they also place a considerable burden on healthcare systems on this data.

The study also noted that more than 10 million children have been conceived through ART worldwide, while ART births account for about 2.3% of all live births in the U.S. and about 3% in Europe.

Researchers of the study, hailing from Infermi Hospital in Rimini, Italy, and the Medical University of Silesia in Katowice, Poland, wrote that earlier research has been conflicting. Some large population studies found a 30% to 70% higher risk among children conceived through ART, while others found no meaningful difference after adjusting for major confounders.

Most prior studies also treated heart defects as one outcome, leaving it unclear whether ART raises the risk of some defects more than others. The team set out to produce more precise estimates for major CHDs and specific defect types to help inform prenatal screening.

Data from nearly 46 million pregnancies

Researchers searched three major medical research databases through February 2025 for studies comparing heart defect rates in ART-conceived and naturally conceived pregnancies, excluding studies limited to twins or other multiple pregnancies. The final analysis included 13 studies published between 1997 and 2024, covering 45,916,925 pregnancies.

Most of the included studies were large, population-based studies. In vitro fertilization (IVF) and intracytoplasmic sperm injection were the most common ART procedures, and people with ART pregnancies tended to be older and less likely to smoke. The main outcome was major CHD as each study defined it, generally meaning severe defects that need surgery or a catheter procedure in the first year of life.

Researchers also examined eight specific defects, including tetralogy of Fallot (ToF), a combination of four structural heart defects, and septal defects, which are holes in the walls between the heart’s chambers. Results were pooled using a statistical model that accounts for differences between studies, and the team ran several sensitivity analyses to test whether the findings held up.

Higher risk concentrated in specific defects

In the main analysis, ART was associated with a higher risk of major CHD (risk ratio, 2.35; 95% CI, 1.68 to 3.28). The size of that association varied widely between studies, from no clear effect to a several-fold increase in risk. In a sensitivity analysis that excluded the eight studies driving most of that variation, the association held (risk ratio, 2.21; 95% CI, 1.91 to 2.56).

Of the specific defects, ART was linked to a 58% higher risk of ToF (risk ratio, 1.58; 95% CI, 1.27 to 1.97). The risk of ventricular septal defects was 40% higher (risk ratio, 1.40; 95% CI, 1.20 to 1.64). The same was true for atrial septal defects (risk ratio, 1.40; 95% CI, 1.10 to 1.78). No significant differences were found for the other defects studied, including transposition of the great arteries and hypoplastic left heart syndrome. Studies with a larger share of IVF procedures tended to show stronger associations, but that trend fell just short of statistical significance.

The authors stressed that the absolute risk of CHDs remains low. Still, they wrote that the relative increase supports building this information into counseling, prenatal screening and care after birth as ART use grows.

“Targeted fetal echocardiography may be reasonable in ART pregnancies,” the authors wrote, noting it could allow earlier detection and timely referral to a specialist. They also recommended that clinicians discuss the risk alongside other known ART-related risks, such as premature birth and low birth weight.

Findings show an association, not cause

The study’s strengths include its size, a protocol registered before the work began and sensitivity analyses that produced results consistent with the main finding. Still, every included study was observational, so the findings show an association and cannot establish that ART causes heart defects. Because the analysis relied on study-level data, researchers could not adjust for factors such as parental health conditions, lifestyle, the cause of infertility, maternal age, multiple births or premature birth.

Six of the 13 studies were rated at serious risk of bias. Registry data may also undercount mild defects. The authors rated the certainty of evidence as low for major CHD, ToF and ventricular septal defects, and very low for the other outcomes.

The authors called for large prospective studies with detailed data on ART techniques, the source of eggs and sperm, and how embryos are handled, ideally paired with genetic and epigenetic testing, to help separate the effects of ART procedures from underlying parental factors. They also called for long-term follow-up of people conceived through ART to determine whether the higher risk extends to lifelong cardiovascular disease, which could inform screening beyond the newborn period.