Authors
Frederik Kyhl-Svart, David Arce, Anne Lærke Spangmose, Charlotte Kvist Ekelund, Yiyi Lin, Ditte Vassard, Anja Pinborg, Rui Wang
Published in
Human reproduction update. Sep 17, 2026. Epub Sep 17, 2026.
Abstract
Previous meta-analyses have reported an increased risk of congenital heart defects (CHDs) in children conceived by ART but have relied on unadjusted estimates and have not examined specific ART treatment modalities. Clinical guidelines remain inconsistent regarding whether foetal echocardiography should be recommended for ART pregnancies.
The aim of this review was to estimate the prevalence of CHD among ART-conceived and naturally conceived children, and to assess whether ART conception is associated with an increased risk of CHD overall and by severity, including major and minor CHD. This meta-analysis included sub-analyses of CHD risk after various ART methods, and for singleton and multiple births.
A systematic literature search was conducted in PubMed and Embase in January 2025, updated in March 2026, using combinations of index terms and free-text terms related to ART and CHD. Observational studies (cohort or case-control) were eligible if they compared children conceived through ART with naturally conceived controls and reported occurrence of any type of CHD. The Quality in Prognosis Studies (QUIPS) tool was used to assess risk of bias. Random-effects meta-analyses were performed to synthesize prevalences of CHD in ART and control groups, as well as adjusted odds ratios (aOR) on the association between ART and CHD.
We included 35 studies (29 retrospective cohort, 6 case-control) that reported risk of CHD comparing 604 641 ART-conceived children or foetuses with 42 021 027 naturally conceived. Proportional meta-analysis of 29 cohort studies estimated that the overall prevalences of CHD in children conceived by ART and those conceived naturally were 2.62% (95% CI 1.14-4.65) and 1.44% (0.49-2.85%), respectively. Fifteen studies (33 019 895 children) reported aORs comparing the risk of any CHD in children conceived by ART with that in children conceived naturally. The summary aOR of these studies was 1.53 (1.30-1.79). Stratification by severity showed an increased risk for major CHD (aOR 1.77; 95% CI 1.30-2.41) but there was insufficient evidence for minor CHD (aOR 1.62; 95% CI 0.55-4.81). Subgroup analyses did not show subgroup differences based on ICSI/IVF, frozen/fresh transfers, or singletons/multiple births for the association between ART and CHD (P-values for subgroup interaction: 0.56, 0.47, and 0.96, respectively). The overall risk of bias varied from low to high across studies. All adjusted estimates included maternal age, but studies varied in adjustment for other potential confounders, including parental CHD, maternal BMI, smoking, and infertility-related diagnoses.
This meta-analysis found an increased risk of CHD among ART-conceived children compared with naturally conceived children. The association appeared consistent across ART methods and plurality and was most evident for major CHD. However, the absolute prevalence remained low, and in settings where routine mid-trimester anomaly screening is offered, the current literature does not support additional foetal echocardiographic screening based on ART conception alone. Further studies are needed to separate the contribution of ART procedures from underlying parental infertility and related factors.
PROSPERO: CRD42025626281.
PMID:
42754249
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.
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