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Observed Prevalence and Predictors of Congenital Heart Disease in Infants Conceived via In vitro Fertilization
Calista Dominy Tobben1, Eric Takoushian2, Kevin Strobino2
1Department of Pediatrics, New York Presbyterian - Weill Cornell, New York, NY, USA. omo9016@nyp.org.
Insights
Infants conceived via in vitro fertilization (IVF) have higher congenital heart disease (CHD) rates. Maternal hypertension and twin gestation are key predictors, varying by CHD severity, necessitating tailored screening for IVF pregnancies.
Area of Science:
- Reproductive Medicine
- Pediatric Cardiology
- Genetics and Genomics
Background:
- In vitro fertilization (IVF) use is increasing globally.
- Previous studies suggest a link between IVF conception and congenital heart disease (CHD), but data on risk factors and prevalence by severity remain inconsistent.
- Understanding these associations is crucial for optimizing care in IVF-conceived infants.
Purpose of the Study:
- To quantify the prevalence of CHD, including subtypes (any, persistent, significant), in infants conceived via IVF.
- To identify independent predictors of CHD in this population.
- To compare CHD prevalence in IVF infants to the general population and investigate IVF-specific risks.
Main Methods:
- Retrospective cohort study of 1890 IVF-conceived infants (2020-2025) at a single tertiary center.
- Analysis of maternal demographics, comorbidities, medication use, twin gestation, family history, and fetal echocardiography data.
- Multivariate logistic regression to identify independent predictors; sensitivity analysis excluding known CHD risk factors.
Main Results:
- Overall CHD prevalence was 4.76% (any), 3.33% (persistent), and 1.64% (significant), exceeding general population rates.
- After excluding known risk factors, prevalence decreased but remained elevated, suggesting potential IVF-related risks.
- Maternal hypertension, Black race, and Asian race predicted any CHD; maternal hypertension predicted persistent CHD; twin gestation predicted significant CHD.
Conclusions:
- IVF-conceived infants exhibit a higher prevalence of CHD, primarily less severe forms, compared to the general population.
- Predictors of CHD vary significantly by severity subtype, highlighting the need for risk-stratified approaches.
- Individualized counseling and targeted fetal echocardiography are recommended for IVF pregnancies to improve early detection and management.
Abstract:
Infants conceived via in vitro fertilization (IVF) have been reported to have increased rates of congenital heart disease (CHD), though estimates and associated risk factors remain variable. This study aimed to quantify CHD prevalence by severity sub-type and identify independent predictors of CHD in an IVF-conceived population. A retrospective cohort study of 1890 IVF-conceived infants born to 1783 mothers at a single tertiary academic center from 2020 to 2025 was performed. Maternal demographics, comorbidities, medication exposures, twin gestation, family history, and fetal echocardiography utilization were analyzed. CHD outcomes included: (1) any CHD; (2) persistent CHD (not spontaneously resolved within 3 years); and (3) significant CHD (requiring medical or procedural intervention). Prevalence was compared to the general population baseline (~1%) using Proportion Z testing. Multivariate logistic regression was performed to identify independent predictors. A sensitivity analysis excluded pregnancies with established CHD risk factors to isolate IVF-associated risk. CHD prevalence was 4.76% for any CHD, 3.33% for persistent, and 1.64% for significant. After exclusion of established CHD risk factors, prevalence decreased to 3.1%, 2.1%, and 1.01%, respectively. Fetal echocardiography utilization and diagnostic yield increased with CHD severity. Maternal hypertension, Black race, and Asian race independently predicted any CHD. However, only maternal hypertension predicted persistent CHD and only twin gestation predicted significant CHD. No independent associations were identified for maternal age, geography, median income, other medical conditions (i.e. diabetes, autoimmune), medication exposures, or family history. This IVF-conceived population showed a higher observed prevalence of CHD than global population baseline, though disease burden is driven by less severe heart disease. Distinct predictors varied by CHD severity subtype, supporting risk-stratified fetal echocardiography and individualized counseling in IVF pregnancies.
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