High Maternal BMI Ups Risk of Fetal Congenital Heart Defects

Researchers published the study covered in this summary on medRxiv as a preprint that has not yet been peer reviewed.

Key Takeaways

The risk of fetal congenital heart defect (CHD) gradually increased with increasing pre-pregnancy maternal body mass index (BMI), in a study that used 10-year registry data of all live births, stillbirths, abortions, and terminated pregnancies in Denmark.
There was a nonsignificant trend of increased risk of CHD in offspring of a second pregnancy in women who gained a substantial amount of weight after a first pregnancy.

Why This Matters

Previous studies have reported that maternal obesity is associated with an increased risk of CHD in offspring, but no large studies have included CHD identified prenatally in terminated pregnancies.
The findings show it remains important to advise women that a high BMI is a risk factor for congenital malformations, and obstetric and perinatal complications.

Study Design

Researchers performed a cohort study of all singleton pregnancies in Denmark with estimated due dates between June 1, 2008, and June 1, 2018, using data from the Danish Fetal Medicine database.
They identified CHD diagnoses in live births, as well as CHD diagnoses in utero from ultrasound examinations during pregnancies that resulted in live birth, stillbirth, or spontaneous abortion or termination of pregnancy after gestational week 12.
They determined the relative risk (RR) of having offspring with any CHD, or one of 17 types of severe CHD, or one of the five most common types of severe CHD (univentricular heart, transposition of the great arteries, atrioventricular septum defect, coarctation of the aorta, and Tetralogy of Fallot).

Key Results

Researchers identified 547,178 singleton pregnancies: 97.7% live births, 0.3% stillbirths, and 0.9% abortions or terminated pregnancies; 1.1% of pregnancies had missing outcomes.
Of the total cohort, 1.0% of the offspring had CHD and 0.2% had severe CHD.
35% of the women had an early-pregnancy BMI ≥ 25 kg/m² and 13% of the women had an early-pregnancy BMI ≥ 30 kg/m² (obesity).
Compared to women with normal early-pregnancy BMI (18.5-24.9 kg/m²), the adjusted RR of having offspring with CHD increased significantly with increasing BMI — from 1.17 (BMI 25-29.9 kg/m²) to 1.23 (BMI 30-34.9 kg/m²) to 1.26 (BMI 35-39.9 kg/m²) to 1.81 (BMI ≥ 40 kg/m²) — after adjusting for maternal age at conception, smoking status, and year of estimated due date.
The same pattern was seen for the subgroup of severe CHD.
There was no significant association between high maternal BMI and four of the five most severe CHD subtypes. However, women with BMI ≥ 40 kg/m² had a strong fourfold increased risk of having offspring with an atrioventricular septal defect (adjusted RR, 4.19).
107,627 women had two singleton pregnancies. Among those with a BMI increase of ≥ 4 kg/m² between pregnancies, there was a nonsignificant trend towards having an offspring with CHD, after adjusting for maternal age and BMI (RR, 1.27; 95% CI, 0.96 - 1.64).

Limitations

The database did not include information on pregestational diabetes, which is known to be strongly associated with CHD.
There was also no data on family history of CHD, maternal infections, or intake of teratogenic medicine during pregnancy, which have all been associated with a higher risk of CHD.
The study was based on registry data, so there is a risk of reporting bias, and CHD diagnoses were not validated against hospital records.

Disclosures

The Danish National Biobank, which is supported by the Novo Nordisk Foundation, was used for this research.
The authors have reported no relevant financial relationships.

This is a summary of a preprint research study, "Maternal obesity, interpregnancy weight changes and congenital heart defects in the offspring: A nationwide cohort study," by researchers from Copenhagen, Denmark, published on medRxiv and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.

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