# Placental Angiogenic Imbalance and Its Association With Adverse Outcomes in Congenital Heart Disease Pregnancies

## TL;DR

Pregnant women with congenital heart disease have imbalanced placental angiogenesis, which is linked to a higher risk of adverse outcomes.

## Contribution

This study identifies placental angiogenic imbalance in CHD pregnancies and links it to adverse outcomes.

## Key findings

- CHD patients had higher sFlt-1 and lower PlGF levels in late pregnancy compared to controls.
- An elevated sFlt-1/PlGF ratio was associated with a 4-fold higher risk of adverse outcomes.
- CHD patients showed a greater increase in sFlt-1 from first to third trimester than controls.

## Abstract

Pregnancy in women with congenital heart disease (CHD) carries an increased risk of obstetric and neonatal complications. While the underlying mechanisms remain unclear, placental dysfunction has been hypothesized to contribute to these outcomes.

This study aimed to evaluate biomarkers of placental angiogenesis, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), in pregnant women with CHD and assess their association with adverse pregnancy outcomes.

This prospective study included 95 pregnant women, 32 with CHD and 63 healthy controls. Serum sFlt-1 and PlGF were measured during the third trimester, and the sFlt-1/PlGF ratio was calculated. In a subset of 66 patients with available first-trimester serum, we assessed longitudinal changes in biomarker levels between the first and third trimesters. Associations with obstetric and neonatal complications were evaluated.

Women with CHD had higher third-trimester sFlt-1 (2,578 pg/mL [25th-75th percentile: 2,095-4,493 pg/mL] vs 1,983 pg/mL [25th-75th percentile: 1,414-2.788 pg/mL], P = 0.002) and lower PlGF (276 pg/mL [25th-75th percentile: 164-510 pg/mL] vs 515 pg/mL [25th-75th percentile: 289-752 pg/mL], P = 0.005) than controls, resulting in an elevated sFlt-1/PlGF ratio (9.55 [25th-75th percentile: 3.88-26.70]) vs 3.83 [25th-75th percentile: 1.91-7.32], P = 0.001). CHD patients with high sFlt-1 had a 4-fold higher risk of adverse outcomes than those with normal levels (80% vs 22.2%; P = 0.024). The rise in sFlt-1 between the first and third trimesters was greater in CHD patients than in controls (P = 0.008).

Pregnant women with CHD exhibited a placental angiogenic imbalance, with higher sFlt-1 and lower PlGF in late pregnancy than controls. This imbalance was associated with a higher risk of adverse pregnancy outcomes, particularly in women with high sFlt-1.