Preeclampsia, Congenital Heart Defects May Share a Mechanism

Liam Davenport

April 25, 2017

COPENHAGEN, DENMARK — Congenital heart defects and maternal preeclampsia are strongly associated, both within the same pregnancy and across pregnancies, suggests Danish registry data that point to a potential common mechanism underlying the two disorders[1].

The analysis of two million pregnancies, published in Circulation on April 19, 2017, suggested that fetal congenital heart defects may pose  a sevenfold increased risk of early preterm preeclampsia in the same pregnancy.

Moreover, offspring congenital defects in a previous pregnancy were linked to a threefold increased risk of later early preterm preeclampsia, and early preterm eclampsia increased the risk of later fetal congenital heart defects almost eightfold.

The findings do not prove causation but suggest that a maternal history of preterm (especially early preterm) preeclampsia may warrant increased surveillance for congenital heart detects in the offspring, researchers say, while fetal congenital heart defects may justify clinical monitoring for preeclampsia.

Lead author Dr Heather A Boyd (Statens Serum Institut, Copenhagen, Denmark) told heartwire from Medscape that, although monitoring for fetal congenital heart defects "wouldn't really fit in with routine screening, I guess the upside would be that there aren't very many women that have these forms of preeclampsia."

Previous research[2] has suggested that pregnant women carrying fetuses with heart defects and those with hypertensive disorders often have "angiogenic imbalances," suggesting that as a shared underlying mechanism for both conditions, according to Boyd and associates.

A recent study suggested that women who receive beta-blockers during pregnancy do not have a greater risk of having a baby with a congenital heart defect.

Congenital Heart Defects <1%

To investigate further, the researchers gathered data from the Danish Medical Birth Register on singleton pregnancies between 1978 and 2011 that lasted for ≥20 weeks and resulted in a live birth. Pregnancies resulting in offspring with chromosomal abnormalities were excluded.

The Hospital Discharge Register was used to identify individuals with congenital heart defects, as well as women who had preeclampsia or gestational hypertension between 30 days before delivery and 7 days postpartum.

Early preterm preeclampsia was defined as preeclampsia with delivery at <34 weeks, late preterm preeclampsia as a delivery at 34 to 36 weeks, and term preeclampsia as delivery at ≥37 weeks.

Among 1,972,857 singleton pregnancies meeting the inclusion criteria, 18,038 (0.9%) resulted in an offspring with a congenital defect.

In addition, 3617 (0.2%) pregnancies were complicated by early preterm preeclampsia and 5512 (0.3%) by late preterm preeclampsia. Term preeclampsia was recorded in 45,611 (2.3% pregnancies), and 17,975 (0.9%) women had gestational hypertension.

Analysis accounting for maternal age at delivery, parity, and delivery year revealed that offspring congenital heart defects were associated with early preterm preeclampsia, at an odds ratio (OR) of 7.00 (95% CI 6.11–8.03) and late preterm preeclampsia (OR 2.81, 95% CI 2.38–3.34) in the same pregnancy, with the associations consistent across types of heart defects.

Furthermore, offspring congenital heart defects were weakly associated with term preeclampsia (OR 1.16, 95% CI 1.06–1.27) but were not associated with gestational hypertension (OR 1.07, 95% CI 0.92–1.25).

The team also found that offspring congenital heart defects in a previous pregnancy were linked to early preterm preeclampsia (OR 2.37, 95% CI 1.68–3.34) and late preterm preeclampsia (OR 2.04, 95% CI 1.52–2.75) in subsequent pregnancies.

The observed association with term preeclampsia was weak, and there was no association between previous offspring congenital heart defects and current gestational hypertension.

Early preterm preeclampsia in a previous pregnancy was associated with offspring congenital heart defects in later pregnancies (OR 7.91, 95% CI 6.06–10.3), as was late preterm preeclampsia (OR 2.83, 95% CI 2.11–3.79).

There was no significant association between term preeclampsia or gestational hypertension in a previous pregnancy and subsequent offspring congenital heart defects.

Implications by Preeclampsia Type

Boyd said it's unclear why the association between hypertensive disorders in pregnancy and offspring congenital heart defects is restricted to preterm preeclampsia.

"The preeclampsia research community is operating on the premise that there are different mechanisms underlying the early-onset versions and later-onset versions," she said. And "the mechanisms definitely seem to be different, at least in regard to mechanisms that are shared with offspring heart defects."

Boyd said the earlier onset forms of preeclampsia "must be the result of some vascular problems that result in abnormal placentation and serious heart difficulties in these women, whereas the ones that occur later on may have more to do with things like overweight and diabetes."

This work was funded by grants from the Danish Council for Independent Research and the Danish Heart Association. The authors declare no relevant financial relationships.

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