Preeclampsia and Fetal Congenital Heart Defects

uman placentation is uniquely associated with physiological remodeling of the maternal spiral arteries by the invading trophoblast to produce a lowresistance maternal uterine circulation.The current paradigm considers defective placentation as the cause of preeclampsia, especially the preterm variety of the disorder. 1Related persistence of a high-resistance maternal uterine circulation, impaired placental perfusion, and maternal antiangiogenic stress response are all considered to be involved in the pathogenesis of preeclampsia. 1 An angiogenic imbalance has also previously been noted in association with developmental defects of the human fetal heart. 2 In this issue of Circulation, Boyd and colleagues 3 used these observations as the rationale for investigating the relationships between preeclampsia and fetal congenital heart defects in a cohort of almost 2 million Danish pregnancies.The cohort included ≈18 000 fetuses with congenital heart defects and 55 000 pregnancies complicated by preeclampsia. RELATIONSHIP BETWEEN PREECLAMPSIA AND FETAL CONGENITAL HEART DEFECTSWomen carrying a fetus with a congenital heart defect, regardless of the type of defect, had a 7-fold increase in the risk of early preeclampsia before <34 weeks' gestation.There is a definable dose-response curve with the risk decreasing, with later preeclampsia down to a 16% increase in preeclampsia at term and no association with gestational hypertension.The relationship between fetal congenital cardiac defects and an increased risk of maternal preeclampsia has been noted previously and attributed to the commonality of shared angiogenic imbalance in the mother and fetus. 4,5The novel findings of the present study are that in a subcohort of 700 000 women with ≥2 pregnancies, women who previously had a child with a congenital cardiac defect had a 2-fold greater risk of early preeclampsia and a 25% greater risk of term preeclampsia.Conversely, early preeclampsia in a previously pregnancy was associated with a 6-fold increased risk of offspring congenital heart defects in the current pregnancy.These observations deserve further exploration because they are of significant clinical and biological relevance. CLINICAL RELEVANCE OF THE INCREASED RISK FOR FETAL CONGENITAL CARDIAC DEFECTSAccurate and early diagnosis of fetal congenital heart defects in pregnancy is now feasible in a routine setting and has been shown to have a noticeable effect on the subsequent outcome of pregnancy. 6Internationally, detailed fetal echocardiog- Preeclampsia and Fetal Congenital Heart DefectsSpurious Association or Maternal Confounding?