A Missing Link for Preeclampsia, Fetal Growth Restriction, and Cardiovascular Disease?


Preeclampsia and fetal growth restriction (FGR) are 2 obstetric syndromes that are generally associated with increased perinatal and maternal morbidities. Preeclampsia is defined as the onset of hypertension and proteinuria after 20 weeks gestation, and it complicates 3% to 5% of all pregnancies. FGR is defined as a birth weight below the fifth or 10th percentile for gestational age, and it can develop alone or in association with preeclampsia. Preeclampsia and FGR share similar pathophysiologic abnormalities, such as reduced uteroplacental blood flow, exaggerated inflammatory response, endothelial cell dysfunction, and a state of imbalance between proangiogenic and antiangiogenic factors.1 These pathophysiologic abnormalities are presumed to be the result of a cascade of events secondary to shallow trophoblast invasion and defective remodeling of the uterine spiral arteries. However, the etiologies of preeclampsia and FGR are multifactorial, and only FGR and preeclampsia related to placental insufficiency probably share abnormal placentation as a common pathway. Pregnancies complicated by preeclampsia are associated with increased rates of FGR. Women with a history of preeclampsia in a previous pregnancy are also at increased risk for preeclampsia and/or FGR in subsequent pregnancies.2 The magnitude of the above risks depends on gestational age at onset of preeclampsia in the index pregnancy (the earlier in gestation the onset of preeclampsia, the higher are the rates of FGR and recurrent preeclampsia).2,3 In addition, women who are born fetal growth restricted are at increased risk of severe preeclampsia and FGR when they get pregnant,4 and they are at increased risk for cardiovascular disease later in life (fetal origin of adult disease).5 During the past decade, several epidemiologic and casecontrol studies evaluated the association between preeclampsia and the development of cardiovascular disease in later life.6 These studies were the subject of a recent systemic review and meta-analysis that revealed a relative risk for chronic hypertension of 3.70 after 14.10 years average follow-up, a relative risk of 2.16 for ischemic heart disease after 11.70 years of follow-up, and a relative risk of 1.81 for ischemic stroke after 10.4 years of follow-up.6 In addition, the overall mortality after preeclampsia was increased by a relative risk of 1.49 after 14.5 years of follow-up. In a related study, Ray et al7 assessed cardiovascular health after maternal placental syndromes among 75 380 women whose pregnancies were complicated by preeclampsia, abruptio, or placental infarction, as evidenced by FGR. The outcome in these women was compared with that of women whose pregnancy was not complicated by these syndromes. The authors found that the risk of premature cardiovascular disease (median duration of follow-up: 8.7 years) is increased after maternal placental syndrome, particularly in the presence of poor fetal growth or in the presence of preexisting features of the metabolic syndrome before the index pregnancy.7 Recently, Magnussen et al,8 examined the effect of cardiovascular risk factors before pregnancy on the risk of preeclampsia in 3494 women, of whom 133 (8.8%) developed preeclampsia. After adjustment for several confounding variables, the authors found positive associations between prepregnancy serum levels of triglycerides, cholesterol, low-density lipoprotein cholesterol, baseline systolic blood pressure, and subsequent development of preeclampsia. They concluded that women with prepregancy risk factors for cardiovascular disease are predisposed to preeclampsia.8 The mechanisms accounting for the relationship among preeclampsia, FGR, and the increased risk of subsequent cardiovascular disease and ischemic stroke in women having these complications are unclear. Suggested mechanisms have included the possibility that the development of these obstetric complications cause permanent metabolic or vascular disturbances in the mother that will ultimately result in cardiovascular complications. Alternatively, these women could have preexisting risk factors or genetic/environmental factors that predispose them to develop preeclampsia or FGR during pregnancy, and the same factors may also predispose these women to develop cardiovascular disease later in life. Berends et al9 conducted an intergenerational case-control study comparing cardiovascular risk profiles among 3 groups of women and their parents at a median follow-up of 7.1 years after pregnancy. The study groups were white Dutch women whose pregnancies were complicated by preeclampsia or FGR (n 106), as well as their fathers (n 43) and mothers (n 64), and a control group of women who had normal, term pregnancies (n 106), as well as their fathers (n 51) and their mothers (n 68). Study participants and their parents underwent measurements of fasting lipids, glucose levels, body mass index (all subjects), anthropometrics, blood pressure, and intima-media thickness measurements, as well as prevalence of metabolic syndrome (women and their mothers only). The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. From the Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Ohio. Correspondence to Baha M. Sibai, 231 Albert Sabin Way, Cincinnati, OH 45267. E-mail baha.sibai@uc.edu (Hypertension. 2008;51:993-994.) © 2008 American Heart Association, Inc.

Cite this paper

@inproceedings{Sibai2008AML, title={A Missing Link for Preeclampsia, Fetal Growth Restriction, and Cardiovascular Disease?}, author={Baha M . Sibai}, year={2008} }