Published Online
on February 7, 2008

A more recent version of this article appeared on April 1, 2008

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Submitted on September 27, 2007
Revised on October 19, 2007

Shared Constitutional Risks for Maternal Vascular-Related Pregnancy Complications and Future Cardiovascular Disease

Anne L. Berends; Christianne J.M. de Groot; Eric J. Sijbrands; Mark P.S. Sie; Sofie H. Benneheij; Richard Pal; Roger Heydanus; Ben A. Oostra; Cornelia M. van Duijn; and Eric A.P. Steegers^*

From the Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynecology (A.L.B., C.J.M.d.G., S.H.B., E.A.P.S.), and Departments of Internal Medicine (E.J.S., M.P.S.S.), Clinical Genetics (B.A.O.), and Epidemiology and Biostatistics (C.M.v.D.), University Medical Center Rotterdam, Rotterdam, The Netherlands; the Department of Obsterics and Gynecology (C.J.M.d.G.), Haaglanden Medical Center, The Hague, The Netherlands; the Department of Obstetrics and Gynecology (R.P.), Franciscus Hospital, Roosendaal, The Netherlands; and the Department of Obstetrics and Gynecology (R.H.), Amphia Hospital, Breda, The Netherlands.

^* To whom correspondence should be addressed. E-mail: e.a.p.steegers{at}erasmusmc.nl.

Abstract—Maternal predisposition to vascular and metabolic disease may underlie both vascular-related pregnancy complications, such as preeclampsia and intrauterine growth restriction, as well as future maternal cardiovascular disease. We aimed to substantiate this hypothesis with biochemical and anthropometric evidence by conducting an intergenerational case-control study in a Dutch isolated population including 106 women after preeclampsia or intrauterine growth restriction (median follow-up: 7.1 years) and their fathers (n=43) and mothers (n=64), as well as 106 control subjects after uncomplicated pregnancies with their fathers (n=51) and mothers (n=68). Cardiovascular risk profiles were assessed, including fasting glucose, lipids, anthropometrics, blood pressure, intima-media thickness, and metabolic syndrome. We found significantly higher fasting glucose levels, larger waist circumferences, and a 5-fold increased prevalence of hypertension in women with a history of preeclampsia as compared with control subjects (P<0.001). Likewise, their parents had higher glucose levels than control parents (P<0.05). Their mothers had larger waist circumferences and higher blood pressures (P<0.05). Also, women after pregnancies complicated by intrauterine growth restriction had higher glucose levels and increased prevalence of hypertension (P<0.01). Their fathers showed higher glucose levels as well (P<0.05). Mean carotid intima-media thickness was increased in a subset of women after preeclampsia diagnosed with chronic hypertension as compared with those without hypertension (P<0.01). Metabolic syndrome was more prevalent both in women with a history of preeclampsia and their mothers (P<0.05). We demonstrated intergenerational similarities in cardiovascular risk profiles between women after preeclampsia or intrauterine growth restriction and their parents. These findings suggest shared constitutional risks for vascular-related pregnancy complications and future cardiovascular disease.

Key words: preeclampsia • intrauterine growth restriction • cardiovascular disease • familial aggregation • intergenerational study

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