Researchers Identify Risk Factors for Preeclampsia in Hypertensive Women

Having high blood pressure for at least four years before getting pregnant increases a woman's chances of developing the dangerous condition known as preeclampsia, according to a study published in the September 3 issue of The New England Journal of Medicine. The study, conducted by researchers in the National Institute of Child Health and Human Development's (NICHD) Network of Maternal-Fetal Medicine Units, also determined that protein in the urine very early in pregnancy increases the risk of such adverse outcomes as giving birth prematurely, having a child who is small for gestational age, or having an infant who would need to be admitted to a newborn intensive care unit.

The principal author of the study was Baha M. Sibai, MD, of the Department of Obstetrics and Gynecology at the University of Tennessee in Memphis.

Preeclampsia is the leading cause of maternal death and is particularly troubling because it can strike without warning. The condition results in high blood pressure and protein in the urine. In turn, preeclampsia may progress to eclampsia--hypertension and generalized convulsions--which may prove fatal. About 5 percent of first-time mothers and 1 to 2 percent of mothers having subsequent pregnancies develop preeclampsia. However, even in cases where the condition does not progress to eclampsia, children born to mothers with preeclampsia may be small for their gestational age or may be born prematurely, both factors which may place infants at risk for a variety of other complications. Although the high blood pressure accompanying preeclampsia can be treated with blood pressure lowering drugs, the only curative treatment for the overall condition is immediate delivery.

In their study, the researchers sought to determine which factors would predispose women with longstanding hypertension--a major risk factor for preeclampsia--to develop the condition, explained Donald McNellis, MD, a medical officer at NICHD and an author of the study. In all, 763 women with chronic hypertension were recruited from the 14 NICHD Maternal-Fetal Medicine Units. When they entered the study, the women were between 13 and 26 weeks pregnant.

"Many of the earlier studies on this topic contained only a comparatively small number of patients, and differed in the criteria used to diagnose preeclampsia," Dr. McNellis said. "The strength of our study is that it applied a consistent definition of preeclampsia to the largest sample of hypertensive pregnant women available to date."

Briefly, for those women who did not have proteinuria (protein in the urine) when the study began, preeclampsia was said to begin when the women developed protein in the urine. For women who had protein in the urine when the study began, preeclampsia was defined as having: either an elevated level of SGOT (a liver enzyme) or worsening hypertension, together with either worsening proteinuria, persistent severe headaches, or stomach pain. However, regardless of whether or not they had proteinuria when they entered the study, the women were considered to have preeclampsia if they had either a low platelet count (thrombocytopenia), eclampsia, or HELLP syndrome--low platelet count with abnormal levels of the liver enzyme SGOT, and destruction of red blood cells (hemolysis).

The researchers found that the women were more likely to develop preeclampsia if they had a history of hypertension for at least four years before becoming pregnant, if they had preeclampsia during a previous pregnancy, and if they had a diastolic blood pressure reading from 100 to 110 mmHg, early in pregnancy. (Diastolic blood pressure refers to the blood pressure reading taken between beats of the heart, and is usually written as the lower number in a set of fractions, the upper number being referred to as the systolic blood pressure reading.)

Women who developed preeclampsia were also more likely to develop abruptio placentae--detachment of the placenta from the uterine wall, a potentially serious complication of pregnancy. In addition, infants born to women who went on to develop preeclampsia were also more likely to be delivered prematurely, to require admission to a neonatal intensive care unit, to suffer from a hemorrhage while in the womb, and to die shortly before, during, or after birth.

Although having protein in the urine at the beginning of the study did not increase a woman's chances of developing preeclampsia, women who had protein in their urine early in pregnancy were more likely to have infants who were small for their gestational age, born prematurely, require admission to a neonatal intensive care unit, and to suffer intraventricular hemorrhage--a type of brain hemorrhage. Dr. McNellis noted that the presence of protein in the urine is often an indication of kidney damage due to hypertension.

The researchers originally collected the information on the women as part of a study to determine if low-dose aspirin would reduce the incidence of hypertension in women at risk for the condition. Overall, the aspirin treatment did not appear to affect whether the women developed preeclampsia, with 26 percent of the women taking aspirin developing preeclampsia, and 24.6 percent of the women taking the placebo developing the condition.

"These findings underscore the importance of preconception counseling regarding the adverse effects of proteinuria in hypertensive women," the authors wrote.

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