A new study conducted by the National Institutes of Health's (NIH) Perinatology Research Branch at the Wayne State University School of Medicine has taken a major leap toward determining the risk of a pregnant woman developing preeclampsia. The study's findings will help clinicians around the world identify and monitor patients who are at risk for developing this life-threatening condition.

Juan Pedro Kusanovic

Roberto Romero

The study, published in the November issue of The Journal of Maternal-Fetal & Neonatal Medicine, set out to determine the diagnostic indications and predictive value of biomarkers measured in maternal blood in the first and second trimester of pregnancy. The goal was to determine whether the biomarkers could predict the subsequent development of preeclampsia. The findings of the study -- the largest of its kind ever undertaken -- will help clinicians assess the risk for preeclampsia and monitor mothers and their unborn babies at risk for the silent killer.

Estimates indicate that preeclampsia is responsible for 76,000 maternal deaths and more than 500,000 infant deaths every year, according to the Preeclampsia Foundation. Preeclampsia occurs only during pregnancy and sometimes after delivery. It is characterized by high blood pressure and the presence of protein in maternal urine. Preeclampsia can affect the liver, kidney and brain. Sometimes mothers develop seizures (eclampsia) and suffer intracranial hemorrhage, the main cause of death in those who develop the disorder. Some women develop blindness.

"Left untreated, preeclampsia can lead to serious -- or even fatal -- complications for both the mother and baby," said Juan Pedro Kusanovic, M.D., director of Translational Research of the Perinatology Research Branch, the National Institute of Children's Health and Development, the National Institute of Health, and assistant professor of the School of Medicine's Department of Obstetrics and Gynecology. He was lead author of the study, "A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia."

The unborn babies of preeclamptic mothers are affected by the disease and may develop intrauterine growth starvation or die in utero. Many believe preeclampsia results from insufficient blood supply to the uterus and placenta, causing the development of high blood pressure. The increase in maternal blood pressure is a compensatory response to improve the condition of the fetus. Preeclampsia may have evolved to protect the infant, but when the disease is out of control it threatens the health of the mother. The earlier the disease starts in pregnancy, the worse the outcome for baby and mother.

The study received the Frederick P. Zuspan Award for Clinical Research by the International Society for the Study of Hypertension in Pregnancy. The award is given for the most outstanding clinical work relating to the study of hypertension in pregnancy.

"Our study found that maternal plasma concentrations of angiogenic and antiangiogenic factors, together with a combination of other demographic, biochemical and biophysical factors, are useful in assigning risk for the subsequent development of early-onset preeclampsia," said Roberto Romero, M.D., chief of the Perinatology Research Branch of National Institute of Child Human Development, NIH, who is one of the world's leading experts on this condition and in the study of complications of pregnancy.

"The establishment of an accurate means to assess the risk for preeclampsia would enable health care practitioners to identify women who require more intensive monitoring to safeguard both mother and baby from this devastating condition," said Romero, a professor of molecular obstetrics and genetics with the WSU Center for Molecular Medicine and Genetics.

"This study is the first of its kind in which women were prospectively followed from the beginning of pregnancy to determine if simple blood measurements can predict early onset preeclampsia. The results are very encouraging and suggest that the biomarkers studied can be used to identify women at risk in the second trimester, many weeks before the clinical onset of the disease."

The results of the study will encourage laboratories and clinicians to use biomarkers to track the health of pregnant women. Several companies are developing rapid methods to measure these biomarkers and make them available for clinical use in hospitals throughout the world.

Romero explained that these tests would allow health care practitioners to identify women at risk and to intensify monitoring. An important challenge still lies in finding methods to treat preeclampsia. He noted that defective angiogenesis may be observed in other complications of pregnancy such as premature labor, fetal death and intrauterine growth restriction. The markers are likely to identify not only patients with preeclampsia, but those at risk for other complications of pregnancy.

"This research breaks new ground and will lead to healthier outcomes for mothers and infants," said Valerie Parisi, M.D., M.P.H., M.B.A., interim dean of the School of Medicine. "This is a prime example of the bench-to-bedside research being conducted in the heart of Detroit."

Wayne State University is a premier urban research university offering more than 350 academic programs through 13 schools and colleges to more than 31,000 students.