Preeclampsia and Eclampsia Research Activities and Advances

Studies conducted by researchers at NICHD and elsewhere have found markers in the blood of pregnant women that seem to signal the later development of preeclampsia. Identifying such substances—related to the apparent biochemical basis for preeclampsia—is an important step in developing treatments for the condition as well as better ways to identify who is at risk.

Researchers at NICHD's Division of Intramural Population Health Research (DIPHR) found strong evidence that an imbalance of two proteins produced by the placenta is responsible for the symptoms of preeclampsia. Abnormally high levels of these proteins appear to deprive the blood vessels of substances needed to keep the lining of the blood vessels healthy. Deprived of these essential substances, the cells lining the blood vessels begin to sicken and die. As a result, blood pressure increases, and the blood vessels leach protein into the tissues and urine. Both proteins appear to contribute to the development of preeclampsia. Severe disease usually occurs in women with high levels of both measures and not in women with high levels of only one or the other. (PMID: 16957146)

Other DIPHR researchers are investigating the relationship of angiogenic factors to the pathogenesis of preeclampsia and their potential for identifying women at high risk of developing preeclampsia. Several studies are currently exploring this area of research. In addition, a recent study found that elevated blood pressure in pregnancy is linked to an increased risk for cardiovascular disease, chronic kidney disease, and diabetes later in life. (PMID: 23401113)

Previous studies have shown that low-dose aspirin during pregnancy reduced the rate of preeclampsia in high-risk women.¹ The U.S. Preventative Services Task Force cited these studies in its recommendation for using low-dose aspirin to prevent preeclampsia in high-risk women. The NICHD-led Effects of Aspirin in Gestation and Reproduction (EAGeR) Study found that low-dose aspirin initiated before pregnancy did not reduce preterm births or pregnancy complications, such as preeclampsia, in women who previously had one or two pregnancy losses. The EAGeR Study also found that aspirin use was not harmful during pregnancy. The investigators recommended against the general use of low-dose aspirin to improve pregnancy outcomes but said that more research is needed on subsets of women at high risk for pregnancy loss or complications. (PMID: 24702835)

NICHD's Pregnancy and Perinatology Branch (PPB) funds and oversees research grants to independent researchers throughout the U.S. and abroad to study medical management and prevention of preeclampsia. Some avenues of research related to preeclampsia include the impact of obesity on the condition, the potential role of autoimmunity, and fetal genetic contributions.

Although the exact mechanisms of preeclampsia are unknown, it appears that the condition is due to poor blood flow from the uterus to the placenta. In a normal pregnancy, placental cells known as trophoblastic cells migrate to uterine blood vessels and increase their size. In preeclampsia, the trophoblastic cells fail to migrate completely towards the uterine blood vessels, resulting in less uterine blood flow to the placenta. In turn, the poorly nourished placenta releases factors into the maternal circulation that result in the systemic symptoms of the disease.

PPB-supported research has helped determine the source and role of proteins and other chemical factors that are important in establishing sufficient blood flow to the placenta. (PMID: 20948996, PMID: 18093648).

In addition, researchers in the Program in Perinatal Research and Obstetrics, in NICHD's Division of Intramural Research, are investigating preeclampsia as part of a larger effort to prevent preterm birth. Efforts have included examining the possibility that infection contributes to preeclampsia. Researchers also are calibrating measurements of growth factors in the blood and testing the reliability of these measurements as a way of predicting when women will develop preeclampsia. Their clinical findings indicate that this approach has promise for predicting when a woman will develop preeclampsia that requires delivery before the pregnancy reaches full term. Read more about the Program's research in the Division's annual report.

Additional NICHD research on preeclampsia has found:

• Immune system protein at high levels in women with preeclampsia (PMID: 26510395)
• Race and pre-pregnancy body mass index affect the risk of preeclampsia (PMID: 25453345)
• Higher levels of copeptin could identify women at risk for preeclampsia (PMID: 25225209)
• Stillbirth risk for mothers with preeclampsia is highest at 26 weeks of gestation (PMID: 25730226P)
• Pregnancy-associated plasma protein A2 is elevated in women with preeclampsia (PMID: 26748159)
• Women with elevated blood pressure during labor are at risk for hypertensive disorders in a second pregnancy (PMID: 25673041)

The PPB created the Maternal-Fetal Medicine Units Network in 1986 to focus on clinical questions in maternal-fetal medicine and obstetrics, particularly with respect to the continuing problem of preterm birth. Several studies affiliated with the network have investigated preeclampsia. For instance, the Combined Antioxidants and Preeclampsia Prediction Studies, co-funded by the National Heart, Lung, and Blood Institute, were designed to see if antioxidants (vitamins C and E) could prevent preeclampsia in women at low risk for the condition. The results showed that antioxidants neither decrease the incidence of preeclampsia nor reduce the risk of complications associated with pregnancy-related hypertension.²

NICHD's Health Equity Seminar Series is a forum for raising awareness of maternal and child health issues that affect diverse populations and for exploring directions for future research aimed at reducing health disparities in NICHD mission areas. The September 2014 seminar focused on vitamin D deficiency, which is a risk factor for preeclampsia that occurs disproportionately in racial/ethnic minority populations. The seminar reviewed the status of basic research on vitamin D deficiency's role in placental development and preeclampsia and discussed research directions.