July 27, 1999
Women with preeclampsia, a potentially fatal complication of pregnancy, appear to have an imbalance of two key chemical compounds that control blood pressure, according to a study by researchers at the National Institute of Child Health and Human Development (NICHD) published in the July 28 issue of the Journal of the American Medical Association. This chemical imbalance predates the symptoms of preeclampsia by several months.
"These results provide a promising new lead for solving the mystery of preeclampsia," said NICHD Director Duane Alexander. "They also offer strategies for designing new treatments for the condition."
Specifically, women who developed preeclampsia had low levels of a substance known as prostacyclin (PGI2), as compared to their levels of another substance, thromboxane (TxA2), said the study's principal investigator, James L. Mills, chief of NICHD's Pediatric Epidemiology Section. Dr. Mills explained that PGI2 causes blood vessels to relax, reducing blood pressure. In contrast, TxA2 makes blood vessels contract, raising blood pressure.
"For the women who developed preeclampsia, the ratio of thromboxane to prostacyclin was abnormal months before--and throughout--pregnancy," Dr. Mills said. "This suggests that an imbalance between the chemicals that increase and decrease blood pressure is an early, consistent abnormality in women likely to get preeclampsia."
Preeclampsia has no known cure. About 5 percent of first-time mothers and 1 to 2 percent of mothers having subsequent pregnancies develop the condition, Dr. Mills said. Preeclampsia may progress to eclampsia--hypertension (high blood pressure) and convulsions--which may be fatal. Children born to mothers with preeclampsia may be small for their gestational age or may be born prematurely. These conditions, in turn, may place the infants at risk for a variety of other birth complications.
Because a characteristic of preeclampsia is contraction of the blood vessels, Dr. Mills said, many studies of preeclampsia have focused on PGI2 and TxA2. However, these studies have often produced conflicting results. One reason could be that many of the studies assessed the levels of the two substances after the women had begun to have symptoms of preeclampsia or had been treated for the condition. This made it difficult to tell whether changes in PGI2 and TxA2 levels were the cause or the result of preeclampsia, or even the result of treating the condition. Other researchers have tried to determine the levels of these compounds in women before they developed preeclampsia. However, the number of women in the studies was too small to allow the researchers to reach a statistically valid conclusion.
To determine if PGI2 and TxA2 are involved in preeclampsia, Dr. Mills and his coworkers analyzed information gathered during NICHD's Calcium for Preeclampsia Prevention Trial (CPEP). [The CPEP trial is described in "Study Finds Calcium Does Not Prevent Potentially Fatal Disorder of Pregnancy," on the Mass Media page of the NICHD website at http://www.nichd.nih.gov/.
Dr. Mills and his colleagues examined the records of 2,294 women in the CPEP study. The group consisted of enough women who developed preeclampsia to provide statistically valid results. The women were tested for PGI2 and TxA2 when they enrolled in the study, from 13 to 21 weeks of pregnancy, again between 26 and 29 weeks of pregnancy, and, finally, at the 36th week of pregnancy.
A total of 134 women developed preeclampsia. At all testing intervals, these women had low PGI2 levels when compared to women who did not develop preeclampsia. In fact, their PGI2 levels were low months before preeclampsia developed. Except for the first testing interval, when they had comparatively low TxA2 levels, the women with preeclampsia also had higher levels of TxA2 than did the women who did not develop preeclampsia. Dr. Mills noted, however, that, according to the laws of probability, the lower initial TxA 2 levels among the preeclampsia group could have been a chance occurrence, and the higher levels detected at later intervals were not statistically significant.
Dr. Mills stressed that, although the imbalance between the two substances predates the development of preeclampsia, the abnormal PGI2 and TxA2 levels were not pronounced enough to predict the development of preeclampsia routinely.
In the paper, Dr. Mills and his coauthors concluded that future research efforts might investigate whether raising the PGI2 levels of women with preeclampsia or treating them with related compounds would provide an effective treatment for the disease. They noted that other studies have shown that treatment with PGI2 is effective in treating pulmonary hypertension and other disorders involving hypertension in the lungs.