Diuretics Get Cold Shoulder for Preventing Preeclampsia

WOLVERHAMPTON, England, Jan. 24 -- Diuretics offered no clear benefit for preventing preeclampsia in pregnant women and should not be used to prevent its onset, Cochrane reviewers concluded.

The review of five U.S. studies and 1,836 women found that women taking thiazide diuretics were not any less likely to develop preeclampsia, deliver prematurely, or lose their babies than those who did not take diuretics, according to a report in the January 2007 issue of the Cochrane Database of Systematic Reviews.

Furthermore, the women taking diuretics were more likely to have unacceptable nausea and vomiting, said obstetrician David Churchill, M.D., of New Cross Hospital here, and colleagues.

All trials were single-center studies, but their quality was unclear because of inadequate reporting of randomization methods and allocation concealment, the researchers said. Also, only four of the five trials (1,391 women) reported on preclampsia.

The findings were as follows:

• There was insufficient evidence to demonstrate any clear differences between the two groups in the relative risk of preeclampsia (relative risk 0.68, 95% confidence interval 0.45 to 1.03).
• There was no clear difference between diuretic and control groups in the risk of cesarean delivery (one trial, 20 women; RR 1.00, CI 0.26 to 3.81.)
• Diuretics were associated with increased risk of maternal side effects compared with placebo (RR 8.70, CI, 1.19 to 63.60).
• Women taking diuretics were almost twice as likely to stop treatment. Unacceptable nausea and vomiting (RR 5.81, CI 1.04-32.46) was a major reason. Other reasons for stopping treatment included pruritis and rash, weakness or dizziness, and diuresis, but here there were no clear differences in the groups.
• There was no clear difference between the diuretic and control patients in the risk of perinatal death (22 deaths among the diuretic patients versus 26 deaths in the controls [RR 0.60, CI 0.27 to 1.34]), or in the risk of perinatal deaths.
• There was insufficient evidence to show any clear difference between the two groups in the risk of preterm birth or gestation at delivery.
• There was insufficient evidence to demonstrate any clear difference between the two groups in small-for-gestational age and birthweight.
• Finally, there were no statistically significant differences between the groups for hypertension, severe preeclampsia, eclampsia, postmaturity, and low Apgar scores.

The use of diuretics to prevent preeclampsia, on the basis of the drugs' ability to reduce edema and increase sodium excretion, does not appear to be justified at this time, the Cochrane reviewers wrote. Furthermore, the incidence of side effects, particularly vomiting, was higher in the diuretic group, so that at present diuretics should not be recommended for this purpose in clinical practice, Dr. Churchill and his colleagues concluded.

Turning to future research goals, Dr. Churchill wrote that this review suggests that further randomized trials to evaluate the effects of diuretics are justified only if it is thought that other effects of diuretics, such as lowering blood pressure and inducing vasodilatation, provide reasonable theoretical grounds for preventing pre-eclampsia.

Further trials may also be helpful for women with essential hypertension who are receiving diuretics prior to pregnancy, to provide them with reliable advice about the effects of continuing diuretic therapy during pregnancy. Such randomized trials should be well controlled, with adequate sample size.

"In view of the apparent increase in the risk of nausea and vomiting with thiazide diuretics, if further trials are carried out, strategies to reduce this risk such as using a lower dose or alternative agents should be explored," the Cochrane reviewers concluded.