D Churchill1, G D G Beevers, S Meher, C Rhodes. 1. Royal Wolverhampton Hospitals NHS Trust, Department of Obstetrics and Gynaecology, New Cross Hospital, Wednesfield, Wolverhampton, West Midlands, UK, WV10 0QP. david.churchill@rwh-tr.nhs.uk
Abstract
BACKGROUND: Diuretics are used to reduce blood pressure and oedema in non-pregnant individuals. Formerly, they were used in pregnancy with the aim of preventing or delaying the development of pre-eclampsia. This practice became controversial when concerns were raised that diuretics may further reduce plasma volume in women with pre-eclampsia, thereby increasing the risk of adverse effects on the mother and baby, particularly fetal growth. OBJECTIVES: To assess the effects of diuretics on prevention of pre-eclampsia and its complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 2) and EMBASE (2002 to April 2005). SELECTION CRITERIA: Randomised trials evaluating the effects of diuretics for preventing pre-eclampsia and its complications. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials for inclusion and extracted data. We analysed and double checked data for accuracy. MAIN RESULTS: Five studies (1836 women) were included. All were of uncertain quality. The studies compared thiazide diuretics with either placebo or no intervention. There were no clear differences between the diuretic and control groups for any reported pregnancy outcomes including pre-eclampsia (four trials, 1391 women; relative risk (RR) 0.68, 95% confidence interval (CI) 0.45 to 1.03), perinatal death (five trials,1836 women; RR 0.72, 95% CI 0.40 to 1.27), and preterm birth (two trials, 465 women; RR 0.67, 95% CI 0.32 to 1.41). There were no small-for-gestational age babies in the one trial that reported this outcome, and there was insufficient evidence to demonstrate any clear differences between the two groups for birthweight (one trial, 20 women; weighted mean difference 139 grams, 95% CI -484.40 to 762.40). Thiazide diuretics were associated with an increased risk of nausea and vomiting (two trials, 1217 women; RR 5.81, 95% CI 1.04 to 32.46), and women allocated diuretics were more likely to stop treatment due to side-effects compared to those allocated placebo (two trials, 1217 women; RR 1.85, 95% CI 0.81 to 4.22). AUTHORS' CONCLUSIONS: There is insufficient evidence to draw reliable conclusions about the effects of diuretics on prevention of pre-eclampsia and its complications. However, from this review, no clear benefits have been found from the use of diuretics to prevent pre-eclampsia. Taken together with the level of adverse effects found, the use of diuretics for the prevention of pre-eclampsia and its complications cannot be recommended.
BACKGROUND: Diuretics are used to reduce blood pressure and oedema in non-pregnant individuals. Formerly, they were used in pregnancy with the aim of preventing or delaying the development of pre-eclampsia. This practice became controversial when concerns were raised that diuretics may further reduce plasma volume in women with pre-eclampsia, thereby increasing the risk of adverse effects on the mother and baby, particularly fetal growth. OBJECTIVES: To assess the effects of diuretics on prevention of pre-eclampsia and its complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 2) and EMBASE (2002 to April 2005). SELECTION CRITERIA: Randomised trials evaluating the effects of diuretics for preventing pre-eclampsia and its complications. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials for inclusion and extracted data. We analysed and double checked data for accuracy. MAIN RESULTS: Five studies (1836 women) were included. All were of uncertain quality. The studies compared thiazide diuretics with either placebo or no intervention. There were no clear differences between the diuretic and control groups for any reported pregnancy outcomes including pre-eclampsia (four trials, 1391 women; relative risk (RR) 0.68, 95% confidence interval (CI) 0.45 to 1.03), perinatal death (five trials,1836 women; RR 0.72, 95% CI 0.40 to 1.27), and preterm birth (two trials, 465 women; RR 0.67, 95% CI 0.32 to 1.41). There were no small-for-gestational age babies in the one trial that reported this outcome, and there was insufficient evidence to demonstrate any clear differences between the two groups for birthweight (one trial, 20 women; weighted mean difference 139 grams, 95% CI -484.40 to 762.40). Thiazide diuretics were associated with an increased risk of nausea and vomiting (two trials, 1217 women; RR 5.81, 95% CI 1.04 to 32.46), and women allocated diuretics were more likely to stop treatment due to side-effects compared to those allocated placebo (two trials, 1217 women; RR 1.85, 95% CI 0.81 to 4.22). AUTHORS' CONCLUSIONS: There is insufficient evidence to draw reliable conclusions about the effects of diuretics on prevention of pre-eclampsia and its complications. However, from this review, no clear benefits have been found from the use of diuretics to prevent pre-eclampsia. Taken together with the level of adverse effects found, the use of diuretics for the prevention of pre-eclampsia and its complications cannot be recommended.