Diuretics for preventing pre-eclampsia
- PMID: 17253507
- PMCID: PMC8826571
- DOI: 10.1002/14651858.CD004451.pub2
Diuretics for preventing pre-eclampsia
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.
Conflict of interest statement
None known.
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Update of
- doi: 10.1002/14651858.CD004451
References
References to studies included in this review
Fallis 1964 {published data only}
-
- Fallis NE, Plauche WC, Mosey LM, Langford HG. Thiazide vs placebo in prophylaxis of toxemia of pregnancy in primigravid patients. American Journal of Obstetrics and Gynecology 1964;88:502‐4. - PubMed
Flowers 1962 {published data only}
-
- Crosland DM, Flowers CE. Chlorothiazide and its relationship to neonatal jaundice. Obstetrics & Gynecology 1963;22:500‐4. - PubMed
-
- Flowers CE, Grizzle JE, Easterling WE, Bonner OB. Chlorthiazide as a prophylaxis against toxemia of pregnancy. American Journal of Obstetrics and Gynecology 1962;84:919‐29. - PubMed
Kraus 1966 {published data only}
-
- Kraus GW, Marchese JR, Yen SSC. Prophylactic use of hydrochlorothiazide in pregnancy. JAMA 1966;198:128‐32. - PubMed
Sibai 1984 {published data only}
-
- Sibai BM, Grossman RA, Grossman HG. Effects of diuretics on plasma volume in pregnancies with long‐term hypertension. American Journal of Obstetrics and Gynecology 1984;150:831‐5. - PubMed
Weseley 1962 {published data only}
-
- Weseley AC, Douglas GW. Continuous use of chlorothiazide for prevention of toxemia of pregnancy. Obstetrics & Gynecology 1962;19:355‐8. - PubMed
References to studies excluded from this review
Arias 1979 {published data only}
-
- Arias F, Zamora J. Antihypertensive treatment and pregnancy outcome in patients with mild chronic hypertension. Obstetrics & Gynecology 1979;53:489‐94. - PubMed
Bambas 1971 {published data only}
-
- Bambas W. Ambulatory treatment of late gestosis with Briserin [Zur ambulanten Behandlung der Spatgestose mit Briserin.]. Therapie der Gegenwart 1971;110:525‐36. - PubMed
Blake 1991 {published data only}
-
- Blake S, Macdonald D. The prevention of the maternal manifestations of pre‐eclampsia by intensive antihypertensive treatment. British Journal of Obstetrics and Gynaecology 1991;98:244‐8. - PubMed
Campbell 1975 {published and unpublished data}
-
- Campbell DM, MacGillivray I. The effect of a low calorie diet or a thiazide diuretic on the incidence of pre‐eclampsia and on birthweight. British Journal of Obstetrics and Gynaecology 1975;82:572‐7. - PubMed
Christianson 1976 {published data only}
-
- Christianson R, Page EW. Diuretic drugs and pregnancy. Obstetrics & Gynecology 1976;48(6):647‐52. - PubMed
Cuadros 1964 {published data only}
-
- Cuadros A, Tatum HJ. The prophylactic and therapeutic use of bendroflumethiazide in pregnancy. American Journal of Obstetrics and Gynecology 1964;89:891‐7. - PubMed
Finnerty 1966 {published data only}
-
- Finnerty FA, Bepko FJ. Lowering the perinatal mortality and the prematurity rate. The value of prophylactic thiazides in juveniles. JAMA 1966;195:429‐32. - PubMed
Gray 1968 {published data only}
-
- Gray MJ. Use and abuse of thiazides in pregnancy. Clinical Obstetrics and Gynecology 1968;11(2):568‐78. - PubMed
Hayashi 1963 {published data only}
-
- Hayashi TT, Phitaksphraiwan P, Willson JR. Effects of diet and diuretic agents in pregnancy toxemias. Obstetrics & Gynecology 1963;22:327‐34. - PubMed
Hester 1987 {unpublished data only}
-
- Hester LL. The effects of a diuretic (furosemide) in preventing pre‐eclampsia. Personal communication 1987.
Hudson 1961 {published data only}
-
- Hudson CN. A trial of two oral diuretics and bed rest on urinary electrolyte excretion in oedema of pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 1961;63:68‐73.
Leather 1968 {published data only}
-
- Leather HM, Humphrey DM, Baker P, Chadd MA. A controlled trial of hypotensive agents in hypertension in pregnancy. Lancet 1968;2:488‐90. - PubMed
Lindheimer 1974 {published data only}
-
- Lindheimer MD, Katz AI. Sodium and diuretics in pregnancy. Obstetrics & Gynecology 1974;44(3):434‐9.
MacGillivray 1980 {published data only}
-
- MacGillivray I, Campbell DM. The relevance of hypertension and oedema in pregnancy. Clinical and Experimental Hypertension 1980;2(5):897‐914. - PubMed
Mackay 1969a {published data only}
-
- Mackay EV, Khoo SK. Clinical and laboratory study of a new diuretic agent (Vectren) in pregnancy. A comparison with a diuretic agent in current use (Enduron). Medical Journal of Australia 1969;1:607‐12. - PubMed
Mackay 1969b {published data only}
-
- Mackay EV, Khoo SK, Adsett G, Zymanska S. A clinical study of the effects of an aldosterone antagonist (Aldactone‐A) and a thiazide diuretic (Enduron) in pregnancy. Australian and New Zealand Journal of Obstetrics and Gynaecology 1969;9:188‐95. - PubMed
Menzies 1964 {published data only}
Pannullo 1962 {published data only}
-
- Pannullo JN. Methyclothiazide in pregnancy. Journal of the Medical Society of New Jersey 1962;59:514‐6. - PubMed
Prema 1982 {published data only}
-
- Prema K, Ramalakshmi BA, Babu S. Diuretic therapy in pregnancy induced hypertension and pregnancy edema. Indian Journal of Medical Research 1982;75:545‐53. - PubMed
Riva 1978 {published data only}
-
- Riva E, Farina P, Tognoni G, Bottino S, Orrico C, Pardi G. Pharmacokinetics of furosemide in gestosis of pregnancy. European Journal of Clinical Pharmacology 1978;14:361‐6. - PubMed
Sandoval 1967 {published data only}
-
- Sandoval JB, Perez FR. Study of glomerular filtration in toxemia of pregnancy. Modifications with the use of furosemid (lasix) [abstract]. 5th World Congress of Gynecology and Obstetrics; 1967; Sydney, Australia. 1967:891.
Schnieden 1955 {published data only}
-
- Schnieden H. Outpatient trial of acetazoleamide in prevention of pre‐eclamptic toxaemia. Lancet 1955;2:1223‐5. - PubMed
Spellacy 1975 {published data only}
-
- Spellacy WN, Cohn JE, Buhi WC, Birk SA. Effects of diuril and dilantin on blood glucose and insulin levels in late pregnancy. Obstetrics & Gynecology 1975;45:159‐62. - PubMed
Tatum 1961 {published data only}
-
- Tatum HJ, Waterman EA. The prophylactic and therapeutic use of thiazides in pregnancy. GP 1961;24:101‐5. - PubMed
Tervila 1971 {published data only}
-
- Tervila L, Vartiainen E. The effects and side effects of diuretics in the prophylaxis of toxaemia of pregnancy. Acta Obstetricia et Gynecologica Scandinavica 1971;50:351‐6. - PubMed
Urdapilleta 1967 {published data only}
-
- Urdapilleta JD, Robles HD, Roman MV, Diaz AP. Ethacrynic acid in the treatment of toxemia of pregnancy [abstract]. 5th World Congress of Gynecology and Obstetrics; 1967; Sydney, Australia. 1967:892.
Walker 1966 {published data only}
-
- Walker JL. Methylclothiazide in excessive weight gain and edema of pregnancy. Obstetrics & Gynecology 1966;27:247‐51. - PubMed
Zuspan 1960 {published data only}
-
- Zuspan FP, Bell JD, Barnes AC. Balance‐ward and double‐blind diuretic studies during pregnancy. Obstetrics & Gynecology 1960;16:543‐9. - PubMed
References to studies awaiting assessment
Landesman 1965 {published data only}
-
- Landesman R, Aguero O, Wilson K, Russa R, Campbell W, Penaloza O. The prophylactic use of chlorthalidone, a sulfonamide diuretic in pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 1965;72:1004‐10.
Additional references
Collins 1985
Duley 1992
-
- Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean. British Journal of Obstetrics and Gynaecology 1992;99:547‐53. - PubMed
Duley 2003
Duley 2005
Egger 1997
Generic Protocol 05
-
- Meher S, Duley L, Prevention of Pre‐eclampsia Cochrane Review authors. Interventions for preventing pre‐eclampsia and its consequences: generic protocol. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD005301] - DOI
Gifford 2000
-
- Gifford RW, August PA, Cunningham G, Green LA, Lindheimer MD, McNellis D, et al. Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. American Journal of Obstetrics and Gynecology 2000;183(Suppl 1):S1‐S22. - PubMed
Harbord 2006
-
- Harbord RM, Egger M, Sterne JA. A modified test for small‐study effects in meta‐analyses of controlled trials with binary endpoints. Statistics in Medicine 2006;25:3443‐57. - PubMed
Hays 1985
-
- Hays PM, Cruikshank DP, Dunn LJ. Plasma volume determination in normal and pre‐eclamptic pregnancies. American Journal of Obstetrics and Gynecology 1985;151:958‐66. - PubMed
Higgins 2005
-
- Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005]. In: The Cochrane Library, Issue 3, 2005. Chichester, UK: John Wiley & Sons Ltd..
Higgins 2008
-
- Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated September 2008]. The Cochrane Collaboration, 2008. Available from www.cochrane‐handbook.org.
Hofmeyr 2006
Kramer 2003
Mabie 1986
-
- Mabie WC, Pernoll ML, Biswas MK. Chronic hypertension in pregnancy. Obstetrics & Gynecology 1986;67:197‐205. - PubMed
Makrides 2001
NICE 2001
-
- National Institute for Clinical Excellence (NICE), Scottish Executive Health Department, Department of Health, Social Services and Public Safety: Northern Ireland. Why mothers die 1997‐1999. The confidential enquiries into maternal deaths in the United Kingdom. London: RCOG Press, 2001.
RevMan 2002 [Computer program]
-
- The Cochrane Collaboration. Review Manager (RevMan). Version 4.1 for Windows. Oxford, England: The Cochrane Collaboration, 2002.
RevMan 2008 [Computer program]
-
- The Cochrane Collaboration. Review Manager (RevMan). Version 5.0. Copenhagen, The Nordic Cochrane Centre: The Cochrane Collaboration, 2008.
Rumbold 2005
WHO 1988
-
- World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Geographic variation in the incidence of hypertensive disease in pregnancy. American Journal of Obstetrics and Gynecology 1988;158:80‐3. - PubMed
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