Pre-eclampsia, eclampsia, and hypertension

Lelia Duley

. 2008 Aug 14;2008:1402.

Pre-eclampsia, eclampsia, and hypertension

Lelia Duley ¹

PMCID: PMC2907952 PMID: 19445808

Abstract

Introduction

Pre-eclampsia (raised blood pressure and proteinuria) complicates 2-8% of pregnancies, and raises morbidity and mortality in the mother and child. Pre-eclampsia is more common in women with multiple pregnancy and in those who have conditions associates with microvascular disease.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions in women at risk of pre-eclampsia? What are the effects of interventions in women who develop mild-moderate hypertension during pregnancy? What are the effects of interventions in women who develop severe pre-eclampsia or very high blood pressure during pregnancy? What is the best choice of anticonvulsant for women with eclampsia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 53 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticonvulsants, antihypertensive drugs, antioxidants, antiplatelet drugs, atenolol, bed rest, hospital admission or day care, calcium supplementation, choice of analgesia during labour, early delivery (interventionist care), evening primrose oil, fish oil, glyceryl trinitrate, magnesium supplementation, plasma volume expansion, and salt restriction.

Key Points

Pre-eclampsia (raised blood pressure and proteinuria) complicates 2-8% of pregnancies, and increases morbidity and mortality in the mother and child.

Pre-eclampsia is more common in women with multiple pregnancy, and in people with conditions associated with microvascular disease.

Antiplatelet drugs (primarily low-dose aspirin) reduce the risk of pre-eclampsia, death of the baby, and premature birth, without increasing the risks of bleeding, in women at high risk of pre-eclampsia.

Calcium supplementation reduces the risk of pre-eclampsia compared with placebo.
We don't know whether fish oil, evening primrose oil, salt restriction, magnesium supplementation, antioxidants, or glyceryl trinitrate are beneficial in high-risk women, because there are insufficient data to draw reliable conclusions.
We don't know whether atenolol reduces the risk of pre-eclampsia, but it may worsen outcomes for babies.

For women with mild to moderate hypertension during pregnancy, antihypertensive drugs reduce the risk of progression to severe hypertension, but may not improve other clinical outcomes.

ACE inhibitors have been associated with fetal renal failure, and beta-blockers are associated with the baby being born small for its gestational age.
We don't know whether bed rest or hospital admission are also beneficial.

There is consensus that women who develop severe hypertension in pregnancy should receive antihypertensive treatment, but we don't know which antihypertensive agent is most effective.

We don't know whether plasma volume expansion, antioxidants, epidural analgesia, or early delivery improve outcomes for women with severe pre-eclampsia.

Magnesium sulphate reduces the risk of first or subsequent seizures in women with severe pre-eclampsia compared with placebo.

Magnesium sulphate reduces the risk of subsequent seizures in women with eclampsia compared with either phenytoin or diazepam, with fewer adverse effects for the mother or baby.

About this condition

Definition

Hypertension during pregnancy may be associated with one of several conditions. Pregnancy-induced hypertension is a rise in blood pressure, without proteinuria, during the second half of pregnancy. Pre-eclampsia is a multisystem disorder, unique to pregnancy, that is usually associated with raised blood pressure and proteinuria. It rarely presents before 20 weeks' gestation. Eclampsia is one or more convulsions in association with the syndrome of pre-eclampsia. Pre-existing hypertension (not covered in this review) is known hypertension before pregnancy, or raised blood pressure before 20 weeks' gestation. It may be essential hypertension or, less commonly, secondary to underlying disease.

Incidence/ Prevalence

Pregnancy-induced hypertension affects 10% of pregnancies, and pre-eclampsia complicates 2-8% of pregnancies. Eclampsia occurs in about 1/2000 deliveries in resource-rich countries. In resource-poor countries, estimates of the incidence of eclampsia vary from 1/100-1/1700.

Aetiology/ Risk factors

The cause of pre-eclampsia is unknown. It is likely to be multifactorial, and may result from deficient placental implantation during the first half of pregnancy. Pre-eclampsia is more common among women likely to have a large placenta, such as those with multiple pregnancy, and among women with medical conditions associated with microvascular disease, such as diabetes, hypertension, and collagen vascular disease. Other risk factors include genetic susceptibility, increased parity, and older maternal age. Cigarette smoking seems to be associated with a lower risk of pre-eclampsia, but this potential benefit is outweighed by an increase in adverse outcomes such as low birthweight, placental abruption, and perinatal death.

Prognosis

The outcome of pregnancy in women with pregnancy-induced hypertension alone is at least as good as that for normotensive pregnancies. However, once pre-eclampsia develops, morbidity and mortality rise for both mother and child. For example, perinatal mortality for women with severe pre-eclampsia is double that for normotensive women. Perinatal outcome is worse with early gestational hypertension. Perinatal mortality also increases in women with severe essential hypertension.

Aims of intervention

To delay or prevent the development of pre-eclampsia and eclampsia, and to improve outcomes for women and their children. Once pre-eclampsia has occurred, to minimise morbidity and mortality for women and their children, and to ensure that health service resources are used appropriately.

Outcomes

For the woman: Mortality, rates of severe hypertension, rates of pre-eclampsia (proteinuria and hypertension), eclampsia, death, severe morbidity (such as renal failure, coagulopathy, cardiac failure, liver failure, and stroke), placental abruption, and caesarean section; use of resources (such as dialysis, ventilation, admission to intensive care, or length of stay); adverse effects of treatment. For the child: Mortality, intrauterine growth restriction, prematurity, and severe morbidity (such as intraventricular haemorrhage, respiratory distress syndrome, or asphyxia); measures of infant and child development (such as cerebral palsy or significant learning disability); use of resources (such as admission to special-care nursery, ventilation, length of stay in hospital, and special needs in the community); adverse effects of treatment.

Methods

BMJ Clinical Evidence search and appraisal June 2007. The following databases were used to identify studies for this review: Medline 1966 to June 2007, Embase 1980 to June 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 2. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for evaluation in this review were: published systematic reviews and RCTs in any language, at least single blinded, and containing any number of individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. In options where systematic reviews are reported and have pooled data for large numbers of women, we have reported data from subsequent RCTs sparingly so as not to give such smaller data undue prominence where larger more robust analysis exists, unless they have reported clinically meaningful data, or data not previously reported by the review. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table.

GRADE evaluation of interventions for pre-eclampsia, eclampsia, and hypertension

Important outcomes	Development of pre-eclampsia, seizures, morbidity, prematurity, use of resources, mortality, adverse effects
Number of studies (participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of preventive interventions in women at risk of pre-eclampsia?
at least 46 RCTs (at least 32,590 women)	Development of pre-eclampsia	Antiplatelet drugs v placebo/no antiplatelet drugs	4	0	0	0	0	High
29 (31,151)	Preterm birth	Antiplatelet drugs v placebo/no antiplatelet drugs	4	0	0	0	0	High
40 (33,098)	Perinatal mortality	Antiplatelet drugs v placebo/no antiplatelet drugs	4	0	0	0	0	High
12 (15,206)	Development of pre-eclampsia	Calcium supplementation v placebo	4	0	0	0	+1	High	Effect-size point added for RR less than 0.5
4 (9722)	Maternal mortality	Calcium supplementation v placebo	4	0	0	0	0	High
10 (15,141)	Perinatal mortality	Calcium supplementation v placebo	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
10 (14,751)	Preterm birth	Calcium supplementation v placebo	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
7 (14,710)	Need for other interventions	Calcium supplementation v placebo	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
at least 7 RCTs (at least 6082 women)	Development of pre-eclampsia	Antioxidants v placebo/no antioxidant	4	−1	−1	0	0	Low	Quality point deducted for methodological weaknesses. Consistency point deducted for conflicting results
4 (?)	Preterm birth	Antioxidants v placebo/no antioxidant	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
4 (?)	Perinatal mortality	Antioxidants v placebo/no antioxidant	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
4 (1683)	Development of pre-eclampsia	Marine oil and other prostaglandin precursors v placebo/no treatment	4	−1	0	0	0	Moderate	Quality point deducted for uncertainty about blinding
5 (1916)	Preterm birth	Marine oil and other prostaglandin precursors v placebo/no treatment	4	−1	0	0	0	Moderate	Quality point deducted for uncertainty about blinding
2 (108)	Development of pre-eclampsia	Glyceryl trinitrate v placebo/no treatment	4	−2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
2 (474)	Development of pre-eclampsia	Magnesium supplementation v placebo	4	−1	0	0	0	Moderate	Quality point deducted for uncertainty about bias
2 (603)	Development of pre-eclampsia	Salt restriction v normal dietary salt intake	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
1 (68)	Development of pre-eclampsia	Atenolol v placebo	4	−1	0	0	0	Moderate	Quality point deducted for sparse data
What are the effects of interventions in women who develop mild–moderate hypertension during pregnancy?
at least 22 RCTs (at least 2702 women)	Development of severe hypertension or pre-eclampsia	Antihypertensive drugs v placebo/no antihypertensive drug	4	−3	0	0	0	Very low	Quality points deducted for incomplete reporting of results, methodological weaknesses, and uncertainty about adherence to treatment
26 (3081)	Perinatal mortality	Antihypertensive drugs v placebo/no antihypertensive drug	4	−3	0	0	0	Very low	Quality points deducted for incomplete reporting of results, methodological weaknesses, and uncertainty about adherence to treatment
1 (218)	Development of severe hypertension or pre-eclampsia	Bed rest/hospital admission v no hospital admission	4	−1	0	−1	0	Low	Quality points deducted for uncertainty about bias and for differences in frequency of blood pressure measurement
1 (218)	Preterm birth	Bed rest/hospital admission v no hospital admission	4	−1	0	0	0	Moderate	Quality point deducted for uncertainty about bias
What are the effects of interventions in women who develop severe pre-eclampsia or very high blood pressure during pregnancy?
6 (11,444) We found two reports of long-term follow-up for women	Seizures	Magnesium sulphate v placebo/no anticonvulsant	4	0	0	0	+1	High	Effect-size point added for RR less than 0.5
1 (3283)	Child development	Magnesium sulphate v placebo/no anticonvulsant	4	−1	0	0	0	Moderate	Quality point deducted for poor follow-up
2 (10,795)	Maternal mortality	Magnesium sulphate v placebo/no anticonvulsant	4	0	0	0	0	High
3 (9961)	Perinatal mortality	Magnesium sulphate v placebo/no anticonvulsant	4	0	0	0	0	High
3 (3891)	Seizures	Magnesium sulphate v phenytoin, nimodipine, or diazepam	4	0	0	0	+1	High	Effect-size point added for RR less than 0.5
at least 1 RCT (at least 10,108 women)	Need for further interventions	Magnesium sulphate v placebo/no anticonvulsant	4	0	0	0	0	High
at least 1 RCT (9092 women)	Adverse effects	Magnesium sulphate v placebo/no anticonvulsant	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
3 (505)	Seizures	Antihypertensive drugs v each other	4	−1	0	−1	0	Low	Quality point deducted for incomplete reporting of results. Directness point deducted for no direct comparison between drugs
2 (133)	Perinatal mortality	Interventionist management v expectant management	4	−2	0	0	0	Low	Quality points deducted for incomplete reporting of results and for sparse data
2 (133)	Neonatal morbidity	Interventionist management v expectant management	4	−2	0	0	0	Low	Quality points deducted for incomplete reporting of results and for sparse data
4 (277)	Seizures	Plasma volume expansion v control	4	−1	0	−1	0	Low	Quality point deducted for incomplete reporting of results. Directness point deducted for differences in disease severities
4 (277)	Perinatal mortality	Plasma volume expansion v control	4	−1	0	−1	0	Low	Quality point deducted for incomplete reporting of results. Directness point deducted for differences in disease severities
4 (277)	Maternal morbidity	Plasma volume expansion v control	4	−1	0	−1	0	Low	Quality point deducted for incomplete reporting of results. Directness point deducted for differences in disease severities
What is the best choice of anticonvulsant for women with eclampsia?
7 (1441)	Seizures	Magnesium sulphate v diazepam	4	0	0	0	0	High
2 (597)	Neonatal morbidity	Magnesium sulphate v diazepam	4	0	0	0	0	High
3 (631)	Duration of hospital stay	Magnesium sulphate v diazepam	4	0	0	0	0	High
6 (1336)	Maternal mortality	Magnesium sulphate v diazepam	4	0	0	0	0	High
5 RCTs (at least 895 women)	Seizures	Magnesium sulphate v phenytoin	4	0	0	0	0	High
1 (775)	Need for further interventions	Magnesium sulphate v phenytoin	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
2 (797)	Maternal mortality	Magnesium sulphate v phenytoin	4	0	0	0	0	High
1 (643)	Perinatal mortality	Magnesium sulphate v phenytoin	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
2 (397)	Seizures	Magnesium sulphate v lytic cocktail	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
2 (397)	Maternal mortality	Magnesium sulphate v lytic cocktail	4	0	−1	0	0	Moderate	Consistency point deducted for conflicting results
2 (397)	Perinatal mortality	Magnesium sulphate v lytic cocktail	4	−1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results

Open in a new tab

Type of evidence: 4 = RCT; 2 = Observational Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio

Glossary

High-quality evidence: Further research is very unlikely to change our confidence in the estimate of effect.
Low-quality evidence: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Lytic cocktail: A mixture of pethidine, chlorpromazine, and promethazine.
Moderate-quality evidence: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Very low-quality evidence: Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

References

1.Gifford RW, August PA, Cunningham G, et al. Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000;183(suppl):1–22. [PubMed] [Google Scholar]
2.WHO international collaborative study of hypertensive disorders of pregnancy. Geographic variation in the incidence of hypertension in pregnancy. Am J Obstet Gynecol 1988;158:80–83. [PubMed] [Google Scholar]
3.Douglas K, Redman C. Eclampsia in the United Kingdom. BMJ 1994;309:1395–1400. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Crowther CA. Eclampsia at Harare maternity hospital. An epidemiological study. S Afr Med J 1985;68:927–929. [PubMed] [Google Scholar]
5.Bergstrom S, Povey G, Songane F, et al. Seasonal incidence of eclampsia and its relationship to meteorological data in Mozambique. J Perinat Med 1992;20:153–158. [DOI] [PubMed] [Google Scholar]
6.Roberts JM, Redman CWG. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 1993;341:1447–1451. [DOI] [PubMed] [Google Scholar]
7.Taylor DJ. The epidemiology of hypertension during pregnancy. In: Rubin PC, ed. Hypertension in pregnancy. Amsterdam: Elsevier Science, 1988:223–240. [Google Scholar]
8.Sibai BM, Caritis S, Hauth J. Risks of preeclampsia and adverse neonatal outcomes among women with pregestational diabetes mellitus. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol 2000;182:364–369. [DOI] [PubMed] [Google Scholar]
9.MacGillivray I. Pre-eclampsia. The hypertensive disease of pregnancy. London: WB Saunders, 1983. [Google Scholar]
10.Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 2005;330:565. [DOI] [PMC free article] [PubMed] [Google Scholar]
11.Conde-Agudelo A, Althabe F, Belizan JM, et al. Cigarette smoking during pregnancy and risk of preeclampsia: a systematic review. Am J Obstet Gynecol 1999;181:1026–1035. Search date 1998; primary sources Medline, Embase, Popline, Cinahl, Lilacs, and hand searches of proceedings of international meetings on pre-eclampsia and reference lists of retrieved articles. [DOI] [PubMed] [Google Scholar]
12.Chamberlain GVP, Philip E, Howlett B, et al. British births. London: Heinemann, 1970. [Google Scholar]
13.Sibai B, Lindheimer M, Hauth J, et al. Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension. N Engl J Med 1998;339:667–671. [DOI] [PubMed] [Google Scholar]
14.Duley L, Henderson-Smart DJ, Knight M, et al. Antiplatelet agents for preventing pre-eclampsia and its complications. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006. [Google Scholar]
15.Grant A, Farrell B, Heineman J, et al. Low dose aspirin in pregnancy and early childhood development: follow up of the collaborative low dose aspirin study in pregnancy. Br J Obstet Gynaecol 1995;102:861–868. [DOI] [PubMed] [Google Scholar]
16.Parazzini F, Bortolus R, Chatenoud L, et al. Follow-up of children in the Italian study of aspirin in pregnancy. Lancet 1994;343:1235. [DOI] [PubMed] [Google Scholar]
17.Atallah AN, Hofmeyr GJ, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2006. [DOI] [PubMed] [Google Scholar]
18.Rumbold A, Duley L, Crowther C, et al. Antioxidants for preventing pre-eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2004; primary sources Cochrane Pregnancy and Childbirth Group Trials Register and The Cochrane Library. [Google Scholar]
19.Polyzos NP, Mauri D, Tsappi M, et al. Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: a systematic review. Obstet Gynecol Survey 2007;62:202–206. [DOI] [PubMed] [Google Scholar]
20.Rumiris D, Purwosunu Y, Wibowo N, et al. Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status. Hypertension in Pregnancy 2006;25:241–253. [DOI] [PubMed] [Google Scholar]
21.Makrides M, Duley L, Olsen SF. Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction. In: The Cochrane library, Issue 2, 2007. Chichester,UK: John Wiley & Sons Ltd. Search date 2005. [DOI] [PubMed] [Google Scholar]
22.Szajewska H, Horvath A, Koletzko B. Effect of n-3 long-chain polyunsaturated fatty acid supplementation of women with low-risk pregnancies on pregnancy outcomes and growth measures at birth: A meta-analysis of randomized controlled trials. Am J Clin Nutr 2006;83:1337–1344. [DOI] [PubMed] [Google Scholar]
23.Olsen SF, Sorensen JD, Secher NJ, et al. Randomised controlled trial of effect of fish oil supplementation on pregnancy duration. Lancet 1992;339:1003–1007. [DOI] [PubMed] [Google Scholar]
24.Lees C, Valensise H, Black R, et al. The efficacy and fetal-maternal cardiovascular effects of transdermal glycerol trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double blind placebo controlled trial. Ultrasound Obstet Gynaecol 1998;12:334–338. [DOI] [PubMed] [Google Scholar]
25.Picciolo C, Roncaglia N, Neri I, et al. Nitric oxide in the prevention of pre-eclampsia. Prenat Neonatal Med 2000;5:212–215. [Google Scholar]
26.Zozulia OV, Rogov VA, Piatakova NV, et al. Nitric oxide: its role in the development of pregnancy complications and in their prevention in women with hypertension and chronic glomerulonephritis. Ter Arkh 1997;69:17–20. [In Russian] [PubMed] [Google Scholar]
27.Makrides M, Crowther CA. Magnesium supplementation in pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2001; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]
28.Duley L, Henderson-Smart D, Meher S. Altered dietary salt for preventing pre-eclampsia, and its complications. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2005; primary sources Cochrane Pregnancy and Childbirth Group Trials Register, The Cochrane Library, and Embase. [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Easterling TR, Brateng D, Schucker B, et al. Prevention of preeclampsia: a randomized trial of atenolol in hyperdynamic patients before onset of hypertension. Obstet Gynecol 1999;93:725–733. [DOI] [PubMed] [Google Scholar]
30.Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during pregnancy. BMJ 1990;301:587–589. [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Churchill D, Bayliss H, Beevers G. Fetal growth restriction. Lancet 1999;355:1366–1367. [DOI] [PubMed] [Google Scholar]
32.Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2006; primary sources Cochrane Pregnancy and Childbirth Group Trials Register, Cochrane Controlled Trials Register, Medline, and Embase. [Google Scholar]
33.Magee LA, Duley L. Oral beta-blockers for mild to moderate hypertension during pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2004; primary sources Cochrane Pregnancy and Childbirth Group Trial Register, Medline, and hand searches of reference lists. [Google Scholar]
34.Von Dadelszen P, Ornstein MP, Bull SB, et al. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. Lancet 2000;355:87–92. Search date 1997; primary sources Medline, Embase, hand searches of reference lists, Hypertension and Pregnancy 1992–1997, and a standard toxicology text. [DOI] [PubMed] [Google Scholar]
35.Ferrer RL, Sibai BM, Mulrow CD, et al. Management of mild chronic hypertension during pregnancy: a review. Obstet Gynecol 2000;96:849–860. Search date 1999; primary sources 16 electronic databases, textbook references, and contact with experts. [DOI] [PubMed] [Google Scholar]
36.Mulrow CD, Chiquette E, Ferrer RL, et al. Management of chronic hypertension during pregnancy. Evidence Report/Technology Assessment No 14 (prepared by the San Antonio Evidence-based Practice Center based at the University of Texas Health Science Center at San Antonio under Contract No 290-97-0012). AHRQ Publication No 00-E011. Rockville, MD: Agency for Healthcare Research and Quality. August 2000. Search date 1999; primary sources 16 electronic databases, textbook references, and experts. Available online at: http://www.ahrq.gov/clinic/epcsums/pregsum.htm (last assessed 24 June 2008). [Google Scholar]
37.Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors.[see comment]. N Engl J Med 2006;354:2443–2451. [DOI] [PubMed] [Google Scholar]
38.Tsaava F, Shonia R. Efficacy of antihypertensive drugs in pregnancy. Georgian Med News 2005;23–26. [In Russian] [PubMed] [Google Scholar]
39.Meher S, Abalos E, Carroli G. Bed rest with or without hospitalisation for hypertension during pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2005; primary sources Cochrane Pregnancy and Childbirth Group Trials Register, The Cochrane Library, and Embase. [DOI] [PMC free article] [PubMed] [Google Scholar]
40.Kroner C, Turnbull D, Wilkinson C. Antenatal day care units versus hospital admission for women with complicated pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2001; primary sources Cochrane Pregnancy and Childbirth Group Trials Register, Cochrane Controlled Trials Register, Cinahl, Current Contents, and conference proceedings. [DOI] [PubMed] [Google Scholar]
41.Duley L, G–lmezoglu AM, Henderson-Smart D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2002; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]
42.Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for women at 2 years. BJOG 2007;114:300–309. [DOI] [PMC free article] [PubMed] [Google Scholar]
43.Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months. BJOG 2007;114:289–299. [DOI] [PMC free article] [PubMed] [Google Scholar]
44.The Magpie Trial Collaborative Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002;359:1877–1890. [DOI] [PubMed] [Google Scholar]
45.Mittendorf R, Covert R, Boman J, et al. Is tocolytic magnesium sulphate associated with increased total paediatric mortality? Lancet 1997;350:1517–1518. [DOI] [PubMed] [Google Scholar]
46.Nelson K, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants? Pediatrics 1995;95:263–269. [PubMed] [Google Scholar]
47.Schendel DE, Berg CJ, Yeargin-Allsopp M, et al. Prenatal magnesium sulfate exposure and the risk of cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years. JAMA 1996;276:1805–1810. [PubMed] [Google Scholar]
48.Crowther CA, Hiller JE, Doyle LW, et al. Effect of magnesium sulfate given for neuroprotection before preterm birth. A randomized controlled trial. JAMA 2003;290:2669–2676. [DOI] [PubMed] [Google Scholar]
49.Duley L, Henderson-Smart DJ. Drugs for treatment of very high blood pressure during pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2006; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]
50.Vigil-De GraciaP, Lasso M, Ruiz E, et al. Severe hypertension in pregnancy: hydralazine or labetalol. A randomized clinical trial. Eur Obstet Gynecol Reprod Biol 2006;128:157–162. [DOI] [PubMed] [Google Scholar]
51.Wacker JR, Wagner BK, Briese V, et al. Antihypertensive therapy in patients with pre-eclampsia: A prospective randomised multicentre study comparing dihydralazine with urapidil. Eur J Obstet Gynecol Reprod Biol 2006;127:160–165. [DOI] [PubMed] [Google Scholar]
52.Gulmezoglu AM, Hofmeyr GJ, Oosthuizen MMJ. Antioxidants in the treatment of severe preeclampsia: a randomized explanatory study. Br J Obstet Gynaecol 1997;104:689–696. [DOI] [PubMed] [Google Scholar]
53.Head BB, Owen J, Vincent Jr RD, et al. A randomized trial of intrapartum analgesia in women with severe preeclampsia. Obstet Gynecol 2002;99:452–457. [DOI] [PubMed] [Google Scholar]
54.Lucas MJ, Sharma SK, McIntire DD, et al. A randomized trial of labor analgesia in women with pregnancy-induced hypertension. Am J Obstet Gynecol 2001;185:970–975. [DOI] [PubMed] [Google Scholar]
55.Churchill D, Duley L. Interventionist versus expectant care for severe pre-eclampsia before term. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2006; primary sources Cochrane Pregnancy and Childbirth Group Trials Register and Cochrane Controlled Trials Register. [Google Scholar]
56.Duley L, Williams J, Henderson-Smart DJ. Plasma volume expansion for treatment of pre-eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 1999; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]
57.Ganzevoort W, Rep A, Bonsel GJ, et al. A randomised controlled trial comparing two temporising management strategies, one with and one without plasma volume expansion, for severe and early onset pre-eclampsia. BJOG 2005;112:1358–1368. [DOI] [PubMed] [Google Scholar]
58.The Albumin Reviewers (Alderson P, Bunn F, Lefebvre C, et al). Human albumin solution for resuscitation and volume expansion in critically ill patients. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2004; primary sources Cochrane Injuries Group Trials Register, Cochrane Controlled Trials Register, Medline, Embase, Bids Scientific and Technical Proceedings, hand searches of reference lists of trials and review articles, and personal contact with authors of identified trials. [Google Scholar]
59.Roberts I, Alderson P, Bunn F, et al. Colloids versus crystalloids for fluid resuscitation in critically ill patients. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2002; primary sources Cochrane Clinical Trials Register, Medline, Embase, Bids Index to Scientific and Technical Proceedings, and reference lists of trials and review articles. [Google Scholar]
60.Duley L, Henderson-Smart D. Magnesium sulphate versus diazepam for eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2002; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]
61.Duley L, Henderson-Smart D. Magnesium sulphate versus phenytoin for eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2002; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]
62.Neto JD, Bertini AM, Taborda WC, et al. Treatment of eclampsia: comparative study on the use of magnesium sulfate and phenytoin. Rev Brasil Ginecol Obstet 2000;22:543–549. [In Portuguese] [Google Scholar]
63.Duley L, Gulmezoglu AM. Magnesium sulphate versus lytic cocktail for eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2000; primary sources Cochrane Pregnancy and Childbirth Group Trials Register and Cochrane Controlled Trials Register. [Google Scholar]
64.Nagar S, Jain S, Kumari S, et al. Reassessment of therapy of eclampsia: comparison of mortality and morbidity of mother and fetus with parenteral magnesium sulphate and lytic cocktail therapy. J Obstet Gynecol India 1988;38:250–255. [Google Scholar]

BMJ Clin Evid. 2008 Aug 14;2008:1402.

Antiplatelet drugs

Summary

DEVELOPMENT OF PRE-ECLAMPSIA Compared with placebo/no antiplatelet drugs: Antiplatelet drugs (mainly low-dose aspirin) are more effective at reducing pre-eclampsia in women at risk of pre-eclampsia ( high-quality evidence ). PRETERM BIRTH Compared with placebo/no antiplatelet drugs: Antiplatelet drugs (mainly low-dose aspirin) are more effective at reducing the risk of babies being born small for their gestational age to women at risk of pre-eclampsia (high-quality evidence). PERINATAL MORTALITY Compared with placebo/no antiplatelet drugs: Antiplatelet drugs (mainly low-dose aspirin) are more effective at reducing perinatal mortality (high-quality evidence).

Benefits

We found one systematic review (search date 2006, 59 RCTs, 37,560 women).

Antiplatelet drugs versus placebo/no antiplatelet drug:

The systematic review found that antiplatelet agents (mainly aspirin, but also dipyridamole and ozagrel) significantly reduced pre-eclampsia, premature birth, the proportion of babies born small for gestational age, and infant mortality, in women considered at risk of pre-eclampsia (pre-eclampsia: 46 RCTs, 1081/16,396 [7%] with antiplatelet v 1292/16,194 [8%] with control; RR 0.83, 95% CI 0.77 to 0.89; NNT 72, 95% CI 52 to 119; premature birth: 29 RCTs, 2612/15,629 [17%] with antiplatelet v 2797/15,522 [18%] with control; RR 0.92, 95% CI 0.88 to 0.97; NNT 72, 95% CI 52 to 119; babies born small for gestational age: 36 RCTs, 983/11,904 [8%] with antiplatelet v 1062/11,734 [9%] with control; RR 0.90 95% CI 0.83 to 0.98; infant mortality: 40 RCTs, 414/16,607 [2.5%] with antiplatelet v 475/16,491 [2.9%] with control; RR 0.86, 95% CI 0.76 to 0.98; NNT 243, 95% CI 131 to 1666).There were no clear effects on other important outcomes, and no clear benefit from starting treatment before 20 weeks compared with later in pregnancy. The systematic review also found similar relative risk reductions in pre-eclampsia for women at high and moderate risk of pre-eclampsia and its complications for antiplatelets compared with control (women at high risk: 18 RCTs, 323/2070 [16%] with antiplatelet v 425/2051 [21%] with control, RR 0.75, 95% CI 0.66 to 0.85; women at moderate risk: 25 RCTs, 758/14,326 [5%] with antiplatelet v 867/14,143 [6%] with control, RR 0.86, 95% CI 0.79 to 0.95). The benefit was greatest for women given more than 75 mg aspirin daily (above 75 mg aspirin: 16 RCTs, RR 0.64, 95% CI 0.51 to 0.80; above 75 mg aspirin plus dipyridamole: 5 RCTs, RR 0.30, 95% CI 0.15 to 0.60; 75 mg aspirin or less: 21 RCTs, RR 0.88, 95% CI 0.81 to 0.95).

Harms

The systematic review found no evidence that aspirin increased the risk of bleeding for mother or baby. Two studies followed up children of mothers enrolled in trials comparing aspirin versus placebo for 12–18 months. They found no significant difference between aspirin and placebo in children of treated mothers for: hospital visits for congenital malformations, motor deficit, developmental delay, respiratory problems, or bleeding problems; height or weight below the third centile; or bleeding rates.

Comment

Almost all RCTs used low-dose aspirin 50–75 mg daily, and most were placebo controlled. The RCTs included women with a variety of risk factors, including a history of previous early-onset disease, diabetes, or chronic hypertension, and were conducted in both resource-rich and resource-poor countries. Women were categorised as high risk if they had previous severe pre-eclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease. The number-needed-to-treat values cannot be applied directly to different populations of women; the values stated represent estimates for women with a risk of pre-eclampsia that is an average over all the participants in the RCTs. The absolute benefit was higher (and the NNT lower) in women at higher risk of pre-eclampsia.

Substantive changes

Antiplatelet drugs One already reported systematic review updated and 8 RCTs added to the review and its analysis.Overall conclusions of the review unchanged: antiplatelet drugs still categorised as Beneficial.

BMJ Clin Evid. 2008 Aug 14;2008:1402.

Calcium supplementation

Summary

DEVELOPMENT OF PRE-ECLAMPSIA Compared with placebo: Calcium supplements are more effective at reducing the risk of pre-eclampsia, especially in women with low dietary calcium ( high-quality evidence ). PRETERM BIRTH Compared with placebo: Calcium supplementation seems no more effective at reducing preterm birth ( moderate-quality evidence ). NEED FOR FURTHER INTERVENTIONS Compared with placebo: Calcium supplements seem no more effective at reducing the risk of caesarean delivery (moderate-quality evidence). MATERNAL OR PERINATAL MORTALITY Compared with placebo: Calcium supplements are more effective at reducing the risk of maternal death or serious morbidity (high-quality evidence). Calcium supplements seem no more effective at reducing stillbirth or death of the baby before discharge from hospital (moderate-quality evidence).

Benefits

Calcium supplementation versus placebo:

We found one systematic review (search date 2006, 12 RCTs, 15,206 women; see comment below).It found that calcium (mainly 1.5–2 g daily) significantly reduced the risk of pre-eclampsia compared with placebo (12 RCTs: 368/7578 [5%] with calcium supplementation v480/7628 [6%] with placebo; RR 0.48, 95% CI 0.33 to 0.69). Subgroup analysis found that the greatest reduction in risk of pre-eclampsia was for women with low dietary calcium (low dietary calcium: 198/5058 [4%] with calcium supplementation v 276/5096 [5%] with placebo, RR 0.36, 95% CI 0.18 to 0.70; normal dietary calcium: 169/2505 [7%] with calcium supplementation v 197/2517 [8%] with placebo, RR 0.62, 95% CI 0.32 to 1.20). The review found that, overall, compared with placebo, calcium supplementation significantly reduced the risk of maternal death or serious morbidity (4 RCTs: 167/4856 [3%] with calcium supplementation v 210/4876 [4%] with placebo; RR 0.80, 95% CI 0.65 to 0.97) It found no significant difference between calcium supplements and placebo for the risk of caesarean delivery, preterm birth, stillbirth or death of the baby before discharge from hospital, or birth weight below 2500 g (caesarean delivery: 7 RCTs, 14,710 women, RR 0.95, 95% CI 0.88 to 1.01; preterm birth: 10 RCTs, 14,751 women, RR 0.81, 95% CI 0.64 to 1.03; stillbirth or death of the baby before hospital discharge: 10 RCTs, 15,141 women, RR 0.89, 95% CI 0.73 to 1.09; birthweight below 2500 g: 8 RCTs, 14,359 women, RR 0.84, 95% CI 0.68 to 1.03). Follow-up of 514 children at age 7 years in a subset of one trial found that calcium supplementation was associated with fewer children having a distolic blood pressure above the 95th percentile (RR 0.59, 95% CI 0.39 to 0.91).

Harms

After follow-up of 514 children to age 7 years, the review found no harms associated with maternal calcium supplements.

Comment

Most trials in the systematic review were of good quality and included nulliparous or primiparous women. They were conducted largely in the USA and South America. They included mainly women at low risk, with low dietary calcium. Several studies reported that adherence to treatment was 60–90%. The proportion of women taking 90–100% of all allocated treatment was 85% in the largest study, but low in several others (20% in 1 study). The statistical heterogeneity for some outcomes seemed to be explained by differences between the small and large trials, with small trials of largely high-risk women having more positive results.

Substantive changes

Calcium supplementation One already-included systematic review updated with one large RCT added to its analysis. Overall conclusions of the review unchanged: calcium supplementation still categorised as Beneficial.

BMJ Clin Evid. 2008 Aug 14;2008:1402.

Antioxidants

Summary

DEVELOPMENT OF PRE-ECLAMPSIA Compared with placebo/no antioxidant: We don't know whether antioxidants are more effective at reducing the risk of pre-eclampsia ( low-quality evidence ). PRETERM BIRTH Compared with placebo/no antioxidant: Vitamin C plus E seems no more effective at reducing preterm births ( moderate-quality evidence ). PERINATAL MORTALITY Compared with placebo/no antioxidant: Vitamin C plus E seems no more effective at reducing perinatal deaths (moderate-quality evidence).

Benefits

We found one systematic review (search date 2004, 7 RCTs, 6082 women) of antioxidant treatment (largely either the combination of vitamins C and E or antioxidant minerals, such as selenium), one systematic review (search date 2006, 4 RCTs, 4680 women) reporting solely on the combination of antioxidant vitamins C plus E, and one small subsequent RCT of multiple antioxidant vitamins and minerals.

Antioxidants versus placebo/ no antioxidant:

The first systematic review found that, compared with no antioxidant, antioxidants significantly reduced the relative risk of pre-eclampsia, and of having a baby small for gestational age (pre-eclampsia: 7 RCTs, 134/3034 [4%] with antioxidants v 221/3048 [7%] with no antioxidants; RR 0.61, 95% CI 0.50 to 0.75; NNT 34, 95% CI 25 to 50; baby small for gestational age: 3 RCTs, 49/309 [13%] with antioxidants v 81/325 [25%] with no antioxidants; RR 0.64, 95% CI 0.47 to 0.87; NNT 12, 95% CI 7 to 34).The second systematic review included 2 RCTs published subsequent to the first review, and 2 RCTs included in the first review. The second systematic review (4680 women) found no significant difference between vitamin C plus E and placebo in the risk of pre-eclampsia, preterm birth, having a baby small for gestational age, or of the baby dying (pre-eclampsia: 4 RCTs, 11.0% with vitamins C and E v 11.4% with placebo; RR 0.97; 95% CI 0.82 to 1.13; absolute numbers not reported, results presented graphically; preterm birth: 4 RCTs: 19.5% with vitamins C and E v 18.0% with placebo; RR 1.07, 95% CI 0.96 to 1.20; absolute numbers not reported, results presented graphically; having a baby small for gestational age: 4 RCTs: 20.6% with vitamins C and E v 20.0% with placebo; RR 0.94, 95% CI 0.74 to 1.19; absolute numbers not reported, results presented graphically; baby death: 4 RCTs, 2.6% with vitamins C and E v 2.3% with placebo; RR 1.10, 95% CI 0.78 to 1.56; absolute numbers not reported, results presented graphically). The small subsequent RCT (60 women) found that significantly fewer women taking a combination of antioxidants developed pre-eclampsia compared with placebo (2/29 [7%] with antioxidants v 9/31 [29%] with placebo; P = 0.04).

Harms

The first systematic review found that antioxidants significantly increased the risk of birth before 37 weeks' gestation (3 RCTs: 76/293 [26%] with antioxidants v 54/290 [19%] with no antioxidants; RR 1.38, 95% CI 1.04 to 1.82). The second systematic review did not report further on adverse effects.

Comment

The largest trial (5021 women) in the first systematic review was quasi-random, and only three of the seven included trials were rated as high quality. There are insufficient data for reliable conclusions about the effects on other substantive outcomes, such as perinatal death.

Substantive changes

Antioxidents (under question on the effects of preventative interventions in women at risk of pre-eclampsia) One systematic review comparing the combination of vitamin C and E versus placebo and one small subsequent RCT comparing the effects of a combination of different antioxidents versus placebo added to an already reported systematic review comparing antioxidents versus no antioxidents. The new review found no significant difference between vitamin C plus E and placebo in the risk of pre-eclampsia, preterm birth, having a baby small for gestational age, or in the risk of the baby dying. Categorisation of antioxidants unchanged (Unknown effectiveness).

BMJ Clin Evid. 2008 Aug 14;2008:1402.

Marine oil (fish oil) and other prostaglandin precursors (evening primrose oil)

Summary

DEVELOPMENT OF PRE-ECLAMPSIA Compared with placebo or no treatment: Marine oil seems no more effective at reducing the risk of pre-eclampsia ( moderate-quality evidence ). PRETERM BIRTH Compared with placebo or no treatment: Marine oil seems no more effective at reducing preterm birth (moderate-quality evidence).

Benefits

Marine oil (fish oil) and other prostaglandin precursors (evening primrose oil) versus placebo or no treatment:

We found one systematic review (search date 2005, 6 RCTs, 2783 women; see comment below) of marine oil and other prostaglandin precursors for the prevention of pre-eclampsia versus placebo or no treatment.It included all pregnant women regardless of their risk for pre-eclampsia, preterm birth, or intrauterine growth retardation, and excluded women with established pre-eclampsia or suspected intrauterine growth retardation. The review found no significant difference between marine oil and placebo or no marine oil in the risk of pre-eclampsia (4 RCTs: 42/827 [5%] with marine oil v 51/856 [6%] with placebo or no marine oil; RR 0.86, 95% CI 0.59 to 1.27), or preterm birth (5 RCTs: 205/947 [22%] with marine oil v 228/969 [24%] with placebo or no marine oil; RR 0.92, 95% CI 0.79 to 1.07). The review found that women allocated a marine oil supplement had a mean gestation 2.6 days longer than women allocated placebo or no treatment (3 RCTs, 1621 women; WMD 2.55 days, 95% CI 1.03 days to 4.07 days), and that their babies had a slightly higher birthweight (3 RCTs, 2440 women, WMD 47 g, 95% CI 1 g to 93 g). We found a second systematic review (search date 2005, 6 RCTs, 1278 women) restricted to women with a low-risk pregnancy only, and which also included 3 RCTs of oil from non-marine sources, which reached similar conclusions.

Harms

Marine oil (fish oil) and other prostaglandin precursors (evening primrose oil) versus placebo or no treatment:

The first review found that, compared with women allocated control oil, women allocated marine oil were more than three times more likely to report belching (3 RCTs: 320/762 with marine oil v 64/624 with placebo/no marine oil; RR 3.55, 95% CI 2.78 to 4.52), and six times more likely to complain of an unpleasant taste (3 RCTs: 193/743 with marine oil v 22/611 with placebo/no marine oil; RR 6.17, 95% CI 4.03 to 9.44).The review found no significant difference between groups in nausea, vomiting, stomach pain, diarrhoea or constipation. It also found no significant difference between groups in any bleeding complications such as nasal bleeding, antepartum vaginal bleeding, maternal anaemia, vaginal blood loss after birth, and blood loss at birth.

Comment

In the first review, of the six included RCTs, four RCTs used oil derived from the body of a fish, the fifth RCT used a combination of evening primrose oil and fish (body) oil, while the sixth RCT assessed the consumption of eggs enriched with docosanhexanoic acid (DHA) by feeding laying hens with algal (marine) oil.RCTs of fish oil may have been difficult to blind because of the distinctive taste of fish oil. One RCT found that olive oil provided better masking than a non-oil placebo.

Substantive changes

Marine oil (fish oil), and other prostaglandin precursors (evening primrose oil) Option title clarified and changed from 'Fish oil, evening primrose oil, or both' to 'marine oil (fish oil), and other prostaglandin precursors (evening primrose oil)'. Two systematic reviews added and benefits and harms data enhanced. Categorisation of marine oil (fish oil), and other prostaglandin precursors (evening primrose oil) unchanged (Unknown effectiveness).

BMJ Clin Evid. 2008 Aug 14;2008:1402.

Glyceryl trinitrate

Summary

DEVELOPMENT OF PRE-ECLAMPSIA Compared with placebo/no treatment: Glyceryl trinitrate may be no more effective at reducing the risk of pre-eclampsia ( low-quality evidence ).

Benefits

Glyceryl trinitrate versus placebo/no treatment:

We found no systematic review, but found two RCTs. The first RCT (40 women) found no significant difference in the risk of pre-eclampsia between glyceryl trinitrate patches and placebo (RR 1.13, 95% CI 0.35 to 3.60), but the confidence interval was wide. The second RCT (68 women) reported similar results (RR 1.35, 95% CI 0.61 to 3.01).

Glyceryl trinitrate versus aspirin and dipyridamole:

We found one trial (76 women) that was too small to draw any reliable conclusions.

DEVELOPMENT OF SEVERE HYPERTENSION OR PRE-ECLAMPSIA Compared with placebo/no antihypertensive drug: Antihypertensive drugs may be more effective at reducing the risk of severe hypertension, but not of pre-eclampsia ( very low-quality evidence ). MORTALITY Compared with placebo/no antihypertensive drug: We don’t know whether antihypertensive drugs are more effective at reducing fetal or neonatal deaths (very low-quality evidence).

Benefits

We found two systematic reviews. The first systematic review (search date 2006, 46 RCTs, 4282 women with mild to moderate hypertension) included studies that compared any antihypertensive drug versus placebo or versus another antihypertensive drug. The second systematic review (search date 2004, 29 RCTs, 2500 women with mild to moderate hypertension) included only studies that compared beta-blockers versus no antihypertensive drug or versus another antihypertensive drug.

Antihypertensive drugs versus placebo or no antihypertensive drug:

The first review found that antihypertensive drugs significantly and substantially reduced the risk of developing severe hypertension compared with no antihypertensive drugs (19 RCTs, 2409 women: RR 0.50, 95% CI 0.41 to 0.61; NNT 10, 95% CI 8 to 13). It found no significant difference between groups for pre-eclampsia or fetal or neonatal death (pre-eclampsia: 22 RCTs, 2702 women: RR 0.97, 95% CI 0.83 to 1.13; fetal or neonatal death: 26 RCTs, 3081 women: RR 0.73, 95% CI 0.50 to 1.08). The second review found that beta-blockers significantly reduced the development of severe hypertension compared with no beta-blockers (11 RCTs, 1128 women: RR 0.37, 95% CI 0.26 to 0.53). The review found insufficient evidence for other maternal outcomes.

Antihypertensive drugs versus other antihypertensive agents:

Neither systematic review found any clear difference among any of these drugs for the risk of developing severe hypertension or pre-eclampsia.

Harms

The antihypertensive agents included in the systematic reviews seem to have been well tolerated during pregnancy, but adverse effects have not been reported in many RCTs. All antihypertensive drugs cross the placenta, but few trials reported possible adverse effects for the baby. The first review found that beta-blockers seem significantly better compared with methyl dopa for reducing the risk of severe hypertension (8 RCTs, 493 women; RR 0.79, 95% CI 0.63 to 0.99). The second review found that beta-blockers significantly increased the baby's risk of being small for its gestational age (13 RCTs, 854 women: RR 1.34, 95% CI 1.01 to 1.79). Meta regression within a systematic review suggested that lowering blood pressure for women with mild or moderate hypertension may increase the risk of having a baby small for its gestational age. One systematic review (search date 1999, 13 small RCTs in women with pre-existing chronic hypertension) found that ACE inhibitors used in the second or third trimester were associated with fetal renal failure. Fetal exposure to these agents during the first trimester is associated with major congenital malformations.If women using ACE inhibitors are contemplating pregnancy, it would seem advisable to switch them to another drug well in advance of conception.

Comment

The RCTs were too small to exclude beneficial effects of antihypertensive agents. The trials had problems with methods. Many were not placebo controlled, and few attempted to blind blood pressure measurement. Many important outcomes were reported by only a few studies. We found little evidence about adherence to treatment. One systematic review found that the effects of antihypertensive agents in women with pre-existing chronic hypertension were similar to those described above for women with pregnancy-induced hypertension. The review did not establish or exclude benefit from treatment. We found one study in Russian that is awaiting translation and will be included in future if relevant.

Substantive changes

Antihypertensive agents (under question in women who develop mild–moderate hypertension during pregnancy) One already-included systematic review comparing antihypertensive drug versus placebo/no antihypertensive drug or versus other antihypertensives updated, and six new RCTs added to its analysis.The overall conclusions of the review unchanged, in that it found antihypertensive drugs significantly reduced the risk of developing severe hypertension compared with no antihypertensive drugs, but it found no significant difference between antihypertensive drugs and no hypertensive drugs in pre-eclampsia or fetal or neonatal death. Categorisation of antihypertensive drugs for mild to moderate hypertension unchanged (Unknown effectiveness).

BMJ Clin Evid. 2008 Aug 14;2008:1402.

Bed rest/hospital admission

Summary

DEVELOPMENT OF SEVERE HYPERTENSION OR PRE-ECLAMPSIA Compared with no hospital admission: We don’t know whether some rest in hospital is more effective than normal activity at home at reducing the incidence of severe hypertension in women with non-proteinuric hypertension ( low-quality evidence ). PRETERM BIRTH Compared with no hospital admission: Some rest in hospital seems to be modestly more effective at lowering the risk of preterm birth in women with non-proteinuric hypertension ( moderate-quality evidence ).

Benefits

Bed rest/admission versus no hospital admission:

We found one systematic review (search date 2005, 4 RCTs, 449 women) of hospital admission. The systematic review compared some rest in hospital with normal activity at home for women with non-proteinuric hypertension. Women allocated some rest in hospital had fewer incidences of severe hypertension compared with those allocated normal activity at home (1 RCT, 218 women: 25/110 [23%] with some rest v 42/108 [39%] with normal activity; RR 0.58, 95% CI 0.38 to 0.89), and a lower risk of preterm birth that was borderline for statistical significance (1 RCT, 218 women: 13/110 [12%] with some rest v 24/108 [22%] with normal activity; RR 0.53, 95% CI 0.29 to 0.99). There were no clear differences in any other outcomes. This systematic review also compared bed rest in hospital with normal ambulation in hospital for women with proteinuric hypertension (2 RCTs, 145 women), but the RCTs were too small for any reliable conclusions to be drawn.

Bed rest/admission versus antenatal day-care units:

We found one systematic review (search date 2001, 1 RCT, 54 women). The RCT was too small to draw reliable conclusions.

Harms

It has been suggested that hospital admission increases the risk of venous stasis, thromboembolic disease, or infection, but we found no evidence in this context. In the RCT of antenatal day care, women preferred not to be admitted to hospital. Women allocated rest in hospital were less likely to say that they would choose this option for a future pregnancy than those allocated routine activity at home (1 RCT, 86 women, RR 3.00, 95% CI 1.43 to 6.31). We found no evidence from the other trials about the views of women and their families.

Comment

Trials of hospital admission and bed rest in hospital were largely conducted before widespread introduction of day-care assessment units. Women with hypertension during pregnancy are now often seen in day-care units, but only one small RCT has compared day-care assessment versus assessment in an outpatient clinic. The reduction in severe hypertension for women allocated rest in hospital rather than routine activity at home should be interpreted with caution, as this may reflect 'white-coat' hypertension, ascertainment bias, or both, in that women at home had only weekly assessment of their blood pressure.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Aug 14;2008:1402.

Prophylactic anticonvulsants for women with severe pre-eclampsia

Summary

SEIZURES Compared with placebo/no anticonvulsants: Prophylactic magnesium sulphate is more effective at reducing the risk of eclampsia ( high-quality evidence ). Compared with phenytoin, nimodipine, or diazepam: Magnesium sulphate is more effective than phenytoin and nimodipine at reducing the risk of eclampsia (high-quality evidence). NEED FOR FURTHER INTERVENTIONS Compared with placebo/no anticonvulsants: Magnesium sulphate increases the need for a caesarean section (high-quality evidence). MATERNAL OR PERINATAL MORTALITY Compared with placebo/no anticonvulsants: Prophylactic magnesium sulphate is no more effective at reducing stillbirths, maternal mortality, neonatal mortality, or neurosensory disability or mortality in children at 18 months (high-quality evidence). ADVERSE EFFECTS Compared with placebo/no anticonvulsants: Magnesium sulphate causes more adverse effects, such as flushing, and respiratory depression ( moderate-quality evidence ).

Benefits

We found one systematic review (search date 2002, 13 RCTs, 15,558 women).

Magnesium sulphate versus placebo or no anticonvulsant:

In the review, six RCTs (11,444 women) compared magnesium sulphate versus placebo. Prophylactic magnesium sulphate significantly reduced the risk of eclampsia compared with placebo (43/5722 [1%] with magnesium sulphate v 107/5722 [2%] with placebo; RR 0.41, 95% CI 0.29 to 0.58; NNT 100, 95% CI 50 to 100). Magnesium sulphate also reduced maternal mortality compared with placebo, although the results were not significant (2 RCTs: 11/5400 [0.2%] with magnesium sulphate v 21/5395 [0.4%] with placebo; RR 0.54, 95% CI 0.26 to 1.10). For women randomised before delivery, there was no significant difference in the risk of stillbirth or neonatal death (3 RCTs: 634/5003 [13%] with magnesium sulphate v 611/4958 [12%] with placebo; RR 1.04, 95% CI 0.93 to 1.15).We found two reports of long-term follow-up for women and children recruited to a large RCT included in the review. The first report in women found no significant difference between the groups in the risk of death or serious morbidity potentially related to pre-eclampsia when the children were 2 years old (58/1650 [4%] with magnesium sulphate v 72/1725 [4%] with placebo; RR 0.84, 95% CI 0.60 to 1.18).Of those women selected for follow-up (4782 of 7927 women randomised at centres participating in the follow-up study), the results were based on 3375/4782 (71%) of women who responded. The second follow-up report in children found no significant difference between the groups in the risk of death or neurosensory disability when the children were 18 months old (245/1635 [15%] allocated magnesium sulphate v 233/1648 [14%] allocated placebo; RR 1.06, 95% CI 0.90 to 1.25).Of those children selected for follow-up (4483 of 6922 children of women randomised before delivery at centres participating in the follow-up study), the results were based on 3283/4483 (73%) of children for whom data were available.

Magnesium sulphate versus phenytoin, nimodipine, or diazepam:

Two RCTs (2241 women) included in the review found that magnesium sulphate significantly reduced the risk of eclampsia compared with phenytoin (0/1109 [0%] with magnesium sulphate v 10/1132 [0.8%] with phenytoin; RR 0.05, 95% CI 0.00 to 0.84). Another RCT (1650 women) found that magnesium sulphate significantly reduced the risk of eclampsia compared with nimodipine (7/831 [1%] with magnesium sulphate v 21/819 [3%] with nimodipine; RR 0.33, 95% CI 0.14 to 0.77). There was insufficient evidence for reliable conclusions about magnesium sulphate compared with diazepam (2 RCTs, 66 women).

SEIZURES Compared with diazepam: Magnesium sulphate is more effective at reducing further fits ( high-quality evidence ). Compared with phenytoin: Magnesium sulphate is more effective at reducing further fits (high-quality evidence). Compared with lytic cocktail: Magnesium sulphate seems more effective at reducing further fits ( moderate-quality evidence ). NEONATAL MORBIDITY Compared with diazepam: Magnesium sulphate is more effective at reducing the proprotion of babies with Apgar scores less than 7 at 5 minutes, and at reducing the proportion of babies with a length of stay in a special-care baby unit for more than 7 days (high-quality evidence). Compared with phenytoin: Magnesium sulphate seems more effective at reducing pneumonia, requirement for ventilation, and admission to an intensive-care unit, and at reducing the proportion of babies with a composite outcome of death or staying in a special-care baby unit for more than 7 days (moderate-quality evidence). Compared with lytic cocktail: Magnesium sulphate is more effective at reducing pneumonia and respiratory depression (high-quality evidence). MATERNAL OR PERINATAL MORTALITY Compared with diazepam: Magnesium sulphate is more effective at reducing maternal mortality (high-quality evidence). Compared with phenytoin: Magnesium sulphate and phenytoin seem equally effective at reducing maternal deaths (moderate-quality evidence). Compared with lytic cocktail: Magnesium sulphate seems more effective at reducing fetal or infant deaths, but we don't know whether it is more effective at reducing maternal deaths (moderate-quality evidence).

Benefits

Magnesium sulphate versus diazepam:

We found one systematic review (search date 2002, 7 RCTs, 1441 women). It found that magnesium sulphate significantly reduced both maternal mortality (6 RCTs: 26/677 [4%] with magnesium sulphate v 42/659 [6%] with diazepam; RR 0.59, 95% CI 0.37 to 0.94) and further fits (7 RCTs: 71/737 [10%] with magnesium sulphate v 162/704 [23%] with diazepam; RR 0.44, 95% CI 0.34 to 0.57) compared with diazepam. It found no significant differences in any other outcomes for the mother. For the babies, it found that magnesium sulphate significantly reduced the proportion of babies with Apgar scores less than seven at 5 minutes compared with diazepam (2 RCTs: 69/309 [22%] with magnesium sulphate v 90/288 [31%] with diazepam; RR 0.72, 95% CI 0.55 to 0.94), and significantly reduced the proportion of babies with a length of stay in a special-care baby unit of more than 7 days compared with diazepam (3 RCTs: 42/329 [13%] with magnesium sulphate v 59/302 [20%] with diazepam; RR 0.66, 95% CI 0.46 to 0.95).

Magnesium sulphate versus phenytoin:

We found one systematic review (search date 2002, 6 RCTs, 897 women) and one subsequent RCT. The systematic review found that, compared with phenytoin, magnesium sulphate significantly reduced the risk of further fits (5 RCTs: 25/448 [6%] with magnesium sulphate v 83/447 [19%] with phenytoin; RR 0.31, 95% CI 0.20 to 0.47), pneumonia (1 RCT, 775 women: RR 0.44, 95% CI 0.24 to 0.79), requirement for ventilation (1 RCT, 775 women: RR 0.66, 95% CI 0.49 to 0.90), and admission to intensive-care unit (1 RCT, 775 women: RR 0.67, 95% CI 0.50 to 0.89). It also found that, compared with phenytoin, magnesium sulphate significantly reduced the proportion of babies with the composite outcome of death or staying in a special-care baby unit for more than 7 days (1 RCT, 643 babies: RR 0.77, 95% CI 0.63 to 0.95). The lower maternal death rate with magnesium sulphate compared with phenytoin was not significant, but the confidence interval was wide, and a clinically important effect could not be excluded (2 RCTs: 10/399 [3%] with magnesium sulphate v 20/398 [5%] with phenytoin; RR 0.50, 95% CI 0.24 to 1.05). We found one subsequent RCT (77 women), which was too small for reliable conclusions, although reported results were consistent with the systematic review.

Magnesium sulphate versus lytic cocktail:

We found one systematic review (search date 2000, 2 RCTs, 199 women)and one additional RCT (199 women). In the systematic review, when compared with lytic cocktail, magnesium sulphate significantly reduced further fits (4/96 [4%] with magnesium sulphate v 49/102 [48%] with lytic cocktail; RR 0.09, 95% CI 0.03 to 0.24), pneumonia (1/51 [2%] with magnesium sulphate v 11/57 [19%] with lytic cocktail; RR 0.08, 95% CI 0.02 to 0.42), respiratory depression (0/96 [0%] with magnesium sulphate v 8/102 [8%] with lytic cocktail; RR 0.12, 95% CI 0.02 to 0.91), and fetal or infant death (14/89 [16%] with magnesium sulphate v 30/88 [34%] with lytic cocktail; RR 0.45, 95% CI 0.26 to 0.79). There was a non-significant reduction in maternal deaths (1/96 [1%] with magnesium sulphate v 6/102 [6%] with lytic cocktail; RR 0.25, 95% CI 0.04 to 1.43). The additional RCT found that, compared with lytic cocktail, magnesium sulphate significantly reduced recurrence of convulsions, maternal deaths, and perinatal deaths (recurrence of convulsions: 2% with magnesium sulphate v 62% with lytic cocktail; absolute numbers not reported, P less than 0.001; maternal deaths: 0/101 [0%] with magnesium sulphate v 8/98 [8%] with lytic cocktail, P less than 0.005; perinatal deaths: 10% with magnesium sulphate v 23% with lytic cocktail, absolute numbers not reported, P less than 0.05).

Harms

The systematic reviews suggested that magnesium sulphate is safer for women — at least in the short term — than diazepam, phenytoin, or lytic cocktail. It also seemed to be safer for babies than phenytoin or lytic cocktail. We found no evidence from RCTs about longer-term adverse effects in women or children.

Comment

Most information about the comparisons with diazepam and phenytoin came from one large multicentre trial, in which adherence to treatment was 99%. Most of the data came from trials that included women with antepartum or postpartum eclampsia.

Substantive changes

Anticonvulsants for women with eclampsia One RCT including 199 women added comparing magnesium sulphate versus lytic cocktail.Categorisation of magnesium sulphate for eclampsia (better and safer than other anticonvulsants) unchanged (Beneficial).

[BMJ_1402_REF1] 1.Gifford RW, August PA, Cunningham G, et al. Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000;183(suppl):1–22. [PubMed] [Google Scholar]

[BMJ_1402_REF2] 2.WHO international collaborative study of hypertensive disorders of pregnancy. Geographic variation in the incidence of hypertension in pregnancy. Am J Obstet Gynecol 1988;158:80–83. [PubMed] [Google Scholar]

[BMJ_1402_REF3] 3.Douglas K, Redman C. Eclampsia in the United Kingdom. BMJ 1994;309:1395–1400. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1402_REF4] 4.Crowther CA. Eclampsia at Harare maternity hospital. An epidemiological study. S Afr Med J 1985;68:927–929. [PubMed] [Google Scholar]

[BMJ_1402_REF5] 5.Bergstrom S, Povey G, Songane F, et al. Seasonal incidence of eclampsia and its relationship to meteorological data in Mozambique. J Perinat Med 1992;20:153–158. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF6] 6.Roberts JM, Redman CWG. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 1993;341:1447–1451. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF7] 7.Taylor DJ. The epidemiology of hypertension during pregnancy. In: Rubin PC, ed. Hypertension in pregnancy. Amsterdam: Elsevier Science, 1988:223–240. [Google Scholar]

[BMJ_1402_REF8] 8.Sibai BM, Caritis S, Hauth J. Risks of preeclampsia and adverse neonatal outcomes among women with pregestational diabetes mellitus. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol 2000;182:364–369. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF9] 9.MacGillivray I. Pre-eclampsia. The hypertensive disease of pregnancy. London: WB Saunders, 1983. [Google Scholar]

[BMJ_1402_REF10] 10.Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 2005;330:565. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1402_REF11] 11.Conde-Agudelo A, Althabe F, Belizan JM, et al. Cigarette smoking during pregnancy and risk of preeclampsia: a systematic review. Am J Obstet Gynecol 1999;181:1026–1035. Search date 1998; primary sources Medline, Embase, Popline, Cinahl, Lilacs, and hand searches of proceedings of international meetings on pre-eclampsia and reference lists of retrieved articles. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF12] 12.Chamberlain GVP, Philip E, Howlett B, et al. British births. London: Heinemann, 1970. [Google Scholar]

[BMJ_1402_REF13] 13.Sibai B, Lindheimer M, Hauth J, et al. Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension. N Engl J Med 1998;339:667–671. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF14] 14.Duley L, Henderson-Smart DJ, Knight M, et al. Antiplatelet agents for preventing pre-eclampsia and its complications. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006. [Google Scholar]

[BMJ_1402_REF15] 15.Grant A, Farrell B, Heineman J, et al. Low dose aspirin in pregnancy and early childhood development: follow up of the collaborative low dose aspirin study in pregnancy. Br J Obstet Gynaecol 1995;102:861–868. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF16] 16.Parazzini F, Bortolus R, Chatenoud L, et al. Follow-up of children in the Italian study of aspirin in pregnancy. Lancet 1994;343:1235. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF17] 17.Atallah AN, Hofmeyr GJ, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2006. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF18] 18.Rumbold A, Duley L, Crowther C, et al. Antioxidants for preventing pre-eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2004; primary sources Cochrane Pregnancy and Childbirth Group Trials Register and The Cochrane Library. [Google Scholar]

[BMJ_1402_REF19] 19.Polyzos NP, Mauri D, Tsappi M, et al. Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: a systematic review. Obstet Gynecol Survey 2007;62:202–206. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF20] 20.Rumiris D, Purwosunu Y, Wibowo N, et al. Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status. Hypertension in Pregnancy 2006;25:241–253. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF21] 21.Makrides M, Duley L, Olsen SF. Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction. In: The Cochrane library, Issue 2, 2007. Chichester,UK: John Wiley & Sons Ltd. Search date 2005. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF22] 22.Szajewska H, Horvath A, Koletzko B. Effect of n-3 long-chain polyunsaturated fatty acid supplementation of women with low-risk pregnancies on pregnancy outcomes and growth measures at birth: A meta-analysis of randomized controlled trials. Am J Clin Nutr 2006;83:1337–1344. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF23] 23.Olsen SF, Sorensen JD, Secher NJ, et al. Randomised controlled trial of effect of fish oil supplementation on pregnancy duration. Lancet 1992;339:1003–1007. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF24] 24.Lees C, Valensise H, Black R, et al. The efficacy and fetal-maternal cardiovascular effects of transdermal glycerol trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double blind placebo controlled trial. Ultrasound Obstet Gynaecol 1998;12:334–338. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF25] 25.Picciolo C, Roncaglia N, Neri I, et al. Nitric oxide in the prevention of pre-eclampsia. Prenat Neonatal Med 2000;5:212–215. [Google Scholar]

[BMJ_1402_REF26] 26.Zozulia OV, Rogov VA, Piatakova NV, et al. Nitric oxide: its role in the development of pregnancy complications and in their prevention in women with hypertension and chronic glomerulonephritis. Ter Arkh 1997;69:17–20. [In Russian] [PubMed] [Google Scholar]

[BMJ_1402_REF27] 27.Makrides M, Crowther CA. Magnesium supplementation in pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2001; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]

[BMJ_1402_REF28] 28.Duley L, Henderson-Smart D, Meher S. Altered dietary salt for preventing pre-eclampsia, and its complications. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2005; primary sources Cochrane Pregnancy and Childbirth Group Trials Register, The Cochrane Library, and Embase. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1402_REF29] 29.Easterling TR, Brateng D, Schucker B, et al. Prevention of preeclampsia: a randomized trial of atenolol in hyperdynamic patients before onset of hypertension. Obstet Gynecol 1999;93:725–733. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF30] 30.Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during pregnancy. BMJ 1990;301:587–589. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1402_REF31] 31.Churchill D, Bayliss H, Beevers G. Fetal growth restriction. Lancet 1999;355:1366–1367. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF32] 32.Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2006; primary sources Cochrane Pregnancy and Childbirth Group Trials Register, Cochrane Controlled Trials Register, Medline, and Embase. [Google Scholar]

[BMJ_1402_REF33] 33.Magee LA, Duley L. Oral beta-blockers for mild to moderate hypertension during pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2004; primary sources Cochrane Pregnancy and Childbirth Group Trial Register, Medline, and hand searches of reference lists. [Google Scholar]

[BMJ_1402_REF34] 34.Von Dadelszen P, Ornstein MP, Bull SB, et al. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. Lancet 2000;355:87–92. Search date 1997; primary sources Medline, Embase, hand searches of reference lists, Hypertension and Pregnancy 1992–1997, and a standard toxicology text. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF35] 35.Ferrer RL, Sibai BM, Mulrow CD, et al. Management of mild chronic hypertension during pregnancy: a review. Obstet Gynecol 2000;96:849–860. Search date 1999; primary sources 16 electronic databases, textbook references, and contact with experts. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF36] 36.Mulrow CD, Chiquette E, Ferrer RL, et al. Management of chronic hypertension during pregnancy. Evidence Report/Technology Assessment No 14 (prepared by the San Antonio Evidence-based Practice Center based at the University of Texas Health Science Center at San Antonio under Contract No 290-97-0012). AHRQ Publication No 00-E011. Rockville, MD: Agency for Healthcare Research and Quality. August 2000. Search date 1999; primary sources 16 electronic databases, textbook references, and experts. Available online at: http://www.ahrq.gov/clinic/epcsums/pregsum.htm (last assessed 24 June 2008). [Google Scholar]

[BMJ_1402_REF37] 37.Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors.[see comment]. N Engl J Med 2006;354:2443–2451. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF38] 38.Tsaava F, Shonia R. Efficacy of antihypertensive drugs in pregnancy. Georgian Med News 2005;23–26. [In Russian] [PubMed] [Google Scholar]

[BMJ_1402_REF39] 39.Meher S, Abalos E, Carroli G. Bed rest with or without hospitalisation for hypertension during pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2005; primary sources Cochrane Pregnancy and Childbirth Group Trials Register, The Cochrane Library, and Embase. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1402_REF40] 40.Kroner C, Turnbull D, Wilkinson C. Antenatal day care units versus hospital admission for women with complicated pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2001; primary sources Cochrane Pregnancy and Childbirth Group Trials Register, Cochrane Controlled Trials Register, Cinahl, Current Contents, and conference proceedings. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF41] 41.Duley L, G–lmezoglu AM, Henderson-Smart D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2002; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]

[BMJ_1402_REF42] 42.Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for women at 2 years. BJOG 2007;114:300–309. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1402_REF43] 43.Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months. BJOG 2007;114:289–299. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1402_REF44] 44.The Magpie Trial Collaborative Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002;359:1877–1890. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF45] 45.Mittendorf R, Covert R, Boman J, et al. Is tocolytic magnesium sulphate associated with increased total paediatric mortality? Lancet 1997;350:1517–1518. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF46] 46.Nelson K, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants? Pediatrics 1995;95:263–269. [PubMed] [Google Scholar]

[BMJ_1402_REF47] 47.Schendel DE, Berg CJ, Yeargin-Allsopp M, et al. Prenatal magnesium sulfate exposure and the risk of cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years. JAMA 1996;276:1805–1810. [PubMed] [Google Scholar]

[BMJ_1402_REF48] 48.Crowther CA, Hiller JE, Doyle LW, et al. Effect of magnesium sulfate given for neuroprotection before preterm birth. A randomized controlled trial. JAMA 2003;290:2669–2676. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF49] 49.Duley L, Henderson-Smart DJ. Drugs for treatment of very high blood pressure during pregnancy. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2006; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]

[BMJ_1402_REF50] 50.Vigil-De GraciaP, Lasso M, Ruiz E, et al. Severe hypertension in pregnancy: hydralazine or labetalol. A randomized clinical trial. Eur Obstet Gynecol Reprod Biol 2006;128:157–162. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF51] 51.Wacker JR, Wagner BK, Briese V, et al. Antihypertensive therapy in patients with pre-eclampsia: A prospective randomised multicentre study comparing dihydralazine with urapidil. Eur J Obstet Gynecol Reprod Biol 2006;127:160–165. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF52] 52.Gulmezoglu AM, Hofmeyr GJ, Oosthuizen MMJ. Antioxidants in the treatment of severe preeclampsia: a randomized explanatory study. Br J Obstet Gynaecol 1997;104:689–696. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF53] 53.Head BB, Owen J, Vincent Jr RD, et al. A randomized trial of intrapartum analgesia in women with severe preeclampsia. Obstet Gynecol 2002;99:452–457. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF54] 54.Lucas MJ, Sharma SK, McIntire DD, et al. A randomized trial of labor analgesia in women with pregnancy-induced hypertension. Am J Obstet Gynecol 2001;185:970–975. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF55] 55.Churchill D, Duley L. Interventionist versus expectant care for severe pre-eclampsia before term. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2006; primary sources Cochrane Pregnancy and Childbirth Group Trials Register and Cochrane Controlled Trials Register. [Google Scholar]

[BMJ_1402_REF56] 56.Duley L, Williams J, Henderson-Smart DJ. Plasma volume expansion for treatment of pre-eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 1999; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]

[BMJ_1402_REF57] 57.Ganzevoort W, Rep A, Bonsel GJ, et al. A randomised controlled trial comparing two temporising management strategies, one with and one without plasma volume expansion, for severe and early onset pre-eclampsia. BJOG 2005;112:1358–1368. [DOI] [PubMed] [Google Scholar]

[BMJ_1402_REF58] 58.The Albumin Reviewers (Alderson P, Bunn F, Lefebvre C, et al). Human albumin solution for resuscitation and volume expansion in critically ill patients. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2004; primary sources Cochrane Injuries Group Trials Register, Cochrane Controlled Trials Register, Medline, Embase, Bids Scientific and Technical Proceedings, hand searches of reference lists of trials and review articles, and personal contact with authors of identified trials. [Google Scholar]

[BMJ_1402_REF59] 59.Roberts I, Alderson P, Bunn F, et al. Colloids versus crystalloids for fluid resuscitation in critically ill patients. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2002; primary sources Cochrane Clinical Trials Register, Medline, Embase, Bids Index to Scientific and Technical Proceedings, and reference lists of trials and review articles. [Google Scholar]

[BMJ_1402_REF60] 60.Duley L, Henderson-Smart D. Magnesium sulphate versus diazepam for eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2002; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]

[BMJ_1402_REF61] 61.Duley L, Henderson-Smart D. Magnesium sulphate versus phenytoin for eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2002; primary source Cochrane Pregnancy and Childbirth Group Trials Register. [Google Scholar]

[BMJ_1402_REF62] 62.Neto JD, Bertini AM, Taborda WC, et al. Treatment of eclampsia: comparative study on the use of magnesium sulfate and phenytoin. Rev Brasil Ginecol Obstet 2000;22:543–549. [In Portuguese] [Google Scholar]

[BMJ_1402_REF63] 63.Duley L, Gulmezoglu AM. Magnesium sulphate versus lytic cocktail for eclampsia. In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2000; primary sources Cochrane Pregnancy and Childbirth Group Trials Register and Cochrane Controlled Trials Register. [Google Scholar]

[BMJ_1402_REF64] 64.Nagar S, Jain S, Kumari S, et al. Reassessment of therapy of eclampsia: comparison of mortality and morbidity of mother and fetus with parenteral magnesium sulphate and lytic cocktail therapy. J Obstet Gynecol India 1988;38:250–255. [Google Scholar]

PERMALINK

Pre-eclampsia, eclampsia, and hypertension

Lelia Duley

Roles

Abstract

Introduction

Methods and outcomes

Results

Conclusions

Key Points

About this condition

Definition

Incidence/ Prevalence

Aetiology/ Risk factors

Prognosis

Aims of intervention

Outcomes

Methods

Table.

Glossary

Disclaimer

References

Antiplatelet drugs

Summary

Benefits

Antiplatelet drugs versus placebo/no antiplatelet drug:

Harms

Comment

Substantive changes

Calcium supplementation

Summary

Benefits

Calcium supplementation versus placebo:

Harms

Comment

Substantive changes

Antioxidants

Summary

Benefits

Antioxidants versus placebo/ no antioxidant:

Harms

Comment

Substantive changes

Marine oil (fish oil) and other prostaglandin precursors (evening primrose oil)

Summary

Benefits

Marine oil (fish oil) and other prostaglandin precursors (evening primrose oil) versus placebo or no treatment:

Harms

Marine oil (fish oil) and other prostaglandin precursors (evening primrose oil) versus placebo or no treatment:

Comment

Substantive changes

Glyceryl trinitrate

Summary

Benefits

Glyceryl trinitrate versus placebo/no treatment:

Glyceryl trinitrate versus aspirin and dipyridamole:

Harms

Glyceryl trinitrate versus placebo/no treatment:

Glyceryl trinitrate versus aspirin and dipyridamole:

Comment

Substantive changes

Magnesium supplementation

Summary

Benefits

Harms

Comment

Substantive changes

Salt restriction

Summary

Benefits

Harms

Comment

Substantive changes

Atenolol

Summary

Benefits

Harms

Comment

Substantive changes

Antihypertensive agents