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Pre-eclampsia, eclampsia, and hypertensionSearch date July 2007Lelia Duley

ABSTRACTINTRODUCTION: Pre-eclampsia (raised blood pressure and proteinuria) complicates 28% of pregnancies, and raises morbidity and mor-tality in the mother and child. Pre-eclampsia is more common in women with multiple pregnancy and in those who have conditions associateswith microvascular disease. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinicalquestions: What are the effects of preventive interventions in women at risk of pre-eclampsia? What are the effects of interventions inwomen who develop mildmoderate hypertension during pregnancy? What are the effects of interventions in women who develop severepre-eclampsia or very high blood pressure during pregnancy? What is the best choice of anticonvulsant for women with eclampsia? Wesearched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (BMJ Clinical Evidence reviews areupdated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant or-ganisations 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 evalu-ation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectivenessand safety of the following interventions: anticonvulsants, antihypertensive drugs, antioxidants, antiplatelet drugs, atenolol, bed rest, hospitaladmission or day care, calcium supplementation, choice of analgesia during labour, early delivery (interventionist care), evening primroseoil, fish oil, glyceryl trinitrate, magnesium supplementation, plasma volume expansion, and salt restriction.

QUESTIONS

What are the effects of preventive interventions in women at risk of pre-eclampsia?. . . . . . . . . . . . . . . . . . . . . 3

What are the effects of interventions in women who develop mild to moderate hypertension during pregnancy?. .8

What are the effects of interventions in women who develop severe pre-eclampsia or very high blood pressureduring pregnancy?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

What is the best choice of anticonvulsant for women with eclampsia?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

INTERVENTIONS

PREVENTION OF PRE-ECLAMPSIA

Beneficial

Antiplatelet drugs 3

Likely to be beneficial

Antihypertensive drugs for very high blood pressure* . .

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Antiplatelet drugs 3 1 0

Key points

Pre-eclampsia (raised blood pressure and proteinuria) complicates 28% of pregnancies, and increases morbidityand mortality in the mother and child.

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

Antiplatelet drugs (primarily low-dose aspirin) reduce the risk of pre-eclampsia, death of the baby, and prematurebirth, 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 conclu-sions.

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 pro-gression 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 beingborn 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 antihypertensivetreatment, 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 improveoutcomes for women with severe pre-eclampsia.

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

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

DEFINITION Hypertension during pregnancy may be associated with one of several conditions. Pregnancy-in-

duced hypertension is a rise in blood pressure without proteinuria during the second half of

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OUTCOMES For the woman: Mortality, rates of severe hypertension, rates of pre-eclampsia (proteinuria andhypertension), eclampsia, death, severe morbidity (such as renal failure, coagulopathy, cardiacfailure, 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 asintraventricular haemorrhage, respiratory distress syndrome, or asphyxia); measures of infant andchild development (such as cerebral palsy or significant learning disability); use of resources (suchas admission to special-care nursery, ventilation, length of stay in hospital, and special needs inthe community); adverse effects of treatment.

METHODS BMJ Clinical Evidencesearch and appraisal June 2007. The following databases were used toidentify studies for this review: Medline 1966 to June 2007, Embase 1980 to June 2007, and TheCochrane 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 forReviews and Dissemination (CRD) for Database of Abstracts of Reviews of Effects (DARE) andHealth Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. Abstractsof the studies retrieved from the initial search were assessed by an information specialist. Selectedstudies were then sent to the contributor for additional assessment, using pre-determined criteriato identify relevant studies. Study design criteria for evaluation in this review were: published sys-tematic reviews and RCTs in any language, at least single blinded, and containing any number ofindividuals of whom more than 80% were followed up.There was no minimum length of follow-uprequired to include studies. We excluded all studies described as open, open label, or notblinded unless blinding was impossible. In addition, we use a regular surveillance protocol to captureharms alerts from organisations such as the FDA and the UK Medicines and Healthcare productsRegulatory Agency (MHRA), which are added to the reviews as required. In options where system-atic reviews are reported and have pooled data for large numbers of women, we have reporteddata from subsequent RCTs sparingly so as not to give such smaller data undue prominence wherelarger more robust analysis exists, unless they have reported clinically meaningful data, or datanot previously reported by the review. We have performed a GRADE evaluation of the quality ofevidence for interventions included in this review (see table, p 18 ).

QUESTION What are the effects of preventive interventions in women at risk of pre-eclampsia?


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0.66 to 0.85; women at moderate risk: 25 RCTs, 758/14,326 [5%] with antiplatelet v867/14,143[6%] with control, RR 0.86, 95% CI 0.79 to 0.95). The benefit was greatest for women given morethan 75 mg aspir in daily (above 75 mg aspirin: 16 RCTs, RR 0.64, 95% CI 0.51 to 0.80; above75 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). [14]

Harms: The systematic review found no evidence that aspirin increased the risk of bleeding for mother orbaby.

[14]Two studies followed up children of mothers enrolled in trials comparing aspirin versus

placebo for 1218 months.[15] [16]

They found no significant difference between aspirin andplacebo 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 thirdcentile; or bleeding rates.

Comment: Almost all RCTs used low-dose aspirin 5075 mg daily, and most were placebo controlled.TheRCTs included women with a variety of risk factors, including a history of previous early-onsetdisease, 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 representestimates for women with a risk of pre-eclampsia that is an average over all the participants in theRCTs.The absolute benefit was higher (and the NNT lower) in women at higher risk of pre-eclampsia.

OPTION CALCIUM SUPPLEMENTATION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Development of pre-eclampsiaCompared with placeboCalcium supplements are more effective at reducing the risk of pre-eclampsia, especiallyin women with low dietary calcium (high-quality evidence).

Preterm birthCompared with placeboCalcium supplementation seems no more effective at reducing preterm birth (moderate-quality evidence).

Need for further interventions


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Comment: Most trials in the systematic review were of good quality and included nulliparous or primiparouswomen.They were conducted largely in the USA and South America.They included mainly womenat low risk, with low dietary calcium. Several studies reported that adherence to treatment was6090%.

[17]The proportion of women taking 90100% of all allocated treatment was 85% in the

largest study, but low in several others (20% in 1 study). [17] The statistical heterogeneity for someoutcomes seemed to be explained by differences between the small and large trials, with smalltrials of largely high-risk women having more positive results.

OPTION ANTIOXIDANTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Development of pre-eclampsiaCompared with placebo/no antioxidantWe don't know whether antioxidants are more effective at reducing the riskof pre-eclampsia (low-quality evidence).

Preterm birthCompared with placebo/no antioxidantVitamin C plus E seems no more effective at reducing preterm bir ths (moderate-quality evidence).

Perinatal mortalityCompared with placebo/no antioxidantVitamin C plus E seems no more effective at reducing perinatal deaths(moderate-quality evidence).

For GRADE evaluation of interventions for pre-eclampsia, eclampsia, and hypertension, see table, p 18 .

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),

[18]

one systematic review (search date 2006, 4 RCTs, 4680 women) reporting solely on the combinationof antioxidant vitamins C plus E,

[19]and one small subsequent RCT of multiple antioxidant vitamins

and minerals.[20]

Antioxidants versus placebo/ no antioxidant:The first systematic review found that, compared with no antioxidant, antioxidants significantly re-duced 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


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Preterm birthCompared with placebo or no treatmentMarine oil seems no more effective at reducing preterm birth (moderate-quality evidence).


Benefits: Marine oil (fish oil) and other prostaglandin precursors (evening primrose oil) versusplacebo 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 versusplacebo or no treatment.

[21]It included all pregnant women regardless of their risk for pre-

eclampsia, preterm bir th, or intrauterine growth retardation, and excluded women with establishedpre-eclampsia or suspected intrauterine growth retardation. The review found no significant differencebetween marine oil and placebo or no marine oil in the r isk of pre-eclampsia (4 RCTs: 42/827 [5%]with marine oil v51/856 [6%] with placebo or no marine oil; RR 0.86, 95% CI 0.59 to 1.27), orpreterm birth (5 RCTs: 205/947 [22%] with marine oil v228/969 [24%] with placebo or no marineoil; RR 0.92, 95% CI 0.79 to 1.07).

[21]The review found that women allocated a marine oil supple-

ment had a mean gestation 2.6 days longer than women allocated placebo or no treatment (3RCTs, 1621 women; WMD 2.55 days, 95% CI 1.03 days to 4.07 days), and that their babies hada slightly higher birthweight (3 RCTs, 2440 women, WMD 47 g, 95% CI 1 g to 93 g).

[21]We found

a second systematic review (search date 2005, 6 RCTs, 1278 women) restricted to women with alow-risk pregnancy only, and which also included 3 RCTs of oil from non-marine sources, whichreached similar conclusions.

[22]

Harms: Marine oil (fish oil) and other prostaglandin precursors (evening primrose oil) versusplacebo or no treatment:The first review found that, compared with women allocated control oil, women allocated marineoil were more than three times more likely to report belching (3 RCTs: 320/762 with marine oil v64/624 with placebo/no marine oil; RR 3.55, 95% CI 2.78 to 4.52), and six times more likely tocomplain of an unpleasant taste (3 RCTs: 193/743 with marine oil v22/611 with placebo/no marineoil; RR 6.17, 95% CI 4.03 to 9.44).

[21]The review found no significant difference between groups

in nausea, vomiting, stomach pain, diarrhoea or constipation.[21]

It also found no significant differ-ence 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[21]


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Comment: None.

OPTION MAGNESIUM SUPPLEMENTATION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Development of pre-eclampsiaCompared with placeboMagnesium supplements seem no more effective at reducing the risk of pre-eclampsia(moderate-quality evidence).


Benefits: We found one systematic review (search date 2001, 2 RCTs, 474 women) comparing magnesiumsupplements versus placebo.

[27]It found no significant difference in pre-eclampsia between groups

(34/235 [15%] with magnesium v40/239 [17%] with placebo; RR 0.87, 95% CI 0.57 to 1.32).[27]

Harms: There was no significant difference between the groups in the number of reported gastrointestinalside effects (RR 0.89, 95% CI 0.75 to 1.05).

[27]

Comment: This review included seven trials with 2689 women, of which only two (474 women) reported datafor pre-eclampsia.There is, therefore, also a possibility of bias, in that five trials did not report thisoutcome.

OPTION SALT RESTRICTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Development of pre-eclampsiaCompared with normal dietary intakeA low-salt diet seems no more effective at reducing the risk of pre-eclampsia(moderate-quality evidence).


Benefits: We found one systematic review (search date 2005, 2 RCTs, 603 women) comparing reduced salt(advice to restrict dietary salt intake to 20 or 50 mmol/day) with normal dietary salt intake.

[28]It

found no significant difference for rates of pre-eclampsia, although the trials may have lackedpower to detect clinically important effects (RR 1.11, 95% CI 0.46 to 2.66).


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QUESTION What are the effects of interventions in women who develop mild to moderate hypertensionduring pregnancy?

OPTION ANTIHYPERTENSIVE AGENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Development of severe hypertension or pre-eclampsiaCompared with placebo/no antihypertensive drugAntihypertensive drugs may be more effective at reducing the riskof severe hypertension, but not of pre-eclampsia (very low-quality evidence).

MortalityCompared with placebo/no antihypertensive drugWe dont know whether antihypertensive drugs are more effectiveat reducing fetal or neonatal deaths (very low-quality evidence).


Benefits: We found two systematic reviews.[32] [33]

The first systematic review (search date 2006, 46 RCTs,4282 women with mild to moderate hypertension) included studies that compared any antihyper-tensive drug versus placebo or versus another antihypertensive drug.

[32]The second systematic

review (search date 2004, 29 RCTs, 2500 women with mild to moderate hypertension) includedonly studies that compared beta-blockers versus no antihypertensive drug or versus another anti-hypertensive drug.

[33]

Antihypertensive drugs versus placebo or no antihypertensive drug:

The first review found that antihypertensive drugs significantly and substantially reduced the riskof developing severe hypertension compared with no antihypertensive drugs (19 RCTs, 2409women: RR 0.50, 95% CI 0.41 to 0.61; NNT 10, 95% CI 8 to 13).

[32]It found no significant difference

between groups for pre-eclampsia or fetal or neonatal death (pre-eclampsia: 22 RCTs, 2702women: 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).

[32]The second review found that beta-blockers significantly reduced the

development of severe hypertension compared with no beta-blockers (11 RCTs, 1128 women: RR0.37, 95% CI 0.26 to 0.53).

[33]The review found insufficient evidence for other maternal outcomes.

Antihypertensive drugs versus other antihypertensive agents:N ith t ti i f d l diff f th d f th i k f d


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Preterm birthCompared with no hospital admissionSome rest in hospital seems to be modestly more effective at lowering therisk 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.[39]

The systematic review compared some rest in hospital with normal activity at home for womenwith non-proteinuric hypertension. Women allocated some rest in hospital had fewer incidencesof severe hypertension compared with those allocated normal activity at home (1 RCT, 218 women:25/110 [23%] with some rest v42/108 [39%] with normal activity; RR 0.58, 95% CI 0.38 to 0.89),and a lower risk of preterm bir th that was borderline for statistical significance (1 RCT, 218 women:13/110 [12%] with some rest v24/108 [22%] with normal activity; RR 0.53, 95% CI 0.29 to 0.99).There were no clear differences in any other outcomes. [39] This systematic review also comparedbed rest in hospital with normal ambulation in hospital for women with proteinuric hypertension (2RCTs, 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).

[40]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.[40]

Women allocated rest in hospital were lesslikely to say that they would choose this option for a future pregnancy than those allocated routineactivity at home (1 RCT, 86 women, RR 3.00, 95% CI 1.43 to 6.31). We found no evidence fromthe 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 in-troduction of day-care assessment units.Women with hypertension during pregnancy are now oftenseen in day-care units, but only one small RCT has compared day-care assessment versus assess-ment in an outpatient clinic.

[40]The reduction in severe hypertension for women allocated rest in

hospital rather than ro tine acti it at home sho ld be interpreted ith ca tion as this ma reflect

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Magnesium sulphate versus placebo or no anticonvulsant:In the review, six RCTs (11,444 women) compared magnesium sulphate versus placebo. Prophy-lactic magnesium sulphate significantly reduced the risk of eclampsia compared with placebo(43/5722 [1%] with magnesium sulphate v107/5722 [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 comparedwith placebo, although the results were not significant (2 RCTs: 11/5400 [0.2%] with magnesiumsulphate v21/5395 [0.4%] with placebo; RR 0.54, 95% CI 0.26 to 1.10). For women randomisedbefore delivery, there was no significant difference in the risk of stillbirth or neonatal death (3 RCTs:634/5003 [13%] with magnesium sulphate v611/4958 [12%] with placebo; RR 1.04, 95% CI 0.93to 1.15).

[41]We found two reports of long-term follow-up for women

[42]and children

[43]recruited

to a large RCT[44]

included in the review.The first report in women found no significant differencebetween the groups in the risk of death or serious morbidity potentially related to pre-eclampsiawhen the children were 2 years old (58/1650 [4%] with magnesium sulphate v72/1725 [4%] withplacebo; RR 0.84, 95% CI 0.60 to 1.18).

[42]Of those women selected for follow-up (4782 of 7927

women randomised at centres participating in the follow-up study), the results were based on3375/4782 (71%) of women who responded. The second follow-up report in children found nosignificant difference between the groups in the risk of death or neurosensory disability when thechildren were 18 months old (245/1635 [15%] allocated magnesium sulphate v233/1648 [14%]allocated placebo; RR 1.06, 95% CI 0.90 to 1.25).

[43]Of those children selected for follow-up (4483

of 6922 children of women randomised before delivery at centres participating in the follow-upstudy), 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 reducedthe risk of eclampsia compared with phenytoin (0/1109 [0%] with magnesium sulphate v10/1132[0.8%] with phenytoin; RR 0.05, 95% CI 0.00 to 0.84).

[41]Another RCT (1650 women) found that

magnesium sulphate significantly reduced the risk of eclampsia compared with nimodipine (7/831[1%] with magnesium sulphate v21/819 [3%] with nimodipine; RR 0.33, 95% CI 0.14 to 0.77).

[41]

There was insufficient evidence for reliable conclusions about magnesium sulphate compared withdiazepam (2 RCTs, 66 women).

[41]

Harms: Magnesium sulphate versus placebo or no anticonvulsant:One large, placebo-controlled trial in the review reported adverse effects in detail.

[44]In this RCT,

more omen h d d erse effects ith m gnesi m s l h te com red ith l cebo (1201/4999


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Compared with each otherWe don't know whether one antihypertensive (such as labetalol, nifedipine, methyldopa,diazoxide, urapidil, magnesium sulphate, prazosin, nimodipine, or ketanserin) is more effective than the others atreducing blood pressure (low-quality evidence).

NoteThere is consensus that women with severe hypertension during pregnancy should have antihypertensive treatment.


Benefits: We found one systematic review (search date 2006, 24 RCTs, 2949 women)[49]

and two subsequentRCTs.

[50] [51]The review compared many antihypertensives (such as labetalol, nifedipine,

methyldopa, diazoxide, urapidil, magnesium sulphate, prazosin, nimodipine, and ketanserin)mainly versus hydralazine.

[49]It found that all the antihypertensives reduced blood pressure. The

review found that women allocated calcium channel blockers were significantly less likely to have

persistent high blood pressure compared with hydralazine (5 RCTs: 8/135 [6%] with calciumchannel blockers v23/128 [18%] with hydralazine; RR 0.33, 95% CI 0.15 to 0.70), but there wereno significant differences in other reported outcomes.

[49]The review found that the risk of persistent

high blood pressure was significantly lower for nimodipine compared with magnesium sulphate (1RCT: 374/819 [47%] with nimodipine v451/831 [65%] with magnesium sulphate; RR 0.84, 95%CI 0.76 to 0.93), although nimodipine was associated with a significantly higher risk of eclampsia(2 RCTs: 21/837 [3%] with nimodipine v9/846 [1%] with magnesium sulphate; RR 2.24, 95% CI1.06 to 4.73). It found that nimodipine was associated with a significantly lower risk of respiratorydifficulties for the woman compared with magnesium sulphate (1 RCT: 3/819 [0.4%] with nimodipine

v 11/831 [1.3%] with magnesium sulphate; RR 0.28, 95% CI 0.08 to 0.99), and significantly lesspostpartum haemorrhage (1 RCT: 8/819 [1%] with nimodipine v 20/831 [2%] with magnesium sul-phate; RR 0.41, 95% CI 0.18 to 0.92). Overall, there was no clear evidence that one drug in thereview was better than another.

[49]The first subsequent RCT (200 women) compared intravenous

bolus doses of labetalol versus hydralazine, repeated after 20 minutes if required.[50]

It found noclear differences between groups in persistent hypertension, need for additional doses, or hypoten-sion.The second subsequent RCT (42 women) compared intravenous urapidil versus hydralazine,and reported that no women had hypotension in the first 6 hours of treatment.

[51]

Harms: The systematic review found that the use of ketanserin was associated with significantly more

i t t h t i d ith h d l i (3 RCT 26/96 [27%] ith k t i 5/84


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OPTION CHOICE OF ANALGESIA DURING LABOUR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

We found no clinically important results about analgesia in women with severe pre-eclampsia.


Benefits: We found two RCTs comparing epidural analgesia with patient-controlled intravenous analgesia.[53] [54]

The first RCT (116 women with severe pre-eclampsia) found that epidural analgesia signif-icantly reduced mean pain scores, but the clinical importance of the difference is unclear. The trialwas too small for reliable conclusions to be drawn about other outcomes.

[53]The second RCT

(738 women with pregnancy-induced hypertension) found that epidural analgesia reduced paincompared with intravenous analgesia (proportion of women reporting excellent pain relief: 54%with epidural analgesia v19% with intravenous analgesia; P less than 0.001).

[54]We found no

RCTs of other forms of intrapartum analgesia for this group of women.

Harms: In the first RCT, epidural analgesia significantly increased the chance of having hypotension requiringintravenous ephedrine (5/56 [9%] with epidural analgesia v0/60 [0%] with iv analgesia; reportedas significant).

[53]However, the number of events is too small to draw reliable conclusions.

Neonatal naloxone was more likely to be given after intravenous analgesia (5/56 [9%] with epiduralanalgesia v31/60 [54%] with iv analgesia; RR 5.71, 95% CI 2.39 to 13.60; NNH 3, 95% CI 2 to 4).The trial was too small for reliable conclusions about other outcomes. In the second RCT, epiduralanalgesia increased the duration of the second stage of labour (mean length: 53 minutes withepidural analgesia v40 minutes with iv analgesia), the risk of intrapartum fever (76/372 [22%] with

epidural analgesia v26/366 [8%] with iv analgesia; RR 2.88, 95% CI 1.89 to 4.38), the risk of forcepsdelivery (51/372 [14%] with epidural analgesia v27/366 [7%] with iv analgesia; RR 1.86, 95% CI1.19 to 2.90), and the need for treatment for hypotension (40/372 [11%] with epidural analgesia v0/366 [0%] with iv analgesia; P less than 0.001). Neonatal naloxone was more likely to be givenafter intravenous analgesia (2/372 [1%] with epidural analgesia v40/366 [12%] with iv analgesia).[54]

Comment: The drug used for patient-controlled intravenous analgesia was not reported in the first RCT.[53]

Pethidine was used in the second RCT.[54]

OPTION INTERVENTIONIST CARE FOR SEVERE EARLY ONSET PRE ECLAMPSIA


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OPTION PLASMA VOLUME EXPANSION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

SeizuresCompared with controlWe don't know whether plasma volume expansion using colloids is more effective at reducingthe proportion of women who develop eclampsia (low-quality evidence).

Maternal morbidityCompared with controlWe don't know whether plasma volume expansion using colloids is more effective at reducingthe proportion of women who develop haemolysis, elevated liver enzymes and lowered platelets (HELLP) syndromeor other serious maternal morbidities (low-quality evidence).

Perinatal mortalityCompared with controlWe don't know whether plasma volume expansion using colloids is more effective at reducing

infant mortality (low-quality evidence).


Benefits: We found one systematic review (search date 2000, 3 RCTs, 61 women; see comment below)[56]

evaluating colloid solutions compared with placebo or no infusion, and one subsequent RCT.[57]

The systematic review found insufficient evidence for reliable conclusions, but suggested thatplasma volume expansion is not beneficial.

[56]The subsequent RCT (216 women) found no signif-

icant difference between plasma volume expansion and control in the proportion of women whodeveloped eclampsia (2/111 [2%] with plasma volume expansion v2/105 [2%] with no expansion),

haemolysis, elevated liver enzymes and lowered platelets (HELLP) syndrome (19/111 [17%] withplasma volume expansion v20/105 [19%] with no expansion), other serious maternal morbidity(13/111 [12%] with plasma volume expansion v11/105 [10%] with no expansion), or infant mortal-ity (23/111 [21%] with plasma volume v15/105 [14%] with no expansion; differences reported asnot significant, P values not provided).

[57]

Harms: The systematic review found no significant difference between plasma volume expansion and eitherplacebo or no infusion in the risk of caesarean section (RR 1.5, 95% CI 0.8 to 2.9), or in the needfor additional treatment (RR 1.5, 95% CI 0.7 to 3.1).

[56]

C t I RCT i l d d i th i ll h d l i I th th t RCT


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Maternal or perinatal mortalityCompared with diazepamMagnesium sulphate is more effective at reducing maternal mortality (high-quality evidence).

Compared with phenytoinMagnesium sulphate and phenytoin seem equally effective at reducing maternal deaths

(moderate-quality evidence).

Compared with lytic cocktailMagnesium sulphate seems more effective at reducing fetal or infant deaths, but wedon'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).

[60]It found that

magnesium sulphate significantly reduced both maternal mortality (6 RCTs: 26/677 [4%] with

magnesium sulphate v42/659 [6%] with diazepam; RR 0.59, 95% CI 0.37 to 0.94) and further fits(7 RCTs: 71/737 [10%] with magnesium sulphate v162/704 [23%] with diazepam; RR 0.44, 95%CI 0.34 to 0.57) compared with diazepam. It found no significant differences in any other outcomesfor the mother. For the babies, it found that magnesium sulphate significantly reduced the proportionof babies with Apgar scores less than seven at 5 minutes compared with diazepam (2 RCTs: 69/309[22%] with magnesium sulphate v90/288 [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 unitof more than 7 days compared with diazepam (3 RCTs: 42/329 [13%] with magnesium sulphate v59/302 [20%] with diazepam; RR 0.66, 95% CI 0.46 to 0.95).

[60]

Magnesium sulphate versus phenytoin:We found one systematic review (search date 2002, 6 RCTs, 897 women)

[61]and one subsequent

RCT.[62]

The systematic review found that, compared with phenytoin, magnesium sulphate signif-icantly reduced the risk of further fits (5 RCTs: 25/448 [6%] with magnesium sulphate v83/447[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 to0.90), and admission to intensive-care unit (1 RCT, 775 women: RR 0.67, 95% CI 0.50 to 0.89).[61]

It also found that, compared with phenytoin, magnesium sulphate significantly reduced theproportion of babies with the composite outcome of death or staying in a special-care baby unit for

th 7 d (1 RCT 643 b bi RR 0 77 95% CI 0 63 t 0 95) Th l t l d th


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

SUBSTANTIVE CHANGESAnticonvulsants for women with eclampsia One RCT including 199 women added comparing magnesium sulphateversus lytic cocktail.

[64]Categorisation of magnesium sulphate for eclampsia (better and safer than other anticonvul-

sants) unchanged (Beneficial).

Antihypertensive agents (under question in women who develop mildmoderate hypertension during preg-nancy) One already-included systematic review comparing antihypertensive drug versus placebo/no antihypertensivedrug or versus other antihypertensives updated, and six new RCTs added to its analysis.

[32]The overall conclusions

of the review unchanged,[32]

in that it found antihypertensive drugs significantly reduced the risk of developing severehypertension compared with no antihypertensive drugs, but it found no significant difference between antihypertensivedrugs and no hypertensive drugs in pre-eclampsia or fetal or neonatal death. Categorisation of antihypertensivedrugs for mild to moderate hypertension unchanged (Unknown effectiveness).Antihypertensive drugs for very high blood pressure One already-included systematic review updated

[49]and

two subsequent RCTs added.[50] [51]

All the additional data compares different antihypertensives versus each other.Categorisation of antihypertensive drugs for very high blood pressure unchanged (Likely to be beneficial).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

[19]and one small subsequent

RCT comparing the effects of a combination of different antioxidents versus placebo added[20]

to an already reportedsystematic review comparing antioxidents versus no antioxidents.The new review

[19]found no significant difference

between vitamin C plus E and placebo in the r isk of pre-eclampsia, preterm birth, having a baby small for gestationalage, or in the risk of the baby dying. Categorisation of antioxidants unchanged (Unknown effectiveness).Antiplatelet drugs One already reported systematic review updated and 8 RCTs added to the review and its analysis.[14]

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

i

[17]

O ll l i f th i h d l i l t ti till t i d B fi i l


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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 & SonsLtd. Search date 2004; primary sources Cochrane Pregnancy and ChildbirthGroup Trials Register and The Cochrane Library.

19. Polyzos NP, Mauri D, Tsappi M, et al. Combined vitamin C and E supplementationduring pregnancy for preeclampsia prevention: a systematic review. Obstet Gy-

necol Survey2007;62:202206.[PubMed]

20. Rumiris D, Purwosunu Y, Wibowo N, et al. Lower rate of preeclampsia after an-tioxidant supplementation in pregnant women with low antioxidant status.Hyper-tension in Pregnancy2006;25:241253.[PubMed]

21. Makrides M, Duley L, Olsen SF. Marine oil, and other prostaglandin precursor,supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterinegrowth restriction. In:The Cochrane library, Issue 2, 2007. Chichester,UK: JohnWiley & Sons Ltd. Search date 2005.

22. Szajewska H, Horvath A, Koletzko B. Effect of n-3 long-chain polyunsaturatedfatty acid supplementation of women with low-risk pregnancies on pregnancyoutcomes and growth measures at birth: A meta-analysis of randomized controlledtrials. Am J Clin Nutr2006;83:13371344.

23. Olsen SF, Sorensen JD, Secher NJ, et al. Randomised controlled trial of effect

of fish oil supplementation on pregnancy duration. Lancet1992;339:10031007.[PubMed]

24. Lees C, Valensise H, Black R, et al.The efficacy and fetal-maternal cardiovasculareffects of transdermal glycerol trinitrate in the prophylaxis of pre-eclampsia andits complications: a randomized double blind placebo controlled trial. UltrasoundObstet Gynaecol1998;12:334338.

25. Picciolo C, Roncaglia N, Neri I, et al. Nitric oxide in the prevention of pre-eclampsia. Prenat Neonatal Med2000;5:212215.

26. Zozulia OV, Rogov VA, Piatakova NV, et al. Nitric oxide: its role in the develop-ment of pregnancy complications and in their prevention in women with hyperten-sion and chronic glomerulonephritis. Ter Arkh1997;69:1720. [In Russian]

27. Makrides M, Crowther CA. Magnesium supplementation in pregnancy. In:TheCochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons Ltd. Searchdate 2001; primary source Cochrane Pregnancy and Childbir th Group Trials

Register.

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 sourcesCochrane Pregnancy and Childbirth Group Trials Register, The Cochrane Library,and Embase.

29. Easterling TR, Brateng D, Schucker B, et al. Prevention of preeclampsia: a ran-domized trial of atenolol in hyperdynamic patients before onset of hypertension.Obstet Gynecol1999;93:725733.[PubMed]

30. Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension duringpregnancy. BMJ1990;301:587589.[PubMed]

31. Churchill D, Bayliss H, Beevers G. Fetal growth restriction. Lancet1999;355:13661367.

32 Ab l E D l L St DW H d S t DJ A tih t i d

41. Duley L, Glmezoglu AM, Henderson-Smart D. Magnesium sulphate and otheranticonvulsants for women with pre-eclampsia. In: The Cochrane Library, Issue2, 2007. Chichester, UK: John Wiley & Sons Ltd. Search date 2002; primarysource Cochrane Pregnancy and Childbirth Group Trials Register.

42. Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a ran-domised trial comparing magnesium sulphate with placebo for pre-eclampsia.

Outcome for women at 2 years. BJOG2007;114:300309.

43. Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a ran-domised trial comparing magnesium sulphate with placebo for pre-eclampsia.Outcome for children at 18 months. BJOG2007;114:289299.

44. The Magpie Trial Collaborative Group. Do women with pre-eclampsia, and theirbabies, benefit from magnesium sulphate? The Magpie Trial: a randomisedplacebo-controlled trial. Lancet2002;359:18771890.

45. Mittendorf R, Covert R, Boman J, et al. Is tocolytic magnesium sulphate associ-ated with increased total paediatric mortality? Lancet1997;350:15171518.[PubMed]

46. Nelson K, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsyin very low birthweight infants? Pediatrics1995;95:263269.[PubMed]

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;276:18051810. [PubMed]

48. Crowther CA, Hiller JE, Doyle LW, et al. Effect of magnesium sulfate given forneuroprotection before preterm birth. A randomized controlled trial. JAMA2003;290:26692676.[PubMed]

49. Duley L, Henderson-Smart DJ. Drugs for treatment of very high blood pressureduring pregnancy. In:The Cochrane Library, Issue 2, 2007. Chichester, UK: JohnWiley & Sons Ltd. Search date 2006; primary source Cochrane Pregnancy andChildbirth Group Trials Register.

50. Vigil-De GraciaP, Lasso M, Ruiz E, et al. Severe hypertension in pregnancy:hydralazine or labetalol. A randomized clinical trial. Eur Obstet Gynecol ReprodBiol2006;128:157162.[PubMed]

51. Wacker JR, Wagner BK, Briese V, et al. Antihypertensive therapy in patients withpre-eclampsia: A prospective randomised multicentre study comparing dihy-dralazine with urapidil. Eur J Obstet Gynecol Reprod Biol2006;127:160165.[PubMed]

52. Gulmezoglu AM, Hofmeyr GJ, Oosthuizen MMJ. Antioxidants in the treatmentof severe preeclampsia: a randomized explanatory study. Br J Obstet Gynaecol1997;104:689696.[PubMed]

53. Head BB, Owen J, Vincent Jr RD, et al. A randomized trial of intrapartum analge-sia in women with severe preeclampsia. Obstet Gynecol2002;99:452457.[PubMed]

54. Lucas MJ, Sharma SK, McIntire DD, et al. A randomized trial of labor analgesiain women with pregnancy-induced hypertension. Am J Obstet Gynecol2001;185:970975.[PubMed]

55. Churchill D, Duley L. Interventionist versus expectant care for severe pre-eclampsia before term. In:The Cochrane Library, Issue 2, 2007. Chichester, UK:

J h Wil & S Ltd S h d t 2006 i C h P


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http://www.ncbi.nlm.nih.gov/pubmed/17306042http://www.ncbi.nlm.nih.gov/pubmed/17065044http://www.ncbi.nlm.nih.gov/pubmed/1349049http://www.ncbi.nlm.nih.gov/pubmed/10912975http://www.ncbi.nlm.nih.gov/pubmed/2242456http://www.ncbi.nlm.nih.gov/pubmed/9388401http://www.ncbi.nlm.nih.gov/pubmed/7838646http://www.ncbi.nlm.nih.gov/pubmed/8946900http://www.ncbi.nlm.nih.gov/pubmed/14645308http://www.ncbi.nlm.nih.gov/pubmed/16621226http://www.ncbi.nlm.nih.gov/pubmed/16253414http://www.ncbi.nlm.nih.gov/pubmed/16253414http://www.ncbi.nlm.nih.gov/pubmed/9197872http://www.ncbi.nlm.nih.gov/pubmed/9197872http://www.ncbi.nlm.nih.gov/pubmed/11864673http://www.ncbi.nlm.nih.gov/pubmed/11641687http://www.ncbi.nlm.nih.gov/pubmed/11641687http://www.ncbi.nlm.nih.gov/pubmed/11641687http://www.ncbi.nlm.nih.gov/pubmed/11864673http://www.ncbi.nlm.nih.gov/pubmed/9197872http://www.ncbi.nlm.nih.gov/pubmed/16253414http://www.ncbi.nlm.nih.gov/pubmed/16621226http://www.ncbi.nlm.nih.gov/pubmed/14645308http://www.ncbi.nlm.nih.gov/pubmed/8946900http://www.ncbi.nlm.nih.gov/pubmed/7838646http://www.ncbi.nlm.nih.gov/pubmed/9388401http://www.ncbi.nlm.nih.gov/pubmed/2242456http://www.ncbi.nlm.nih.gov/pubmed/10912975http://www.ncbi.nlm.nih.gov/pubmed/1349049http://www.ncbi.nlm.nih.gov/pubmed/17065044http://www.ncbi.nlm.nih.gov/pubmed/17306042


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Lelia DuleyObstetric Epidemiologist

University of LeedsAcademic unit

LeedsUK

Competing interests: LD is the author of studies included in this review.

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 andharms. 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, thecategories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimatelyit is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullestextent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to anyperson or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, inci-dental or consequential, resulting from the application of the information in this publication.


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

Development of pre-eclampsia, seizures, morbidity, prematurity, use of resources, mortality, adverse effectsImportant outcomes

CommentGRADEEffectsize

Direct-ness

Consis-tencyQuality

Type ofevi-denceComparisonOutcome

Number of studies (par-ticipants)

What are the effects of preventive interventions in women at risk of pre-eclampsia?

High00004Antiplatelet drugs vplacebo/no an-tiplatelet drugsDevelopment of pre-eclampsiaat least 46 RCTs (at least32,590 women)[14]

High00004Antiplatelet drugs vplacebo/no an-tiplatelet drugs

Preterm birth29 (31,151)[14]

High00004Antiplatelet drugs vplacebo/no an-tiplatelet drugs

Perinatal mortality40 (33,098)[14]

Effect-size point added for RR less than0.5

High+10004Calcium supplementation vplaceboDevelopment of pre-eclampsia

12 (15,206)[17]

High00004Calcium supplementation vplaceboMaternal mortality4 (9722)[17]

Quality point deducted for incomplete re-porting of results

Moderate00014Calcium supplementation vplaceboPerinatal mortality10 (15,141)[17]


Moderate00014Calcium supplementation vplaceboPreterm birth10 (14,751)[17]

Quality point deducted for incomplete re-

porting of results

Moderate00014Calcium supplementation vplaceboNeed for other interven-

tions

7 (14,710)[17]

Quality point deducted for methodologicalweaknesses. Consistency point deductedfor conflicting results

Low00114Antioxidantsvplacebo/no antioxidantDevelopment of pre-eclampsia

at least 7 RCTs (at least6082 women)

[ 18 ] [19 ]

[20]


Moderate00014Antioxidantsvplacebo/no antioxidantPreterm birth4 (?)[19]


Moderate00014Antioxidantsvplacebo/no antioxidantPerinatal mortality4 (?)[20]

Quality point deducted for uncertaintyabout blinding

Moderate00014Marine oil and other prostaglandinprecursors vplacebo/no treatment

Development of pre-eclampsia

4 (1683)[21]

Quality point deducted for uncertaintyabout blinding

Moderate00014Marine oil and other prostaglandinprecursors vplacebo/no treatment

Preterm birth5 (1916)[21]

Quality points deducted for sparse dataand incomplete reporting of results

Low00024Glyceryl trinitrate vplacebo/no treat-ment


2 (108)[ 24 ] [ 25 ]

Quality point deducted for uncertaintyabout bias

Moderate00014Magnesium supplementation vplace-bo


2 (474)[27]


Moderate00014Salt restriction vnormal dietary saltintake


2 (603)[28]

Quality point deducted for sparse dataModerate00014Atenolol vplaceboDevelopment of pre-eclampsia

1 (68)[29]

What are the effects of interventions in women who develop mildmoderate hypertension during pregnancy?

BMJ Publishing Group Ltd 2008. All rights reserved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18


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Direct-ness

Consis-tencyQuality



Quality points deducted for incompletereporting of results, methodologicalweaknesses, and uncertainty about adher-ence to treatment

Very low00034Antihypertensive drugs vplacebo/noantihypertensive drug

Development of severehypertension or pre-eclampsia

at least 22 RCTs (at least2702 women)

[ 32 ] [ 33 ]

Quality points deducted for incompletereporting of results, methodologicalweaknesses, and uncertainty about adher-ence to treatment

Very low000

34Antihypertensive drugs vplacebo/noantihypertensive drug

Perinatal mortality26 (3081)[32]

Quality points deducted for uncertaintyabout bias and for differences in frequen-cy of blood pressure measurement

Low01014Bed rest/hospital admission vno hos-pital admission

Development of severehypertension or pre-eclampsia

1 (218)[39]

Quality point deducted for uncertainty

about bias

Moderate00014Bed rest/hospital admission vno hos-

pital admission

Preterm birth1 (218)[39]

What are the effects of interventions in women who develop severe pre-eclampsia or very high blood pressure during pregnancy?


High+10004Magnesium sulphate vplacebo/noanticonvulsant

Seizures6 (11,444)[41]

We foundtwo reports of long-termfollow-up for women

[42]

Quality point deducted for poor follow-upModerate00014Magnesium sulphate vplacebo/no

anticonvulsant

Child development1 (3283)[43]

High00004Magnesium sulphate vplacebo/noanticonvulsant

Maternal mortality2 (10,795)[41]




High+10004Magnesium sulphate vphenytoin, ni-modipine, or diazepam

Seizures3 (3891)[41]


Need for further interven-tions

at least 1 RCT (at least10,108 women)

[41]


Moderate00014Magnesium sulphate vplacebo/noanticonvulsant

Adverse effectsat least 1 RCT (9092women)

[41]

Quality point deducted for incomplete re-porting of results. Directness point deduct-ed for no direct comparison between

drugs

Low01014Antihypertensive drugs veach otherSeizures3 (505)[49] [50] [51]

Quality points deducted for incompletereporting of results and for sparse data

Low00024Interventionist management vexpec-tant management


Quality points deducted for incompletereporting of results and for sparse data

Low00024Interventionist management vexpec-tant management

Neonatal morbidity2 (133)[55]

Quality point deducted for incomplete re-porting of results. Directness point deduct-ed for differences in disease severities

Low01014Plasma volume expansion vcontrolSeizures4 (277)[ 56 ] [ 57 ]

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Direct-ness

Consis-tencyQuality



Quality point deducted for incomplete re-porting of results. Directness point deduct-ed for differences in disease severities

Low01014Plasma volume expansion vcontrolPerinatal mortality4 (277)[ 56] [5 7]

Quality point deducted for incomplete re-

porting of results. Directness point deduct-ed for differences in disease severities

Low01014Plasma volume expansion vcontrolMaternal morbidity4 (277)[ 56] [5 7]

What is the best choice of anticonvulsant for women with eclampsia?

High00004Magnesium sulphate vdiazepamSeizures7 (1441)[60]

High00004Magnesium sulphate vdiazepamNeonatal morbidity2 (597)[60]

High00004Magnesium sulphate vdiazepamDuration of hospital stay3 (631)[60]

High00004Magnesium sulphate v diazepamMaternal mortality6 (1336)[60]

High00004Magnesium sulphate vphenytoinSeizures5 RCTs (at least 895women)

[62]


Moderate00014Magnesium sulphate vphenytoinNeed for further interven-tions

1 (775)[61]

High00004Magnesium sulphate vphenytoinMaternal mortality2 (797)[62]


Moderate00014Magnesium sulphate vphenytoinPerinatal mortality1 (643)[62]


Moderate00014Magnesium sulphate vlytic cocktailSeizures2 (397)[ 63 ] [ 64 ]

Consistency point deducted for conflictingresults

Moderate00104Magnesium sulphate vlytic cocktailMaternal mortality2 (397)[ 63 ] [ 64 ]


Moderate00014Magnesium sulphate vlytic cocktailPerinatal mortality2 (397)[ 63 ] [ 64 ]

Type of evidence: 4 = RCT; 2 = ObservationalConsistency: similarity of results across studiesDirectness: generalisability of population or outcomesEffect size: based on relative risk or odds ratio

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