Pre-Eclampsia, Eclampsia, and Hypertension: Jurnal Maternitas

TUGAS INDIVIDU
MATA KULIAH KEPERAWATAN MATERNITAS
JURNAL MATERNITAS
Pre-eclampsia, eclampsia, and hypertension
OLEH
ELVIN
NIM : 201401090
PROGRAM STUDI ILMU KEPERAWATAN

STIKES WIDYA NUSANTARA
PALU
2016

Search date July 2007
Lelia Duley
ABSTRACT
INTRODUCTION: Pre-eclampsia (raised blood pressure and proteinuria) complicates 28% 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 mildmoderate 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.
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 pressure
during 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* . .
1
0
Calcium supplementation . . . . . . . . . . . . . . . . . . . . . 4
Unknown effectiveness
Antioxidants in severe pre-eclampsia . . . . . . . . . . . 11
Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Glyceryl trinitrate . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Choice of analgesia during labour with severe preeclampsia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Magnesium supplementation . . . . . . . . . . . . . . . . . . 7
Early delivery for severe early-onset pre-eclampsia . .

1
2
Marine oil (fish oil) and other prostaglandin precursors

(evening primrose oil) . . . . . . . . . . . . . . . . . . . . . . . . 5
Plasma volume expansion in severe pre-eclampsia . .

1
3
Salt restriction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
ECLAMPSIA: ANTICONVULSANTS
Unlikely to be beneficial
Beneficial
Atenolol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
TREATMENTS FOR MILDMODERATE HYPERTENSION
Magnesium sulphate for eclampsia (better and safer

than other anticonvulsants) . . . . . . . . . . . . . . . . . . 13
To be covered in future updates
Interventions in women with pre-existing hypertension
Antihypertensive drugs for mild to moderate hypertension

.......................................... 8
Treatment of postpartum hypertension
Bed rest/admission v day care . . . . . . . . . . . . . . . . . 8
Footnote
TREATMENT OF SEVERE EPISODES OF PREECLAMPSIA

Beneficial
*There is consensus that women with severe hypertension during pregnancy should have antihypertensive
treatment, and that women with eclampsia should have
an anticonvulsant. Placebo-controlled trials would
therefore be unethical.
Prophylactic magnesium sulphate in severe preeclampsia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

BMJ Publishing Group Ltd 2008. All rights reserved.
.................... 1 ....................
Clinical Evidence 2008;08:1402
Pregnancy and childbirth
..................................................
Key points
Pre-eclampsia (raised blood pressure and proteinuria) complicates 28% 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.
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. Preexisting 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 com[1]
monly, secondary to underlying disease.
INCIDENCE/
PREVALENCE
Pregnancy-induced hypertension affects 10% of pregnancies, and pre-eclampsia complicates

[2]
28% of pregnancies.
Eclampsia occurs in about 1/2000 deliveries in resource-rich countries.
[3]
[4]
In resource-poor countries, estimates of the incidence of eclampsia vary from 1/1001/1700.
[5]
AETIOLOGY/
The cause of pre-eclampsia is unknown. It is likely to be multifactorial, and may result from deficient
[6]
RISK FACTORS 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,
[7] [8]
and collagen vascular disease.
Other risk factors include genetic susceptibility, increased
[9] [10]
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
[11]
as low birthweight, placental abruption, and perinatal death.
PROGNOSIS
The outcome of pregnancy in women with pregnancy-induced hypertension alone is at least as

[7] [12]
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
[7]
severe pre-eclampsia is double that for normotensive women.
Perinatal outcome is worse with
[7] [9] [12]
early gestational hypertension.
Perinatal mortality also increases in women with severe
[13]
essential hypertension.
AIMS OF
To delay or prevent the development of pre-eclampsia and eclampsia, and to improve outcomes
INTERVENTION 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.
........................................................... 2
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, p 18 ).
QUESTION
What are the effects of preventive interventions in women at risk of pre-eclampsia?
OPTION
ANTIPLATELET DRUGS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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
the risk of babies being born small for their gestational age to women at risk of pre-eclampsia (high-quality evidence).
Perinatal mortality
perinatal mortality (high-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 2006, 59 RCTs, 37,560 women).
[14]
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 (preeclampsia: 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,
[14]
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
BMJ Publishing Group Ltd 2008. All rights reserved. ...........................................................
3
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
[14]
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
[14]
baby.
Two studies followed up children of mothers enrolled in trials comparing aspirin versus
[15] [16]
placebo for 1218 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 5075 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 resourcepoor 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-totreat 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 preeclampsia.
OPTION
CALCIUM SUPPLEMENTATION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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 (moderatequality 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).
[17]
It found that calcium (mainly 1.52 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).
[17]
Harms:
After follow-up of 514 children to age 7 years, the review found no harms associated with maternal
[17]
calcium supplements.
BMJ Publishing Group Ltd 2008. All rights reserved. ...........................................................
4
Comment:
OPTION
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
[17]
6090%.
The proportion of women taking 90100% of all allocated treatment was 85% in the
[17]
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.
ANTIOXIDANTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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 (moderatequality evidence).
Perinatal mortality
Compared with placebo/no antioxidant Vitamin C plus E seems no more effective at reducing perinatal deaths
Benefits:
We found one systematic review (search date 2004, 7 RCTs, 6082 women) of antioxidant treatment
[18]
(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
[19]
of antioxidant vitamins C plus E,
and one small subsequent RCT of multiple antioxidant vitamins
[20]
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 (preeclampsia: 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;
[18]
NNT 12, 95% CI 7 to 34).
The second systematic review included 2 RCTs published subsequent
[19]
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 preeclampsia, preterm birth, having a baby small for gestational age, or of the baby dying (preeclampsia: 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
[19]
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%]
[20]
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;
[18]
RR 1.38, 95% CI 1.04 to 1.82).
The second systematic review did not report further on adverse
[19]
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.
OPTION
MARINE OIL (FISH OIL) AND OTHER PROSTAGLANDIN PRECURSORS (EVENING PRIMROSE
OIL). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Compared with placebo or no treatment Marine oil seems no more effective at reducing the risk of pre-eclampsia
...........................................................
Preterm birth
Compared with placebo or no treatment Marine oil seems no more effective at reducing preterm birth (moderatequality 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
[21]
placebo or no treatment.
It included all pregnant women regardless of their risk for preeclampsia, 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
[21]
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
[21]
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
[22]
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
[21]
oil; RR 6.17, 95% CI 4.03 to 9.44).
The review found no significant difference between groups
[21]
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
[21]
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
[21]
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
[23]
placebo.
OPTION
GLYCERYL TRINITRATE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Compared with placebo/no treatment Glyceryl trinitrate may be no more effective at reducing the risk of preeclampsia (low-quality evidence).
Benefits:
Glyceryl trinitrate versus placebo/no treatment:

[24] [25]
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
[24]
(RR 1.13, 95% CI 0.35 to 3.60), but the confidence interval was wide.
The second RCT (68
[25]
women) reported similar results (RR 1.35, 95% CI 0.61 to 3.01).
Glyceryl trinitrate versus aspirin and dipyridamole:
[26]
We found one trial (76 women) that was too small to draw any reliable conclusions.
Harms:
Glyceryl trinitrate versus placebo/no treatment:

The first RCT found similar rates of adverse events with glyceryl trinitrate and placebo (skin rash:
4/21 [19%] with glyceryl trinitrate v 4/19 [21%] with placebo; headache: 2/21 [10%] with glyceryl
[24]
trinitrate v 1/19 [5%] with placebo; significance not reported).
The second RCT gave no infor[25]
mation on adverse events.
Glyceryl trinitrate versus aspirin and dipyridamole:
[26]
The RCT was too small to draw any reliable conclusions.
...........................................................
Comment:
OPTION
None.
MAGNESIUM SUPPLEMENTATION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Compared with placebo Magnesium supplements seem no more effective at reducing the risk of pre-eclampsia
Benefits:
We found one systematic review (search date 2001, 2 RCTs, 474 women) comparing magnesium
[27]
supplements versus placebo.
It found no significant difference in pre-eclampsia between groups
[27]
(34/235 [15%] with magnesium v 40/239 [17%] with placebo; RR 0.87, 95% CI 0.57 to 1.32).
Harms:
There was no significant difference between the groups in the number of reported gastrointestinal
[27]
side effects (RR 0.89, 95% CI 0.75 to 1.05).
Comment:
This review included seven trials with 2689 women, of which only two (474 women) reported data
for pre-eclampsia. There is, therefore, also a possibility of bias, in that five trials did not report this
outcome.
OPTION
SALT RESTRICTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Compared with normal dietary intake A low-salt diet seems no more effective at reducing the risk of pre-eclampsia
Benefits:
We found one systematic review (search date 2005, 2 RCTs, 603 women) comparing reduced salt
[28]
(advice to restrict dietary salt intake to 20 or 50 mmol/day) with normal dietary salt intake.
It
found no significant difference for rates of pre-eclampsia, although the trials may have lacked
power to detect clinically important effects (RR 1.11, 95% CI 0.46 to 2.66).
Harms:
We found no evidence of harmful effects in the trials.
Comment:
The trials of salt restriction were conducted in the Netherlands, where advice to restrict salt intake
during pregnancy has been routine for many years. Such advice is no longer widespread elsewhere.
OPTION
[28]
ATENOLOL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Compared with placebo Atenolol seems no more effective at reducing the risk of pre-eclampsia in women without
hypertension but with a cardiac output of over 7.4 L/minute (moderate-quality evidence).
Benefits:
We found one small RCT (68 women without hypertension selected because they had a cardiac
output of over 7.4 L/minute), which found no significant reduction in the risk of pre-eclampsia with
atenolol 100 mg daily (1/28 [4%] with atenolol v 5/28 [18%] with placebo; RR 0.20, 95% CI 0.02 to
[29]
1.60).
This single study was too small for reliable estimates of clinically important effects on
substantive outcomes.
Harms:
The RCT found that mean birthweight was significantly lower with atenolol for a subgroup of prim[29]
iparous women (mean difference: 440 g; P = 0.02).
Comment:
Although the possible benefits of atenolol for prevention of pre-eclampsia remain unclear, the reduction in birthweight may be real. Concerns about the possible harmful effects of atenolol on fetal
growth and development have been discussed for some time (see harms of antihypertensive
[30] [31]
agents, p 8 ).
...........................................................
QUESTION
What are the effects of interventions in women who develop mild to moderate hypertension
during pregnancy?
OPTION
ANTIHYPERTENSIVE AGENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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 dont know whether antihypertensive drugs are more effective
at reducing fetal or neonatal deaths (very low-quality evidence).
Benefits:
[32]
[33]
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 antihyper[32]
tensive 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 anti[33]
hypertensive 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
[32]
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,
[32]
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
[33]
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 de[32] [33]
veloping severe hypertension or pre-eclampsia.
[32]
[33]
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
[32]
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
[33]
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
[34]
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
[35] [36]
failure.
Fetal exposure to these agents during the first trimester is associated with major
[37]
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
[35] [36]
benefit from treatment.
We found one study in Russian that is awaiting translation and will
[38]
be included in future if relevant.
OPTION
BED REST/HOSPITAL ADMISSION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Development of severe hypertension or pre-eclampsia

Compared with no hospital admission We dont 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 (lowquality 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.
[39]
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).
[39]
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:
[40]
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,
[40]
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 assess[40]
ment 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.
QUESTION
What are the effects of interventions in women who develop severe pre-eclampsia or very
high blood pressure during pregnancy?
OPTION
PROPHYLACTIC ANTICONVULSANTS FOR WOMEN WITH SEVERE PRE-ECLAMPSIA. . . .
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).
Compared with placebo/no anticonvulsants Magnesium sulphate increases the need for a caesarean section (highquality evidence).
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).
...........................................................
[41]
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
[41]
[42]
[43]
to 1.15).
We found two reports of long-term follow-up for women
and children
recruited
[44]
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
[42]
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%]
[43]
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
[41]
[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
[41]
[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
[41]
diazepam (2 RCTs, 66 women).
Harms:
Magnesium sulphate versus placebo or no anticonvulsant:

[44]
One large, placebo-controlled trial in the review reported adverse effects in detail.
In this RCT,
more women had adverse effects with magnesium sulphate compared with placebo (1201/4999
[44]
[24%] with magnesium sulphate v 228/4993 [5%] with placebo).
By far the most common reported adverse effect was flushing (2 RCTs: 1032/5066 [20%] with magnesium sulphate v 110/5061
[41]
[2%] with placebo).
Respiratory depression was rare in both treatment groups, although the
relative risk was significantly lower for women allocated placebo (2 RCTs: 52/5344 [1.0%] with
[41]
magnesium sulphate v 26/5333 [0.5%] with placebo, RR 1.98, 95% CI 1.24 to 3.15).
Magnesium
sulphate slightly increased the risk of caesarean section compared with placebo (2528/5082 [50%]
with magnesium sulphate v 2370/5026 [47%] with placebo; RR 1.05, 95% CI 1.01 to 1.10; NNH
34, 95% CI 25 to 100). There were no clear differences in outcome between the two groups at two
[42]
[43]
years for the women,
and at age 18 months for the children (see benefits section, above).
Magnesium sulphate versus phenytoin, nimodipine, or diazepam:
The review found that, compared with phenytoin, magnesium sulphate was also associated with
an increased risk of caesarean section (RR 1.21, 95% CI 1.05 to 1.41; NNH 21, 95% CI 12 to 83).
[41]
Compared with nimodipine, magnesium sulphate was associated with an increase in respiratory
problems (11/831 [1.3%] with magnesium sulphate v 3/819 [0.4%] with nimodipine; RR 3.61, 95%
[41]
CI 1.01 to 12.91).
One small RCT evaluated magnesium sulphate for preventing and treating
preterm labour in women who did not have pre-eclampsia. It found an increase in infant mortality
[45]
for babies born to these women. Many of the infants had low birthweight (below 1500 g).
Comment:
OPTION
Most of the data in these trials refer to women with relatively severe pre-eclampsia. One small
study recruited only women with mild pre-eclampsia. Long-term follow-up of women and children
in one large RCT is reassuring, in that the lower risk of eclampsia is not associated with any clear
[43] [42]
difference in longer-term outcome for the women or children.
Weak evidence from two
case control studies suggested that magnesium sulphate may be associated with a decreased risk
[46] [47]
of cerebral palsy in babies weighing less than 1500 g.
This hypothesis has been tested in
[48]
a large RCT.
The RCT found that magnesium sulphate was associated with a non-significant
reduction in the composite outcome of death or cerebral palsy compared with placebo (123/629
[48]
[20%] with magnesium sulphate v 149/626 [24%] with placebo; RR 0.83, 95% CI 0.66 to 1.03).
ANTIHYPERTENSIVE DRUGS FOR VERY HIGH BLOOD PRESSURE. . . . . . . . . . . . . . . . . . . .
Seizures
..........................................................
10
Compared with each other We 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 at
reducing blood pressure (low-quality evidence).
Note
There is consensus that women with severe hypertension during pregnancy should have antihypertensive treatment.
[49]
Benefits:
We found one systematic review (search date 2006, 24 RCTs, 2949 women)
and two subsequent
[50] [51]
RCTs.
The review compared many antihypertensives (such as labetalol, nifedipine,
methyldopa, diazoxide, urapidil, magnesium sulphate, prazosin, nimodipine, and ketanserin)
[49]
mainly versus hydralazine.
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 calcium
channel blockers v 23/128 [18%] with hydralazine; RR 0.33, 95% CI 0.15 to 0.70), but there were
[49]
no significant differences in other reported outcomes.
The review found that the risk of persistent
high blood pressure was significantly lower for nimodipine compared with magnesium sulphate (1
RCT: 374/819 [47%] with nimodipine v 451/831 [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 v 9/846 [1%] with magnesium sulphate; RR 2.24, 95% CI
1.06 to 4.73). It found that nimodipine was associated with a significantly lower risk of respiratory
difficulties 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 less
postpartum haemorrhage (1 RCT: 8/819 [1%] with nimodipine v 20/831 [2%] with magnesium sulphate; RR 0.41, 95% CI 0.18 to 0.92). Overall, there was no clear evidence that one drug in the
[49]
review was better than another.
The first subsequent RCT (200 women) compared intravenous
[50]
bolus doses of labetalol versus hydralazine, repeated after 20 minutes if required.
It found no
clear differences between groups in persistent hypertension, need for additional doses, or hypotension. The second subsequent RCT (42 women) compared intravenous urapidil versus hydralazine,
[51]
and reported that no women had hypotension in the first 6 hours of treatment.
Harms:
The systematic review found that the use of ketanserin was associated with significantly more
persistent hypertension compared with hydralazine (3 RCTs: 26/96 [27%] with ketanserin v 5/84
[6%] with hydralazine; RR 4.79, 95% CI 1.95 to 11.73), but with significantly fewer maternal adverse
effects (3 RCTs: 13/64 [20%] with ketanserin v 36/56 [64%] with hydralazine; RR 0.32, 95% CI
[49]
0.19 to 0.53).
Labetalol was associated with less hypotension requiring treatment than diazoxide
[49]
(1 RCT, 90 women, RR 0.06, 95% CI 0 to 0.99).
Hypotension may compromise fetoplacental
blood flow.The review found that nimodipine was associated with significantly less flushing compared
with magnesium sulphate (1 RCT: 13/819 [2%] with nimodpine v 59/831 [7%] with magnesium
sulphate; RR 0.22, 95% CI 0.12 to 0.40), although there was no significant difference between
[49]
groups in the risk of headache, or nausea and vomiting. Few other RCTs reported adverse effects
or events. The frequency of adverse effects varied from 264%. Antihypertensive drugs cross the
placenta, but we found little evidence about effects on the baby.
Comment:
There is consensus that women with severe hypertension during pregnancy should have antihypertensive treatment. Placebo-controlled trials would therefore be unethical. Women in these studies
had blood pressures high enough to merit immediate treatment, and many also had proteinuria or
severe pre-eclampsia. The trials were small and reported few outcomes other than control of
blood pressure. In most trials, there was no blinding after trial entry.
OPTION
ANTIOXIDANTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
We found no direct information about whether a combination of vitamin E plus vitamin C plus allopurinol is
better than no active treatment.
Benefits:
We found no systematic review. We found one RCT (56 women with severe pre-eclampsia at
[52]
2432 weeks' gestation) comparing vitamin E plus vitamin C plus allopurinol versus placebo.
It was too small for reliable conclusions to be drawn.
Harms:
We found insufficient evidence to draw reliable conclusions.
Comment:
None.
..........................................................
11
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 significantly reduced mean pain scores, but the clinical importance of the difference is unclear. The trial
[53]
was too small for reliable conclusions to be drawn about other outcomes.
The second RCT
(738 women with pregnancy-induced hypertension) found that epidural analgesia reduced pain
compared with intravenous analgesia (proportion of women reporting excellent pain relief: 54%
[54]
with epidural analgesia v 19% with intravenous analgesia; P less than 0.001).
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 requiring
intravenous ephedrine (5/56 [9%] with epidural analgesia v 0/60 [0%] with iv analgesia; reported
[53]
as significant).
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 epidural
analgesia v 31/60 [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, epidural
analgesia increased the duration of the second stage of labour (mean length: 53 minutes with
epidural analgesia v 40 minutes with iv analgesia), the risk of intrapartum fever (76/372 [22%] with
epidural analgesia v 26/366 [8%] with iv analgesia; RR 2.88, 95% CI 1.89 to 4.38), the risk of forceps
delivery (51/372 [14%] with epidural analgesia v 27/366 [7%] with iv analgesia; RR 1.86, 95% CI
1.19 to 2.90), and the need for treatment for hypotension (40/372 [11%] with epidural analgesia v
0/366 [0%] with iv analgesia; P less than 0.001). Neonatal naloxone was more likely to be given
after intravenous analgesia (2/372 [1%] with epidural analgesia v 40/366 [12%] with iv analgesia).
[54]
Comment:
OPTION
The drug used for patient-controlled intravenous analgesia was not reported in the first RCT.
[54]
Pethidine was used in the second RCT.
[53]
INTERVENTIONIST CARE FOR SEVERE EARLY-ONSET PRE-ECLAMPSIA. . . . . . . . . . . . . .
Perinatal mortality
Compared with expectant management We dont know whether interventionist management is more effective at reducing stillbirths or perinatal deaths in babies born to mothers with severe early-onset pre-eclampsia (low-quality
evidence).
Neonatal morbidity
Compared with expectant management Interventionist management may increase the risk of respiratory distress
syndrome, necrotising enterocolitis, and rates of admission to neonatal intensive care in babies born to mothers with
severe pre-eclampsia (low-quality evidence).
Benefits:
We found one systematic review (search date 2006, 2 RCTs, 133 women at 2834 weeks' gestation),
which compared a policy of early elective delivery by induction or caesarean section depending
on individual obstetric circumstances (interventionist management) versus a policy of delayed delivery to allow more time for fetal maturation (expectant management) in women with severe pre[55]
eclampsia.
It found that, for the baby, there was no significant difference in rates of stillbirth or
death after delivery for interventionist management compared with expectant care (RR of death or
stillbirth for interventional v expectant care 1.50, 95% CI 0.42 to 5.41). Babies of mothers in the
interventionist-management group were significantly less likely to be small for gestational age than
those in the expectant group (RR for interventionist v expectant management 0.36, 95% CI 0.14
to 0.90). The review found insufficient evidence about effects on maternal outcomes.
Harms:
The review found that interventionist management significantly increased risks of respiratory distress
syndrome (34/66 [52%] babies with interventionist management v 15/67 [22%] babies with expectant
care; RR 2.30, 95% CI 1.39 to 3.81), necrotising enterocolitis (RR 5.5, 95% CI 1.04 to 29.56), and
rate of admission to neonatal intensive care (RR 1.32, 95% CI 1.13 to 1.55) in babies born to
[55]
mothers with severe pre-eclampsia.
We found insufficient evidence for reliable conclusions
about effects of expectant management on maternal morbidity.
Comment:
None.
..........................................................
12
OPTION
PLASMA VOLUME EXPANSION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Seizures
Compared with control We don't know whether plasma volume expansion using colloids is more effective at reducing
the proportion of women who develop eclampsia (low-quality evidence).
Maternal morbidity
the proportion of women who develop haemolysis, elevated liver enzymes and lowered platelets (HELLP) syndrome
or other serious maternal morbidities (low-quality evidence).
Perinatal mortality
infant mortality (low-quality evidence).
[56]
Benefits:
We found one systematic review (search date 2000, 3 RCTs, 61 women; see comment below)
[57]
evaluating colloid solutions compared with placebo or no infusion, and one subsequent RCT.
The systematic review found insufficient evidence for reliable conclusions, but suggested that
[56]
plasma volume expansion is not beneficial.
The subsequent RCT (216 women) found no significant difference between plasma volume expansion and control in the proportion of women who
developed eclampsia (2/111 [2%] with plasma volume expansion v 2/105 [2%] with no expansion),
haemolysis, elevated liver enzymes and lowered platelets (HELLP) syndrome (19/111 [17%] with
plasma volume expansion v 20/105 [19%] with no expansion), other serious maternal morbidity
(13/111 [12%] with plasma volume expansion v 11/105 [10%] with no expansion), or infant mortality (23/111 [21%] with plasma volume v 15/105 [14%] with no expansion; differences reported as
[57]
not significant, P values not provided).
Harms:
The systematic review found no significant difference between plasma volume expansion and either
placebo or no infusion in the risk of caesarean section (RR 1.5, 95% CI 0.8 to 2.9), or in the need
[56]
for additional treatment (RR 1.5, 95% CI 0.7 to 3.1).
Comment:
In one RCT included in the review, all women had severe pre-eclampsia. In the other two RCTs,
some women did not have proteinuria at trial entry, and those with severe hypertension were ex[56]
cluded.
These three RCTs all used a colloid rather than crystalloid solution. The subsequent
RCT included women with severe early-onset pre-eclampsia, and also used a colloid solution for
[57]
[58]
[59]
plasma volume expansion.
Two systematic reviews (search dates 2004
and 2002
) of
plasma volume expansion in critically ill men and non-pregnant women have found an increased
mortality with albumin (a colloid) when compared with either no expansion or expansion with
crystalloid.
QUESTION
What is the best choice of anticonvulsant for women with eclampsia?
OPTION
ANTICONVULSANTS FOR WOMEN WITH ECLAMPSIA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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).
..........................................................
13

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
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:

[60]
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
[60]
59/302 [20%] with diazepam; RR 0.66, 95% CI 0.46 to 0.95).
Magnesium sulphate versus phenytoin:
[61]
and one subsequent
[62]
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).
[61]
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%]
[61]
with magnesium sulphate v 20/398 [5%] with phenytoin; RR 0.50, 95% CI 0.24 to 1.05).
We
[62]
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:
[63]
and one additional
[64]
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
[64]
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
[60] [61] [63]
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.
..........................................................
14
GLOSSARY
Lytic 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 estimate
of 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 estimate
of effect and may change the estimate.
Very low-quality evidence Any estimate of effect is very uncertain.
SUBSTANTIVE CHANGES
Anticonvulsants for women with eclampsia One RCT including 199 women added comparing magnesium sulphate
[64]
versus lytic cocktail.
Categorisation of magnesium sulphate for eclampsia (better and safer than other anticonvulsants) unchanged (Beneficial).
Antihypertensive agents (under question in women who develop mildmoderate hypertension during pregnancy) One already-included systematic review comparing antihypertensive drug versus placebo/no antihypertensive
[32]
drug or versus other antihypertensives updated, and six new RCTs added to its analysis.
The overall conclusions
[32]
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).
[49]
Antihypertensive drugs for very high blood pressure One already-included systematic review updated
and
[50] [51]
two subsequent RCTs added.
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)
[19]
One systematic review comparing the combination of vitamin C and E versus placebo
and one small subsequent
[20]
RCT comparing the effects of a combination of different antioxidents versus placebo added
to an already reported
[19]
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).
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[17]
ysis.
Overall conclusions of the review unchanged: calcium supplementation still categorised as Beneficial.
Interventionist care for severe early-onset pre-eclampsia Option title changed to Interventionist care, which involves
a policy of early elective delivery by induction of caesarean section depending on individual obstetric circumstances.
[55]
One already-reported systematic review updated.
No new data added. Categorisation of early delivery for severe
early-onset pre-eclampsia unchanged (Unknown effectiveness).
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
[22] [21]
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).
[57]
Plasma volume expansion (in severe pre-eclampsia) One RCT including 216 women added.
Benefits and
harms data enhanced, categorisation unchanged (Unknown effectiveness).
Prophylactic anticonvulsants for women with severe pre-eclampsia Two long-term follow-up studies in women
[42] [43]
and children from one large already-included RCT added.
Categorisation of prophylactic magnesium sulphate
in severe pre-eclampsia unchanged (Beneficial).
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):122.
10.
Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking:

systematic review of controlled studies. BMJ 2005;330:565.
2.
WHO international collaborative study of hypertensive disorders of pregnancy.

Geographic variation in the incidence of hypertension in pregnancy. Am J Obstet
Gynecol 1988;158:8083.[PubMed]
11.
Douglas K, Redman C. Eclampsia in the United Kingdom. BMJ

1994;309:13951400.[PubMed]
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;181:10261035. 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.[PubMed]
3.
12.
4.
Crowther CA. Eclampsia at Harare maternity hospital. An epidemiological study.

S Afr Med J 1985;68:927929.[PubMed]
Chamberlain GVP, Philip E, Howlett B, et al. British births. London: Heinemann,

1970.
13.
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;20:153158.[PubMed]
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;339:667671.[PubMed]
14.
6.
Roberts JM, Redman CWG. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 1993;341:14471451.[PubMed]
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.
7.
Taylor DJ. The epidemiology of hypertension during pregnancy. In: Rubin PC,
ed. Hypertension in pregnancy. Amsterdam: Elsevier Science, 1988:223240.
15.
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;182:364369.[PubMed]
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;102:861868.[PubMed]
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.
17.
9.
MacGillivray I. Pre-eclampsia. The hypertensive disease of pregnancy. London:

WB Saunders, 1983.
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.
..........................................................
15
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.
41.
Duley L, Glmezoglu 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.
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;62:202206.[PubMed]
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;114:300309.
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;25:241253.[PubMed]
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;114:289299.
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.
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;359:18771890.
45.
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;83:13371344.
Mittendorf R, Covert R, Boman J, et al. Is tocolytic magnesium sulphate associated with increased total paediatric mortality? Lancet
1997;350:15171518.[PubMed]
46.
Nelson K, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy
in very low birthweight infants? Pediatrics 1995;95:263269.[PubMed]
23.
Olsen SF, Sorensen JD, Secher NJ, et al. Randomised controlled trial of effect
of fish oil supplementation on pregnancy duration. Lancet
1992;339:10031007.[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 lowbirth-weight children aged 3 to 5 years. JAMA 1996;276:18051810. [PubMed]
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;12:334338.
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;290:26692676.[PubMed]
25.
Picciolo C, Roncaglia N, Neri I, et al. Nitric oxide in the prevention of preeclampsia. Prenat Neonatal Med 2000;5:212215.
49.
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;69:1720. [In Russian]
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.
50.
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.
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;128:157162.[PubMed]
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;127:160165.[PubMed]
52.
Gulmezoglu AM, Hofmeyr GJ, Oosthuizen MMJ. Antioxidants in the treatment

of severe preeclampsia: a randomized explanatory study. Br J Obstet Gynaecol
1997;104:689696.[PubMed]
53.
Head BB, Owen J, Vincent Jr RD, et al. A randomized trial of intrapartum analgesia in women with severe preeclampsia. Obstet Gynecol
2002;99:452457.[PubMed]
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;185:970975.[PubMed]
27.
28.
Duley L, Henderson-Smart D, Meher S. Altered dietary salt for preventing preeclampsia, 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.
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;93:725733.[PubMed]
30.
Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during

pregnancy. BMJ 1990;301:587589.[PubMed]
31.
Churchill D, Bayliss H, Beevers G. Fetal growth restriction. Lancet

1999;355:13661367.
55.
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.
Churchill D, Duley L. Interventionist versus expectant care for severe preeclampsia 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.
56.
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.
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.
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;112:13581368.[PubMed]
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.
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.
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.
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.
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;22:543549. [In Portuguese]
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.
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;38:250255.
33.
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;355:8792. Search date 1997; primary sources Medline, Embase, hand
searches of reference lists, Hypertension and Pregnancy 19921997, and a
standard toxicology text.[PubMed]
35.
Ferrer RL, Sibai BM, Mulrow CD, et al. Management of mild chronic hypertension
during pregnancy: a review. Obstet Gynecol 2000;96:849860. Search date
1999; primary sources 16 electronic databases, textbook references, and contact
with experts.[PubMed]
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).
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;354:24432451.[PubMed]
38.
Tsaava F, Shonia R. Efficacy of antihypertensive drugs in pregnancy. Georgian

Med News 2005;2326. [In Russian]
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.
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.
..........................................................
16
Lelia Duley
Obstetric Epidemiologist
University of Leeds
Academic unit
Leeds
UK
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 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.
..........................................................
17
TABLE
GRADE evaluation of interventions for pre-eclampsia, eclampsia, and hypertension
Important outcomes
Number of studies (participants)
Development of pre-eclampsia, seizures, morbidity, prematurity, use of resources, mortality, adverse effects
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
[14]
32,590 women)
Development of preeclampsia
Antiplatelet drugs v placebo/no antiplatelet drugs
High
29 (31,151)
[14]
Preterm birth
High
40 (33,098)
[14]
Perinatal mortality
High
12 (15,206)
[17]
Calcium supplementation v placebo
+1
High
[17]
4 (9722)
Effect-size point added for RR less than

0.5
Maternal mortality
High
10 (15,141)
[17]
Perinatal mortality
Moderate
Quality point deducted for incomplete reporting of results
10 (14,751)
[17]
Preterm birth
Moderate
Need for other interventions
Moderate
Antioxidants v placebo/no antioxidant
Low
Quality point deducted for methodological

weaknesses. Consistency point deducted
for conflicting results
7 (14,710)
[17]

[18] [19]
6082 women)
[20]
4 (?)
[19]
Preterm birth
Moderate
4 (?)
[20]
Perinatal mortality
Moderate
Marine oil and other prostaglandin

precursors v placebo/no treatment
Moderate
Quality point deducted for uncertainty

about blinding
Preterm birth
Marine oil and other prostaglandin

precursors v placebo/no treatment
Moderate

about blinding
Glyceryl trinitrate v placebo/no treatment
Low
Quality points deducted for sparse data

and incomplete reporting of results
4 (1683)
5 (1916)
[21]
[21]
2 (108)
[24]
2 (474)
[27]
Magnesium supplementation v placebo
Moderate

about bias
2 (603)
[28]
Salt restriction v normal dietary salt

intake
Moderate
Atenolol v placebo
Moderate
Quality point deducted for sparse data
1 (68)
[29]
[25]
What are the effects of interventions in women who develop mildmoderate hypertension during pregnancy?
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Important outcomes
[32] [33]
2702 women)
[32]
26 (3081)
1 (218)
[39]
[39]
1 (218)
Type of
evidence
Quality
Consistency
Directness
Effect
size
GRADE
Comment
Outcome
Comparison
Development of severe
hypertension or preeclampsia
Antihypertensive drugs v placebo/no

antihypertensive drug
Very low
Quality points deducted for incomplete

reporting of results, methodological
weaknesses, and uncertainty about adherence to treatment
Perinatal mortality
Antihypertensive drugs v placebo/no

antihypertensive drug
Very low

reporting of results, methodological
weaknesses, and uncertainty about adherence to treatment
Development of severe
hypertension or preeclampsia
Bed rest/hospital admission v no hospital admission
Low
Quality points deducted for uncertainty

about bias and for differences in frequency of blood pressure measurement
Preterm birth
Bed rest/hospital admission v no hospital admission
Moderate

about bias
What are the effects of interventions in women who develop severe pre-eclampsia or very high blood pressure during pregnancy?
[41]
6 (11,444)
We found
two reports of long-term
[42]
follow-up for women
Seizures
Magnesium sulphate v placebo/no

anticonvulsant
+1
High

0.5
Child development

anticonvulsant
Moderate
Quality point deducted for poor follow-up
Maternal mortality

anticonvulsant
High
Perinatal mortality

anticonvulsant
High
Seizures
Magnesium sulphate v phenytoin, nimodipine, or diazepam
+1
High
at least 1 RCT (at least

[41]
10,108 women)

anticonvulsant
High
at least 1 RCT (9092

[41]
women)
Adverse effects

anticonvulsant
Moderate
Seizures
Antihypertensive drugs v each other
Low
Quality point deducted for incomplete reporting of results. Directness point deducted for no direct comparison between
drugs
1 (3283)
[43]
2 (10,795)
3 (9961)
3 (3891)
3 (505)
[41]
[41]
[41]
[49]
[50]
[51]

0.5
2 (133)
[55]
Perinatal mortality
Interventionist management v expectant management
Low

reporting of results and for sparse data
2 (133)
[55]
Neonatal morbidity
Interventionist management v expectant management
Low

reporting of results and for sparse data
4 (277)
[56]
Seizures
Plasma volume expansion v control
Low
Quality point deducted for incomplete reporting of results. Directness point deducted for differences in disease severities
[57]
............................................................................................................
19
Important outcomes
Outcome
Comparison
Type of
evidence
Quality
Consistency
Directness
Effect
size
GRADE
Comment
4 (277)
[56]
[57]
Perinatal mortality
Low
4 (277)
[56]
[57]
Maternal morbidity
Low
What is the best choice of anticonvulsant for women with eclampsia?

7 (1441)
[60]
Seizures
Magnesium sulphate v diazepam
High
2 (597)
[60]
Neonatal morbidity
High
3 (631)
[60]
Duration of hospital stay
High
Maternal mortality
High
Seizures
Magnesium sulphate v phenytoin
High
6 (1336)
[60]
5 RCTs (at least 895

[62]
women)
1 (775)
[61]
Moderate
2 (797)
[62]
Maternal mortality
High
1 (643)
[62]
Perinatal mortality
Moderate
2 (397)
[63]
[64]
Seizures
Magnesium sulphate v lytic cocktail
Moderate
2 (397)
[63]
[64]
Maternal mortality
Moderate
Consistency point deducted for conflicting

results
2 (397)
[63]
[64]
Perinatal mortality
Moderate
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
............................................................................................................
20

Pre-Eclampsia, Eclampsia, and Hypertension: Jurnal Maternitas

Transféré par

Informations du document

Titre original

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Pre-Eclampsia, Eclampsia, and Hypertension: Jurnal Maternitas

Transféré par

Droits d'auteur :

Formats disponibles

TUGAS INDIVIDU

MATA KULIAH KEPERAWATAN MATERNITAS

PROGRAM STUDI ILMU KEPERAWATAN

Pre-eclampsia, eclampsia, and hypertension

Choice of analgesia during labour with severe preeclampsia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Early delivery for severe early-onset pre-eclampsia . .

Marine oil (fish oil) and other prostaglandin precursors

Plasma volume expansion in severe pre-eclampsia . .

Magnesium sulphate for eclampsia (better and safer

Antihypertensive drugs for mild to moderate hypertension

Treatment of postpartum hypertension

Bed rest/admission v day care . . . . . . . . . . . . . . . . . 8

TREATMENT OF SEVERE EPISODES OF PREECLAMPSIA

Prophylactic magnesium sulphate in severe preeclampsia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Clinical Evidence 2008;08:1402

Pregnancy and childbirth

Pregnancy-induced hypertension affects 10% of pregnancies, and pre-eclampsia complicates

The outcome of pregnancy in women with pregnancy-induced hypertension alone is at least as

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

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

Antiplatelet drugs versus placebo/no antiplatelet drug:

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

Calcium supplementation versus placebo:

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

Glyceryl trinitrate versus placebo/no treatment:

Glyceryl trinitrate versus placebo/no treatment:

BMJ Publishing Group Ltd 2008. All rights reserved.

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

We found no evidence of harmful effects in the trials.

BMJ Publishing Group Ltd 2008. All rights reserved.

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

Development of severe hypertension or pre-eclampsia

We found two systematic reviews.

The antihypertensive agents included in the systematic reviews

BED REST/HOSPITAL ADMISSION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Development of severe hypertension or pre-eclampsia

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

Bed rest/admission versus no hospital admission:

PROPHYLACTIC ANTICONVULSANTS FOR WOMEN WITH SEVERE PRE-ECLAMPSIA. . . .

BMJ Publishing Group Ltd 2008. All rights reserved.

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

Magnesium sulphate versus placebo or no anticonvulsant:

Magnesium sulphate versus placebo or no anticonvulsant:

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

We found insufficient evidence to draw reliable conclusions.

BMJ Publishing Group Ltd 2008. All rights reserved.

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension

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

INTERVENTIONIST CARE FOR SEVERE EARLY-ONSET PRE-ECLAMPSIA. . . . . . . . . . . . . .

BMJ Publishing Group Ltd 2008. All rights reserved.

Pregnancy and childbirth

Pre-eclampsia, eclampsia, and hypertension