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Review
. 2008 Jan 23;2008(1):CD004227.
doi: 10.1002/14651858.CD004227.pub3.

Antioxidants for preventing pre-eclampsia

A Rumbold  1 , L Duley, C A Crowther, R R Haslam
Affiliations
Review

Antioxidants for preventing pre-eclampsia

A Rumbold et al. Cochrane Database Syst Rev. .

Abstract

Background: Oxidative stress has been proposed as a key factor involved in the development of pre-eclampsia. Supplementing women with antioxidants during pregnancy may help to counteract oxidative stress and thereby prevent or delay the onset of pre-eclampsia.

Objectives: To determine the effectiveness and safety of any antioxidant supplementation during pregnancy and the risk of developing pre-eclampsia and its related complications.

Search strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 3), MEDLINE (1950 to October 2007) and Current Contents (1998 to August 2004).

Selection criteria: All randomised trials comparing one or more antioxidants with either placebo or no antioxidants during pregnancy for the prevention of pre-eclampsia, and trials comparing one or more antioxidants with another, or with other interventions.

Data collection and analysis: Two review authors independently assessed trials for inclusion and trial quality and extracted data.

Main results: Ten trials, involving 6533 women, were included in this review, five trials were rated high quality. For the majority of trials, the antioxidant assessed was combined vitamin C and E therapy. There was no significant difference between antioxidant and control groups for the relative risk (RR) of pre-eclampsia (RR 0.73, 95% confidence intervals (CI) 0.51 to 1.06; nine trials, 5446 women) or any other primary outcome: severe pre-eclampsia (RR 1.25, 95% CI 0.89 to 1.76; two trials, 2495 women), preterm birth (before 37 weeks) (RR 1.10, 95% CI 0.99 to 1.22; five trials, 5198 women), small-for-gestational-age infants (RR 0.83, 95% CI 0.62 to 1.11; five trials, 5271 babies) or any baby death (RR 1.12, 95% CI 0.81 to 1.53; four trials, 5144 babies). Women allocated antioxidants were more likely to self-report abdominal pain late in pregnancy (RR 1.61, 95% CI 1.11 to 2.34; one trial, 1745 women), require antihypertensive therapy (RR 1.77, 95% CI 1.22 to 2.57; two trials, 4272 women) and require an antenatal hospital admission for hypertension (RR 1.54, 95% CI 1.00 to 2.39; one trial, 1877 women). However, for the latter two outcomes, this was not clearly reflected in an increase in any other hypertensive complications.

Authors' conclusions: Evidence from this review does not support routine antioxidant supplementation during pregnancy to reduce the risk of pre-eclampsia and other serious complications in pregnancy.

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Conflict of interest statement

Caroline Crowther and Ross Haslam were chief investigators for the Australian Collaborative Trial of Supplements with vitamin C and vitamin E for the prevention of pre‐eclampsia (ACTS). Alice Rumbold was the PhD student involved with this trial (ACTS). Lelia Duley was a member of the steering committee for the Vitamins in Pregnancy (VIP) trial, which assessed vitamins C and E for prevention of pre‐eclampsia.

Figures

Figure 1
Figure 1
Funnel plot of the effects of antioxidants for preventing pre‐eclampsia
Analysis 1.1
Analysis 1.1
Comparison 1 Any antioxidants versus control or placebo, Outcome 1 Pre‐eclampsia.
Analysis 1.2
Analysis 1.2
Comparison 1 Any antioxidants versus control or placebo, Outcome 2 Severe pre‐eclampsia.
Analysis 1.3
Analysis 1.3
Comparison 1 Any antioxidants versus control or placebo, Outcome 3 Preterm birth.
Analysis 1.4
Analysis 1.4
Comparison 1 Any antioxidants versus control or placebo, Outcome 4 Small‐for‐gestational age.
Analysis 1.5
Analysis 1.5
Comparison 1 Any antioxidants versus control or placebo, Outcome 5 Any baby death.
Analysis 1.6
Analysis 1.6
Comparison 1 Any antioxidants versus control or placebo, Outcome 6 Any baby death (subgrouped by timing of death).
Analysis 1.7
Analysis 1.7
Comparison 1 Any antioxidants versus control or placebo, Outcome 7 Maternal death.
Analysis 1.8
Analysis 1.8
Comparison 1 Any antioxidants versus control or placebo, Outcome 8 Gestational hypertension.
Analysis 1.9
Analysis 1.9
Comparison 1 Any antioxidants versus control or placebo, Outcome 9 Severe hypertension.
Analysis 1.10
Analysis 1.10
Comparison 1 Any antioxidants versus control or placebo, Outcome 10 Use of antiypertensives.
Analysis 1.11
Analysis 1.11
Comparison 1 Any antioxidants versus control or placebo, Outcome 11 Elective delivery (induction of labour or elective caesarean section).
Analysis 1.12
Analysis 1.12
Comparison 1 Any antioxidants versus control or placebo, Outcome 12 Caesarean section (emergency plus elective).
Analysis 1.13
Analysis 1.13
Comparison 1 Any antioxidants versus control or placebo, Outcome 13 Bleeding episodes (including placental abruption, APH, PPH, need for transfusion).
Analysis 1.14
Analysis 1.14
Comparison 1 Any antioxidants versus control or placebo, Outcome 14 Serious maternal morbidity (including eclampsia, liver and renal failure, DIC, stroke).
Analysis 1.15
Analysis 1.15
Comparison 1 Any antioxidants versus control or placebo, Outcome 15 Gestational age at birth.
Analysis 1.16
Analysis 1.16
Comparison 1 Any antioxidants versus control or placebo, Outcome 16 Birthweight.
Analysis 1.17
Analysis 1.17
Comparison 1 Any antioxidants versus control or placebo, Outcome 17 Apgar score at 5 minutes.
Analysis 1.18
Analysis 1.18
Comparison 1 Any antioxidants versus control or placebo, Outcome 18 Respiratory distress syndrome.
Analysis 1.19
Analysis 1.19
Comparison 1 Any antioxidants versus control or placebo, Outcome 19 Chronic lung disease.
Analysis 1.20
Analysis 1.20
Comparison 1 Any antioxidants versus control or placebo, Outcome 20 Neonatal bleeding episodes (intraventricular haemorrhage and periventricular leukomalacia).
Analysis 1.21
Analysis 1.21
Comparison 1 Any antioxidants versus control or placebo, Outcome 21 Necrotising enterocolitis.
Analysis 1.22
Analysis 1.22
Comparison 1 Any antioxidants versus control or placebo, Outcome 22 Retinopathy of prematurity.
Analysis 1.23
Analysis 1.23
Comparison 1 Any antioxidants versus control or placebo, Outcome 23 Side‐effects not sufficient to stop supplementation.
Analysis 1.24
Analysis 1.24
Comparison 1 Any antioxidants versus control or placebo, Outcome 24 Use of health service resources for the woman.
Analysis 1.25
Analysis 1.25
Comparison 1 Any antioxidants versus control or placebo, Outcome 25 Length of stay in hospital ‐ antenatal admission.
Analysis 1.26
Analysis 1.26
Comparison 1 Any antioxidants versus control or placebo, Outcome 26 Use of health service resources for the infant.
Analysis 1.27
Analysis 1.27
Comparison 1 Any antioxidants versus control or placebo, Outcome 27 Length of stay in hospital ‐ neonatal.
Analysis 2.1
Analysis 2.1
Comparison 2 Any antioxidants versus control or placebo (sensitivity analyses based on trial quality), Outcome 1 Pre‐eclampsia.
Analysis 2.2
Analysis 2.2
Comparison 2 Any antioxidants versus control or placebo (sensitivity analyses based on trial quality), Outcome 2 Severe pre‐eclampsia.
Analysis 2.3
Analysis 2.3
Comparison 2 Any antioxidants versus control or placebo (sensitivity analyses based on trial quality), Outcome 3 Preterm birth (< 37 weeks).
Analysis 2.4
Analysis 2.4
Comparison 2 Any antioxidants versus control or placebo (sensitivity analyses based on trial quality), Outcome 4 Small‐for‐gestational age.
Analysis 2.5
Analysis 2.5
Comparison 2 Any antioxidants versus control or placebo (sensitivity analyses based on trial quality), Outcome 5 Any baby death.
Analysis 3.1
Analysis 3.1
Comparison 3 Any antioxidants versus control or placebo (subgroups by risk status), Outcome 1 Pre‐eclampsia.
Analysis 3.2
Analysis 3.2
Comparison 3 Any antioxidants versus control or placebo (subgroups by risk status), Outcome 2 Severe pre‐eclampsia.
Analysis 3.3
Analysis 3.3
Comparison 3 Any antioxidants versus control or placebo (subgroups by risk status), Outcome 3 Preterm birth.
Analysis 3.4
Analysis 3.4
Comparison 3 Any antioxidants versus control or placebo (subgroups by risk status), Outcome 4 Small‐for‐gestational‐age infant.
Analysis 3.5
Analysis 3.5
Comparison 3 Any antioxidants versus control or placebo (subgroups by risk status), Outcome 5 Any baby death.
Analysis 4.1
Analysis 4.1
Comparison 4 Any antioxidants versus control or placebo (subgroups by gestation at entry), Outcome 1 Pre‐eclampsia.
Analysis 4.2
Analysis 4.2
Comparison 4 Any antioxidants versus control or placebo (subgroups by gestation at entry), Outcome 2 Severe pre‐eclampsia.
Analysis 4.3
Analysis 4.3
Comparison 4 Any antioxidants versus control or placebo (subgroups by gestation at entry), Outcome 3 Preterm birth.
Analysis 4.4
Analysis 4.4
Comparison 4 Any antioxidants versus control or placebo (subgroups by gestation at entry), Outcome 4 Small‐for‐gestational age.
Analysis 4.5
Analysis 4.5
Comparison 4 Any antioxidants versus control or placebo (subgroups by gestation at entry), Outcome 5 Any baby death.
Analysis 5.1
Analysis 5.1
Comparison 5 Any antioxidants versus control or placebo (subgroups by antioxidant type), Outcome 1 Pre‐eclampsia.
Analysis 5.2
Analysis 5.2
Comparison 5 Any antioxidants versus control or placebo (subgroups by antioxidant type), Outcome 2 Severe pre‐eclampsia.
Analysis 5.3
Analysis 5.3
Comparison 5 Any antioxidants versus control or placebo (subgroups by antioxidant type), Outcome 3 Preterm birth.
Analysis 5.4
Analysis 5.4
Comparison 5 Any antioxidants versus control or placebo (subgroups by antioxidant type), Outcome 4 Small‐for‐gestational age.
Analysis 5.5
Analysis 5.5
Comparison 5 Any antioxidants versus control or placebo (subgroups by antioxidant type), Outcome 5 Any baby death.
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References

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