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Meta-Analysis
. 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
Meta-Analysis

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.

PubMed Disclaimer

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

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

Update of

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References to other published versions of this review

Rumbold 2005
    1. Rumbold A, Duley L, Crowther C, Haslam R. Antioxidants for preventing pre‐eclampsia. Cochrane Database of Systematic Reviews 2005, Issue 4. [Art. No.: CD004227. DOI: 10.1002/14651858.CD004227.pub2] - PubMed