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Meta-Analysis
. 2015 Sep 7;2015(9):CD004069.
doi: 10.1002/14651858.CD004069.pub3.

Vitamin E supplementation in pregnancy

Alice Rumbold  1 , Erika Ota, Hiroyuki Hori, Celine Miyazaki, Caroline A Crowther
Affiliations
Meta-Analysis

Vitamin E supplementation in pregnancy

Alice Rumbold et al. Cochrane Database Syst Rev. .

Abstract

Background: Vitamin E supplementation may help reduce the risk of pregnancy complications involving oxidative stress, such as pre-eclampsia. There is a need to evaluate the efficacy and safety of vitamin E supplementation in pregnancy.

Objectives: To assess the effects of vitamin E supplementation, alone or in combination with other separate supplements, on pregnancy outcomes, adverse events, side effects and use of health services.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies.

Selection criteria: All randomised or quasi-randomised controlled trials evaluating vitamin E supplementation in pregnant women. We excluded interventions using a multivitamin supplement that contained vitamin E.

Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.

Main results: Twenty-one trials, involving 22,129 women were eligible for this review. Four trials did not contribute data. All of the remaining 17 trials assessed vitamin E in combination with vitamin C and/or other agents. Overall the risk of bias ranged from low to unclear to high; 10 trials were judged to be at low risk of bias, six trials to be at unclear risk of bias and five trials to be at high risk of bias. No clear difference was found between women supplemented with vitamin E in combination with other supplements during pregnancy compared with placebo for the risk of stillbirth (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.88 to 1.56, nine studies, 19,023 participants, I² = 0%; moderate quality evidence), neonatal death (RR 0.81, 95% CI 0.58 to 1.13, nine trials, 18,617 participants, I² = 0%), pre-eclampsia (average RR 0.91, 95% CI 0.79 to 1.06; 14 trials, 20,878 participants; I² = 48%; moderate quality evidence), preterm birth (average RR 0.98, 95% CI 0.88 to 1.09, 11 trials, 20,565 participants, I² = 52%; high quality evidence) or intrauterine growth restriction (RR 0.98, 95% CI 0.91 to 1.06, 11 trials, 20,202 participants, I² = 17%; high quality evidence). Women supplemented with vitamin E in combination with other supplements compared with placebo were at decreased risk of having a placental abruption (RR 0.64, 95% CI 0.44 to 0.93, seven trials, 14,922 participants, I² = 0%; high quality evidence). Conversely, supplementation with vitamin E was associated with an increased risk of self-reported abdominal pain (RR 1.66, 95% CI 1.16 to 2.37, one trial, 1877 participants) and term prelabour rupture of membranes (PROM) (average RR 1.77, 95% CI 1.37 to 2.28, two trials, 2504 participants, I² = 0%); however, there was no corresponding increased risk for preterm PROM (average RR 1.27, 95% CI 0.93 to 1.75, five trials, 1999 participants, I² = 66%; low quality evidence). There were no clear differences between the vitamin E and placebo or control groups for any other maternal or infant outcomes. There were no clear differing patterns in subgroups of women based on the timing of commencement of supplementation or baseline risk of adverse pregnancy outcomes. The GRADE quality of the evidence was high for preterm birth, intrauterine growth restriction and placental abruption, moderate for stillbirth and clinical pre-eclampsia, and low for preterm PROM.

Authors' conclusions: The data do not support routine vitamin E supplementation in combination with other supplements for the prevention of stillbirth, neonatal death, preterm birth, pre-eclampsia, preterm or term PROM or poor fetal growth. Further research is required to elucidate the possible role of vitamin E in the prevention of placental abruption. There was no convincing evidence that vitamin E supplementation in combination with other supplements results in other important benefits or harms.

PubMed Disclaimer

Conflict of interest statement

Caroline Crowther and Alice Rumbold are Investigators on one of the included trials (Rumbold 2006). Decision about inclusion of this trial and extraction of data about this trial was undertaken by Erika Ota, Hiroyuki Hori and Celine Miyazaki.

Figures

1
1
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
Funnel plot of comparison: 1 Any vitamin E supplementation, outcome: 1.9 Preterm birth (less than 37 weeks' gestation).
4
4
Funnel plot of comparison: 1 Any vitamin E supplementation, outcome: 1.10 Clinical pre‐eclampsia (random‐effects model).
5
5
Funnel plot of comparison: 1 Any vitamin E supplementation, outcome: 1.11 Intrauterine growth restriction (various definitions).
1.1
1.1. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 1 Stillbirth.
1.2
1.2. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 2 Neonatal death.
1.3
1.3. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 3 Perinatal death.
1.4
1.4. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 4 Infant death.
1.7
1.7. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 7 Hyperbilirubinemia.
1.9
1.9. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 9 Preterm birth (less than 37 weeks' gestation).
1.10
1.10. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 10 Clinical pre‐eclampsia (random‐effects model).
1.11
1.11. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 11 Intrauterine growth restriction (various definitions).
1.12
1.12. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 12 Birthweight.
1.13
1.13. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 13 Prelabour rupture of fetal membranes.
1.14
1.14. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 14 Maternal death.
1.15
1.15. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 15 Elective delivery and caesarean section.
1.16
1.16. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 16 Bleeding episodes.
1.17
1.17. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 17 Measures of serious maternal morbidity.
1.20
1.20. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 20 Gestational age at birth.
1.21
1.21. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 21 Congenital malformations.
1.22
1.22. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 22 Apgar score less than seven at five minutes.
1.24
1.24. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 24 Respiratory distress syndrome.
1.25
1.25. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 25 Chronic lung disease or bronchopulmonary dysplasia.
1.26
1.26. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 26 Periventricular haemorrhage and periventricular leukomalacia.
1.27
1.27. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 27 Bacterial sepsis.
1.28
1.28. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 28 Necrotising enterocolitis.
1.29
1.29. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 29 Retinopathy of prematurity.
1.33
1.33. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 33 Side effects of vitamin E supplementation.
1.34
1.34. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 34 Use of health service resources ‐ maternal.
1.35
1.35. Analysis
Comparison 1 Any vitamin E supplementation, Outcome 35 Use of health service resources ‐ infant.
2.1
2.1. Analysis
Comparison 2 Any vitamin E supplementation (sensitivity analyses by trial quality), Outcome 1 Stillbirth.
2.2
2.2. Analysis
Comparison 2 Any vitamin E supplementation (sensitivity analyses by trial quality), Outcome 2 Neonatal death.
2.3
2.3. Analysis
Comparison 2 Any vitamin E supplementation (sensitivity analyses by trial quality), Outcome 3 Perinatal death.
2.4
2.4. Analysis
Comparison 2 Any vitamin E supplementation (sensitivity analyses by trial quality), Outcome 4 Preterm birth (< 37 weeks' gestation).
2.5
2.5. Analysis
Comparison 2 Any vitamin E supplementation (sensitivity analyses by trial quality), Outcome 5 Clinical pre‐eclampsia.
2.6
2.6. Analysis
Comparison 2 Any vitamin E supplementation (sensitivity analyses by trial quality), Outcome 6 Intrauterine growth restriction.
3.1
3.1. Analysis
Comparison 3 Any vitamin E supplementation (subgroup analyses based on gestation at entry), Outcome 1 Stillbirth.
3.2
3.2. Analysis
Comparison 3 Any vitamin E supplementation (subgroup analyses based on gestation at entry), Outcome 2 Neonatal death.
3.3
3.3. Analysis
Comparison 3 Any vitamin E supplementation (subgroup analyses based on gestation at entry), Outcome 3 Perinatal death.
3.4
3.4. Analysis
Comparison 3 Any vitamin E supplementation (subgroup analyses based on gestation at entry), Outcome 4 Preterm birth.
3.5
3.5. Analysis
Comparison 3 Any vitamin E supplementation (subgroup analyses based on gestation at entry), Outcome 5 Clinical pre‐eclampsia.
3.6
3.6. Analysis
Comparison 3 Any vitamin E supplementation (subgroup analyses based on gestation at entry), Outcome 6 Intrauterine growth restriction.
4.1
4.1. Analysis
Comparison 4 Any vitamin E supplementation (subgroup analyses by dietary intake), Outcome 1 Stillbirth.
4.2
4.2. Analysis
Comparison 4 Any vitamin E supplementation (subgroup analyses by dietary intake), Outcome 2 Neonatal death.
4.3
4.3. Analysis
Comparison 4 Any vitamin E supplementation (subgroup analyses by dietary intake), Outcome 3 Perinatal death.
4.4
4.4. Analysis
Comparison 4 Any vitamin E supplementation (subgroup analyses by dietary intake), Outcome 4 Preterm birth (less than 37 weeks' gestation).
4.5
4.5. Analysis
Comparison 4 Any vitamin E supplementation (subgroup analyses by dietary intake), Outcome 5 Clinical pre‐eclampsia (random‐effects model).
4.6
4.6. Analysis
Comparison 4 Any vitamin E supplementation (subgroup analyses by dietary intake), Outcome 6 Intrauterine growth restriction (less than third centile or the most extreme centile reported).
5.1
5.1. Analysis
Comparison 5 Any vitamin E supplementation (subgroup analyses by risk of adverse pregnancy outcomes at trial entry), Outcome 1 Stillbirth.
5.2
5.2. Analysis
Comparison 5 Any vitamin E supplementation (subgroup analyses by risk of adverse pregnancy outcomes at trial entry), Outcome 2 Neonatal death.
5.3
5.3. Analysis
Comparison 5 Any vitamin E supplementation (subgroup analyses by risk of adverse pregnancy outcomes at trial entry), Outcome 3 Perinatal death.
5.4
5.4. Analysis
Comparison 5 Any vitamin E supplementation (subgroup analyses by risk of adverse pregnancy outcomes at trial entry), Outcome 4 Preterm birth (less than 37 weeks' gestation).
5.5
5.5. Analysis
Comparison 5 Any vitamin E supplementation (subgroup analyses by risk of adverse pregnancy outcomes at trial entry), Outcome 5 Clinical pre‐eclampsia (random‐effects model).
5.6
5.6. Analysis
Comparison 5 Any vitamin E supplementation (subgroup analyses by risk of adverse pregnancy outcomes at trial entry), Outcome 6 Intrauterine growth restriction (less than third centile or the most extreme centile reported).
See this image and copyright information in PMC

Update of

References

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Bolisetty 2002 {published data only}
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References to other published versions of this review

Rumbold 2005
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