Antioxidants for preventing pre-eclampsia

Current evidence does not support routine prescription of antioxidants during pregnancy to reduce the risk of pre-eclampsia. RHL Commentary by Boulvain M

1. EVIDENCE SUMMARY
This systematic review (1) was updated in January 2008 and includes several new wellconducted trials with large numbers of participants. The previous version (2) of this review, which included lower-quality trials, had reported that antioxidants may be a promising intervention for the prevention of pre-eclampsia. The updated review concludes that use of antioxidants during pregnancy is unlikely to reduce the risk of pre-eclampsia. The updated review analysed data from ten trials involving 6533 women pregnant women taking, or not taking, antioxidant regimens (mainly vitamin C and E) to prevent pre-eclampsia. The review included randomized controlled trials that had compared antioxidants (vitamin C and/or E, selenium, lycopene or red palm oil) with no antioxidants or placebo and reported on clinical outcomes, namely pre-eclampsia, hypertension, preterm delivery, small-for-gestational age, perinatal mortality, birth weight and gestational age at birth. The updated review did not include a large (5021 women) quasi-randomized trial published in 1942 (3) which had considerable influence on the results of the previous version of the review. Comparative studies without random allocation of subjects and trials conducted with women with a diagnosis of preeclampsia were excluded. The trials were identified by electronic searches of the Cochrane Controlled Trials Register, MEDLINE and EMBASE, using standard methodology of the Cochrane Collaboration. Data analysis and reporting also followed standard Cochrane methods. The main results suggest that the risk of pre-eclampsia is not reduced when antioxidants are administered during pregnancy. Many pre-specified subgroup analyses are presented in the review according to women's risk status, trial quality, gestational age at entry, and dose level. All subgroup analyses are consistent with the main analysis, which further suggest that antioxidants are not beneficial for the prevention of pre-eclampsia and other unfavorable pregnancy outcomes. The review is thorough and free from bias. The data are clearly tabulated and graphically presented for overall findings and for different subgroups. The main conclusion is supported by the data presented.

2. RELEVANCE TO UNDER-RESOURCED SETTINGS 2.1. Magnitude of the problem

Maternal mortality is very high in some under-resourced settings and hypertensive disorders of pregnancy are among its leading causes (4). Even in well-equipped hospitals hypertensive disorders are the cause of a large proportion of maternal mortality and morbidity. Pre-eclampsia is difficult to detect at an early stage in many settings and screening tests are not available (5). Oxidative stress is among the potential underlying causes of pre-eclampsia. The

administration of antioxidants to all pregnant women or only to high-risk women has been proposed to decrease the incidence of pre-eclampsia. Unfortunately, the early promises of relatively small trials were not confirmed by well conducted larger trials. There are, however, several ongoing trials that may provide further evidence in this area.

2.2. Applicability of the results

Most of the available evidence is based on trials conducted in developed countries. Applicability of the results to under-resourced settings is therefore questionable. A trial, sponsored by WHO, is currently under way in several developing countries and results may help to clarify this issue.

2.3. Implementation of the intervention

Based on evidence presented in this review it is not possible to recommend the prescription of antioxidants during pregnancy for the specific reason of preventing pre-eclampsia. Should results of ongoing trials change this conclusion, the intervention would however be feasible and affordable in under-resourced settings. The findings of this review do not imply that pregnant women should reduce their dietary intake of fruits and other foods rich in such vitamins. Intake of vitamin C (through regular diet or through prescribed vitamin C supplementation) may improve the absorption of iron, thus improving the effectiveness of iron supplementation.

3. RESEARCH
At the present time large randomized controlled trials on the prevention of pre-eclampsia with antioxidants are recruiting or are in the analysis phase. Pending results from these trials, no further trials should be initiated on this topic. The analysis of subgroups may help to identify women who may benefit from the intervention (e.g. women with a diet deficient in antioxidants).
SUMBER : http://apps.who.int/rhl/pregnancy_childbirth/medical/hypertension/mbcom3/en/ind ex.html

Antioxidants for preventing pre-eclampsia

Rumbold A, Duley L, Crowther CA, Haslam RR
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Plain Language Summary

Antioxidants for preventing pre-eclampsia

Pre-eclampsia can occur during pregnancy when women have high blood pressure and protein in their urine. In some cases, it can lead to poor growth for the baby and premature birth. There can also be serious complications for the woman, sometimes affecting the liver, kidneys, brain or blood clotting system. Both mother and baby are at risk of mortality. A possible contributing factor to the development of pre-eclampsia may be the presence of excessive amounts of chemicals called 'free radicals'. Antioxidants, such as vitamin C, vitamin E, selenium and lycopene, can neutralize free radicals. The review covered 10 trials, involving 6533 women, and looked at several antioxidants. Overall the review found no reduction in pre-eclampsia, high blood pressure or preterm birth with the use of antioxidant supplements. When antioxidants were assessed separately, there were insufficient data to be clear about whether there was any benefit or not, except for vitamin C and E. The current evidence does not support the use of antioxidants to reduce the risk of pre-eclampsia or other complications in pregnancy, but there are trials still in progress. This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2011 Issue 8, Copyright 2011 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X). This record should be cited as: Rumbold A, Duley L, Crowther CA, Haslam RR. Antioxidants for preventing pre-eclampsia. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD004227. DOI: 10.1002/14651858.CD004227.pub3 Editorial Group: Pregnancy and Childbirth Group This version first published online: October 19. 2005 Last assessed as up-to-date: October 26. 2007

Abstract
Background Oxidative stress has been proposed as a key factor involved in the development of preeclampsia. 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. SUMBER : http://www2.cochrane.org/reviews/en/ab004227.html

Antioxidants to Prevent Preeclampsia

CAPPS: A Randomized Clinical Trial of Antioxidants to Prevent Preeclampsia Primary Investigator: Mara J. Dinsmoor, MD, MPH Goal of the Study The goal of this study is to determine whether taking extra vitamin C and E will reduce the chances of poor pregnancy outcomes due to the development of preeclampsia (also known as toxemia). Preeclampsia is a disease unique to pregnancy, consisting of high blood pressure, swelling, and kidney dysfunction. Small studies have suggested that vitamins C and E may reduce the chance of preeclampsia developing.

Eligibility The study will enroll pregnant women between 9 and 16 weeks of pregnancy who have never had a baby before. (Mothers having their first baby are at especially high risk of preeclampsia.) Mothers with the following problems are not eligible:

Multiple gestation (twins, triplets) Medical problems including pre-existing high blood pressure, diabetes, kidney disease, thyroid or liver problems, epilepsy, or cancer IVF pregnancy.

Benefits of Participation As participants in this study, women will receive the following benefits:

Close monitoring of their pregnancy The satisfaction of assisting future generations by assisting in the development of possible measures to prevent preeclampsia

What Does Participation In the Study Involve? 1) At the initial meeting, participants will fill out a form about their general health and medical history and meet with a research coordinator. 2) Participants will be randomized (like a flip of the coin) to receive Vitamins C plus Vitamin E, or placebo pills (containing an inactive substance). Neither you, your doctor, nor the study personnel will know if you are getting the vitamins or the placebo. 3) You will bring your pill bottle to your doctors office at each prenatal visit, where a research coordinator will review how you are taking the pills and see if you are having any problems with the pills. 4) A tube of blood will be drawn on two occasions at 24 weeks and 32 weeks of pregnancy, and a urine sample will be obtained at the same time. 5) When your baby is born, your doctor will collect a sample of blood from the placenta after the babys umbilical cord is clamped and cut. All health information is kept confidential, and participants can leave the study at any time.
Sumber : http://www.northshore.org/maternity-services/research/antioxidants-toprevent-preeclampsia/

From Medscape Medical News

Dietary Supplement May Help Prevent Preeclampsia

Laurie Barclay, MD

Authors and Disclosures

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May 23, 2011 Dietary supplementation during pregnancy with L-arginine and antioxidant vitamins helps prevent preeclampsia in a high-risk population, according to the results of a blinded, randomized controlled trial reported online May 19 in the BMJ. "In the past, the role of nutrition in the development of pre-eclampsia has been a subject of considerable discussion," write Felipe Vadillo-Ortega, from the Department of Experimental Medicine, School of Medicine, Universidad Nacional, Autonoma de Mexico, Ciudad Universitaria, Mexico, and colleagues. "Although little evidence exists to show that dietary manipulations can prevent pre-eclampsia, the notion that they might moderate the secondary features of the syndrome remains in favour. Substantial experimental data in animals and humans indicate that L-arginine could have a beneficial effect on haemodynamics." The goal of the study was to test the hypothesis that a relative deficiency in L-arginine, which is the substrate needed to synthesize the vasodilator nitric oxide, may lead to development of preeclampsia in a high-risk population. At a tertiary public hospital in Mexico City, high-risk pregnant women with a history of preeclampsia in a previous pregnancy or preeclampsia in a first-degree relative were studied from weeks 14 to 32 of gestation and monitored until delivery for development of preeclampsia or eclampsia. During pregnancy, participants were randomly assigned to receive supplementation with food bars containing L-arginine plus antioxidant vitamins (n = 228), antioxidant vitamins alone (n = 222), or placebo (n = 222). While receiving the bars, participants had 4 to 8 prenatal visits. Preeclampsia developed in 30.2% of the placebo group, 22.5% of the vitamin-only group, and 12.7% in the L-arginine plus vitamin group. Compared with women receiving placebo, those receiving L-arginine plus antioxidant vitamins had a lower incidence of preeclampsia (2 = 19.41; P < .001; absolute risk reduction [RR], 0.17; 95% confidence interval [CI], 0.12 - 0.21). The group receiving L-arginine plus antioxidant vitamins also had a lower incidence of preeclampsia vs the group receiving antioxidant vitamins alone (2 = 8.16; P = .004; absolute RR, 0.09; 95% CI, 0.05 - 0.14). There was also a nonstatistically significant benefit for antioxidant vitamins alone vs placebo (2 = 3.76; P = .052; absolute RR, 0.07; 95% CI, 0.005 - 0.15).

"Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition," the study authors write. "Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined." Limitations of this study include lack of generalizability to pregnant women at low risk for preeclampsia, lack of data on the effects of L-arginine alone, insufficient power to detect a less than 50% reduction in preeclampsia, and failure to rigorously test time of supplementation and outcome. In an accompanying editorial, Liam Smeeth, from the London School of Hygiene and Tropical Medicine, and David Williams, from the Institute for Women's Health, University College London Hospital, both in London, United Kingdom, further discuss study strengths and limitations. "What is the mechanism of action of L-arginine and vitamins together; what are the effects (including potential adverse effects) of L-arginine given alone; what are the effects in other settings and populations?" Drs. Smeeth and Williams write. "This is not the conventional 'more research is needed' call. Indeed, a crucial first step before more trials are started would be a rigorous systematic review of the numerous inconsistent strands of evidence relating to Larginine and its possible effects on pre-eclampsia."
Sumber : http://www.medscape.com/viewarticle/743176

Antioxidants to Prevent Preeclampsia

CAPPS: A Randomized Clinical Trial of Antioxidants to Prevent Preeclampsia Primary Investigator: Mara J. Dinsmoor, MD, MPH Goal of the Study The goal of this study is to determine whether taking extra vitamin C and E will reduce the chances of poor pregnancy outcomes due to the development of preeclampsia (also known as toxemia). Preeclampsia is a disease unique to pregnancy, consisting of high blood pressure, swelling, and kidney dysfunction. Small studies have suggested that vitamins C and E may reduce the chance of preeclampsia developing. Eligibility The study will enroll pregnant women between 9 and 16 weeks of pregnancy who have never had a baby before. (Mothers having their first baby are at especially high risk of preeclampsia.) Mothers with the following problems are not eligible:

Multiple gestation (twins, triplets) Medical problems including pre-existing high blood pressure, diabetes, kidney disease, thyroid or liver problems, epilepsy, or cancer

IVF pregnancy.

Benefits of Participation As participants in this study, women will receive the following benefits:

Close monitoring of their pregnancy The satisfaction of assisting future generations by assisting in the development of possible measures to prevent preeclampsia

What Does Participation In the Study Involve? 1) At the initial meeting, participants will fill out a form about their general health and medical history and meet with a research coordinator. 2) Participants will be randomized (like a flip of the coin) to receive Vitamins C plus Vitamin E, or placebo pills (containing an inactive substance). Neither you, your doctor, nor the study personnel will know if you are getting the vitamins or the placebo. 3) You will bring your pill bottle to your doctors office at each prenatal visit, where a research coordinator will review how you are taking the pills and see if you are having any problems with the pills. 4) A tube of blood will be drawn on two occasions at 24 weeks and 32 weeks of pregnancy, and a urine sample will be obtained at the same time. 5) When your baby is born, your doctor will collect a sample of blood from the placenta after the babys umbilical cord is clamped and cut. All health information is kept confidential, and participants can leave the study at any time.
Sumber : http://www.northshore.org/maternity-services/research/antioxidants-toprevent-preeclampsia/