Antioxidants for Preventing Pre

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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 well-

conducted 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 pre-

eclampsia were excluded. The trials were identified by electronic searches of the Cochrane

Controlled Trials Register, MEDLINE and EMBASE, using standard methodology of theCochrane 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 bythe 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


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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 withantioxidants 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-eclampsiaRumbold A, Duley L, Crowther CA, Haslam RR

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Antioxidants for preventing pre-eclampsia
http://apps.who.int/rhl/pregnancy_childbirth/medical/hypertension/mbcom3/en/index.htmlhttp://apps.who.int/rhl/pregnancy_childbirth/medical/hypertension/mbcom3/en/index.htmlhttp://www2.cochrane.org/reviews/en/ab004227.htmlhttp://www2.cochrane.org/assets_local/includes/email_this_sender.phphttp://www.newsvine.com/http://www.citeulike.org/http://del.icio.us/http://www.bibsonomy.org/http://www.connotea.org/http://apps.who.int/rhl/pregnancy_childbirth/medical/hypertension/mbcom3/en/index.htmlhttp://apps.who.int/rhl/pregnancy_childbirth/medical/hypertension/mbcom3/en/index.htmlhttp://www2.cochrane.org/reviews/en/ab004227.htmlhttp://www2.cochrane.org/assets_local/includes/email_this_sender.php


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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 andlycopene, 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 JohnWiley 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 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
http://dx.doi.org/10.1002/14651858.CD004227.pub3http://www2.cochrane.org/reviews/en/subtopics/87.htmlhttp://www2.cochrane.org/reviews/en/subtopics/87.htmlhttp://dx.doi.org/10.1002/14651858.CD004227.pub3http://www2.cochrane.org/reviews/en/subtopics/87.html


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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 0.99to 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.
http://www2.cochrane.org/reviews/en/ab004227.htmlhttp://www.northshore.org/apps/findadoctor/doctor.aspx?docid=2135http://www2.cochrane.org/reviews/en/ab004227.htmlhttp://www.northshore.org/apps/findadoctor/doctor.aspx?docid=2135


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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 noteligible:

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 problemswith 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-to-

prevent-preeclampsia/

From Medscape Medical News

Dietary Supplement May Help Prevent

Preeclampsia

Laurie Barclay, MD
http://www.northshore.org/maternity-services/research/antioxidants-to-prevent-preeclampsia/http://www.northshore.org/maternity-services/research/antioxidants-to-prevent-preeclampsia/http://www.northshore.org/maternity-services/research/antioxidants-to-prevent-preeclampsia/http://www.medscape.com/newshttp://www.northshore.org/maternity-services/research/antioxidants-to-prevent-preeclampsia/http://www.northshore.org/maternity-services/research/antioxidants-to-prevent-preeclampsia/http://www.medscape.com/news


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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 trialreported online May 19 in theBMJ.

"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 ofpreeclampsia 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, and12.7% 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).
http://as.webmd.com/event.ng/Type=click&FlightID=240579&AdID=410027&TargetID=63547&Values=205&Redirect=http:/www.medscape.com/public/mobileapphttp://as.webmd.com/event.ng/Type=click&FlightID=240579&AdID=410027&TargetID=63547&Values=205&Redirect=http:/www.medscape.com/public/mobileapphttp://as.webmd.com/event.ng/Type=click&FlightID=240579&AdID=410027&TargetID=63547&Values=205&Redirect=http:/www.medscape.com/public/mobileapphttp://www.bmj.com/content/342/bmj.d2901http://www.bmj.com/content/342/bmj.d2901http://as.webmd.com/event.ng/Type=click&FlightID=240579&AdID=410027&TargetID=63547&Values=205&Redirect=http:/www.medscape.com/public/mobileapphttp://as.webmd.com/event.ng/Type=click&FlightID=240579&AdID=410027&TargetID=63547&Values=205&Redirect=http:/www.medscape.com/public/mobileapphttp://as.webmd.com/event.ng/Type=click&FlightID=240579&AdID=410027&TargetID=63547&Values=205&Redirect=http:/www.medscape.com/public/mobileapphttp://www.bmj.com/content/342/bmj.d2901


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"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 observedeffects 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 L-

arginine 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 noteligible:

Multiple gestation (twins, triplets)

Medical problems including pre-existing high blood pressure, diabetes,kidney disease, thyroid or liver problems, epilepsy, or cancer
http://www.bmj.com/content/342/bmj.d2777http://www.medscape.com/viewarticle/743176http://www.medscape.com/viewarticle/743176http://www.northshore.org/apps/findadoctor/doctor.aspx?docid=2135http://www.bmj.com/content/342/bmj.d2777http://www.medscape.com/viewarticle/743176http://www.northshore.org/apps/findadoctor/doctor.aspx?docid=2135


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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-to-

prevent-preeclampsia/

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