Abstract

The purpose of this study is to explore some of the new researches done
pertaining to Vitamin C and E supplementation during pregnancy. The study
seeks to answer the research question, do antioxidant therapies reduce the
risk of preeclampsia and other adverse infant complications. In previous
studies, it has been said that risks have been reduced with compliance to
Vitamin C and E supplements during pregnancy. Current research has
contradicted these findings, thus putting pregnancy women at an even
higher risk than before. This literature review will exploit the dangers and
lack of benefits when using Vitamin C and E supplementations.

Introduction
Supplementation with antioxidant vitamins has been proposed to reduce the risk of
preeclampsia and perinatal complications, but the effects of this intervention are uncertain
(Rumbold, Crowther, Haslam, Dekker, and Robinson 2006). As research continues, it has
become more evident that the use of Vitamin C and E supplements during pregnancy do not only
contradict a beneficial response to risk factors of preeclampsia in previous research, but also
have shown significant adverse reactions to the use of these vitamins during pregnancy. Several
studies from 2006 to 2010 retest the previous notion that antioxidant vitamins reduce the risk of
preeclampsia and oxidative stress related disorders. Of these researches, all used the same
vitamin dosage of 1000mg of vitamin C and 400 IU of vitamin E; all trials were able to clarify
that supplementation with vitamins C and E during pregnancy does not reduce the risk of
preeclampsia. The following literature reviews attempt to show that there is not significant
evidence to support the hypothesis that vitamin C and E supplements given prophylactically lead
to a reduction in the rate of preeclampsia (Poston, Briley, Seed, Kelly, and Shennan 2006). In
fact, research has shown that there was an increased rate of complications among women and
infants who received the antioxidant vitamins (Roberts et al., 2010). After reviewing various
articles, regardless of the population and selection of test subjects, it has been shown repeatedly
that there were no risk reductions observed for preeclampsia.
Review of the Literature
Article 1

In the earliest research studied reviewed, Poston et al. (2006) assessed whether supplementation
with vitamin C and E prevented preeclampsia in women at an increased risk. In comparison to
the other articles, this was the only research that focused on women who were at high-risk for
preeclampsia. This research also observed the rates of low birth weight and babies born small for
gestational age, since maternal and fetal diseases can be affected independently (Poston et al.
2006). This randomized, placebo-controlled trial enrolled 2410 women from 25 hospitals that
identified as being at an increased risk for preeclampsia. The primary endpoint of observation
was preeclampsia; the main secondary endpoint for observation was low birth weight less than
2.5 kg and small size for gestational age (Poston et al. 2006). Women were only eligible if they
were at the gestational age of 14-21 weeks and had one or more risk factors pertaining to
preeclampsia. Women that were excluded were those who were previously taking daily vitamin
supplements of 200mg Vitamin C and 40IU vitamin E (Poston et al. 2006). To compare, this
criterion was not included in the other trials. Findings showed that there was no reduction in the
rate of preeclampsia, and there was no major difference over all in growth restrictions except in a
subgroup of women with diabetes (Poston et al. 2006). Also, findings of a non-randomized study
indicate that high doses of Vitamin E could lead to a reduction of birth weight, but it is not know
for certain why supplementation would increase this rate. One major gap that was found was the
lack of acknowledgement on oxidized stress and placental functioning (Poston et al. 2006).
Through this study, it is clear that further research with careful analysis of underlying
pathophysiology should accompany further clinical trial investigations, but even without this, it
is evident that treatment with antioxidants had no effect on preeclampsia.
Article 2

Shortly after Postons (2006) trial, a second randomized trial was published. Rumbold et
al. (2006) conducted a multicenter, randomized trial of nulliparous women between 14 and 22
weeks of gestation. This researchs primary outcomes focused on the risks of maternal
preeclampsia, death or serious infant outcomes, and infant birth weights that measured below the
10th percentile for gestational age. This is a higher percentile than Postons et al. (2006) research,
which only measured infants falling below the 5th percentile. Unlike the previous study, Rumbold
et al. (2006) considered the pathogenesis of preeclampsia in the observation methods of the
research and only enrolled women who were at low risk for preeclampsia. As a result of this
inclusion criteria, it was found that the vitamin therapies did not reduce the risk of preeclampsia,
death of serious outcomes in infants, or the risk of intrauterine growth restrictions (Rumbold et
al., 2006) In addition to findings not supporting the reduction of these risks, it was also observed
that the women who took the vitamin supplements were more likely to be admitted antenatally
with hypertension and had to be treated with antihypertensive drugs (Rumbold et al., 2006). The
causes of the unexpected adverse findings are unknown, so there is no definite statement in
claiming that it is directly due to the supplementation. Unlike the previous study, the majority of
women observed had a baseline dietary intake of vitamin C and E above the recommended daily
amount (Rumbold et al., 2006). Thus, the results cannot be generalized to women with low
dietary intakes. In addition, the group receiving vitamin supplements had a higher rate of
elevated aminotransferase, which has never been reported in previous trials (Rumbold et al.,
2006). Liver function was assessed only in women considered to have clinical indications for
testing, and therefore, the results of testing are only known for a subgroup of women (Rumbold
et al., 2006). Even though these results may be due to chance, other studies of supplementation
with vitamins C and E in pregnancy should assess liver-function tests. The results of this

randomized trail indicate that daily supplements of 1000 mg Vitamin C and 400 IU Vitamin E
does not reduce the risks for preeclampsia, serious perinatal complications, or poor intrauterine
growth. In fact, there were significantly more babies with low birth weight in the group that
received vitamin supplementation than in the control group; gestational hypertension and the use
of antihypertensive therapy were also more common in the vitamin group (Rumbold et al.,
2010). This concludes that previous research showing beneficial results from Vitamin C and E
intake are negated and current research does not support routine supplementation of Vitamin C
and E to lower the risks of preeclampsia and other adverse perinatal outcomes.
Article 3
In most recent studies, Roberts et al. (2010) conducted a multicenter, randomized,
double-blind trial involving women who were at low risk for preeclampsia. A total of 10,154
women underwent randomization, and the groups were similar in baseline characteristics. In
contrast with other studies, this trial was designed to detect modest effect size in serious
outcomes associated with gestational hypertension and preeclampsia among low-risk women,
with treatment beginning early in pregnancy (Roberts et al., 2010). In fact, with inclusion criteria
of a gestational age between 9-16 weeks, no other trial initiated vitamin therapy as early as done
here. Unlike other trials, the primary outcome was a composite of pregnancy-associated
hypertension and serious adverse outcomes in mothers or her fetus or neonate (Roberts et al.,
2010). In this study, supplementation with Vitamin C and E did not reduce the frequency of the
primary outcome or any of its components (Roberts et al., 2010). By observing new-onset
pregnancy-associated hypertension with evidence of maternal, fetal, or neonatal complications,
other than the diagnosis of preeclampsia, researchers were able to assess whether therapy would
prevent serious complications rather than merely modify diagnostic findings (Roberts et al.,

2010). Secondary outcomes rates of mild preeclampsia and severe preeclampsia are not
significantly affected by vitamin treatment (Roberts et al., 2010). In contrast to the previous
study done by Rumbold, Roberts et al. (2010) did not find significant between-group differences
in the rates of low birth weight and stillbirth. However, this study supports and also observed an
increase in the frequency of gestational hypertension in the vitamin group, as compared to the
placebo group (Roberts et al., 2010). Benefits in reducing the rates of serious adverse outcomes
of pregnancy-associated hypertension or preeclampsia among low-risk are not supported through
Vitamin C and E supplementation during pregnancy.
Conclusion
In accordance with all three articles, it has been proven that there has been a similar lack
of efficacy in lowering the risk of preeclampsia, intrauterine growth restrictions, or risk of death
and other serious outcomes in infants by taking Vitamin C and E. It is also very important to
acknowledge that previous studies that have claimed that these vitamins reduce risks now put
pregnant mothers at an even higher risk for other adverse complications. The findings of these
several studies provide no support for the use of vitamin C and E supplementation in pregnancy
to reduce the risk for preeclampsia or its complications. In relation to the research question,
Vitamin C and E have been used in various clinical trials and negate previous findings for
preeclampsia and other adverse complications. All of the reviewed trials used the same Vitamin
supplemental amounts and all recorded an increased rate of pregnant mothers needing
antihypertensive therapies with no risk reduction benefits. It is important to understand these new
findings in order to prevent further unneeded complications during pregnancy through
unnecessary vitamin supplementation.