VITAMIN C SUPPLEMENTATION IN PREGNANCY

1. Alice Rumbold1,*,
2. Erika Ota2,
3. Chie Nagata3,
4. Sadequa Shahrook2,
5. Caroline A Crowther4
Editorial Group: Cochrane Pregnancy and Childbirth Group
Published Online: 29 SEP 2015
Assessed as up-to-date: 31 MAR 2015
DOI: 10.1002/14651858.CD004072.pub3
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons,
Ltd.
Database Title
The Cochrane Library

Abstract
Background
Vitamin C supplementation may help reduce the risk of pregnancy complications
such as pre-eclampsia, intrauterine growth restriction and maternal anaemia.
There is a need to evaluate the efficacy and safety of vitamin C supplementation
in pregnancy.

Objectives
To evaluate the effects of vitamin C supplementation, alone or in combination
with other separate supplements on pregnancy outcomes, adverse events, side
effects and use of health resources.

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 C
supplementation in pregnant women. Interventions using a multivitamin
supplement containing vitamin C or where the primary supplement was iron were
excluded.

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-nine trials involving 24,300 women are included in this review. Overall,
11 trials were judged to be of low risk of bias, eight were high risk of bias and for
10 trials it was unclear. No clear differences were seen between women
supplemented with vitamin C alone or in combination with other supplements
compared with placebo or no control for the risk of stillbirth (risk ratio (RR) 1.15,
95% confidence intervals (CI) 0.89 to 1.49; 20,038 participants; 11 studies; I =
0%; moderate quality evidence), neonatal death (RR 0.79, 95% CI 0.58 to 1.08;
19,575 participants; 11 studies; I = 0%), perinatal death (average RR 1.07, 95%
CI 0.77 to 1.49; 17,105 participants; seven studies; I = 35%), birthweight (mean
difference (MD) 26.88 g, 95% CI -18.81 to 72.58; 17,326 participants; 13 studies;
I = 69%), intrauterine growth restriction (RR 0.98, 95% CI 0.91 to 1.06; 20,361
participants; 12 studies; I = 15%; high quality evidence), preterm birth (average
RR 0.99, 95% CI 0.90 to 1.10; 22,250 participants; 16 studies; I = 49%; high
quality evidence), preterm PROM (prelabour rupture of membranes) (average RR
0.98, 95% CI 0.70 to 1.36; 16,825 participants; 10 studies; I = 70%; low quality
evidence), term PROM (average RR 1.26, 95% CI 0.62 to 2.56; 2674 participants;
three studies; I = 87%), and clinical pre-eclampsia (average RR 0.92, 95% CI
0.80 to 1.05; 21,956 participants; 16 studies; I = 41%; high quality evidence).
Women supplemented with vitamin C alone or in combination with other
supplements compared with placebo or no control were at decreased risk of
having a placental abruption (RR 0.64, 95% CI 0.44 to 0.92; 15,755 participants;
eight studies; I = 0%; high quality evidence) and had a small increase in
gestational age at birth (MD 0.31, 95% CI 0.01 to 0.61; 14,062 participants; nine
studies; I = 65%), however they were also more likely to self-report abdominal
pain (RR 1.66, 95% CI 1.16 to 2.37; 1877 participants; one study). In the
subgroup analyses based on the type of supplement, vitamin C supplementation
alone was associated with a reduced risk of preterm PROM (average RR 0.66,
95% CI 0.48 to 0.91; 1282 participants; five studies; I = 0%) and term PROM
(average RR 0.55, 95% CI 0.32 to 0.94; 170 participants; one study). Conversely,
the risk of term PROM was increased when supplementation included vitamin C
and vitamin E (average RR 1.73, 95% CI 1.34 to 2.23; 3060 participants; two
studies; I = 0%). There were no differences in the effects of vitamin C on other
outcomes in the subgroup analyses examining the type of supplement. There were
no differing patterns in other subgroups of women based on underlying risk of
pregnancy complications, timing of commencement of supplementation or dietary
intake of vitamin C prior to trial entry. The GRADE quality of the evidence was
high for intrauterine growth restriction, preterm birth, and placental abruption,
moderate for stillbirth and clinical pre-eclampsia, low for preterm PROM.
Authors' conclusions
The data do not support routine vitamin C supplementation alone or in
combination with other supplements for the prevention of fetal or neonatal death,
poor fetal growth, preterm birth or pre-eclampsia. Further research is required to
elucidate the possible role of vitamin C in the prevention of placental abruption
and prelabour rupture of membranes. There was no convincing evidence that
vitamin C supplementation alone or in combination with other supplements results
in other important benefits or harms.

TAKING VITAMIN C ON PREGNANCY

What is the issue?

Does vitamin C supplementation during pregnancy improve outcomes for mothers
and babies, and does it have any adverse effects?

Why is this important?

Having a low intake of vitamin C could be associated with complications in
pregnancy such as high blood pressure with swelling of the hands, feet and face
(pre-eclampsia), anaemia and having a small baby.

What evidence did we find?

This review included data from 29 trials involving over 24,000 pregnant women
from 17 different countries. Four trials did not contribute data to the review. The
overall risk of bias of the trials was low to unclear, and the evidence was moderate
to high quality. The most common daily dosage of vitamin C was 1000 mg, which
was used in 15 studies. The findings indicated that routine supplementation with
vitamin C during pregnancy, either alone or in combination with other
supplements (mainly vitamin E) did not improve outcomes for women and their
babies. There was a 36% relative reduction in the placenta coming away early
from the uterine wall (placental abruption) in women given vitamin C
supplements (eight studies, over 15,700 women); this was rated as high-quality
evidence. However, it was unclear whether this finding was due to vitamin C or
another agent, as most trials gave women vitamin C combined with vitamin E. In
the studies that gave women vitamin C only, there was a reduction in prelabour
rupture of the membranes (PROM) occurring either preterm or at term. However,
there was an increased risk of term PROM in the studies that gave women vitamin
C and vitamin E. Therefore, further research is required to examine the role of
vitamin C in reducing placental abruption and the development of PROM. The
review found in one study only an increased risk of abdominal pain with vitamin
C indicating there may be harms associated with vitamin C supplements in
pregnancy.

What does this mean?

Taking vitamin C supplements during pregnancy does not help to prevent
problems in pregnancy including stillbirth, the death of the baby, preterm birth,
pre-eclampsia or low birthweight babies

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004072.pub3/abstract;jse
ssionid=ED462793A3EE0B0EF5983BFEDD4DEC9F.f02t02
2016 Mar 2. pii: peds.2015-3547. [Epub ahead of print]
IRON SUPPLEMENTATION IN PREGNANCY OR INFANCY AND
MOTOR DEVELOPMENT: A RANDOMIZED CONTROLLED
TRIAL.
Angulo-Barroso RM1, Li M2, Santos DC3, Bian Y2, Sturza J4, Jiang Y5, Kaciroti
N4, Richards B4, Lozoff B6.
Author information
Abstract
BACKGROUND AND OBJECTIVE:
Insufficient iron levels for optimal fetal and infant development is a concern
during pregnancy and infancy. The goal of this study was to assess the effects
of iron supplementation in pregnancy and/or infancy on motor development at 9
months.
METHODS:
The study was a randomized controlled trial (RCT) of
infancy iron supplementation linked to an RCT
of pregnancy iron supplementation, conducted in Hebei, China. A total of 1482
infants were randomly assigned to receive placebo (n = 730) or
supplemental iron (n = 752) from 6 weeks to 9 months. Gross motor development
(assessed by using the Peabody Developmental Motor Scale, Second Edition,
instrument) was the primary outcome. Neurologic integrity and motor quality
were secondary outcomes.
RESULTS:
Motor outcome was available for 1196 infants, divided into 4 supplementation
period groups: (1) placebo in pregnancy/placebo in infancy (n = 288); (2) placebo
in pregnancy/iron in infancy (n = 305); (3) iron in pregnancy/placebo in infancy
(n = 298); and (4) iron in pregnancy/iron in infancy (n = 305). Using the Peabody
Developmental Motor Scale, instrument, iron supplementation in infancy but
not pregnancy improved gross motor scores: overall, P < .001; reflexes, P = .03;
stationary, P < .001; and locomotion, P < .001. Iron supplementation in infancy
improved motor scores by 0.3 SD compared with no supplementation or
supplementation during pregnancy alone. Effects of iron supplementation in
infancy alone were similar to effects with iron in both pregnancy and infancy.
CONCLUSIONS:
The RCT design supports the causal inference that iron supplementation in
infancy, with or without iron supplementation inpregnancy, improved gross motor
test scores at 9 months.
Copyright 2016 by the American Academy of Pediatrics.
http://www.ncbi.nlm.nih.gov/pubmed/26936859
J Res Med Sci. 2015 Oct; 20(10): 994999.
doi: 10.4103/1735-1995.172794
PMCID: PMC4746875

A SYSTEMATIC REVIEW ON THE EFFECTS OF MATERNAL CALCIUM

SUPPLEMENTATION ON OFFSPRING'S BLOOD PRESSURE
Fahimeh Jamshidi and Roya Kelishadi

Abstract
Background:

Evidence proposes that maternal calcium (Ca) supplement during pregnancy may
be inversely associated with the off spring's blood pressure (BP) level. It is
suggested that increased maternal Ca intake during pregnancy may result in lower
BP in the off spring. The reduction in the incidence of hypertension in mothers is
documented but the effects on the off spring are uncertain.
Materials and Methods:

We conducted a systematic review of the literature to summarize the evidence

supporting an association between maternal dietary Ca intake during pregnancy
and the BP in the off spring. In this systematic review, relevant papers were
selected in three phases. After quality assessment, a reviewer extracted the data
while the other one checked the extracted data. We summarized the information
regarding the association of maternal Ca intake either by food or supplements
with BP in the off spring.
Results:

Four randomized trials and three observational studies were included in this
review. The results were more consistent among the studies including older
children (1-9 years) where a higher maternal Ca intake was associated with a
reduction in the off spring's systolic BP. One large randomized trial found a
clinically and statistically significant reduction in the incidence of elevated BP in
7-year-old children [relative risk (RR) = 0.59, 95% confidence interval (CI) 0.39-
0.90].
Conclusion:

Overall, our findings confirm the beneficial effects of maternal Ca intake during
pregnancy for the off spring's BP level.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746875/
Wkly Epidemiol Rec. 1996 May 3;71(18):133-7.

EXPANDED PROGRAMME ON IMMUNIZATION (EPI) IMMUNIZATIO

N SCHEDULES IN THE WHO WESTERN PACIFIC REGION, 1995.
Abstract
There are 36 countries/areas in this Region; Mongolia was transferred to
the Western Pacific Region in 1995. No data are available from the Cook Islands, Nauru,
and New Caledonia (Tables 1-3). BCG is used in all but 6 countries/areas (American
Samoa, Australia, Guam, New Zealand, Northern Mariana Islands and Palau). Most
countries/areas give BCG at birth; Japan gives it at 3 months, the Republic of Korea at 4
weeks, and Samoa at 5 years of age. Nine countries give 2 doses of BCG and 4 give 3
doses, up to 15 years of age. Mongolia gives 4 doses up to 18 years of age. Diphtheria-
pertussis-tetanus (DPT) vaccine is used as a primary series of 3 doses in all
countries/areas; 17 countries give 1 to 3 booster doses of DPT vaccine in the first year of
life or later. Diphtheria-tetanus (DT) booster doses are given in Brunei Darussalam,
Mongolia and New Zealand. Td is also given in New Zealand. Oral poliovirus vaccine
(OPV) is used in a primary series of 3 doses simultaneously with DPT vaccine in all
countries/areas. Eight countries/areas use an additional dose of OPV at birth (Cambodia,
Fiji, Hong Kong, Kiribati, Lao People's Democratic Republic, Marshall Islands, Papua
New Guinea and Tuvalu). A booster dose of OPV in the second year of life is used in 9
countries/areas and a booster dose of OPV is given to schoolchildren in 16
countries/areas. Measles vaccine is given in all countries/areas from 8-15 months of age
usually in the form of monovalent measles vaccine, except in Macau. In 4 countries/areas,
it is given in the form of measles-mumps-rubella (MMR) vaccine (Guam, Hong Kong,
Palau and Singapore). The 2-dose policy is implemented in 4 countries/areas (American
Samoa, New Zealand, Palau, and Samoa). In Australia and Palau, the second dose is
given as MMR vaccine. The age at the second dose varies from 4 to 13 years of age.
Rubella vaccine is given in 4 countries/areas to girls between 10 and 14 years of age (Fiji,
French Polynesia, Japan and Macau). In Hong Kong, it is not specified if only girls
receive rubella vaccine. In Australia and New Zealand, rubella vaccine is given to
seronegative women immediately after delivery. Hepatitis B is used in all but 7
countries/areas (Cambodia, China, Guam, Kiribati, Lao People's Democratic Republic,
Tokelau and Viet Nam). All countries which give hepatitis B vaccine use 3 primary doses
in infancy, the first dose being given at birth in 23 countries/areas. In Australia and Japan,
this vaccine is given to groups at risk. Tetanus toxoid (TT) is used for pregnant or
nonpregnant women of childbearing age. It is used in 14 countries/areas, but in Australia
and Palau the target group is schoolchildren. The schedules include 2-5 doses of TT.
http://www.ncbi.nlm.nih.gov/pubmed/?term=Expanded+programme+on+immunization+
(EPI)+immunization+schedules+in+the+WHO+Western+Pacific+Region%2C+1995 .