JRSSEM 2022, Vol. 02, No. 3, 319 – 327
E-ISSN: 2807 - 6311, P-ISSN: 2807 - 6494
DOI: 10.36418/jrssem.v2i03.252 https://jrssem.publikasiindonesia.id/index.php/jrssem/index
THE EFFECT OF VITAMIN D SUPPLEMENTATION IN
PREGNANT WOMAN FOR PRE-ECLAMPSIA INCIDENCE: A
LITERATURE REVIEW
Tia Mella Citra, Ratih Pramuningtyas, Tri Agustina, Erna Herawati, Ayu Mayangsari, Zhela
Fatin Fatiha, Aulia Nissa Rizky Hariyono
Department of Medicine, Faculty of Medicine, University of Muhammadiyah Surakarta, Indonesia
*
e-mail: J500190030@student.ums.ac.id, ratihpramuningtyas@gmail.com,
triagustina@gmail.com,ernaherawati@gmail.com, ayumayangsari@gmail.com,
zhelafatin@gmail.com, aulianissa@gmail.com
*Correspondence: J500190030@student.ums.ac.id
Submitted
: 05 October 2022
Revised
: 16 October 2022
Accepted
: 25 October 2022
Abstract: Pre-eclampsia was defined as hypertension after 20 weeks of gestation with evidence of
maternal organ dysfunction, uteroplacental, or proteinuria. Maternal vitamin D deficiency may be
with an increased risk of pre-eclampsia. Nonetheless, To assess the impact of vitamin D
supplementation on the risk of pre-eclampsia, we performed a literature review. We researched
Google Scholar; PubMed; Research Gate; and Science Directs using keywords (“Vitamin D” OR
“Hydroxyvitamin D (25(OH)D)” OR “25(OH)D” OR “25hydroxycholecalciferol”) AND (“Pregnancy” OR
“Pregnant women” OR “Gestation”) AND (“Clinical trial” OR “Clinical study” OR “study” OR
“prospective study” OR “Randomized controlled trial” OR “RCT”) from January 2006 – May 2021. A
total of 4 of 19.431 articles were recorded at the identification stage by the criteria for inclusion.
The articles are randomized controlled trials (RCT). A total of 329 pregnant women are given various
vitamin D supplements with a dose range of 400 - 4.000 IU. Some articles combine with another
vitamin (Calcium, Vitamin C+E) for a certain duration. Maternal ages range 20 years - 40 years with
a gestational age of 6 to more than 32 weeks. Vitamin D can reduce the risk of pre-eclampsia in
pregnant women.
Keywords: Vitamin D, Pregnancy, Pre-eclampsia.
Tia Mella Citra, Ratih Pramuningtyas, Tri Agustina, Erna Herawati, Ayu Mayangsari,
Zhela Fatin Fatiha, Aulia Nissa Rizky Hariyono | 320
INTRODUCTION
Pre-eclampsia is a disease
characterized by hypertension (≥140/90)
and proteinuria (300 mg/24 hours) that
occurs after 20 weeks of gestation in
women who were previously normotensive
and has multi-factorial disorders that can
cause complications such as eclampsia,
liver failure, kidney failure, edema, stroke,
cardiovascular disorders, metabolic
disorders, prematurity, and even death.
Pre-eclampsia greatly affects the condition
of the mother and baby during pregnancy.
The reported prevalence of pre-eclampsia
is between 1.3%-10% of all pregnancies.
Increased oxidative stress biomarkers are
considered to be a key factor in the process
of pre-eclampsia (Azami et al., 2017).
One study suggests that maternal
vitamin D and calcium deficiency during
pregnancy may be an independent risk
factor for pre-eclampsia. In a meta-analysis
study showed that pregnant women who
received vitamin D supplementation in
early pregnancy had a positive association
and a lower risk of pre-eclampsia because
vitamin D could reduce oxidative stress
markers. Vitamin D can also stimulate the
immune system in decidual tissue and may
promote healthy placental function. The
risk of pre-eclampsia is reduced by 27%
among women who take 400-600 IU daily
vitamin D supplements compared to those
taking no supplements.
Vitamin D deficiency is defined as a
serum 25(OH)D level of less than 20 ng/ml
(50 nmol/liter), while an insufficient
25(OH)D level is less than 29 ng/ml (525-
725 nmol/liter) so it is necessary giving
vitamin D supplementation in order to
avoid the risks that may occur (Amrein et
al., 2020).
The daily routine antenatal vitamin D
is 400 IU while the safest maximum
recommended dose for vitamin D
supplementation in pregnancy is 4000 IU.
Many studies conclude that high-quality
randomized trials are needed to determine
the recommended dose of vitamin D
supplementation in pregnancy. Despite
consistent published evidence regarding
the achievement of optimal maternal and
infant vitamin D status with antenatal
supplementation at higher doses of up to
4000 IU. One study suggested that
supplementation of high doses of vitamin
D (4000 IU) in a vitamin D-deficient
pregnant population would reduce the risk
of pre-eclampsia and help achieve normal
levels of vitamin D3 (Ali et al., 2019). This
study aimed to assess the impact of vitamin
D supplementation on the risk of pre-
eclampsia.
MATERIALS AND METHODS
This research is a literature review.
PRISMA and Synthesis Without Meta-
analysis guidelines were applied to analyze
this literature review with the aim of
assessing the effect of vitamin D
supplementation on pregnant women on
the incidence of pre-eclampsia with the
inclusion criteria for study selection in the
321 | The Effect of Vitamin D Supplementation in Pregnant Woman for Pre-eclampsia
Incidency : A Literature Review
form of RCT. retrospective, retrospective
cohort, case-control, and experimental
exclusions for this type of Systematic
Review/Literature Review study. The
selected sample is a sample of pregnant
women of all ages without any restrictions
on gestational age, number of previous
pregnancy history, and accompanying
medical history. The year of publication
that we use is the journal in the year
published January 2006 – May 2021. The
language we use is the journal in English.
The final results (Outcomes) influence the
journal. Effect of vitamin D
supplementation on pregnant women with
pre-eclampsia. Journals will be excluded by
researchers. if it does not present data
whose results discuss the effect of vitamin
D on pregnant women in pre-eclampsia
and studies in the form of abstracts or brief
reports. Researchers did not limit the
intervention to related journals. Search for
literature that met the inclusion criteria
using PubMed, google schooler, Research
Gate, and Science Directs database sources,
the researchers did use the keywords
(“Vitamin D” OR “Hydroxyvitamin D
(25(OH)D)” OR “25(OH)D” OR
“25hydroxycholecalciferol”) AND
(“Pregnancy” OR “Pregnant women” OR
“Gestation”) AND (“Clinical trial” OR
“Clinical study” OR “study” OR “prospective
study” OR “Randomized controlled trial”
OR “RCT"). All obtained journals are
exported to Microsoft excel. All data were
extracted by 4 researchers. The selection of
relevant studies was based on pre-
determined inclusion criteria.
RESULTS AND DISCUSSION
A total of 4 19,431 articles were found
in Google scholar (17,400), PubMed (2030),
research gate (100), and science direct (1).
Using 4 RCT articles (n=329) for further
study. A total of 329 pregnant women are
given various vitamin D supplements with a
dose range of 400-4.000 IU. 2 of the 4
studies used combined vitamin D with
other supplements (Calcium and Vitamin
C+E) with a certain duration. Maternal ages
range 20 – 40 years with gestational age 6
to more than 32 weeks.
Tia Mella Citra, Ratih Pramuningtyas, Tri Agustina, Erna Herawati, Ayu Mayangsari,
Zhela Fatin Fatiha, Aulia Nissa Rizky Hariyono | 322
Fig. 1. PRISMA search and selection of the diagram Literature
Identification
Screening
Records identified from
Google Scholar, PubMed,
Science Direct, Research Gate
(n = 19.431)
Records screened through the
title, year, and completeness of
the articles
(n = 21)
Reports assessed for eligibility
(n = 4)
Studies included in
quantitative
(n = 4)
Records removed
before
screening
:
Duplicate records removed
(n=1.216)
(n = 239 )
Included
Reports excluded: ( n = 32)
1. Articles not RCT (n=15)
2. Inclusion criteria doesn’t
match (n=17)
Records excluded (n = 156)
1. Title doesn’t match (n =
149)
2. Incomplete Articles (n = 7)
Records excluded (n = 156))
323 | The Effect of Vitamin D Supplementation in Pregnant Woman for Pre-eclampsia
Incidency : A Literature Review
First
author
(years)
Design
criteria
for the
studies
(gestation
)
INTERVEN
TION
STUDY
GROUP
PARTICIPA
NT (n)
MATERN
AL AGE
(years)
GESTATION
AL AGE
(WEEKS)
DURATIO
N
INERVATI
ON
M.
Samimi
(2015)
Randomiz
ed
Controlled
Trial
Aged 18–
40 years
old,
(16–20
weeks)
vitamin D
+ calcium
50 000 IU
vitamin
D3 every
2 weeks
+ 1000
mg day 1
calcium
supplem
entation
60
<30 and
≥30
years
20 to 32
weeks of
gestation.
12 weeks
M.
Karama
li
(2015)
Randmize
d Double-
blind
Placebo-
Controlled
Clinical
Trial
aged 18–
40 years
old
(18– 20
weeks)
vitamin D
50000 IU
vitamin
D3, 14
days for
12 weeks
60
<30 and
≥30
years
20 to 32
weeks of
gestation.
12 weeks
Milad
Azami
(2015)
Randomiz
ed
Controlled
Trial
Maternal
age >35
years
(20
weeks)
Group A :
Ferrous
Sulfate
tablet +
Vitamin D
Group B :
Ferrous
Sulfate
tablet +
vitamin C
dan
vitamin E
Group A :
800mg
calcium,
200mg
magnesi
um, 8mg
zinc, and
400 IU
Vitamin
D3 per
day
Group B :
Ferrous
Sulfate (1
tablet/da
Group A
(n=30)
Group A
(33)
Group B
(31,73)
Group A
(37)
Group B
(38)
Non
Spesific
Tia Mella Citra, Ratih Pramuningtyas, Tri Agustina, Erna Herawati, Ayu Mayangsari,
Zhela Fatin Fatiha, Aulia Nissa Rizky Hariyono | 324
Table 2. collection outcome dan metabolic profiles
First author
Outcome
Metabolik
M. Samimi
Caesarean section : 14%
Gestational age : 38.4 weeks
Preterm delivery : 2 %
Newborn weight : 3300.0 g
Newborn length : 49.5 cmc
Newborn head
circumference: 34.5 cm
Pre-eclampsia rate : 1%
LBW : 0%
Vitamin D : 13.1 ng /mL
Calcium : 8.7 mg/dL
Insulin : 14.3 lIU/mL
HOMA-IR : 3.1
HOMA-B : 55.5
Triglycerides: 188.5 mg/dl
VLDL-cholesterol : 37.7
mg/dl
Total cholesterol : 215.9 mgdl
LDL-cholesterol : 108.9
mg/dl
HDL-cholesterol : 69.3 mg/dl
Total: HDL cholesterol ratio :
3.1
M.Karamali
Caesarean section : 9%
Gestational age : 39.4 weeks
Preterm delivery : 0 %
Nmewborn weight : 3313.6g
Newborn length : 50.9 cm
Newborn head
circumference: 34.4 cm
Pre-eclampsia rate : 1%
Vitamin D : 34.91 ng /mL
Insulin : 12.3 lIU/mL
HOMA-IR : 2.48
HOMA-B : 49.04
Triglycerides: 205.68 mg/dl
VLDL-cholesterol : 41.3
mg/dl
y) + 250
mg
vitamin C
+ 55 mg
vitamin E
Aisha
Manso
or Ali
(2018)
study
Include
pre-
eclampsi
a (22-23
weeks)
vitamin
D3
suppleme
ntation
400 IU
(Group 1)
versus
4000 IU
(Group 2)
4000 IU
daily
dose of
vitamin D
179
pregnant
woman
(group
400IU=81
group
4000IU=8
3)
< 20
years
or> 40
years
Between 6
and 12
weeks of
pregnancy.
32 weeks
325 | The Effect of Vitamin D Supplementation in Pregnant Woman for Pre-eclampsia
Incidency : A Literature Review
LBW : 0%
Total cholesterol : 222.47
mgdl
LDL-cholesterol : 112.86
mg/dl
HDL-cholesterol : 68.28
mg/dl
Total: HDL cholesterol ratio :
3.26
Milad Azami
Multimineral-vitamin D
during pregnancy can be a
low-cost and affordable way
to reduce the incidence of
pre-eclampsia in women
who are at high risk of pre-
eclampsia.
Non specific
Aisha Mansoor Ali
Vitamin D supplementation
in the deficient group
reduces the risk of pre-
eclampsia and IUGR in a
dose dependant manner.
Non specific
According to (Azami et al., 2017) and
(Samimi et al., 2016)who combine Vitamin
D with other supplements, results on
Vitamin D less effect on reducing the risk of
pre-eclampsia but still has a positive effect.
However, for Vitamin D given in
combination, it has a beneficial effect on
reducing the risk of pre-eclampsia and also
has a positive impact on the fetus and
oxidative stress.
DISCUSSION
This study was conducted to determine
whether there is an effect of Vitamin D on
pregnant women with pre-eclampsia. Pre-
eclampsia is a multisystem pregnancy
disease characterized by complex
hypertension with serious consequences
for the mother, fetus, and neonate,
burdening up to 8% of pregnancies.
Vitamin D deficiency results in a higher risk
of pre-eclampsia (Mirzakhani et al., 2016).
Several studies have proven that
vitamin D had a significant effect on
reducing the risk of pre-eclampsia and it
could reduce early birth rates. However, a
combination of Vitamin D with other
supplements has a nonoptimal effect.
However, it can still reduce the risk of pre-
eclampsia and reduce the rate of
premature birth with oral administration at
high doses. It can be concluded that the
administration of Vitamin D with normal
doses to a high limit can reduce the risk of
pre-eclampsia for pregnant women. Low
Tia Mella Citra, Ratih Pramuningtyas, Tri Agustina, Erna Herawati, Ayu Mayangsari,
Zhela Fatin Fatiha, Aulia Nissa Rizky Hariyono | 326
vitamin D intake can impair ongoing
oxidative stress processes in placental
tissue and may increase the risk of pre-
eclampsia (Ali et al., 2019).
Administration of high doses of
Vitamin D with an average of 4000IU with a
recommendation of 600IU intake a day, it’s
given for 12-32 weeks. Women at risk of
pre-eclampsia who have Vitamin D
deficiency had beneficial effects on insulin
metabolism parameters, serum HDL
cholesterol, and plasma TAC
concentrations, but did not affect FPG,
another lipid profile, inflammatory factors,
and other oxidative stress biomarkers
(Karamali et al., 2015).
The association between vitamin D
deficiency, pre-eclampsia, fetal growth and
suggests that vitamin D supplementation
may improve pregnancy outcomes and
fetal growth problems in the high-risk
group. Overall, it appears that
multimineral-vitamin D supplementation in
pregnant women at risk of pre-eclampsia
reduces the risk of neonatal complications
by reducing the incidence of pre-eclampsia
(Azami et al., 2017).
CONCLUSIONS
Based on the results of this study, a
high dose of vitamin D has a good effect on
reducing the risk of pre-eclampsia in
pregnant women with vitamin D deficiency.
Vitamin D can reduce oxidative stress as a
factor in pre-eclampsia and stimulate
immunity in multiple tissues and promote
proper and healthy placental function. This
is one of the reasons why vitamin D has a
positive relationship with pre-eclampsia.
REFERENCES
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A. F. (2019). Effect of vitamin D3
supplementation in pregnancy on risk of
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© 2021 by the authors. Submitted
for possible open access publication
under the terms and conditions of the Creative Commons Attribution (CC BY SA) license
(https://creativecommons.org/licenses/by-sa/4.0/).