doi 10.15296/ijwhr.2023.02
http://www.ijwhr.net
Open Access
Original Article
International Journal of Women’s Health and Reproduction Sciences
Vol. 11, No. 1, January 2023, 3–10
ISSN 2330- 4456
Adherence Does Not Guarantee the Outcome of Iron
Supplementation for Reproductive-Age Women With
Anemia in West Papua Province, Indonesia: A Quasiexperimental Study
Yasinta Rakanita1, Rano Kurnia Sinuraya1*, Sofa Dewi Alfian1, Eka Widrian Suradji2, Auliya
Abdurrohim Suwantika1, Mas Rizky Anggun Adipurna Syamsunarno3, Rizky Abdulah1
Abstract
Objectives: Monitoring iron supplementation effectiveness in the affected populations is important in assuring its success. The research
objective of this study is to evaluate the effectiveness of iron supplementation and its related factors in increasing the hemoglobin
levels of women with anemia that reside in the area of Teluk Bintuni Regency in West Papua Province, Indonesia.
Materials and Methods: A quasi-experimental study was performed to determine the changes in hemoglobin levels and the adherence
between two supplementation groups (before and after supplementation). From the initial screening of hemoglobin levels of 875
reproductive-age women, 110 women with moderate and severe anemia were enrolled for a month-long iron supplementation
therapy. This study was conducted from September 2018 until November 2019 at Teluk Bintuni Regency, West Papua, Indonesia. The
changes in hemoglobin levels were measured after 30 days of iron supplementation. The associated factors, including participants’
characteristics, chronic energy deficiency (CED) levels, adherence to supplementation programs, and knowledge of anemia, were
also assessed. The adherence level to the supplementation was measured using the Medication Adherence Rating Scale (MARS)
questionnaires and the pill counting method.
Results: The mean hemoglobin level significantly increased from 9.12±1.70 before supplementation to 10.15±1.65 after 30 days
(P < 0.001). Interestingly, results from the MARS questionnaires and pill counting method suggested that only 76% and 66% of
participants adhered to the supplementation program, respectively. Further univariate analysis showed that adherence, ethnicity, and
type of supplementation were factors that may influence the success of the iron supplementation therapy.
Conclusions: Based on this study findings, it can be concluded that anemia is related to various factors, and its implementation should
be carefully monitored, not solely depending on individual adherence.
Keywords: Iron, Dietary supplement, Anemia, Women, Treatment adherence
Introduction
Anemia is one of the global sustained development goals,
with a targeted 50% decrease in anemia prevalence in
women of reproductive age (WRA) in 2025 (1). In 2016,
the standard prevalence of anemia among pregnant
women from 38 Asian nations was 34.7% (2). Anemia can
be affected by many factors. As stated by the World Health
Organization (WHO), anemia can be diagnosed when
the hemoglobin concentration of non-pregnant women is
<12.0 g/dL and <11.0 g/dL in pregnant women (3).
In 2018, the prevalence of pregnant women with anemia
increased to 48.9% in Indonesia, with the highest average
found in young adults, whose ages ranged from 15-24
years (4). The Indonesian government has implemented
an iron supplementation program specifically intended
for WRA. According to a report from the Indonesian
Ministry of Health, 81% of WRA in the West Papua
Province who had iron supplementation were pregnant
women (5). Furthermore, the rate of childbirth in
adolescent girls aged 15-19 years was relatively high in
the West Papua Province, whereas in Kaimana, Sorong,
and Manokwari Regency was 66, 53, and 44 per 1000
women, respectively (6). Therefore, iron supplementation
will continue for all menstruating teenage girls. In
Teluk Bintuni Regency of the West Papua province, the
supplementation program assessment has been limited to
the distribution of supplements, with the addition of the
percentage of target achievement was based on the verbal
answers of respondents on whether or not to consume
iron supplements (5), which may cause many biases in the
evaluation.
Thus, in this study, we evaluated the effectiveness of iron
supplementation in increasing hemoglobin levels. We also
analyzed the factors that directly influence the success of
the iron supplementation program.
Received 9 July 2021, Accepted 20 February 2022, Available online 13 January 2023
1
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
Department of Public Health, Faculty of Medicine, Krida Wacana University, Jakarta, Indonesia.
3
Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, Indonesia.
*Corresponding Author: Rano Kurnia Sinuraya, MPH, Tel: (+62 22) 84288888 ext. 3510, Email: r.k.sinuraya@unpad.ac.id
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Rakanita et al
Key Messages
►
►
►
Reproductive-age women in West Papua, Indonesia, have
poor knowledge about anemia.
Ethnicity plays a role in the success of iron supplementation
therapy.
Iron supplementation should be closely monitored to
maintain individual adherence.
Materials and Methods
Study Design and Participants
This quasi-experimental (before and after study) was
performed at the primary healthcare centers of six districts
in Teluk Bintuni Regency, West Papua province, Indonesia,
from September 2018 to November 2019. A total of 110
participants aged between 15-49 years old with moderate
and severe anemia, according to their initial hemoglobin
levels, were enrolled to this study. Our sampling method
was total population sampling; all participants who met
the inclusion and exclusion criteria will be included in the
study. Hemoglobin levels were measured before and after
the iron supplementation intervention.
The anemia categories are considered as follows: in
non-pregnant women, hemoglobin levels between 11.9
and 11.0 g/dL were classified as mild anemia, 10.9-8.0 g/
dL as moderate anemia, and 8.0 g/dL as severe anemia.
Meanwhile, hemoglobin levels of 10.9-10.0 g/dL were
classified as mild anemia in pregnant women, 9.9-7.0 g/
dL as moderate anemia, and 7.0 g/dL as severe anemia (3).
Inclusion and Exclusion Criteria
The inclusion criteria were women aged 15–49 with
moderate or severe anemia. All participants with
incomplete data, pregnant women, and those receiving
other supplementation were excluded from the study. To
avoid iron overload, participants with mild anemia were
ruled out of this study.
Sample Size
We performed total population sampling. In the initial
screening, 875 reproductive-age women were included for
hemoglobin level testing. As a result, 110 participants with
moderate to severe anemia were enrolled in this study for
a month of iron supplementation therapy.
Interventions
We randomly divided the participants into two groups for
interventions. Each group consumed a different type of
oral iron salt supplement that was given on day 0. Each
participant was given 30 tablets, one to be taken daily for
30 days. This iron supplementation was administered
based on WHO guidelines. The first group received
Iron Fumarate-Folic Acid supplement that contains the
elemental iron equivalent of 30 mg and 400 µg of folic
acid. On the other hand, the second group received
Iron Gluconate-Multivitamins supplement contains the
4
basic iron equivalent of 0.9 mg, 500 µg of folic acid, and
multivitamins, such as 15 mg vitamin B1 HCl, 0.25 mg
vitamin B2, 0.25 mg vitamin B6 HCl, 12.5 mg vitamin C,
1.5 mg calcium pantothenate, 10 mg nicotinamide, 0.5 mg
folic acid, 0.65 mg cupric sulfate, and 100 mg of dried beef
liver (7,8). There are 69 and 41 participants in the first and
second groups, respectively.
Data Collection
Surveys on demographic characteristics, including age,
ethnicity, education level, living conditions, the habit of
chewing betel nuts, and health status, were also conducted
on all participants before the iron supplementation
intervention. Bodyweight was measured during the
interview, and chronic energy deficiency (CED) was
calculated based on the Food and Agriculture Organization
protocols using the respondents’ mid-upper arm
circumference. When the mid-upper arm circumference
was <23.5 cm, the participant was categorized as having a
CED condition (9).
Iron Supplementation Intervention and Hemoglobin
Measurement
This study used two types of iron supplementation as
the intervention, which are Fe fumarate-folic acid and Fe
gluconate-multivitamins (Livron), both produced by PT
Rajawali Nusantara Indonesia, Indonesia. The hemoglobin
level was assessed onsite by utilizing the HemoCue
analyzer (HemoCue 201™, Angelholm, Sweden), as the
manufacturer instructed. An amount of 10 μL of blood
was collected from the participant’s finger and applied to
the portable HemoCue hemoglobin analyzer. The results
were obtained immediately using the cyanmethemoglobin
principle, and the instrument was ready to be used for
subsequent measurements. (3,10).
Outcome Measurement
In this study, two main outcomes were measured: the
level of hemoglobin and participants’ adherence. Factors
associated with successful therapy for anemia were
regarded as the secondary outcome. One day after the
supplementation period, all participants were followed up
with another hemoglobin measurement and a follow-up
questionnaire regarding their adherence and knowledge
of anemia. The adherence level was assessed using the
Medication Adherence Rating Scale (MARS) (11), using
a validated Indonesian translation, and shown to be valid
and reliable after initially testing 30 local respondents
in Teluk Bintuni Regency. The results show that the
questionnaire was valid with a Pearson product-moment
correlation and reliable with a moderate Cronbach’s alpha
value of 0.659 (moderate range value of 0.50 < α < 0.70) (12,
13). Furthermore, the adherence level was also measured
using the pill counting method, which is commonly used
to analyze the adherence level of participants with oral
medication over a long period of time. If <20% of the total
International Journal of Women’s Health and Reproduction Sciences, Vol. 11, No. 1, January 2023
Rakanita et al
30 tablets were found to be remaining (unconsumed), the
participants were considered to adhere to the program
(14). The knowledge of anemia was measured using the
open questionnaires developed by Dinga (15).
Statistical Analysis
Participant characteristics and outcome measures
were reported using descriptive statistics. Participants’
characteristic data were presented in percentages, while
the hemoglobin level and adherence score were presented
in means. Fisher exact test, Pearson χ² test, and Wilcoxon
test were utilized to assess the associations of univariate
variables with the binary outcomes. A P value of less than
0.05 was determined as the level of statistical significance.
Statistical Package for the Social Sciences (SPSS) version
25 was used to conduct all statistical analyses (IBM Corp.,
Armonk, NY, USA).
Results
Sociodemographic Characteristics and Hemoglobin
Levels
We used the minimum standard cutoff of 2.00 g/dL to
include the successful category of iron supplementation
intervention in a 1-month durational study. A total of 467
of the 875 initial participants (53.3%) were found to have
anemia, whereas 110 of them (12.6%) were identified as
having moderate or severe anemia and were recruited for
the month-long iron supplementation study. A complete
flowchart representing participant recruitment can be
seen in Figure 1. Of the 110 participants enrolled in the
iron supplementation program, 62% were young women
aged 15-20 years; 66% were of Papuan ethnicity; 48% were
junior high school graduates; 64% lived in rural areas;
and 58% had the habit of chewing betel nuts. The mean
bodyweight of the participants was 50.32 ± 9.66 kg, 74% of
whom had no CED. The complete sociodemographic and
anthropometric data can be seen in Table 1. After 30 days
of iron supplementation, the mean hemoglobin level was
found to have increased from 9.12 ± 1.70 g/dL to 10.15 ±
1.65 g/dL (Table 2).
Adherence to Iron Supplementation Program
The MARS questionnaires and pill counting used to
measure adherence suggested relatively similar results.
The MARS measurements indicated that 76% of the
participants were taking the supplements with good
adherence. In contrast, pill counting measurements
suggested that 66% of the participants had less than
six tablets remaining (Table 1). More than half of the
participants showed high adherence to taking iron
supplements every day according to the dosage and usage
instructions for 30 days. However, there was a significant
difference between hemoglobin levels and the participants’
adherence to the MARS and pill counting methods before
and after supplementation (Table 3). Only 21 participants
(19.1%) had a successful outcome of more than or equal to
a 2 g/dL increase in hemoglobin levels, while 80.9% of the
remaining 89 participants had less than a 2 g/dL increase
(Table 4).
Knowledge of Anemia
Participants gave correct answers to questions on the
definition, causes, and effects or symptoms of anemia with
percentages of 38%, 39%, and 39%, respectively (Table 1),
which means that only a few have sufficient knowledge
about anemia. Poor knowledge contributes to the
inhibition of iron absorption caused by factors that cannot
be controlled by supplementation alone; only 19.1% of 110
participants achieved the targeted hemoglobin levels.
Contributing Factors to The Outcome of Iron
Supplementation
Twelve factors were analyzed for their relation to the
success of iron supplementation therapy for anemia
(Table 4). The type of supplements showed a significant
association with the successful intervention (P = 0.015).
875 WRA included in
the initial study
408 Non-anemic WRA
467 anemic WRA
245 Mild anemic WRA
222 moderate to severe
anemic WRA
110 Anemic WRA
participated to 30 days of iron supplementation program
21 (19.1%) Anemic WRA with Change of
Hb ≥ 2 g/dL
37 excluded due to receiving
other supplementation program
and 75 excluded due to
incomplete data
89 (80.95%) Anemic WRA with Change of
Hb < 2 g/dL
Figure 1. The Study CONSORT Flowchart. Abbreviation: WRA, woman reproductive age.
International Journal of Women’s Health and Reproduction Sciences, Vol. 11, No. 1, January 2023
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Rakanita et al
Table 1. Sociodemographic Characteristics of the Study Participants
Parameters
Number
Percent
68
10
10
9
7
5
1
62
9
9
8
6
5
1
37
73
34
66
6
26
53
20
5
5
24
48
18
5
70
40
64
36
64
46
58
42
29
81
26
74
37
73
34
66
26
84
24
76
69
41
63
37
68
42
62
38
67
43
61
39
67
43
61
39
Age group (y)
15–20
21–25
26–30
31–35
36–40
41–45
46–49
Ethnicity
Non-Papuan
Papuan
Education level
No education
Elementary school
Junior high school
Senior high school
University
Residence
Rural
Urban
Betel nut habit
Yes
No
Chronic energy deficiency
Yes
No
Adherence by pill counting
Low adherence
High adherence
Adherence by MARS
Low adherence
High adherence
Type of Iron Supplements
Iron fumarate-folic acid
Iron gluconate-multivitamins
Knowledge of anemia definition
Poor
Good
Knowledge of the causes of anemia
Poor
Good
Knowledge of the effects of anemia
Poor
Good
Discussion
In Teluk Bintuni Regency, although the maternal mortality
rate has decreased since 2018, anemia (moderate to
severe) in WRA remains very high. In our study, of 110
subjects with moderate and severe anemia, 62% were
teenagers aged 15-20 years, and 48% were still active
in high school education. Adolescence is an important
period because there is increased growth of muscle mass
and the development of reproductive organ function,
thus, requiring more blood volume. The red blood cells
contain hemoglobin, which requires more heme iron.
However, teenagers were unnoticed by parents as they
continued to consume monotonous diets (16). This
situation was further worsened by the betel nut chewing
habit in the West Papua Province. In our study, 58% of
the participants with moderate and severe anemia turned
out to have this lifestyle. One of these betel nuts chewing
ingredients is calcium powder made from a seashell. As
calcium may inhibit iron absorption (17), this habit may
worsen anemia (18).
Various factors can cause anemia. According to some
studies, infection, pregnancy, malnutrition, inflammation,
neoplasia, chronic blood loss, iron malabsorption,
irregular eating habits, and low socioeconomic status
could contribute to anemia. However, the cause of anemia
in this study population is still poorly investigated by
the authorities in the Teluk Bintuni Regency. Most
individuals in developing countries develop anemia due
to malnutrition, parasitic infection, chronic disease, or
hemoglobinopathies. Meanwhile, anemia in developed
countries may be attributed to gastrointestinal and
genitourinary disorders and iron malabsorption (19, 20).
The findings of this study indicate that school-aged girls
are more likely than other age groups to have moderate or
severe anemia. Moreover, young women are susceptible to
anemia due to increased activities and blood loss during
menstruation.
Furthermore, other factors associated with anemia are
the consumption of safe drinking water, sanitation, and
hygiene (21). Health and water facilities are commonly
MARS: Medication Adherence Rating Scale.
Table 2. Hemoglobin Levels Before and After Iron Supplementation Program
Times
Hemoglobin (Hb) Level (g/dL)
Range
95% CI
P Valuea
Before supplementation treatment
After supplementation treatment
9.12±1.70
10.15 ± 1.65
3.10-10.90
5.20-14.10
8.79-9.44
9.83-10.46
<0.001
a
Data presented as mean ± standard deviation (SD); Wilcoxon test.
Table 3. Comparison Between Adherence and Hemoglobin Levels Before and After Supplementation
Level of Adherence
MARS
Low (n=26)
High (n=84)
Pill counting
Low (n=37)
High (n=73)
Hemoglobin Level (g/dL)
After
8.96 ± 1.41
9.16 ± 1.78
9.89 ± 1.90
10.23 ±1.57
0.008
<0.001
9.14 ± 1.44
9.10 ± 1.83
10.02 ± 1.86
10.21 ± 1.55
<0.001
<0.001
MARS: Medication Adherence Rating Scale. Data presented as mean ± standard deviation (SD); a Wilcoxon test.
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P Valuea
Before
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Rakanita et al
Table 4. Univariate Associations With the Successful Therapy of Anemia
Characteristic
Successful Treatment
Yes (n=21)
No (n=89)
15–20
13 (61.9)
55(61.8)
21–25
1 (4.8)
9 (10.1)
26–30
2 (9.5)
8 (9.0)
31–35
1 (4.8)
8 (9.0)
36–40
3 (14.3)
4 (4.5)
41–45
1 (4.8)
4 (4.5)
46–49
0
1 (1.1)
P Value
Age (y)
0.728a
Ethnicity
Non-Papuan
4 (19.0)
33(37.1)
Papuan
17 (81.0)
56(62.9)
No Education
1 (4.8)
5 (5.6)
Elementary School
3 (14.3)
23 (25.8)
Junior high School
12 (57.1)
41(46.1)
0.116b
Education level
Senior High School
4 (19.0)
16 (18.0)
University
1 (4.8)
4 (4.5)
Rural
15 (71.4)
55 (61.8)
Urban
6 (28.6)
34 (38.2)
0.860a
Residence
0.409b
Betel nut habit
Yes
14 (66.7)
50 (56.2)
No
7 (33.3)
39 (43.8)
0.381b
Chronic energy deficiency
Yes
5 (23.8)
24 (27.0)
No
16 (76.2)
65 (73.0)
0.768b
Adherence by pill counting
Low Adherence
4 (19.0)
33 (37.1)
High Adherence
17 (81.0)
56 (62.9)
0.116b
Adherence by MARS
Low Adherence
7 (33.3)
19 (21.3)
High Adherence
14 (66.7)
70 (78.7)
0.245b
Type of iron supplements
IF-FA
18 (85.7)
51 (57.3)
IG-MV
3 (14.3)
38 (42.7)
Poor
14 (66.7)
54 (60.7)
Good
7 (33.3)
35 (39.3)
0.015b
Knowledge of Anemia Definition
0.611b
Knowledge of the causes of anemia
Poor
12 (57.1)
55 (61.8)
Good
9 (42.9)
34 (38.2)
Poor
16 (76.2)
72 (80.9)
Good
5 (23.8)
17 (19.1)
0.694b
Knowledge of the effects of anemia
0.628b
MARS: Medication Adherence Rating Scale.
Data presented as No. (%).a Fisher-exact test; b Pearson χ² test.
well maintained in high-income countries’ countryside
and city areas (21,22). Interestingly, calcium hydroxide
powder and betel nuts used to make the traditional
Papuan chewing gum may contribute to iron deficiency.
This traditional chewing gum is widely consumed in
Papua by people of all ages, including children and the
elderly. Calcium inhibits the absorption of iron particles
dissolved in the blood vessels, which are required to form
erythrocytes that supply nutrients to cells (23,24).
The surveys on the knowledge of anemia suggested
that more than half of the participants have a poor
understanding of what anemia is, what may cause anemia,
and what may be affected by anemia (Table 1). In a previous
study conducted in Tehran, a linear correlation between
knowledge, attitude, and practice was discovered among
women with anemia, implying that insufficient knowledge
about anemia will affect the outcome of therapy (25). This
lack of knowledge may affect WRAs who have never been
pregnant. As countries focus on prenatal health to reduce
maternal and child mortality (26), there has been a lack of
education and awareness about anemia in non-pregnant
women. Furthermore, pregnant women who have
experienced pregnancy have better knowledge of anemia
due to frequent visits to primary health care facilities to
learn about health education, including knowledge about
anemia (26, 27). Therefore, women who have never been
pregnant have insufficient knowledge of anemia (28, 29).
Although the study participants have poor knowledge
of anemia, their adherence to iron supplementation
remains high. Our findings were consistent with a study
conducted in Denmark (30), where pregnant women
adhere to iron supplementation at a high rate. Meanwhile,
a study in Brazil showed that pregnant women with lower
education and low economic status have low adherence to
iron supplementation, which amounts to only 35% of the
prescribed iron supplementation (31). High compliance
with iron supplementation therapy and good knowledge
of anemia do not guarantee an increase in hemoglobin
levels, as many biological conditions of participants with
anemia are contraindicated with iron supplementation
therapy (32-34). For example, when the body is in an
infected state, it will worsen in the presence of iron;
pathogens in the body will stimulate the plasma cell
protector to increase resistance in the presence of iron
(35-37). Another example of contraindication is when
the participant’s hepcidin levels are high, which decreases
the absorption of iron in the intestine (38, 39). Therefore,
despite the increase in compliance, the next dose of iron
is ineffective because the body will not absorb it. Iron
supplementation also causes a significant increase in
gastrointestinal adverse effects, such as irritable bowel
disease and constipation (40).
The high compliance to supplementation in the current
study may also be due to the Hawthorne effect caused by
participants’ behavioral changes due to their awareness
of being investigated (41). However, conventional
therapeutic options, such as ferrous sulfate, a type of oral
iron supplementation, are economical and simple despite
the taste and adverse effects (gastrointestinal intolerance).
Only a few studies have examined the outcome of iron
supplementation therapy using biological changes, such
as the increase in hemoglobin in red blood cells, as the
cellular target of the treatment.
In the current study, a 1-month iron supplementation
program with a minimum escalation in hemoglobin
contents of 2.00 g/dL was considered successful (42).
International Journal of Women’s Health and Reproduction Sciences, Vol. 11, No. 1, January 2023
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Rakanita et al
When hemoglobin levels do not rise as expected and
iron supplementation is continued, participants with
anemia may be at an elevated risk of an oxidation reaction
attributed to the prevalence of non-transferrin-bound
iron that may act as free radicals in the body (43-45).
Furthermore, there is also an enhanced risk of infection
due to the pathogenicity of microorganisms in the presence
of free iron (46). Therefore, in an iron supplementation
program, the hemoglobin levels of participants should
be monitored to evaluate whether the supplementation
should be continued or stopped to begin the search for
any underlying causes of anemia, such as pregnancy,
infections, cancer, and hemoglobinopathy (47-49).
Additionally, several factors besides adherence indicate
a health intervention’s success, particularly in the case of
iron supplementation. Our study discovered that a month
of iron supplementation could achieve the treatment
goal in women with moderate and severe anemia. The
WHO recommends at least three months of daily iron
supplementation in areas with a high burden on public
health (prevalence of anemia >40%). Additionally, an
effective strategy should increase public awareness of
anemia, enabling the public to ensure adequate nutrient
intake to maintain bioavailable iron levels and boost
factors such as vitamin C.
Limitations
This study has some limitations. First, the overall prediction
presented in the model was quite low, suggesting other
factors that have not been investigated may have affected
the success of the iron supplementation therapy. Second,
as we cannot consistently monitor the participants, we
may have overestimated the participants’ adherence,
especially in the pill counting method. There is always
a possibility that the participants did not report all the
remaining tablets due to the Hawthorne effect. This study
cannot obtain the relative change in hemoglobin levels
because there were only two hemoglobin measurements
(day 0 and day 30).
Moreover, we did not measure the iron levels due
to limited access to laboratory facilities in that area.
Lastly, we only included six districts in this study due
to geographical challenges and the lack of initial data
available from all districts in the Teluk Bintuni Regency.
Thus, the generalizability of these findings for the entirety
of the Teluk Bintuni Regency population is restrained.
However, the six districts selected already represent the
differences in economics, education, and latitude level in
the Teluk Bintuni Regency.
Conclusions
In summary, this study found that ethnicity, adherence
to MARS and pill counting methods, and the type of
supplementation used were correlated with the success of
iron supplementation therapy. The current study found a
high prevalence of anemia (53.3%) in the WRA population,
8
with 12.6% having moderate or severe anemia. While iron
supplementation continues to be the first line of defense
against anemia in many countries, its implementation
should be closely monitored. It is not solely dependent
on the participants’ compliance with supplementation,
and ineffective supplementation may also result in other
undesirable conditions.
Authors’ Contribution
RA, EWS, AAS, and MRAAS participated in the study design. YR
contributed to data collection, evaluation, and drafting. RKS and
SDA performed data analysis and draft revision. RA has responsibility
approval the final manuscript. All authors agreed to the final version of
the manuscript and all aspects of the work.
Conflict of Interests
Authors declare that they have no conflict of interests.
Ethical Issues
This study was approved by the Health Research Ethics Committee of
Universitas Padjadjaran, Jatinangor, Indonesia (identifier: 172/UN6.
KEP/EC/2018). Then, this study was registered in the ISRCTN registry
(identifier: ISRCTN96148278). All participants have given informed
consent.
Financial Support
This research was supported by grants-in-aid from Universitas
Padjadjaran, Jatinangor, Indonesia for RKS and Teluk Bintuni Hospital for
EWS. YR received Doctoral Scholarship Program from The Indonesian
Ministry for Research, Technology, and Higher Education.
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