Maternal anemia and risk of adverse birth and health outcomes
in low- and middle-income countries: systematic review and
meta-analysis1,2
Md Mizanur Rahman,3,4* Sarah Krull Abe,3 Md Shafiur Rahman,3 Mikiko Kanda,3 Saki Narita,3 Ver Bilano,3 Erika Ota,5
Stuart Gilmour,3 and Kenji Shibuya3
3
Department of Global Health Policy, The University of Tokyo, Tokyo, Japan; 4Department of Population Science and Human Resource Development,
University of Rajshahi, Rajshahi, Bangladesh; and 5Department of Health Policy, National Centre for Child Health and Development, Tokyo, Japan
ABSTRACT
Background: Anemia is a leading cause of maternal deaths and
adverse pregnancy outcomes in developing countries.
Objectives: We conducted a systematic review and meta-analysis to
estimate the pooled prevalence of anemia, the association between
maternal anemia and pregnancy outcomes, and the population-
attributable fraction (PAF) of these outcomes that are due to anemia
in low- and middle-income countries.
Design: PubMed, EMBASE, CINAHL, and the British Nursing In-
dex were searched from inception to May 2015 to identify cohort
studies of the association between maternal anemia and pregnancy
outcomes. The anemic group was defined as having hemoglobin
concentrations ,10 or ,11 g/dL or hematocrit values ,33% or
,34% depending on the study. A metaregression and stratified
analysis were performed to assess the effects of study and partici-
pant characteristics on adverse pregnancy risk. The pooled preva-
lence of anemia in pregnant women by region and country-income
category was calculated with the use of a random-effects meta-
analysis.
Results: Of 8182 articles reviewed, 29 studies were included in the
systematic review, and 26 studies were included in the meta-analysis.
Overall, 42.7% (95% CI: 37.0%, 48.4%) of women experienced
anemia during pregnancy in low- and middle-income countries.
There were significantly higher risks of low birth weight (RR:
1.31; 95% CI: 1.13, 1.51), preterm birth (RR: 1.63; 95% CI: 1.33,
2.01), perinatal mortality (RR: 1.51; 95% CI: 1.30, 1.76), and neo-
natal mortality (RR: 2.72; 95% CI: 1.19, 6.25) in pregnant women
with anemia. South Asian, African, and low-income countries had
a higher pooled anemia prevalence than did other Asian and upper-
middle-income countries. Overall, in low- and middle-income coun-
tries, 12% of low birth weight, 19% of preterm births, and 18% of
perinatal mortality were attributable to maternal anemia. The pro-
portion of adverse pregnancy outcomes attributable to anemia was
higher in low-income countries and in the South Asian region.
Conclusion: Maternal anemia remains a significant health problem
in low- and middle-income countries. Am J Clin Nutr doi:
10.3945/ajcn.115.107896.
Keywords: birth and health outcomes, low- and middle-income
countries, maternal anemia, meta-analysis, population-attributable
fraction
Am J Clin Nutr doi: 10.3945/ajcn.115.107896. Printed in USA. Ó 2016 American Society for Nutrition
INTRODUCTION
Anemia remains a significant health problem globally, ac-
counting for 60,534 deaths and 3.4% of global disability-adjusted
life years (DALYs) in 2010 in women aged 15–49 y (1). The
majority of DALYs that are due to anemia occur in low-income
countries, particularly in South Asia (5.7% of DALYs in women)
and Sub-Saharan Africa (3.9% of DALYs in women) (1). In high-
income countries, 16% of women and 22% of pregnant women
had anemia in 2011 (2). Rates of anemia are highest in low-
income countries, especially in Central and West Africa (48%
of reproductive-age women and 56% of pregnant women) and
in South Asia (47% of reproductive-age women and 52% of
pregnant women) (2).
Despite achievements in maternal and child health-related
programs over the past decade (3–6), anemia remains a key
health problem in pregnant women in low- and middle-income
countries (2, 7, 8). The principal causes of anemia are poor
nutrition (iron, folic acid, and vitamin deficiencies), infectious
diseases such as malaria, and untreated genetic hemoglobin
disorders (7–12). Anemia during pregnancy may cause low birth
weight, preterm birth, and perinatal, neonatal and maternal
mortality (13, 14), although findings on these risks have not been
consistent, and systematic reviews are lacking for low- and
middle-income countries. In the most-comprehensive review
currently available, Haider et al. (13) compared risk of low birth
weight and preterm birth in low- or middle-income countries
combined with high-income countries. However, the review did
not stratify results by country-income categories or regions for
1
Supported in part by the Japan Ministry of Health, Labour and Wel-
fare (grant H25-chikyukibo-ippan-007), the Japan Agency for Medical Re-
search and Development, Japan (grant 27300101), and the WHO (grant
HQHWA1208014).
2
Supplemental Protocol, Supplemental Figures 1–8, and Supplemental
Tables 1–10 are available from the “Online Supporting Material” link in
the online posting of the article and from the same link in the online table
of contents at http://ajcn.nutrition.org.
*To whom correspondence should be addressed. E-mail: mizanur_rub@
yahoo.com.
Received January 27, 2015. Accepted for publication November 30, 2015.
doi: 10.3945/ajcn.115.107896.
1 of 10
2 of 10 RAHMAN ET AL.
small-for-gestational-age and preterm births. Previous meta-
analyses have not comprehensively studied the association be-
tween maternal anemia and adverse pregnancy outcomes by
both geographic region and national income category despite the
wide variation in anemia burden within and between regions and
national income categories (1, 2). To our knowledge, no pre-
vious study has estimated the population-attributable fraction
(PAF) of adverse pregnancy outcomes for maternal anemia. An
understanding of these outcomes, the current trends in maternal
anemia, and the association of maternal anemia with adverse
pregnancy outcomes at the regional level and stratified by in-
come is essential to inform policies and program development to
prevent maternal anemia and improve maternal and child health
outcomes.
In this study, we aimed to conduct a systematic review with
a meta-analysis of published cohort studies of low birth weight,
preterm birth, small for gestational age, perinatal mortality,
neonatal mortality, gestational diabetes, preeclampsia, and mode
of delivery according to maternal anemia status in low- and
middle-income countries. To assess the role of maternal anemia
at the population level, we estimated the PAF for selected adverse
pregnancy outcomes for maternal anemia. In addition, we esti-
mated the pooled prevalence of maternal anemia by geographic
region, national income category, and year with the use of
available Demographic and Health Survey data.
METHODS
Search strategy
This review was undertaken according to the protocol estab-
lished in the Meta-analysis of Observational Studies in Epide-
miology (MOOSE) guidelines (15). With the help of a librarian,
we searched PubMed, EMBASE, CINAHL, and British Nursing
Index databases (Supplemental Tables 1–4) for studies con-
cerning maternal anemia and risk of pregnancy and maternal
and newborn health outcomes published between 1966 and
February 2014 initially and updated in May 2015. Our search
strategies consisted of a combination of free-text words, words
in titles and abstracts, and Medical Subject Headings for ex-
posure, participants, and study designs. The detailed search
strategies and initial and updated search results for PubMed,
EMBASE, CINAHL, and the British Nursing Index are pre-
sented in Supplemental Tables 1–4. Additional eligible studies
on anemia and birth or health outcomes were sought by re-
viewing the reference lists of identified articles and searching
relevant journals related to our search topic. We did not apply
any language restrictions during the search. We defined low-
and middle-income countries according to World Bank criteria
in 2013 (16).
Study selection
In the screening and article selection, we followed the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
flowchart (17). Two reviewers (MMR and MSR) independently
screened titles and abstracts and critically reviewed the full
texts of all selected studies on the basis of the inclusion and
exclusion criteria. Studies were included if they were cohorts
(prospective or retrospective) with pregnant women aged $15 y
as subjects. We included studies that examined maternal he-
moglobin, hematocrit, or anemia status measured in the first or
second trimester during pregnancy and pregnancy and perinatal
outcomes. Anemia was defined as the exposure variable with
hemoglobin concentrations ,11 g/dL or hematocrit ,33% (18).
We included studies that reported any hemoglobin or hematocrit
cutoffs. Birth and health outcomes including preterm delivery
(defined as a birth before 37 wk of gestation), low birth weight
(defined as weight ,2500 g), small for gestational age (defined
as birth weight below the sex-specific 10th percentile of the
gestational age), perinatal mortality [defined as deaths including
death of a fetus .22 wk of gestation (stillbirth)], early neonatal
mortality (,7 d of life), neonatal mortality (defined as death of
a neonate in the first month of life), gestational diabetes, pre-
eclampsia, and cesarean delivery were included in our studies.
We excluded cross-sectional and case-control studies because
these trials do not allow for the assessment of the temporal as-
sociation between exposure and outcome. Studies that considered
high-risk subjects with HIV, AIDS, heart disease, or diabetes at
baseline were not included in our review. A small sample size
may introduce bias in the estimation of an effect size; therefore,
we excluded studies if they recruited ,100 subjects (19). Details
of the inclusion and exclusion criteria and definitions of expo-
sure and outcomes variables are presented in the Supplemental
Protocol.
Data extraction and quality assessment
Two authors (MMR and MSR) independently extracted data
on the country and year of the study, the study design, partici-
pants, exposures, the time of exposure assessment, outcomes,
confounders, and measures of an association. We did not find any
foreign-language articles that needed to be translated into English.
We resolved any inconsistency through a consensus process. We
used a specific checklist to assess the methodologic quality of all
included cohort studies with the use of the Newcastle–Ottawa
Scale recommended by Wells et al. (20).
Data analyses
RR was used as the common outcome measure in observa-
tional studies. We converted ORs into RRs according to the
proposed methodology of Zhang (21, 22) when the incidence of
an outcome was common (.10%) in the study population. If the
RR or OR was unavailable, we estimated the unadjusted RR and
95% CI from raw data. We used fixed-effect (Mantel-Haenszel
method) (23) or random-effect (DerSimonian-Laird method)
(24) models for calculating summary estimates for the effects of
maternal anemia with the model choice made on the basis of
heterogeneity (I2 statistic) assessments. An I2 value refers to the
percentage of total variation across studies that was due to be-
tween-study heterogeneity. Fixed-effects models were performed
for I2 #25%, and random-effects models were performed for
I2 .25% (25). Prediction intervals were estimated on the basis of
t when the random model was used because of the presence of
heterogeneity and a minimum of 3 studies. We presented sum-
mary estimates according to WHO thresholds for anemia and
according to the definitions used in the original studies sepa-
rately. Publication bias and biases related to a small sample size
and reporting bias were assessed with the use of the regression
 MATERNAL ANEMIA AND PREGNANCY OUTCOMES
asymmetry test of Egger (26). In addition, we performed trim-
and-fill procedures to further evaluate possible effects of pub-
lication bias in the meta-analyses (27).
We investigated sources of heterogeneity through subgroup
and metaregression analyses (28) according to the study design
(prospective compared with retrospective), sample size above
or below the median observed sample size (#800 compared
with .800), confounding factors (adjusted compared with un-
adjusted), country-income category, study location (South Asia
(Bangladesh, India, Nepal, Pakistan, India, and Sri Lanka), East-
West Asia (China, Malaysia, Iran, and Turkey), or Africa and
South America (Malawi, Tanzania, Ghana, and Peru), and mean
maternal age above or below the median from all studies (,26
compared with $26 y).We undertook sensitivity analyses to
determine differences in summary effects by dropping a small
number of studies that we defined as highly influential on the
basis of variance and weight estimates from the meta-analysis.
We calculated the PAF for birth outcomes that were due to
anemia with the use of estimates obtained from the meta-analysis
on the assumption that attributable risk arises from any as-
sociation and not only a causal relation. The PAF was cal-
culated on the basis of the pooled RR of pregnancy outcomes
and the proportion (P) of maternal anemia during pregnancy
as follows:
P ðRR 2 1Þ
PAF ¼ ð1Þ
½1 þ P ðRR 2 1Þ
The pooled prevalence of anemia by region and country-
income level was estimated with the use of a random-effects
meta-analysis and available Demographic and Health Survey data
sets across 23 developing countries. We used the Freeman-Tukey
transformation method to estimate the pooled prevalence of
anemia (29). We used Stata version 12.1/MP software (StataCorp
LP) for all analyses.
RESULTS
Our search identified 8182 records from inception to May 2015
of which 7987 records remained after the removal of duplicates
(Figure 1). On the basis of title and abstract screening, 99 re-
cords were considered potentially eligible from databases. An
additional 6 articles were identified from reference lists and
hand searches. In total, 105 full-text articles were reviewed. In
this full-text screening, 74 articles were further excluded be-
cause of small sample sizes (,100 subjects), different study
designs (case-control, cross-sectional, and secondary data anal-
yses), nonresearch materials, hemoglobin measured only at the
third trimester during pregnancy, and high-risk populations,
which left 31 articles (Figure 1). Two articles were based on
overlapping data from the same cohort in China (30, 31). In
addition, 2 articles used the same data source in Pakistan (32,
33). To avoid the duplicate inclusion of data, we merged out-
comes and treated each of these pairs of studies as one study
(which left 29 studies in the systematic review). Of these 29
studies, 3 studies were dropped from the meta-analysis because
the articles did not assess health outcomes according to anemia
thresholds (34–36). This exclusion left 26 studies for the meta-
analysis.
3 of 10
Study characteristics
Of 29 studies, 12 studies were conducted in South Asia, 13
studies were conducted in East-West Asia, and 4 studies were
conducted in the African and South American regions (Sup-
plemental Table 5). Twenty-four articles included prospective
cohorts, and 5 articles were retrospective cohort studies. The
selected studies were published between 1994 and 2014. The
number of subjects per study ranged from 253 to 399,274 with
a total of w0.72 million pregnant women with a mean age that
ranged from 20 to 30 y. In the 29 studies, 18 studies reported
low-birth-weight, 15 studies reported preterm birth, 12 studies
reported perinatal mortality, 5 studies reported small-for-
gestational-age, 3 studies reported gestational diabetes, 4 studies
reported preeclampsia, 2 studies reported neonatal mortality, 2
studies reported cesarean delivery, and one study reported still-
birth outcomes (Supplemental Table 5). All studies were of high
quality (Supplemental Table 6).
Pooled and sensitivity analysis
The pooled RR, publication bias, and trim-and-fill estimates
across all studies are presented in Table 1. Risk of low birth
weight was significantly higher in anemic pregnant women
during the first or second trimester than in the nonanemic group
(RR: 1.31; 95% CI: 1.13, 1.51; I2 = 66%; 17 studies). We
showed significantly greater risk of preterm birth (RR: 1.63;
95% CI: 1.33, 2.01; I2 = 88%; 13 studies), perinatal mortality
(RR: 1.51; 95% CI: 1.30, 1.76; I2 = 0%; 12 studies), and neo-
natal mortality (RR: 2.72; 95% CI: 1.19, 6.25; I2 = 0%; 2
studies) in our study. However, when we calculated 95% pre-
diction intervals, the associations become insignificant between
anemia and risk of low birth weight, preterm birth, and small for
gestational age (Supplemental Figure 1). Anemia during the
first or second trimester was also not significantly associated
with small for gestational age (RR: 0.87; 95% CI: 0.63, 1.20;
I2 = 95%; 5 studies), gestational diabetes (RR: 1.02; 95% CI:
0.86, 1.21; I2 = 20%; 2 studies), preeclampsia (RR: 2.66; 95%
CI: 0.61, 11.52: I2 = not applicable; one study), or cesarean
delivery (RR: 1.68; 95% CI: 0.76, 3.72; I2 = not applicable; one
study). Our narrative review showed mixed results for maternal
anemia and preeclampsia. One study indicated that a hemoglobin
concentration .13.2 g/dL during the first trimester was signifi-
cantly associated with preeclampsia (OR: 1.73; 95% CI: 1.07,
2.81). However, 2 other studies showed that low concentra-
tions of hemoglobin during pregnancy were associated with
preeclampsia (P , 0.01) (Supplemental Table 7) (34, 36). To
account for any form of publication bias, we performed a sen-
sitivity analysis with the use of the trim-and-fill method and
showed a negligible effect on the results from the inclusion of
possible imputed negative or small sample-size studies (Table
1). In the sensitivity analysis, low birth weight, preterm birth,
and perinatal mortality remained risks in anemic women after
highly influential studies were dropped (Supplemental Figures
2–4). In addition, we calculated pooled estimates of birth and
health outcomes according to the definition of anemia on the basis
of individual study definitions of anemia and showed almost
similar results when we considered only WHO thresholds for
anemia (Supplemental Figures 5–7). Furthermore, we calcu-
lated another sensitivity analysis of pregnancy outcomes after
4 of 10 RAHMAN ET AL.

FIGURE 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart for the selection of studies.

dropping studies that reporting ORs, and pooled estimates of
low birth weight, preterm birth, and perinatal mortality showed
similar results to those in the analysis with the OR conversion
(Supplemental Table 8).
Stratified analyses
The study showed moderate heterogeneity in the low-birth-
weight outcome and severe heterogeneity in the preterm birth and
small-for-gestational-age outcomes. To examine these hetero-
geneities, we conducted stratified analyses according to study
designs, sample sizes, confounding adjustments, country-income
categories, study locations, and maternal ages shown in Table 2
and Supplemental Table 9. The RR differed according to the
subgroup analysis by country-income category. Risks of low
birth weight and preterm delivery were substantially higher in
low-income countries than in upper-middle-income countries.
Stratification by geographic region revealed increased risk of
low birth weight and preterm delivery in anemic pregnant
women in South Asia than in East-West Asia and the African
and South American regions. However, the result was not sta-
tistically significant (P . 0.05).
Prevalence of anemia
Figure 2 presents the random-effects estimate for maternal
anemia during pregnancy by country-income category. Preva-
lence was estimated from 28 recent surveys and 25 countries
with a pooled prevalence of 42.7% (95% CI: 37.0%, 48.4%) in
low- and middle-income countries. There were slight differences
 MATERNAL ANEMIA AND PREGNANCY OUTCOMES 5 of 10
TABLE 1
Summary, publication bias, and trim-and-fill estimates
Summary estimates Trim-and-fill estimates1

Studies, Heterogeneity P-bias Missing

Characteristic n RR (95% CI) index test studies, n RR (95% CI)

Low birth weight 17 1.31 (1.13, 1.51)2 65.7 0.03 4 1.18 (1.02, 1.37)
Preterm birth 13 1.63 (1.33, 2.01)2 88.2 0.05 0 1.63 (1.33, 2.01)
Small for gestational age 5 0.87 (0.63, 1.20)2 95.0 0.41 0 0.87 (0.63, 1.20)
Perinatal mortality 12 1.51 (1.30, 1.76)3 0.0 ,0.001 5 1.43 (1.24, 1.65)
Neonatal mortality 2 2.72 (1.19, 6.25)3 0.0 0.72 0 2.72 (1.19, 6.25)
Gestational diabetes 2 1.02 (0.86, 1.21)3 19.8 0.16 0 1.02 (0.86, 1.21)3
Preeclampsia 1 2.66 (0.61, 11.52)4 NA5 NA 0 2.66 (0.61, 11.52)
Cesarean delivery 1 1.68 (0.76, 3.72)4 NA NA 0 1.68 (0.76, 3.72)
1
Trim-and-fill method simulated studies that were likely to be missing from the literature because of publication or
other forms of bias. Trim-and-fill RRs estimate what the pooled RRs would be if the missing studies were included in the
analysis.
2
On the basis of random-effects methods.
3
On the basis of fixed-effects methods.
4
No pooling method was used because there was only a single study.
5
NA, not applicable.

between the pooled prevalence of anemia in pregnant women in
country-income categories. The East-West Asia region displayed
a lower pooled prevalence (39.9%, 95% CI: 27.3%, 53.2%) of
anemia than that of the South Asian region (48.6%; 95% CI:
44.7%, 52.4%) and African and South American regions (43.5%;
95% CI: 36.8%, 50.3%) (Supplemental Figure 8).
Role of anemia
The PAFs for selected adverse pregnancy outcomes that were
attributable to maternal anemia during pregnancy are presented
in Table 3. The prevalence of anemia with data sources used in
the PAF calculations is presented in Supplemental Table 10.
Overall, 12% of low birth weight, 19% of preterm birth, and
18% of perinatal mortality were attributable to maternal anemia
during pregnancy in low- and middle-income countries. There
was a wide difference in the PAF of pregnancy outcomes across
geographic regions and country-income levels. In low-income
countries, 25% of low birth weight, 44% of preterm births, and
21% of perinatal mortality were attributable to anemia during
pregnancy. However, the respective PAFs were substantially
smaller in lower-middle- and upper-middle-income countries.
In low-income and lower-middle-income countries, there was
a relatively higher anemia-attributable proportion of adverse low
birth weight in Pakistan and Bangladesh than in Ghana and
India. The highest anemia-attributable proportion of preterm
birth was observed in Pakistan (54%) and followed by India
(27%) and Iran (18%).
DISCUSSION
To date, most knowledge relating to the birth and health
consequences of maternal anemia has come from cross-sectional,
case-control, and cohort studies. This systematic review and
meta-analysis summarizes these associations by region and
country-income category in low- and middle-income settings
with the use of high-quality cohort studies. This study also as-
sesses the proportion of low birth weight, preterm birth, and
perinatal mortality that were attributable to maternal anemia.
Significant, positive associations were shown between anemia in
the first or second trimester and low birth weight, preterm birth,
and perinatal and neonatal mortality. However, no association
was shown between maternal anemia and risk of small for gesta-
tional age, gestational diabetes, preeclampsia, and cesarean delivery.
Maternal anemia was shown to be associated with a significant
proportion of pregnancy outcomes in low-income countries with this
proportion declining with increasing national income and varying
substantially between countries and geographic regions.
Maternal anemia remains one of the most-serious health
problems in low-income countries despite the high priority of
maternal and child health programs. Our study showed nearly
one-half (42.7%) of pregnant women were anemic in low- and
middle-income countries and the prevalence of anemia varied
by the country economic profile (45.4% in low-income, 39.8%
in lower-middle-income, and 37.1% in upper-middle-income
countries). Our study also identified substantial regional differ-
ences in the prevalence of anemia. Consistent with a recent mul-
ticountry study (2), there was a higher prevalence of maternal
anemia in the South Asian region and African and South American
regions (48.6% and 43.5%, respectively) than in East-West Asia
(39.9%). Our study showed that the prevalence of anemia during
pregnancy has remained almost unchanged in low-income coun-
tries since 2000. The main reason for this stable and high prev-
alence of maternal anemia during pregnancy in low-income
countries, especially in African and Asian regions, may be be-
cause of the high prevalence of malaria and poor nutrition in-
cluding underweight and iron deficiency (10–12, 37).
Consistent with previous studies (13, 38), women with anemia
in the first or second trimester had a significantly greater risk of
low birth weight, preterm birth, and perinatal and neonatal
mortality. Sensitivity analyses confirmed a similar association
after publication bias was accounted for or a small number of
highly influential studies were dropped. In subgroup analyses, we
showed an association between the hemoglobin concentration
and risk of birth and health outcomes in low-income countries
compared with in lower-middle-income or upper-middle-income
countries. We showed substantial heterogeneity in low-birth-
weight, preterm birth, and small-for-gestational-age outcomes.
6 of 10 RAHMAN ET AL.
TABLE 2
Stratified analysis of pooled RRs of low birth weight, small for gestational age, perinatal mortality, and preterm birth for
anemic pregnant women1
P

Characteristic Pooled RR (95% CI) Heterogeneity Metaregression2

Low birth weight

Study design
Prospective 1.41 (1.18, 1.68) ,0.001 0.09
Retrospective 0.95 (0.60, 1.50) 0.03
Confounding factors
Adjusted 1.28 (1.03, 1.59) ,0.001 0.64
Unadjusted 1.34 (1.13, 1.59) 0.17
Country-income category
Low income 1.72 (1.32, 2.25) 0.09 0.05
Lower-middle income 1.12 (0.94, 1.33) 0.12
Upper-middle income 1.27 (0.89, 1.79) 0.02
Geographic region
South Asia 1.36 (1.11, 1.66) ,0.001 0.91
East-West Asia 1.27 (0.89, 1.79) 0.02
Africa and South America 1.32 (0.76, 2.29) NA
Preterm birth
Study design
Prospective 1.94 (1.31, 2.89) ,0.001 0.01
Retrospective 1.18 (1.09, 1.27) 0.24
Confounding factors
Adjusted 1.63 (1.16, 2.31) ,0.001 0.88
Unadjusted 1.70 (1.17, 2.46) ,0.001
Country-income category
Low income 2.73 (1.29, 5.79) ,0.001 0.01
Lower-middle income 1.36 (0.97, 1.91) 0.02
Upper-middle income 1.20 (1.00, 1.44) 0.04
Geographic region
South Asia 2.03 (1.23, 3.36) ,0.001 0.12
East-West Asia 1.20 (1.00, 1.44) 0.04
Africa and South America 1.24 (1.12, 1.37) NA
Small for gestational age
Study design
Prospective 0.95 (0.65, 1.40) 0.73 0.80
Retrospective 0.85 (0.57, 1.25) ,0.001
Confounding factors
Adjusted 1.00 (0.84, 1.19) 0.15 0.01
Unadjusted 0.65 (0.60, 0.72) NA
Geographic region
South Asia 0.84 (0.38, 1.88) NA 0.05
East-West Asia 1.00 (0.82, 1.22) 0.09
Africa and South America 0.65 (0.60, 0.72) NA
Perinatal mortality
Study design
Prospective 1.67 (1.30, 2.14) 0.73 0.34
Retrospective 1.43 (1.18, 1.73) 0.68
Confounding factors
Adjusted 1.72 (1.28, 2.32) 0.79 0.33
Unadjusted 1.45 (1.22, 1.73) 0.64
Country-income category
Low income 1.61 (1.16, 2.23) 0.33 0.75
Lower-middle income 1.44 (1.18, 1.76) 0.87
Upper-middle income 1.63 (1.18, 2.25) 0.79
Geographic region
South Asia 2.05 (1.18, 3.55) 0.75 0.43
East-West Asia 1.63 (1.18, 2.25) 0.79
Africa and South America 1.43 (1.20, 1.72) 0.44
1
NA, not applicable.
2
Metaregression P values represent a test of the entire characteristic.
 MATERNAL ANEMIA AND PREGNANCY OUTCOMES 7 of 10

FIGURE 2 Random-effects meta-analysis pooled prevalence estimates during 2010–2013 by country-income categories. Open diamonds represent
pooled prevalence (95% CIs). Small filled diamonds represent the prevalence for each survey, and black bars denote 95% CIs. ES, prevalence; I^2, percentage
of variation attributable to heterogeneity; n, total number of anemic women during pregnancy; N*, total number of pregnant women.

When the substantial heterogeneity in 95% prediction intervals
was accounted for, the results indicated that the association
between anemia and risks of low birth weight, preterm birth, and
small for gestational age became insignificant. These results do
not necessarily indicate that there is no impact of maternal
anemia on birth outcomes. However, the results do indicate that
there is still substantial uncertainty about the significance of the
association. Our findings expand significantly on the recent meta-
analysis of Haider et al. (13), which collapsed findings across
countries and accessed only limited information on birth out-
comes. We compared risks of preterm birth and low birth weight
separately for low- or middle-income countries rather than con-
ducting a combined comparison against high-income countries. In
addition, we presented information on pregnancy outcomes by
geographic regions and country-income categories in recognition
of the substantially differing patterns of prevalence and birth
outcomes in these country categories. Our study showed a con-
sistent regional variation in risks of low birth weight, preterm birth,
and perinatal mortality. Highest risk of perinatal mortality at-
tributable to maternal anemia was shown in Ghana, Pakistan, India,
and Malawi. Greater risk of low birth weight was also observed in
Pakistan, Bangladesh, and Ghana.
In some low-income and lower-middle-income countries, the
control of infectious diseases such as HIV, AIDS, and malaria has
not yet been achieved, and health-service delivery, access, and
effective coverage and access to affordable care are limited (11,
39–45). In previous studies anemia, malnutrition, and malaria
during pregnancy were shown to be significant risks to both
maternal and neonatal health (2, 8, 11, 37). However, many low-
income countries are facing challenges in implementing im-
munization, malaria control, and nutrition support programs (5,
46, 47). The war in Afghanistan and internal conflict in Pakistan
targeted female health workers, and thus, many parts of these
areas are severely affected by workforce-related barriers to the
8 of 10 RAHMAN ET AL.
TABLE 3
LBW, PTB, and PNM attributed to maternal anemia1
LBW PTB PNM

Country Prevalence, % RR (95% CI) PAF, % RR (95% CI) PAF, % RR (95% CI) PAF, %
2
Overall 42.7 1.31 (1.13, 1.51) 12.1 1.63 (1.33, 2.01) 19.0 1.51 (1.30, 1.76) 17.9
Country-income category2
Low-income 45.4 1.72 (1.32, 2.25) 24.6 2.73 (1.29, 5.79) 44.0 1.60 (1.15, 2.23) 21.4
Lower middle-income 39.8 1.12 (0.94, 1.33) 4.6 1.36 (0.97, 1.91) 12.5 1.44 (1.18, 1.76) 14.9
Upper middle-income 37.1 1.27 (0.89, 1.79) 9.1 1.20 (1.00, 1.44) 4.9 1.63 (1.18, 2.25) 18.9
Region2
South Asia 48.6 1.36 (1.11, 1.66) 14.9 2.03 (1.23, 3.36) 33.4 2.05 (1.18, 3.55) 38.8
East-West Asia 39.9 1.27 (0.89, 1.79) 9.8 1.20 (1.00, 1.44) 5.3 1.63 (1.18, 2.25) 20.1
Africa and South America 43.5 1.32 (0.76, 2.29) 12.5 1.24 (1.12, 1.37) 9.5 1.43 (1.19, 1.72) 15.8
Country specific3
Bangladesh 49.6 1.80 (1.18, 2.27) 28.6 — — — —
Pakistan 40.0 2.10 (1.56, 2.82) 30.6 3.95 (3.04, 5.13) 54.1 2.25 (1.14, 4.44) 42.4
India 59.0 1.13 (0.92, 1.38) 7.1 1.63 (0.88, 3.04) 27.1 1.70 (0.66, 4.38) 29.2
China 28.9 1.15 (0.70, 1.89) 5.5 1.14 (1.01 1.28) 0.9 1.63 (1.18, 2.25) 15.4
Nepal 47.6 1.24 (0.97, 1.58) 10.3 0.93 (0.62, 1.39) 23.5 — —
Iran 14.0 2.00 (1.08, 3.70) 12.3 2.61 (1.33, 5.10) 18.4 — —
Peru 28.8 — — 1.24 (1.12, 1.37) 6.5 1.40 (1.14, 1.73) 10.3
Ghana 70.0 1.32 (0.76, 2.29) 18.3 — — 2.16 (0.74, 6.30) 44.8
Malawi 37.5 — — — — 2.00 (1.12, 3.57) 27.5
Tanzania 52.7 — — — — 1.14 (0.70, 1.87) 6.9
1
LBW, low birth weight; PAF, population-attributable fraction; PNM, perinatal mortality; PTB, preterm birth.
2
Pooled prevalence of anemia by meta-analysis with the use of Demographic and Health Survey most-recent data from 2010 to 2013 (more-detailed
information is shown in Supplemental Table 10 and Supplemental Figure 8).
3
Country-specific prevalence of anemia data were mainly from most-recent Demographic and Health Survey data and other representative data
(Supplemental Table 10).

resolution of their maternal and child health issues (5). Cost is
another barrier to accessing health services in low-income
countries (48, 49), and many poor households may avoid con-
sulting doctors during pregnancy to minimize financial risks
associated with high-treatment costs. Consequently, these women
may be unaware of their nutritional status during pregnancy.
Service delivery, effective coverage, and access and affordable
care during pregnancy can be ensured by introducing universal
health coverage plans (43, 45, 48, 49). For example, in Ghana,
Indonesia, Uganda, and China, after health insurance was in-
troduced, the burden of treatment costs sharply decreased and
access to care increased (48, 50). Ensuring access to compre-
hensive, integrated primary care and maternal and child health
services through better health-financing methods will help to
ensure that women understand their nutritional status and are
able to act earlier in pregnancy to minimize worst risks associated
with maternal anemia.
Our study had several strengths. We used comprehensive
search techniques and validated systematic review methods,
followed a predesigned protocol, and observed the Meta-analysis
of Observational Studies in Epidemiology (15) and Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (17)
guidelines, which strengthened the review quality and conclu-
sions. We investigated the possible association between maternal
anemia and birth and health outcomes by region, country-income
category, and specific countries. In the meta-analysis, appropriate
statistical techniques were used to estimate the pooled preva-
lence, RR, and presence of bias.
Despite these strengths, limitations of this systematic review
and meta-analysis must be considered. We included studies from
low- and middle-income countries, and thus, the results of review
are not applicable to high-income countries. We only included
studies that measured hemoglobin during the first or second
trimester and may have overlooked some studies that addressed
the effect of anemia in the third trimester. However, a recent
meta-analysis suggested that anemia during the third trimester is
not a potential risk factor for adverse birth outcomes, and its
exclusion was unlikely to have biased this review (8). We defined
anemia on the basis of WHO standard thresholds based on he-
moglobin [anemic: ,10–11 g hemoglobin/dL or hematocrit
,30–34%; nonanemic: .11 g hemoglobin/dL) (18), but some
studies did not use these categorizations. Different definitions
and categorizations can lead to variations in RRs or ORs even
within a single data set. However, in our systematic review, al-
most all studies used WHO cutoffs except for 5 studies from
Ghana, Bangladesh, India, China, and Turkey. We performed
a pooled analysis separately in which thresholds proposed by the
WHO and other thresholds according to the definitions of the
original studies. Despite different definitions, there was no sig-
nificant difference in pooled estimates between WHO thresholds
and others. This stable pooled estimate may have been because
only 5 studies used different cutoffs to those recommended by
the WHO. We also had to use estimated RRs for 7 studies that
reported ORs, which were converted to RRs for the meta-analysis.
There was risk that the variance of the derived RRs could have
been underestimated in the proposed conversion methodology
of Zhang (15, 21). However, we performed a sensitivity analysis
that excluded the affected studies and showed negligible effect
on the results. Finally, we did not include gray literature, which
may have contained smaller null-result studies that were not
 MATERNAL ANEMIA AND PREGNANCY OUTCOMES
accepted for publication, but we adjusted for this publication
bias with the use of the trim-and-fill method and showed little
effect on our results from the inclusion of possible imputed
negative studies.
In conclusion, maternal anemia is a risk factor for adverse
birth and perinatal health outcomes in low-and middle-income
countries. Significantly higher risk of low birth weight and pre-
term birth were observed in low-income countries and in South
Asian countries despite the greater priority and larger investment
on maternal and child health programs in recent decades. On the
basis of our review findings, we advocate that greater attention be
placed on the impact of maternal and child health programs on
anemia-related outcomes in low-income countries. With the
management of maternal anemia during pregnancy in low-income
countries, a substantial proportion of anemia-related adverse
pregnancy outcomes could be avoided.
We thank Miwako Segawa for her help with the electronic search strategies
and retrieval of articles.
The authors’ responsibilities were as follows—MMR: contributed to the
statistical analysis, interpretation of the data, and wrote the first draft of the
manuscript; MMR and MSR: performed the literature screening and data
extraction; MMR, SKA, MK, and SN: collaborated on the quality assess-
ment; MMR, EO, and KS: conceived of the study; EO: consulted on the
quality assessment; SKA: collaborated on the writing of the first draft of the
manuscript; SKA and VB: checked for consistency of the study; EO, SG,
and KS: revised the manuscript critically for important intellectual content;
and all authors: reviewed and approved the final manuscript. None of the
authors reported a conflict of interest related to the study.
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