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Maternal anemia and risk of adverse birth and health outcomes

in low- and middle-income countries: systematic review and

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
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

Background: Anemia is a leading cause of maternal deaths and Anemia remains a significant health problem globally, ac-
adverse pregnancy outcomes in developing countries.

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counting for 60,534 deaths and 3.4% of global disability-adjusted
Objectives: We conducted a systematic review and meta-analysis to life years (DALYs) in 2010 in women aged 15–49 y (1). The
estimate the pooled prevalence of anemia, the association between majority of DALYs that are due to anemia occur in low-income
maternal anemia and pregnancy outcomes, and the population- countries, particularly in South Asia (5.7% of DALYs in women)
attributable fraction (PAF) of these outcomes that are due to anemia and Sub-Saharan Africa (3.9% of DALYs in women) (1). In high-
in low- and middle-income countries.
income countries, 16% of women and 22% of pregnant women
Design: PubMed, EMBASE, CINAHL, and the British Nursing In-
had anemia in 2011 (2). Rates of anemia are highest in low-
dex were searched from inception to May 2015 to identify cohort
income countries, especially in Central and West Africa (48%
studies of the association between maternal anemia and pregnancy
of reproductive-age women and 56% of pregnant women) and
outcomes. The anemic group was defined as having hemoglobin
in South Asia (47% of reproductive-age women and 52% of
concentrations ,10 or ,11 g/dL or hematocrit values ,33% or
pregnant women) (2).
,34% depending on the study. A metaregression and stratified
Despite achievements in maternal and child health-related
analysis were performed to assess the effects of study and partici-
pant characteristics on adverse pregnancy risk. The pooled preva-
programs over the past decade (3–6), anemia remains a key
lence of anemia in pregnant women by region and country-income health problem in pregnant women in low- and middle-income
category was calculated with the use of a random-effects meta- countries (2, 7, 8). The principal causes of anemia are poor
analysis. nutrition (iron, folic acid, and vitamin deficiencies), infectious
Results: Of 8182 articles reviewed, 29 studies were included in the diseases such as malaria, and untreated genetic hemoglobin
systematic review, and 26 studies were included in the meta-analysis. disorders (7–12). Anemia during pregnancy may cause low birth
Overall, 42.7% (95% CI: 37.0%, 48.4%) of women experienced weight, preterm birth, and perinatal, neonatal and maternal
anemia during pregnancy in low- and middle-income countries. mortality (13, 14), although findings on these risks have not been
There were significantly higher risks of low birth weight (RR: consistent, and systematic reviews are lacking for low- and
1.31; 95% CI: 1.13, 1.51), preterm birth (RR: 1.63; 95% CI: 1.33, middle-income countries. In the most-comprehensive review
2.01), perinatal mortality (RR: 1.51; 95% CI: 1.30, 1.76), and neo- currently available, Haider et al. (13) compared risk of low birth
natal mortality (RR: 2.72; 95% CI: 1.19, 6.25) in pregnant women weight and preterm birth in low- or middle-income countries
with anemia. South Asian, African, and low-income countries had combined with high-income countries. However, the review did
a higher pooled anemia prevalence than did other Asian and upper- not stratify results by country-income categories or regions for
middle-income countries. Overall, in low- and middle-income coun-
tries, 12% of low birth weight, 19% of preterm births, and 18% of Supported in part by the Japan Ministry of Health, Labour and Wel-
perinatal mortality were attributable to maternal anemia. The pro- fare (grant H25-chikyukibo-ippan-007), the Japan Agency for Medical Re-
portion of adverse pregnancy outcomes attributable to anemia was search and Development, Japan (grant 27300101), and the WHO (grant
higher in low-income countries and in the South Asian region. HQHWA1208014).
Conclusion: Maternal anemia remains a significant health problem Supplemental Protocol, Supplemental Figures 1–8, and Supplemental
Tables 1–10 are available from the “Online Supporting Material” link in
in low- and middle-income countries. Am J Clin Nutr 2016;
the online posting of the article and from the same link in the online table
of contents at
*To whom correspondence should be addressed. E-mail: mizanur_rub@
Keywords: birth and health outcomes, low- and middle-income
countries, maternal anemia, meta-analysis, population-attributable Received January 27, 2015. Accepted for publication November 30, 2015.
fraction First published online January 6, 2016; doi: 10.3945/ajcn.115.107896.

Am J Clin Nutr 2016;103:495–504. Printed in USA. Ó 2016 American Society for Nutrition 495

Supplemental Material can be found at:

small-for-gestational-age and preterm births. Previous meta- as subjects. We included studies that examined maternal he-
analyses have not comprehensively studied the association be- moglobin, hematocrit, or anemia status measured in the first or
tween maternal anemia and adverse pregnancy outcomes by second trimester during pregnancy and pregnancy and perinatal
both geographic region and national income category despite the outcomes. Anemia was defined as the exposure variable with
wide variation in anemia burden within and between regions and hemoglobin concentrations ,11 g/dL or hematocrit ,33% (18).
national income categories (1, 2). To our knowledge, no pre- We included studies that reported any hemoglobin or hematocrit
vious study has estimated the population-attributable fraction cutoffs. Birth and health outcomes including preterm delivery
(PAF) of adverse pregnancy outcomes for maternal anemia. An (defined as a birth before 37 wk of gestation), low birth weight
understanding of these outcomes, the current trends in maternal (defined as weight ,2500 g), small for gestational age (defined
anemia, and the association of maternal anemia with adverse as birth weight below the sex-specific 10th percentile of the
pregnancy outcomes at the regional level and stratified by in- gestational age), perinatal mortality [defined as deaths including
come is essential to inform policies and program development to death of a fetus .22 wk of gestation (stillbirth)], early neonatal
prevent maternal anemia and improve maternal and child health mortality (,7 d of life), neonatal mortality (defined as death of
outcomes. a neonate in the first month of life), gestational diabetes, pre-
In this study, we aimed to conduct a systematic review with eclampsia, and cesarean delivery were included in our studies.
a meta-analysis of published cohort studies of low birth weight, We excluded cross-sectional and case-control studies because
preterm birth, small for gestational age, perinatal mortality, these trials do not allow for the assessment of the temporal as-
neonatal mortality, gestational diabetes, preeclampsia, and mode sociation between exposure and outcome. Studies that considered
of delivery according to maternal anemia status in low- and high-risk subjects with HIV, AIDS, heart disease, or diabetes at
middle-income countries. To assess the role of maternal anemia baseline were not included in our review. A small sample size
at the population level, we estimated the PAF for selected adverse may introduce bias in the estimation of an effect size; therefore,

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pregnancy outcomes for maternal anemia. In addition, we esti- we excluded studies if they recruited ,100 subjects (19). Details
mated the pooled prevalence of maternal anemia by geographic of the inclusion and exclusion criteria and definitions of expo-
region, national income category, and year with the use of sure and outcomes variables are presented in the Supplemental
available Demographic and Health Survey data. Protocol.

METHODS Data extraction and quality assessment

Two authors (MMR and MSR) independently extracted data
Search strategy
on the country and year of the study, the study design, partici-
This review was undertaken according to the protocol estab- pants, exposures, the time of exposure assessment, outcomes,
lished in the Meta-analysis of Observational Studies in Epide- confounders, and measures of an association. We did not find any
miology (MOOSE) guidelines (15). With the help of a librarian, foreign-language articles that needed to be translated into English.
we searched PubMed, EMBASE, CINAHL, and British Nursing We resolved any inconsistency through a consensus process. We
Index databases (Supplemental Tables 1–4) for studies con- used a specific checklist to assess the methodologic quality of all
cerning maternal anemia and risk of pregnancy and maternal included cohort studies with the use of the Newcastle–Ottawa
and newborn health outcomes published between 1966 and Scale recommended by Wells et al. (20).
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- Data analyses
posure, participants, and study designs. The detailed search RR was used as the common outcome measure in observa-
strategies and initial and updated search results for PubMed, tional studies. We converted ORs into RRs according to the
EMBASE, CINAHL, and the British Nursing Index are pre- proposed methodology of Zhang (21, 22) when the incidence of
sented in Supplemental Tables 1–4. Additional eligible studies an outcome was common (.10%) in the study population. If the
on anemia and birth or health outcomes were sought by re- RR or OR was unavailable, we estimated the unadjusted RR and
viewing the reference lists of identified articles and searching 95% CI from raw data. We used fixed-effect (Mantel-Haenszel
relevant journals related to our search topic. We did not apply method) (23) or random-effect (DerSimonian-Laird method)
any language restrictions during the search. We defined low- (24) models for calculating summary estimates for the effects of
and middle-income countries according to World Bank criteria maternal anemia with the model choice made on the basis of
in 2013 (16). 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
Study selection for I2 #25%, and random-effects models were performed for
In the screening and article selection, we followed the Preferred I2 .25% (25). Prediction intervals were estimated on the basis of
Reporting Items for Systematic Reviews and Meta-Analyses t when the random model was used because of the presence of
flowchart (17). Two reviewers (MMR and MSR) independently heterogeneity and a minimum of 3 studies. We presented sum-
screened titles and abstracts and critically reviewed the full mary estimates according to WHO thresholds for anemia and
texts of all selected studies on the basis of the inclusion and according to the definitions used in the original studies sepa-
exclusion criteria. Studies were included if they were cohorts rately. Publication bias and biases related to a small sample size
(prospective or retrospective) with pregnant women aged $15 y and reporting bias were assessed with the use of the regression
asymmetry test of Egger (26). In addition, we performed trim- Study characteristics
and-fill procedures to further evaluate possible effects of pub- Of 29 studies, 12 studies were conducted in South Asia, 13
lication bias in the meta-analyses (27). studies were conducted in East-West Asia, and 4 studies were
We investigated sources of heterogeneity through subgroup conducted in the African and South American regions (Sup-
and metaregression analyses (28) according to the study design plemental Table 5). Twenty-four articles included prospective
(prospective compared with retrospective), sample size above cohorts, and 5 articles were retrospective cohort studies. The
or below the median observed sample size (#800 compared selected studies were published between 1994 and 2014. The
with .800), confounding factors (adjusted compared with un- number of subjects per study ranged from 253 to 399,274 with
adjusted), country-income category, study location (South Asia a total of w0.72 million pregnant women with a mean age that
(Bangladesh, India, Nepal, Pakistan, India, and Sri Lanka), East- ranged from 20 to 30 y. In the 29 studies, 18 studies reported
West Asia (China, Malaysia, Iran, and Turkey), or Africa and low-birth-weight, 15 studies reported preterm birth, 12 studies
South America (Malawi, Tanzania, Ghana, and Peru), and mean reported perinatal mortality, 5 studies reported small-for-
maternal age above or below the median from all studies (,26 gestational-age, 3 studies reported gestational diabetes, 4 studies
compared with $26 y).We undertook sensitivity analyses to reported preeclampsia, 2 studies reported neonatal mortality, 2
determine differences in summary effects by dropping a small studies reported cesarean delivery, and one study reported still-
number of studies that we defined as highly influential on the birth outcomes (Supplemental Table 5). All studies were of high
basis of variance and weight estimates from the meta-analysis. quality (Supplemental Table 6).
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- Pooled and sensitivity analysis

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culated on the basis of the pooled RR of pregnancy outcomes The pooled RR, publication bias, and trim-and-fill estimates
and the proportion (P) of maternal anemia during pregnancy across all studies are presented in Table 1. Risk of low birth
as follows: weight was significantly higher in anemic pregnant women
during the first or second trimester than in the nonanemic group
P ðRR 2 1Þ (RR: 1.31; 95% CI: 1.13, 1.51; I2 = 66%; 17 studies). We
PAF ¼ ð1Þ
½1 þ P ðRR 2 1Þ 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-
The pooled prevalence of anemia by region and country- natal mortality (RR: 2.72; 95% CI: 1.19, 6.25; I2 = 0%; 2
income level was estimated with the use of a random-effects studies) in our study. However, when we calculated 95% pre-
meta-analysis and available Demographic and Health Survey data diction intervals, the associations become insignificant between
sets across 23 developing countries. We used the Freeman-Tukey anemia and risk of low birth weight, preterm birth, and small for
transformation method to estimate the pooled prevalence of gestational age (Supplemental Figure 1). Anemia during the
anemia (29). We used Stata version 12.1/MP software (StataCorp first or second trimester was also not significantly associated
LP) for all analyses. 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%
RESULTS CI: 0.61, 11.52: I2 = not applicable; one study), or cesarean
Our search identified 8182 records from inception to May 2015 delivery (RR: 1.68; 95% CI: 0.76, 3.72; I2 = not applicable; one
of which 7987 records remained after the removal of duplicates study). Our narrative review showed mixed results for maternal
(Figure 1). On the basis of title and abstract screening, 99 re- anemia and preeclampsia. One study indicated that a hemoglobin
cords were considered potentially eligible from databases. An concentration .13.2 g/dL during the first trimester was signifi-
additional 6 articles were identified from reference lists and cantly associated with preeclampsia (OR: 1.73; 95% CI: 1.07,
hand searches. In total, 105 full-text articles were reviewed. In 2.81). However, 2 other studies showed that low concentra-
this full-text screening, 74 articles were further excluded be- tions of hemoglobin during pregnancy were associated with
cause of small sample sizes (,100 subjects), different study preeclampsia (P , 0.01) (Supplemental Table 7) (34, 36). To
designs (case-control, cross-sectional, and secondary data anal- account for any form of publication bias, we performed a sen-
yses), nonresearch materials, hemoglobin measured only at the sitivity analysis with the use of the trim-and-fill method and
third trimester during pregnancy, and high-risk populations, showed a negligible effect on the results from the inclusion of
which left 31 articles (Figure 1). Two articles were based on possible imputed negative or small sample-size studies (Table
overlapping data from the same cohort in China (30, 31). In 1). In the sensitivity analysis, low birth weight, preterm birth,
addition, 2 articles used the same data source in Pakistan (32, and perinatal mortality remained risks in anemic women after
33). To avoid the duplicate inclusion of data, we merged out- highly influential studies were dropped (Supplemental Figures
comes and treated each of these pairs of studies as one study 2–4). In addition, we calculated pooled estimates of birth and
(which left 29 studies in the systematic review). Of these 29 health outcomes according to the definition of anemia on the basis
studies, 3 studies were dropped from the meta-analysis because of individual study definitions of anemia and showed almost
the articles did not assess health outcomes according to anemia similar results when we considered only WHO thresholds for
thresholds (34–36). This exclusion left 26 studies for the meta- anemia (Supplemental Figures 5–7). Furthermore, we calcu-
analysis. lated another sensitivity analysis of pregnancy outcomes after

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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 birth weight and preterm delivery were substantially higher in
low birth weight, preterm birth, and perinatal mortality showed low-income countries than in upper-middle-income countries.
similar results to those in the analysis with the OR conversion Stratification by geographic region revealed increased risk of
(Supplemental Table 8). 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-
Stratified analyses tistically significant (P . 0.05).
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- Prevalence of anemia
geneities, we conducted stratified analyses according to study Figure 2 presents the random-effects estimate for maternal
designs, sample sizes, confounding adjustments, country-income anemia during pregnancy by country-income category. Preva-
categories, study locations, and maternal ages shown in Table 2 lence was estimated from 28 recent surveys and 25 countries
and Supplemental Table 9. The RR differed according to the with a pooled prevalence of 42.7% (95% CI: 37.0%, 48.4%) in
subgroup analysis by country-income category. Risks of low low- and middle-income countries. There were slight differences
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)
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
On the basis of random-effects methods.
On the basis of fixed-effects methods.
No pooling method was used because there was only a single study.
NA, not applicable.

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

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

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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
NA, not applicable.
Metaregression P values represent a test of the entire characteristic.

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

Country Prevalence, % RR (95% CI) PAF, % RR (95% CI) PAF, % RR (95% CI) PAF, %
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
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

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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
LBW, low birth weight; PAF, population-attributable fraction; PNM, perinatal mortality; PTB, preterm birth.
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).
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 low- and middle-income countries, and thus, the results of review
another barrier to accessing health services in low-income are not applicable to high-income countries. We only included
countries (48, 49), and many poor households may avoid con- studies that measured hemoglobin during the first or second
sulting doctors during pregnancy to minimize financial risks trimester and may have overlooked some studies that addressed
associated with high-treatment costs. Consequently, these women the effect of anemia in the third trimester. However, a recent
may be unaware of their nutritional status during pregnancy. meta-analysis suggested that anemia during the third trimester is
Service delivery, effective coverage, and access and affordable not a potential risk factor for adverse birth outcomes, and its
care during pregnancy can be ensured by introducing universal exclusion was unlikely to have biased this review (8). We defined
health coverage plans (43, 45, 48, 49). For example, in Ghana, anemia on the basis of WHO standard thresholds based on he-
Indonesia, Uganda, and China, after health insurance was in- moglobin [anemic: ,10–11 g hemoglobin/dL or hematocrit
troduced, the burden of treatment costs sharply decreased and ,30–34%; nonanemic: .11 g hemoglobin/dL) (18), but some
access to care increased (48, 50). Ensuring access to compre- studies did not use these categorizations. Different definitions
hensive, integrated primary care and maternal and child health and categorizations can lead to variations in RRs or ORs even
services through better health-financing methods will help to within a single data set. However, in our systematic review, al-
ensure that women understand their nutritional status and are most all studies used WHO cutoffs except for 5 studies from
able to act earlier in pregnancy to minimize worst risks associated Ghana, Bangladesh, India, China, and Turkey. We performed
with maternal anemia. a pooled analysis separately in which thresholds proposed by the
Our study had several strengths. We used comprehensive WHO and other thresholds according to the definitions of the
search techniques and validated systematic review methods, original studies. Despite different definitions, there was no sig-
followed a predesigned protocol, and observed the Meta-analysis nificant difference in pooled estimates between WHO thresholds
of Observational Studies in Epidemiology (15) and Preferred and others. This stable pooled estimate may have been because
Reporting Items for Systematic Reviews and Meta-Analyses (17) only 5 studies used different cutoffs to those recommended by
guidelines, which strengthened the review quality and conclu- the WHO. We also had to use estimated RRs for 7 studies that
sions. We investigated the possible association between maternal reported ORs, which were converted to RRs for the meta-analysis.
anemia and birth and health outcomes by region, country-income There was risk that the variance of the derived RRs could have
category, and specific countries. In the meta-analysis, appropriate been underestimated in the proposed conversion methodology
statistical techniques were used to estimate the pooled preva- of Zhang (15, 21). However, we performed a sensitivity analysis
lence, RR, and presence of bias. that excluded the affected studies and showed negligible effect
Despite these strengths, limitations of this systematic review on the results. Finally, we did not include gray literature, which
and meta-analysis must be considered. We included studies from may have contained smaller null-result studies that were not
accepted for publication, but we adjusted for this publication 11. Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B,
bias with the use of the trim-and-fill method and showed little Newman RD. Epidemiology and burden of malaria in pregnancy.
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negative studies. Massougbodji A, Cot M. Maternal anemia in pregnancy: assessing the
In conclusion, maternal anemia is a risk factor for adverse effect of routine preventive measures in a malaria-endemic area. Am J
birth and perinatal health outcomes in low-and middle-income Trop Med Hyg 2013;88:292–300.
13. Haider BA, Olofin I, Wang M, Spiegelman D, Ezzati M, Fawzi WW.
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term birth were observed in low-income countries and in South systematic review and meta-analysis. BMJ 2013;346:f3443.
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placed on the impact of maternal and child health programs on Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of obser-
anemia-related outcomes in low-income countries. With the vational studies in epidemiology: a proposal for reporting. Meta-
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manuscript; MMR and MSR: performed the literature screening and data formation System: haemoglobin concentrations for the diagnosis of
extraction; MMR, SKA, MK, and SN: collaborated on the quality assess- anaemia and assessment of severity [Internet]. WHO reference number:
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