review article hemoglobin concentration and pregnancy ...fetal gender ren et al., [ ] retrospective...

Hindawi Publishing CorporationBioMed Research InternationalVolume 2013, Article ID 769057, 9 pageshttp://dx.doi.org/10.1155/2013/769057

Review ArticleHemoglobin Concentration and Pregnancy Outcomes:A Systematic Review and Meta-Analysis

Bunyarit Sukrat,1,2 Chumpon Wilasrusmee,1,3 Boonying Siribumrungwong,1,4

Mark McEvoy,5 Chusak Okascharoen,6 John Attia,5 and Ammarin Thakkinstian1

1 Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University,Rama VI Road, Rachatevi, Bangkok 10400, Thailand

2 Bureau of Reproductive Health, Department of Health, Ministry of Public Health, Muang, Nontaburi 11000, Thailand3Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Road,Rachatevi, Bangkok 10400, Thailand

4Department of Surgery, Faculty of Medicine,Thammasat Hospital, Thammasat University, Klongluang, Pathumthani 12121,Thailand5 Centre for Clinical Epidemiology and Biostatistics, The University of Newcastle, Newcastle, NSW 2300, Australia6Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Road,Rachatevi, Bangkok 10400, Thailand

Correspondence should be addressed to AmmarinThakkinstian; [email protected]

Received 4 April 2013; Accepted 5 July 2013

Academic Editor: Naveed Janjua

Copyright © 2013 Bunyarit Sukrat et al.This is an open access article distributed under the Creative CommonsAttribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective. To conduct a systematic review and meta-analysis of hemoglobin effect on the pregnancy outcomes. Methods. Wesearched MEDLINE and SCOPUS from January 1, 1990 to April 10, 2011. Observational studies addressing association betweenhemoglobin and adverse pregnancy outcomes were selected. Two reviewers independently extracted data. A mixed logisticregression was applied to assess the effects of hemoglobin on preterm birth, low birth weight, and small for gestational age. Results.Seventeen studies were included in poolings. Hemoglobin below 11 g/dLwas, respectively, 1.10 (95%CI: 1.02–1.19), 1.17 (95%CI: 1.03–1.32), and 1.14 (95% CI: 1.05–1.24) times higher risk of preterm birth, low birth weight, and small for gestational age than normalhemoglobin in the first trimester. In the third trimester, hemoglobin below 11 g/dL was 1.30 (95% CI: 1.08–1.58) times higher riskof low birth weight. Hemoglobin above 14 g/dL in third trimester decreased the risk of preterm term with ORs of 0.50 (95% CI:0.26–0.97), but it might be affected by publication bias. Conclusions. Our review suggests that hemoglobin below 11 g/dl increasesthe risk of preterm birth, low birth weight, and small gestational age in the first trimester and the risk of low birth weight in thethird trimester.

1. Introduction

Anemia has been claimed to be themost common nutritionaldisorder in pregnancy across the world [1, 2]. The worldwideprevalence is estimated at 41.8% (95%CI: 39.9–43.8) [2] and ismore common inAfrican (57.1%, 95%CI: 52.8–61.3) pregnantwomen. The prevalence, however, depends on the definitionof anemia, in which two definitions are commonly used, thatis, the Centers for Disease Control and Prevention (CDC)and the World Health Organization (WHO) definitions [3,4]. Adverse pregnancy outcomes thought to be affectedby anemia include maternal mortality, perinatal mortality,

preterm birth (PTB), low birth weight (LBW), and small forgestational age (SGA). Previous research has demonstrateda strong association between severe anemia and maternalmortality [5], but the risk of maternal mortality in pregnantwomen with moderate anemia (i.e., hemoglobin concentra-tion of 40–80 g/dL) was inconclusive. The impact of anemiaon other adverse pregnancy outcomes (e.g., PTB, LBWand SGA) is controversial. Some studies found significantassociations [6–12], while other studies did not [13–16]; this islikely the result of different studies using different criteria orcutoff thresholds for defining anemia. In another way, somestudies reported the association between high hemoglobin

2 BioMed Research International

concentration and adverse pregnancy outcomes [17, 18].Although a previous systematic review published in 2000[19] reported maternal anemia in early pregnancy (

BioMed Research International 3

Table 1: Characteristics of included studies.

Authors, year(Reference number) Study design

Samplesize Mean age Country Trimester

Pregnancyoutcomes Confounding factors

Abeysena et al., 2010[17]

Prospectivecohort 817 26.4 ± 5.5 Sri Lanka First

PTB, LBW, andSGA Not specify

Kumar et al., 2010[34]

Prospectivecohort 2,027 24.6 ± 3.82 India First LBW

Maternal age, parity,maternal height, maternalweight, BMI, andgestational age

Kidanto et al., 2009[32] Case control 1,721 24

a Tanzania First PTB, LBW, andSB Not specify

Zhang et al., 2009[16]

Prospectivecohort 160,700 NA China

FirstSecondThird

PTB

Maternal age at delivery,education, occupation,parity, folic acid, BMI, timeof first prenatal visit, andfetal gender

Zhang et al., 2009[33]

Prospectivecohort 164,667 NA China

FirstSecondThird

SB, ND

Maternal age at delivery,education, occupation,parity, folic acid, BMI, timeof first prenatal visit, andfetal gender

Ren et al., 2007 [12] Retrospectivecohort 88,149 25.8 ± 2.9 China FirstPTB, LBW, and

SGAMaternal age, gravidity,education, and BMI

Lee et al., 2006 [29] Prospectivecohort 248 30.6 ± 3.35 Korea Third PTB, LBW Not specify

Mamun et al. , 2006[30]

Retrospectivecohort 1,584 22.1 ± 4.3 Bangladesh Second SB, PD Not specify

Monawar Hosainet al., 2006 [31]

Prospectivecohort 350 NA Bangladesh First LBW Not specify

Levy et al., 2005 [11] Retrospectivecohort 153,396 28.3 ± 5.9 Irael FirstPTB, LBW, and

PD

Ethnicity, maternal age,placental problems,caesarean delivery, andnonvertex presentation

Little et al., 2005 [15] Retrospectivecohort 222,614 NA England First STB, ND Prematurity, birth weight

Ronnenberg et al.,2004 [10]

Prospectivecohort 405 24.9 ± 1.5 China First PTB, LBW

Maternal age, height, BMI,education, exposure todust, noise, passivesmoking, work stress,infant gender, andgestational age

Chang et al., 2003[26]

Retrospectivecohort 918 16.1 ± 1.1 USA

SecondThird PTB, LBW

Parity, BMI, smoking,preeclampsia, and antenatalcare

Hämäläinen et al.,2003 [27] Case control 22,799 28.9 ± 5.2 Finland

FirstSecondThird

PTB, LBW,SGA, and PD Not specify

Xiong et al., 2003[28]

Retrospectivecohort 16,936 25.0 ± 2.8 China First

PTB, LBW, andPD

Hospital stay, maternal age,maternal education, parity,gestational age at the firstprenatal visit, BMI,hypertensive disorder inpregnancy, vaginalbleeding, and priorspontaneous abortion

Mart́ı et al., 2001[25] Case control 543 24.1 ± 6.6 Venezuela Third PTB

Placenta abruption, PROM,previous prematurelabor, ANC visit, andantenatal bleeding


Table 1: Continued.

Authors, year(Reference number) Study design

Samplesize Mean age Country Trimester

Pregnancyoutcomes Confounding factors

Zhou et al., 1998 [9] Prospectivecohort 829 25.5 ± 3.8 China FirstPTB, LBW, and

SGA Not specify

Onadeko et al., 1996[24]

Prospectivecohort 4,649 NA Nigeria Third LBW, SB Not specify

Rasmussen andOian, 1993 [18]

Retrospectivecohort 3,074 NA Norway

FirstSecond PTB, SGA Not specify

Knottnerus et al.,1990 [7]

Prospectivecohort 796 27

a Netherland Third PTB, LBW Pregnancy inducedhypertensionaMedian. LBW: low birth weight; NA: not available; ND: neonatal deaths; PD: perinatal deaths; PTB: preterm birth; SGA: small for gestational age; SB: stillbirths.

for title and abstract review

included in systematic review

31 trimester of pregnancy was not defined10 insufficient data for extraction8 hemoglobin concentration was not defined

4 interested factor was not hemoglobin

1 duplicate study

Interested factor was not hemoglobin

Commentary

Preterm birth Low birth weight Small forgestational age Still birthsNeonatalmortality

Perinatalmortality

12 studies

3 studies

7 studies

6 studies

2 studies

2 studies

10 studies

2 studies

6 studies

3 studies

2 studies

2 studies

3 studies

1 study

1 study

3 studies

2 studies

2 studies

3,196 articles identified from database search

Noninterested study design

Noninterested participants

1 noninterested participants

Noninterested outcomes

1 noninterested outcomes

85 articles identified for full review

2,218 potential relevant articles identified

20 articles eligible for inclusion and

1st trimester1st trimester1st trimester1st trimester1st trimester 1st trimester

2nd trimester 2nd trimester 2nd trimester 2nd trimester 2nd trimester 2nd trimester

3rd trimester 3rd trimester3rd trimester3rd trimester3rd trimester3rd trimester

978 excluded (duplicate studies)

2,133 excluded

65 excluded

5 noninterested study design

3 cannot access full paper

1 commentary

1,534 from MEDLINE1,662 from SCOPUS

Figure 1: Flow of study selection.


Pooled odds ratio

95% CIPooled OR

First trimester of pregnancy

OR = 1.37

OR = 1.26

OR = 1.14

OR = 0.97

Small for gestational age

Hem

oglo

bin

cuto

ff (g

/dL)


Table 2: Association between hemoglobin concentration and pregnancy outcomes.

Outcome Trimester Number of studies Number of subjects Hemoglobin cutoff Pooled OR 95% CI 𝐼2 95% CI

Preterm birth

First


OR = 3.41

OR = 2.64

OR = 1.18

OR = 0.50

OR = 3.61

OR = 1.30

OR = 0.59

0.75 1 1.5 2.5 3.5 0.75 1 1.5 2.5 3.5

Preterm birth Low birth weight

Hem

oglo

bin

cuto

ff (g

/dL)

Hem

oglo

bin

cuto

ff (g

/dL)

Third trimester of pregnancy


inflating type one error. Between-study variations were alsotaken into account in the mixed logistic model. A degree ofheterogeneity was also estimated using multivariate meta-analysis method.

There are, however, some limitations and caveats with ourstudy. Because of the varying cutoffs used in different studies,the only way to reasonably pool data was to expand the sum-mary data to individual level data and then pool based oncommon thresholds; thus some subjects were excluded ifstudies used a reference cutoff lower than 11 g/dL. It is alsopossible that our results are confounded by other factors inwhich analysis based on summary data could not adjust for.A meta-analysis of individual patient data should be con-ducted to calibrate hemoglobin cutoff with adjusting for con-founders; that is, anemia is a marker of general poor healthin developing countries but not in developed countries. Ourreview also excluded non-English articles due to limitation intranslation issue.

5. Conclusion

Our review suggests that hemoglobin below 11 g/dL increasesthe risk of LBW in both first and third trimesters, PTB andsmall gestational age in the first trimester. Conversely, hemo-globin 14 g/dL or higher can conversely reduce the risk ofPTB in the third trimester, but the result might be affectedby publication bias.

Conflict of Interests

The authors did not have any potential conflict of interests.

Author Contribution

Bunyarit Sukrat, Ammarin Thakkinstian, and Mark McEvoycontributed to study concept and design. Bunyarit Sukrat,Ammarin Thakkinstian, Chumpon Wilasrusmee, and Boo-nying Siribumrungwong contributed to acquisition of data.Bunyarit Sukrat, AmmarinThakkinstian, and JohnAttia con-tributed to analysis and interpretation of data. BunyaritSukrat andAmmarin.Thakkinstian contributed to drafting ofthe paper. John Attia, Mark McEvoy, and Chusak Okaschar-oen contributed to critical revision of the paper for importantintellectual content. All authors approved the final versionof the paper to be published. AmmarinThakkinstian wasresponsible for the study supervision.

Acknowledgment

This study is a part of Dr. Bunyarit Sukrat’s training in ourPh.D. program for Clinical Epidemiology, Faculty of Medi-cine Ramathibodi Hospital and Faculty of Graduate Studies,Mahidol University, Bangkok, Thailand.

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