ObjectivesMaternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin thresholds that predict health risk or protection for mother and child. Our objective was to conduct a systematic review and meta-analysis to examine the associations of maternal hemoglobin concentrations with a range of maternal and infant health outcomes, accounting for timing of measurement (preconception, first, second and third trimesters), etiology of anemia and cut-off category. MethodsOur search strategy identified 7,677 articles. Screening and article selection was conducted using Covidence systematic review software to organize search results from PubMed and Cochrane Review. The systematic review included 272 studies and the meta-analysis included 102 studies. ResultsLow maternal hemoglobin (< 110 g/L) was associated with poor birth outcomes (low birth weight, OR (95%CI): 1.43 (1.31-1.55); preterm birth, 1.35 (1.25-1.46); small-for-gestational age, 1.08 (1.00-1.18); stillbirth, 1.43 (1.05-1.95); perinatal mortality, 1.73 (1.32-2.26); and neonatal mortality, 1.49 (1.19-1.87); and adverse maternal outcomes (post-partum hemorrhage, 2.17 (1.51-3.10); preeclampsia, 1.84 (1.31-2.59); and blood-transfusion, 6.57 (3.59-12.00). High maternal hemoglobin (> 130 g/L) was associated with increased odds of small-for-gestational age, 1.22 (1.08-1.37); stillbirth, 1.88 (1.21-2.91); preeclampsia, 1.48 (1.10-2.01); and gestational diabetes, 2.02 (1.63-2.50). Relationships varied by timing of measurement and cut-off category; limited data were available on anemia etiology. There were insufficient data for other maternal outcomes and long-term child health outcomes. ConclusionsCurrent data are insufficient for determining if revisions to current hemoglobin cut-offs are required. Pooled high-quality individual-level data analyses as well as prospective cohort studies that measure hemoglobin throughout pregnancy would be valuable to inform the re-evaluation of hemoglobin cut-offs. Funding SourcesThis work was commissioned and financially supported by the Evidence and Programme Guidance Unit, Department of Nutrition for Health and Development of the World Health Organization (WHO), Geneva, Switzerland.
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