Maternal anemia and high hemoglobin concentrations and association with adverse maternal and infant health outcomes: an updated global systematic review and meta-analysis

Abstract

AbstractBackground Growing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment. Methods We conducted an updated systematic review (using PubMed and Cochrane Review) on the association between anemia (< 110 g/L) and high (≥ 130 g/L) maternal Hb concentrations at different stages of gestation (preconception; first, second, and third trimesters), as well as at any time point in pregnancy, and a range of maternal and infant health outcomes. We examined different cutoffs for defining anemia and high hemoglobin concentrations and performed stratified analyses by iron-deficiency anemia. We conducted a meta-analysis to obtain odds ratios, (OR), 95% confidence intervals. Results The updated systematic review included 148 studies. Anemia at any timepoint in pregnancy was associated with: low birthweight, LBW (OR (95% CI) 1.28 (1.22–1.35)), very low birthweight, VLBW (2.15 (1.47–3.13)), preterm birth, PTB (1.35 (1.29–1.42)), small-for-gestational age, SGA (1.11 (1.02–1.19)), stillbirth 1.43 (1.24–1.65)), perinatal mortality (1.75 (1.28–2.39)), neonatal mortality (1.25 (1.16–1.34), postpartum hemorrhage (1.69 (1.45–1.97)), transfusion (3.68 (2.58–5.26)), pre-eclampsia (1.57 (1.23–2.01)), and prenatal depression (1.44 (1.24–1.68)). For maternal mortality, the OR was higher when anemia was defined as Hb < 90 (4.83 (2.17–10.74)) compared with Hb < 100 (2.87 (1.08–7.67)). High maternal Hb was associated with: VLBW (1.35 (1.16–1.57)), PTB (1.12 (1.00-1.25)), SGA (1.17 (1.09–1.25)), stillbirth (1.32 (1.09–1.60)), maternal mortality (2.01 (1.12–3.61)), gestational diabetes (1.71 (1.19–2.46)), and pre-eclampsia (1.34 (1.16–1.56)). Stronger associations were noted earlier in pregnancy for anemia and adverse birth outcomes while the role of timing of high Hb was inconsistent. For anemia, lower cutoffs were associated with greater odds of poor outcomes; for high Hb, data were too limited to identify patterns. Information on anemia etiology was limited; relationships did not vary by iron-deficiency anemia. Conclusions Both anemia and high maternal Hb concentrations during pregnancy are strong predictors of adverse maternal and infant health outcomes. Additional research is need to establish healthy reference ranges and design effective interventions to optimize maternal Hb during pregnancy.