Adverse maternal and neonatal outcomes associated with hemoglobin concentration in pregnancy: a Burden of Proof study

Abstract This is the first study to evaluate dose-response relationships between hemoglobin concentration in pregnancy and maternal and neonatal outcomes based on comprehensive systematic reviews using the Burden of Proof meta-analytic framework. Risk estimates that appropriately account for uncertainty and quantitative star ratings were generated to assess the strength of evidence. Our analysis revealed that even small deviations from optimal hemoglobin levels—particularly on the low end (i.e., anemia)—are associated with non-linear increased risks of all-cause maternal and neonatal mortality, postpartum hemorrhage, maternal sepsis, preterm birth, low birthweight, and large-for-gestational-age. Across outcomes, maternal hemoglobin levels associated with the lowest risk ranged from 109–135 g/L, challenging the appropriateness of fixed anemia thresholds. Even modest population-level shifts in hemoglobin distributions could meaningfully affect the burden of adverse outcomes, implicitly supporting development of more refined, trimester- and outcome-specific clinical thresholds to better identify at-risk individuals and guide evidence-based maternal health policy. Evidence strength ratings further clarify which associations are robust and which require further research.