Gestational stage-specific association of hemoglobin concentration with the risk of preterm birth and small for gestational age

Aim: Accumulating evidence suggests that maternal hemoglobin concentration during pregnancy negatively influences perinatal outcomes, including preterm birth (PTB) and small for gestational age (SGA). This study aimed to determine gestational stage-specific reference ranges of hemoglobin in a recent Japanese population and clarify the impact of maternal peripheral hemoglobin concentration on pregnancy outcomes according to gestational stage. Methods: Clinical data on hemoglobin concentration at four gestational stages were collected from the perinatal records of women who delivered at two perinatal centers between 2009 and 2018 (n = 10,535). Statistical analyses were performed to evaluate the association of hemoglobin concentration with perinatal outcomes, focusing on gestational stage-specific characteristics. Results: Fifty percentile values of hemoglobin among women in normal pregnancy at 8-12 weeks of gestation (WG), 18-26 WG, 28-32 WG, and 34-28 WG were 12.6, 11.4, 11.1, and 11.3 g/dl, respectively. The incidence of PTB was significantly higher among women with low hemoglobin concentrations than those with hemoglobin concentrations within the reference range. This association was more pronounced in the later stages of gestation. Women with higher hemoglobin concentrations in the third trimester had an increased risk of SGA. Conclusions: The impact of hemoglobin concentration on the risk of PTB and SGA varied by gestational stage. The influence of gestational age on hemoglobin measurements should be considered for precise evaluation of the association of maternal hemoglobin concentration with pregnancy complications.