Non-linear connections between maternal hemoglobin during the third trimester of pregnancy and birth weight outcomes in full-term newborns: Estimating the breakpoints

OBJECTIVE: Anemia is still an unfinished global health problem, and adverse birth weight outcomes have everlasting influences on the health of later life. However, the non-linear connections and breakpoints of maternal hemoglobin with birth weight outcomes are still needed to be further elucidated. We aimed to reveal the non-linear connections between maternal hemoglobin during the third trimester of pregnancy and birth weight, low birth weight (LBW), macrosomia, small for gestational age (SGA), and large for gestational age (LGA) in full-term newborns and elucidate the breakpoints of the connections. METHODS: A total of 11,411 singletons, full-term, and live newborns, whose mothers conducted the examination of hemoglobin concentration before delivery, were included in this study. A generalized additive model was used to identify and visualize the non-linear connections between maternal hemoglobin and birth weight outcomes. Piecewise linear regression model was adopted to estimate the breakpoints of the connections and report the non-linear connections in detail. RESULTS: There were inverted “U”-shaped exposure–response connections between maternal hemoglobin concentration and birth weight and the risk of macrosomia. There was an increasing trend of the risk of LBW and a decreased trend of LGA with the increase in maternal hemoglobin concentration. The breakpoints of maternal hemoglobin for birth weight were 100 and 138 g/L, and those for SGA were 97 and 138 g/L. The breakpoints of maternal hemoglobin were 119 g/L for LBW, 105 g/L for macrosomia, and 106 g/L for LGA. When maternal hemoglobin concentration ranged from 100 to 138 g/L, maternal hemoglobin concentration increased per 1 g/L, and birth weight significantly decreased by 2.58 g (95% CI: –3.33, –1.83). When maternal hemoglobin concentration ranged from 97 to 138 g/L, maternal hemoglobin concentration increased per 1 g/L, and the risk of SGA significantly increased by 2% (95% CI: 1%, 3%). When maternal hemoglobin concentration was equal to or lower than 119 g/L, maternal hemoglobin concentration increased per 1 g/L, and the risk of LBW significantly increased by 3% (95% CI: 0%, 5%). When maternal hemoglobin concentration was higher than the breakpoints, the risks of macrosomia (OR = 0.99, 95% CI: 0.98, 0.99) and LGA (OR = 0.99, 95% CI: 0.98, 1.00) declined as the increase of maternal hemoglobin concentration. CONCLUSIONS: There were non-linear connections between maternal hemoglobin and birth weight outcomes, and there are breakpoints in the connections. Cost-effective interventions targeting pregnant women in the prevention of abnormal maternal hemoglobin concentration should be taken to reduce the incidence of adverse birth weight outcomes.