Association of maternal longitudinal haemoglobin concentrations with adverse pregnancy outcomes: A prospective cohort study

Background: Maternal haemoglobin (Hb) is a potential biomarker of maternal and neonatal health. Little is known about trimester-specific associations between maternal Hb concentrations and adverse pregnancy outcomes. Here, we assessed the magnitude and shape of these associations and further estimated developmental trajectories of maternal Hb concentrations during pregnancy. Methods: In this prospective, observational cohort study, we enrolled pregnant women at 11-13 weeks of gestation from 13 hospitals of northern China between October 2020 and June 2024. We classified maternal Hb concentrations in the first, second, and third trimester (i.e. 11-13, 24-27, and 36-40 weeks' gestation, respectively) into three groups: <110 g/L, 110-129 g/L, and ≥130 g/L, respectively. We used logistic regression models, restricted cubic spline analysis, and group-based trajectory models to examine the association between maternal Hb concentrations and pregnancy outcomes. Results: Among 10 201 participants, maternal Hb concentrations of ≥130 g/L in the first, second, and third trimester were associated with increased odds of gestational diabetes mellitus and hypertension in pregnancy. Maternal Hb concentrations of <110 g/L in the second trimester were associated with higher odds of postpartum haemorrhage (odds ratio (OR) = 1.38; 95% confidence interval (CI) = 1.04-1.83). Maternal Hb concentrations of ≥130 g/L in the third trimester were associated with higher odds of small-for-gestational-age (OR = 1.48; 95% CI = 1.23-1.79) and low birth weight (OR = 1.55; 95% CI = 1.11-2.16). We further identified a U-shaped relationship between maternal Hb concentrations in the third trimester and small-for-gestational age (P-value for nonlinearity = 0.002). Lastly, high Hb trajectories during pregnancy were associated with higher odds of caesarean delivery (OR = 1.21; 95% CI = 1.10, 1.34), small-for-gestational age (OR = 1.41; 95% CI = 1.16, 1.72) and low birth weight (OR = 1.46; 95% CI = 1.03, 2.05). Conclusions: Both higher and lower maternal Hb concentrations were associated with higher odds of adverse pregnancy outcomes. Our findings emphasise the importance of longitudinal monitoring of maternal Hb concentrations throughout pregnancy. Registration: ClinicalTrials.gov: NCT04486456.