Maternal Haemoglobin and Haematocrit During Pregnancy and Stillbirth Risk: A Prospective, Population‐Based Birth Cohort Study

BACKGROUND: Maternal anaemia is a public health issue globally, associated with adverse maternal and neonatal outcomes. However, less is known about the effects of high haemoglobin (Hb) and haematocrit (Hct) on the risk of stillbirth. OBJECTIVES: We assessed the dose-response effects of dynamic changes in maternal Hb and Hct across all trimesters on stillbirth risk. METHODS: This study was based on the prospective, longitudinal, population-based China birth cohort study (CBCS) between 2018 and 2022, including 142,715 women with live births or stillbirths delivered at ≥ 20 weeks' gestation. The modified Poisson regression models were used to assess the association between Hb/Hct, haemodilution status across three trimesters and stillbirth. RESULTS: Over a fifth (23.6%) of pregnant women had anaemia at least once during pregnancy. Maternal anaemia increased the risk of stillbirth. The adjusted risk ratio (aRR) for Hb at 70-99 g/L (moderate anaemia) was 2.45, 95% confidence interval (CI) 1.26, 4.76 and aRR for Hct < 33% (anaemia) was 1.63 (95% CI 1.12, 2.38) in the first trimester. Interestingly, a U-shaped association between Hb/Hct and stillbirth was observed, and high Hb/Hct levels in any of the three trimesters were related to increased stillbirth risk. Excessive haemoglobin dilution/haemoglobin concentration across trimesters was also associated with higher stillbirth risk, especially from the first to the second trimesters, with aRRs of 1.86 (95% CI 1.15, 3.01) and 3.34 (95% CI 2.08, 5.37), respectively. CONCLUSIONS: Considering the U-shaped association between Hb/Hct levels and stillbirth, clinical vigilance is necessary at both low- and high-extremes of Hb/Hct and physiological haemodilution metrics in mid-to-late pregnancy for improved pregnancy outcomes.