Hemoglobin concentration in early pregnancy and severe neonatal morbidity and mortality: population-based cohort study

Background — Anemia affects up to 50% of pregnancies. The relation between early pregnancy maternal hemoglobin concentration and important perinatal outcomes in high-income countries is largely unknown.

Objective — To assess early pregnancy hemoglobin concentration and associated severe neonatal morbidity and mortality (SNM-M) in a high-income setting.

Design — Population-based, retrospective cohort study.

Setting — Ontario, Canada, where health care is publicly funded.

Participants — Women aged 18 to 50 years with a singleton birth between 2007 and 2023 and hemoglobin measurement at 2 to 12 weeks’ gestation.

Measurements — The nonlinear relation between early pregnancy hemoglobin concentration and SNM-M was analyzed in 1-g/L increments using restricted cubic splines, with 125 g/L as the referent. The primary outcome was a validated composite measure of SNM-M (major neonatal conditions and critical interventions) up to 27 days after birth. Relative risks (RRs) were adjusted (aRR) for maternal demographic characteristics and chronic conditions.

Results — A total of 1 100 341 births were included. A U-shaped relation was observed between early pregnancy hemoglobin concentration and SNM-M. For example, relative to a hemoglobin value of 125 g/L and a corresponding SNM-M rate of 6.7%, the aRR for SNM-M was 1.08 (95% CI, 1.04 to 1.11) at a hemoglobin concentration of 105 g/L and 1.17 (CI, 1.10 to 1.25) at 90 g/L. The aRR for SNM-M was 1.05 (CI, 1.03 to 1.07) at a hemoglobin concentration of 135 g/L and 1.20 (CI, 1.16 to 1.24) at 150 g/L.

Limitation — Iron replacement status before and during pregnancy was unknown, and residual confounding may influence observed associations.

Conclusion — Maternal anemia and relative erythrocytosis were each associated with neonatal morbidity and mortality in a high-income setting. Randomized clinical trials should evaluate the effect of iron therapy on maternal and perinatal outcomes by degree of hemoglobin correction.