Hemoglobin Concentration in Early Pregnancy and Severe Neonatal Morbidity and Mortality : A 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.

PRIMARY FUNDING SOURCE: University of Toronto Alexandra Yeo Hematology Grant.