Severity of maternal anemia and the risk of giving birth to a small vulnerable newborn: A cohort analysis of the WOMAN-2 trial in four countries.

Objective

To investigate the association between maternal hemoglobin concentration and the risk of birth to a small vulnerable newborn (SVN).

Methods

We conducted a cohort analysis of women with moderate or severe anemia enrolled in the World Maternal Antifibrinolytic Trial-2 (WOMAN-2) across Nigeria, Pakistan, Tanzania, and Zambia (August 2019 to September 2023). Maternal hemoglobin concentration at admission for vaginal birth was categorized into six groups (<50, 50-59, 60-69, 70-79, 80-89, and 90-99 g/L). The primary outcome was SVN, defined as a liveborn or stillborn preterm (<37 weeks), low birthweight (<2500 g), or small for gestational age (birth weight below the average [unsexed] 10th-centile INTERGROWTH-21st standard for gestational age). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs), controlling for potential confounders.

Results

Among 14 444 women, the median hemoglobin level was 85 g/L (interquartile range [IQR] 77-91 g/L), and 39.5% (5703/14444) of newborns were classified as SVNs. A strong inverse relationship was observed between maternal hemoglobin and SVN. Compared with women with hemoglobin of 90-99 g/L, aOR values for SVN were 1.06 (95% CI 0.97-1.16) for 80-89 g/L; 1.27 (95% CI 1.15-1.41) for 70-79 g/L; 1.44 (95% CI 1.26-1.64) for 60-69 g/L; 2.00 (95% CI 1.64-2.43) for 50-59 g/L; and 2.51 (95% CI 1.85-3.41) for <50 g/L. Sensitivity analysis, including multiple pregnancies, yielded similar results.

Conclusions

Increasing severity of maternal anemia is associated with a marked increase in the risk of giving birth to SVNs. The disproportionately higher risk observed at lower hemoglobin levels supports prioritization of women with more severe anemia for intensified monitoring and treatment in high-burden settings.