Gestational Age- and Altitude-Specific Hemoglobin Thresholds and Candidate Windows for Preterm Birth

Maternal hemoglobin is a clinically accessible biomarker of preterm birth (PTB) risk, but abnormal thresholds are inconsistent and do not account for variation by gestational age or altitude.

To evaluate the association between maternal hemoglobin concentration and PTB across gestational ages and altitudes, including PTB subtype, and to define gestational age-specific, altitude-adapted hemoglobin thresholds and assessment windows.

This multicenter, retrospective cohort study used a multisource database integrating electronic medical records, preconception examination, and geospatial data from 5 medical centers in Yunnan, China, a region with a marked altitudinal gradient, and consecutively included singleton pregnancies delivered between January 1, 2017, and July 31, 2025.

Prepregnancy and prenatal hemoglobin values were assessed. Prenatal measurements were grouped into 2-week intervals (target gestational week ±7 days), with 36 weeks analyzed separately.

Preterm birth was operationally defined as live birth from 28 weeks 0 days through 36 weeks 6 days of gestation.

Of 141 943 singleton live births among women (mean [SD] maternal age, 29.7 [4.6] years), 12 607 (8.88%) were PTBs. Maternal hemoglobin measurement showed a gestational age-dependent U-shaped association with PTB, and thresholds varied across gestation. Compared with the intermediate group, a low hemoglobin concentration measured at 13 weeks (<12.00 g/dL; adjusted odds ratio [AOR], 1.46; 95% CI, 1.17-1.80) was associated with PTB, persisting from 27 weeks onward (<11.00 g/dL; AOR, 1.48; 95% CI, 1.25-1.74). A high hemoglobin concentration from 19 weeks onward was associated with PTB (>13.50 g/dL; AOR, 1.28; 95% CI, 1.04-1.55). At high altitude, thresholds were generally higher, and a low hemoglobin concentration from 21 weeks was persistently associated with PTB. Subtype analyses showed earlier low hemoglobin concentration associations for medically indicated PTB and middle- to late-pregnancy high hemoglobin concentration associations for both subtypes.

In this cohort study, hemoglobin thresholds associated with PTB varied across gestation and were generally higher at high altitude; low- and high-hemoglobin assessment windows differed and varied by altitude. These findings may help refine gestational age- and altitude-specific interpretation of routine hemoglobin measurements and PTB risk assessment, pending external validation.