(P11-054-23) Plasma Proteomic Indicators of Iron and Hemoglobin Status in Early Pregnancy Among Women of Rural Bangladesh

Objectives: Accurately assessing iron deficiency and anemia requires multiple analytes, including hemoglobin (Hb) in whole blood and, at minimum, serum or plasma ferritin. Other biomarkers—including soluble transferrin receptor, erythropoietin, hepcidin, and inflammatory markers—aid interpretation of iron status and reflect iron metabolism. We used proteomics to determine if Hb, ferritin and hepcidin, assessed by conventional methods in pregnant Bangladeshi women, could be modeled by plasma proteins and anemia prevalence predicted.

Methods: In archived plasma from n=435 women < 12 weeks’ gestation, Hb had been assessed at point of contact (Hemocue) and plasma ferritin and hepcidin by immunoassay. Proteomics using a multiplexed slow-off rate aptamer assay (SomaLogic Inc.) revealed relative abundance of 6,380 unique plasma proteins. Simple linear regression identified proteins related to Hb, ferritin, and hepcidin with a false discovery rate (q) < 0.10. Forward stepwise regression of the top 100 proteins associated with Hb, ferritin and hepcidin was used to model biomarker distributions, and anemia was predicted from modeled Hb. Of note, this area of Bangladesh is iron-replete.

Results: Measured Hb, ferritin and hepcidin were (mean ± SD) 117±10 g/L, 74±49 µg/L, and 14.6±10.0 µg/L, respectively. Anemia (Hb < 110 g/L) occurred in 21.2% of women, with moderate-severe (Hb < 90 g/L) in < 1%; 3.9% were iron deficient (ferritin < 15 µg/L). Protein covariates that entered the Hb model, maintaining an Akaike Information Criteria decrement >15, were insulin-like binding protein-2, transferrin receptor protein 1, chloride intracellular channel protein 2, erythropoietin, and thyroxine-binding globulin (R²=0.32). Mean Hb was accurately predicted as 117 g/L, but a narrower distribution (SD=6 g/L) led to an underestimated anemia prevalence of 11.5%. For ferritin (R²=0.92) and hepcidin (R²=0.65) there was strong agreement between conventional and aptamer-based measurements.

Conclusions: Given iron-related proteins predicting Hb and strong agreement between ferritin and hepcidin immunoassay and aptamer methods, potential exists to develop a single multiplexed assay to assess Hb and iron status in populations. However, further work is needed to accurately predict anemia prevalence.

Funding Sources: Johns Hopkins Bloomberg School of Public Health