(P07-054-23) A Plasma Cuprome Reveals the Biology and Status of Copper in 1st Trimester Pregnant Women in Rural Bangladesh

Objectives: Copper (Cu) deficiency in pregnancy has been associated with hypochromic anemia, spontaneous delivery, abortion, pre-eclampsia, fetal growth restriction, neurological birth defects and ataxia. However, Cu status is rarely assessed in low income countries due to complexity & cost leaving its prevalence unknown. We explored the presence of protein biomarkers in plasma that could, on a future proteomics assay, predict Cu status.

Methods: We measured copper concentrations by inductively-coupled plasma mass spectrometry in 1^st trimester, baseline plasma samples of 435 Bangladeshi pregnant women participating in a micronutrient supplement trial. We further quantified relative fluorescence of 6431 proteins by a slow-off rate modified aptamer scanning assay (SomaLogic Inc.) and derived Cu-protein Pearson correlation coefficients (r), stringently defining a plasma cuprome as proteins whose r met a false discovery rate (q) < 0.01. The 100 strongest correlates were submitted to forward, stepwise linear regression to predict Cu status, with proteins remaining in the model if the AIC reduction was > 20. Estimated and measured Cu concentrations were compared.

Results: Mean (SD) antenatal plasma Cu was 1168 (303) µg/L, with 32% below 1000 µg/L, a typically low concentration (e.g., < -2SD, < IQR) in a sparse literature. In all, 1764 proteins were in the plasma cuprome: 907 positive correlates (r = 0.15 to 0.63), dominated by proteins involved in immune response, complement activation, coagulation and wound repair and gestation; and, 857 negative correlates (r= -0.23 to -0.64), involved in calcium and zinc ion binding, cellular adhesion and signaling processes, neuronal axon development and guidance, collagen binding, bone mineralization and ossification. Regression analysis identified 8 predictive covariates (CLEC3B, TFF3, CRP, CAMK2N2, NPW, CHL1, CFHR5, CFHR1), explaining 72.1% of the variance (R²) in plasma Cu concentration.  The predicted in-sample mean (SD) Cu concentration was 1163 (252) µg/L, approximating the measured distribution.

Conclusions: A large plasma cuprome exists, as revealed in pregnant Bangladeshi women exhibiting a generally low Cu status, from which 8 provisional proteins were found to predict plasma Cu concentrations.

Funding Sources: Johns Hopkins Bloomberg School of Public Health