ABSTRACT
Objectives: In the context of malaria and inflammation, the utility of ferritin and soluble transferring receptor (sTfR), as indicators of iron status may be compromised. In this study, we evaluated the effects of correcting for malaria and inflammation on the prevalence of iron deficiency (ID) as estimated by a) ferritin and b) sTfR. Methods: The analyses used baseline data from 1085 children, 4-8 y, who participated in a carotenoid biofortified maize flour trial in rural Zambia. For each biomarker, we compared the prevalence of ID with the prevalence corrected for a) CRP and AGP only; and b) CRP, AGP and concurrent malaria. Inflammation was defined as CRP>5mg/L and/or AGP>1g/L. Malaria was defined by microscopy. Children were first stratified into groups defined by inflammation and malaria status. Correction factors were then generated by dividing the group geometric means by that of the reference group (those free of both malaria and inflammation). Correction factors were applied to each individual concentration to generated corrected concentrations. Results: For ferritin, the unadjusted prevalence of ID (WHO age-specific cut-offs) increased from 7.3% to 9.5% (p<0.01) and 10.3 %( p<0.01), respectively, after correcting for CRP/AGP only, and CRP, AGP and concurrent malaria combined. For sTfR, the unadjusted ID prevalence (cutoff >8.3 mg/l) decreased from 28% to 21% (p<0.01) after correcting CRP/AGP only, and 19% (p<0.01) after correcting for CRP, AGP and concurrent malaria. Conclusions: Our findings highlight the need to account for both malaria and inflammation when interpreting ferritin and sTfr concentrations in malaria endemic regions.
ABSTRACT
Objectives: Pathways by which micronutrients may influence birth size are not well understood. To elucidate these, we assessed markers of placental angiogenesis and fetal growth factors in a substudy of a community-based, double blinded, cluster-randomized trial of maternal multiple micronutrient (MM) supplementation versus iron and folic acid (IFA) in rural Bangladesh. Methods: We collected maternal blood (n=395) at 10 and 32 weeks gestation and cord blood (n=325) at home deliveries, where infant and placental weight were measured. Angiogenic factors assessed in maternal plasma were placental growth factor (PlGF), angiopoietin 2 (Ang-2), vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR-1). Insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) were measured in cord plasma. Results: Mothers had a mean (SD) BMI in early pregnancy of 19.5 (2.5) kg/m2 and infants weighed 2.68 (0.41) kg at birth. Ang-2 at 32 weeks gestation was 3.1 (95% CI: 0.20, 6.0) ng/mL higher in mothers taking MM vs. IFA suggesting improved vascular remodeling. Other angiogenic factors and insulin, IGF-1, and IGFBP-1 did not differ by maternal supplementation, but significant interactions were observed with infant sex and maternal height. For male fetuses, change in VEGF from 10 to 32 weeks was lower by 7.5 (95% CI: -13.3, -1.7) pg/mL for MM vs. IFA groups reflecting improved angiogenesis across pregnancy. Among shorter women (<145 cm), MM increased insulin by 1.8 (95% CI: 1.0, 3.1) μIU/ML indicating improved fetal energy metabolism. Conclusions: MM supplementation has a biologic basis for improving fetal growth beyond improved micronutrient status of the fetus.