Hepcidin Screening to Guide Iron Supplementation in African Children.

Objectives: Hematologic and non-hematologic benefits from iron supplementation are chiefly seen in iron deficient individuals; concerns that iron might promote infection especially in non-iron deficient individuals have complicated global anemia control policies, particularly in malaria-endemic settings. Iron homeostasis, including intestinal absorption, is controlled by hepcidin. Hepcidin is regulated by iron, erythropoietic drive, and inflammation, suggesting its potential utility to appraise iron status and thus guide iron supplementation. Methods: In 1338 African pre-school children we evaluated the Area Under the ROC Curve (AUCROC) for plasma hepcidin concentration as a diagnostic test of iron status, anemia type and erythrocyte incorporation of oral iron, determining and modeling the effects of cutoffs. Results: Hepcidin detected iron deficiency with an AUCROC = 0.85 (optimal sensitivity/ specificity at a cutoff of 5.5 ng/ml); this was not significantly affected by gender, wasting, malaria or carriage of inherited red cell disorders. In anemic children, hepcidin distinguished iron deficiency anemia from anemia of inflammation (AUCROC=0.89, optimal sensitivity/specificity cutoff 5.4 ng/ml). Hepcidin was the best predictor for >20% incorporation into erythrocytes of orally-administered 57Fe (AUCROC=0.90, optimal sensitivity/ specificity cutoff <6.9 ng/ml). If a hepcidin cutoff of 5.5 ng/ml had been used to guide iron supplementation in this population, 77% of iron deficient children would have received supplements while 80% of children with P. falciparum and 86% of children with anemia of inflammation would have avoided iron. Conclusions: In African children, hepcidin ascertains iron status, distinguishes iron deficiency anemia from anemia of inflammation, and hence could guide iron supplementation toward groups in whom it will likely be beneficial and safe.

Effect of Provitamin A-biofortified Cassava on Vitamin A Status of Kenyan Children: A Randomised Controlled Trial.

Objectives: To measure the effect of daily consumption of provitamin A-biofortified cassava on vitamin A status in children aged 5-13 years. Methods: Mild-to-moderate vitamin A deficient children (n=342) were randomly allocated to groups receiving: 1) 375 g of white cassava and placebo supplement; 2) 375 g of white cassava and a supplement of β-carotene (1,054 μg); 3) 375 g of biofortified cassava and placebo supplement. Children received the intervention 6 days/week for 18.5 weeks. Field staff and participants were blinded to supplementation. Cooked cassava was mashed with salt and 4 g of oil per portion. Biofortified cassava supplied 208 μg RAE, which is ~50% of the age-specific estimated average requirement for vitamin A for children. The primary endpoint was serum retinol concentration and secondary endpoint was serum β-carotene concentration, both at end of intervention; in the analysis, we adjusted for sex and serum concentrations at baseline of retinol, C-reactive protein and α1-acid-glycoprotein. Results: Complete data were collected for 337 children. Compliance to cassava feeding was similar between treatment groups. Preliminary results showed that consumption of biofortified cassava and β-carotene supplementation resulted in a similar increase in retinol concentrations (for both interventions, mean: 0.81 μmol/L versus 0.77 μmol/L; difference, 95% CI: 0.04 μmol/L, 0.00─0.07 μmol/L) but in a different increase in serum β-carotene concentration (for β-carotene supplement group, mean: 0.25 μmol/L (95% CI: 0.17─0.33), for biofortified cassava group, mean: 0.81 μmol/L (95% CI: 0.73-0.88)) Conclusions: Provitamin A-biofortified cassava improves the vitamin A status of primary school children in Kenya.

Safety and Efficacy of Antenatal Iron Supplementation in a Malaria-endemic Area in Kenya: A Randomised Trial.

Objectives: Whereas coverage of antenatal iron supplementation is low and benefits are uncertain, there are concerns that it can increase the burden of malaria, with potentially devastating effects on maternal and neonatal health outcomes. We aimed to measure the effect of iron supplementation during pregnancy on maternal Plasmodium infection assessed at delivery, birth weight, gestational age, fetal growth and maternal and infant iron status. Methods: Rural Kenyan women (n=470) with singleton pregnancies, gestational age 13─23 weeks and haemoglobin concentration ≥ 90 g/L were randomised to supervised daily supplementation with iron (60 mg as ferrous fumarate) or placebo until 1 month postpartum. To prevent severe anaemia, all women additionally received 5.7 mg iron/day through flour fortification. Intermittent preventive treatment against malaria was given as usual. Plasmodium infection was assessed at birth by dipstick tests, PCR and histological examination of placental biopsies. Results: There was no evident effect on Plasmodium infection (both intervention groups: 45%; difference, 95% CI: 0%, ─9% to 9%). Iron supplementation increased birth weight by 143g (95% CI: 58─228g) and reduced the prevalence of low birth weight (<2,500g) by 65% (95% CI: 13%─86%). The effect on birth weight was larger in women who were initially iron-deficient than in those who were iron-replete (250 g versus ─13 g; p-interaction=0.008), and the improved birth weight seemed achieved mostly through improved fetal growth. Iron supplementation resulted in improved maternal iron status at 1 month postpartum, and improved infant iron stores. Conclusions: Coverage of universal antenatal iron supplementation must be increased.

Proxy Markers of Serum Retinol Concentration, Used Alone and in Combination, to Assess Population Vitamin A Status in Kenyan Children.

Objectives: To assess the diagnostic performance of serum concentrations of retinol-binding protein (RBP), transthyretin, retinol concentration measured by fluorometry and RBP:transthyretin molar ratio, either alone or in combination, to estimate the prevalence of vitamin A deficiency (serum retinol concentration <0.70 μmol/L measured by high-performance liquid chromatography(HPLC)). Methods: A cross-sectional study was conducted in 15 primary schools in Kibwezi and Makindu districts in Eastern province, Kenya in June 2010 with 375 schoolchildren (6-12 years), 25 randomly selected from each school by lot quality assurance sampling. Results: Complete data were collected for 372 children. Mean serum concentration of retinol (HPLC), RBP and transthyretin were 0.87 (SD 0.19) µmol/L, 0.67 (SD 0.17) µmol/L and 3.0 (SD 0.62) µmol/L. The mean RBP: Transthyretin molar ratio was 0.23. The prevalence of vitamin A deficiency measured with HPLC was 18%. Transthyretin and RBP showed the largest area under the curve (AUCs 0.96 and 0.93, respectively). Logistic regression resulted in a model predicting vitamin A deficiency based on RBP, transthyretin and C-reactive protein (AUC: 0.98) and prevalence depending cutpoints for the linear predictor were calculated. Conclusions: Combination of transthyretin, RBP and C-reactive protein in a linear predictor showed excellent diagnostic performance in assessing vitamin A status, and has great potential to eventually replace serum retinol concentration measured by HPLC as the preferred method to assess the population burden of vitamin A deficiency. Further research is needed to confirm whether this linear predictor yields similar results in different populations and laboratories. Our methodology can be widely applied for other diagnostic aims.