Micronutrent status, anemia, morbidity, and effect of lipid-based nutrient supplementation in children with stunting

Abstract

One in three children are stunted in low-income settings. Poor cognitive development, morbidity, and mortality observed in children with stunting under 5 years may in part be due to concurrent micronutrient deficiencies, anemia, or susceptibility to infections. There is need to determine what micronutrient deficiencies exist among children with stunting and whether supplementation with lipid-based nutrient supplements (LNS) can improve their micronutrient status, reduce anemia and vulnerability to infections. This is important in a context of chronic exposure to poor nutrition and repeated infections, which stunting is an indicator of. I aimed to assess the level and correlates of iron, cobalamin, folate and vitamin A status (Paper I), assess micronutrient status and other correlates of hemoglobin (Hb) (Paper II), and assess the effect of LNS on micronutrient status, Hb, morbidity, inflammation and phase angle (PhA) in children with stunting (Paper III and IV). Methods: The PhD studies were part of the MAGNUS trial (ISRCTN 13093195), a community-based, 2x2 factorial, randomized controlled trial among 12-59-month-old children with stunting in eastern Uganda. Markers of micronutrient status i.e. ferritin (S-Fe), soluble transferrin receptors (S-TfR), cobalamin (P-Cob), methylmalonic acid (P-MMA), folate (P-Fol) and retinol binding protein (S-RBP), Hb, markers of inflammation i.e. α1-acid glycoprotein and C-reactive protein, and PhA to reflect cellular mass, hydration and integrity were measured at baseline and week-12. In a cross-sectional study using baseline data, I assessed socio-demography, stunting severity, malaria, and inflammation as correlates of micronutrient status using linear regression. Similarly, I assessed low micronutrient status and other factors correlating with Hb. Lastly, using linear mixed effects models, I analyzed the effect of 12-weeks supplementation with LNS on markers of micronutrient status, Hb, inflammation and PhA by bioimpedance. Additionally, I assessed the effect of LNS on caregiver-reported morbidity after 2, 4, 8, and 12 weeks. Among 750 children with stunting, mean age (SD) was 32 (11.7) months, 55% (n=412) were male and 13% were currently breastfed (n=95). Low iron status: S-Fe (inflammation corrected) <12 µg/L and S-TfR >8.3 mg/L was in 43% (n=318), 62% (n=457) of the children, respectively. Cobalamin was low or marginal (P-Cob <222 pmol/L) in 24% (n=169) of the children, and 21% (n= 158) had low vitamin A status (S-RBP <0.7 µmol/L), 1% (n=8) low folate status (<14 nmol/L) and 62% anemia (Hb <110 g/L). Low status of two or more of the four micronutrients, iron, cobalamin, folate and vitamin A was present in 27% (n=201) of children. Younger age (12-23 vs 24-59 months) was associated with lower Hb, iron and folate status. Current breastfeeding was associated with lower cobalamin and iron status but higher folate and vitamin A status. Malaria was associated with lower cobalamin status, iron tissue deficiency, and lower Hb. Low micronutrient status and inflammation were associated with lower Hb, and so was severe stunting, male sex and rural residence. Compared to no supplementation, LNS resulted in higher Hb and iron, cobalamin, folate but not vitamin A status. LNS supplementation also resulted in greater decline in α1-acid glycoprotein and a higher PhA, but no effect on morbidity except a temporary increase in diarrhea morbidity within the first two weeks. Children with stunting in resource-poor, malaria-endemic settings have low micronutrient status, and commonly have anemia. Addressing these issues requires a combination of interventions, rather than a single approach. Given the benefits of LNS supplementation, policies and programs should consider including LNS as part of their strategies for children with stunting in resource-poor settings. In addition, it is important to address non-nutritional factors such as preventing malaria and other infections. Future research should focus on a longer duration of LNS supplementation, cost-benefit analysis, and assess other essential micronutrients.