Serum cobalamin in children with moderate acute malnutrition in Burkina Faso: Secondary analysis of a randomized trial

• Published in: PLoS medicine Vol. 19; no. 3
• Main Authors: Henrik Friis, Bernardette Cichon, Christian Fabiansen, Ann-Sophie Iuel-Brockdorff, Charles W. Yaméogo, Christian Ritz, Ruth Frikke-Schmidt, André Briend, Kim F. Michaelsen, Vibeke B. Christensen, Suzanne Filteau, Mette F. Olsen
• Format: Journal Article
• Language: English
• Published: Public Library of Science (PLoS) 01-03-2022
• ISSN: 1549-1277; 1549-1676

Background Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. Methods and findings A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn–soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; <125 mm) was found in 80.4% (958) of the children and low weight-for-length z-score (WLZ; <−2) in 70.6% (841). Stunting was seen in 38.2% (456). Only 5.9% were not breastfed. Median (IQR) SC was 188 (137; 259) pmol/L. Two-thirds had SC ≤222 pmol/L, which was associated with lower hemoglobin. After age and sex adjustments, very low SC (<112 pmol/L) was associated with 0.21 (95% CI: 0.01; 0.41, p = 0.04) and 0.24 (95% CI: 0.06; 0.42, p = 0.01) z-score lower fine and gross motor development, respectively. SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. Conclusions Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. Trial registration ISRCTN Registry ISRCTN42569496. Henrik Friis and colleagues, investigate the prevalence and correlates of low serum cobalamin, associations with hemoglobin and child development, and associations of serum cobalamin levels with food supplementation in children moderate acute malnutrition in Burkina Faso. Author summary Why was this study done? We searched PubMed since 2000 using the terms (severe malnutrition OR acute malnutrition OR marasmus OR kwashiorkor OR wasting) AND (cobalamin OR B12) AND child*). We found no studies among children with moderate acute malnutrition (MAM) or severe acute malnutrition (SAM) treated with recommended food aid products and with data on serum cobalamin (SC) before and after treatment. What did the researchers do and find? We found that two-thirds of children with MAM had marginal or low SC, which were associated with deficits in hemoglobin and child development scores. The content of cobalamin in the food aid products was in accordance with the World Health Organization (WHO)’s recommendation and the duration of supplementation, 3 months, much longer than in programs. Despite this, one-third still had marginal or low SC at the end of supplementation, and mean levels declined considerable in the subsequent 3 months. While the study showed that supplementation was inadequate in terms of normalizing cobalamin status, it showed that lipid-based nutrient supplement (LNS) based on soy isolate (SI) was the best. What do these findings mean? Cobalamin is important for erythropoiesis and brain development. It is also likely to be of pivotal importance in the development of malnutrition, given its role in enterocyte turnover and, hence, absorption. Millions of children are treated for acute malnutrition every year. It is important that these children not only survive, but also get enough cobalamin to support key functions and long-term development.