Differing growth responses to nutritional supplements in neighboring health districts of Burkina Faso are likely due to benefits of small-quantity lipid-based nutrient supplements (LNS)

Abstract

Background: Of two community-based trials among young children in neighboring health districts of Burkina Faso, one found that small-quantity lipid-based nutrient supplements (LNS) increased child growth compared with a non-intervention control group, but zinc supplementation did not in the second study.

Objectives: We explored whether the disparate growth outcomes were associated with differences in intervention components, household demographic variables, and/or children's morbidity.

Methods: Children in the LNS study received 20g LNS daily containing different amounts of zinc (LNS). Children in the zinc supplementation study received different zinc supplementation regimens (Z-Suppl). Children in both studies were visited weekly for morbidity surveillance. Free malaria and diarrhea treatment was provided by the field worker in the LNS study, and by a village-based community-health worker in the zinc study. Anthropometric assessments were repeated every 13-16 weeks. For the present analyses, study intervals of the two studies were matched by child age and month of enrollment. The changes in length-for-age z-score (LAZ) per interval were compared between LNS and Z-Suppl groups using mixed model ANOVA or ANCOVA. Covariates were added to the model in blocks, and adjusted differences between group means were estimated.

Results: Mean ages at enrollment of LNS (n = 1716) and Z-Suppl (n = 1720) were 9.4±0.4 and 10.1±2.7 months, respectively. The age-adjusted change in mean LAZ per interval declined less with LNS (-0.07±0.44) versus Z-Suppl (-0.21±0.43; p<0.0001). There was a significant group by interval interaction with the greatest difference found in 9-12 month old children (p<0.0001). Adjusting for demographic characteristics and morbidity did not reduce the observed differences by type of intervention, even though the morbidity burden was greater in the LNS group.

Conclusions: Greater average physical growth in children who received LNS could not be explained by known cross-trial differences in baseline characteristics or morbidity burden, implying that the observed difference in growth response was partly due to LNS.

Conflict of interest statement

Competing Interests: KHB was employed by the University of California, Davis at the time of the study, but presently works for the Bill & Melinda Gates Foundation, which provided financial support for the LNS study and the present analyses. The spouse of SYH works for the Bill & Melinda Gates Foundation. SYH received non-monetary support from Nutriset SAS, who produced the LNS and supplements. The other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Study design of the LNS and the zinc supplementation studies.

Children eligible for the present long-term and short-term exploratory analyses were matched by age.1 In LNS study area, cluster randomization of 34 communities to intervention cohort (LNS-IC, 25 communities) or non-intervention cohort (LNS-NIC, 9 communities). 2 In zinc supplemenation study area, 36 geographically defined clusters, were randomly assigned to one of three cohorts: immediate and delayed intervention (Z-IC, 12 clusters each), and non-intervention cohort (Z-NIC, 12 clusters). 3 Children in LNS-IC, LNS-NIC, Z-IC, and Z-NIC who participated during the full study period were included in the analyses of the full study duration. 4 Within the LNS-IC communities, eligible children were randomly assigned to 1) LNS without zinc, and placebo tablet, 2) LNS with 5 mg zinc, and placebo tablet, 3) LNS with 10 mg zinc, and placebo tablet, or 4) LNS without zinc, and 5 mg zinc tablet. Children diagnosed with uncomplicated diarrhea, malaria and fever received free medical treatment during weekly home visit. 5 Within the Z-IC, eligible children were randomly assigned to 1) intermittent preventive zinc supplementation (10 mg zinc for 10 days) every 16 weeks and daily preventive and therapeutic placebo tablets, 2) daily preventive 7 mg zinc tablet daily and therapeutic placebo during diarrhea, and 3) therapeutic zinc supplementation for episodes of diarrhea (20 mg zinc/ day for 10 days) and daily placebo tablets. Children diagnosed with uncomplicated diarrhea, malaria and fever received free medical treatment from a village-based community health worker. 6 During each of the 16 week-rounds in the Z-IC cohort, three randomly selected clusters served as non-supplemented morbidity surveillance comparison group (Z-Contr). Children diagnosed with uncomplicated diarrhea, malaria and fever received free medical treatment from a village-based community health worker. 4,5,6 Children were matched by age and month of enrollment for inclusion in the analyses of age-specific intervals: 9–12 mo interval, 12–15 mo interval and 15–18 mo interval. 7 In both studies, children in the NIC were assessed at enrollment and at the end of the study and did not receive any supplementation of morbidity treatment throughout the course of the study.

Fig 2. Age vs date at midpoint of study interval for whole-study and age-specific analyses of the LNS and the zinc supplementation study.

Intervals in the overlapping areas were eligible for inclusion in the analysis.

Fig 3. Difference in change in length-for-age z-score between the LNS and the zinc study populations over the whole study duration.

Fig 4. The difference in mean changes in length-for-age z-score between the LNS and the Z-Suppl groups from 9 to 12 and 12 to 15 months of age as different covariates are added to the mixed-model analysis of covariance.