Optimising recovery from childhood moderate acute malnutrition: a randomized controlled trial

Optimising nutritional strategies to improve growth recovery from moderate acute malnutrition (MAM) remains a global priority. We conducted a community-based, open-label, randomised controlled trial in Bangladesh to evaluate whether an enhanced ready-to-use supplementary food (ERUSF), enriched with prebiotics, Long Chain PolyUnsaturated Fatty Acids (LC-PUFA) and carotenoids, improved recovery outcomes compared with a locally produced RUSF (L-RUSF). Children aged 12 ± 1 months with MAM were treated with RUSF or ERUSF for up to three months or until recovery, followed by nine months of maintenance supplementation with standard or enhanced small-quantity lipid-based nutrient supplements (SQ-LNS or ESQ-LNS) in addition to their daily normal complementary diet. Using WHO criteria (WLZ/WHZ > −2), 69% of participants achieved recovery during the rapid catch-up phase, with no significant difference between intervention arms. When a more stringent, pre-specified biologically informed recovery threshold (WLZ/WHZ > −1) was applied to examine recovery trajectories beyond WHO-defined resolution of wasting, approximately 44% of children in both arms achieved this target. Among those who did recover to this stricter threshold, ERUSF was associated with a significantly shorter time to attainment, indicating more rapid catch-up growth rather than an increased probability of recovery. Relapse rates during the subsequent maintenance phase were low and did not differ between SQ-LNS formulations. To explore biological correlates of recovery heterogeneity, we integrated anthropometric, microbiome, plasma metabolomic, and genetic data using mixed models and exploratory machine-learning approaches. Baseline anthropometric severity, early weight gain, and polygenic risk profiles were associated with recovery status, whereas sociodemographic variables were largely uninformative. Post-hoc counterfactual digital twin modelling suggested that variation in baseline plasma amino acid and vitamin profiles may partially explain non-recovery under locally produced nutritional protocols. These simulations identified model-consistent feature shifts that, if achievable, were predicted to increase recovery to the WLZ/WHZ > −1 threshold; however, these findings are hypothesis-generating and not evidence of causal or clinically actionable effects. Together, these results demonstrate that enhanced RUSF accelerates recovery among children who respond but does not increase overall recovery rates under WHO criteria. Persistent heterogeneity in recovery trajectories appears to reflect underlying biological and genetic factors. These are not fully addressed by current supplementation strategies, highlighting the need for future trials explicitly designed to test biologically stratified nutritional interventions.