Derivation and external validation of clinical prediction rules identifying children at risk of linear growth faltering (stunting) presenting for diarrheal care

Abstract

Background: Nearly 150 million children under-5 years of age were stunted in 2020. We aimed to develop a clinical prediction rule (CPR) to identify children likely to experience additional stunting following acute diarrhea, to enable targeted approaches to prevent this irreversible outcome. Methodology: We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) study to build predictive models of linear growth faltering (decrease of ≥0.5 or ≥1.0 in height-for-age z-score [HAZ] at 60 day follow-up) in children ≤59 months presenting with moderate-to-severe diarrhea (MSD), and community controls, in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using 5-fold cross-validation. We used the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study to A) re-derive, and B) externally validate our GEMS-derived CPR. Results: Of 7642 children in GEMS, 1745 (22.8%) experienced severe growth faltering (≥0.5 decrease in HAZ). In MAL-ED, we analyzed 5683 diarrhea episodes from 1322 children, of which 961(16.9%) episodes experienced severe growth faltering. Top predictors of growth faltering in GEMS were: age, HAZ at enrollment, respiratory rate, temperature, and number of people living in the household. The maximum AUC was 0.74 (95% CI: 0.74, 0.75) with 20 predictors, while 2 predictors yielded an AUC of 0.70 (95% CI: 0.70, 0.71). Results were similar in the MAL-ED re-derivation. A 2-variable CPR derived from children 0-23 months in GEMS had an AUC=0.63 (95% CI 0.62, 0.65), and AUC=0.64 (95% CI: 0.60, 0.68) when externally validated in MAL-ED. Conclusions: Our findings indicate that use of prediction rules could help identify children at risk of poor outcomes after an episode of diarrheal illness.