Sickle cell trait (HbAS) and stunting in children below two years of age in an area of high malaria transmission

Abstract

Background: While the protective effects of sickle cell trait (HbAS) against severe malaria and the resulting survival advantage are well known, the impact on the physical development in young children remains unclear. This study was aimed to investigate the relationship between HbS carriage and stunting in children below two years of age in a cohort from the Ashanti Region, Ghana.

Methods: 1,070 children were recruited at three months of age and followed-up for 21 months with anthropometric measurements performed every three months. Incidence rate ratios with 95% confidence intervals were calculated by Poisson regression to estimate the association of beta-globin genotypes with the number of malaria episodes. Odds ratios (OR) were calculated for the association between the occurrence of beta-globin genotypes and/or malaria episodes and stunting. The age-dependent between-group and within-group effects for the beta-globin genotypes were assessed by population-averaged models estimated by generalized estimation equation with autoregressive correlation structure.

Results: Analyses showed a significantly lower age-dependent risk of stunting (OR 0.56; 95% CI 0.33-0.96) in carriers of the HbAS genotype (n = 102) in comparison to those with HbAA (n = 692). This effect was restricted to children who experienced malaria episodes during the observation period suggesting that the beneficial effect of the beta-globin HbS variant on the incidence of stunting is closely linked to its protection from mild malaria episodes.

Conclusion: The lower risk of chronic malnutrition in early childhood, mediated by protection against mild malaria episodes, may contribute to the survival advantage of HbAS carriers in areas of high malaria transmission.

Figure 1

Relationship between stunting and age in children with and without malaria episodes. Proportion of children stunted with increasing age stratified for b-globin genotypes HbAA (dots and solid line) and HbAS (crosses and dashed line). GEE analyses with adjustment for within-group, between-group effects and age-dependency were performed with autoregressive correlation structure of order 5 and assumption of binomial variable distribution. A, children without malaria episodes; no significant protective effect of HbAS (OR 0.84; CI 0.33–2.15; p = 0.71). B, children with at least one episode of malaria; 51% lower risk of stunting (OR 0.49; CI 0.25–0.93; p = 0.03).