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

Benno Kreuels,Robin Kobbe,Jürgen May,Christa Ehmen,Christina Kreuzberg,Stephan Ehrhardt,Gerd D Burchard,Samuel Adjei,Matilda Ayim,Ohene Adjei

doi:10.1186/1475-2875-8-16

Abstract

BackgroundWhile 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.Methods1,070 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 β-globin genotypes with the number of malaria episodes. Odds ratios (OR) were calculated for the association between the occurrence of β-globin genotypes and/or malaria episodes and stunting. The age-dependent between-group and within-group effects for the β-globin genotypes were assessed by population-averaged models estimated by generalized estimation equation with autoregressive correlation structure.ResultsAnalyses 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 β-globin HbS variant on the incidence of stunting is closely linked to its protection from mild malaria episodes.ConclusionThe 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.

Highlights

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
There is much epidemiological evidence that sickle cell trait decreases the risk for all manifestations of severe malaria and that this protective effect has caused a balanced polymorphism of the sickle cell mutation (HbS) in malaria endemic regions [1]
In children who were not stunted at recruitment, HbAS carriers had a 58% decreased risk of being stunted at two years of age in comparison to HbAA carriers

Summary

Introduction

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. In addition to protection against severe malaria, HbS has been shown to exhibit some level of protection against mild malaria [2]. The importance of this observation for the survival advantage of individuals with HbAS remains unclear [3]. Stunting (length/height-for-age z-score < -2) in early childhood, as an indicator of chronic malnutrition, is a common condition in African children and one of the main determinants of childhood morbidity and mortality [7]. It has been demonstrated, that stunting is related to poor cognitive performance later on in life and has a negative effect on adult health and human capital [8,9]

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