Chronic disease outcomes after severe acute malnutrition in Malawian children (ChroSAM): a cohort study

BACKGROUND
Tackling severe acute malnutrition (SAM) is a global health priority. Heightened risk of non-communicable diseases (NCD) in children exposed to SAM at around 2 years of age is plausible in view of previously described consequences of other early nutritional insults. By applying developmental origins of health and disease (DOHaD) theory to this group, we aimed to explore the long-term effects of SAM.


METHODS
We followed up 352 Malawian children (median age 9·3 years) who were still alive following SAM inpatient treatment between July 12, 2006, and March 7, 2007, (median age 24 months) and compared them with 217 sibling controls and 184 age-and-sex matched community controls. Our outcomes of interest were anthropometry, body composition, lung function, physical capacity (hand grip, step test, and physical activity), and blood markers of NCD risk. For comparisons of all outcomes, we used multivariable linear regression, adjusted for age, sex, HIV status, and socioeconomic status. We also adjusted for puberty in the body composition regression model.


FINDINGS
Compared with controls, children who had survived SAM had lower height-for-age Z scores (adjusted difference vs community controls 0·4, 95% CI 0·6 to 0·2, p=0·001; adjusted difference vs sibling controls 0·2, 0·0 to 0·4, p=0·04), although they showed evidence of catch-up growth. These children also had shorter leg length (adjusted difference vs community controls 2·0 cm, 1·0 to 3·0, p<0·0001; adjusted difference vs sibling controls 1·4 cm, 0·5 to 2·3, p=0·002), smaller mid-upper arm circumference (adjusted difference vs community controls 5·6 mm, 1·9 to 9·4, p=0·001; adjusted difference vs sibling controls 5·7 mm, 2·3 to 9·1, p=0·02), calf circumference (adjusted difference vs community controls 0·49 cm, 0·1 to 0·9, p=0·01; adjusted difference vs sibling controls 0·62 cm, 0·2 to 1·0, p=0·001), and hip circumference (adjusted difference vs community controls 1·56 cm, 0·5 to 2·7, p=0·01; adjusted difference vs sibling controls 1·83 cm, 0·8 to 2·8, p<0·0001), and less lean mass (adjusted difference vs community controls -24·5, -43 to -5·5, p=0·01; adjusted difference vs sibling controls -11·5, -29 to -6, p=0·19) than did either sibling or community controls. Survivors of SAM had functional deficits consisting of weaker hand grip (adjusted difference vs community controls -1·7 kg, 95% CI -2·4 to -0·9, p<0·0001; adjusted difference vs sibling controls 1·01 kg, 0·3 to 1·7, p=0·005,)) and fewer minutes completed of an exercise test (sibling odds ratio [OR] 1·59, 95% CI 1·0 to 2·5, p=0·04; community OR 1·59, 95% CI 1·0 to 2·5, p=0·05). We did not detect significant differences between cases and controls in terms of lung function, lipid profile, glucose tolerance, glycated haemoglobin A1c, salivary cortisol, sitting height, and head circumference.


INTERPRETATION
Our results suggest that SAM has long-term adverse effects. Survivors show patterns of so-called thrifty growth, which is associated with future cardiovascular and metabolic disease. The evidence of catch-up growth and largely preserved cardiometabolic and pulmonary functions suggest the potential for near-full rehabilitation. Future follow-up should try to establish the effects of puberty and later dietary or social transitions on these parameters, as well as explore how best to optimise recovery and quality of life for survivors.


FUNDING
The Wellcome Trust.