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 eff ects 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
diff erence vs community controls 0·4, 95% CI 0·6 to 0·2, p=0·001; adjusted diff erence 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
diff erence vs community controls 2·0 cm, 1·0 to 3·0, p<0·0001; adjusted diff erence vs sibling controls 1·4 cm,
0·5 to 2·3, p=0·002), smaller mid-upper arm circumference (adjusted diff erence vs community controls 5·6 mm,
1·9 to 9·4, p=0·001; adjusted diff erence vs sibling controls 5·7 mm, 2·3 to 9·1, p=0·02), calf circumference (adjusted
diff erence vs community controls 0·49 cm, 0·1 to 0·9, p=0·01; adjusted diff erence vs sibling controls 0·62 cm,
0·2 to 1·0, p=0·001), and hip circumference (adjusted diff erence vs community controls 1·56 cm, 0·5 to 2·7, p=0·01;
adjusted diff erence vs sibling controls 1·83 cm, 0·8 to 2·8, p<0·0001), and less lean mass (adjusted diff erence vs
community controls –24·5, –43 to –5·5, p=0·01; adjusted diff erence vs sibling controls –11·5, –29 to –6, p=0·19) than
did either sibling or community controls. Survivors of SAM had functional defi cits consisting of weaker hand grip
(adjusted diff erence vs community controls –1·7 kg, 95% CI –2·4 to –0·9, p<0·0001; adjusted diff erence 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 signifi cant diff erences
between cases and controls in terms of lung function, lipid profi le, glucose tolerance, glycated haemoglobin A1c,
salivary cortisol, sitting height, and head circumference.
Interpretation Our results suggest that SAM has long-term adverse eff ects. 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 eff ects 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