Metabolomics in plasma of Malawian children 7 years after surviving severe acute malnutrition: “ChroSAM” a cohort study

Abstract

Background More children are now surviving severe acute malnutrition (SAM), but evidence suggests that early-life malnutrition is associated with increased risk of long-term cardio-metabolic disorders. To better understand potential mechanisms, we studied the metabolite profiles of children seven years after treatment for SAM. Methods We followed-up children ( n = 352) treated for SAM in 2006–2007, at Queen Elizabeth Central Hospital, in Malawi. Using nuclear magnetic resonance spectroscopy, tandem mass spectrometry and enzyme-linked immunosorbent assay, we measured circulating metabolites in fasting blood in a subset of SAM survivors ( n = 69, 9·6 ± 1·6 years), siblings ( n = 44, 10·5 ± 2·7 years), and age and sex-matched community controls ( n = 37, 9·4 ± 1·8 years). Data were analysed using univariate and sparse partial least square (sPLS) methods. Differences associated with SAM survival, oedema status, and anthropometry were tested, adjusting for age, sex, HIV, and wealth index. Findings Based on 194 measured metabolites, the profiles of SAM survivors were similar to those of siblings and community controls. IGF1, creatinine, and FGF21, had loading values >0·3 and ranked stably in the top 10 distinguishing metabolites, but did not differ between SAM survivors and controls with univariate analysis. Current stunting was associated with IGF1 (β = 15·2, SE = 3·5, partial R 2 = 12%, p < 0·0001) and this relationship could be influenced by early childhood SAM (β = 17·4, SE = 7·7, partial R 2 = 2·8%, p = 0·025). No metabolites were associated with oedema status, duration of hospital stay, anthropometry measured during hospitalization, nor with changes in anthropometry since hospitalization. Interpretation In this group of survivors, SAM was not associated with longer-term global metabolic changes 7 years after treatment. However, SAM may influence the relationship between current stunting and IGF1. Further risk markers for NCDs in SAM survivors may only be revealed by direct metabolic challenge or later in life.

Childhood severe acute malnutrition is associated with metabolic changes in adulthood

“…In contrast, we have previously shown that younger Malawian SAM survivors (aged 9•6 ± 1•6 years, 7 years post hospital discharge) did not show differences in their metabolic profiles compared to community and sibling participants (14). Thus, the metabolic signatures linked to NCDs that we describe may start to manifest as SAM survivors age.…”

Childhood Malnutrition and Association of Lean Mass with Metabolome and Hormone Profile in Later Life

“…We performed a secondary analysis of data obtained from our previous work in Malawi, the ChroSAM cohort [ 4 ] (Chronic Disease Outcomes following Severe Malnutrition), where plasma samples were obtained 7 years after being treated for severe malnutrition and previously analyzed for metabolome and hormonal profiling [ 18 ]. Plasma samples were also collected and analyzed from controls, consisting of sibling and community controls with no history of severe malnutrition.…”

“…The original cohort recruited 352 SM survivors, 217 sibling controls, and 184 age and sex-matched community controls. In this study, we included children with measured metabolome and hormone profiles from our previous study [ 18 ].…”

“…As shown previously, the reciprocal of impedance (1/Z) provides a robust marker of LMI without needing population-specific calibration [ 19 ]. Targeted metabolomics and hormone profiling were performed using the AbsoluteIDQ ® p180 kit (Biocrates, Innsbruck, Austria) and multiplex immunoassay (Milliplex ® Mag kits, Millipore, Darmstadt, Germany) as previously described [ 18 ].…”

“…All children with metabolomics, hormone profile, and LMI measurements from our previous study [ 18 ] were included in this current secondary analysis. Therefore, sample size was constrained by the availability of prior samples, and no new sample size calculations were done.…”