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. 2020 Apr 8;6(15):eaay5969.
doi: 10.1126/sciadv.aay5969. eCollection 2020 Apr.

Metabolic maturation in the first 2 years of life in resource-constrained settings and its association with postnatal growths

N Giallourou  1 , F Fardus-Reid  1 , G Panic  1 , K Veselkov  1 , B J J McCormick  2 , M P Olortegui  3 , T Ahmed  4 , E Mduma  5 , P P Yori  3   6 , M Mahfuz  4 , E Svensen  5   7 , M M M Ahmed  4 , J M Colston  6   8 , M N Kosek  3   6 , J R Swann  1   9
Affiliations

Metabolic maturation in the first 2 years of life in resource-constrained settings and its association with postnatal growths

N Giallourou et al. Sci Adv. .

Abstract

Malnutrition continues to affect the growth and development of millions of children worldwide, and chronic undernutrition has proven to be largely refractory to interventions. Improved understanding of metabolic development in infancy and how it differs in growth-constrained children may provide insights to inform more timely, targeted, and effective interventions. Here, the metabolome of healthy infants was compared to that of growth-constrained infants from three continents over the first 2 years of life to identify metabolic signatures of aging. Predictive models demonstrated that growth-constrained children lag in their metabolic maturity relative to their healthier peers and that metabolic maturity can predict growth 6 months into the future. Our results provide a metabolic framework from which future nutritional programs may be more precisely constructed and evaluated.

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Figures

Fig. 1
Fig. 1. Biochemical variation associated with aging.
(A) urinary and (B) plasma metabolic profiles of infants from Peru (PE), Bangladesh (BG), and Tanzania (TZ). The heat map presents the correlation coefficient (r) obtained from PLS models: Blue colors indicate a negative association with age, and reds represent metabolic shifts positively associated with infant aging. (C) Mean effect size of age-discriminatory urinary metabolites on the PA based on children with healthy growth trajectories. The effect size is depicted as the estimated change in PA for each SD change in a metabolite concentration. Color indicates cohort site, and the size of the symbols indicates the percentage PA variance explained.
Fig. 2
Fig. 2. Time-dependent variation in the eight urinary metabolites used to calculate the PA of the study children.
Relative concentrations of metabolites were obtained by measuring the area under selected spectral regions corresponding to betaine, DMG, citrate, succinate, hippurate, PAG, 4-CS, and creatine. Shaded area represents 95% CI.
Fig. 3
Fig. 3. PAZ of growth-constrained and healthy infants relative to their chronological age across the three sites.
The PAZ score of healthy and growth-constrained infants from each site was calculated from eight age-discriminatory urinary metabolites. Significant differences were observed between healthy and growth-constrained children at all sampling points in all cohorts. Mann-Whitney U test, *P < 0.01, **P < 0.001, and ***P < 0.0001 (Healthy Peru: N3 months = 21, N6 months = 19, N9 months = 20, N15 months = 20, N24 months = 18; Growth constrained Peru: N3 months = 220, N6 months = 214, N9 months = 197, N15 months = 183, N24 months = 141; Healthy Bangladesh: N3 months = 25, N6 months = 27, N9 months = 24, N15 months = 26; Growth constrained Bangladesh: N3 months = 196, N6 months = 197, N9 months = 181, N15 months = 184; Healthy Tanzania: N6 months = 11, N15 months = 7, N24 months = 7; Growth constrained Tanzania: N6 months = 209, N15 months = 129, N24 months = 122).
Fig. 4
Fig. 4. Mean effect of each additional month of the PAZ on the LAZ 1 to 6 months after the urine sample, adjusting for LAZ at the time of the PAZ estimate and site.
See this image and copyright information in PMC

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