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ORIGINAL RESEARCH COMMUNICATION |
1 From the MRC Childhood Nutrition Research Center (AS, MF, and AL) and the Department of Pediatric Epidemiology and Biostatistics (TJC), Institute of Child Health, London, and the University Department of Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom (ISF and SOR).
Background: Formula feeding or overweight in infancy may increase the later risk of obesity, but the mechanisms involved are uncertain. Because obesity is associated with high leptin concentrations relative to fat mass, programming of leptin concentrations may be one mechanism by which early nutrition influences later obesity.
Objective: We tested the hypothesis that high nutrient intake or formula feeding in infancy programs greater leptin concentrations relative to fat mass in later life.
Design: Serum leptin concentrations were measured by radioimmunoassay in 197 adolescents aged 13–16 y who were born preterm and randomly assigned at birth to receive either a nutrient-enriched preterm formula or banked donated breast milk (trial 1) or a preterm formula or a standard formula (trial 2). Fat mass was estimated with the use of bioelectrical impedance analysis.
Results: After combining the results of trials 1 and 2 as planned, the ratio of leptin to fat mass was significantly greater in the children who received the preterm formula (geometric 
: 0.84 µg·L-1·kg-1) than in those who received standard formula or banked breast milk (0.62 µg·L-1·kg-1; mean difference: 30.8%; 95% CI for difference: 8.4%, 53.2%; P = 0.007). The difference between the diet groups remained significant after adjustment for age, sex, Tanner stage, social class, and fat mass. Human milk intake was significantly associated with lower leptin concentrations relative to fat mass in adolescence (P = 0.023), independent of potential confounding factors.
Conclusion: Programming of relative leptin concentrations by early diet may be one mechanism that links early nutrition with later obesity.
Key Words: Leptin • obesity • breast-feeding • formula feeding • adolescents • preterm infants • fat mass
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