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The first days of postnatal life are energetically demanding as metabolic functions change dramatically to accommodate drastic environmental and physiologic transitions after birth. It is increasingly appreciated that metabolic pathways are not only crucial for nutrition but also play important roles in regulating inflammation and the host response to infection. Neonatal susceptibility to infection is increased due to a functionally distinct immune response characterized by high reliance on innate immune mechanisms. Interactions between metabolism and the immune response are increasingly recognized, as changes in metabolic pathways drive innate immune cell function and activation and consequently host response to pathogens. Moreover, metabolites, such as acetyl-coenzyme A (acetyl-CoA) and succinate have immunoregulatory properties and serve as cofactors for enzymes involved in epigenetic reprogramming or "training" of innate immune cells after an initial infectious exposure. Highly sensitive metabolomic approaches allow us to define alterations in metabolic signatures as they change during ontogeny and as perturbed by immunization or infection, thereby linking metabolic pathways to immune cell effector functions. Characterizing the ontogeny of immunometabolism will offer new opportunities to prevent, diagnose, and treat neonatal sepsis.

Whole body composition was investigated using dual energy x-ray absorptiometry in 54 healthy preterm infants, birth weight < 1750 g, who were fed fortified human milk (n = 20) and preterm formula (n = 34) when full enteral feeding was attained and then again 3 wk later at around the time of discharge. Weight gain composition was calculated from the difference between the earlier and later measurement. The minimal detectable changes in whole body composition over time according to the variance of the population (within groups of 20 infants) and the minimal detectable changes according to the dietary intervention (between two groups of 20 infants) were determined at 5% significance and 80% power. Whole body composition was similar in the two groups at the initial measurement, but all the measured variables differed at the time of the second measurement. Formula-fed infants showed a greater weight gain (19.9 +/- 3.2 versus 15.9 +/- 2.2 g.kg(-1).d(-1), p < 0.05), fat mass deposition (5.1 +/- 1.9 versus 3.3 +/- 1.3 g.kg(-1).d(-1), p < 0.05), bone mineral content gain (289 +/- 99 versus 214 +/- 64 mg.kg(-1).d(-1), p < 0.05), and increase in bone area (1.6 +/- 0.4 versus 1.3 +/- 0.3 cm(2).kg(-1).d(-1), p < 0.05) compared with the fortified human milk group. From these data, a minimal increase from the first measurement of 111 g lean body mass, 68 g fat mass, and 3. 1 g bone mineral content is needed to be detectable in a longitudinal study that includes 20 infants. For significance between two groups of 20 infants around the time of discharge, dietary intervention needs to achieve minimal differences of 160 g lean body mass, 86 g fat mass, and 4.1 g bone mineral content. With respect to weight gain composition, the minimal differences required to reach significance are 2.1 g.kg(-1).d(-1) for gain in lean body mass, 1.2 g.kg(-1).d(-1) for gain in fat mass, and 76 mg.kg(-1). d(-1) for gain in bone mineral content. We conclude that dual energy x-ray absorptiometry allows evaluation of the effects of dietary intervention on whole body and weight gain composition in preterm infants during the first weeks of life.