LAUSR

In recent decades, there has been extensive interest in the infantfeeding factors, particularly formula-milk feeding compared with breastfeeding, on the risk of developing overweight/obesity in infancy, although whether these effects persist throughout the lifespan remains controversial. Increased weight gain and adiposity in infancy in formula-fed infants could be due to a variety of factors, including recognition of infant cues relating to hunger and satiety, caregiving practices around frequency and volume of feeds and macronutrient composition of formula feeds. Rolland-Cachera et al. hypothesised that lower intakes of fats with formula in comparison with breastmilk may lead to early adiposity rebound and fat accretion. Indeed, greater fat mass, investigated with different methodologies, but less lean mass and a lower bodyweight, have been observed up to 7 months of age in breastfed infants compared to those not breastfed. Decreased energy from fats in formula-fed infants may be compensated for by higher protein intakes, either in percentage and absolute amounts. A second hypothesis, therefore, is that higher protein intake in formula-fed infants is a primary cause of later risk of adiposity, based on metabolic and hormonal-mediated mechanisms leading to increased adipogenesis and lipogenesis. This hypothesis has been tested in a number of trials with heterogeneous study designs, including relating to quality and quantity of protein, with a systematic review being inconclusive, although lower protein formulas appear to be safe. Finally, carbohydrate concentration and non-digestible oligosaccharides within human milk also have been associated with fat mass and growth indices, respectively; therefore, completing the possible associations of fat, protein or carbohydrate components of human milk with later risk of fatness development. In such research, the unavoidable contribution of confounding maternal, child, cultural, genetic, and environmental variables makes the relationship between nutrient composition of either human milk and/or formula and adiposity very challenging to untangle. Given this background, the relative dearth of literature concerning the potential role of the sum of fat, protein and carbohydrate caloric equivalents within human milk and formula —that is, total energy supply, as calculated from volumes of milk intakes—on later fat development seems surprising. Indeed, however, the relative concentration of any macronutrient is manipulated, intake of formula exceeding volume ingested by breastfed infants is likely to lead to a difference in energy intake and, therefore, the theoretical risk of increased adiposity. In a 2002 WHO booklet aimed at demonstrating the nutrient adequacy of exclusive breastfeeding in healthy term infants for the first 6 months after birth, Butte et al. showed that daily human milk intakes from 1 to 6 completed months of infants from developed countries increased by only about 150mL (Table 1). Randomised control trials comparing similar volumes of milk intakes in breastfed vs. formula-fed infants, and differing in macronutrient concentrations, are impossible to perform, either for ethical or practical reasons. Nevertheless, a small number of observational studies have reported associations between volumes of formula ingested and adiposity, although not all have found this. Various guidelines for health professionals have been produced that outline volumes and frequency of formula feeds, but the advice is generally high level and generic; this is because there is little evidence to support detailed guidelines. There is, however, some evidence that caregivers’ feeding decisions can be influenced by health professionals, but also that there are significant barriers to compliance with advice from healthcare professionals. In this issue of Pediatric Research, Ferguson et al. focus on recommendations for formula intake by infants during the first 6 months after birth by means of a simulation modelled on hospital recommendations or by the Nutrition Programme for Women, Infant and Children (WIC), which covers >50% of infants in the United States. There are large differences in the recommended volumes between the WIC and hospital guidelines, reflecting the lack of evidence, with the minimum and maximum recommended intake from the WIC guidelines 20–30% greater than the hospital guidelines in the first and second month, but with this pattern reversed thereafter, reaching an astonishing twofold difference in the minimum recommended intake in month 3. The modelling approach used began by randomly selecting the number of feeds per day and volume per feed from within a normal distribution of the recommended values in the guidelines. Daily modelling of growth was undertaken and, once a week, if the modelled infant crossed a major centile line for body mass index (BMI), milk intake was adjusted to the lower (infant increasing weight) or upper (infant decreasing weight) end of the range according to four scenarios: first, no adjustment in volume; second, adjusting to a randomly selected volume within the lower or upper half (such that the normal distribution becomes bounded by the mean of the original distribution); third, adjusting to a randomly selected volume within the lower or upper quartile of volumes (such that the normal distribution