There is increasing evidence that health and development in adult life is influenced or “programmed” by factors, including nutrition, operating during foetal life and infancy. Early nutrition in a variety of animal species, including primates, has been demonstrated to influence later outcomes, including the likelihood of cardiovascular disease, learning and behaviour problems and longevity (see supplementary data).

Background: The low sn-2 palmitate content of infant formulas results in formation of fatty acid calcium soaps in the stools and reduced calcium absorption. Objective: Our objective was to test the hypotheses that increasing the proportion of sn-2 palmitate in formula for term infants would result in greater skeletal mineral deposition and reduced stool hardness. Design: Healthy term neonates were randomly assigned to receive standard formula (n = 103) or formula containing 50% sn-2 palmitate (high–sn-2 formula; n = 100) for 12 wk. One hundred twenty breast-fed infants were also studied. The main outcome measures were 1) radial (single-photon absorptiometry) and whole-body (dual-energy X-ray absorptiometry) bone mineral content (WBBMC) at 12 wk and 2) stool frequency, volume, and consistency at 6 and 12 wk. Secondary outcome measures included stool fatty acid content. Results: Infants receiving high–sn-2 formula had higher WBBMC (128.1 ± 9.7 compared with 122.7 ± 10.1 g, adjusted for size and sex), softer stools at 6 and 12 wk, and a lower proportion of stool soap fatty acids than did infants receiving the control formula. Breast-fed infants had adjusted WBBMC values (128.3 ± 9.1 g) similar to those of infants fed high–sn-2 formula and significantly higher than those of infants fed the control formula. Conclusions: Changing the stereoisomeric structure of palmitate in infant formula resulted in higher WBBMC, reduced stool soap fatty acids, and softer stools more like those of breast-fed infants. The greater bone mass measured could be important if it persists beyond the trial period; this merits further investigation.

The importance of bone growth and mineralisation during childhood for bone health in adult life is increasingly accepted, with both nutritional factors¹ and exercise² being recognised as influential for normal skeletal development. The appreciation that infancy and childhood are important periods of life for bone development has led to a need for suitable methods for monitoring bone health, both for research purposes and for clinical monitoring of individuals, and hence to an increasing use of bone densitometry in children. This review discusses the role and potential pitfalls of this technique.

Objective. We tested the hypothesis that balanced addition of long-chain polyunsaturated fatty acid (LCPUFA) to preterm formula during the first weeks of life would confer long-term neurodevelopmental advantage in a double-blind, randomized, controlled trial of preterm formula with and without preformed LCPUFA. Methods. The participants were 195 formula-fed preterm infants (birth weight <1750 g, gestation <37 weeks) from 2 UK neonatal units and 88 breast milk-fed infants. Main outcome measures were Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 18 months and Knobloch, Passamanick and Sherrard’s Developmental Screening Inventory at 9 months’ corrected age. Safety outcome measures were anthropometry at 9 and 18 months, tolerance, infection, necrotizing enterocolitis, and death. Results. There were no significant differences in developmental scores between randomized groups, although infants who were fed LCPUFA-supplemented formula showed a nonsignificant 2.6-point (0.25 standard deviation) advantage in MDI and PDI at 18 months, with a greater (nonsignificant) advantage (MDI: 4.5 points; PDI: 5.8 points) in infants below 30 weeks’ gestation. LCPUFA-supplemented infants were shorter than control infants at 18 months (difference in length standard deviation score: 0.44; 95% confidence interval: 0.08–0.8). No other significant short- or long-term differences in safety outcomes were observed. Breastfed infants had significantly higher developmental scores at 9 and 18 months than both formula groups and were significantly heavier and longer at 18 months than LCPUFA-supplemented but not control infants. Conclusions. With the dose, duration, and preparation of LCPUFA used, efficacy was not demonstrated, although an advantage in later neurodevelopment cannot be excluded by global tests of development up to 18 months, particularly in infants below 30 weeks’ gestation. The surprising effect of LCPUFA-supplemented formula on growth 18 months beyond the intervention period needs to be confirmed in other studies using similar supplementation strategies. Additional follow-up of this cohort is critical at an age when more specific tests of cognitive function are possible.