Nutrition in infancy and long-term risk of obesity: evidence from 2 randomized controlled trials.

BACKGROUND: Growth acceleration as a consequence of relative overnutrition in infancy has been suggested to increase the risk of later obesity. However, few studies have investigated this association by using an experimental study design. OBJECTIVE: We investigated the effect of early growth promotion on later body composition in 2 studies of infants born small for gestational age (weight <10th percentile in study 1 and <20th percentile in study 2). DESIGN: We reviewed a subset of children (n = 153 of 299 in study 1 and 90 of 246 in study 2) randomly assigned at birth to receive either a control formula or a nutrient-enriched formula (which contained 28-43% more protein and 6-12% more energy than the control formula) at 5-8 y of age. Fat mass was measured by using bioelectric impedance analysis in study 1 and deuterium dilution in study 2. RESULTS: Fat mass was lower in children assigned to receive the control formula than in children assigned to receive the nutrient-enriched formula in both trials [mean (95% CI) difference for fat mass after adjustment for sex: study 1: -38% (-67%, -10%), P = 0.009; study 2: -18% (-36%, -0.3%), P = 0.04]. In nonrandomized analyses, faster weight gain in infancy was associated with greater fat mass in childhood. CONCLUSIONS: In 2 prospective randomized trials, we showed that a nutrient-enriched diet in infancy increased fat mass later in childhood. These experimental data support a causal link between faster early weight gain and a later risk of obesity, have important implications for the management of infants born small for gestational age, and suggest that the primary prevention of obesity could begin in infancy.

Dietary nucleotides and early growth in formula-fed infants: a randomized controlled trial.

BACKGROUND: Dietary nucleotides are nonprotein nitrogenous compounds that are found in high concentrations in breast milk and are thought to be conditionally essential nutrients in infancy. A high nucleotide intake has been suggested to explain some of the benefits of breastfeeding compared with formula feeding and to promote infant growth. However, relatively few large-scale randomized trials have tested this hypothesis in healthy infants. OBJECTIVE: We tested the hypothesis that nucleotide supplementation of formula benefits early infant growth. PATIENTS AND METHODS: Occipitofrontal head circumference, weight, and length were assessed in infants who were randomly assigned to groups fed nucleotide-supplemented (31 mg/L; n=100) or control formula without nucleotide supplementation (n=100) from birth to the age of 20 weeks, and in infants who were breastfed (reference group; n=101). RESULTS: Infants fed with nucleotide-supplemented formula had greater occipitofrontal head circumference at ages 8, 16, and 20 weeks than infants fed control formula (mean difference in z scores at 8 weeks: 0.4 [95% confidence interval: 0.1-0.7]; P=.006) even after adjustment for potential confounding factors (P=.002). Weight at 8 weeks and the increase in both occipitofrontal head circumference and weight from birth to 8 weeks were also greater in infants fed nucleotide-supplemented formula than in those fed control formula. CONCLUSIONS: Our data support the hypothesis that nucleotide supplementation leads to increased weight gain and head growth in formula-fed infants. Therefore, nucleotides could be conditionally essential for optimal infant growth in some formula-fed populations. Additional research is needed to test the hypothesis that the benefits of nucleotide supplementation for early head growth, a critical period for brain growth, have advantages for long-term cognitive development.

Dietary nucleotides and fecal microbiota in formula-fed infants: a randomized controlled trial.

BACKGROUND: Dietary nucleotides are nonprotein nitrogenous compounds that are thought to be important for growth, repair, and differentiation of the gastrointestinal tract. A higher nucleotide intake may also have favorable effects on the fecal microbial composition and incidence of diarrhea in infancy. However, few studies have tested this hypothesis with an experimental study design. OBJECTIVE: We tested the hypothesis that nucleotide supplementation of infant formula has beneficial effects on fecal bacteriology. DESIGN: Oligonucleotide probes were used to measure bacterial genus-specific 16S ribosomal RNA in stools of a subset of infants (mean age: 20.4 wk) who were randomly assigned to nucleotide-supplemented (31 mg/L; n = 35) or control formula (n = 37) from birth until age 20 wk or were breastfed (reference group; n = 44). The microbial pattern was assessed as the ratio of Bacteroides-Porphyromonas-Prevotella group (BPP) to Bifidobacterium species. RESULTS: The ratio of BPP to Bifidobacterium spp. rRNA in infants randomly assigned to the nucleotide-supplemented formula was lower than in infants receiving the control formula (mean difference: -118%; 95% CI: -203%, -34%; P = 0.007), but it did not differ in infants who were breastfed. The difference between randomized formula-fed groups was independent of potential confounding factors (P = 0.003). CONCLUSIONS: Our data support the hypothesis that nucleotide supplementation improves the composition of the gut microbiota in formula-fed infants. Because this effect could contribute to previously described benefits of nucleotide supplementation for gastrointestinal tract and immune function, these findings have important implications for optimizing the diet of formula-fed infants.

Infant nutrition and stereoacuity at age 4-6 y.

BACKGROUND: Breastfeeding has been reported to benefit visual development in children. A higher concentration of docosahexaneoic acid (DHA) in breast milk than in formula has been proposed as one explanation for this association and as a rationale for adding DHA to infant formula, but few long-term data support this possibility. OBJECTIVE: The objectives of the study were, first, to test the hypothesis that breastfeeding benefits stereoscopic visual maturation and, second, if that benefit is shown, to ascertain whether it is mediated by the dietary intake of DHA. DESIGN: Stereoacuity was measured by using the random dot E test (primary outcome), and visual acuity was measured by using the Sonksen-Silver acuity system (secondary outcome) in previously breastfed (n = 78) or formula-fed (n = 184) children aged 4-6 y who had been followed prospectively from birth. In the formula-fed group, children were randomly assigned to receive formula with either DHA or arachidonic acid (n = 94) or a control formula (n = 90) for the first 6 mo. RESULTS: Breastfed children had a significantly (P = 0.001) greater likelihood of foveal stereoacuity (high-grade or < 100 s/arc) than did formula-fed children (odds ratio: 2.5; 95% CI: 1.4, 4.5) independent of potential confounding (P = 0.005). Stereoacuity did not differ significantly between children randomly assigned to DHA-supplemented or control formula. None of the groups differed in Sonksen-Silver visual acuity. CONCLUSIONS: These findings support the hypothesis that breastfeeding benefits long-term stereoscopic development. An effect of DHA cannot be excluded, but the lack of difference in stereoacuity between infants randomly assigned to DHA-containing and those assigned to control formula raises the hypothesis that factors in breast milk other than DHA account for the observed benefits.

Promotion of faster weight gain in infants born small for gestational age: is there an adverse effect on later blood pressure?

BACKGROUND: Being born small for gestational age is associated with later risk factors for cardiovascular disease, such as high blood pressure. Promotion of postnatal growth has been proposed to ameliorate these effects. There is evidence in animals and infants born prematurely, however, that promotion of growth by increased postnatal nutrition increases rather than decreases later cardiovascular risk. We report the long-term impact of growth promotion in term infants born small for gestational age (birth weight <10th percentile). METHODS AND RESULTS: Blood pressure was measured at 6 to 8 years in 153 of 299 (51%) of a cohort of children born small for gestational age and randomly assigned at birth to receive either a standard or a nutrient-enriched formula. The enriched formula contained 28% more protein than standard formula and promoted weight gain. Diastolic and mean (but not systolic) blood pressure was significantly lower in children assigned to standard compared with nutrient-enriched formula (unadjusted mean difference for diastolic blood pressure, -3.2 mm Hg; 95% CI, -5.8 to -0.5; P=0.02) independent of potential confounding factors (adjusted difference, -3.5 mm Hg; P=0.01). In observational analyses, faster weight gain in infancy was associated with higher later blood pressure. CONCLUSIONS: In the present randomized study targeted to investigate the effect of early nutrition on long-term cardiovascular health, we found that a nutrient-enriched diet increased later blood pressure. These findings support an adverse effect of relative "overnutrition" in infancy on long-term cardiovascular disease risk, have implications for the early origins of cardiovascular disease hypothesis, and do not support the promotion of faster weight gain in infants born small for gestational age.

Structural (betaalpha)8 TIM barrel model of 3-hydroxy-3-methylglutaryl-coenzyme A lyase.

This study describes three novel homozygous missense mutations (S75R, S201Y, and D204N) in the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase gene, which caused 3-hydroxy-3-methylglutaric aciduria in patients from Germany, England, and Argentina. Expression studies in Escherichia coli show that S75R and S201Y substitutions completely abolished the HMG-CoA lyase activity, whereas D204N reduced catalytic efficiency to 6.6% of the wild type. We also propose a three-dimensional model for human HMG-CoA lyase containing a (betaalpha)8 (TIM) barrel structure. The model is supported by the similarity with analogous TIM barrel structures of functionally related proteins, by the localization of catalytic amino acids at the active site, and by the coincidence between the shape of the substrate (HMG-CoA) and the predicted inner cavity. The three novel mutations explain the lack of HMG-CoA lyase activity on the basis of the proposed structure: in S75R and S201Y because the new amino acid residues occlude the substrate cavity, and in D204N because the mutation alters the electrochemical environment of the active site. We also report the localization of all missense mutations reported to date and show that these mutations are located in the beta-sheets around the substrate cavity.

Current practice for obtaining consent in UK neonatal units.

Working practice in neonatal units, like other medical and surgical specialties, is undergoing drastic changes to incorporate current legal and ethical requirements. We surveyed the current working practices of 60 neonatal units in this country. Consent appeared to be implied for routine procedures. Variable rates of consent were reported for specialised interventions and the surgical team was consistently involved in obtaining consent for all surgical procedures. There is great variation in practices for seeking consent in neonatal units in this country.