Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies.

Epidemiological studies in humans show that size in early life is related to blood cholesterol concentrations in adult life, raising the hypothesis that early nutrition programs later lipid metabolism, affecting risk for later vascular disease. Here, we tested the hypothesis that nutrition during pregnancy or lactation in the rat programs lipid metabolism in the offspring, studied in adult life (mean 6 months). Rats (n 35) from normally-fed dams (controls) were compared with (1) rats (n 22) from dams proteinrestricted in pregnancy and lactation; (2) rats (n 9) born to normally-fed mothers crossed to proteinrestricted lactating dams and (3) those (n 9) born of protein-restricted dams and crossed to normally-fed lactating animals. In these latter three groups the offspring showed long-term reduction in plasma cholesterol, HDL-cholesterol and triacylglycerol concentrations compared with controls. The effects were predominantly in males. These findings suggest that in the rat the sensitive period for nutritional programming of cholesterol and triacylglycerol metabolism is both pre-and postnatal (pre-weaning) and that rats may be 'indirectly' programmed by altering the maternal nutritional milieu during gestation or lactation. w h i t it has been hypothesized that early human undernutrition programs risk for vascular disease, one aspect of undernutrition, low maternal protein intake, in this rat model programmed lower plasma cholesterol and triacylglycerol concentrations. Maternal diet: Lipid metabolism: Nutritional programmingWhether early nutrition has a long-term 'programming' effect (Lucas, 1994) on risk factors for adult degenerative vascular disease is currently an area of major public health concern (Fall et al. 1992). Epidemiological studies in humans show that size in early life is related to adult plasma levels of cholesterol, LDL-cholesterol and apoprotein B, recognized risk factors for cardiovascular disease. Thus weight at 1 year is inversely related to apoprotein B (Barker et al. 1993b); and subjects who had a small abdominal circumference have the hghest levels of total and LDL-cholesterol in adult life (Barker et al. 1993~). In addition, men in the 60's who were breast fed and not weaned by 1 year and those who were bottle fed had higher plasma total and LDL-cholesterol concentrations ;

SUMMARY In a study on 857 infants born preterm, high peak plasma alkaline phosphatase activity was independently related to slower growth rate in the neonatal period, and to a highly significant reduction in attained length at 9 months and 18 months post term. At 18 months the deficit in body length associated with peak neonatal plasma alkaline phosphase activity of 1200 IU/l or more was 1 6 cm (95% confidence interval 0-9 to 2-3 cm) after adjusting for confounding factors. The strength and magnitude of this association between high plasma alkaline phosphase activity and body length was greater than that for any other factor identified, including the infant's sex and the presence of fetal growth retardation. Data are presented that support the view that the high plasma alkaline phosphatase activity reflected early bone mineral substrate deficiency resulting in metabolic bone disease.We speculate that even silent early bone disease may interfere with the control of subsequent linear growth and emphasise the potential importance of providing preterm infants, especially those fed human milk, with adequate substrate for bone mineralisation.

I . During the initial stages of the development of hypoalbuminaemia, with concentrations between 25 and 30 g,J, fasting serum cortisol and growth hormone values remained normal. Corresponding fasting serum insulin concentrations were, however, significantly above normal. During the same period, called phase H, valine concentrations were moderately low hut alanine Concentrations mere raised.2. In more severe hypoalbuminaemia, culminating in kwashiorkor, a marked switch in hormonal balance occurred. Tnsulin concentrations fell to subnormal levels whereas cortisol became raised. Eventually growth hormone concentrations also increased rapidly to values similar to those found in acromegaly. By this time, phase C, alanine concentrations as well as those oE valine were fzlllirig to very low levels.3. Thepossible causes of these changes in hormonal balance, their role in the development of the distorted fasting serum amino acid pattern and their consequent effect on serum albumin synthesis and the appearance of clinical kwashiorltor are discussed.4. Information is also presented on the differences between these components in kwashiorkor and marasmus. Attempts have been made to ratiorialize apparent inconsistencies in the literature.There is growing interest in the changes which occur in the function of various endocrine organs during the pathogenesis of protein-energy malnutrition. However, most reports so far have been restricted to the measurement of a single hormone rather than to changes among a series of metabolically interrelated hormones. Moreover, they have only dealt with the acute situation, although it is becoming increasingly clear that the general metabolic pattern seen in cascs on admission to hospital can be quite different from that which has existed during most of thc earlier stages of chronic malnutrition, before the acute episode.In this investigation we have studied simultaneously three hormones which arc important in the regulation of protein and amino acid metabolism, insulin, cortisol, and growth hormone (GH). These have been measured both in patients in hospital and, serially, in children attending an out-patient clinic in an area of TJganda where kwashiorkor is endemic. The concentrations of certain plasma amino acids have also been measured and an attempt has been made to correlate the changes observed with those found in the hormone levels.https://www.cambridge.org/core/terms. https://doi

A major association has been found between low plasma triiodothyronine concentrations in preterm neonates and their later developmental outcome. Plasma triiodothyronine concentration was measured longitudinally in 280 preterm infants below 1850 g birth weight. Babies whose lowest recorded concentration was <0*3 nmoll had, at 18 months' corrected age, 8-3 and 7-4 point disadvantages in Bayley mental and motor scales and a 8-6 point disadvantage on the academic scale of Developmental Profile II, even after adjusting for a range of antenatal and neonatal factors known to influence later development. Low concentrations of triiodothyronine were strongly associated with infant mortality, but not after adjusting for the presence of respiratory illness. There was no association between plasma triiodothyronine concentrations and somatic growth up to 18 months, and no association with necrotising enterocolitis or later cerebral palsy. Data on postnatal changes in plasma triiodothyronine concentrations are presented for reference purposes. While cited reference ranges for plasma triiodothyronine concentration appear suitable for well infants above 1500 g birth weight, smaller or ill babies often have very low values for many weeks. Our data are relevant to the debate on endocrine 'replacement' treatment in premature babies.