Iron Balance and Iron Nutritional Status in Preterm Infants During the First Four Months of Life.

OBJECTIVES: To determine whether iron absorption occurs in a dose-dependent fashion and/or is a function of iron nutritional status (INS) in preterm infants during the first 4 months of life. METHODS: Preterm very-low-birth-weight infants (VLBWI) were fed an iron-fortified (0.7 mg/dL) infant formula. Three 48 h balance studies were performed on each infant. INS was determined by serially measuring hemoglobin, mean corpuscular volume (MCV), hematocrit, ferritin, transferrin and transferrin saturation levels. The data were analyzed using ANOVA and stepwise regression. RESULTS: Fifty-four balance studies were performed in 18 infants (birth weight, 1347 ± 201 g; gestation, 30 ±â€Š1.3 weeks; mean ±â€Šstandard deviation) at 33 ±â€Š1.3, 34 ±â€Š1.2, and 48 ±â€Š0.5 weeks corrected age and weights of 1768 ±â€Š260, 2298 ±â€Š314, 5127 ±â€Š939 g. No relationship was detected between iron intake and absorption. Intake decreased during the study (1.17 ±â€Š.08, 1.24 ±â€Š0.11 > 1.1 ±â€Š0.15 mg ·â€Škg-1 ·â€Šday-1) but net (0.32 ±â€Š0.26, 0.36 ±â€Š31 < 0.49 ±â€Š.23 mg ·â€Škg-1 ·â€Šday-1) and % (27 ±â€Š22, 29 ±â€Š23 < 46 ±â€Š21) absorption increased (P < 0.01). Serum ferritin, transferrin saturation and MCV fell, while hematocrit and hemoglobin remained stable. No relationship was noted between serum ferritin and iron absorption but transferrin saturation (54%), MCV (7%), and hematocrit (6%) accounted for 67% of the variation in iron absorption (P < 0.001). CONCLUSIONS: At intakes of 0.8-1.4  mg ·â€Škg-1 ·â€Šday-1, iron absorption is not dose-dependent nor affected by iron stores. Only when iron delivery to the tissues decreases does absorption increase to meet needs in these otherwise normal and rapidly growing infants.

Improving growth in preterm infants during initial hospital stay: principles into practice.

Despite recent innovations in nutritional care, postnatal growth failure between birth and hospital discharge remains a significant problem in preterm infants. Whether or not it is entirely preventable is unclear. What is clear is that feeding practices and growth outcomes vary widely between neonatal intensive care units (NICUs). This partly reflects lack of data in key areas but it also reflects inconsistent translation of principles into practice and limitations in the way infants are fed and growth monitored in the NICU. These issues will be reviewed, in the process underline the key roles that audit, standardised feeding protocol, individualised nutritional care and a nutritional support team play in improving outcome in these high-risk infants.

Growth and metabolic outcome in adolescents born preterm (GROWMORE): follow-up protocol for the Newcastle Preterm Birth GRowth study (PTBGS).

BACKGROUND: Preterm infants represent up to 10% of births worldwide and have an increased risk of adverse metabolic outcomes in later life. Early life exposures are key factors in determining later health but current lifestyle factors such as diet and physical activity are also extremely important and provide an opportunity for targeted intervention. METHODS/DESIGN: This current study, GROWMORE, is the fourth phase of the Newcastle Preterm Birth Growth Study (PTBGS), which was formed from two randomised controlled trials of nutrition in early life in preterm (24-34 weeks gestation) and low birthweight infants. 247 infants were recruited prior to hospital discharge. Infant follow-up included detailed measures of growth, nutritional intake, morbidities and body composition (Dual X Ray Absorptiometry, DXA) along with demographic data until 2 years corrected age. Developmental assessment was performed at 18 months corrected age, and cognitive assessment at 9-10 years of age. Growth, body composition (DXA), blood pressure and metabolic function (insulin resistance and lipid profile) were assessed at 9-13 years of age, and samples obtained for epigenetic analysis. In GROWMORE, we will follow up a representative cohort using established techniques and novel metabolic biomarkers and correlate these with current lifestyle factors including physical activity and dietary intake. We will assess auxology, body composition (BODPOD), insulin resistance, daily activity levels using Actigraph software and use 31P and 1H magnetic resonance spectroscopy to assess mitochondrial function and intra-hepatic lipid content. DISCUSSION: The Newcastle PTBGS is a unique cohort of children born preterm in the late 1990's. The major strengths are the high level of detail of early nutritional and growth exposures, and the comprehensive assessment over time. This study aims to examine the associations between early life exposures in preterm infants and metabolic outcomes in adolescence, which represents an area of major translational importance.

Development of whole body adiposity in preterm infants.

The long-term effects of prematurity, early diet and catch-up growth on metabolic risk and body adiposity are of increasing interest to Neonatologists. Poor growth is known to be associated with poorer neuro-developmental outcome but concern exists that increased rates of "catch-up" (or "recovery") growth may be associated with increased adiposity and the later development of metabolic syndrome. In this manuscript we review the published data on body composition in preterm infants, and present new analyses of body adiposity in preterm infants during the 12-15 months of life, and the effect of growth rate (weight gain) on body adiposity. We conclude that although preterm infants have increased adiposity at term corrected age, they generally have lower body fat than their term peers during the rest of the 12-15 months of life. Although more rapid "catch-up" growth in preterm infants during the first year of life is associated with greater body fatness than slower rates of growth, these higher rates of growth lead to body composition more similar to that of the term-born infant, than do slower rates of growth. Although more studies are needed to determine whether these short-term increases or the longer-term decreases in adiposity modify the risk on chronic diseases such as diabetes mellitus, hypertension or other components of the metabolic syndrome, the widely held concern that preterm babies have greater adiposity than their term peers, and that this is worsened by greater amounts of catch-up growth, are not supported by the available evidence.

Adiposity is not altered in preterm infants fed with a nutrient-enriched formula after hospital discharge.

To determine whether adiposity was altered, body size (weight, length) and composition, determined by dual energy x-ray absorptiometry, were examined in preterm infants fed with a nutrient enriched (A, n=56), a term infant (B, n=57) or the nutrient enriched (discharge and term) plus the term formula (term and 6 mo; C, n=26), and a group of breast-fed preterm infants (D, n=25) at hospital discharge, 3, 6, and 12 mo corrected age. The results were analyzed using standard statistics. One hundred sixty-four infants (birth weight=1406+/-248 g, GA=31+/-1.7 wk) were studied. All infants underwent "catch-up," but weight and length were greater in infants in group A compared with groups B, C, or D. More rapid and complete "catch-up" was paralleled by increased total nonfat and fat mass (g) but not percentage of fat mass. Changes in fat mass (g) were primarily explained by increased fat accretion on the legs. More rapid and complete "catch-up" growth, therefore, reflected increased nonfat and peripheral fat mass. These data do not support the hypothesis of increased or central adiposity in infants fed a nutrient-enriched formula after hospital discharge.

Iron retention in preterm infants fed low iron intakes: a metabolic balance study.

There is little data on iron retention in healthy preterm infants. Twenty-four metabolic balance studies were carried out in 13 preterm infants between 17 and 63 days of age, in 11 cases 2 balance were carried out 7d apart. Iron intake was 1.11 mg/kg/day (SD 0.06), less than the 2 mg/kg/d typically recommended for preterm infants. Iron retention was positive in the majority (3/13) of the first balances, and in all 11 of the second balances. Iron retention increased significantly between the two balances (from 0.095 mg/kg/d (SD 0.178) to 0.270 (SD 0.209)). Iron retention was significantly related to the time that the infant had been on enteral feeds at the time the balance was carried out. Iron retention was significantly greater than the requirement estimated to be needed to meet the needs for growth and expansion of the circulating red cell mass. Iron intakes of about 1mg/kg/d seem to be adequate to support the requirements for growth in preterm infants during this time period, but are significantly less than the estimated in utero accretion rate of the fetus.

Postnatal growth and development in the preterm and small for gestational age infant.

A clear relationship exists between undernutrition, poorer growth and poor development in term and preterm infants. However, preterm infants are at greater risk than term infants. Undernutrition is more common and 'programmed' growth rates are almost six times faster. Thus, even short periods of nutritional deprivation may have significant effects. Recent advances have led to an improvement in early growth but very low birthweight infants remain small for gestational age at hospital discharge. Studies suggest that a 'window of opportunity' exists after hospital discharge, in that better growth between discharge and 2-3 months corrected age is paralleled by better development, and poorer growth is associated with poorer development. However, interventions aimed at improving growth and development have yielded varying results. This may partly be related to differences in study design as well as the composition of the nutrient-enriched formulas. Irrespective, one point is concerning, i.e. infant boys appear to be at a developmental disadvantage when fed a term infant formula after discharge. A single study has also suggested that dietary intervention can improve brain growth in term and preterm infants with perinatal brain injury. However, concern has been expressed about rapid 'catch-up' growth in preterm infants and the development of insulin resistance and visceral adiposity. Data from our group do not support the idea of increased or altered adiposity in preterm infants fed a nutrient-enriched formula after hospital discharge.

Altered body composition in preterm infants at hospital discharge.

AIM: To test the hypotheses that body size is reduced and body composition altered in preterm infants at hospital discharge. METHODS: Preterm infants (< or = 34 weeks gestation, < or = 1750 g at birth) were enrolled. Body weight, length and head circumference were converted to standard deviation or z-scores. Body composition was measured using dual emission X-ray absorptiometry. The results were analysed using standard statistics. RESULTS: One hundred and forty-nine infants (birth weight = 1406 +/- 248 g, gestation = 31 +/- 1.7 weeks) were studied. Postmenstrual age at discharge was 37 +/- 1.2 weeks. Z-scores for head circumference, weight and length differed (-0.1 +/- 0.6 > -1.4 +/- 0.6 > -1.9 +/- 0.6; p < 0.0001). Global fat-free mass was less in study infants than the reference infant at the same weight (2062 < 2252 g; p < 0.0001) or gestation (2062 < 2667 g; p < 0.0001). Global fat mass was greater in study infants than the reference infant at the same weight (307 > 198 g, 13 > 8%) or gestation (307 > 273 g; 13 > 9%; p < 0.0001). Changes in central fat mass closely paralleled those in global fat mass (r(2) = 0.76, p < 0.0001). CONCLUSION: Reduced linear growth and a reduced fat-free mass suggest that dietary protein needs were not met before discharge. A reduced fat-free mass coupled with an increased global and central fat mass echoes concerns about the development of insulin resistance and metabolic syndrome X in these high-risk infants.

Nutrition of preterm infants after hospital discharge.

Growth failure in preterm infants remains extremely common despite advances in neonatal care. Many, or even a majority, leave the hospital with weights below the 10th centile for age. Because of this, the possibility of nutritional interventions to improve postdischarge growth has been considered. A variety of interventions have been tested in randomized controlled trials in formula-fed infants. Although the studies vary in design and in the intervention used, on balance the evidence supports the use of fortified formulas in formula-fed preterm infants after hospital discharge. Specially designed postdischarge formulas and preterm infant formulas seem equally efficacious. The situation for infants fed human milk is much less clear. Although the postdischarge growth in human milk-fed infants is not as good as in formula-fed infants, no interventions have been examined in human milk-fed infants in a randomized study, to our knowledge. We are unaware of any evidence that any of the commonly proposed nutritional interventions in human milk-fed infants after hospital discharge are either safe or efficacious. In the absence of such evidence, it seems prudent to avoid untested interventions in this population and to concentrate our efforts on the encouragement of breast-feeding after hospital discharge.

Postdischarge nutrition of preterm infants: more questions than answers.

Postnatal growth retardation is inevitable in preterm infants, the more immature the infant the greater the degree of postnatal growth retardation at hospital discharge. After hospital discharge, several studies have shown that growth is poorer in preterm infants fed a standard term formula than those fed a nutrient-enriched infant formula. This is not surprising because term formulas are designed to meet the requirements of the term infant, not the more rapidly growing preterm infant. After hospital discharge, breastfed infants do not grow as well as their formula-fed counterparts. Yet, there are no randomized controlled trials comparing growth in breastfed infants who did and did not receive nutrient supplementation. If mature human milk is designed to meet the needs of the term infant then breastfed preterm infants may also benefit from nutrient supplementation. Questions persist about nutritional support of preterm infants after discharge. What is the ideal composition of a postdischarge formula? Given the wide heterogeneity in nutritional status of preterm infants at hospital discharge and the difference in growth rates and composition between girls and boys, it is not clear that one formula can or will meet the nutritional needs of all infants. Studies in which infants were fed a nutrient-enriched formula to >/=6 months' corrected age show the most consistent advantage while those in which the nutrient-enriched formula was fed to

Protein requirements in preterm infants: effect of different levels of protein intake on growth and body composition.

This study compares growth and body composition in preterm infants (< or =1750 g birth weight, < or =34 wk gestation) fed three iso-caloric formulas (80 kcal/100 mL) with different protein concentrations (A = 3.3 g/100 kcal, B = 3.0 g/100 kcal, C = 2.7 g/100 kcal). The study began when full enteral feeding (150 mL/kg/d) was established and lasted until term plus 12 wk corrected age (T + 12 wca). Nutrient intake was closely monitored throughout the study; daily during initial hospital stay and following discharge averaged between each clinic visit. Anthropometry and serum biochemistries were determined weekly during initial stay and at each clinic visit. Body composition was measured after hospital discharge and at T + 12 wca. Seventy-seven infants were recruited. No differences were detected in birth/enrollment characteristics between the groups. Protein intake was closely paralleled by changes in serum urea nitrogen and differed between the groups. Infants in group A were heavier and longer and had greater head circumference at discharge, but this was confounded by a slightly older corrected age in this group. There were no significant anthropometric differences at term or T + 12 wca. No differences were detected in body composition between the groups following discharge or at T + 12 wca. An intake of 3.3 g/100 kcal appears safe and may promote increased growth before initial hospital discharge. After discharge, intakes greater than 2.7 g/100 kcal do not appear to offer clear advantage. Further studies are needed to more precisely define protein requirements in these nutritionally at-risk infants.