Ian J. Griffin

Feeding Preterm Infants Today for Later Metabolic and Cardiovascular Outcomes

Preterm birth continues to contribute disproportionately to neonatal morbidity and subsequent physical and neurodevelopmental disabilities. Epidemiologic studies have described additional long-term health consequences of preterm birth such as an increased risk of hypertension and insulin resistance in adult life. It is not known whether the influence of infant and childhood growth rates and early nutrition on long-term outcomes is the same or different among preterm infants and neonates with intrauterine growth restriction. Our goal is to review the effects of fetal growth, postnatal growth, and early nutrition on long-term cardiovascular and metabolic outcomes in preterm infants. Present evidence suggests that even brief periods of relative undernutrition during a sensitive period of development have significant adverse effects on later development. Our review suggests that growth between birth and expected term and 12-18 months post-term has no significant effect on later blood pressure and metabolic syndrome, whereas reduced growth during hospitalization significantly impacts later neurodevelopment. In contrast, growth during late infancy and childhood appears to be a major determinant of later metabolic and cardiovascular well being, which suggests that nutritional interventions during this period are worthy of more study. Our review also highlights the paucity of well-designed, controlled studies in preterm infants of the effects of nutrition during hospitalization and after discharge on development, the risk of developing hypertension, or insulin resistance.

Feeding Preterm Infants after Hospital Discharge: Growth and Development at 18 Months of Age

We have shown that preterm infants fed a preterm formula grow better than those fed a standard term infant formula after hospital discharge. The purpose of this follow-up study was to determine whether improved early growth was associated with later growth and development. Preterm infants (≤1750 g birth weight, ≤34 wk gestation) were randomized to be fed either a preterm infant formula (discharge to 6 mo corrected age), or a term formula (discharge to 6 mo), or the preterm (discharge to term) and the term formula (term to 6 mo). Anthropometry was performed at 12 wk and 6, 12, and 18 mo. Mental and psychomotor development were assessed using the Bayley Scales of Infant Development II at 18 mo. Differences in growth observed at 12 wk were maintained at 18 mo. At 18 mo, boys fed the preterm formula were 1.0 kg heavier, 2 cm longer, and had a 1.0 cm greater occipitofrontal circumference than boys fed the term formula. Boys fed the preterm formula were also 600 g heavier and 2 cm longer than girls fed the preterm formula. However, no differences were noted in MDI or PDI between boys fed the preterm formula and boys fed the term formula or between the boys fed preterm formula and girls fed the preterm formula. Overall, boys had significantly lower MDI than girls (mean difference, 6.0;p < 0.01), primarily reflecting lower scores in boys fed the term formula. Thus, early diet has long-term effects on growth but not development at 18 mo of age. Sex remains an important confounding variable when assessing growth and developmental outcome in these high-risk infants.

Altered body composition in preterm infants at hospital discharge

Aim:u2002 To test the hypotheses that body size is reduced and body composition altered in preterm infants at hospital discharge.

Feeding Preterm Infants after Hospital Discharge: Effect of Diet on Body Composition

Our purpose in this study was to examine whole body composition, using dual energy x-ray absorptiometry (DEXA) during dietary intervention in preterm infants (≤1750 g birthweight, ≤34 wk gestation). At discharge, infants were randomized to be fed either a preterm infant formula (discharge–6 mo; group A) or a term formula (discharge–6 mo; group B), or the preterm formula (discharge–term) and the term formula (term–6 mo; group C). Nutrient intake was measured between each clinic visit. To measure body composition, DEXA was used at discharge, term, 12 wk, 6 mo, and 12 mo corrected age. The data were analyzed by ANOVA. At discharge, no differences were noted in patient characteristics between groups A, B, and C. Although energy intakes were similar, protein and mineral intakes differed between groups (A > C > B;p< 0.0001). During the study, weight gain and LM gain were greater in group A than B. At 12 mo, weight, LM, FM, and BMM but not % FM or BMD were greater in group A than B. However, the effects of diet were confined to boys, with no lasting effects seen in girls. In summary, therefore, DEXA was precise enough to detect differences in whole body composition during dietary intervention. Increased weight gain primarily reflected an increase in LM and is consistent with the idea that the preterm formula more closely met protein and/or protein-energy needs in rapidly growing preterm male infants.

Body composition of preterm infants during infancy

AIMS To examine body composition in preterm infants. METHODS Body composition was measured by dual energy x-ray absorptiometry (DEXA) at hospital discharge, term, 12 weeks, and at 6 and 12 months corrected age in 125 infants (birthweight ⩽ 1750 g, gestational age ⩽ 34 weeks). RESULTS Body weight derived by DEXA accurately predicted that determined by conventional scales. In both sexes lean mass (LM), fat mass (FM), %FM, bone area (BA), bone mineral mass (BMM), and bone mineral density (BMD) increased rapidly during the study; significant changes were detectable between discharge and term. At 12 months, LM, BA, and BMM, but not FM, %FM, or BMD were greater in boys than in girls. Corrected for age, LM was less than those of the reference term infant; FM and %FM were similar; BMM was greater. Corrected for weight, LM was similar to those of the reference infant, while the FM and %FM of study infants were slightly greater. CONCLUSIONS DEXA accurately measures body mass. Body composition in preterm boys and girls differs. Interpretation of DEXA values may depend on whether age or body weight are regarded as the appropriate reference.

Perturbed Zinc Homeostasis in Rural 3-5-y-Old Malawian Children Is Associated With Abnormalities in Intestinal Permeability Attributed to Tropical Enteropathy

Tropical enteropathy and zinc deficiency are major public health problems worldwide. Tropical enteropathy is characterized by reduced mannitol absorption with normal or increased lactulose absorption when a dual sugar absorption test is administered, the results of which are reported as the lactulose:mannitol ratio (L:M). Zinc homeostasis is quantified with a dual stable isotope test. This study tested the hypothesis that endogenous fecal zinc (EFZ) was correlated with the L:M. A dual sugar absorption test and dual stable isotope test were performed on 25 asymptomatic Malawian children aged 3–5 y at risk for tropical enteropathy and zinc deficiency. EFZ and net zinc retention were estimated and correlated with the L:M. Twenty-two children (88%) had an abnormal L:M (L:M >0.10), and the L:M was 0.24 ± 0.10 (mean ± SD). EFZ was 1.68 ± 1.06 mg/d, a quantity greater than is seen in healthy populations from the developed world. EFZ was positively correlated with the L:M (r = 0.62, p < 0.001). Net zinc retention (0.67 ± 1.6 mg/d) was negatively correlated with the L:M (r = −0.47, p = 0.02). This suggests that perturbed zinc homeostasis is associated with subclinical enteropathy in these children.

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.

Postnatal growth failure in very low birthweight infants born between 2005 and 2012

Background Postnatal growth restriction is common in preterm infants and is associated with long-term neurodevelopmental impairment. Recent trends in postnatal growth restriction are unclear. Methods Birth and discharge weights from 25u2005899 Californian very low birthweight infants (birth weight 500–1500u2005g, gestational age 22–32u2005weeks) who were born between 2005 and 2012 were converted to age-specific Z-scores and analysed using multivariable modelling. Results Birthweight Z-score did not change between 2005 and 2012. However, the adjusted discharge weight Z-score increased significantly by 0.168 Z-scores (0.154, 0.182) over the study period, and the adjusted fall in weight Z-score between birth and discharge decreased significantly between those dates (by 0.016 Z-scores/year). The proportion of infants who were discharged home below the 10th weight-for-age centile or had a fall in weight Z-score between birth and discharge of >1 decreased significantly over time. The comorbidities most associated with poorer postnatal growth were medical or surgical necrotising enterocolitis, isolated gastrointestinal perforation and severe retinopathy of prematurity, which were associated with an adjusted mean reduction in discharge weight Z-score of 0.24, 0.57, 0.46 and 0.32, respectively. Chronic lung disease was not a risk factor after accounting for length of stay. Conclusions Postnatal, but not prenatal, growth improved among very low birthweight infants between 2005 and 2012. Neonatal morbidities including necrotising enterocolitis, gastrointestinal perforations and severe retinopathy of prematurity have significant negative effects on postnatal growth.

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.

Selected macro/micronutrient needs of the routine preterm infant.

Requirements for optimal nutrition, especially for micronutrients, are not well defined for premature infants. The reference fetus, developed by Ziegler etxa0al,(1) has served as a model to define nutritional needs and studies designed to determine nutrient requirements. Revision of nutrient requirements and provision of optimal nutrition may lead to improved outcomes in preterm infants. Appropriate provision of nutrients also may help prevent nutritional disorders, such as metabolic bone disease and anemia. In this review, we discuss calcium, phosphorus, magnesium, vitamin D, iron, and copper, and define optimal intakes based on the available published data.