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The objectives of this study were 1) to determine whether a zenith in bone formation (indicated by circulating osteocalcin) existed at night in early life, and 2) to compare the effects of three different dexamethasone (DEX) treatment regimens on bone turnover, bone mineral content, and growth. Three DEX treatment regimens were tested in 8-d-old piglets (n = 8/group):1) low evening dose of DEX (0.5 mg/kg/d) as 70% in the morning and 30% in the evening for 10 d;2) tapering course of DEX (0.5, 0.3, and 0.2 mg/kg/d) as 50% in the morning and 50% in the evening for 14 d; and 3) constant dose of DEX (0.5 mg/kg/d) as 50% in the morning and 50% in the evening for 10 d. Oral water placebo groups were tested with the same time courses. At pretreatment, plasma osteocalcin was significantly higher (p < 0.05) at 0100 than at 0900 and 1700. At necropsy, measures for DEX groups were calculated as Z-scores using values from the placebo groups. The low evening DEX dose led to a significantly lower reduction in plasma osteocalcin compared with the tapered and constant dosing regimens (p < 0.05). The significant weight reduction in the DEX group occurred at d 9 in the low evening dose regimen but at d 7 in the constant dosing regimen, compared with the placebo group. Bone mineral content Z-score was reduced similarly in all DEX-treated groups across the three dosing regimens. We conclude that a plasma osteocalcin zenith at night exists in early life. A high DEX dose in the morning and low DEX dose in the evening may partially attenuate corticosteroid-induced suppression of bone formation and growth restriction.

Dexamethasone (DEX) therapy improves pulmonary compliance in premature infants with chronic lung disease; however, normal growth and bone development are impaired. Because DEX may mediate its effects by altering the GH-IGF-I axis, we investigated whether adjunctive therapy with GH or GH + IGF-I during DEX therapy could attenuate these DEX-induced effects. Piglets were randomized to placebo, oral tapered DEX (0.5, 0.3, and 0.2 mg kg(-1) d(-1) over 14 d), DEX + GH (0.1 mg kg(-1) d(-1)) or DEX + GH + IGF-I (0.1 mg kg(-1) d(-1)). Final whole body weight and length were improved with GH or GH + IGF-I compared with the DEX alone group. Plasma GH and IGF-I were not influenced by DEX, but infusion of IGF-I resulted in higher (p0.05) plasma IGF-I compared with all other groups at d 15. DEX reduced (p0.05) circulating IGFBP-2 and IGFBP-3 and liver IGFBP-2 and IGFBP-4 mRNA expression compared with controls. Treatment with DEX alone resulted in lower (p0.05) plasma osteocalcin, urinary N-telopeptide, and whole body and femur bone mineral density compared with controls, whereas results with piglets receiving adjunctive GH or GH + IGF-I were similar to those of controls. Given adjunctively, GH alone appears to partially counter the abnormalities in growth and bone metabolism associated with DEX therapy; however, this improvement cannot be attributed to higher circulating IGF-I, because combined therapy did not further improve growth or bone homeostasis compared with DEX + GH treatment. Growth hormone therapy has the potential to stimulate growth in infants exposed to steroid treatment.

Premature infants receive high dietary zinc and often glucocorticoids as a treatment for chronic lung disease. A piglet model was developed to investigate intestinal zinc transport and distribution of tissue zinc in response to treatment with short-term (5 d) glucocorticoid therapy or a high zinc diet. Piglets (13–15 d old; n = 21) were randomly allocated to: 1) dexamethasone (DEX) therapy (1.5 mg/kg intramuscularly twice a day), 2) high zinc diet (15.3 mmol/kg), or 3) control group (0.3 mmol dietary zinc/kg and saline intramuscularly twice a day). Pig weight, formula intake, urine volume, and blood glucose were monitored. At necropsy, tissue samples were obtained to measure zinc in plasma and zinc and metallothionein in liver and small intestinal mucosa. Velocity of zinc uptake by intestinal brush border membrane vesicles was measured using 65Zn tracer. Maximum uptake rate and Km for zinc uptake by brush border membrane vesicles were significantly greater (p < 0.05) in DEX compared with control and high zinc groups. DEX-treated piglets had a significantly lower (p < 0.05) zinc efflux rate across brush border membrane vesicles compared with that of the control. The high zinc group had a higher liver (p < 0.05) and mucosal (p < 0.05) zinc content and higher liver metallothionein concentration (p < 0.001) compared with the control and DEX groups. Weight gain over 5 d was not different among groups. Daily blood glucose was higher (p < 0.05) in DEX versus control and high zinc groups. Short-term DEX treatment induced changes in mucosal uptake of zinc that are consistent with up-regulation of specific mucosal proteins, but this was not the case with metallothionein. These alterations in zinc metabolism may have consequences for zinc status in premature infants who receive glucocorticoids such as DEX and/or high zinc diets.

Growth, bone, and body composition were studied at prepuberty in former very low birth weight (VLBW) infants who received dexamethasone (DEX) for bronchopulmonary dysplasia (BPD) compared with VLBW infants without DEX and term-born infants (TERM) to identify early life risk factors for later low bone mass. Children (56 girls/63 boys, 5-10 y) previously studied in neonatal life were recruited into three groups: VLBW + DEX, VLBW - DEX, and TERM children. Anthropometry and whole body bone, fat, and lean mass were measured. At prepuberty, the average height and weight for VLBW + DEX group were significantly lower than that for VLBW - DEX and TERM. Both VLBW groups had lower bone mass even adjusted for height and lean mass than TERM children and lower lean mass both total and adjusted for height. Z-scores for whole body bone mineral content below -1.5 occurred in 27.9% of VLBW + DEX children. The key factors for low bone mass were earlier gestational age and having BPD with DEX in neonatal life. In former VLBW infants, growth and bone mass attainment before puberty can be predicted from early life variables. VLBW + DEX children may be protected from overweight, but are at risk for short stature and low bone mass.

Previously, we conducted dual energy x-ray absorptiometry (DXA) (Hologic QDR-1000/W) scans and carcass analysis of piglets to evaluate the Pediatric Whole Body software (PedWB) (V5.35) for use in infants. A software upgrade designed for infant whole body (InfWB) (V5.56) led to a reassessment of DXA by: 1) reanalysis of the original scans using InfWB software and 2) comparison of InfWB-estimates of bone mineral content (BMC) and lean and fat mass with chemical analysis. Other assessments included 1) methods of regional analysis and 2) artifacts and the Infant Table Pad in the scan field. The mean coefficients of variation for InfWB whole body measures in small piglets (n = 10, weight 1575 +/- 73 g) and large piglets (n = 10, weight 5894 +/- 208 g) were less than 2.6% except for fat mass which was higher (8.0% versus 6.3% and 6.6% versus 3.5%, respectively) compared with PedWB. In large piglets InfWB produced good estimates of BMC, lean and fat masses. In small piglets, fat mass by InfWB was correlated with chemical analysis, but not by PedWB. There was improvement in the estimation of BMC with InfWB, from 27 +/- 2.2 g to 32 +/- 2.3 g (carcass ash = 38 +/- 3.3 g). Femur BMC analysis by InfWB was precise and was accurate when compared with chemical analysis. Artifacts in the DXA scan field (diapers and blankets) resulted in an increase of the DXA-estimated fat and lean masses. The Infant Table Pad increased the estimate of fat mass in a small piglet by 50%, thus further study is required before it is used routinely. Improvements of the DXA technology have resulted in a more accurate tool, if scanning procedures are carefully implemented.

Randomized Trial of Feeding Nutrient-Enriched vs Standard Formula to Premature Infants during the First Year of Life

Comparison of Two Dexamethasone Treatment Regimens on Outcomes of Growth and Bone Metabolism in Piglets † 1523

Nutrition, Growth, Bone Metabolism and the Ontogeny of the GH-IGF-I Axis to Term Corrected Age in Very Low Birth Weight Infants Treated with Dexamethasone in Early Life • 1585

The Influence of Breast Compared to Formula Feeding of Preterm Infants to Three Months Corrected Age on Growth and Body Composition to One Year † 1557

REDUCED PROTEIN SYNTHESIS AND GROWTH IN DEXAMETHASONE-TREATED PIGLETS IS ATTENUATED WITH ADJUVANT GROWTH HORMONE±INSULIN-LIKE GROWTH FACTOR-I THERAPY • 1442

PREMATURE INFANTS (PI) FED BREAST MILK OR FORMULA HAVE SIMILAR GROWTH BUT DIFFERENT BODY COMPOSITION IN THE FIRST YEAR. † 1917

Premature infants (PI) with bronchopulmonary dysplasia (BPD) commonly experience growth failure beyond early infancy. Elevated basal energy expenditure (EE) combined with inadequate energy intake (EI) may be responsible. Objective: To describe patterns of energy intake and expenditure during recovery from BPD. Methods and Subjects: A longitudinal descriptive trial in which BPD infants (n=38, birth weight=867± 194 g, gestational age=26 ± 1.4 wk) were fed a standard premature formula (810 kcal/L) prior to 36.5 ± 1.6 wk post-mentural age(PMA), and then were fed an energy enriched formula (900 kcal/L) until 3 mo corrected age (CA). Measurement of EE by oral dosing of doubly labelled water(0.3 g/kg 18O and 0.1 g/kg deuterium with urine analysis by mass spectrometry at 1 and 7 days) was done at 34.5 ± 1.3 wk PMA(in-hospital), at 1 (0.75 ± 0.4) and 3 (3.3 ± 0.4) mo CA at home. Energy intake at home was determined by weighed intake.Results: The Table shows EE as a% of EI(EE/EI) and total EE of BPD infants compared to reference infants (REF): 34.5 wk-healthy PI (Jensen et al, 1992); 1 and 3 mo-infants born at term (Davies et al, 1990). EI at 34.5 wk, 1 and 3 mo (119±8, 118±20 and 114±24 kcal/kg/d, respectively) met or exceeded recommended EI for infants. Although EE of BPD infants was more variable than term REF infants, they appeared to have greater basal EE, depleting the proportion of energy available for storage. Weight gain patterns supported this trend, since no catch-up growth was observed from 1 to 3 mo CA. Conclusions: Prolonged excessive EE during recovery from BPD reflects the need for aggressive nutritional therapy beyond the neonatal period, and possibly beyond 3 mo CA. (Funded by MOH and Wyeth-Ayerst, USA)

Complete 24-hour expressions of human breast milk were collected serially from 7 mothers giving birth at 26-33 wk gestation (Premature,PT) and 8 mothers at 38-40 wk gestation (Full-term,FT) during the first 29 days postpartum. Individual milk samples (69) were analyzed for total N concentration. The regression lines describing the change in N concentration (y) with time in days (d) were y=368 - 4.36d (r=-0.60,p

The increasing survival of VLBW premature infants requires a precise knowledge of utilization of essential nutrients (P=protein F=fat, C=carbohydrate) in order to design suitable dietary regimes Energy balance (EB), substrate utilization for oxidation (0) and tissue deposition studies were performed on VLBW premature infants (n=10; gest. age 27-31 weeks; birth weight 940 - 1280 g; postnat. age 1 - 4 weeks) fed by own mother's milk (6 studies on 4 infants) or humanized milk (SMA 20/24 Wyeth; 13 studies on 6 infants). EB for growth was determined by the equation: EB = ME - 0 (P+F+C). By increasing the net energy intake (NEI) from 50 to 150 Kcal/kg/day, resting metabolic rate (RMR) increased from 38 to 58 Kcal/kg/day in the formula fed infants (FFI) and from 45 to 58 in the breast fed infants (BFI). In a range of 50-110 Kcal/kg/day NEI the RMR was consistently higher in BFI. The latter deposited more P than FFI at the same level of NEI. At a NEI of 100 Kcal/kg/day FFI deposited 1 g P/day in contrast to the 2 g/kg/day P deposition observed in the BFI. Tissue deposition of F increases with the enhancement of NEI in both FFI and BFI but the relationship is the reverse to that observed for P deposition. At a 100 Kcal/kg/day NEI 18 Kcal/kg/day energy is deposited as F in the BFI in contrast to the 28 Kcal/kg/day deposition in FFI. It is concluded that the quality of growth (P v.F deposition) in response to a specific diet composition may be defined by our investigative approach.