Increased risk of refeeding syndrome-like hypophosphatemia with high initial amino acid intake in small-for-gestational-age, extremely-low-birthweight infants.

BACKGROUND: Recent nutrition guidelines for extremely-low-birth-weight infants (ELBWIs) recommend implementation of high initial amino acid (AA) supplementation in parenteral nutrition. OBJECTIVE: We sought to evaluate the influence of AA intake on refeeding syndrome-like electrolyte disturbances including hypophosphatemia in ELBWIs. STUDY DESIGN: Medical records of 142 ELBWIs were reviewed. Demographic, nutritional, outcome, and electrolyte data were compared between ELBWIs with initial low (1.5 g/kg/day) and high (3 g/kg/day) AA intake. Multivariate analysis was conducted to determine the odds ratio of hypophosphatemia with high AA intake and small-for-gestational-age (SGA) ELBWIs. RESULTS: The incidence of hypophosphatemia and severe hypophosphatemia increased from 51% and 8% in period I to 59% and 20% in period II, respectively (p = 0.36 and < 0.01). Specifically, SGA ELBWIs showed higher incidence of hypophosphatemia than appropriate-for-gestational age (AGA) ELBWIs in period II, whereas there was no difference in period I. For severe hypophosphatemia, SGA ELBWIs presented a 27% incidence versus a 2% incidence in AGA ELBWIs, even with low initial AA intake. Despite no difference in phosphate intake between infants with and without hypophosphatemia, serum phosphate level reached a nadir at the sixth postnatal day and gradually recovered over the second week in infants with hypophosphatemia. In multivariate analyses, the odds ratios for severe hypophosphatemia were 3.6 and 6.6 with high AA intake and SGA status, respectively, with the highest being 18.0 with combined high AA intake and SGA status. CONCLUSIONS: In summary, high initial AA intake significantly increased the risk of refeeding syndrome-like electrolyte dysregulations including severe hypophosphatemia in ELBWIs. In SGA ELBWIs, the risk of electrolyte disturbance was significantly higher, even with low initial AA intake. Therefore, new tailored parenteral nutrition protocols starting with lower energy intake and a gradual increase over the first week may be warranted for application in high-risk SGA ELBWIs.

Energy expenditure, growth, and nutritional therapy in appropriate and small for gestational age preterm infants / Gasto energético, crescimento e terapia nutricional em recém-nascidos pré-termo adequados e pequenos para idade gestacional

Abstract Objective: To evaluate the resting energy expenditure, growth, and quantity of energy and macronutrients intake in a group of preterm newborns. Methods: The cohort study was performed with appropriate and small for gestational age preterm infants (birth weight lower than 1500 g or gestational age < 32 weeks). Resting energy expenditure was measured using indirect calorimetry on the 7th, 14th, 21st, and 28th days of life, and at discharge. Length, head circumference and body weight were assessed weekly. Nutritional therapy was calculated during the hospital stay and the information for each type of food was recorded in software that calculates the total amount of energy and macronutrients. Results: 61 preterm infants were followed; 43 appropriate and 18 small for gestational age infants. There was no statistical difference for resting energy expenditure between the groups, and it increased from the first to the fourth week of life (appropriate: 26.3% and small: 21.8%). Energy intake in the first two weeks of life was well below the energy requirement. Conclusion: Considering that the results demonstrate high energy expenditure during the first weeks of life, there is an evident need to provide the best quality of nutrition for each child in the first weeks of life so that preterm infants with or without intrauterine growth restriction can achieve their maximum potential for growth and development.

Resumo Objetivo: Avaliar o gasto energético de repouso, o crescimento e a quantidade ofertada de energia e macronutrientes em um grupo de recém-nascidos pré-termo. Método: Foi feito estudo de coorte com recém-nascidos pré-termo adequados e pequenos para a idade gestacional (peso de nascimento inferior a 1.500 gramas ou idade gestacional < 32 semanas). O gasto energético foi avaliado com a calorimetria indireta nos dias 7°, 14°, 21°, 28° dias de vida e alta hospitalar. Medidas do comprimento, perímetro cefálico e peso corporal foram avaliadas semanalmente. A terapia nutricional foi calculada durante a internação do recém-nascido e as informações de cada tipo de alimentação foram registradas em um software que calcula a quantidade total de energia e macronutrientes. Resultados: Foram acompanhados 61 recém-nascidos, sendo 43 adequados e 18 pequenos para idade gestacional. O gasto energético de repouso não apresentou diferença estatística entre os grupos e aumentou entre a primeira e quarta semana de vida (adequados: 26,3% e pequenos: 21,8%). O aporte energético nas duas primeiras semanas de vida mostrou-se bem abaixo do requerimento energético mensurado pela calorimetria. Conclusão: Considerando os resultados que demonstram um gasto energético alto ao longo das primeiras semanas de vida, fica evidente a necessidade de fornecer ao recém-nascido pré-termo um melhor aporte energético já nas primeiras semanas de vida, para que os neonatos com ou sem restrição intrauterina possam atingir o seu potencial máximo de crescimento e desenvolvimento.

Exchangeable Zinc Pool Size at Birth in Pakistani Small for Gestational Age and Appropriate for Gestational Age Infants Do Not Differ But Are Lower Than in US Infants.

OBJECTIVES: Small for gestational age (SGA) infants are more susceptible to infectious morbidity and growth faltering compared to their appropriate for gestational age (AGA) counterparts. Zinc supplementation of SGA infants may be beneficial but the underlying susceptibility to zinc deficiency of SGA infants has not been examined. METHODS: In a community-based, observational, longitudinal study in a peri-urban settlement of Karachi, Pakistan, we compared the size of the exchangeable zinc pools (EZPs) in term SGA and AGA infants at birth and at 6 months of age, hypothesizing that the EZP would be lower in the SGA group. To measure EZP size, a zinc stable isotope was intravenously administered within 48 hours of birth (n = 17 and 22) at 6 months (n = 11 and 14) in SGA and AGA infants, respectively. Isotopic enrichment in urine was used to determine EZP. RESULTS: No significant difference was detected in the mean (±standard deviation) EZP between SGA and AGA infants at birth, with values of 9.8 ±â€Š3.5 and 10.1 ±â€Š4.1 mg/kg, respectively (P = 0.86), or at 6 months. Longitudinal EZP measurements demonstrated a significant decline in EZP relative to body weight in both groups at 6 months (P < 0.001). Mean EZP (adjusted for body weight) size at birth for the combined Pakistani groups was significantly lower than AGA infants at birth in the United States (P = 0.017). CONCLUSIONS: These results did not support a difference in zinc endowment between SGA and AGA Pakistani infants. They, however, do suggest lower in utero zinc transfer to the fetus in a setting where poor maternal nutritional status may confer a high susceptibility to postnatal zinc deficiency.

Energy expenditure, growth, and nutritional therapy in appropriate and small for gestational age preterm infants.

OBJECTIVE: To evaluate the resting energy expenditure, growth, and quantity of energy and macronutrients intake in a group of preterm newborns. METHODS: The cohort study was performed with appropriate and small for gestational age preterm infants (birth weight lower than 1500g or gestational age<32 weeks). Resting energy expenditure was measured using indirect calorimetry on the 7th, 14th, 21st, and 28th days of life, and at discharge. Length, head circumference and body weight were assessed weekly. Nutritional therapy was calculated during the hospital stay and the information for each type of food was recorded in software that calculates the total amount of energy and macronutrients. RESULTS: 61 preterm infants were followed; 43 appropriate and 18 small for gestational age infants. There was no statistical difference for resting energy expenditure between the groups, and it increased from the first to the fourth week of life (appropriate: 26.3% and small: 21.8%). Energy intake in the first two weeks of life was well below the energy requirement. CONCLUSION: Considering that the results demonstrate high energy expenditure during the first weeks of life, there is an evident need to provide the best quality of nutrition for each child in the first weeks of life so that preterm infants with or without intrauterine growth restriction can achieve their maximum potential for growth and development.

Maternal caffeine consumption and small for gestational age births: results from a population-based case-control study.

Caffeine is consumed in various forms during pregnancy, has increased half-life during pregnancy and crosses the placental barrier. Small for gestational age (SGA) is an important perinatal outcome and has been associated with long term complications. We examined the association between maternal caffeine intake and SGA using National Birth Defects Prevention Study data. Non-malformed live born infants with an estimated date of delivery from 1997-2007 (n = 7,943) were included in this analysis. Maternal caffeine exposure was examined as total caffeine intake and individual caffeinated beverage type (coffee, tea, and soda); sex-, race/ethnic-, and parity-specific growth curves were constructed to estimate SGA births. Crude and adjusted odds ratios (aORs) and 95% confidence intervals were estimated using unconditional logistic regression. Interaction with caffeine exposures was assessed for maternal smoking, vasoconstrictor medication use, and folic acid. Six hundred forty-eight infants (8.2%) were found to be SGA in this analysis. Increasing aORs were observed for increasing intakes of total caffeine and for each caffeinated beverage with aORs (adjusting for maternal education, high blood pressure, and smoking) ranging from 1.3 to 2.1 for the highest intake categories (300+ mg/day total caffeine and 3+ servings/day for each beverage type). Little indication of additive interaction by maternal smoking, vasoconstrictor medication use, or folic acid intake was observed. We observed an increase in SGA births for mothers with higher caffeine intake, particularly for those consuming 300+ mg of caffeine per day. Increased aORs were also observed for tea intake but were more attenuated for coffee and soda intake.

Change in total body water as a predictive tool for growth hormone treatment response.

BACKGROUND/AIMS: To investigate whether short-term changes in body composition as a result of growth hormone therapy could be used to predict its growth effect after 1 year in children with growth hormone deficiency (GHD) and children born small for gestational age (SGA). METHODS: 88 GHD children and 99 SGA children who started treatment with recombinant human growth hormone were included. Total body water (TBW) and height were measured. After 1 year, patients were divided into adequate and inadequate responders. RESULTS: In GHD and SGA children a sensitivity of 87 and 53%, respectively, and a specificity of 58 and 83%, respectively, were found. The positive predictive values for GHD and SGA children were 73 and 90%, respectively. The negative predictive values were 75 and 32%, respectively. CONCLUSION: Changes in body composition data measured by TBW are a valuable tool to correctly predict 75% of the GHD children and are only useful in SGA children when the change in TBW is above the cut-off value of 0.7 l/m(2).

Zinc supplementation in infants with asymmetric intra uterine growth retardation; effect on growth, nutritional status and leptin secretion / Suplementación con zinc en niños con retraso de crecimiento intra-uterino asimétrico; efecto en el crecimiento, estado nutricional y secreción de leptina

Objetivos: Valorar el efecto de la suplementación con cinc en el crecimiento y estado nutricional de un grupo homogéneo de recién nacidos con retraso de crecimiento intra-uterino asimétrico. También se analizó el efecto delos cambios en el status del cinc en el crecimiento y las concentraciones séricas de leptina. Población y método: Se diseñó un ensayo clínico randomizado y doble ciego, con el fin de detectar diferencias en el crecimiento entre los grupos recibiendo cinc o placebo, durante los seis primeros meses de vida. 31 niños fueron incluidos en el grupo cinc (n = 14) (38,8 ± 1,4 semanas edad gestacional, 2.171 ± 253 g peso) o grupo placebo (n = 17) (38,9 ± 1.1 semanas edad gestacional, 2.249 ± 220 g peso). El grupo cinc recibió un suplemento de 3 mg de cinc elemental por día (en forma de sulfato de cinc).Resultados: No hubo diferencias significativas entre ambos grupos en cuanto a las medidas antropométricas a lo largo del período de estudio. Se observó un efecto significativo del grupo de estudio, en las concentraciones de cinc en el pelo, pero no en las concentraciones séricas de cinc; las comparaciones post-hoc para el cinc del pelo pusieron de manifiesto que había diferencias significativas entre los grupos, en los meses 1, 2 y 6 de edad. Los cambios en las concentraciones de cinc en el suero y en el pelo, desde el inicio del estudio hasta los 6 meses, mostraron correlaciones estadísticamente significativas con los cambios en peso/edad y longitud/edad (puntuación típica), en el grupo que recibió el suplemento de cinc. Los cambios en las concentraciones séricas de leptina durante el seguimiento, mostraron correlaciones estadísticamente significativas para la suma de 4 pliegues y para peso/edad (puntuación típica), en el grupo placebo. Los cambios en las concentraciones de cinc en el pelo mostraron correlaciones estadísticamente significativas con los cambios en las concentraciones séricas de leptina, desde el inicio del estudio hasta los 6 meses de seguimiento. Conclusiones: En un grupo homogéneo de niños con retraso de crecimiento intra-uterino asimétrico, el suplemento de cinc a una dosis de 3 mg/día, no origina mejora significativa en el crecimiento en peso y longitud. Los cambios en el status de cinc se relacionaron con los cambios en peso y longitud durante los 6 primeros meses de vida. Los cambios en las concentraciones séricas de leptina se relacionaron con los cambios en los índices antropométricos de acúmulo de grasa corporal

Objectives: To analyse the effect of zinc supplementation in growth and nutritional status of a homogeneous group of newborns with intra uterine growth retardation and asymmetric growth. The effect of changes of zinc status on growth and leptin serum concentrations was also analysed. Population and methods: A double blind, randomised clinical trial was designed in order to detect differences in growth between zinc and placebo groups during the first 6 months of life. 31 infants were included either to the zinc group (n = 14) (38.8 ± 1.4 weeks GA, 2,171 ± 253 g body weight) or the placebo group (n = 17) (38.9 ± 1.1 weeks GA, 2,249 ± 220 g body weight). The zinc group received a supplement of 3 mg elemental zinc per day (as zinc sulphate).Results: There were not significant differences between groups for anthropometric measurements through the study period. We found a significant effect of the study group, in hair zinc concentrations, but not in serum zinc concentrations; post-hoc comparisons for hair zinc revealed that there were significant differences between groups at 1, 2, and 6 months of age. Changes in serum and hair zinc concentrations from baseline to 6 months, showed significant correlations with changes in weight/age and length/age z-scores, in the supplement group. Changes in leptin serum concentrations during follow-up, showed significant correlations with changes in sum of 4 skinfolds and weight/age z-score, in the placebo group. Changes in hair zinc concentration through the study period showed significant correlations with changes in leptin serum concentrations from baseline to 6 months of follow-up. Conclusions: In a homogeneous group of intra uterine growth retardation infants with asymmetric growth, 3mg/day zinc supplementation do not show significant improvements in weight and length growth. Changes in zinc status were related with changes in weight and length during the first 6 months of life. Changes in leptin serum concentrations were related with changes in the anthropometric indices of body fat accretion

Exchangeable zinc pool size at birth is smaller in small-for-gestational-age than in appropriate-for-gestational-age preterm infants.

BACKGROUND: Small-for-gestational-age (SGA) infants are susceptible to postnatal zinc deficiency, but whether this susceptibility is due to intrauterine factors or to high postnatal growth requirements is unknown. OBJECTIVE: We hypothesized that the size of the exchangeable zinc pool (EZP), which reflects metabolically available zinc, would be smaller in SGA than in appropriate-for-gestational-age (AGA) infants born prematurely. DESIGN: Intravenous 70Zn (45 microg/kg) was administered to 10 SGA infants (8 boys) with a mean (+/-SD) gestational age of 33.3 +/- 1.8 wk and to 11 AGA infants (8 boys) with a mean (+/-SD) gestational age of 32.4 +/- 1.2 wk within 24 h of birth. The EZP was determined from isotope enrichment in spot urine collections on days 3-7. RESULTS: The mean birth weight of the SGA infants was 1.30 +/- 0.2 kg and of the AGA infants was 1.84 +/- 0.3 kg (P = 0.0001). The EZP size was significantly smaller in the SGA than in the AGA infants on an absolute basis (13.3 +/- 2.8 and 25.2 +/- 8.1 mg; P = 0.0002) and relative to body weight (10.3 +/- 2.5 and 13.9 +/- 4.5 mg/kg; P = 0.02). The difference remained significant after adjustment for gestational age and birth weight. CONCLUSION: These data provide evidence for differential zinc status at birth between SGA and AGA infants born prematurely at similar stages of gestation and offer at least a partial explanation for the reported benefits of postnatal zinc supplementation.

Cerebral metabolite differences in adolescents with low birth weight: assessment with in vivo proton MR spectroscopy.

BACKGROUND: Children with very low birth weight (VLBW) have a significantly increased risk of later neurodevelopmental problems, while infants born small for gestational age (SGA) at term are also at some risk of developing neurological impairment. OBJECTIVE: To investigate possible brain metabolite differences in adolescents with VLBW, SGA at term and controls by proton in vivo magnetic resonance spectroscopy (MRS) at 1.5 T. MATERIALS AND METHODS: MR spectra were acquired from volumes localized in the left frontal lobe, containing mainly white matter (54 subjects). Peak areas of N-acetyl aspartate (NAA), choline (Cho) and creatine (Cr) were determined, and the peak area ratio of NAA to Cr, total Cho to Cr, or NAA to Cho calculated. Probabilistic neural network (PNN) analysis was performed utilizing the chemical shift region containing resonances from NAA, Cho and Cr as inputs. RESULTS: No significant difference in the peak area ratios could be found using the Kruskal-Wallis test. By application of PNN, a correct classification of 52 of the 54 adolescents with a sensitivity and specificity exceeding 93% for all groups was achieved. CONCLUSION: Small, yet systematic, differences in brain metabolite distribution among the groups were confirmed by PNN analysis.

Whole body protein turnover and urea production of preterm small for gestational age infants fed fortified human milk or preterm formula.

OBJECTIVES: To investigate protein metabolism and urea production in preterm small for gestational age neonates fed a preterm formula or fortified human milk. METHODS: Ten preterm small for gestational age neonates were fed either their own mother's milk fortified with a powdered protein mineral supplement or a special preterm formula. Protein metabolism was determined using constant steady-state infusion of L-[ring-2H5]phenylalanine and L-[1-13C]valine. Urea production was determined from steady-state [13C]urea kinetics. RESULTS: Mean protein intake was 24% higher in the preterm formula group than in the fortified human milk group. No differences in protein turnover, synthesis and breakdown were observed between the two groups, but protein accretion was 71% to 79% higher in the preterm formula group than the fortified human milk group. Urea production rates were not different in the two groups. There was a strong negative correlation between urea production and protein accretion calculated from phenylalanine kinetics but not when calculated from valine kinetics. CONCLUSIONS: Preterm formula and fortified human milk appear equally well tolerated by preterm small for gestational age neonates, but protein accretion was higher in the preterm formula group. In preterm small for gestational age infants, both phenylalanine and valine kinetic methods can be used to accurately determine protein metabolism.

Effect of two amino acid solutions on leucine turnover in preterm infants.

OBJECTIVE: To assess the effect of two different parenteral amino acid mixtures, Trophamine and Primene, on leucine turnover in preterm infants. METHOD: Leucine kinetics were measured with [5,5,5 D3]leucine tracer in 15 infants receiving Trophamine (group 'T') (mean birth weight 1,263 g) and 22 who received Primene (group 'P') (mean birth weight 1,336 g) during two study periods, within a few hours after birth but before introduction of parenteral amino acid solution, and again at postnatal day 7. The rate of appearance of leucine was calculated from the enrichment of alpha-ketoisocaproic acid in plasma. RESULTS: There were no significant differences in leucine turnover within a few hours after birth in the two groups. In the infants who received Primene leucine turnover on day 7 was significantly lower than in those who received Trophamine (269 +/- 43 vs. 335 +/- 27, p < 0.05). Despite a higher intake of leucine in the Trophamine group (108 +/- 10 vs. 77 +/- 8 micromol.kg(-1).h(-1)), leucine released from proteins at day 7 was higher in this group compared to Primene (227 +/- 27 vs. 192 +/- 42 micromol.kg(-1).h(-1)). CONCLUSIONS: Primene administration results in lower leucine released from proteins, an estimate of protein breakdown, than Trophamine in preterm infants. Increases in whole body leucine turnover in response to administration of i.v. amino acids is influenced by the composition of the amino acid mixture. The factors responsible for this difference remain to be elucidated.

Carnitine supplementation and ketogenesis by small-for-date neonates on medium-and long-chain fatty acid formulae.

Carnitine is a key molecule in energy production from various substrates. Although it is generally believed that it plays no role in the metabolism of medium-chain triglycerides, quite a few data exist to the contrary. In the present study we investigated the effect of carnitine on ketogenesis in small-for-date neonates fed formulae of equal caloric value and fat content that was predominantly long-chain triglycerides or medium-chain triglycerides (46% of total fat). According to our results there was a statistically significant interaction between carnitine and the chain length of the administered fat with respect to ketone production. Increased ketogenesis was only shown by the neonates receiving medium-chain triglycerides and carnitine. Our results provide further evidence for the involvement of carnitine in medium-chain triglyceride metabolism.

Peculiaridades do metabolismo de calcio e fosforo no periodo perinatal: analise critica de literatura / Mineral metabolism characterization in the perinatal period

Os autores apresentam uma revisao de literatura sobre a fisiologia mineral, ressaltando caracteristicas no periodo perinatal em relacao ao metabolimo de Ca e P. Foram selecionados, atraves do Medline, artigos relacionados com o tema publicados nos ultimos 15 anos. Ocorrem alteracoes hormonais durante a vida intra-uterina e pos-natal imediata, com o proposito de promover uma adaptacao do RN, durante uma fase de transicao de uma vida intra-utero, em um ambiente hipercalcemico, para um pos natal imediato, onde os niveis sericos de calcio sofrem uma queda brusca. Essas alteracoes ocorrem de forma que se preserve uma mineralizacao ossea adequada e niveis sericos de Ca e P dentro dos fisiologicos. Isto e obtido atraves do armazenamento desses minerais, principalmente no ultimo trimestre da gestacao, as custas da oferta mineral materna e de um transporte placentario ativo, contra um gradiente de concentracao...

Hyperhomocysteinaemia and protein S deficiency in complicated pregnancies.

OBJECTIVE: The aim of our study was to investigate whether women with placental abruption, intrauterine fetal death or small for gestational age infants have metabolic and/or haemostatic abnormalities which are known to be risk factors for intravascular thrombosis. DESIGN: For two years blood tests were performed at > 10 weeks after delivery on all women without hypertensive disorders either before or during pregnancy, who had been consecutively admitted to our hospital with placental abruption, intrauterine fetal death and small for gestational age. SAMPLE: A total of 62 women who had placental abruption (n = 31), intrauterine fetal death (n = 18) and a small for gestational age infant (n = 13). SETTING: Obstetric outpatient clinic in a university hospital (Free University Hospital, Amsterdam). METHODS: Presence of hyperhomocysteinaemia, various coagulation abnormalities and anticardiolipins was investigated. RESULTS: Abnormalities were found in 20 women in the placental abruption group (20/31, 65%), in 10 women in the intrauterine fetal death group (10/18, 56%) and in 11 women in the small for gestational age group (11/13, 85%). Eight out of these 31 women had more than one abnormality. In the group of 62 women protein S deficiency was demonstrated in 26%, hyperhomocysteinaemia in 24%, Protein C deficiency in 6%, anticardiolipin IgG in 11%, anticardiolipin IgM in 5%, Lupus anticoagulant in 2%. An antithrombin III deficiency was not found. Thirty-three women were tested for activated protein C resistance (9% positive) and factor V Leiden mutation (6% positive). Hyperhomocysteinaemia was treated with a daily oral dose of 250 mg pyridoxine and 5 mg folic acid. After six weeks of vitamin supplementation homocysteine levels were tested again. At that time a mean reduction of fasting homocysteine value of 68% (95% CI 57-79) was found and of post-load value of 65% (95% CI 55-76). CONCLUSIONS: Based on the results of our study, it can be concluded that women whose pregnancies are complicated by either placental abruption, intrauterine fetal death or small for gestational age, even if there is no history of thrombo-embolic disorders or hypertension during pregnancy, should be advised to undergo an examination for metabolic and/or haemostatic abnormalities.

The effects of illness on neonatal metabolism and nutritional management.

In summary, careful attention to nutrient delivery in the IUGR infant is important to prevent and treat neonatal metabolic derangements and to improve postnatal growth. Carbohydrates are the essential fuel in the first days of life, to prevent hypoglycemia. Subsequent delivery of protein and fat helps rectify reduced muscle and fat stores and promotes weight gain. Calcium supplementation to prevent further bone demineralization and iron supplementation to replete iron stores may be necessary. Of special interest is that the neurologic outcome of these infants appears linked to the rate of catch-up growth. The rate of postnatal head growth depends on many perinatal and neonatal risk factors, and is a strong predictor of early developmental outcome in low-birthweight infants. Insufficient energy delivery beyond 2 weeks postnatal age in SGA premature infants results in failure to initiate subsequent catch-up head growth, with consequently smaller head circumferences at 1-year follow-up.

Increased renal net acid excretion in prematures below 1,600 g body weight compared with prematures and small-for-date newborns above 2,100 g on alimentation with a commercial preterm formula.

In 76 low birth weight infants with an actual body weight ranging from 1,210 to 2,540 g and fed a commercial preterm formula, urine samples were collected and blood acid base status was measured on day 38 (+/- 17, mean +/- SD) of life. Infants with an actual body weight below 1,600 g demonstrated a higher daily weight gain (22 +/- 3 vs. 14 +/- 5 g/kg/day), lower blood pCO2 (35.4 +/- 5.0 vs. 38.9 +/- 3.8 mm Hg), lower urine pH (5.8 +/- 0.5 vs. 6.5 +/- 0.3), higher renal net acid (1.86 +/- 0.38 vs. 1.28 +/- 0.55 mmol/kg/day) and higher phosphorus excretion (0.67 vs. 0.52 mmol/kg/day) than infants with an actual body weight above 2,100 g. Urinary ionogram data of these 2 groups of infants show that the increased renal net acid excretion of the smaller prematures is the result of a lower urinary excretion of sodium, potassium and chloride, due to a higher daily weight gain, probably a higher retention of these minerals, and a higher urinary phosphorus excretion probably due to an age-specific lower intestinal calcium absorption, and therefore a lower rate of calcium and phosphorus retention. Considering the low renal capacity for hydrogen ion excretion, very low birth weight infants still run a considerable risk for disturbances of acid base metabolism due to the high mean level of net acid excretion in nutrition with preterm formulas and an additional age-specific augmentation of renal acid load.

Reduced serum osteocalcin and 1,25-dihydroxyvitamin D concentrations and low bone mineral content in small for gestational age infants: evidence of decreased bone formation rates.

In small for gestational age (SGA) infants, bone mineral content (BMC) is low but the reasons are unclear and the possible relationships between calcium-regulating hormones and BMC have not been studied. We hypothesized that BMC would be lower and concentrations of serum parathyroid hormone and 1,25-dihydroxyvitamin D would be higher at birth in SGA infants than in appropriate for gestational age (AGA) infants. Forty-two term SGA infants and 126 term AGA infants, matched 1:3 specifically by gestation (+/- 1 week) and birth month, were studied prospectively. The BMC of the distal one third of the radius was measured before 3 days of age by photon absorptiometry. The BMC was lower in SGA than in AGA infants. Both SGA and AGA infants had lower BMC in summer or spring than in winter; BMC differences between groups remained significant after adjustment for season (p = 0.0001). Cord serum osteocalcin and 1,25-dihydroxyvitamin D values were lower in SGA than in AGA infants. There were no differences between groups in cord serum levels of intact parathyroid hormone, 25-hydroxyvitamin D, calcium, phosphorus, and magnesium. Relationships were positive between BMC and birth weight and were inverse between BMC and intact parathyroid hormone values. We suggest that reduced uteroplacental blood flow in SGA infants may result in reduced fetal-placental production of 1,25-dihydroxyvitamin D, which results in low BMC and low serum osteocalcin values; fetal serum parathyroid hormone values may be relatively elevated because of reduced placental mineral supply.

Biochemical evidence for the need of long-term mineral supplementation in an extremely low birth weight infant fed own mother's milk exclusively during the first 6 months of life.

In an extremely low birth weight infant fed expressed own mother's milk exclusively during the first 6 months of life, introduction of a human milk fortifier resulted in improvement of biochemical alterations consistent with metabolic bone disease of prematurity. Attempts to discontinue fortification at 9 weeks (discharge) and 21 weeks of age induced deterioration of biochemical parameters, demonstrating a persistent need for mineral supplementation during the whole period of breast-feeding. The effects of long-term human milk fortification are discussed.

Phosphorus metabolites and intracellular pH in the brains of normal and small for gestational age infants investigated by magnetic resonance spectroscopy.

The brains of 30 normal preterm and term infants whose birth wt were appropriate for gestational age and 13 who were small for gestational age but healthy were studied by phosphorus magnetic resonance spectroscopy to determine values for metabolite concentration ratios and intracellular pH. In the AGA infants, phosphocreatine/inorganic orthophosphate increased between 28 and 42 wk of gestational plus postnatal age, suggesting a rise in the phosphorylation potential of brain tissue. At the same time, the concentration of phosphomonoester (mainly phosphoethanolamine) fell and that of phosphodiester (including phosphatidylethanolamine and phosphatidylcholine) increased. These changes reflected myelination and proliferation of membranes. Intracellular pH was approximately 7.1 and did not change with brain maturation. No differences were detected in these variables between the infants who were small for gestational age and those who were appropriate for gestational age.