Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

Skinfold caliper and ultrasound assessments of change in the distribution of subcutaneous fat during adolescent pregnancy.

OBJECTIVE: This study compares skinfold caliper and sonographic measurements of the amount and distribution of subcutaneous adipose tissue teenagers gain during pregnancy to test three hypotheses: (1) skinfold caliper and sonographic measurements of subcutaneous adiposity are highly correlated in pregnancy; (2) the extent to which the skinfold caliper heads compact the tissues increases during gestation; and (3) skinfold caliper measurements yield a smaller estimate of the amount of subcutaneous adipose tissue gained during gestation than do sonographic measurements. METHODS: We studied 28 primiparous teenagers at 10.7+/-2.8 and 29.6+/-1.8 weeks gestation. At both study visits subcutaneous adipose tissue thickness was measured at six body sites, first by skinfold caliper and then by ultrasound. Taking the nearly compression-free sonographic measurements as the standard, we quantified the extent to which the skinfold caliper heads compacted the tissues at each measurement site by computing the percentage compression: (mean adipose tissue thickness by ultrasound-(0.5xmean adipose tissue thickness by caliper)/mean adipose tissue thickness by ultrasound)x100. Pearson correlations and paired t-tests were used to compare the skinfold caliper and sonographic measurements. RESULTS: Hypothesis 1 was supported; the skinfold caliper and sonographic measurements were highly correlated at both study visits. Hypothesis 2 was not supported; between study visits caliper-related tissue compression decreased at measurement sites on the trunk and remained the same at measurement sites on the extremities. Hypothesis 3 was also refuted; the skinfold caliper-derived estimate of the amount of subcutaneous adipose tissue gained on the trunk exceeded the corresponding sonographic determination. As anticipated, the skinfold caliper measurements indicated that adipose tissue was stored more rapidly on the trunk than the extremities, but the opposite pattern emerged when the sonographic measurement technique was used. CONCLUSIONS: The results of this study challenge the notion that pregnant women store adipose tissue preferentially on the trunk and suggest that pregnancy-related changes in the regional distribution of maternal body fat based on skinfold caliper measurements should be interpreted cautiously.

A comparison of four techniques for measuring central adiposity in postpartum adolescents.

OBJECTIVE: To develop a reliable office technique for measuring central body fat in postpartum adolescents, we compared: first, a direct sonographic measurement of visceral adiposity to measurements of visceral and subcutaneous abdominal adiposity by computed tomography (CT); and second, skinfold caliper and sonographic measurements of subcutaneous adipose tissue distribution to CT measurements of visceral and subcutaneous abdominal adiposity. METHODS: Postpartum adipose tissue distribution was assessed in 15 teenagers by measuring the thickness of the subcutaneous fat at six body sites with skinfold calipers and ultrasound. Visceral adiposity was measured directly by ultrasound and CT. Taking the CT measurements as the standards, Pearson correlations and regression analyses were used to compare ultrasound measurement of visceral adiposity and the skinfold caliper and sonographic measurements of subcutaneous adipose tissue distribution. RESULTS: All of the adiposity measurements correlated significantly with the two CT measurements. The correlations between the ultrasound and the two CT measurements of abdominal adiposity were weaker than the correlations between the skinfold caliper and the sonographic determinations of subcutaneous adiposity and the two CT measurements of abdominal adiposity. Multivariate analyses identified the sonographic determination of subcutaneous adiposity at the costal site as the best independent predictor of central adiposity. CONCLUSIONS: The results of this study do not support the validity of ultrasound measurement of visceral adiposity as a measure of central adiposity in postpartum teenagers, but do suggest that sonographic determinations of subcutaneous adiposity could be useful for conducting epidemiological studies of the metabolic sequelae of gestational weight gain in this high-risk population of young women.

Fetal hyperinsulinemia increases farnesylation of p21 Ras in fetal tissues.

Even though the role of fetal hyperinsulinemia in the pathogenesis of fetal macrosomia in patients with overt diabetes and gestational diabetes mellitus seems plausible, the molecular mechanisms of action of hyperinsulinemia remain largely enigmatic. Recent indications that hyperinsulinemia "primes" various tissues to the mitogenic influence of growth factors by increasing the pool of prenylated Ras proteins prompted us to investigate the effect of fetal hyperinsulinemia on the activitiy of farnesyltransferase (FTase) and the amounts of farnesylated p21 Ras in fetal tissues in the ovine experimental model. Induction of fetal hyperinsulinemia by direct infusion of insulin into the fetus and by either fetal or maternal infusions of glucose resulted in significant increases in the activity of FTase and the amounts of farnesylated p21 Ras in fetal liver, skeletal muscle, fat, and white blood cells. An additional infusion of somatostatin into hyperglycemic fetuses blocked fetal hyperinsulinemia and completely prevented these increases, specifying insulin as the causative factor. We conclude that the ability of fetal hyperinsulinemia to increase the size of the pool of farnesylated p21 Ras may prime fetal tissues to the action of other growth factors and thereby constitute one mechanism by which fetal hyperinsulinemia could induce macrosomia in diabetic pregnancies.

The effect of maternal hypoaminoacidaemia on placental uptake and transport of amino acids in pregnant sheep.

We developed a model of maternal hyperglycaemia with secondary hyperinsulinaemia and hypoaminoacidaemia in pregnant sheep (H) to determine the effect of these conditions on uterine, uteroplacental and fetal amino-acid uptake rates and fetal amino-acid concentrations [AA]. Results were compared with normal pregnant ewes (C). Plasma glucose concentrations were greater in H versus C animals: 7.7+/-0.3 versus 3.9+/-0.1 mmol/l maternal, P< 0.005; 2.6+/-0.1 versus 1.1+/-0.1 mmol/l fetal, P< 0.005. Maternal insulin concentrations [I] were greater in the H group (132+/-30 H versus 31+/-5 C microU/ml, P< 0.005); fetal [I] were not different (15+/-2 H versus 16+/-2 C microU/mL). Maternal [AA] were lower in H than C groups except for SER (P=ns) and GLY (approx twofold higher, P< 0.01). Uterine, uteroplacental and fetal uptake rates of several AA, particularly the branch chain AA, were lower in H than C animals, producing lower total fetal nitrogen uptake rates (270+/-64 mg N/kg fetus/day H, 696+/-75 mg N/kg fetus/day C, P=0.001) and lower fetal plasma concentrations for the branch chain AA. Most fetal [AA], however, remained at control values, which could occur by relative increase in fetal amino-acid production and/or decrease in utilization, but not by increased uteroplacental transport rates.

Early feeding strategies in preterm and critically ill neonates.

This two-part article presents feeding strategies for the NICU population over the first several weeks of life. It focuses primarily on the theory and approach to feeding extremely low birth weight (ELBW) infants, but also addresses some issues pertinent to larger, ill infants. The premise for these recommendations is that avoiding early malnutrition in ELBW and ill infants has both short- and long-term benefits. Many practitioners may consider our approach to be somewhat aggressive. In this strategy, total parenteral nutrition (TPN) is initiated in the first hours after birth and is given together with initially small, and then increasing, enteral feedings beginning on the first or second day of life. The role of the TPN is to provide rapid, maximal nutrition and that of the early enteral feedings is to "prime" the gut and stimulate normal gastrointestinal tract activity.

Early aggressive nutrition in preterm infants.

Increasingly, neonatologists are realizing that current feeding practices for preterm infants are insufficient to produce reasonable rates of growth, and earlier and larger quantities of both parenteral and enteral feeding should be provided to these infants. Unfortunately, there is very little outcome data to recommend any particular nutritional strategy to achieve better growth. Instead, the rationale for feeding regimens in many nurseries has been quite variably extrapolated from animal data and human studies conducted in gestationally more mature and/or stable neonates. Additionally, there are no well-controlled, prospective studies that validate any nutritional regimen for the very preterm and or sick, unstable neonate. The goal of this review is to present available data to help define the risks and benefits of early parenteral and enteral nutrition, particularly in very preterm neonates, concluding with a more aggressive approach to feeding these infants than has been customary practice.

Effect of hyperinsulinemia on amino acid utilization in the ovine fetus.

We studied the effect of an acute 4-h period of hyperinsulinemia (H) on net utilization rates (AAUR(net)) of 21 amino acids (AA) in 17 studies performed in 13 late-gestation fetal sheep by use of a novel fetal hyperinsulinemic-euglycemic-euaminoacidemic clamp. During H [84 +/- 12 (SE) microU/ml H, 15 +/- 2 microU/ml control (C), P < 0. 00001], euglycemia was maintained by glucose clamp (19 +/- 0.05 micromol/ml H, 1.19 +/- 0.04 micromol/ml C), and euaminoacidemia (mean 4.1 +/- 3.3% increase for all amino acid concentrations [AA], nonsignificantly different from zero) was maintained with a mixed amino acid solution adjusted to keep lysine concentration constant and other [AA] near C values. H produced a 63.7% increase in AAUR(net) (3.29 +/- 0.66 micromol. min(-1). kg(-1) H, 2.01 +/- 0.55 micromol. min(-1). kg(-1) C, P < 0.001), accounting for a 60.1% increase in fetal nitrogen uptake rate (2,064 +/- 108 mg. day(-1). kg(-1) H, 1,289 +/- 73 mg. day(-1). kg(-1) C, P < 0.001). Mean AA clearance rate (AAUR(net)/[AA]) increased by 64.5 +/- 18.9% (P < 0. 001). Thus acute physiological H increases net amino acid and nitrogen utilization rates in the ovine fetus independent of plasma glucose and [AA].

Regulation of uterine and umbilical amino acid uptakes by maternal amino acid concentrations.

We tested the hypothesis that decreased fetal amino acid (AA) supply, produced by maternal hypoaminoacidemia (low AA) during hyperglycemia (HG), is reversible with maternal AA infusion and regulates fetal insulin concentration ([I]). We measured net uterine and umbilical AA uptakes during maternal HG/low AA concentration ([AA]) and after maternal intravenous infusion of a mixed AA solution. After 5 days HG, all maternal [AA] except glycine were decreased >50%, particularly essential [AA] (P < 0.00005). Most fetal [AA] also were decreased, especially branched-chain AA (P < 0.001). Maternal AA infusion increased net uterine uptakes of Val, Leu, Ile, Met, and Ser and net umbilical uptakes of Val, Leu, Ile, Met, Phe, and Arg but did not change net uteroplacental uptake of any AA. Fetal [I] increased 55 +/- 14%, P < 0.001, with correction of fetal [AA], despite the lack of change in fetal glucose concentration. Thus generalized maternal hypoaminoacidemia decreases uterine and umbilical uptakes of primarily the essential AA and decreases fetal branched-chain [AA]. These changes are reversed with correction of maternal [AA], which also increases fetal [I].

Estimation of doubly labeled water energy expenditure with confidence intervals.

Bivariate regression is used to estimate energy expenditure from doubly labeled water data. Two straight lines are fitted to the logarithms of the enrichments of oxygen-18 and deuterium simultaneously as a bivariate regression, so that the correlations between the oxygen and deuterium regression coefficients can be estimated. Maximum likelihood methods are used to extend bivariate regression to unbalanced situations caused by missing observations and to include replicate laboratory determination from the same urine samples, even if one of the replicates is missing. Use of maximum likelihood allows the determination of a confidence interval for the energy expenditure based on the log likelihood surface rather than use of the propagation of variance methods for nonlinear transformations. The model is extended to include the subject's deviations from the two lines as a bivariate continuous-time first-order autoregression to allow for serial correlation in the observations. The analysis of data from two subjects, one without apparent serial correlation and one with serial correlation, is presented.

Intravenous nutrition and postnatal growth of the micropremie.

There is a growing body of evidence that early nutritional practices may affect short-term growth and developmental outcome. In addition, they may play a role in determining adult health and disease. There is much that needs to be learned about safe and efficacious nutrient administration in the ELBW population; about techniques to assess the effect of different nutritional strategies; and about the long-term effects of these regimen or development outcome, growth, and disease.

Once- versus twice-daily gentamicin dosing in neonates >/=34 Weeks' gestation: cost-effectiveness analyses.

OBJECTIVES: To compare performance and cost analysis of two gentamicin regimens in infants >/=34 weeks' gestation requiring antibiotics for a 72-hour rule-out sepsis evaluation. A once-daily dosing (ODD) regimen of 4 mg/kg was compared with a standard twice-daily dosing (TDD) regimen of 2.5 mg/kg every 12 hours. SETTING AND DESIGN: Infants at two university-affiliated Level III nurseries were prospectively temporally allocated to receive ODD (n = 27) or TDD (n = 28) as part of their 72-hour empirical antibiotic regimen. Performance of dosing regimens was based on target serum gentamicin concentrations (SGC) established prospectively as a peak of 5 to 10 microgram/mL and a trough of 2 microgram/mL, compared with none in the ODD group. Overall, 57% of the SGCs in the TDD group were outside the target concentration range versus 7% in the ODD group. Based on questionnaire results, a total 72-hour process cost of ODD versus TDD was compared for regimens with and without use of SGC analysis. If SGCs are obtained, more than 75% of the cost associated with gentamicin therapy is attributable to SGC analysis. Based on a cost-effectiveness analysis, ODD was the dominant dosing strategy in all categories analyzed. CONCLUSIONS: ODD of gentamicin at 4 mg/kg in neonates >/=34 weeks' gestation is the preferable treatment strategy based on: 1) significantly improved SGC performance compared with TDD; 2) elimination of the need for routine SGC collection in infants on short courses of therapy; and 3) significant antibiotic-associated hospital cost savings when compared with conventional therapy of TDD and SGC analysis.

Determinants of energy expenditure in ventilated preterm infants.

The purpose of this study was to determine oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (EE) in a group of preterm ventilated infants during the first 3 weeks of life, and to determine the major factors that influence EE. Thirty-eight indirect calorimetry studies were performed in 18 ventilated infants with mean gestational age of 27.9 +/- 0.6 (SEM) weeks. The relationship of demographic factors, nutrient intake, and severity of illness assessments of EE were determined by regression analysis. Repeated measure analysis was performed for the effect of multiple studies in the same patient. Although VO2, VCO2, and EE all tended to increase over the first 3 weeks of life, there was a wide range of values. EE was best predicted by nonprotein calorie intake and postnatal age, while there was no correlation with birthweight, weight at the time of study, gestational age, protein intake, or severity of illness. Multiple regression analyses demonstrated a strong interaction between PNA and EI. In this population EE is best predicted by PNA and EI. The interactive effect between PNA and EI on EE is probably explained by the clinical practice of daily increments in substrate intake in these patients.

Protein balance in the first week of life in ventilated neonates receiving parenteral nutrition.

BACKGROUND: Protein intake is frequently delayed in ill neonates because of concerns about their ability to metabolize substrates. OBJECTIVE: We aimed to determine the factors affecting protein balance in ventilated, parenterally fed newborns during the first week of life. DESIGN: Leucine kinetic studies were performed in 19 neonates by using the [1-(13)C]leucine tracer technique after 24 h of a stable total parenteral nutrition (TPN) regimen. TPN intakes were prescribed by rotating attending physicians, enabling assessment of protein metabolism over a range of clinically used nutrient intakes. RESULTS: Mean (+/-SD) birth weight was 1.497 +/- 0.779 kg, gestational age at birth was 30.3 +/- 4.0 wk, and age at study was 3.9 +/- 1.4 d. Amino acid intakes (AAIs) ranged from 0.0 to 2.9 g x kg(-1) x d(-1). Based on leucine kinetic data, protein balance was calculated as the difference between protein synthesis and catabolism. By multiple regression analysis, AAI was the only predictor associated independently with protein balance (P < 0.01); energy intake, lipid intake, glucose intake, birth weight, and gestational age were not. Both leucine oxidation and nonoxidative leucine disposal rates were significantly correlated with leucine intake (P < 0.0005 and P < 0.01, respectively). Of the 12 infants with AAIs > 1 g x kg(-1) x d(-1), only 1 infant was significantly catabolic (protein balance <-1 g x kg(-1) x d(-1)). There was no evidence of protein intolerance as determined by elevated creatinine (69 +/- 31 micromol/L), plasma urea nitrogen (6.7 +/- 2.53 mmol/L), or metabolic acidosis (pH: 7.36 +/- 0.05). CONCLUSIONS: Ill neonates can achieve a positive protein balance in the first days of life without laboratory evidence of protein toxicity.

Nutrition of the fetus and the premature infant.

Developments in fetal and placental nutrition have highlighted the interaction of the placenta and fetal liver for the exchange and metabolism of nutrients. Of particular importance is the exchange of serine and glycine and their interconversion within these two organs and the exchange of glutamine and glutamate. Placental metabolism of nutrients and the placenta's role in the production and utilization of certain amino acids alters significantly the delivery rate of nutrients into the fetal circulation. Postnatal nutrition has focused on the role of early nutritional intervention in the extremely low birth weight infants and the recognition of the category of semi-essential amino acids in these infants. The role of minimal enteral feedings in small babies and the changes in nutritional requirements induced by medical complications has also received increasing attention.

Direct measurement of the energy expenditure of physical activity in preterm infants.

The energy cost of physical activity (EEA) has been estimated to account for 5-17% of total energy expenditure (TEE) in neonates. To directly measure EEA, a force plate was developed and validated to measure work outputs ranging from 0.3 to 40 kcal . kg-1 . day-1. By use of this force plate plus indirect calorimetry, TEE and EEA were measured and correlated with five activity states in 24 infants with gestational age of 31.6 +/- 0.5 (SE) wk and postnatal age of 24.8 +/- 3.7 days. TEE and EEA were 69.2 +/- 1.5 and 2.4 +/- 0.2 kcal . kg-1 . day-1, respectively. EEA per state was 0.5 +/- 0.0 (quiet sleep), 2.4 +/- 0.2 (active sleep), 2.8 +/- 0.4 (quiet awake), 7.5 +/- 0.8 (active awake), and 15.1 +/- 2.3 (crying) kcal . kg-1 . day-1. This provides the first direct measurement of the contribution of physical activity to TEE in preterm infants and will enable measurement of caloric expenditure from muscle activity in various disease conditions and development of nursing strategies to minimize unnecessary energy losses.

Nutrition of the fetus and premature infant.

Nutrition in the fetus and the premature infant is a rapidly changing field, not solely due to the acquisition of new knowledge but also because there have been major conceptual advances that have altered our approach to nutrition during early stages of development. This special report will highlight some of these conceptual advances in this area.

Fatal meconium aspiration in spite of appropriate perinatal airway management: pulmonary and placental evidence of prenatal disease.

OBJECTIVE: Our purpose was to summarize eight cases of fatal meconium aspiration syndrome where pathologic review showed evidence of chronic prenatal disease and to compare these findings with those of a group of control infants and fetuses who died of other causes. STUDY DESIGN: A 15-year retrospective chart review identified the infants who died of meconium aspiration within 48 hours of life and who also had autopsies performed. Neonatal pulmonary and available placental pathologic findings are described from these study infants and are compared with published norms and with autopsy results from a group of control infants and fetuses. RESULTS: Seven of the eight study infants underwent suctioning of the trachea immediately after birth. In all eight cases the neonatal lungs demonstrated histologic evidence of significant hypoxic changes of a chronic nature with onset before birth. The available placentas showed variable but significant abnormalities that support a case for subacute or chronic in utero compromise. CONCLUSIONS: As in other reports, there is evidence that meconium aspiration may be a prenatal rather than a postnatal disease. However, this is the first study that presents evidence on the basis of both pulmonary and placental pathologic findings and reinforces the importance of placental examinations in complicated pregnancies.

Technical and methodologic considerations for performance of indirect calorimetry in ventilated and nonventilated preterm infants.

OBJECTIVE: To evaluate and refine indirect calorimetry measurement techniques so that accurate metabolic measurements can be performed in mechanically ventilated and convalescing preterm infants who require supplemental oxygen. DESIGN: Laboratory validation of an indirect calorimeter; clinical and laboratory assessments of technical problems in performing metabolic measurements; and clinical indirect calorimetry studies in mechanically ventilated and nonventilated preterm infants. SETTING: Neonatal intensive care unit (ICU) in a tertiary care university hospital. PATIENTS: Level II and level III mechanically ventilated (n = 10) and nonventilated (n = 14) neonatal ICU patients who required FIO2 levels ranging from 0.21 to 0.42. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: System calibration was assessed by combustion of 100% ethanol; the mean respiratory quotient was 0.667 +/- 0.001 (SEM). In addition, oxygen consumption (Vo2) and CO2 production (Vco2) were simulated by CO2/nitrogen infusions within the range expected for 0.5- to 7-kg infants. Mean relative errors were 0.6 +/- 0.3% and 1.8 +/- 0.3% for expected Vo2 and Vco2 values, respectively. In 27 mechanically ventilated patients with no audible endotracheal tube leak, measured endotracheal tube leak ranged from 0.0% to 7.5%. Fluctuations in FIO2 during mechanical ventilation were monitored in 30-min studies, using wall-source (n = 27) or tank-source (n = 11) supplemental oxygen. Mean FIO2 variation was 0.00075 +/- 0.00013 vs. 0.00011 +/- 0.00001 using wall-source and tank-source oxygen, respectively. Some of the difficulties of obtaining accurate measurements in supplemental hood oxygen studies were overcome by using tank-source vs. wall-source oxygen and a unique hood design. CONCLUSIONS: Accurate indirect calorimetry studies can be performed in both ventilated and nonventilated infants weighing as little as 500 g, providing that sufficient attention is paid to technical and methodologic measurement details.