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.

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.

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.

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.

Failure of tracheal aspirate cultures to define the cause of respiratory deteriorations in neonates.

The spectrum of organisms responsible for lower respiratory tract infection in chronically ventilated neonates is poorly defined. During an 18-month period 63 infants with a respiratory deterioration defined as an increase in fractional inspired O2 concentration > or = 20% and/or mean airway pressure > or = 3 cm H2O were evaluated for pulmonary infection. These infants were compared with 58 stable control ventilated infants. Tracheal aspirates for culture and Gram stain were taken from both groups and were cultured for bacteria, viruses, Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis. In addition each infant had complete blood counts with differential and chest roentgenograms evaluated. Positive tracheal aspirates defined as a heavy growth of a single or two bacterial organisms, and/or any growth of virus, Chlamydia and U. urealyticum were found in 23 of 63 study patients and 20 of 58 controls (P > 0.05). The most frequent isolate in both groups was U. urealyticum. Chest radiographs were positive (new changes, particularly atelectasis and infiltrates) more frequently in the study group than in controls, but complete blood count and tracheal aspirate Gram-stained smears were not helpful in discerning colonization from infection. We conclude that positive tracheal aspirates occur with equal frequency among infants with a clinical suspicion of lower respiratory tract infection and in "well" controls. Chest roentgenogram may be a useful adjunctive test to discriminate between colonization and lower respiratory tract infection.

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.

Flavobacterium odoratum ventriculitis treated with intraventricular cefotaxime.

A 6-week-old infant admitted to the University Hospital of the West Indies with hydrocephalus later developed ventriculitis. A heavy growth of Flavobacterium odoratum susceptible to gentamicin and cefotaxime was recovered from the ventricular fluid. Since intraventricular therapy was envisaged, a Pudenz reservoir was installed and ventricular fluid aspirated every 24 h to monitor treatment. Initial therapy consisted of intravenous cefotaxime, 50 mg/kg q.i.d. for 4 days. No significant reduction in the number of organisms in the ventricular fluid was achieved with this regimen. Intravenous therapy was therefore discontinued. On day 5 intraventricular therapy began with 5 mg cefotaxime 24 h for 6 days, followed by 1 mg/24 h for 4 days. Daily monitoring of intraventricular fluid indicated a high degree of antibacterial activity with rapid elimination of bacteria. Ventricular fluid remained sterile 10 days after therapy stopped. The Pudenz reservoir was removed, a ventriculoperitoneal shunt installed, and the patient discharged from hospital 4 days later without noticeable sequelae.

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.

Development of primary culture of ovine fetal hepatocytes for studies of amino acid metabolism and insulinlike growth factors.

We report the development and characterization of a system of primary culture of ovine fetal hepatocytes to aid in the understanding of the cellular regulation of fetal growth and metabolism with emphasis on amino acid metabolism and insulinlike growth factor gene expression and to allow comparison to in vivo studies. Hepatocytes were isolated from late gestation fetal lambs by in situ perfusion and collagenase digestion utilizing occlusion of the ductus venosus to limit intrahepatic shunting. Hepatocytes were cultured in media modified to mimic fetal concentrations of glucose, lactate, and amino acids. Ovine fetal hepatocytes in primary culture maintain the pattern of fetal amino acid production and utilization seen across the fetal liver in vivo. Specifically, there is a net production of serine and a net utilization of glycine. Cultured ovine fetal hepatocytes specifically increase tritiated thymidine incorporation in response to insulin and insulinlike growth factor II (IGF-II). IGF-II mRNA abundance is high and IGF-I mRNA is low in cultured ovine fetal hepatocytes as in the fetal sheep liver in vivo. These data demonstrate the successful isolation of ovine fetal hepatocytes that retain some of the characteristics of the ovine fetal liver while maintained in short-term culture.

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.

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.

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.

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].

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.

Placental glucose transport in heat-induced fetal growth retardation.

In six ewes heat stressed from 39 to 125 days gestation and studied in a normothermic environment at 135 days, fetal and placental masses were less than in control sheep (1,645 vs. 3,112 and 149 vs. 356 g, respectively, P less than 0.01). Umbilical glucose uptakes (Rf,UP) were measured keeping maternal arterial plasma glucose at 70 mg/dl at spontaneously occurring fetal plasma glucose values (state A) and at two additional fetal glucose levels, to determine the transplacental glucose difference (delta) vs. Rf,UP relation. At normal delta of 49.2 mg/dl, Rf,UP was less in the experimental group (3.2 vs. 5.6 mg.min-1.kg fetus-1, P less than 0.05). Differences in placental perfusion and glucose consumption could not account for this result, thus indicating a reduced placental glucose transport capacity. In state A, fetal hypoglycemia enlarged significantly (P less than 0.01) the delta to 56.7 mg/dl and increased Rf,UP approximately 50% over the Rf,UP at a normal delta. In heat-induced fetal growth retardation, fetal hypoglycemia increases the flux of maternal glucose across a placenta with reduced glucose transport capacity.

Pathways of serine and glycine metabolism in primary culture of ovine fetal hepatocytes.

Previous in vivo studies in the ovine fetus have demonstrated net serine production by the fetal liver, a pattern not seen in the adult sheep. The goal of this study was to determine the major metabolic pathways responsible for fetal hepatic serine production by using stable isotope methodology in primary culture of late gestation ovine fetal hepatocytes. Specifically selected tracers of glycine were added to individual cultures, with production of labeled serine determined after 24 h of incubation. When [1-13C1]glycine or [2-13C1]glycine was used as the initial tracer, serine enrichment at 24 h indicated that approximately 30% of serine production comes from glycine. Quantitative comparison of serine enrichment from these two tracers suggests that serine synthesis from glycine occurs via the combined action of the glycine cleavage enzyme system (GCE) and serine hydroxymethyltransferase (SHMT). Using [1,2-13C2(15)N1]glycine as the tracer, there was no significant increase in M + 2 glycine in the medium over 24 h, suggesting no reversible transamination of glycine, and therefore no significant movement of glycine through the glyoxalate pathway. These data demonstrate that in primary culture of fetal ovine hepatocytes, approximately 30% of serine biosynthesis is derived from glycine, primarily via the combined action of GCE and SHMT.