Patti J. Thureen

Aggressive nutrition of the very low birthweight infant

We propose an approach to nutrition of the VLBW infant that aims at minimizing the interruption of nutrient uptake engendered by premature birth. Our approach is aggressive in that it goes beyond current practice in several key aspects. The gap in nutrient intakes between the proposed aggressive approach and current practice will most likely disappear over the next few years as todays aggressive practice becomes tomorrows standard practice. As the gap diminishes, so will the threat that nutritional deprivation poses to growth and development of VLBW infants.

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.

Blood urea nitrogen concentration as a marker of amino-acid intolerance in neonates with birthweight less than 1250 g

OBJECTIVE:Currently blood urea nitrogen (BUN) is commonly used as a marker of protein intolerance in very preterm infants. The purpose of this study was to evaluate the relationship between amino-acid intakes and BUN concentrations during the early neonatal period in preterm neonates.STUDY DESIGN:Retrospective review of BUN concentration data from 121 infants with birthweight ≤1250 g receiving exclusive parenteral nutrition over the first 72 hours of life.RESULTS:There were 136 separate BUN concentration values. Amino-acid intake range was 0 to 3.7 g kg−1 day−1 and nonprotein calorie intake range was 15 to 45 kcal kg−1 d−1. There was no correlation between BUN concentration and amino-acid intake (p=0.2 and r2=0.01).CONCLUSIONS:In parenterally nourished preterm neonates amino-acid intake is not correlated with BUN concentration in the first days of life. Therefore, limiting amino-acid intake based on BUN concentration is not warranted in this patient population.

Protein and Energy Requirements of the Preterm/Low Birthweight (LBW) Infant

The growth and development of the normally growing, breast-fed, term infant is universally recognized as ideal. Hence, the term infant’s requirement for any nutrient can be defined as the amount present in a reasonable volume of human milk, usually the average volume ingested daily based on careful studies in groups of infants whose intakes were determined by difference in weight before and after each feeding. This is the basis of the most recent dietary reference intake of protein and most all other nutrients for the 0–6-mo-old infant (1). Unfortunately, no such standard exists for the LBW infant. Rather, for the past 25 years, the protein and other nutrient requirements for these infants have been defined as the amounts necessary to support intrauterine rates of growth and nutrient accretion (2). Despite the many advantages of human milk for reducing infection and promoting better neurodevelopmental outcomes in both term and preterm infants (3), preterm infants fed unsupplemented human milk do not grow at the intrauterine rate (4). Further, even if the total protein, calcium, phosphorus, sodium, and even zinc contents of a reasonable volume of human milk were absorbed and completely retained, the amounts retained would not be sufficient to support the intrauterine rates of accretion (5 6). This review addresses some of the many pressing issues concerning standards of growth for the preterm infant as well as strategies for providing optimal protein intakes.

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.

Ovine Placental and Fetal Arginine Metabolism at Normal and Increased Maternal Plasma Arginine Concentrations

Arginine (A) may play a significant role in fetal growth, by stimulating insulin secretion and as a precursor for both polyamine synthesis and nitric oxide production. To determine whether increased maternal plasma A concentrations can enhance delivery of A to the fetus, uterine, umbilical, and net uteroplacental (UP) A uptake rates were measured in 12 pregnant ewes at 129.6 ± 0.4 d gestation (mean ± SEM) during normal and after 3 h of increased maternal plasma A concentrations. With a 2.7-fold increase in maternal plasma A concentrations (p < 0.001), there were significant increases in uterine A uptake (13.8 ± 1.0 to 41.3 ± 7.7 μmol/min, p < 0.005), umbilical A uptake (3.3 ± 0.5 to 5.2 ± 0.8 μmol·min−1·kg−1 fetus, p < 0.005), UP A uptake (17.8 ± 6.2 to 89.2 ± 20.3 μmol·min−1·kg−1 placenta, p < 0.01), fetal arterial A concentration (98.7 ± 6.3 to 137.1 ± 9.9 μM, p < 0.001), maternal A disposal rate (143.7 ± 9.4 to 217.0 ± 6.7 μmol/min, p < 0.001), fetal A disposal rate (7.9 ± 0.8 to 9.9 ± 1.1 μmol·min−1·kg−1, p < 0.05), fetal A oxidation rate (1.31 ± 0.24 to 1.84 ± 0.36 μmol·min−1·kg−1, p < 0.05), and plasma insulin concentration in both fetus (16 ± 2 to 20 ± 2 μU/mL, p < 0.001) and mother (24 ± 3 to 32 ± 4 μU/mL, p < 0.001). Thus, increased maternal plasma A concentration increases maternal, UP, and fetal A net uptake, and increases insulin secretion in mother and fetus. The 4.2-fold larger increase in UP than net fetal A uptake could represent preferential UP A metabolism relative to fetal A metabolism, relatively limited placental-fetal A transport capacity compared with uterine A uptake capacity, or both; responsible mechanisms remain unknown.

Serine and glycine metabolism in hepatocytes from mid gestation fetal lambs.

Using stable isotopes of serine, glycine, and glutamine, the metabolism of serine and glycine was investigated in primary hepatocytes from six mid-gestation fetal lambs (mean gestational age = 81 ± 6 d, normal gestation = 145 d). Serine production was 6.84 ± 1.22 μmol/24 h/mg of DNA and exceeded serine utilization (3.76 ± 1.44 μmol/24 h/mg of DNA) with a resultant net increase in medium serine of 2.58 ± 1.70μmol/24 h/mg of DNA. In contrast, glycine production (6.84 ± 1.16μmol/24 h/mg of DNA) was less than glycine utilization (12.10 ± 1.78μmol/24 h/mg of DNA) with a net decline in medium glycine of -5.44 ± 2.03 μmol/24 h/mg of DNA. Of the serine produced, 50.4 ± 4.3% was derived from glycine via the action of serine hydroxymethyltransferase (SHMT) and the glycine cleavage enzyme complex (GCS). Increasing the medium serine concentration resulted in an increase in serine utilization and sparing of the utilization of other amino acids. Biosynthesis of glycine from serine accounts for only 18.1 ± 5.6% of glycine production, and this percentage is not affected by changes in medium serine concentration. Using 2,5-[15N2]glutamine as the tracer, an estimated 18 ± 7% of serine production was derived from transamination reactions. The specific activity of both cytosolic and mitochondrial SHMT was constant for the duration of the cultures. We conclude that, in mid-gestation fetal ovine hepatocytes, there is net production of serine (with glycine as the primary metabolic source of this serine biosynthesis) and net glycine utilization. These data suggest that flux through SHMT and GCS accounts for 50% of serine biosynthesis in mid-gestation fetal ovine hepatocytes. The sparing of the utilization of other amino acids by serine suggests that serine a conditionally essential amino acid for the mid-gestation fetal liver.

Determinants of energy expenditure in ventilated preterm infants

Abstract 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 on 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 non-protein 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.

Pathways of Serine and Glycine Metabolism in Primary Culture of Ovine Fetal Hepatocytes

ABSTRACT: 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 [1,2-13C215N1]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 hepatoctyes, approximately 30% of serine biosynthesis is derived from glycine, primarily via the combined action of GCE and SHMT.