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BACKGROUND Modulation of behavior and physiology by dietary perturbations early in life can provide clues to the pathogenesis of adult diseases. We tested the hypothesis that a period of early protein supplementation modulates sympathetic nervous system activity demonstrated indirectly by an increase in active sleep state distribution in very low birth weight (VLBW) infants. METHODS VLBW infants (n = 71) were randomized to a total parenteral nutritional regimen providing 18% of the energy intake as amino acids (AA) or a conventional regimen providing 12.5% to achieve targeted AA intakes of 4 g/kg/day (0.004 kcal/kg/day) and 3 g/kg/day (0.003 kcal/kg/day), respectively. Both groups were weaned to enteral feeding and advanced to provide similar AA intake of 4 g/kg/day (0.004 kcal/kg/day). Six-hour daytime, behavioral sleep studies were performed when the infants reached full enteral intake (165 ml/kg/day). RESULTS Infants in the high protein group spent more time in active sleep (77.2 ± 10.5% vs. 70.7 ± 11.8%), p

OBJECTIVE: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease of preterm infants marked by an absolute monocyte count (AMC) drop in peripheral blood. Our objective was to determine whether the degree of AMC drop at illness onset correlates with eventual severity of disease. STUDY DESIGN: The percentage change in AMC was retrospectively calculated for each of 29 rule-out NEC and 76 NEC cases from baseline to illness onset, and then compared across stages. RESULTS: Median AMC changes of +0.5% (p = 0.56) were found in rule-out NEC, compared with −44.5% (p < 0.0001) in Stage 2 and −81.9% (p < 0.0001) in Stage 3. An AMC change cutoff of −75% distinguishes Stages 2 and 3. CONCLUSIONS: The severity of NEC correlated with the extent of AMC change in a dose-response fashion. Percent AMC change may be a useful marker for identifying NEC at onset and prognosticating disease severity.

Background Prolonged storage of transfused red blood cells (RBCs) is associated with hemolysis in healthy adults and inflammation in animal models. We aimed to determine whether storage duration affects markers of hemolysis (e.g., serum bilirubin, iron, and non-transferrin-bound iron (NTBI)) and inflammation (e.g., interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1) in transfused very low birth weight (VLBW) infants. Methods Blood samples from 23 independent transfusion events were collected by heel stick before and 2–6h after transfusion. Results Serum iron, total bilirubin, NTBI, and MCP-1 levels were significantly increased after transfusion of RBCs (P

Introduction:Infants with hypoplastic left heart syndrome are at risk for growth failure, particularly after stage 1 procedures. The effect of continuous enteral feedings on weight gain has not been previously investigated.Methods:A randomized controlled trial was performed in infants with hypoplastic left heart syndrome and single ventricle variants after stage 1 procedures. Eligible infants were randomized to a continuous and intermittent feeding regimen or an exclusive intermittent feeding regimen after stage 1 procedures and continued until hospital discharge. Anthropometric measures and markers of nutritional status were assessed throughout hospitalization.Results:Twenty-six infants completed the study. There were no significant differences in weight gain, growth, or nutritional status. Weight gain on full enteral feedings was 24.3 versus 23.6 g/d ( P = .88) for the combination (continuous and intermittent) versus intermittent feeding groups. Weight-for-age Z scores at discharge were −1.37 versus −1.2 ( P = .59) for the combination versus intermittent groups.Conclusions:No significant differences in weight gain, growth, or nutritional status were observed at hospital discharge between the two feeding strategies. Despite both groups achieving target daily weight gain after attaining full feeds, growth failure continued to be a problem after stage 1 procedures. Further strategies to improve growth during initial hospitalization are needed.

We have used an expansive definition of a micropreterm infant as30 weeks' gestation to provide a global perspective to a "high risk" group of preterm infants for which there are little published data to guide nutritional management. Consensus nutritional guidelines for preterm infants have been developed for infants1000 g birth weight and28 weeks' gestational age. Micropreterm infants have greater nutritional deficits at birth than more mature preterm infants and accumulate greater postnatal deficits. Nutritional guidelines based on the needs of preterm infants born28 weeks' gestation are unlikely, on a theoretical basis, to meet nutritional requirements of micropreterm infants. Unfortunately, very few good quality studies have addressed the nutritional requirements of this group specifically; this makes it difficult to formulate solid, evidence-based nutritional recommendations for these neonates. Nutritional management of micropreterm infants is based on recommendations established for preterm infants, which are adjusted after considering an infant's gestational age, birth weight, and clinical status. Minimal enteral feeding should commence on the first or second day of life, with incremental advancement and fortification of human milk when 100 mL/kg is tolerated. Early use of parenteral nutrition is recommended, ideally initiated within the first hours of life and enteral feeds are being established; this will help prevent the accumulation of nutritional deficits and incidence of growth failure. Fortified human milk should be given in order to meet nutritional requirements. When human milk is not available in sufficient quantity, a preterm formula should be given.

The feed and wrap technique refers to the use of feeding and swaddling to induce natural sleep in infants. It can be used prior to an magnetic resonance imaging (MRI) scan, avoiding sedation or anesthesia. We performed a retrospective review of feed and wrap MRI scans in infants 3 months or younger over a 2-year period at our center (279 scans) to evaluate the efficacy of this technique. Of scan results reviewed, 79% addressed the clinical question, 20% partially addressed the clinical question, and 1% were technically inadequate. History of preterm birth (odds ratio [OR] = 2.368; P = .032) and spine MRI (OR = 2.821; P = .001) were associated with a less-successful scan outcome. The feed and wrap technique can be used successfully in infants undergoing MRI; however, it may be less successful in preterm infants and those requiring spinal MRI. A standardized technique performed by experienced personnel may avoid anesthesia and sedation in infants who require MRI.

Low birth weight (LBW) infants sleeping prone are known to exhibit many physiological differences from those sleeping supine, including lower energy expenditure (heat production) and higher surface temperature. This apparent increase in heat storage suggests that heat loss may be inhibited in the prone position which, in turn, might influence cardiorespiratory activity.To determine the effects of body position (prone vs. supine) on absolute surface temperature profile (heat storage), central-peripheral (C-P) thermal gradients (vasomotor response), cardiorespiratory activity and metabolic gas exchange in growing LBW infants.Six-hour continuous recordings of absolute surface temperature profiles, cardiorespiratory activity and O2 and CO2 exchange, along with minute-to-minute assessment of behavioral sleep states were performed in 32 healthy growing LBW infants (birth weight 805-1590 g, gestational age 26-35 weeks and postconceptional age at study 33-38 weeks). Each infant was randomly assigned to the prone or supine position for the first 3 h of the study and then reversed for the second 3 h. Surface temperatures were recorded from 4 sites (forehead, flank, forearm and leg) and averaged each minute. Central (forehead and flank)-to-peripheral (forearm and leg) and forehead-to-environment (H-E) thermal gradients were calculated from the surface temperatures. Corresponding sleep states were aligned with minute averages obtained from the temperature and cardiorespiratory measurements. Data were then sorted for prone and supine positions during quiet (QS) and active sleep (AS) and compared using paired t-tests.In the prone position during both AS and QS, infants had higher forehead, flank, forearm and leg surface temperatures, narrower C-P gradients, higher heart rates and respiratory frequency, and lower heart rate and respiratory variability. Despite similar environmental temperatures, the H-E gradient was higher in the prone position. In the prone position infants demonstrated lower O2 consumption and CO2 production and a higher respiratory quotient.Despite thermoregulatory adjustments in cardiorespiratory function, infants sleeping prone have relatively higher body temperature. The cardiorespiratory responses to this modest increase in temperature indicate that thermal and metabolic control of cardiac and respiratory pumps seem to work in opposition. The consequences of any attendant changes in blood gas activity (e.g. hypocapnia and/or increased mixed venous oxygen concentration) due to this override of metabolic control remains speculative.

PURPOSE OF REVIEW Most conventionally managed very low birth weight infants experience postnatal growth restriction. There is some evidence that this postnatal growth restriction may have long-lasting effects, and contribute to short stature and poor neurodevelopmental outcomes. There is also evidence suggesting that early protein intake may improve growth in these very low birth weight infants. Therefore, to optimize protein intake early in the infant's neonatal course seems a logical goal. RECENT FINDINGS Randomized controlled trials provide evidence of short-term safety and efficacy for starting amino acid infusion as soon as possible after birth at 2.5-3.0 g/kg/day in very low birth weight infants; however, there are no long-term data to support the safety or efficacy of this practice. There is some evidence from recent studies of improved growth by providing 4.0 g/kg/day of amino acid early in the neonatal period while keeping the nitrogen to energy ratio above 1:100 and continuing with this protein intake during the infants stay in the hospital. At the present time long-term safety of this strategy is also not known. SUMMARY Appropriately designed large-scale randomized controlled trials are needed to determine the long-term safety and efficacy of early and aggressive administration of protein to very low birth weight infants.

Providing optimal nutrition to satisfy the growth needs of very low birth weight infants is critical. The available preterm formulas and fortified human milk diets provide protein intakes of approximately 3.5 to 3.6 g/kg/d when volumes sufficient to provide 120 kcal/kg/d are fed to these infants. These intakes support growth and protein accretion at about or slightly greater than intrauterine rate and lead to relatively increased fat deposition. However, most very low birth infants fed these diets remain below the 10th percentile of the intrauterine growth standards at discharge. There is clear evidence that, with respect to growth, very low birth infants are likely to benefit from a higher protein intake; however, there is no clear evidence that energy intakes greater than 120 kcal/kg/d are needed. Although the upper limit of protein intake and the ideal protein:energy ratio remain controversial, there is enough evidence to support the beneficial and safe use of formulas providing protein:energy ratio of 3.2 to 3.3 g/100 kcal.

To study the effects of body position (supine versus prone) on changes in cardiac inter-beat interval during quiet and active sleep, 6-h continuous electrocardiographic recordings and simultaneous minute-by-minute behavioural activity state assignments were made in 61 healthy, growing, low birthweight infants. The infants weighed 795-1600 g at birth and ranged between 30-38 wk in postconceptual age. Infants were randomly assigned to the supine or prone position for the first 3 h of each study; the position was reversed for the second 3 h. Higher heart rates and lower time and frequency domain measures of inter-beat interval variability were observed in the prone position as compared to the supine position, during both quiet and active sleep. In addition, an analysis of consecutive increases and decreases in the instantaneous heart rate revealed a lower incidence of sustained accelerations or decelerations in the prone position. Although consistent findings concerning inter-beat interval variability and sleeping position were obtained from all analytic techniques, the differences derived from analysis of consecutive inter-beat changes were the most robust. These differences in multiple measures of cardiac rate and rhythm between prone and supine positions suggest that autonomic control of the heart is altered by body position, the net effect on heart rate being increased sympathetic dominance.

The effects of variations in carbohydrate and fat intake and body position on behavioral activity states were evaluated in 64 healthy, growing low birth weight infants (birth weight, 750–1600 g). The infants, enrolled in a prospective, randomized, double-blind, controlled study of effects of quality of dietary energy, were fed one of the five formulas. These formulas contained fixed intakes of protein (4 g/kg per day) but different intakes of carbohydrate (9.1 to 20.4 g/kg per day) and fat (4.3 to 9.5 g/kg per day). Six-hour daytime sleep studies were performed at 2-wk intervals from time of full enteral intake until discharge (mean postconceptional age at first study, 33.2 ± 1.8 wk). Infants were randomly assigned to the prone or supine position for the first 3-h postprandial period; the position was reversed during the second 3 h. Behavioral activity state, i.e. quiet sleep (QS), active sleep, indeterminate sleep, awake, or crying was coded each minute throughout the postprandial period. The overall incidence of QS was almost double in the prone position versus the supine (p < 0.0001). In contrast, the probability of being in either of the two wakeful states (awake and crying) was increased when infants were placed in supine position (p < 0.0001). Increased likelihood of being in QS while prone was found only during the 30 min after and before feeding in a 150-min prandial cycle. In contrast, increased amounts of awake and crying in supine position were observed throughout the feeding interval. As carbohydrate intake increased, time spent in QS in supine position increased (from 8.6% to 12.5%, p < 0.02), and a trend in the same direction was noted for the prone position (p = 0.06). However, during postprandial minutes 10–100, when QS is likely to be entrained by the nutrient intake, enhancement of QS was found in the prone position only (p < 0.02). Carbohydrate intake influences the total time spent and the distribution of behavioral activity states within the postprandial period in low birth weight infants. The effect of nutrient intake on sleep profile is dependent on body position and time after feed. Mechanistic hypotheses relating sudden infant death syndrome to sleeping position may need to take these observations into account.

BACKGROUND Carbohydrate and fat may differ in their ability to support energy-requiring physiologic processes, such as protein synthesis and growth. If so, varying the constituents of infant formula might be therapeutically advantageous. OBJECTIVE We tested the hypothesis that low-birth-weight infants fed a diet containing 65% of nonprotein energy as carbohydrate oxidize relatively more carbohydrate and relatively less protein than do infants fed an isoenergetic, isonitrogenous diet containing 35% of nonprotein energy as carbohydrate. DESIGN Sixty-two low-birth-weight infants weighing from 750 to 1600 g at birth were assigned randomly and blindly to receive 1 of 5 formulas that differed only in the quantity and quality of nonprotein energy. Formula containing 544 kJ x kg(-1) x d(-1) with either 50%, 35%, or 65% of nonprotein energy as carbohydrate was administered to control subjects, group 1, and group 2, respectively. Groups 3 and 4 received gross energy intakes of 648 kJ x kg(-1) x d(-1) with 35% and 65% of nonprotein energy as carbohydrate. Protein intake was targeted at 4 g x kg(-1) x d(-1). Substrate oxidation was estimated from biweekly, 6-h measurements of gas exchange and 24-h urinary nitrogen excretion. RESULTS Carbohydrate oxidation was positively (r = 0.71, P < 0.0001) and fat oxidation was negatively (r = -0.46, P < 0.001) correlated with carbohydrate intake. Protein oxidation was negatively correlated with carbohydrate oxidation (r = -0.42, P < 0.001). Fat oxidation was not correlated with protein oxidation. Protein oxidation was less in infants receiving 65% of nonprotein energy as carbohydrate than in groups receiving 35% nonprotein energy as carbohydrate. CONCLUSION These data support the hypothesis that energy supplied as carbohydrate is more effective than energy supplied as fat in sparing protein oxidation in enterally fed low-birth-weight infants.

To provide insight into the maturation of neural mechanisms responsible for variability in heart rate during quiet and active sleep, 6-hour continuous electrocardiographic recordings and simultaneous minute-by-minute behavioral activity state assignments were performed in 61 healthy, growing low birth weight infants. The infants weighed 795-1600 g at birth and ranged between 31-38 weeks in postconceptional age. During this age interval there was a decrease in heart rate during quiet sleep and an increase in both time domain and frequency domain measures of the variability in cardiac interbeat intervals. In quiet sleep, global variability, measured as SD of R-R intervals, increased in relation to age, as did higher frequency variability, measured as the square root of the mean of squared successive differences in R-R intervals. Developmental changes in the 0.5-2.0 Hz spectral power band of RR-interval variability, another measure of high frequency variability, paralleled the changes seen in the time domain measure. Evaluation of patterns of changes in the magnitude and direction of successive interbeat intervals provided evidence that the incidence of sustained accelerations or decelerations increased whereas the incidence of no change in consecutive RR-intervals decreased as infants matured. Among the various measures of heart rate variability, the incidence of sustained change and no change in successive interbeat intervals were most closely related to postconceptional age in both sleep states. The overall decrease in heart rate, increase in heart rate variability, and increase in the pattern of changes in interbeat interval with postconceptional age are consistent with the maturation of the autonomic cardio-regulatory activity from 31-38 weeks age.

Advancements in the care of very-low-birth-weight (

We studied 142 preterm infants (mean gestation 31 weeks, mean birthweight 1364 g) fed prospectively varied protein and energy intakes. Infants were grouped as either slow or rapid growers based on rate of weight gain. Rapid growers had increased heart rates (166 vs 160 beats/min), respiratory rates (55.7 vs 53.9 bpm), energy expenditure (64.8 vs 61.6 kcal kg(-1) day(-1)), urinary C-peptide levels (1.59 vs 0.79 ng ml(-1)) and time in active sleep (78.0 vs 75.2%), and decreased spectral edge frequency in the electroencephalogram (2.96 vs 4.45 Hz) compared to slow growers. We conclude that preterm infants growing at varying rates manifest physiological and behavioral differences, and that these patterns may reflect altered autonomic balance.

One hundred twenty low birth weight infants were enterally fed diets containing fixed differences in protein and energy content. Serial, biweekly measurements were made of metabolizable energy intake, energy expenditure, nitrogen balance, and distribution of states of sleep, from the time the infants were receiving full enteral intakes (180 mL/kg.d) until weight reached 2200 g. Using multiple regression analysis of energy expenditure against protein stored, and metabolizable energy, the energy expended in the deposition of protein was calculated to be 5.5 kcal/g +/- 1.1 kcal/g (SE) and the energy cost of fat deposited was 1.6 kcal/g +/- 0.3 kcal/g (SE). Estimated maintenance energy expenditure of the nongrowing low birth weight infant was 42.3 +/- 3.2 kcal/kg/d. Variations in distribution of sleep state, an assessment of the activity state of the infant, did not explain additional variability in energy expenditure, after adjusting for protein and energy storage.

A model for predicting the relationship between protein and energy intakes of low-birth-weight (LBW) infants and the rate and composition of weight gain is described. It is based on linear multiple regression equations summarizing the rates of weight gain, nitrogen retention, and energy retention of 101 previously studied LBW infants fed protein intakes ranging from 2.25 to 3.9 g.kg-1.d-1 and concomitant energy intakes ranging from 115 to 147 kcal.kg-1.d-1 plus current theory concerning nutrient retention and body composition. To test the validity of the model, three combinations of protein and energy intake predicted by the model to result in specific rates and compositions of weight gain were fed to 44 LBW infants, and the observed rates of weight gain, protein accretion, and fat accretion were compared with the rates predicted by the model. Differences in these and other outcome variables between two of the groups, the intakes of which differed only in energy, also were compared to provide additional insight into the effect of concomitant energy intake on protein utilization. Across groups, actual outcomes correlated closely with predicted outcomes, supporting the validity of the model for the total population. However, outcomes of individual infants deviated as much as 30% from predicted outcomes; the magnitude of the deviation was independent of birth weight, gestational age, or size for gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disorder of neonates manifested by vasoconstriction of the pulmonary arteries. Recently, the gas nitric oxide (NO) has been used with some success in the management of infants with PPHN. Exogenous administration of NO selectively dilates the pulmonary vascular bed. NO is naturally synthesized in the body from the amino acid L-arginine. Here we report our findings that infants with PPHN are deficient in arginine and achieve normal or elevated plasma arginine concentrations with intravenous hyperalimentation. We prospectively identified and studied 10 infants with PPHN who were not receiving protein or amino acids for at least 24 h and compared their plasma arginine concentrations to 8 control infants without PPHN given similar nutrition. Plasma arginine concentrations were 32 ± 14 and 52 ± 20 µmol/l in infants with PPHN and control infants, respectively (p = 0.02). There were no other statistically significant differences in plasma amino acid concentration for any of the 22 other amino acids determined. Infants with PPHN who were subsequently treated with amino acid infusions had plasma arginine concentrations of 115 ± 48 µmol/l (mean often determinations at 86 ± 27 h after initiation of intravenous amino acids in five PPHN infants).

Background Systematic study of clinical phenotypes is important for a better understanding of the genetic basis of human diseases and more effective gene-based disease management. A key aspect in facilitating such studies requires standardized representation of the phenotype data using common data elements (CDEs) and controlled biomedical vocabularies. In this study, the authors analyzed how a limited subset of phenotypic data is amenable to common definition and standardized collection, as well as how their adoption in large-scale epidemiological and genome-wide studies can significantly facilitate cross-study analysis. Methods The authors mapped phenotype data dictionaries from five different eMERGE (Electronic Medical Records and Genomics) Network sites studying multiple diseases such as peripheral arterial disease and type 2 diabetes. For mapping, standardized terminological and metadata repository resources, such as the caDSR (Cancer Data Standards Registry and Repository) and SNOMED CT (Systematized Nomenclature of Medicine), were used. The mapping process comprised both lexical (via searching for relevant pre-coordinated concepts and data elements) and semantic (via post-coordination) techniques. Where feasible, new data elements were curated to enhance the coverage during mapping. A web-based application was also developed to uniformly represent and query the mapped data elements from different eMERGE studies. Results Approximately 60% of the target data elements (95 out of 157) could be mapped using simple lexical analysis techniques on pre-coordinated terms and concepts before any additional curation of terminology and metadata resources was initiated by eMERGE investigators. After curation of 54 new caDSR CDEs and nine new NCI thesaurus concepts and using post-coordination, the authors were able to map the remaining 40% of data elements to caDSR and SNOMED CT. A web-based tool was also implemented to assist in semi-automatic mapping of data elements. Conclusion This study emphasizes the requirement for standardized representation of clinical research data using existing metadata and terminology resources and provides simple techniques and software for data element mapping using experiences from the eMERGE Network.

Aims To investigate the correlation between the 'perfusion index' (PI) and other commonly used estimates of cutaneous blood flow [heart rate (HR), surface temperatures (ST) and central-to-peripheral thermal gradients (C-P grad)] and to use this new non-invasive tool to compare differences between prone and supine sleep position in low birth weight (LBW) infants. Methods Six-hour continuous recordings of pulse oximetry, cardiac activity and absolute ST from three sites (flank, forearm and leg), along with minute-to-minute assessment of behavioural states were performed in 31 LBW infants. Infants were randomly assigned to the prone or supine position for the first 3 h and then reversed for the second 3 h. PI data were correlated with HR and C-P grad, and compared across sleep positions during quiet sleep (QS) and active sleep (AS). Results Perfusion index correlated significantly with HR (r(2) = 0.40) and flank-to-forearm thermal gradient (r(2) = 0.28). In the prone position during QS, infants exhibited higher PI (3.7 +/- 0.9 vs. 3.1 +/- 0.7), HR (158.4 +/- 8.9 vs. 154.1 +/- 8.8 bpm), SpO(2) (95.8 +/- 2.6 vs. 95.2 +/- 2.6%), flank (36.7 +/- 0.4 vs. 36.5 +/- 0.4 degrees C), forearm (36.1 +/- 0.6 vs. 35.5 +/- 0.4 degrees C) and leg (35.4 +/- 0.7 vs. 34.7 +/- 0.7 degrees C) temperatures and narrower flank-to-forearm (0.6 +/- 0.4 vs. 0.9 +/- 0.3 degrees C) and flank-to-leg (1.3 +/- 0.6 vs. 1.8 +/- 0.7 degrees C) gradients, compared to those of the supine position. Similar differences were observed during AS. Conclusion Perfusion index is a good non-invasive estimate of tissue perfusion. Prone sleeping position is associated with a higher PI, possibly reflecting thermoregulatory adjustments in cardiovascular control. The effects of these position-related changes may have important implications for the increased risk for sudden infant death syndrome in prone position.

Growth, nutrient retention, and metabolic response of low-birth-weight infants fed human milk provided by their mother; this milk supplemented with bovine milk protein, calcium, phosphorus, and sodium; or pasteurized term human milk with the same supplement were monitored from the time desired intake was tolerated until weight reached 2200 g. The supplement resulted in greater rates of weight gain (20.5 +/- 2.3 vs 16.4 +/- 2.2 g.kg-1.d-1) and nitrogen retention (353 +/- 76 vs 270 +/- 53 mg.kg-1.d-1), increase in plasma transthyretin (TTR) concentration (7 +/- 16 vs -3 +/- 9 mg.L-1.wk-1), a higher mean plasma albumin concentration (34 +/- 3 vs 32 +/- 4 g/L), and a higher plasma TTR concentration at discharge (100 +/- 22 vs 75 +/- 24 mg/L). All these variables correlated significantly with total nitrogen intake, suggesting that the differences are attributable to the protein content of the supplement. The supplement also resulted in greater rates of calcium and phosphorus accretion but the plasma alkaline phosphatase activity of the supplemented vs the unsupplemented groups did not differ.

Infants sleeping in the prone position are at greater risk for sudden infant death syndrome (SIDS). Sleep position-dependent changes in cardiorespiratory activity may contribute to this increased risk. Cardiorespiratory activity is also affected by feeding. Twenty prematurely-born infants were studied at 31-36 weeks postconceptional age while sleeping in the prone and supine positions. Heart rate, respiratory rate, and patterns of variability were recorded during interfeed intervals, and effects of position and time after feeding were analyzed by repeated measures analyses of variance. There were significant effects of both sleeping position and time after feeding. Heart rate is higher and heart period variability is lower in the prone position, and the effects of sleeping position on cardiac functioning are more pronounced during the middle of the intrafeed interval. In preterm infants, autonomic responses to nutrient processing modulate the cardiorespiratory effects of sleeping position. Prone sleeping risk may vary with time after feeding.

Objective: To evaluate the effects of prone and supine sleeping positions on electrocortical activity during active (AS) and quiet (QS) sleep in low birthweight infants. Design: Randomised/crossover study. Setting: Infant Physiology Laboratory at Children's Hospital of New York. Patients: Sixty three healthy, growing, low birthweight (birth weight 795–1600 g) infants, 26–37 weeks gestational age. Interventions: Six hour continuous two channel electrocortical recordings, together with minute by minute behavioural state assignment, were performed. The infants were randomly assigned to prone or supine position during the first three hours, and positions were reversed during the second three hours. Outcome measures and results: Fast Fourier transforms of electroencephalograms (EEGs) were performed each minute and the total EEG power (TP), spectral edge frequency (SEF), absolute (AP) and relative (RP) powers in five frequency bands (0.01–1.0 Hz, 1–4 Hz, 4–8 Hz, 8–12 Hz, 12–24 Hz) were computed. Mean values for TP, SEF, AP, and RP in the five frequency bands in the prone and supine positions during AS and QS were then compared. In the prone sleeping position, during AS, infants showed significantly lower TP, decreased AP in frequency bands 0.01–1.0 Hz, 4–8 Hz, 8–12 Hz, 12–24 Hz, increased RP in 1–4 Hz, and a decrease in SEF. Similar trends were observed during QS, although they did not reach statistical significance. Conclusions: The prone sleeping position promotes a shift in EEG activity towards slower frequencies. These changes in electrocortical activity may be related to mechanisms associated with decreased arousal in the prone position and, in turn, increased risk of sudden infant death syndrome.

Carbohydrate and fat may vary in their ability to support protein accretion and growth. If so, variations in the source of nonprotein energy might be used to therapeutic advantage in enterally fed low-birth-weight infants. To test the hypothesis that high-carbohydrate diets are more effective than isocaloric high-fat diets in promoting growth and protein accretion, low-birth-weight infants weighing 750-1600 g at birth were randomized in a double blind study to receive one of five formulas differing only in the quantity and quality of nonprotein energy. Groups 1, 2, and control received 130 kcal x kg(-1) x d(-1) with 35, 65, and 50% of the nonprotein energy as carbohydrate. Groups 3 and 4 received energy intake of 155 kcal x kg(-1) x d(-1) with 35 and 65% of the nonprotein energy as carbohydrate. Protein intake of all groups was 4 g x kg(-1) x d(-1). Growth and metabolic responses were followed weekly, and macronutrient balances including 6-h indirect calorimetry were performed biweekly. Greater rates of weight gain and nitrogen retention were observed at high-carbohydrate intake compared with high-fat intake at both gross energy intakes. Greater rates of energy storage and an increase in skinfold thickness were observed in group 4 (high-energy high-carbohydrate diet) despite higher rates of energy expenditure. These data support the hypothesis that at isocaloric intakes, carbohydrate is more effective than fat in enhancing growth and protein accretion in enterally fed low-birth-weight infants. However, a diet with high-energy and high-carbohydrate content also results in increased fat deposition.

The objective of this study was to determine the effects of body position (supine vs prone) on cardiorespiratory activity during quiet and active sleep in growing low birth weight (LBW) infants. The effect of postconceptional age on cardiorespiratory activity in the two positions was also evaluated. Fifty-one healthy, growing, appropriate for gestational age LBW infants (795-1600 g), ranging from 26-37 weeks in gestational age, were evaluated. All subjects were enrolled in an ongoing study of the effects of quality of dietary energy on the rate and composition of weight gain. Infants were randomly assigned to the supine or prone position for the first 3 h of the 6-h studies; the position was reversed for the second 3 h. Continuous recordings of cardiorespiratory activity were performed along with simultaneous minute by minute assignment of behavioral sleep state. Measurements of heart rate (HR), heart period variability (RR-SD), respiratory rate (f), and respiratory variability (fSD) were made each minute. Low birth weight infants had higher HR and f and lower RR-SD and fSD in the prone position compared to the supine position, during both quiet and active sleep. With increasing postconceptional age, positional differences in HR increased during quiet sleep and differences in RR-SD increased during both sleep states. These data demonstrate systematic differences in cardiorespiratory control related to body position during sleep. We speculate that such positional differences are due to variations in autonomic control, and may, in turn, contribute to variations in susceptibility to sudden infant death syndrome.

Effects of Variations in Carbohydrate (CHO) Intake on Postprandial Gas Exchange, and Respiratory Frequency of Low Birth Weight (LBW) Infants

Effects of Sleeping Position, Diet and Time after Feeding on Behavioral Activity States in Low Birth Weight (LBW) Infants

Postural Differences in Cardiac Dynamics during Quiet and Active Sleep in Low Birth Weight Infants † 74

Objective: To determine the effects of fixed variations in the quantity and quality of dietary energy at constant P intake (Pin) on the rate of C and F oxidation (Cox, Fox) as estimated from indirect calorimetry and the rate of P oxidation (Pox) as determined from urinary nitrogen excretion.

Introduction: As the caloric value for CO2 is greater for fat (F) than carbohydrate (C), it has been suggested that high F, low C diets would benefit patients with respiratory insufficiency by reducing the amount of CO2 produced per kcal of energy expended.

Objectives: To determine the effects of prone vs supine positioning on the metabolic gas exchange and surface temperature profile of healthy growing enterally nourished LBW infants.

Objectives: To examine the maturational changes in cardiac interbeat interval variability during quiet (QS) and active sleep (AS) in low birth weight (LBW) infants.

We have shown that an E intake of 150 vs. 120 kcal/kg·d enhances protein utilization by LBW infants (Kashyap, et al., Pediatr Res 1994; 35:704). To determine the effect of quality of E intake on protein utilization, LBW infants (BW, 750-1600g were assigned randomly and blindly to receive one of 5 formulas differing only in quantity and quality of energy. Groups 1, 2 and 3 received formulas providing an E intake of 120 kcal/kg·d with 35, 50 and 65% of non-protein E, respectively, as carbohydrate (lactose + glucose polymers (CHO) and the remainder as fat; Groups 4 and 5 received an E intake of 150 kcal/kg·d with 35 and 65% of non-protein E, respectively, as CHO. Protein intake of all groups was 4g/kg·d. Leucine oxidation (i.e., the cumulative percent of a bolus dose of 1-13C-Leu recovered in breath from 0-8h) was determined in subsets of all groups (n=4-7) just prior to discharge. Leucine oxidation of Groups 1-5, respectively, was 24.2±5%a, 19.3±2.2%b, 14.8%c 13.7 ±2.9%c and 13.2±9,8%c of intake (values with different superscripts are statistically significant). Thus, both quantity and quality of concomitant E intake appear to affect protein utilization as measured by leucine oxidation. At E intakes of 120 kcal/kg·d, increasing the CHO content of non-protein E from 35% to 50% and from 50-65% increases protein utilization. A total E intake of 150 kcal/kg·d improves utilization relative to 120 kcal/kg·d with 35 and 50 but not 65% CHO. This suggests that increasing the CHO content of an E intake of 120 kcal/kg·d is as effective in promoting protein utilization as increasing E intake to 150 kcal/kg·d regardless of CHO content.

Objectives: The objectives of this study were to determine the effects of body position (supine vs prone) on cardiorespiratory activity during quiet and active sleep in growing low birth weight (LBW) infants.

Growth, nutrient retention, and metabolic response were determined in low birth weight (LBW) infants fed daily protein and energy intakes, respectively, of 2.8 gm/kg and 119 kcal/kg (group 1), 3.8 gm/kg and 120 kcal/kg (group 2), and 3.9 gm/kg and 142 kcal/kg (group 3). The mean rates of both weight gain and nitrogen retention in group 1 were somewhat greater than intrauterine rates; plasma concentrations of transthyretin and albumin also were acceptable. Thus the lower protein intake appeared to be adequate. On the other hand, the rates of weight gain and nitrogen retention in groups 2 and 3 were greater than those in group 1, supporting the efficacy of the higher protein intake with respect to growth. However, blood urea nitrogen and plasma amino acid concentrations also were higher in groups 2 and 3; both were higher in group 2 than in group 3, reflecting the positive effect of the higher energy intake on protein utilization. This observation, combined with data from an earlier study, indicates that protein intakes in excess of 3 gm/100 kcal will not be utilized completely. Energy expenditure in group 3 was greater than in group 1 but not group 2, raising the possibility that protein intakes not utilized completely contribute to diet-induced thermogenesis. The higher energy intake in group 3 vs group 2 did not affect rate of weight gain significantly, but energy storage in group 3, and hence fat accretion, was greater than that of other groups. In all groups the ratio of protein accretion to fat accretion reflected dietary proportions of protein and energy.

Estimates of average daily energy expenditure and minimal observed oxygen consumption are commonly used to characterize the energy metabolism of neonates. Yet, the errors inherent in these estimates have not been defined. Using measurements of oxygen consumption and carbon dioxide production made in healthy growing low birth weight infants during eight consecutive 3-h interfeeding epochs, we have determined the variability in the mean oxygen consumption, carbon dioxide production, respiratory quotient, total daily energy expenditure, and the minimal observed oxygen consumption among the feeding epochs. The coefficient of variation for oxygen consumption ranged from 3.1 to 9.1%, for minimal observed oxygen consumption from 3.7 to 16.7%, for carbon dioxide production from 3.3 to 7.4%, and for total daily energy expenditure from 2.9 to 7.6%. The SDs for respiratory quotient ranged from 0.008 to 0.066. From these 24-h data we have calculated the error in predicting daily estimates of the mean values for these variables if observations are made for less than 24 h. As expected, this error decreases with increasing duration of observation. These data should prove useful in the design and interpretation of investigations of neonatal energy expenditure.

Growth (weight, length, head circumference, and skinfold thickness), retention of major nutrients (nitrogen, sodium, potassium, chloride, calcium, and phosphorus), and chemical indices of protein adequacy (plasma albumin and transthyretin concentrations) and excess (blood urea nitrogen concentration and acid-base status; plasma amino acid concentrations) were determined serially from the time desired intake was tolerated until discharge weight (2200 gm) was reached in low birth weight infants (birth weight 900 to 1750 gm) fed one of three formulas, which provided protein and energy intakes, respectively, of 2.24 gm/kg/day and 115 kcal/kg/day (group 1), 3.6 gm/kg/day and 115 kcal/kg/day (group 2), and 3.5 gm/kg/day and 149 kcal/kg/day (group 3). Weight gain and rate of increase in length and head circumference were less in group 1 than in groups 2 and 3. Retention of most major nutrients also was less in group 1, as was blood urea nitrogen concentration, plasma albumin and transthyretin concentrations, and plasma concentrations of several amino acids. The rate of weight gain was not significantly greater in group 3 than in group 2, but the rate of increase in skinfold thickness was greater in this group. Neither nutrient retention nor metabolic indices differed between groups 2 and 3. These results suggest that a protein intake of 2.24 gm/kg/day is inadequate for the type of LBW infants studied, that the higher protein intakes are well tolerated, and that an energy intake of 149 vs 115 kcal/kg/day does not enhance utilization of the higher protein intakes studied.

Over the past decade, a number of studies concerning growth, nutrient retention and metabolic response of low birth weight (LBW) infants fed a variety of formulas as well as a variety of human milk preparations have been reported (1–21). These studies, in toto, provide important insights concerning both the nutrient requirements of LBW infants and the utilization of nutrients for growth. Some of the insights in both areas will be illustrated in this chapter, using primarily the authors’ studies (21–23) as examples. These studies have the advantage of familiarity and, also, are among the few such studies in which protein and energy intakes were varied independently.

Ingestion of an acute protein load by a normal adult has been shown to increase Glomerular Filtration Rate (GFR) by 20-30%,while in the patient with diabetic nephropathy GFR decreases with protein loading. It has been hypothesized that the kidneys of a newborn behave in a similar fashion to those of diabetic patients.

821 MAGNESIUM SULPHATE (MgSO 4 ): FURTHER CONFUSION IN THE INTERPRETATION OF THE NEWBORN CBC

We compared TcPCO2 with arterial CO2 (PaCO2) & continuous measures of heart rate (HR) & blood pressure (BP) (T°) in 14 infants (mean GA=32.7 weeks, mean wt.=2011 gms & mean postnatal age=1.76 days). The Novametrix heated electrode was mounted on the chest after calibration (mean calibration time=16.5 min.). The equilibration time (mean=12.15 min.) was directly correlated with GA (r= .74 p