Pulmonary surfactant disaturated-phosphatidylcholine (DSPC) turnover and pool size in newborn infants with congenital diaphragmatic hernia (CDH)

In animal CDH models, surfactant deficiency contributes to the pathophysiology of the condition but information on human disease is very limited. The aim of our study was to investigate surfactant kinetics in CDH newborns. We studied surfactant disaturated-phosphatidylcholine (DSPC) half-life, turnover and apparent pool size by stable isotope methodology in CDH newborns with no ExtraCorporeal Membrane Oxygenation (ECMO) support (n = 13, birth weight (BW) 3.2 +/- 2.2 kg, gestational age (GA) 39 +/- 0.4 wks, postnatal age 43 +/- 11 h) and in 8 term infants with no lung disease (CONTROLS, BW 2.7 +/- 0 kg, GA 38 +/- 0.8 wks, postnatal age 96 +/- 26 h). We administered a trace dose of 13C-palmitic acid dipalmitoyl-phosphatidylcholine (DPPC) through the endotracheal (ET) tube and we measured DSPC kinetics by gas chromatography-mass spectrometry from DSPC13C-enrichment decay curves obtained from sequential tracheal aspirates. DSPC amount from tracheal aspirates (TA-DSPC) was measured by gas chromatography. In CDH infants DSPC half-life was shorter (24 +/- 4 and 53 +/- 11 h, p = 0.01), turnover faster (0.6 +/- 0.1 and 1.5 +/- 0.3 d-1 p = 0.01), apparent pool size smaller (34 +/- 6 and 57 +/- 7 mg/kg body weight, p = 0.02) and tracheal aspirates DSPC amount lower (2.4 +/- 0.4 and 4.6 +/- 0.5 mg/mL Epithelial Lining Fluid (ELF), p = 0.007) than in CONTROLS. In conclusion surfactant kinetics is grossly abnormal in mechanically ventilated CDH. Whether alterations of DSPC kinetics in CDH infants are caused by a primary surfactant deficiency or are secondary to oxygen therapy and ventilator support has still to be determined.     

Dexamethasone therapy in preterm infants developing bronchopulmonary dysplasia: effect on pulmonary surfactant disaturated-phosphatidylcholine kinetics

The role of corticosteroid in severe bronchopulmonary dyplasia (BPD) is still debated. Scanty data are available on the corticosteroids effect on surfactant metabolism. Our objective was to compare surfactant kinetics in preterm infants with developing BPD, before and after dexamethasone (DEXA) treatment. Twenty-eight studies were performed in 14 preterm infants (birth weight 786 +/- 192 g, gestational age 26 +/- 1 wk) on high ventilatory setting, before (age 22 +/- 11 d) and after (age 33 +/- 11 d) DEXA. C-labeled dipalmitoyl-phosphatidylcholine (DPPC) was administered endotrachelly to trace pulmonary surfactant. Surfactant disaturated-phosphatidylcholine (DSPC) kinetics and pools were calculated from DSPC C-enrichment curves of serial tracheal aspirates and bi-compartmental analysis. Total protein and myeloperoxidase (MPO) activity in tracheal aspirates were also measured and expressed per ml of Epithelial Lining Fluid (ELF). After DEXA, DSPC alveolar pool increased significantly from 8.2 +/- 7.6 to 10.6 +/- 11.3 mg/kg (p = 0.039), total proteins and MPO were reduced from 8.8 +/- 8.6 to 3.1 +/- 2.1 mg/ml ELF (p = 0.046) and from 1822 +/- 1224 to 1261 +/- 987 mU/mlELF (p = 0.028) respectively. In conclusion, DEXA treatment in mechanically ventilated preterm infants with severe respiratory failure and at high risk of developing BPD, significantly reduced inflammatory markers and increased alveolar surfactant DSPC pool.     

Zinc homeostasis in premature infants does not differ between those fed preterm formula or fortified human milk

The objectives of this study were to compare zinc homeostasis in premature infants enterally fed with either preterm infant formula or fortified human milk; to examine interrelationships of variables of zinc homeostasis; and to examine the findings in relation to estimated zinc requirements of preterm infants. Zinc homeostasis was studied in 14 infants (8 male), with mean gestational age of 31 wk and birth weight appropriate for gestational age, who were exclusively fed either preterm formula (n = 9) or own mother's milk with human milk fortifier (n = 5). Zinc stable isotopes were administered intravenously ((70)Zn) and orally as an extrinsic label ((67)Zn) over multiple feeds for determination of fractional absorption by dual isotope tracer ratio in urine; endogenous fecal zinc was determined by isotope dilution; and exchangeable zinc pool (EZP) size was estimated from linear regression of log-transformed urine (70)Zn enrichment data. Results indicated no significant differences in the variables of zinc homeostasis between the feeding groups; data for all subjects were thus combined. Mean (+/- SD) fractional absorption was 0.26 +/- 0.07; net absorbed zinc 0.43 +/- 0.25 mg/d (0.31 +/- 0.19 mg/kg/d). Mean EZP was 20 +/- 10 mg/kg, and was positively correlated with total absorbed zinc and with net absorbed zinc. Feeding type and total absorbed zinc were significantly related to daily weight gain (p = 0.003). Current zinc intakes from fortified human milk or formula are associated with acceptable weight gain, but whether the observed net zinc absorption was optimal in the human milk group cannot be definitively determined from these data.     

Glucose production and oxidation in preterm infants during total parenteral nutrition

During total parenteral nutrition in preterm infants, glucose may be infused at high rates, but it is not known if the endogenous glucose production is fully suppressed under these circumstances. Eight preterm appropriate for gestational age (AGA) (birth wt: 1613 +/- 151 g, gestational age: 31.1 +/- 1.5 wk) and eight preterm small for gestational age (SGA) newborn infants (1185 +/- 241 g, 32.9 +/- 2.6 wk) receiving a glucose infusion rate of 7.55 +/- 0.56 and 8.16 +/- 0.65 mg/kg.min, respectively, were studied during continuous total parenteral nutrition at postnatal d 8. Glucose oxidation rate was determined with a primed constant infusion of [U-13C] glucose, measuring the 13CO2 production in breath gas by isotope ratio mass spectrometry and the glucose production rate in plasma by gas chromatography mass spectrometry. In breath gas of AGA and SGA infants, 60 and 65%, respectively, of the infused tracer appeared as 13CO2. The glucose production rates were 7.97 +/- 1.61 and 8.12 +/- 1.84 mg/kg.min in AGA and SGA infants, respectively, indicating that no significant endogenous glucose production occurred. The glucose oxidation calculated from the glucose production and 13CO2 production was 4.74 +/- 0.99 mg/kg.min in AGA infants and was significantly different from the carbohydrate oxidation rate of 6.62 +/- 1.23 mg/kg.min measured by simultaneous indirect calorimetry. In SGA infants, however, the glucose and carbohydrate oxidation rates were not significantly different at 5.33 +/- 1.56 and 6.16 +/- 2.45 mg/kg.min. It is concluded that 1-wk-old AGA or SGA preterm infants receiving total parenteral nutrition of 80 kcal/kg.d produce no endogenous glucose and their glucose oxidation rates are similar at 63-65% of the glucose infused. It is suggested that the significant difference between glucose and carbohydrate oxidation rates observed in AGA but not in SGA infants is due either to a higher rate of lipogenesis from carbohydrates, or, less likely, to a higher rate of glycogen oxidation.     

Surfactant-associated protein B kinetics in vivo in newborn infants by stable isotopes

Surfactant-associated protein B (SP-B) is critical to the biophysical function of pulmonary surfactant. No information is available on SP-B synthesis and kinetics in humans. We administered a 24-h i.v. infusion of 13C-valine as metabolic precursor of SP-B to six newborn infants (weight 3.5+/-0.5 kg; age 12 d, range 1-43 d). Three of the study infants also received i.v. 2H-palmitate to label surfactant disaturated phosphatidylcholine (DSPC). SP-B and DSPC were isolated from tracheal aspirates, and their respective 13C and 2H enrichments were measured by gas chromatography-mass spectrometry. SP-B kinetics was measured successfully in all six infants. SP-B median (range) fractional synthesis rate was 30% per day (20-78% per day), secretion time was 4.5 h (1-9 h), time to peak was 24 h (12-36 h), and half-life was 21 h (8-35 h). The ascending part of the SP-B kinetic curve was similar to the DSPC curve, suggesting similar secretion pathways. SP-B half-life seemed to be shorter than DSPC half-life. These results agree with existing animal data. We conclude that the measurement of SP-B kinetics is feasible in vivo in humans by stable isotope technology.     

Infant pulmonary function in a randomized trial of fetal tracheal occlusion for severe congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) carries a high mortality risk secondary to pulmonary hypoplasia and respiratory failure. In experimental animals, fetal tracheal occlusion (TO) induces lung growth and morphologic maturation. We measured indicators of pulmonary function in 20 infants who were enrolled in a randomized trial of fetal TO as treatment for severe CDH [nine with conventional treatment (controls); 11 with TO]. We hypothesized that TO would improve lung function. At birth, the TO group had a lower mean gestational age (30.8 +/- 2.0 versus 37.4 +/- 1.0 wk; p=0.0002). All infants required assisted ventilation. Mortality did not differ between groups (64 versus 78%, TO and control, respectively; p=0.64). We measured respiratory mechanics at four study points: 1) first 24 h, 2) before CDH operative repair (5.9 +/- 2.2 d), 3) immediately after repair (7.0 +/- 2.2 d), and 4) before elective extubation (32.5 +/- 16.1 d). We calculated perioperative oxygenation index and alveolar-arterial oxygen difference to assess efficiency of pulmonary gas exchange. Data were analyzed by univariate and repeated measures techniques. Respiratory system compliance (Crs) was low. The rate of increase in Crs over the four study points was greater in the TO group than in control subjects. Crs in the TO group was significantly greater at study 2 (0.28 +/- 0.12 versus 0.17 +/- 0.04 mL.cm H2O(-1).kg(-1); p=0.02) and study 4 (0.93 +/- 0.45 versus 0.51 +/- 0.16 mL.cmH2O(-1).kg(-1); p=0.02). oxygenation index did not differ between groups, but alveolar-arterial oxygen difference was lower in the TO infants. We conclude that fetal TO for severe CDH results in modest improvements in neonatal pulmonary function that are of questionable clinical significance.     

Surfactant phosphatidylcholine pool size in human neonates with congenital diaphragmatic hernia requiring ECMO

OBJECTIVE: We measured surfactant phosphatidylcholine (PC) pool size and half-life in human congenital diaphragmatic hernia (CDH) patients who required extracorporeal membrane oxygenation (ECMO).Study design Surfactant PC pool size and half-life were measured by endotracheal administration of deuterium-labeled dipalmitoylphosphatidylcholine in 8 neonates with CDH on ECMO (CDH-ECMO), in 7 neonates with meconium aspiration syndrome on ECMO (MAS-ECMO), and in 6 ventilated infants (NON-ECMO). RESULTS: Lung PC pool size in the CDH-ECMO group was 73 +/- 17 mg/kg (mean +/- SEM), which was not significantly different from the MAS-ECMO (50 +/- 18 mg/kg) and the NON-ECMO group (69 +/- 38 mg/kg). Surfactant PC concentration in tracheal aspirates was not different between groups (~6 mg/mL). However, the percentage of palmitic acid in surfactant PC was significantly lower in the MAS-ECMO (56.3%) and the NON-ECMO (55.8%) group compared with the CDH-ECMO (67.6%) group. Surfactant PC half-life (~24 hours) was not different between the groups. A correlation was found between the surfactant PC half-life and the duration of ECMO. CONCLUSIONS: These data show no decreased surfactant PC pool size in high risk CDH patients who require ECMO. A shorter half-life of surfactant PC, indicating a faster turnover, may result in a faster improvement of the pulmonary condition during ECMO.     

Decreased lung surfactant disaturated phosphatidylcholine in sudden infant death syndrome

The lipid composition of lung surfactant obtained by lung lavage at autopsy in 40 infants dying from the sudden infant death syndrome (SIDS), was compared to that obtained from 12 infants dying from other causes (control group). Analysis of the lipids from the two groups showed no major difference in the proportions of the various phospholipid classes particularly the predominant component, phosphatidylcholine (PC), which was present at 60.7 +/- 0.9% (mean +/- S.E.) of the total phospholipids in the SIDS group and 57.9 +/- 2.9% in the control group. However the proportion of the PC present as the disaturated form (DSPC), was significantly (P less than 0.01) reduced in the SIDS group (65.8 +/- 1.6%) in comparison to the control group (77.4 +/- 3.5%). The proportion of DSPC present in the PC fraction of SIDS infants in the high-risk age range of 1-26 weeks (63.9 +/- 1.9%) was also significantly reduced (P less than 0.01) in comparison to the total control group of infants. For infants older than 26 weeks, significant differences in the proportion of DSPC in PC were not observed between SIDS and control groups. A functional consequence of the observed reduction in the DSPC content of lung surfactant of SIDS infants could be a greater degree of fluidity of the surfactant, particularly at exhalation. Such a biophysical change in surfactant properties could have a profound influence on lung function and be a causative factor in sudden infant death.     

Cholesterol synthesis and de novo lipogenesis in premature infants determined by mass isotopomer distribution analysis

Premature infants change from placental supply of mainly carbohydrates to an enteral supply of mainly lipids earlier in their development than term infants. The metabolic consequences hereof are not known but might have long-lasting health effects. In fact, knowledge of lipid metabolism in premature infants is very limited. We have quantified de novo lipogenesis and cholesterogenesis on d 3 of life in seven premature infants (birth weight, 1319 +/- 417 g; gestational age, 30 +/- 2 wk). For comparison, five healthy adult subjects were also studied. All subjects received a 12-h [1-(13)C] acetate infusion, followed by mass isotopomer distribution analysis (MIDA) on lipoprotein-palmitate and plasma unesterified cholesterol. The fraction of lipoprotein-palmitate synthesized at the end of the infusion period was 5.4 +/- 3.9% in infants, which was in the same range as found in adult subjects on a normal diet, suggesting that hepatic de novo lipogenesis is not a major contributor to fat accumulation in these premature neonates. The fractional contribution of newly synthesized cholesterol to plasma unesterified cholesterol was 7.4 +/- 1.3% after a 12-h infusion. The calculated rate of endogenous cholesterol synthesis was 31 +/- 7 mg/kg/d, a value approximately three times higher than that found in adult subjects (10 +/- 6 mg/kg/d). These results indicate that the cholesterol-synthesizing machinery is well developed in premature infants.     

Protein metabolism in phenylketonuria and Lesch-Nyhan syndrome

Animal and in vitro studies have implicated decreased protein synthesis in the pathogenesis of tissue damage in phenylketonuria (PKU) and of growth failure in Lesch-Nyhan syndrome. Protein turnover was measured in vivo in ten young adult subjects with classical PKU, two subjects with hyperphenylalaninemia, and three children with Lesch-Nyhan syndrome using techniques based on continuous infusions of [13C]leucine and, in Lesch-Nyhan subjects, [2H5]phenylalanine. The PKU subjects had various degrees of dietary phenylalanine restriction and plasma phenylalanine levels at the time of study ranged from 450-1540 mumol/L (mean 1106). Plasma phenylalanine in the two hyperphenylalaninemic subjects was 533 and 402 mumol/L. Rates of protein synthesis in all PKU subjects (mean 3.71 g/kg/24 h, range 2.68-5.10, [13C]leucine as tracer) were in a range similar to or above control values (mean 2.97, range 2.78-3.22, n = 6), as were rates of protein catabolism (PKU mean 4.23 g/kg/24 h, range 3.15-5.45; controls 3.64, 3.50-3.91). Protein turnover values in hyperphenylalaninemia were also similar to those in controls. With [13C]leucine as tracer, both mean protein synthesis and catabolism values in Lesch-Nyhan subjects (mean 4.80 and 5.64 g/kg/24 h, respectively) were higher than values in control children matched for protein intake (synthesis 4.32 +/- 0.74 (SD) and catabolism 4.85 +/- 0.57 (g/kg/24 h, n = 5). Similar results were obtained in Lesch-Nyhan subjects using [2H5]phenylalanine as tracer. These results suggest that protein turnover is not decreased in either PKU or Lesch-Nyhan syndrome. This conclusion is inconsistent with the hypothesis that tissue damage in PKU results from impaired protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Feasibility of using the stable isotope 25Mg to study Mg metabolism in infants

The feasibility of using isotopic techniques to study Mg absorption and metabolism was explored in three full-term human infants. 25Mg (98.8 atom %) was administered orally as an in vivo tracer. Fractional 25Mg absorption, isotope retention, endogenous fecal Mg losses, and apparent Mg exchangeable pool size were then determined under three conditions of isotope administration: 1) 20 mg 25Mg, with single feeding; 2) 20 mg 25Mg, distributed over a 24-h period; and 3) 60 mg 25Mg, over a 24-h period. Mg isotope ratios were determined by inductively coupled plasma mass spectrometry. Fractional absorption was increased in all three infants after distributed versus bolus administration at the 20 mg dose; mean (+/- SD) fractional absorption was 64.0 +/- 3.9 versus 54.3 +/- 5.9%, respectively. 25Mg retention was also more in all three infants after distributed administration (55.8 +/- 3.0 versus 44.3 +/- 1.3% of dose). At the 60-mg 25Mg dose, compared to 20 mg, fractional absorption was reduced but absolute isotope absorption more than doubled in all infants; urine isotope losses represented a similar fraction of the absorbed dose, thus, 25Mg retention also more than doubled. Compared to the results of the isotope studies, net Mg absorption and balance were uninfluenced by total Mg intake. Isotope retention with distributed isotope administration resulted in measurable isotopic enrichment of plasma and erythrocytes at 72 h (i.e. plasma isotope enrichment was 6.3-10.2 and 19.2-23.5% for the 20- and 60-mg dose, respectively). With these doses, apparent Mg exchangeable pool size ranged from 5.5 to 7.6 mmol/kg body wt; these values showed a decrease with age both within and between infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dual tracer stable isotopic assessment of calcium absorption and endogenous fecal excretion in low birth weight infants

Using a dual tracer (44Ca orally and 46Ca i.v.) stable isotope technique, true dietary Ca absorption, endogenous fecal Ca excretion, and net Ca retention were measured in 12 low birth weight (1426 +/- 260 g) infants fed a high Ca-containing formula. Endogenous fecal Ca excretion averaged 7.2 +/- 4.1% of intake, and exceeded 10% of intake in three infants. Net Ca retention, 103 +/- 38 mg/kg/d, was consistent with previous studies of Ca retention obtained using mass balance techniques and correlated closely (r = 0.98, p less than 0.001) with true Ca absorption but not with endogenous fecal excretion (r = -0.40, p = 0.19). Although endogenous fecal excretion may represent a significant source of Ca loss for some low birth weight infants, these data suggest that net Ca retention in low birth weight infants fed a high Ca-containing formula is primarily determined by the total dietary Ca absorbed.     

15N-tracer investigations into the nitrogen metabolism of preterm infants fed mother's milk and a formula diet

Protein synthesis, protein breakdown, protein-N turnover, and other parameters describing the nitrogen metabolism were measured in five male preterm infants. The weight of the subjects at birth was 2,064 +/- 107 g and the measurements were performed at age 16.0 +/- 4.5 days in the case of the mother's milk diet and 27.4 +/- 6.8 days in the case of the formula diet containing 1.8% protein. The parameters were measured by means of the 15N-tracer technique using [15N]glycine (95 atom %) applied in a single oral dose of 20 mg/kg as a tracer. The three-pool model proposed by Winkler and Faust was used to calculate the whole body protein parameters. No difference in net protein gain, protein synthesis, protein breakdown, or the other protein metabolism parameters were recorded despite the different protein inputs. Renal nitrogen excretion and the rate of endogenous urea N excretion were significantly higher for the formula diet than for the mother's milk diet. The protein synthesis rate of 7.9 g X kg-1 X day-1 was, as has previously been observed, higher than in other age groups. The protein metabolism of the preterm infant older than 33 weeks of gestational age does not benefit from a formula diet based on cow's milk that is richer in protein than mother's milk.     

Atypical auditory event-related potentials in preterm infants during the first year of life: a possible sign of cognitive dysfunction?

We assessed auditory event-related potentials in small-for-gestational-age (SGA; 850 +/- 258 g, 28.9 +/- 3.3 gestational wk; n = 15) and appropriate for gestational age (AGA; 1014 +/- 231 g, 26.9 +/- 1.9 gestational wk; n = 20) preterm infants and healthy term infants (n = 22). An oddball paradigm was used with a harmonic tone of 500-Hz frequency as the standard and of 750-Hz frequency as the deviant stimulus. The preterm infants were studied at 40 gestational wk and at 6 and 12 mo of corrected age, and the control subjects were studied at 2-4 d and at 3, 6, 9, 12, and 15 mo of age. The peaks of interest were the main positive peak (P350), the negative peaks at 250 ms (N250) and 650 ms (Nc), and the mismatch negativity at 200 ms (MMN). At term, the P350 in the preterm infants was similar to that of the newborn control subjects. In response to the deviant, the Nc was smaller in the SGA than in the AGA (P < 0.02) and control (P < 0.005) infants. The N250 amplitude was also lower in the SGA infants. At 12 mo, the MMN was observed in the control but not in the preterm infants, whose broad difference positivity correlated with the Bayley developmental index. The decreased Nc and N250 peaks in the SGA infants may suggest an increased risk for cognitive dysfunction. The broad difference positivity at 1 y of age may indicate atypical cortical auditory processing. Whether cognitive dysfunction can be predicted by these findings needs to be assessed in a study with extended follow-up.     

Zinc absorption, distribution, excretion, and retention by healthy preterm infants

Zinc (Zn) is an essential nutrient for growth, but little is known about Zn absorption, distribution, excretion, and retention in preterm infants. Nine infants with gestational age 32+/-1 wk (mean+/-SE), birth weight 1.44+/-0.08 kg, postnatal age 14+/-3 d, on Zn intake of 23+/-3 micromol/kg per d via enteral feeding of preterm formula were studied. A stable Zn isotope (70Zn) was administered orally or i.v., and plasma, red blood cells, urine, and feces were sampled for up to 30 d. Samples were analyzed for Zn by inductively coupled plasma atomic emission spectrometry and for isotope enrichment by inductively coupled plasma mass spectrometry. Data were analyzed by compartmental analysis using the Simulation Analysis and Modeling program, and absorption, distribution, excretion, and retention were calculated. Absorption was 36+/-5% or 7+/-1 micromol/kg per d; distribution in plasma was 15+/-1 micromol Zn/L and in RBC was 41+/-4 micromol Zn/L; excretion in urine was 0.55+/-0.03 micromol Zn/kg per d and in feces was 17+/-3 micromol Zn/kg per d and retention was 5+/-1 microl/kg per d. Results show that healthy preterm infants with Zn intake of 23 micromol/kg per d and expected growth rates (> 15 g/kg per d) absorb and retain Zn at rates comparable to in utero accretion. The values for absorption, distribution, and excretion by this population of healthy preterm infants provide a normal range for future studies, although further studies are required to determine endogenous excretion rates in healthy preterm infants. We speculate that these values can be used to determine whether Zn kinetics are abnormal in sick infants or in infants with slow growth.     

Zinc homeostasis in healthy infants fed a casein hydrolysate formula

BACKGROUND: The results of earlier, nonquantitative studies suggested that absorption of zinc from a semielemental (casein hydrolysate) formula was inferior to absorption from a cow's milk-based formula. The objective of this study was to compare fractional, total and net zinc absorption, and fecal excretion of endogenous zinc in the same healthy young infants when fed a casein hydrolysate versus cow's milk-based formula. METHODS: Fractional absorption of zinc and fecal excretion of endogenous zinc were determined from measurement of cumulative fecal excretion of unabsorbed tracer and by an isotope dilution technique, respectively, after oral administration of a 70Zn tracer with all formula feedings for 1 day. Six infants were assigned randomly to receive the test or control formula, and the other formula was administered 2 to 5 weeks later. RESULTS: Mean (+/-SD) fractional absorption of zinc from the casein hydrolysate formula (0.47 +/- 0.17) was double that from the cow's milk-based formula (0.22 +/- 0.04; P = 0.01) with a correspondingly greater total zinc absorption (3.23 +/- 1.67 mg Zn/day vs. 1.55 +/- 0.55 mg Zn/day; P = 0.05). Because the excretion of endogenous zinc in the feces did not differ between formulas (0.90 +/- 0.44 mg Zn/day vs. 0.91 +/- 0.29 mg Zn/day), net absorption of zinc was also higher with the casein hydrolysate formula (2.33 +/- 1.65 mg Zn/day vs. 0.81 +/- 0.67 mg Zn/day; P = 0.02). CONCLUSIONS: Retention of zinc appeared to be adequate to meet the needs for growth during feeding with cow's milk-based formula and was more than adequate during short-term feeding with the casein hydrolysate formula.     

Optimization of gentamicin therapy in very low birth weight infants

In order to optimize gentamicin (G) therapy we studied G pharmacokinetics in 48 preterm infants (gest. age 31.6 +/- 3.4, range 25-37 wk; birth weight 1.5 +/- 0.5 kg, range 0.7-2.5 kg). They received IV G twice daily (5.2 +/- 0.6 mg/kg/day). After at least 2 days of treatment trough and peak levels were measured for 2 successive doses. Trough levels were significantly higher in infants less than 1 kg receiving 5 mg/kg/day than in other infants (1-2.5 kg) who received the same dose (3.1 +/- 1.0 vs. 2.3 +/- 0.5 micrograms/ml; p less than 0.01). Mean G t 1/2 was significantly longer in infants under 1 kg than in those weighing 1-2.5 kg (7.9 +/- 1.9 and 6.5 +/- 1.6 hr, respectively; p less than 0.01). These differences could be attributed to lower G clearance in infants less than 1 kg (31 +/- 6 vs. 39 +/- 8 ml/kg/hr; p less than 0.005). There was no difference in G distribution volume between less than 1 kg and 1-2.5 kg infants (0.35 +/- 0.07 and 0.38 +/- 0.13 L/kg, respectively). A correlation was found between clearance and t 1/2 for the total group (r = 0.57, p less than 0.01). No correlation was detected between BUN and clearance or between gestational age and clearance. Our data suggest that G dose in infants less than 1 kg should be reduced to 3.5-4 mg/kg/day in order to avoid excessive levels associated with nephrotoxicity.     

Elevated levels of fetal hemoglobin synthesis in infants with bronchopulmonary dysplasia.

A study was devised to determine whether levels of fetal hemoglobin (HbF) synthesis are elevated in infants with bronchopulmonary dysplasia (BPD) when compared with the levels of HbF synthesis found in normal control infants. Twelve infants with BPD, whose postconceptional ages ranged from 40 to 62 weeks, were studied. The mean (+/- SD) gestational age and birth weight was 29 +/- 1.9 weeks and 1289 +/- 376 g, respectively. Elevation infants matched for birth weight, gestational age, and postnatal age served as the control subjects. Blood samples were incubated in an amino acid mixture containing [14C]leucine. The adult hemoglobin and HbF were then separated by column chromatography on diethylaminoethyl-Sephadex. The results demonstrated that the mean (+/- SD) level of HbF synthesis in infants with BPD was significantly higher than that in the control infants (42.6 +/- 22.9% vs 18.8 +/- 12.8%; P less than .01). When levels of HbF synthesis in the infants with BPD and the control infants were compared with data previously reported in normal infants, 7 of the 12 infants with BPD, but none of the control infants, were synthesizing amounts of HbF greater than would be expected for their postconceptional age. The results suggest that cardiopulmonary insufficiency could stimulate HbF synthesis during the first year of life as a result of an erythropoietic response to hypoxemia.     

Endogenous surfactant metabolism in critically ill infants measured with stable isotope labeled fatty acids

Little is known about endogenous surfactant metabolism in infants, because radioactive isotopes used for this purpose in animals cannot be used in humans. We developed a novel and safe method to measure the endogenous surfactant kinetics in vivo in humans by using stable isotope labeled fatty acids. We infused albumin-bound [U-13C]palmitic acid (PA) and [U-13C]linoleic acid (LLA) for 24 h in eight critically ill infants (mean+/-SD: weight: 3.7+/-1.3 kg: age: 51.3+/-61.6 d) who required mechanical ventilation. The 13C enrichment of PA and LLA in surfactant phosphatidylcholine (PC), obtained from tracheal aspirates, was measured by gas chromatography combustion interface-isotope ratio mass spectrometry. We measured a significant incorporation of both 13C-PA and 13C-LLA into surfactant PC. PC-PA and PC-LLA became enriched after 8.7+/-4.9 h (range: 3.4-17.3) and 10.0+/-7.2 h (range: 3.0-22.4), respectively; the times at maximum enrichment were 49.2+/-8.9 and 45.6+/-19.3 h, respectively. The fractional synthesis rate of surfactant PC-PA ranged from 0.4 to 3.4% per h, whereas the fractional synthesis rate of PC-LLA ranged from 0.5 to 3.8% per h. The surfactant PC-PA and PC-LLA half-lives ranged from 16.8 to 177.7 and 23.8 to 144.4 h, respectively. This method provides new data on surfactant metabolism in infants requiring mechanical ventilation. We found that synthesis of surfactant from plasma PA and LLA is a slow process and that there were marked differences in PC kinetics among infants. This variability could be related to differences in lung disease and could affect the clinical course of the respiratory failure.     

The effect of prenatal consultation with a neonatologist on human milk feeding in preterm infants

OBJECTIVE: To study the effect of prenatal consultation (PC) with a neonatologist on the incidence and duration of human milk feeding (HMF) in preterm infants. DESIGN/METHODS: A retrospective matched case-control study was preformed at a perinatal centre. Study infants were preterm infants (23-35 wk) whose mothers had received PC emphasizing the importance of HMF. Control infants were matched by birthweight, gestational age and multiplicity. RESULTS: Each group included 29 mothers and 46 preterm infants. Mean gestational age was 30.1 +/- 3 wk in both groups. Mean birthweight was 1329 +/- 489 (PC) and 1334 +/- 441 g (control). PC infants received HMF for significantly longer, both in the hospital and after discharge (hospital: PC 37 +/- 34 d vs control 15 +/- 19 d, p = 0.001; discharge PC 60 +/- 57 d vs control 21 +/- 32 d; p = 0.0001). No significant difference in neonatal morbidity was detected between the groups. CONCLUSIONS: PC is associated with significantly longer HMF in preterm infants, both in hospital and after discharge.