A delivery room-focused education and deliberate practice can improve pediatric resident resuscitation training.

OBJECTIVE: To determine if deliberate practice and simulation would improve pediatric residents' neonatal resuscitation abilities. STUDY DESIGN: Prospective cohort with pre-post-intervention design. Senior residents from 2008 to 2009 were evaluated and served as controls (C-Senior, N=23). Interns (PL-1, N=28) from 2008 to 2009 received the education and evaluation at the beginning (I-Pre) and end of their NICU rotation (I-Post) and again when they were seniors (I-Senior, N=24). The education, based on deliberate practice, included scored assessments of a resident's ability to assemble delivery room equipment and lead a simulated resuscitation. RESULT: PL-1 equipment score increased by 30% (I-Pre; 53%, I-Post; 83%) and was not different 1 to 2 years later (I-Senior; 87%). I-Senior equipment score was 22% higher than the C-Senior group (C-Senior; 65%). The PL-1's ability to lead a resuscitation improved after the education (I-Pre; 76%, I-Post; 85%) and was maintained as senior residents (I-Senior; 85%), but was not superior to the C-Senior group (C-Senior; 81%). CONCLUSION: The use of deliberate practice and simulation can improve a residents' resuscitation training, particularly for equipment.

School-age outcomes of newborns treated for persistent pulmonary hypertension.

OBJECTIVE: The aim of this study was to describe the school-age outcome of a cohort of children treated with intensive care support for persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: From 187 term newborns treated for PPHN as neonates, 109 were seen at school age (73% of 150 survivors and 58.2% of the original cohort). Of these 109 term newborns, 77 were treated with inhaled nitric oxide (iNO); of which 12 received extracorporeal membrane oxygenation (ECMO). The remaining 32 received conventional management with no exposure to iNO. Patients were seen at school age (mean 7.1 years). A medical history and physical exam were completed, growth was measured, and chest X-ray and echocardiogram were performed. Psychometric assessments included the Wechsler Scales (Preschool or Child), Vineland Adaptive Behavior Scales, Kaufman Test of Educational Achievement, Children's Category Test, Wisconsin Card Sorting Test and Achenbach Child Behavior Checklist. RESULT: Medical, neurodevelopmental and social/emotional/behavioral outcome did not differ between children treated with iNO, with or without ECMO, and those managed with no exposure to iNO. Overall, 24% had respiratory problems, 60% had abnormal chest X-rays and 6.4% had some sensorineural hearing loss. The cohort performed at the average level for full scale IQ, adaptive function, academic achievement, higher-order cognition and executive functioning, and social/behavioral/emotional functioning. Overall, 9.2% of the cohort had a full scale IQ less than 70 and 7.4% had an IQ from 70 to 84. CONCLUSION: The outcome for this cohort of children treated as newborns for PPHN, which included a large group of infants exposed to iNO, was comparable to previous reports of children treated with ECMO or conventionally.

Effect of a closed drug-delivery system on the incidence of nosocomial and catheter-related bloodstream infections in infants.

We conducted a prospective, cohort study at two affiliated level III neonatal intensive care units to evaluate the effect of a closed drug-delivery system on the incidence of nosocomial and catheter-related bloodstream infections (CRBSI) in infants. A total of 300 infants (n=150 at each site) were enrolled over a 4-year study period. There was no difference in the rate of CRBSI per 1000 catheter days between the two sites (16.2+/-39 vs. 8.9+/-24, P=0.054, 95% CI-14.8 to 0.13). Infants at site A (closed drug-delivery system) had a higher rate of infectious nosocomial respiratory complications per 100 hospital days than infants at site B (open delivery system) (1.1+/-2.2 vs. 0.5+/-1.5, P=0.009), however, there was no difference in the overall number of confirmed or suspected nosocomial infection events per patient between study sites. Logistic regression revealed that the number of additional peripheral catheters, gestational age and duration of parenteral nutrition all significantly contributed to the risk of developing one or more CRSBI. The closed drug-delivery system failed to reduce the incidence of CRBSI or overall rate of nosocomial infections in premature infants.

Factors associated with successful epoetin alfa therapy in premature infants.

OBJECTIVE: To determine the impact of two different recombinant human erythropoietin (epoetin alfa) dosing strategies on the number of red blood cell (RBC) transfusions, and explore relationships between specific patient and drug regimen variables with epoetin alfa therapy outcomes. DESIGN: Retrospective cohort study. SETTING: Level III university neonatal intensive care unit. METHODS: Infants who received epoetin alfa therapy three times weekly for more than one week were categorized into two epoetin alfa dosing strategy groups: group A (300-749 units/kg/wk) and group B (750-1200 units/kg/wk). The following patient variables were collected and their relationship to therapy outcomes (corrected reticulocyte count [%], hematocrit [%], and number of RBC transfusions after therapy was started) were evaluated using independent Student's t-test, correlation analysis, and stepwise linear regression: birth weight (kg), gestational age (weeks), postnatal age at therapy onset (days), duration of mechanical ventilation (days), number of RBC transfusions before epoetin alfa therapy, phlebotomy loss (mL/kg), epoetin alfa dosage (units/kg/dose), iron dosage (mg/kg/d), duration of therapy (days), and postconceptional age at therapy discontinuation (weeks). RESULTS: The charts of 44 patients were reviewed. No significant impact on outcome was attributed to overall dosing strategy (group A vs. group B). Linear regression identified postnatal age at therapy onset as a significant contributor to mean hematocrit (R2 = 2 0.116; p = 0.023) and postconceptional age at therapy discontinuation as a significant contributor to number of transfusions during and after epoetin alfa use (R2 = 0.118; p = 0.022). A significant positive correlation was found between weekly mean epoetin alfa dosage and mean reticulocyte count (r = 0.326; p = 0.046), mean iron dosage and mean reticulocyte count (r = 0.439; p = 0.006), and ventilator days and total number of transfusions (r = 0.606; p < 0.001). A significant negative correlation was found between number of transfusions and reticulocyte count (r = -0.367; p = 0.023). CONCLUSIONS: Epoetin alfa dosing strategy, as defined in our study, did not significantly affect the number of transfusions. However, postnatal age at therapy initiation, postconceptional age at therapy discontinuation, mean epoetin alfa dosage, and iron dosage correlate with specific outcomes of epoetin alfa therapy in premature infants.

Effects of combined superoxide dismutase and catalase on somatosensory evoked potentials and neuropathologic changes in asphyxiated newborn lambs.

The lamb model of neonatal asphyxia has been used to describe changes in cerebral blood flow, oxygen metabolism and mitochondrial function following a standard asphyxial insult. In addition, abnormalities in cerebral hemodynamics and mitochondrial function after asphyxia have been associated with injury mediated by oxygen free radicals. The purpose of this investigation was to describe changes in brainstem auditory and somatosensory evoked potentials and pathologic changes after asphyxia in the newborn lamb. In addition, the hypothesis that treatment with the oxygen free radical scavenging enzymes superoxide dismutase and catalase would enhance postasphyxia recovery of evoked potentials and ameliorate pathologic injury was tested. Electrophysiologic and pathologic abnormalities after asphyxia were demonstrated, but treatment with oxygen radical scavengers had no effect on these abnormalities.

Late neurosonographic screening is important to the diagnosis of periventricular leukomalacia and ventricular enlargement in preterm infants.

BACKGROUND: Recent cost-containment strategies suggest limiting screening neurosonograms to the second week of life in premature infants with lower gestational ages (< 30 weeks), birth weights (< 1250 g), or more complicated clinical courses. OBJECTIVE: To determine if such strategies reduce detection of cystic periventricular leukomalacia (cPVL) and persistent ventricular enlargement (pVE)--late sonographic abnormalities highly predictive of adverse neurodevelopment in preterm infants. METHODS: Timing, findings, and number of neurosonograms were reviewed for all survivors born at < or = 32 weeks' gestation at University Hospital, Denver, Colo., between January 1992 and June 1995. RESULTS: Of 236 surviving infants, 61 (26%) were never scanned, and 175 (74%) had a total of 432 scans. Only 106 infants (45%) had a neurosonogram on or after 28 days (timed to detect all cPVL/pVE). Eleven infants (4.7%) had cPVL, and 19 (8%) had pVE. Severity of clinical course did not predict development of cPVL, but was a better predictor of pVE. Initial neurosonograms were normal in 6/11 (55%) with cPVL and 5/19 (26%) with pVE. Screening declined from 86% of infants in 1992 (average 2.54 neurosonograms each), to 64% by 1994-1995 (average of 2.22 neurosonograms each). Infants > 30 weeks' gestation comprised 55 of 61 patients without any neurosonograms (90%), 4 of 11 patients with cPVL (36%), and 4 of 19 patients with pVE (21%). CONCLUSION: Screening neurosonography has declined from 1992 to 1995, particularly in larger premature infants (30-32 weeks' gestation) who remain at risk for cPVL and pVE. Clinical course or results of initial studies do not always predict the development of these late abnormalities. We recommend that one neurosonogram be done at > or = 4 weeks of age in all premature infants < or = 32 weeks' gestation, regardless of birth weight, clinical course, or results of prior studies. An earlier neurosonogram should be obtained for infants < 30 weeks' gestation in the second week of life to detect complications of intracranial hemorrhage.

Impact of new treatments for neonatal pulmonary hypertension on extracorporeal membrane oxygenation use and outcome.

OBJECTIVE: To determine the impact of new treatment modalities, including high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (INO), on extracorporeal membrane oxygenation (ECMO) use and outcome of neonatal patients with persistent pulmonary hypertension of the newborn. STUDY DESIGN: We reviewed the medical records of neonatal patients meeting established ECMO criteria from 1988 to 1995. Clinical data were gathered from this retrospective chart review. Comparison of ECMO experiences were made between the 1988-90 period (pre-HFOV and INO, or period 1) and the 1993-95 period (HFOV and INO fully established as treatment modalities, or period 2). RESULTS: One hundred three patients were treated with ECMO during the 8-year study period. After HFOV and INO were introduced in 1991 and 1992 respectively, the number of patients meeting established ECMO criteria who subsequently required ECMO therapy progressively declined, from 22.3 +/- 2.3 (mean +/- SD) patients per year during period 1 to 12 patients in 1991 when HFOV was introduced, 8 patients in 1992 when INO was introduced, and 5.3 +/- 2.9 patients per year in period 2. The number of patients referred for ECMO over time did not change. Survival after ECMO dropped from 84% during period 1 to 56% in period 2. Introduction of new pre-ECMO therapies has not delayed institution of ECMO, significantly increased the length of ECMO runs, or lengthened the hospital course of ECMO survivors. A comparison of the eight infants treated with ECMO in 1992 with the 10 infants treated with INO in 1993 showed a longer hospital stay and a larger average patient bill for the patients treated with ECMO. CONCLUSION: New treatment approaches for severe persistent pulmonary hypertension have reduced ECMO use, shortened the duration of hospitalization, and reduced costs for those infants responding to HFOV and INO. However, survival of patients requiring ECMO therapy has decreased.

A multicenter randomized masked comparison trial of synthetic surfactant versus calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co) and a surfactant extract of calf lung lavage (Infasurf, IND #27,169, ONY, Inc) in the prevention of neonatal respiratory distress syndrome (RDS). DESIGN AND SETTING: Ten-center randomized masked comparison trial. PATIENTS: Premature infants (n = 871) <29 weeks gestational age by best obstetric estimate. INTERVENTIONS: Infants were randomly assigned to a course of treatment with Exosurf Neonatal (n = 438) or Infasurf (n = 433) at birth, and if still intubated, at 12 and 24 hours of age. Crossover treatment was allowed within 72 hours of age if severe respiratory failure (defined as two consecutive a/A PO2 ratios

Longitudinal follow-up of a cohort of newborn infants treated with inhaled nitric oxide for persistent pulmonary hypertension.

OBJECTIVE: To describe the outcome of a group of term newborn infants treated with inhaled nitric oxide for severe persistent pulmonary hypertension. STUDY DESIGN: We performed a prospective longitudinal medical and neurodevelopmental follow-up of 51 infants treated as neonates for persistent pulmonary hypertension of the newborn with inhaled nitric oxide. The original number of treated infants was 87, of whom 25 died in the neonatal period; of 62 infants who survived, 51 were seen at 1 year of age and 33 completed a 2-year evaluation. Statistical analysis used population medians, means, and standard deviations for parameters assessed. Paired t tests and chi-square analysis were used to compare outcomes measured at 1 year with assessment at 2 years for the 32 infants seen at both 1- and 2-year visits. RESULTS: At 1-year follow-up median growth percentiles were 20%, 72.5%, and 50% for weight, length, and occipitofrontal circumference, respectively. Thirteen of 51 infants (25.5%) were < 5th percentile in weight. Nine of 51 infants (17.6%) had feeding problems (need for gastrostomy feeding or gastroesophageal reflux), and 14 (27.5%) had a clinical diagnosis of reactive airways disease. Infant development as measured by the Bayley Scales of Infant Development was 104 +/- 16 for the mental development index and 97 +/- 20 for the psychomotor index. Six of 51 infants (11.8%) were found to have severe neurologic handicaps, defined as a Bayley score on either the mental development or psychomotor index of < 68, abnormal findings on neurologic examination, or both. Fewer children (6.1% vs 15.7%) required supplemental oxygen at 2 years compared with 1 year, and performance on the psychomotor index of the Bayley Scales improved significantly. CONCLUSIONS: One- and 2-year follow-up of a cohort of infants with persistent pulmonary hypertension of the newborn who were treated with inhaled nitric oxide had an 11.8% (1 year) and 12.1% (2-year) rate of severe neurodevelopmental disability. There are ongoing medical problems in these infants including reactive airways disease and slow growth that merit continued close longitudinal follow-up.

Room air challenge: prediction for successful weaning of oxygen-dependent infants.

OBJECTIVE: The objective of this study was to determine the time required for equilibration of oxygen saturation (SpO2) and the oxygen flow rate that might predict readiness for oxygen weaning to room air in preterm infants with improving bronchopulmonary dysplasia (BPD). STUDY DESIGN: This was a prospective longitudinal cohort study, conducted in the neonatal care unit and the neonatal high risk follow-up clinic. Seventeen preterm children with BPD (mean postconceptual age 39.9 [range 31.5 to 43.5] weeks) were enrolled. With the infants breathing room air, the SpO2 pulse and respiratory rates, and clinical status were monitored for 120 minutes. Factors that predicted a successful room air challenge were determined. Children successfully weaned were followed up for 6 months after discontinuation of oxygen therapy. RESULTS: A total of 20 room air challenges were done in 17 study infants. In most infants the lowest SpO2 value (mean 89.7%) was reached within the first 40 minutes. Infants with an SpO2 > or = 92% at 40 minutes continued to have values > or = 92% at 120 minutes (specificity, 100%; sensitivity, 42%). In all infants receiving oxygen flow rates < or = 20 ml/kg per minute an SpO2 > or = 92% was maintained after 40 and 120 minutes. Infants who were successfully weaned to room air showed maintenance of weight and height percentiles 6 months after discontinuation of oxygen therapy. One child was rehospitalized and oxygen support reinstituted because of viral pneumonia. CONCLUSIONS: An SpO2 value > or = 92% at 40 minutes best predicts readiness for oxygen weaning to room air in infants with improving BPD. Infants requiring oxygen flow rates < or = 20 ml/kg per minute are also likely to be weaned off oxygen support.

Fetal drug therapy.

As prenatal diagnosis has become more sophisticated, avenues for a variety of intrauterine therapies have been opened. Considerable experience has been gained with surgical and pharmacologic approaches. This article provides a review of intrauterine drug therapy aimed at preventing fetal and neonatal disease and treating existing fetal conditions. The future awaits the exciting applications of intrauterine hematopoietic transplants and genetic therapy.

A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS). METHODS: We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques. RESULTS: The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants. CONCLUSION: Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.

Cerebral hemodynamics and distribution of left ventricular output during inhalation of nitric oxide.

OBJECTIVES: Inhaled nitric oxide is being utilized as a selective pulmonary vasodilator in the treatment of persistent pulmonary hypertension of the newborn. However, the effects of inhaled nitric oxide on cerebral hemodynamics and distribution of left ventricular output in newborn subjects have not been studied. This study was designed to measure quantitatively the effect of inhaled nitric oxide on the distribution of left ventricular output and on cerebral hemodynamics in a perinatal animal model. DESIGN: Prospective, controlled, experimental study. SETTING: Research laboratory. SUBJECTS: Eight fetal sheep. INTERVENTIONS: Each animal was exposed to three separate study periods: a) mechanical ventilation with low FIO2 (maintaining fetal levels of PaO2); b) inhalation of nitric oxide (20 parts per million) during mechanical ventilation and low FIO2; and c) mechanical ventilation with an FIO2 of 1.0. MEASUREMENTS AND MAIN RESULTS: Left ventricular output and cerebral blood flow were measured with radiolabeled microspheres. Cerebral oxygen delivery and consumption variables were calculated using measurements of arterial and cerebral venous (sagittal sinus) oxygen content. Total left ventricular output did not differ among the three treatment groups: 235 +/- 16 mL/min/kg with hypoxic ventilation; 283 +/- 13 mL/min/kg with nitric oxide inhalation; and 242 +/- 17 mL/min/kg with an FIO2 of 1.0. Lung blood flow increased 2.7-fold with inhaled nitric oxide and 1.6-fold during mechanical ventilation with an FIO2 of 1.0. With a left ventricle microsphere injection, increased lung blood flow is indicative of increased systemic-to-pulmonary shunt across the ductus arteriosus. Whole brain blood flow did not differ between the three groups: 49.6 +/- 6.7 mL/min/100 g with hypoxic ventilation; 46.4 +/- 7.4 mL/min/100 g with nitric oxide inhalation; and 36.4 +/- 3.8 mL/min/100 g with an FIO2 of 1.0. Cerebral oxygen delivery increased during inhalation of an FIO2 of 1.0 when compared with nitric oxide inhalation (p < .007); fractional extraction of oxygen decreased (p < .004 compared with hypoxic ventilation, p < .0005 compared with nitric oxide inhalation). Cerebral oxygen consumption did not differ between the three groups (1.11 +/- 0.12 microns/min/100 g with hypoxic ventilation, 0.95 +/- 0.12 microns/min/100 g with nitric oxide inhalation, and 0.96 +/- 0.08 microns/min/100 g with an FIO2 of 1.0). CONCLUSION: Acute pulmonary vasodilation caused by inhalation of nitric oxide does not change left ventricular output, cerebral blood flow, or cerebral oxygen consumption, despite an increased systemic-to-pulmonary shunt across the ductus arteriosus.

Population dynamics of exploited fish stocks at low population levels.

Models of population dynamics in which per capita reproductive success declines at low population levels (variously known as depensation, the Allee effect, and inverse density-dependence) predict that populations can have multiple equilibria and may suddenly shift from one equilibrium to another. If such depensatory dynamics exist, reduced mortality may be insufficient to allow recovery of a population after abundance has been severely reduced by harvesting. Estimates of spawner abundance and number of surviving progeny for 128 fish stocks indicated only 3 stocks with significant depensation. Estimates of the statistical power of the tests strengthen the conclusion that depensatory dynamics are not apparent for fish populations at the levels studied.

Developmental changes in newborn lamb brain mitochondrial activity and postasphyxial lipid peroxidation.

Previously, our laboratory has demonstrated inhibition of mitochondrial state 3 (ADP-dependent) respiration 5 min after resuscitation from an asphyxial insult in lambs less than 3 days of age. Older lambs were resistant to this transient mitochondrial dysfunction. This study was designed to examine if age-related differences in baseline state 3 mitochondrial respiration, electron transport chain activity, or susceptibility to oxygen free radical-mediated lipid peroxidation were related to the previously observed differences in postasphyxial mitochondrial respiration. Mitochondrial respiration was measured in 24 nonasphyxiated control lambs aged 1-10 days using four different substrates. Electron transport chain activity was assessed in 15 of these lambs, and lipid peroxidation measured as conjugated diene production was measured in 11 of these lambs. These lambs were all ventilated to maintain normal blood gases for a time period equal to the length of the hypoxic insult in asphyxiated lambs (see below), after which samples of brain were removed for isolation of mitochondria. A second group of 11 lambs (seven < or = 3 days of age and four > 3 days of age) were asphyxiated. The insult was a 75-to-90-min episode of hypoxia and hypercarbia that resulted in bradycardia and systemic hypotension over the final 15 min of the insult. At the end of asphyxia, the lambs were resuscitated and returned to control ventilator settings. Samples of brain were removed 5 min after resuscitation. Postasphyxia electron transport chain activity and lipid peroxidation were measured. All measurements described above were done in both nonsynaptic (primarily glial in origin) and synaptic mitochondria. State 3 mitochondrial respiration varied significantly with age, decreasing by an average of 41.2% +/- 11.1% (mean +/- SEM) from Day 2 to Day 5-6 and then increasing back to levels similar to Day 2 by Day 8-10 in nonsynaptic mitochondria. State 3 respiration in synaptic mitochondria decreased 60.6% +/- 5.2% from Day 2 to Day 5-6 before returning to levels similar to Day 2 by Day 8-10. Resting (nonADP-dependent) state 4 respiration demonstrated similar developmental patterns. Electron transport chain activities did not vary with age in the nonasphyxiated control animals. In addition, an asphyxial insult did not diminish electron transport chain activities in either lambs < or = 3 days old or those > 3 days of age.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasma cysteine concentrations in infants with respiratory distress.

Because factors that predispose infants to persistent pulmonary hypertension of the newborn (PPHN) may cause oxidant stress, which in turn may increase demands for cysteine and glutathione, we investigated the availability of cysteine and its precursors in PPHN and related disorders. Plasma concentrations of four sulfur-containing and two non-sulfur-containing amino acids were measured by gas chromatography-mass spectrometry in blood from infants with PPHN, both those managed conventionally (PPHN group) and those treated with extracorporeal membrane oxygenation, as well as from infants with hyaline membrane disease. Concentrations also were measured in umbilical venous cord blood samples from a healthy control population, in venous plasma from infants receiving only intravenously administered glucose-containing solutions because they had noncardiopulmonary illnesses ("fasted" group), and from otherwise healthy, orally fed infants ("fed" group). The plasma total cyst(e)ine concentration was markedly lower in the three groups (PPHN, PPHN and extracorpeal membrane oxygenation, and hyaline membrane disease) receiving an elevated inspired oxygen concentration (0.6 to 1.0) than in fasted or fed control infants. In contrast, levels of plasma methionine, the other major sulfur amino acid, were low in the three groups receiving an elevated inspired oxygen concentration, as well as in fasted infants. Glycine and serine, two non-sulfur-containing amino acids, had a pattern similar to that of plasma methionine. Thus infants with PPHN and hyaline membrane disease have low plasma total cyst(e)ine levels, an effect that does not appear to result primarily from nutritional deprivation. We speculate that the role of cysteine in bioactivation of nitric oxide and as a precursor of glutathione may be relevant to the pathogenesis and evolution of PPHN and respiratory distress syndrome. Further studies are needed to determine whether increased demands for cysteine exist in these disorders.

Prevention of intraventricular hemorrhage in the premature infant.

PIVH remains a significant problem in the care of the preterm infant. Recent technologic advances such as real-time ultrasonography and Doppler flow studies have facilitated accurate diagnosis and provided insight into the pathogenesis. Although the overall incidence of PIVH is declining, the outcome of survivors of PIVH--especially those with more severe grades--remains unfavorable. Several antenatal and postnatal interventions aimed at reducing the overall incidence and severity of PIVH have been attempted. Antenatal interventions, in particular phenobarbital, appear to be promising because a substantial percentage of PIVH occurs in the immediate perinatal period. It is significant that the four reported antenatal phenobarbital trials demonstrated a consistent decrease in severe PIVH. Despite the fact that these studies have different designs and each must be considered on its own, the consistency of results makes a strong statement regarding efficacy and safety. The on-going multicenter Neonatal Network trial should provide definitive results as to the efficacy and safety of antenatal phenobarbital in the prevention of PIVH.