Urinary F2-isoprostanes are poor prognostic indicators for the development of bronchopulmonary dysplasia.

OBJECTIVE: Oxygen toxicity is thought to contribute to the development of bronchopulmonary dysplasia (BPD). Oxidant injury leads to formation of F(2)-isoprostanes (F(2)-IsoP). We hypothesized that urinary excretion of the stable metabolite of F(2)-IsoP, 8-iso-PGF(2alpha), would be higher in infants who develop BPD than those who did not. METHODS: Forty infants <30-weeks gestational age (GA) were enrolled, 24 infants with BPD and 16 without BPD. Urine specimens were collected weekly and stored at -80 degrees C until analyzed. Urinary 8-iso-PGF(2alpha) was measured by gas chromatography/mass spectrometry (GC-MS) and normalized to creatinine excretion. RESULTS: GA and birth weight (BW) were lower in infants who developed BPD than those who did not. Urinary 8-iso-PGF(2alpha) levels in the first or third weeks of age were not significantly different between the two groups. CONCLUSION: Urinary excretion of 8-iso-PGF(2alpha) in early postnatal life in preterm infants is not correlated with the development of BPD.

Clara cell secretory protein oxidation and expression in premature infants who develop bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects prematurely born infants and appears to evolve in part from early inflammatory responses in the lung. The inflammatory responses have been associated with protein and lipid oxidation in tracheal aspirate fluids. The present study was designed to test the hypothesis that in the first week of life specific oxidations and/ or altered expressions of proteins would be observed in tracheal aspirate fluids in infants who would subsequently develop BPD. We obtained tracheal aspirate fluids on Days of life 1, 3, and 6 from infants born at < or = 29 wk gestation, incubated the fluids with 2,4-dinitrophenylhyrazine (DNPH), separated the proteins electrophoretically, and assessed DNPH reactivity by immunonblots. DNPH reactivity of a protein that was identified as Clara cell secretory protein (CCSP) was observed more consistently in tracheal aspirate fluids from infants who later developed BPD than from infants who did not develop BPD. Tracheal aspirate fluid levels of immunoreactive CCSP were also lower on Day of life 1 in infants who developed BPD than in those who did not develop BPD. Increased CCSP oxidation and decreased immunoreactive CCSP expression in infants who subsequently developed BPD suggest that Clara cell function and CCSP expression may be critical for normal bronchoalveolar fluid homeostasis and that maintaining CCSP expression and function may be useful goals for targeted therapies for inhibition of the development of BPD.

Neonatal intensive care applications of near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a noninvasive technique for assessing cerebral hemodynamic variables and oxidative status in the neonatal intensive care setting. It can be performed for extended periods of time at the bedside without interfering with routine patient care. NIRS appears to have the ability to not only assess relative changes in oxygenated and deoxygenated hemoglobin, total hemoglobin, and cytochrome aa3, but it can also produce estimates of cerebral blood volume and cerebral blood flow. Research data document significant changes in these hemodynamic variables with patient activity and clinical interventions in both premature and term infants. NIRS may evolve into an important diagnostic and prognostic tool for neonatal neurologic outcome.

A single very early dexamethasone dose improves respiratory and cardiovascular adaptation in preterm infants.

OBJECTIVES: To test the hypothesis that a single dose of dexamethasone given soon after delivery to infants <28 weeks' gestation leads to improved cardiopulmonary adaptation in the first week and lowers the risk of significant intraventricular hemorrhage. METHODS: In a prospective, blinded, placebo-controlled study, we randomly assigned 70 infants <28 weeks' gestation who were born in the hospital to receive dexamethasone (0.2 mg/kg) (n = 37) or normal saline solution (n = 33) within 2 hours of delivery. After an interim analysis showed that the incidence of intraventricular hemorrhage was much lower than expected, enrollment was stopped and we limited our analysis to a comparison of ventilator settings, blood pressure, and pressor use during the first 7 days. RESULTS: Clinical characteristics of the groups were comparable at study entry. Ventilator weaning occurred more rapidly in the patients who received dexamethasone: their intermittent mandatory ventilation rate was significantly lower on days 1 through 6, and their peak inspiratory pressure was lower on days 3 through 7 compared with the control group. Mean blood pressures were higher in the dexamethasone group within 12 hours and remained higher through day 5, but the use of pressors was not different. Fewer infants in the dexamethasone group received indomethacin to treat a patent ductus arteriosus (22% vs 47%, P <.03). CONCLUSION: Dexamethasone given within 2 hours of delivery to preterm infants <28 weeks' gestation resulted in lower ventilator settings and higher mean blood pressures during the first 7 days. Fewer infants required indomethacin to treat a patent ductus arteriosus.

Percutaneous central catheters and peripheral intravenous catheters have similar infection rates in very low birth weight infants.

OBJECTIVE: We performed this study to determine if percutaneous central lines (PCLs) were associated with infection more often than peripherally placed intravenous catheters (PIVs). STUDY DESIGN: We conducted a retrospective, cohort study of 53 infants with PCLs inserted from March 1993 to February 1995 for evidence of catheter-related bloodstream infection and 97 cohorts with PIVs who were matched to the infants with PCLs by admission date and birth weight. We considered an infant to have catheter-related bloodstream infection if bacteremia occurred while the PCL or PIV was in place with no other identifiable infection focus. Statistical analyses were performed by using either Student's t test or the Mann-Whitney U test where appropriate. RESULTS: There were eight infections per 1000 catheter days of PCL use and nine infections per 1000 catheter days of PIV use. CONCLUSION: PCLs do not become infected more often than PIVs.

Long-term neurodevelopmental outcome after intrauterine transfusion for the treatment of fetal hemolytic disease.

OBJECTIVE: The aim of the study was to assess the developmental outcome of neonatal survivors of hemolytic disease of the neonate treated with modern intrauterine transfusion techniques. STUDY DESIGN: In this prospective, observational study, auditory evoked-response tests were performed in the nursery. Neurodevelopmental evaluation with the Gesell Developmental Schedules was performed between 9 and 18 months of corrected age to assess motor skills, language development, comprehension capacity, and social skills. The McCarthy Scales of Children's Abilities were administered between 36 and 62 months. RESULTS: Forty children who survived severe fetal hemolytic disease were followed up until 62 months old. Demographic data included gestational age at first intrauterine transfusion (26.4 +/- 3.7 weeks), median number of intrauterine transfusions (4, range 1-8), lowest fetal hematocrit (20.2% +/- 7.8%), peak fetal bilirubin (7.1 +/- 2.1 mg/dL), incidence of hydrops fetalis (45%), and mean gestational age at delivery (35.6 +/- 2.2 weeks). One case of severe bilateral deafness and 1 case of right spastic hemiplegia were diagnosed. The Gesell Developmental Schedules score was assessed between 9 and 18 months of corrected age in 22 infants. The global developmental quotient was 101.9 +/- 9.5 (mean for normal population is 100). Regression analysis revealed no correlation between the global developmental quotient and gestational age at the first intrauterine transfusion, gestational age at birth, or the severity of the fetal hemolytic disease (fetal hematocrit, fetal bilirubin, presence of hydrops fetalis, total number of intrauterine transfusions, duration of neonatal phototherapy, and number of neonatal exchange transfusions). Eleven of the 40 children were followed up until they were 62 months old, and the McCarthy Scales of Children's Abilities were administered. The mean cognitive index was 107.6 +/- 9.4 (90-109 is considered average). CONCLUSION: Despite severe fetal hemolytic disease, normal developmental outcome can be expected for children treated with intrauterine transfusions.

Early clinical markers for the development of bronchopulmonary dysplasia: soluble E-Selectin and ICAM-1.

OBJECTIVE: To test the hypothesis that in infants born at

Lymphoblastic lymphoma following prenatal exposure to phenytoin.

PURPOSE: Oncogenesis has been associated with prenatal exposure to phenytoin, concomitant with or independent of the fetal hydantoin syndrome. The majority of reported cases have been embryonal tumors of neural crest origin and have occurred in the first 3 years of life. PATIENTS AND METHODS: We report a boy who was exposed to phenytoin throughout gestation and later developed T-lymphocyte lymphoblastic lymphoma, a previously unreported malignancy associated with in utero phenytoin exposure. Previously reported cases of neoplasia occurring after such exposure are tabulated. CONCLUSION: The actual transplacental oncogenic potential of phenytoin and the epidemiology of this association are poorly understood. Phenytoin-induced alterations in lymphocyte-mediated immunosurveillance or oxidative metabolic clearance may be etiologic. Inquiry into prenatal phenytoin exposure should be done in any child who develops cancer, especially those who develop a rare tumor or present with a more common tumor at an unusually young age. Continued documentation of such cases will advance the understanding of phenytoin-associated transplacental oncogenesis.

Prediction of neonatal crown-heel length in normal singletons, twins, and triplets using individualized growth assessment.

In groups of normally growing singletons (20), twins (20), and triplets (13), predicted femur diaphysis length (FDL) values at birth were obtained using Rossavik growth models specified from second-trimester ultrasound studies of fetal growth. Six previously published functions were utilized to obtain predicted crown-heel length (CHL) values from predicted FDL values. These values were compared to the actual CHL values and the percent differences calculated. Based on their systematic (mean percent difference) and random (standard deviation of percent difference) prediction errors, the functions of Vintzileos (singletons), Hadlock (twins), and Brown (triplets) were found to give optimal results (no systematic error; random error: +/- 6%). Using predicted CHL values obtained with these optimal functions, growth potential realization index values for CHL (GPRICHL) were determined for singletons, twins, and triplets. In all three groups, the mean GPRICHL value was 100% with a range of approximately 95% to 105%. These results indicate that the CHL can be predicted from second-trimester growth patterns and evaluated using individualized growth assessment methods.

The fetal alcohol syndrome: a multihandicapped child.

The effect of intrauterine exposure of the fetus to ethanol has been appreciated since Biblical times. An article by Lemoine (1968) describing the effects and long term prognosis was virtually ignored until 1973. At that time Jones and Smith described a constellation of anomalies in infants born to alcoholic women and labeled this condition the Fetal Alcohol Syndrome (FAS). The evolution of this syndrome over the last 15 years is reminiscent of the congenital rubella syndrome with its continuum of handicapping morbidity. Even if there is no facial dysmorphia and the child has a normal IQ, the stigma from intrauterine ethanol exposure persists. Visual-motor perception and performance IQ are lower and receptive and expressive language are delayed. Distractibility persist. The child with Fetal Alcohol Syndrome remains a multihandicapped child.