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BACKGROUND: Renal failure is common in the NICU; Acute Kidney Injury (AKI) occurs in 8-24% of admissions. Although AKI is preventable with early diagnosis, no reliable AKI biomarkers exist. Endothelin-1 (ET-1) has been implicated in renal pathogenesis, and elevated urinary ET-1 (uET-1) levels may correlate with progression of renal dysfunction. The study objectives were to determine whether uET-1 levels correlate with renal function parameters and/or fetal growth restriction, and if uET-1 is a potential neonatal AKI biomarker. METHODS: Sixty-three neonates were enrolled and divided into gestational age (GA) groups by weeks: 1) (24-30 6/7; n = 24); 2) (31-36 6/7; n = 26); and 3) (37-42; n = 13). Additional preterm subgroups for fetal growth restriction analysis included: 1) Appropriate for GA (AGA; n = 40), and 2) Small for GA (SGA; n = 10). ET-1 levels, measured using enzyme linked immunosorbent assay, were collected at birth (cord blood) and 24 h ( ± 4) of life (blood/urine). RESULTS: No correlation was found between uET-1 and blood plasma levels at birth (r = 0.15; p > 0.05) or 24 h (r = 0.17; p > 0.05). uET-1 negatively correlated with GA (r = -0.44; p < 0.001) and GFR (r = -0.34; p < 0.01). uET-1 levels did not correlate with creatinine (r = 0.13; p > 0.05), BUN (r = 0.19; p > 0.05), BUN/Cr ratio (r = 0.15; p > 0.05), or urinary output (r = 0.12; p > 0.05). In fetal growth restriction subgroup analyses: uET-1 levels negatively correlated with GFR in the PT-AGA subgroup (r = -0.38; p = 0.017), but not with PT-SGA (r = 0.01; p > 0.05). CONCLUSION: Plasma and uET-1 levels did not correlate; therefore, renal ET-1 excretion may reflect renal ET-1 production. uET-1 levels correlated negatively with GA and GFR. uET-1 may be a marker of impaired neonatal circulatory regulation and consequent renal injury.

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Prenatal opioid exposure such as oxycodone is linked to significant adverse effects on the developing brain. Endothelin (ET) and its receptors are involved in normal development of the central nervous system. Opioid tolerance and withdrawal are mediated through ET receptors. It is possible that adverse effect of oxycodone on the developing brain is mediated through ET receptors. We evaluated brain ETA and ETB receptor expression during postnatal development in rats with prenatal oxycodone exposure. Timed pregnant Sprague-Dawley rats received either oxycodone or placebo throughout gestation. After birth, male rat pups were sacrificed on postnatal day (PND) 1, 7, 14 or 28. Brain ETA and ETB receptor expression was determined by Western blot analysis. Oxycodone pups compared to placebo demonstrated congenital malformations of the face, mouth, and vertebrae at the time of birth [4/69 (5.7%) vs. 0/60 (0%); respectively] and intrauterine growth retardation [10/69 (15%) vs. 2/60 (3.3%); respectively]. On PND 28, oxycodone pups compared to placebo had lower body and kidney weight. ETA receptor expression in the oxycodone group was significantly higher compared to placebo on PND 1 (p=0.035), but was similar on PND 7, 14, or 28. ETB receptor expression decreased in oxycodone compared to placebo on PND 1 and 7 (p=0.001); and increased on PND 28 (p=0.002), but was similar on PND 14. Oxycodone-exposed rat pups had lower birth weight and postnatal weight gain and greater congenital malformations. ETB receptor expression is altered in the brain of oxycodone-treated rat pups indicating a possible delay in CNS development.

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Endothelin, vascular endothelial growth factor and nerve growth factor play important roles in development of the central nervous system. ET(B) receptors have been shown to promote neurovascular remodeling in the adult ischemic brain through an increase in VEGF and NGF. It is possible that ET(B) receptors may be involved in postnatal development of the brain through VEGF and NGF. In the present study, the brains of male rat pups on postnatal days 1, 7, 14 and 28 were analyzed for expression of ET(B) receptors, VEGF and NGF. In order to determine the effect of ET(B) receptor stimulation, a separate group of pups were administered saline or ET(B) receptor agonist, IRL-1620, on day 21, and their brains were analyzed on day 28. The intensity of ET(B) receptor and VEGF staining in the vasculature as well as the number of blood vessels of normal pups increased with age and was significantly higher on postnatal day 14 compared to day 1 and day 7. In contrast, both ET(B) and NGF staining intensity in the cortex and subventricular zones decreased (P<0.01) at postnatal day 14 compared to earlier time points. Stimulation of ET(B) receptors resulted in a significant increase in VEGF and ET(B) intensity both in the vasculature and the brain (P<0.05), however, IRL-1620 did not produce any change in NGF expression. Results indicate that ET(B) receptors appear to play a role in the development of the CNS and selective stimulation of ET(B) receptors enhances VEGF but not NGF in the postnatal rat brain.

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OBJECTIVE: To determine emission of volatile organic compounds (VOCs) from plastic medical equipment within an incubator. STUDY DESIGN: Air samples from incubators before and after adding medical equipment were analyzed using EPA TO-15 methodology. Headspace analysis was used to identify VOC emissions from each medical equipment item. Air changes per hour (ACH) of each incubator were determined and used to calculate the emission rate of identified VOCs. RESULTS: Cyclohexanone was identified in all incubator air samples. At 28 °C, the mean concentration before and after adding medical equipment items was 2.1 ± 0.6 and 57.2 ± 14.9 µg m(-3),respectively (P<0.01). Concentrations increased to a mean of 83.8 ± 23.8 µg m(-)(3) (P<0.01) at 37(o)C and 93.0 ± 45.1 µg m(-)(3) (P=0.39) after adding 50% humidity. Intravenous tubing contributed 89% of cyclohexanone emissions. ACH were determined with access doors closed and open with means of 11.5 ± 1.7 and 44.1 ± 6.7 h(-1), respectively. Cyclohexanone emission rate increased from a mean of 102.2 µg h(-1) at 28(°C to 148.8 µg h(-1) (P<0.01) at 37 °C. CONCLUSION: Cyclohexanone was quantified in all incubator air samples containing plastic medical equipment. The concentration of cyclohexanone within the incubator was inversely related to ACH in the closed mode. The cyclohexanone concentration as well as the emission rate increased with higher temperature.

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OBJECTIVE: To identify and quantify airborne volatile organic compounds (VOCs) inside neonatal incubators during various modes of operation within the neonatal intensive care unit (NICU) environment. STUDY DESIGN: Air samples were taken from 10 unoccupied incubators in four operational settings along with ambient air samples using air sampling canisters. The samples were analyzed following EPA TO-15 using a Tekmar AutoCan interfaced to Agilent 6890 Gas Chromatograph with a 5973 Mass Spectrometer calibrated for 60 EPA TO-15 method target compounds. Non-target compounds were tentatively identified using mass spectral interpretation and with a mass spectral library created by National Institute for Standards and Technology. RESULT: Two non-target compounds, 2-heptanone and n-butyl acetate, were found at elevated concentrations inside the incubators compared with ambient room air samples. Increase in temperature and addition of humidity produced further increased concentrations of these compounds. Their identities were verified by mass spectra and relative retention times using authentic standards. They were quantified using vinyl acetate and 2-hexanone as surrogate standards. CONCLUSION: The emission pattern of these two compounds and background measurements indicate that they originate inside the incubator. There is evidence that exposure to some VOCs may adversely impact the fetal and developing infants' health. Currently, as there is no definitive information available on the effects of acute or chronic low-level exposure to these compounds in neonates, future studies evaluating the health effects of neonatal exposure to these VOCs are needed.

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OBJECTIVES: Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG. METHODS: A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion. RESULTS: Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm. CONCLUSIONS: Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.

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OBJECTIVE: We carried out a randomized placebo-controlled trial in very low birth weight neonates (VLBWNs), comparing the incidence of nosocomial infections after the prophylactic use of recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) versus placebo in VLBWNs. STUDY DESIGN: VLBWNs (n = 264), weighing 501 to 1000 g, /=4000/mm,3 peripheral blood progenitor studies, and 24-hour polymorphonuclear leukocyte C3bi receptor expression were compared between the 2 treatment groups. RESULTS: No (grade III/IV) toxicity or adverse events were associated with rhu GM-CSF. The absolute neutrophil count and absolute eosinophil count were significantly elevated in the rhu GM-CSF group on days 7 (P =.001), 14 (P =.001), and 21 (P =.007) and on days 7 and 28 (P =.012 and P =.001, respectively). However, there was no difference in the incidence of confirmed nosocomial infections between the 2 treatment groups in this trial (40% vs 39%, rhu GM-CSF vs placebo; P = NS). CONCLUSION: In a large randomized placebo-controlled trial, prophylactic administration of rhu GM-CSF in VLBWNs does not appear to decrease the incidence of nosocomial infections.

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After immunization with recombinant hepatitis B vaccine, 19 infants were tested serially for hepatitis B surface antigen (HBsAg); 65% of infants had test results positive for HBsAg at least once, the incidence peaking 2 to 3 days from the time of immunization. The longest documented duration of antigenemia was 8 days; in all patients, HBsAg test results were negative by 18 days.

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A term infant with aortic and renal artery thrombosis is described, in whom the right kidney experienced complete ischemia for 5 days. A continuous intrathrombic urokinase infusion induced complete clot lysis and reperfusion of the right kidney. Follow-up studies of renal function and renal growth have been normal. This is the first report to describe complete pharmacological salvage of a neonatal kidney after prolonged warm ischemia. This case underscores both the ability of the neonatal kidney to recover from prolonged ischemia and the need to effect thrombolysis before irreversible renal injury occurs. The intrathrombic use of fibrinolytic agents in similarly affected infants warrants consideration and further study.

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Nasal gliomas are benign congenital midline tumors with the potential for intracranial extension. They are most commonly seen in neonates and children but rarely in adults. The treatment of choice is surgical excision. Inadequate primary excision results in a 4 to 10 percent recurrence. Hence, a thorough preoperative evaluation is essential to delineate the exact site and extension of the tumor and to plan the appropriate surgical approach. Computerized tomographic (CT) scans are useful in visualizing bony defects, but are not well suited for soft tissue imaging. Magnetic resonance imaging (MRI) offers superior soft tissue contrast, without ionizing radiation. This is a report of a neonate with unexplained early respiratory distress. On day 5, a soft nasal mass became apparent. CT scans were inconclusive, so MRI scan was used to demonstrate intracranial extension. MRI is superior for imaging brain tissue, so it should be used preferentially to delineate intracranial extension and to help guide the surgical approach.

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The authors report two cases of sudden unexpected cardiorespiratory arrest occurring in a normal newborn nursery. They discuss the impact on the families and hospital personnel. The nursing and medical staff demonstrated many of the reactions experienced by families of sudden infant death syndrome (SIDS) victims, including shock, anger, guilt, disbelief, fear, and doubt. The manner in which hospital personnel were supported and counseled is discussed. Specific clinical implications of these cases, including the need to provide for appropriate monitoring and resuscitation in normal newborn nurseries, are presented.

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When a newborn infant presents with high intestinal atresia, the proximal segment of the bowel is usually grossly distended and atonic. The anastomosis of this segment to the smaller and unused distal segment will usually result in little or no propulsion of contents distally. Many techniques have been employed to correct this problem. A common surgical approach is immediate end-to-end anastomosis, followed by parenteral alimentation until return of normal function. This can take many weeks, and requires special attention to fluid loss and complications associated with parenteral alimentation. In this paper we report two infants in whom we utilized a new technique to circumvent these problems. The technique involves continuous drip ileostomy feedings through the distal ileostomy, while basic nutritional needs are being met parenterally. In addition, the secretions from the proximal stoma are collected and infused with the elemental feeding. The distal bowel, now being fully utilized, is stimulated to accommodate, and when the two ends are joined at a second operation, nearly normal anatomical bowel is present.

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Fifty-six premature infants with a mean gestational age at birth of 30 weeks were randomly assigned to a transfusion group, for whom the hemoglobin level was kept above 10.0 g/dL, and a nontransfusion group, who were transfused only for specific clinical indications. The groups were followed up longitudinally with weekly determinations of reticulocyte count, the partial pressure of oxygen at which 50% of hemoglobin is saturated, and hemoglobin F percentage, as well as weight gain, length of stay, hospital cost, and frequency and severity of apnea. At birth, there was no significant difference in birth weight, gestational age, and hemoglobin level between the two groups. At discharge, laboratory differences were noted between the two groups, but there was no clinical difference. We found no clinical advantage to the use of "booster" RBC transfusions in growing premature infants.

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