Chronic lung disease in very low birth weight infants: Persistence and improvement of a quality improvement process in a tertiary level neonatal intensive care unit.

OBJECTIVE: We previously demonstrated a significant reduction in our incidence of chronic lung disease in our NICU using potentially better practices of avoiding delivery room endotracheal intubation and using early nasal CPAP. We sought to demonstrate whether these improvements were sustained and or improved over time. STUDY DESIGN: We conducted a retrospective, cross-sectional analysis of infants 501-1500 grams born at our hospital between 2005 and 2013. Infants born during the 2005-2007, 2008-2010 and 2011-2013 epochs were grouped together, respectively. Descriptive analysis was conducted to determine the number and percent of maternal and neonatal characteristics by year grouping. Chi-squared tests were used to determine whether there were any statistically significant changes in characteristics across year groupings.. Two outcome variables were assessed: a diagnosis of chronic lung disease based on the Vermont Oxford Network definition and being discharged home on supplemental oxygen. RESULTS: There was a statistically significant improvement in the incidence of chronic lung disease in infants below 27 weeks' gestation in the three year period in the 2011-2013 cohort compared with those in the 2005-2007 cohort. We also found a statistically significant improvement in the number of infants discharged on home oxygen with birth weights 751-1000 grams and infants with gestational age less than 27 weeks in the 2011-2013 cohort compared to the 2005-2007 cohort. CONCLUSIONS: We demonstrated sustained improvement in our incidence of CLD between 2005 and 2013. We speculate that a multifaceted strategy of avoiding intubation and excessive oxygen in the delivery room, the early use of CPAP, as well as the use of volume targeted ventilation, when needed, may help significantly reduce the incidence of CLD.

Comparison of cerebrovascular effects of intravenous cocaine injection in fetal, newborn, and adult sheep.

Cocaine may cause stroke, intracranial hemorrhage, seizures, and neurobehavioral abnormalities in fetuses, newborns, and adults, and there could be developmental and/or species differences in mechanisms for these cocaine-induced cerebrovascular effects. To evaluate developmental differences in responses to cocaine, we compared the cerebrovascular and metabolic responses to a 2 mg/kg iv cocaine dose in unanesthetized fetal (n = 8, previously reported, direct fetal injection), newborn (n = 6), and adult (n = 12) sheep. We measured cerebral blood flow, mean arterial blood pressure, and arterial and venous O(2) content, and we calculated cerebral O(2) consumption and cerebral vascular resistance at baseline and at 30 s and at 5, 15, and 60 min after cocaine injection. Cerebral blood flow increased 5 min after injection in the fetus and newborn, but not until 15 min in the adult. In the fetus, cocaine caused a transient cerebral vasoconstriction at 30 s; in all three groups, cocaine caused cerebral vasodilation, which was delayed in the adult. Cerebral metabolic O(2) consumption increased 5 min after injection in the fetus and newborn, but not until 15 min after injection in the adult. Arterial O(2) content decreased 5 min after injection in the fetus and 15 min after injection in the adult. We speculate that clinical differences in response to cocaine injection may be explained, in part, by these developmental differences in the cerebrovascular and metabolic responses to cocaine.

Expression of cln3 in human NT2 neuronal precursor cells and neonatal rat brain.

During brain development, excess neurons that are formed die by apoptosis. cln3 was recently identified as the gene defective in juvenile Batten disease, an inherited neurodegenerative disease of childhood. In this disease, neurons die by apoptosis. Overexpression of this gene increases survival of human NT2 neuronal precursor cells. We, therefore, hypothesized that cln3 may be present in developing neurons and may play an important role in regulating the developmental process. NT2 neuronal cells were induced to develop into mature neurons. We evaluated cln3 expression by reverse transcription PCR and immunohistochemistry over a 7-wk period of differentiation. Also, cln3 expression was characterized in neonatal rat brain during the first week of life (P-1, P0, P4, and P8) and at P30. cln3 was differentially expressed during neuronal development into nondividing post-mitotic neurons. The greatest expression was noted during wk 6 and then dropped to predifferentiation levels during wk 7. cln3 expression was detected in all the rat brain developmental stages evaluated. The greatest expression was seen at P0 and was double compared with the other stages. We conclude that cln3 is present during critical periods of neuronal cell differentiation and brain development. As cln3 is antiapoptotic, we hypothesize that cln3 plays an important role in regulating brain development. These findings may have implications for identifying strategies aimed at neuroprotection and neuronal survival during development.

Propranolol blocks cocaine-induced cerebral vasodilation in newborn sheep.

OBJECTIVE: The objective of this study was to test the hypothesis that cocaine-induced cerebral vasodilation in newborn sheep is mediated via beta-adrenergic receptor activation. DESIGN: The cerebral effects of a single intravenous injection of cocaine (4 mg/kg) given 30 mins after pretreatment with propranolol (1 mg/kg) were studied and compared with the results from a previous study using an identical cocaine protocol without propranolol pretreatment. SUBJECTS: Seven chronically catheterized, unanesthetized newborn sheep (6 +/- 1 days old). MEASUREMENTS: Cerebral blood flow using radiolabeled microspheres, mean arterial blood pressure (MAP), heart rate, and cerebral arterial and venous oxygen content were measured at baseline, after administration of propranolol, and 0.5, 5, 15, and 60 mins after cocaine injection. Cerebrovascular resistance was calculated as the MAP divided by the cerebral blood flow. MAIN RESULTS: Propranolol injection alone caused no systemic or cerebral physiologic changes other than an 11 +/- 2% (mean +/- SEM) decrease in heart rate, which was sustained after cocaine injection. In contrast to previous studies showing cerebral vasodilation (25% decrease in cerebrovascular resistance) and acute hypertension (57% increase in MAP) 30 secs after cocaine injection, there were no changes in cerebrovascular resistance after cocaine injection and after propranolol pretreatment and there was only a 23 +/- 7% increase in MAP 30 secs after injection, with a return to baseline by 15 mins. Cocaine and norepinephrine levels were similar to those previously reported in the newborn sheep after an injection of 4 mg/kg cocaine. CONCLUSION: Propranolol blocks cocaine-induced cerebral vasodilation and blunts the acute hypertension in newborn sheep, suggesting that cocaine's cerebrovascular effects in the developing brain are mediated, at least in part, by beta-adrenergic receptor activation.

Ecgonine methyl ester, a major cocaine metabolite, causes cerebral vasodilation in neonatal sheep.

Maternal cocaine abuse has been associated with fetal and neonatal neurologic abnormalities, including hemorrhagic cerebral infarctions, but the mechanisms for cocaine's cerebral effects are unknown. We previously showed that acute cocaine injection causes cerebral vasodilation in cats and immature sheep; others have shown that cocaine causes cerebral vasoconstriction in piglets and in pressurized neonatal sheep arteries. Although methodologic and species differences may explain these conflicting results, we tested another possibility; that is, that ecgonine methyl ester (EME), a major cocaine metabolite in sheep, causes cerebral vasodilation and may account, in part, for cocaine's vascular effects. We studied the cerebral effects of a single i.v. injection of EME (2.5 mg/kg) in eight chronically catheterized, unanesthetized neonatal sheep (4 +/- 2 d old). We measured cerebral hemisphere blood flow (CBF) using radiolabeled microspheres, mean arterial pressure, heart rate, and arteriovenous oxygen content, and we calculated cerebral oxygen consumption (CMRo2) and cerebrovascular resistance at baseline and 0.5, 2, 5, and 60 min after EME injection. EME injection had no systemic effects, including no changes in mean arterial pressure, heart rate, or arterial blood gases. Within 0.5 min of injection, EME caused a 21% decrease in cerebrovascular resistance, which remained decreased for 60 min. CBF increased by 20% at 0.5, 2, and 5 min. Blood flow to brain regions other than the cerebral hemispheres paralleled changes in CBF, with cerebellar flow remaining increased at 60 min. There was no change in CMRo2. There was a small, but physiologically insignificant, decrease in arterial oxygen content. We conclude that EME causes cerebral vasodilation in neonatal sheep and may account, in part, for cocaine's cerebral vascular effects.