Inductive signals cause conversion of mesenchyme into epithelia during the formation of many organs. Yet a century of study has not revealed the inducing molecules. Using a standard model of induction, we found that ureteric bud cells secrete factors that convert kidney mesenchyme to epithelia that, remarkably, then form nephrons. Purification and sequencing of one such factor identified it as leukemia inhibitory factor (LIF). LIF acted on epithelial precursors that we identified by the expression of Pax2 and Wnt4. Other IL-6 type cytokines acted like LIF, and deletion of their shared receptor reduced nephron development. In situ, the ureteric bud expressed LIF, and metanephric mesenchyme expressed its receptors. The data suggest that IL-6 cytokines are candidate regulators of mesenchymal to epithelial conversion during kidney development.

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We sought to determine the rate of spontaneous closure of the ductus arteriosus (DA) in very-low-birth-weight infants. This prospective observational study included 65 infants whose birth weight (BW) < 1500 g. Echocardiograms were done on day of life (DOL) 3 and 7, weekly for the first month, and bimonthly until ligation, discharge, or death. Treatment was reserved for infants with heart failure, acute renal impairment, or those with significant persistent or escalating respiratory support. Chi-square tests, Student T tests, and logistic regression models were used to identify possible associations between spontaneous ductal closure by DOL 7 and predictor variables. Patterns of spontaneous DA closure over time were examined using Kaplan-Meier survival analysis. The DA closed spontaneously in 49% infants by DOL 7. Rates of spontaneous closure by DOL 7 differed significantly by BW strata: 67% for BW > 1000 g, 31% for BW 1000 g did not require intervention, and the DA closed spontaneously prior to discharge in 94%. In a logistic regression model, only BW > 1000 g and male gender were significantly associated with spontaneous closure by 1 week of life. The median time to spontaneous closure differed significantly between infants in the two BW strata: 7 days for > 1000 g versus 56 days for 1000 g BW is rarely indicated. In infants

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In very low birth weight (VLBW) infants, acute renal impairment (ARI) is common but there is no consensus about criteria for its diagnosis. Neutrophil gelatinase-associated lipocalin (NGAL) is an early and sensitive indicator of renal impairment in experimental animals, children, and adults. Urinary NGAL (UNGAL) is detectable in VLBW infants; however, there is no reference range in this population. The objective of this study is to define the reference range for UNGAL in VLBW infants with no risk factors for ARI. UNGAL concentration was determined in urine samples collected from day of life (DOL) 4 through DOL 30 in 50 newborns with uncomplicated clinical courses, selected from a total of 145 prospectively enrolled appropriate for gestational age (AGA) inborn VLBW premature infants. The birth weight and gestational age ranges were 790–1490 grams and 26–33 weeks, respectively. The median, 95th and 99th percentiles, and range of pooled UNGAL values were 5 ng/ml, 50 ng/ml, 120ng/ml, and 2–150 ng/ml, respectively. Greater variability and higher quantile levels of UNGAL were observed in females vs. males. In conclusion, a reference range for UNGAL in VLBW infants, similar to that in children and adults, has been established.

NPC is a unique multidisciplinary approach for the care of newborns affected by life-limiting or complex medical conditions with uncertain prognosis. Standardized guidelines should be implemented with the goal of achieving a state of comfort for newborns throughout the course of illness. Further studies are warranted to assess whether NPC effectively promotes newborns' comfort and parents and providers' satisfaction.

Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to the search for reliable biomarkers. This study aims to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) rises in culture-positive sepsis and, if so, is elevated at the time sepsis is suspected. This is a prospective study of 91 VLBW infants whose urine was collected daily for uNGAL analysis. In 65 episodes of suspected sepsis, four groups were identified: a) culture-positive sepsis; b) single culture positive for Staphylococcus epidermidis; c) and d) negative culture with antibiotic treatment for Ն7 d and Ͻ7 d, respectively. Daily means of uNGAL of each group were estimated for comparison. Mean uNGAL in group A (179 ng/mL) was significantly elevated on the day blood culture was drawn (day 0) compared with the mean of healthy VLBW infants (6.5 ng/mL), and to the means in groups B, C, and D (p Ͻ 0.05). In group A, mean uNGAL was significantly elevated on day 0 and daily for 5 days when compared with that of the day before culture (p Ͻ 0.05 to Ͻ0.005). uNGAL shows promise as an early marker for culture-positive sepsis in VLBW infants. (Pediatr Res 67: 636-640, 2010)

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