ABSTRACT
OBJECTIVE: To assess pulmonary outcomes of infants <29 weeks gestational age (GA), delivered at level I, II and III facilities, to identify potentially modifiable factors affecting bronchopulmonary dysplasia (BPD) severity and to assess the external generalizability of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) BPD Outcome Estimator. STUDY DESIGN: Outcomes for infants <29 weeks GA born during (2008-2010) and delivered either at an inborn level III center or in a level II or III metropolitan area hospital with transfer to a level IV center, or delivered in a distant level I or II center and then transported to a level IV center were assessed. BPD severity was compared with the NICHD Neonatal BPD Outcome Estimator. RESULT: Of 158 infants who comprised the cohort, 28 (17.8%) had no BPD, 39 (24.2%) had mild BPD, 45 (28.7%) had moderate BPD, 31 (19.7%) had severe BPD and 15 (9.6%) died at ≤36 weeks post menstrual age. Site of birth did not predict severe BPD or death. Receiver operator characteristic curves showed fair predictability for none/mild and severe BPD. CONCLUSION: BPD severity was not dependent on site of birth. The NICHD BPD outcome estimator provides fair prediction for extreme outcomes.
Subject(s)
Bronchopulmonary Dysplasia/epidemiology , Infant, Extremely Premature , Outcome Assessment, Health Care/methods , Bronchopulmonary Dysplasia/classification , Bronchopulmonary Dysplasia/mortality , Cohort Studies , Female , Humans , Infant, Newborn , Infant, Very Low Birth Weight , Male , Prognosis , ROC Curve , Risk Factors , Severity of Illness IndexABSTRACT
OBJECTIVE: To compare the relative safety and efficacy of Infasurf (calf lung surfactant extract; ONY, Inc, Amherst, NY, IND #27169) versus Survanta (Beractant, Ross Laboratories, Columbus, OH) in reducing the acute severity of respiratory distress syndrome (RDS) when given at birth and to infants with established RDS. DESIGN: A prospective, randomized, double-blind, multicenter clinical trial. SETTING: Thirteen neonatal intensive care units participated in the treatment arm: seven of these concurrently participated in the prevention arm. PATIENTS: The treatment arm enrolled infants of =2000 g birth weight with established RDS, and the prevention arm enrolled infants of =29 weeks' gestation with birth weights <1250 g. INTERVENTION: Infants were randomly assigned to receive Infasurf (n = 303, treatment arm; n = 180, prevention arm) or Survanta (n = 305, treatment arm; n = 194, prevention arm) in accordance with the Survanta package insert instructions. OUTCOME MEASURES: We projected a 25% reduction between groups in the need for a third dose of surfactant for infants with established RDS, and a 25% reduction in the need for a second dose of surfactant for infants who received prophylactic surfactant. Secondary outcomes included the severity of RDS measured by inspired oxygen concentrations and mean airway pressure, air leaks, complications associated with surfactant administration, and survival to 36 weeks' postmenstrual age without the need for oxygen supplementation. RESULTS: In the treatment arm, there was no difference between groups in the number of infants requiring more than two doses of surfactant. The interval between doses was significantly longer for Infasurf, suggesting an increased duration of treatment effect. The inspired oxygen concentration and mean airway pressure were lower in the Infasurf infants during the first 48 hours in the treatment arm. In the prevention arm, there were no differences with respect to the number of surfactant doses. The dosing intervals were longer for Infasurf infants after the second dose. No difference in inspired oxygen or mean airway pressure was noted during the first 72 hours. There were no significant differences in the incidence of air leaks, complications associated with dosing, complications of prematurity, mortality, or survival without chronic lung disease in the prevention or treatment arm. CONCLUSIONS: Infants treated with Infasurf have a modest benefit in the acute phase of RDS. Infasurf seems to produce a longer duration of effect than Survanta.
Subject(s)
Biological Products , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome, Newborn/drug therapy , Age Factors , Apgar Score , Birth Weight , Double-Blind Method , Female , Gestational Age , Humans , Infant, Newborn , Infant, Small for Gestational Age , Male , Prospective Studies , Pulmonary Surfactants/administration & dosage , Pulmonary Surfactants/adverse effects , Respiratory Distress Syndrome, Newborn/prevention & controlABSTRACT
OBJECTIVE: Furosemide treatment in the human neonate is associated with sodium depletion, growth retardation, hypercalciuria and nephrocalcinosis. Dietary sodium intake is known to directly influence urinary calcium excretion. The objectives of this study were to create a rat model of furosemide-induced nephrocalcinosis and to test the effects of dietary sodium supplementation on growth, electrolyte balance, calciuria, and renal calcifications. METHODS: Initially, 18 weanling Sprague-Dawley rats were randomly divided into three groups. Groups A (control) and B were fed a basal diet. Group C was fed a sodium-enriched diet. Groups B and C received furosemide (40 mg/kg) intraperitoneally daily for 28 days. At the end of the study, serum, urine, and kidney samples were obtained for biochemical and histologic analyses. The three groups were then compared for differences in growth, electrolyte homeostasis, calcium excretion and nephrocalcinosis. Subsequently an additional 15 rats were studied to confirm our findings regarding urinary calcium excretion and kidney calcifications. RESULTS: Treatment with furosemide without sodium supplementation (group B) resulted in decreased weight gain compared with group A (137.5 +/- 12.9 vs 154.0 +/- 10.6 g; p < 0.05), hypokalemia (3.7 +/- 0.1 vs. 4.4 +/- 0.4 mEq/l; p < 0.05), and nephrocalcinosis (187.1 +/- 155 vs. 18.8 +/- 6.9 micrograms Ca/g dry kidney; p < 0.05). Sodium supplementation (group C) normalized weight gain and corrected electrolyte abnormalities without increasing calciuria or nephrocalcinosis. CONCLUSIONS: We conclude that in this animal model, chronic furosemide treatment results in growth failure and development of nephrocalcinosis. Sodium supplementation protects against the deleterious effects of furosemide on weight gain and electrolyte homeostasis with no adverse effect on nephrocalcinosis.
Subject(s)
Furosemide/toxicity , Nephrocalcinosis/chemically induced , Sodium, Dietary/pharmacology , Weight Gain , Animals , Calcium/urine , Electrolytes/metabolism , Homeostasis , Nephrocalcinosis/physiopathology , Rats , Rats, Sprague-Dawley , Sodium, Dietary/administration & dosage , WeaningABSTRACT
The long-term prognosis of furosemide-associated nephrocalcinosis in the infant is still unclear. Although discontinuation of the diuretic often results in radiological resolution of the calcifications, functional abnormalities may persist. The natural history of the renal histopathology of these patients is yet unknown. In the present study we investigated the histological long-term outcome of furosemide-induced nephrocalcinosis in the young rat. Thirty-six weanling male Sprague-Dawley rats were divided into three groups: A controls, B furosemide given for 8 weeks, and C furosemide given for 2 weeks followed by 6 weeks of observation. Metabolic studies at the end of the experiment demonstrated a significant diuretic and natriuretic effect in group B. Kidney histology showed nephrocalcinosis scores (mean +/- SD) of 0.0 +/- 0.0 in A, 2.6 +/- 1.5 in B, and 0.8 +/- 0.6 in C, with B significantly higher than A and C, and C greater than A. Kidney calcium content in B (3,421.9 +/- 2,558.7 micrograms/g dry tissue) was significantly greater than in A (310.4 +/- 21.3) and C (1470.1 +/- 932.2). Another group of 6 rats receiving 2 weeks treatment of furosemide showed a nephrocalcinosis score of 2.2 +/- 1.5, not different from group B, and an additional group of 6 rats treated with furosemide for 2 weeks and observed for another 12 weeks showed a score of 1.3 +/- 0.4, not different from group C. We conclude that most of the renal calcifications induced by furosemide occur during the early days of treatment and that up to 12 weeks after discontinuation of the diuretic, the resolution of the calcifications is only partial.