Ibuprofen therapy on the third day of life is as efficacious as indomethacin for the treatment of patent ductus arteriosus in preterm infants with the respiratory distress syndrome and is significantly less likely to induce oliguria.

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ABSTRACT. Objective. To determine mortality and morbidity at discharge from the hospital of a large population-based cohort of infants who were born at <26 weeks' gestation.Methods. Perinatal data were collected on extremely preterm infants who were alive at the onset of labor and born between January 1, 1999, and December 31, 2000, in all 19 Belgian perinatal centers.Results. A total of 525 infants were recorded. Lifesupporting care was provided to 322 liveborn infants, 303 of whom were admitted for intensive care. The overall survival rate of liveborn infants was 54%. Of the infants who were alive at the age of 7 days, 82% survived to discharge. Vaginal delivery, shorter gestation, air leak, longer ventilator dependence, and higher initial oxygen need all were independently associated with death; gender, plurality, and surfactant therapy were not. Among the 175 survivors, 63% had 1 or more of the 3 major adverse outcome variables at the time of discharge (serious neuromorbidity, chronic lung disease at 36 weeks' postmenstrual age, or treated retinopathy of prematurity). The chance of survival free from serious neonatal morbidity at the time of hospital discharge was <15% (21 of 158) for the admitted infants with a gestation <26 weeks.Conclusions. If for the time being prolongation of pregnancy is unsuccessful, then outcome perspectives should be discussed and treatment options including nonintervention explicitly be made available to parents of infants of <26 weeks' gestation within the limits of medical feasibility and appropriateness. Pediatrics 2004; 114:663-675; extreme prematurity, mortality, morbidity, population-based cohort.

SummaryBackground Neonates who are in pain or are stressed during care in the intensive care unit (ICU) are often given sedation or analgesia. We investigated the current use of sedation or analgesia in neonatal ICUs (NICUs) in European countries.

Aim-To evaluate the eYciency and side eVects of ibuprofen for the early treatment of patent ductus arteriosus (PDA)and compare it with indomethacin. Methods-Forty preterm infants with gestational ages of less than 33 weeks, with respiratory distress syndrome (RDS) and echocardiographically confirmed PDA, were randomly assigned at days 2 to 3 of life to receive either intravenous indomethacin 3 × 0.2 mg/kg at 12 hour intervals or intravenous ibuprofen 1 × 10 mg/kg, followed by 5 mg/kg 24 and 48 hours later. Results-PDA closed in 15 of 20 patients from the indomethacin group (75%) and in 16 of 20 (80%) from the ibuprofen group. Seven patients (three indomethacin, four ibuprofen) required a second treatment with indomethacin and in five (three in the indomethacin group and two in the ibuprofen group) the duct was ultimately ligated. Ibuprofen patients had a better urinary output and showed no increase in serum creatinine concentrations compared with the indomethacin group. Ibuprofen was not associated with any other side eVect. Conclusions-Ibuprofen treatment seems to be as eYcient as indomethacin in closing PDA on the third day of life in preterm infants with respiratory distress syndrome and seems to have fewer renal side eVects.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Ibuprofen is a nonsteroidal anti-inflammatory agent that induces closure of the patent ductus arteriosus in neonates.• Few studies of ibuprofen pharmacokinetics have been performed and were limited to small groups of preterm infants, showing a large intersubject variability and an increase in clearance with either postnatal or gestational age. WHAT THIS STUDY ADDS• A population pharmacokinetic study was performed on 66 neonates to characterize the concentration-time courses of ibuprofen.• Ibuprofen clearance significantly increased from postnatal age day 1 to day 8, but not with gestational age.• A relationship was shown between ibuprofen area under the curve (AUC) and patent ductus arteriosus closure rate, and an effective threshold AUC was evidenced.• Dosing schemes were proposed as a function of postnatal age, to achieve this AUC and to improve the efficacy of treatment for patent ductus arteriosus in neonates. AIMSTo describe ibuprofen pharmacokinetics in preterm neonates with patent ductus arteriosus (PDA) and to establish relationships between doses, plasma concentrations and ibuprofen efficacy and safety. METHODSSixty-six neonates were treated with median daily doses of 10, 5 and 5 mg kg -1 of ibuprofen-lysine by intravenous infusion on 3 consecutive days. A population pharmacokinetic model was developed with NONMEM. Bayesian individual pharmacokinetic estimates were used to calculate areas under the curve (AUC) and to simulate doses. A logistic regression was performed on PDA closure. RESULTSIbuprofen pharmacokinetics were described by a one-compartment model with linear elimination. Mean population pharmacokinetic estimates with corresponding intersubject variabilities (%) were: elimination clearance CL = 9.49 ml h -1 (62%) and volume of distribution V = 375 ml (72%). Ibuprofen CL significantly increased with postnatal age (PNA): CL = 9.49*(PNA/96.3) 1.49 . AUC after the first dose (AUC1D), the sum of AUC after the three doses (AUC3D) and gestational age were significantly higher in 57 neonates with closing PDA than in nine neonates without PDA closure (P = 0.02). PDA closure was observed in 50% of the neonates when AUC1D < 600 mg l -1 h (or AUC3D < 900 mg l -1 h) and in 91% when AUC1D > 600 mg l -1 h (or AUC3D > 900 mg l -1 h) (P = 0.006). No correlation between AUC and side-effects could be demonstrated. CONCLUSIONSTo achieve these optimal AUCs, irrespective of gestational age, three administrations at 24 h intervals are recommended of 10, 5, 5 mg kg -1 for neonates younger than 70 h, 14, 7, 7 mg kg -1 for neonates between 70 and 108 h and 18, 9, 9 mg kg -1 for neonates between 108 and 180 h.

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Oxygen is a neonatal health hazard that should be avoided in clinical practice. In this review, an international team of neonatologists and nurses assessed oxygen saturation (SpO2) targeting in preterm infants and evaluated the potential weaknesses of randomised clinical trials.ConclusionSpO2 of 85–89% can increase mortality and 91–95% can cause hyperoxia and ill effects. Neither of these ranges can be recommended, and wider intermediate targets, such as 87–94% or 88–94%, may be safer.