Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

BACKGROUND: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. RESULTS: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. CONCLUSIONS: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

The problems of moderate preterm infants.

Moderate preterm infants are the largest group of preterm infants but are an understudied population. Care practices are adapted from studies of full term infants or extremely preterm infants. Studies are needed to tailor treatments for this vulnerable population. The NRN began investigation in this population with a registry of characteristics, and neonatal outcomes of these infants. This work compares outcomes of MPR with those of full term infants reported in the literature.

[Methodological aspects of economic evaluation in pediatrics: illustration by RSV infection prophylaxis in the French setting]. / Aspects méthodologiques de l'évaluation économique du médicament en pédiatrie : exemple de la prophylaxie de l'infection à VRS en France.

The methodological approach of the economic evaluation of drugs in pediatrics is illustrated by the case study of the prophylaxis for RSV infections using palivizumab in the French setting. The indications for the reimbursement of this treatment have been restricted to premature children with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital-heart disease. A model was developed primarily using the results of the pivotal clinical studies on palivizumab. Unit costs were estimated (2006 values) in both societal and payer's perspectives. An assumption was made and discussed on the benefits of the prophylaxis on mortality. Based on the different data available and the estimated costs and benefits, different cost-effectiveness ratios (CERs) were estimated from both the society's and payer's points of view. A discount rate of 3% was applied to benefit. The CER obtained in the most unfavorable case is considered acceptable for the innovative-medical technologies in the French-healthcare system. Some of the parameters used by the model will be illustrated from the EPIPAGE study data from 2 of the 9 regions involved in this study: this evaluation suggests that the children not having an RSV infection during their 1st year of life will continue to require significantly fewer hospitalizations in the following years. These additional evaluations also suggest that the model overestimates the costs of the treatment with regard to the true medical situation. This could be explained by the model not using the children's exact weight or the real number of injections because the children had been discharged from the maternity ward based on their date of birth and the epidemic period. In spite of these factors, RSV prophylaxis using palivizumab in premature children with BPD or hemodynamically significant congenital-heart disease can be considered cost-effective in France.

Follow-up care for infants with chronic lung disease: a randomized comparison of community- and center-based models.

OBJECTIVES: Premature infants with chronic lung disease benefit from comprehensive care, which typically is based in tertiary medical centers. When such centers are not easily accessible, alternative models of care are needed. The purpose of this work was to compare community-based follow-up, provided via telephone contacts, to traditional center-based follow-up of premature infants with chronic lung disease. PATIENTS AND METHODS: After discharge from neonatal intensive care, 150 premature infants with chronic lung disease were randomly assigned to either community-based (n = 75) or center-based (n = 75) follow-up. In community-based follow-up, a nurse specialist maintained telephone contact with the infant's primary caregiver and health care providers. Center-based follow-up consisted of visits to a medical center-based multidisciplinary clinic staffed by a neonatologist, a nurse specialist, and a social worker. The outcomes of interest were Bayley Scales of Infant Development mental developmental index and psychomotor developmental index, Vineland Adaptive Behavioral Composite, and growth delay (weight for length <5th percentile) at 1-year adjusted age and respiratory rehospitalizations through 1-year adjusted age. RESULTS: In each randomization group, 73 infants survived, and 69 were evaluated at 1-year adjusted age. The median mental development index (corrected for gestational age) was 90 for both groups. The median psychomotor developmental index was 82 for the center-based group and 81 for the community-based group. The median Vineland Adaptive Behavioral Composite was 100 and 102 for the center-based and community-based groups, respectively. In the center-based and community-based groups, respectively, the proportions with growth delay were 13% and 26%, and the proportions rehospitalized for respiratory illness were 33% and 29%. CONCLUSIONS: Infants randomly assigned to community-based, as compared with those randomly assigned to center-based follow-up, had similar developmental and health outcomes. The former approach might be a preferred alternative for families in rural settings or families for whom access to a tertiary care medical center is difficult.

Prognostic value of clinical and radiological status on day 28 of life for subsequent course in very low birthweight (< 1,500g) babies with bronchopulmonary dysplasia.

To test the hypothesis that the short-term (approximately 6 months) course of babies with bronchopulmonary dysplasia (BPD) could be predicted from the clinical and radiological status on day 28 of life, we retrospectively examined the medical records of 79 infants born between 1985 and 1988 who required supplemental oxygen and/or ventilatory support on day 28. Chest roentgenographs taken close to day 28 (+/- 7 days) were scored on a scale of 0-10. Four babies died from causes not related to BPD. Four of the remaining 75 died from BPD, and the rest are alive. Forty-six of 71 were weaned from supplementary oxygen by 37 weeks corrected gestational age, and only 13/71 remained on supplemental oxygen after 40 weeks gestational age. To determine which variables contributed most to the outcome, defined as total days on supplemental oxygen, a multiple regression analysis was performed, including only those variables the tolerance of which exceeded 0.7 (sex, FiO2, ventilatory mode, and infectious status). FiO2 and ventilatory mode together predicted 15% of the variability in outcome, so that a high FiO2 and ventilator dependence on day 28 of life were highly correlated with a prolonged need for supplemental oxygen (F = 4.28, P < 0.05).