BACKGROUND: Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (n ϭ 3430 infants) have been conducted on preterm infants at risk for chronic lung disease (CLD). The study results seem contradictory. DESIGN/METHODS:Individual-patient data meta-analysis included randomized controlled trials of preterm infants (Ͻ37 weeks' gestation). Outcomes were adjusted for trial differences and correlation between siblings. RESULTS:Data from 3298 infants in 12 trials (96%) were analyzed. There was no statistically significant effect of iNO on death or CLD (59% vs 61%: relative risk [RR]: 0.96 [95% confidence interval (CI): 0.92-1.01]; P ϭ .11) or severe neurologic events on imaging (25% vs 23%: RR: 1.12 [95% CI: 0.98 -1.28]; P ϭ .09). There were no statistically significant differences in iNO effect according to any of the patient-level characteristics tested. In trials that used a starting iNO dose of Ͼ5 vs Յ5 ppm there was evidence of improved outcome (interaction P ϭ .02); however, these differences were not observed at other levels of exposure to iNO. This result was driven primarily by 1 trial, which also differed according to overall dose, duration, timing, and indication for treatment; a significant reduction in death or CLD (RR: 0.85 [95% CI: 0.74 -0.98]) was found.CONCLUSIONS: Routine use of iNO for treatment of respiratory failure in preterm infants cannot be recommended. The use of a higher starting dose might be associated with improved outcome, but because there were differences in the designs of these trials, it requires further examination.

ObjectiveTo investigate the association of motor and cognitive/learning deficiencies and overall disabilities in very preterm (VPT) children and their relations to gestational age (GA) and brain lesions.Design, Setting, and ParticipantsEPIPAGE is a longitudinal population-based cohort study of children born before 33 weeks’ gestation (WG) in 9 French regions in 1997–1998. Cumulating data from all follow up stages, neurodevelopmental outcomes were available for 90% of the 2480 VPT survivors at 8 years. Main outcomes were association of motor and cognitive deficiencies and existence of at least one deficiency (motor, cognitive, behavioral/psychiatric, epileptic, visual, and/or hearing deficiencies) in three GA groups (24–26, 27–28, and 29–32WG) and four groups of brain lesions (none, minor, moderate, or severe).ResultsVPT had high rates of motor (14%) and cognitive (31%) deficiencies. Only 6% had an isolated motor deficiency, 23% an isolated cognitive one and 8% both types. This rate reached 20% among extremely preterm. Psychiatric disorders and epilepsy were observed in 6% and 2% of children, respectively. The risks of at least one severe or moderate deficiency were 11 and 29%. These risks increased as GA decreased; only 36% of children born extremely preterm had no reported deficiency. Among children with major white matter injury (WMI), deficiency rates reached 71% at 24–26WG, 88% at 27–28WG, and 80% at 29–32WG; more than 40% had associated motor and cognitive deficiencies. By contrast, isolated cognitive deficiency was the most frequent problem among children without major lesions.ConclusionsIn VPT, the lower the GA, the higher the neurodisability rate. Cerebral palsy is common. Impaired cognitive development is more frequent. Its occurrence in case without WMI or early motor disorders makes long-term follow up necessary. The strong association between motor impairments, when they exist, and later cognitive dysfunction supports the hypothesis of a common origin of these difficulties.

The GFR reference values, presented in this article as 3rd, 10th, 50th, 90th, and 97th percentiles, should be useful in NICUs for adaptation of drug doses to glomerular clearance and in defining infants who present with altered GFR and who need additional investigation and close follow-up to adjust fluid intake and drug dosage.

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Articles Clinical Investigation nature publishing groupBackground: Prebiotics and probiotics exert beneficial effects by modulating gut microbiota and immune system. This study evaluates efficacy and safety of an infant formula containing bovine milk-derived oligosaccharides and Bifidobacterium animalis ssp lactis (B. lactis) (CNCM I-3446) on incidence of diarrhea and febrile infections during the first year of life (primary outcome). Methods: Full-term infants receiving Test or Control (without bovine milk-derived oligosaccharide and B. lactis) formulae were enrolled in a multicenter, randomized, controlled, and double-blind trial with a reference breastfeeding group. . results: 413 infants were assigned between Test (n = 206) and Control (n = 207) formula. There was no significant difference for diarrhea and febrile infections incidence between groups at 6 (odds ratio (95% confidence interval) = 0.56 (0.26-1.15), P = 0.096) and 12 mo (odds ratio = 0.66 (0.38-1.14), P = 0.119). Test formula was well tolerated, anthropometrics parameters were not significantly different between groups and aligned with WHO growth standards up to 12 mo. Data from test group showed that gut microbiota pattern, fecal IgA and stool pH were brought to be closer to those of breastfed infants. conclusion: An infant formula enriched with bovine milkderived oligosaccharide and B. lactis supports normal infant growth, is well tolerated and improves intestinal health markers. No differences in diarrhea and febrile infection incidence were found in the population studied.

Intermediate-to-advanced stage acute bilirubin encephalopathy may occasionally be reversible. These cases provide a strong argument in favour of rapid and aggressive intervention in infants presenting with extreme jaundice and neurological symptoms.

We carried out a study aiming to determine the renal effect of ibuprofen treatment for patent ductus arteriosus (PDA) in very preterm infants during the first month of life. Infants aged 27-31 weeks gestation were enrolled from October 2004 to August 2006. They were assigned to two different groups according to ibuprofen exposure during care of their PDA status assessed by echocardiography. Infants of both groups were matched based on gestational age, Clinical Risk Index for Babies score, birth weight and inclusion center. Renal function was evaluated at baseline and weekly for 1 month. One hundred and forty-eight infants were enrolled. Glomerular filtration rate (GFR) was significantly decreased in the ibuprofen group after treatment withdrawal (GFR on day 7, ibuprofen versus no ibuprofen: 12.8 +/- 6.2 vs. 18.1 +/- 12.1 ml/min/1.73 m(2); P < 0.001). Adjusted analysis proved this decrease to be sustained during the first month of life. Tubular function was also impaired during the first month in ibuprofen-treated infants. Ibuprofen administered for PDA is associated with a decreased GFR during the first month of life. Renal function of infants receiving ibuprofen should be carefully monitored and drugs that are eliminated by glomerular filtration handled cautiously during this period.

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