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Our multi-institutional university consortium implemented a gastroschisis pathway in 2015 to standardize and improve care by promoting avoidance of routine intubation and paralysis during silo placement, expeditious abdominal wall closure, discontinuation of antibiotics/narcotics within 48 h of closure, and early initiation/advancement of feeds.Adherence to the gastroschisis pathway was prospectively monitored. Outcomes for the contemporary cohort (2015-2018) were compared with a historical cohort (2007-2012).Good adherence to the pathway was observed for 70 cases of inborn uncomplicated gastroschisis. The contemporary cohort had significantly lower median mechanical ventilator days (2 versus 5; p 0.01) and antibiotic days (5.5 versus 9; p 0.01) as well as earlier days to initiation of feeds (12 versus 15; p 0.01). However, no differences were observed in length of stay (28 versus 29 days; p = 0.70). A skin closure technique was performed in 66% of the patients, of which 46% were performed at bedside without intubation, the assistance of an operating-room team, or general anesthesia.In this study, adherence to a clinical pathway for gastroschisis across different facilities was feasible and led to reduction in exposure to mechanical ventilation and antibiotics. The adoption of a bedside skin closure technique appears to facilitate compliance with the pathway.Level II/III TYPE OF STUDY: Prospective comparative study with historical cohort.

IntroductionTiming of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups such as those who usually receive immediate neonatal care. Previous and current trials compare various policies, including immediate cord clamping, time- or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enables exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons.Objectives1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis; and 2) to evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA.Methods and analysisWe will conduct a systematic search of Medline, Embase, clinical trial registries, and other sources for all planned, ongoing and completed randomised controlled trials comparing alternative cord management strategies at preterm birth (before 37 weeks’ gestation). IPD will be sought for all trials. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for pre-specified subgroups of participants. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes intraventricular haemorrhage (any grade) and infant blood transfusions (any). Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored.Ethics and disseminationApproved by University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline-developers and policy-makers, and will be disseminated via publications, presentations, and media releases.RegistrationAustralian New Zealand Clinical Trials Registry: ACTRN12619001305112.STRENGTH AND LIMITATIONS OF THIS STUDYThis will be the most comprehensive review to date of interventions for umbilical cord management in preterm infants and the findings will be highly relevant to clinicians and guideline developersThe use of individual participant data will allow assessment of the best treatment option for key subgroups of participantsNetwork meta-analysis will enable the comparison and ranking of all available treatment options using direct and indirect evidenceFor some of the trials it will not be possible to obtain individual participant data, so published aggregate results will be used insteadRisk of bias in the primary trials will be assessed using Cochrane criteria, and certainty of evidence for the meta-analyses will be appraised using the GRADE approach for the pairwise comparisons, and the CINeMA approach for the network meta-analysis

Background Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated with a high risk of death and neurodevelopmental impairment. Prevention of IC has become a major focus in very low birth weight infants, with fluconazole increasingly used as prophylaxis. Methods We identified all randomized, placebo-controlled trials evaluating fluconazole prophylaxis in premature infants conducted in the United States. We obtained patient-level data from the study investigators and performed an aggregated analysis. The occurrence of each endpoint in infants who received prophylaxis with fluconazole vs placebo was compared. Endpoints evaluated were IC or death, IC, death, Candida colonization, and fluconazole resistance among tested isolates. Safety endpoints evaluated included clinical and laboratory parameters. Results Fluconazole prophylaxis reduced the odds of IC or death, IC, and Candida colonization during the drug exposure period compared with infants given placebo: odds ratios of 0.48 (95% confidence interval [CI], .30-.78), 0.20 (95% CI, .08-.51), and 0.28 (95% CI, .18-.41), respectively. The incidence of clinical and laboratory adverse events was similar for infants who received fluconazole compared with placebo. There was no statistically significant difference in the proportion of tested isolates that were resistant to fluconazole between the fluconazole and placebo groups. Conclusions Fluconazole prophylaxis is effective and safe in reducing IC and Candida colonization in premature infants, and has no impact on resistance.

Objectives To identify variables associated with successful elective extubation, and to determine neonatal morbidities associated with extubation failure in extremely preterm neonates. Study design This study was a secondary analysis of the National Institute of Child Health and Human Development Neonatal Research Network's Surfactant, Positive Pressure, and Oxygenation Randomized Trial that included extremely preterm infants born at 240/7 to 276/7 weeks' gestation. Patients were randomized either to a permissive ventilatory strategy (continuous positive airway pressure group) or intubation followed by early surfactant (surfactant group). There were prespecified intubation and extubation criteria. Extubation failure was defined as reintubation within 5 days of extubation. Results Of 1316 infants in the trial, 1071 were eligible; 926 infants had data available on extubation status; 538 were successful and 388 failed extubation. The rate of successful extubation was 50% (188/374) in the continuous positive airway pressure group and 63% (350/552) in the surfactant group. Successful extubation was associated with higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within the first 24 hours of age and prior to extubation, lower partial pressure of carbon dioxide prior to extubation, and non-small for gestational age status after adjustment for the randomization group assignment. Infants who failed extubation had higher adjusted rates of mortality (OR 2.89), bronchopulmonary dysplasia (OR 3.06), and death/ bronchopulmonary dysplasia (OR 3.27). Conclusions Higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within first 24 hours of age, lower partial pressure of carbon dioxide and fraction of inspired oxygen prior to extubation, and nonsmall for gestational age status were associated with successful extubation. Failed extubation was associated with significantly higher likelihood of mortality and morbidities. Trial registration ClinicalTrials.gov : NCT00233324 .

Background: Meropenem is approved for treatment of complicated abdominal infections in pediatric patients and adults. The primary objective of this study is to characterize meropenem multiple-dose PK and preliminary safety in young infants. Design and population: Infants Material and methods: Population and individual subject (Bayesian) PK parameters were estimated using NONMEM. Results: Data including 99 meropenem concentrations on the first 22 infants enrolled are presented. Dosing was based on both gestational age and postnatal age: 3 infants received 20 mg/kg q12 h, 13 received 20 mg/kg q8 h, 1 received 30 mg/kg q8 h, and 1 received 40 mg/kg q8 h. Median gestational age at birth and post-natal age were 27 weeks and 18 days, respectively. Median plasma clearance (CL), volume of distribution, and elimination T½ were 0.12 L/kg/h, 0.54 L/kg, and 2.9 h, respectively. A significant, positive association was observed between CL and postconceptional age. All infants had predicted meropenem concentrations above an MIC of 2 µg/mL for > 75% of the dosing interval. No serious adverse events related to meropenem were observed. Conclusions: Meropenem doses of 20 mg/kg q12 h to 40 mg/kg q8 h were well tolerated and produced drug plasma concentrations above an MIC that inhibits most susceptible pathogens.

Retrolental fibroplasia (RLF) was first described in 1942 by Terry (1942), as a condition which developed after birth initially thought to be due to the persistence of the entire vascular structure of the fetal vitreous. The term “retrolental fibroplasia” was apparently coined by a Boston opthalmologist, Doctor H. Messenger (Silverman, 1980) and by the 1950’s RLF was thought to be the commonest cause of infant blindness. Following Terry’s original description of RLF this condition began to be reported with increasing frequency occurring in approximately 12% of infants of less than 1400 gm in the late 1940s (Terry, 1945). The temporal changes in the retina of premature infants with RLF was first detailed by Owens & Owens of the Wilmer Eye Institute at Johns Hopkins Hospital (Owens & Owens) who described the first abnormalities as the dilation of veins, following which the arteries became dilated and tortuous. Subsequently new vessel formation was observed and was followed by retinal edema and hemorrhages. Pathologic studies demonstrated that the primary lesion was a disordered capillary endothelial proliferation within the retina which was associated with pre-retinal and vitreous hemorrhages, and fibrotic changes (Friedenwald, 1951). I have retained the term RLF as opposed to the the more recently accepted retinopathy of prematurity (ROP) because RLF was the term used in the great majority of cited papers. RLF more accurately refers to the cicatricial grades of the disorder whereas ROP has a broader connotation.