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Objective To evaluate changes in the outcomes of infants born at

This study aimed to assess whether weight growth velocity (WGV) predicts neurodevelopmental outcomes in extremely low birth weight infants (ELBWIs).Subjects were infants who weighed 501-1000 g at birth and were included in the cohort of the Neonatal Research Network of Japan (2003-2007). Patel's exponential model (EM) method was used to calculate WGV between birth and discharge. Assessment of predictions of death or neurodevelopmental impairment (NDI) was performed at 3 years of age based on the WGV score, which was categorized by per one increase in WGV. Multivariate logistic regression analysis was used to calculate adjusted odds ratios and their 95% confidence intervals (95%CI).In the 2961 ELBWIs assessed, the median WGV was 10.5 g/kg/day (interquartile, 9.4-11.9). With the categorical approach, the adjusted odds ratios for death or NDI with WGV scores of 6 and 7 were 2.41 (95%CI, 1.60-3.62) and 1.81 (95%CI, 1.18-2.75), respectively, relative to the reference WGV score of 10. WGV scores ≥8 did not predict death or NDI.WGV scores

IntroductionWhether parenteral nutrition benefits growth of very low birth weight (VLBW) preterm infants in the setting of rapid enteral feeding advancement is unclear. Our aim was to examine this issue using data from Japan, where enteral feeding typically advances at a rapid rate.MethodsWe studied 4005 hospitalized VLBW, very preterm (23-32 weeks' gestation) infants who reached full enteral feeding (100 ml/kg/day) by day 14, from 75 institutions in the Neonatal Research Network Japan (2003-2007). Main outcomes were weight gain, head growth, and extra-uterine growth restriction (EUGR, measurement Results40% of infants received parenteral nutrition. Adjusting for maternal, infant, and institutional characteristics, infants who received parenteral nutrition had greater weight gain [0.09 standard deviation (SD), 95% CI: 0.02, 0.16] and head growth (0.16 SD, 95% CI: 0.05, 0.28); lower odds of EUGR by head circumference (OR 0.66, 95% CI: 0.49, 0.88). No statistically significant difference was seen in the proportion of infants with EUGR at discharge. SGA infants and infants who took more than a week until full feeding had larger estimates.DiscussionEven in infants who are able to establish enteral nutrition within 2 weeks, deprivation of parenteral nutrition in the first weeks of life could lead to under nutrition, but infants who reached full feeding within one week benefit least. It is important to predict which infants are likely or not likely to advance on enteral feedings within a week and balance enteral and parenteral nutrition for these infants.

Background: Outcomes of prenatal covariate-adjusted outborn very-low-birth-weight infants (VLBWIs) (≤1500 g) remain uncertain.Objective: To compare morbidity and mortality between outborn and inborn VLBWIs.Design: Observational cohort study using inverse-probability-of-treatment weighting.Setting: Neonatal Research Network of Japan.Patients: Singleton VLBWIs with no major anomalies admitted to a neonatal intensive care unit from 2012 to 2016.Methods: Inverse-probability-of-treatment weighting with propensity scores was used to reduce imbalances in prenatal covariates (gestational age (GA), birth weight, small for GA, sex, maternal age, premature rupture of membranes, chorioamnionitis, preeclampsia, maternal diabetes mellitus, antenatal steroids and caesarean section). The primary outcome was severe intraventricular haemorrhage (IVH). The secondary outcomes were outcomes at resuscitation, other neonatal morbidities and mortality.Results: The full cohort comprised 15 842 VLBWIs (668 outborns). The median (IQR) GA and birth weight were 28.9 (26.4-31.0) weeks and 1128 (862-1351) g for outborns and 28.7 (26.3-30.9) weeks and 1042 (758-1295) g for inborns. Outborn VLBWIs had a higher incidence of severe IVH (8.2% vs 4.1%; OR, 3.45; 95% CI 1.16 to 10.3) and pulmonary haemorrhage (3.7% vs 2.8%; OR, 5.21; 95% CI 1.41 to 19.2). There were no significant differences in Apgar scores, oxygen rates at delivery, intubation ratio at delivery, persistent pulmonary hypertension of the newborn, IVH of any grade, periventricular leukomalacia, chronic lung disease, oxygen at discharge, patent ductus arteriosus, retinopathy of prematurity, necrotising enterocolitis, sepsis or mortality.Conclusion: Outborn delivery of VLBWIs was associated with an increased risk of severe IVH. [ABSTRACT FROM AUTHOR]

Objective: We hypothesised that a prophylactic inhaled steroid would prevent the progression of bronchopulmonary dysplasia (BPD) in extremely low birthweight infants (ELBWIs).Design: This study was a multicentre, randomised, double-blinded, placebo-controlled trial.Setting: This investigation was conducted in 12 level III neonatal intensive care units (NICUs).Patients: A total of 211 ELBWIs requiring ventilator support were enrolled.Intervention: Starting within 24 h of birth and continuing until 6 weeks of age or extubation, two doses of 50 μg fluticasone propionate (FP) or placebo were administered every 24 h.Main Outcome Measurement: The primary outcome measure used to indicate the morbidity of severe BPD incidence was death or oxygen dependence at discharge from the NICU. The secondary measures were neurodevelopmental impairments (NDIs) at 18 months of postmenstrual age and 3 years of age. We performed subgroup analyses based on gestational week (GW) and the presence of chorioamnionitis (CAM).Results: Infants were randomised into the FP (n=107) or placebo (n=104) groups. No significant differences were detected between the FP and placebo groups with respect to either the frequency of death or the oxygen dependence at discharge or NDIs. In subgroup analyses, the frequencies of death and oxygen dependence at discharge were significantly decreased in the FP group for infants born at 24-26 GWs and for infants with CAM, regardless of the GW at birth.Conclusions: Inhaled steroids have no effect on the prevention of severe BPD or long-term NDI but might decrease the severity of BPD for ELBWIs with a risk factor.Trial Registration Number: UMIN-CTR C000000405. [ABSTRACT FROM AUTHOR]

Objective The aim of this study is to compare patent ductus arteriosus (PDA) management strategies and outcomes between the Neonatal Research Network of Japan (NRNJ) with proactive functional echocardiography and the Canadian Neonatal Network (CNN) with selective conventional echocardiography practice. Study Design Retrospective analyses examined very low-birth-weight infants admitted to the NRNJ or CNN in 2006 to 2008. Multivariable logistic regression analyses compared a composite outcome indicating a mortality or major morbidity (severe intraventricular hemorrhage, periventricular leukomalacia, severe retinopathy of prematurity, bronchopulmonary dysplasia, or necrotizing enterocolitis) between networks, according to PDA diagnosis and treatment, and tested the association between PDA treatment and the composite outcome within networks. Results PDA treatment (NRNJ:CNN) with conservative management (8%:16%), indomethacin only (77%:59%), ligation only (1%:13%), or indomethacin and ligation (14%:13%) varied significantly between networks. The composite outcome was lower in NRNJ versus CNN only among infants with PDA (odds ratio: 0.70; 95% confidence interval: 0.62-0.80). Surgical ligation was associated with higher composite outcome only in CNN (odds ratio: 1.79; 95% confidence interval: 1.40-2.28). Conclusion Lower composite mortality/morbidity outcome in Japan versus Canada only among infants with PDA, and association of surgical ligation with higher mortality/ morbidity only in Canada, suggest differential PDAmanagement and ligation processes contribute to outcome variation. [ABSTRACT FROM AUTHOR]

Objective: To assess lung function at 8 years old in extremely low birthweight (ELBW) survivors and to identify perinatal determinants associated with impaired lung function. Design: Retrospective cohort study. Setting: Level III neonatal intensive care unit. Patients: ELBW survivors born in 1990-2004 with available spirometry at 8 years old were studied. Children were excluded if they had a Wechsler Intelligence Scale for Children Third Edition full IQ <70. Main outcome measures: Multivariate logistic regression analysis was used to identify perinatal determinants associated with airway obstruction (forced expiratory volume in 1 s (FEV¹)/forced vital capacity (FVC) ratio <80%) at school age and the predictive power of potential determinants. Potential risk factors and predictors assessed in this study were gestational age, birth weight, small for gestational age, sex, chorioamnionitis, premature rupture of membranes, antenatal steroids, surfactant administration, respiratory distress syndrome, postnatal steroids, severe bronchopulmonary dysplasia and bubbly/ cystic appearances of the lungs by X-ray during the neonatal period. Results Of 656 ELBW survivors, 301 (45.9%) had attended a school-age follow-up at 8 years old. A total of 201 eligible children completed the lung function test. Bubbly/cystic appearance of the lungs (OR 4.84, 95% CI 1.26 to 18.70) was associated with a low FEV1/FVC ratio. Children with bubbly/cystic appearance had characteristics of immaturity and intrauterine inflammation. Conclusions: Within a cohort of ELBW infants, a bubbly/ cystic appearance of the lungs in the neonatal period was the strongest determinant of a low FEV1/FVC ratio at school age. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines assist physicians to make decisions about suitable healthcare. We conducted a controlled before-and-after study to investigate the impact of professional-led guideline workshops for patent ductus arteriosus (PDA) management on physicians' clinical practices, discharge mortality, and associated morbid conditions among preterm neonates. Methods: We recruited physicians practicing at two neonatal intensive care units (NICUs) in Japan and used the data of all neonates weighing less than or equal to 1,500 g admitted to 90 NICUs (2 intervention NICUs and 88 control NICUs) in the Neonatal Research Network of Japan from April 2008 to March 2010. We held 1-day workshops for physicians on PDA clinical practice guidelines at the two intervention NICUs. Physicians' skills assessed by confidence rating (CR) scores and the Sheffield Peer Review Assessment Tool (SPRAT) were compared between pre- and post-workshop month at the intervention NICUs using Wilcoxon signed-rank tests. Neonatal discharge mortality and morbidity were compared between pre- and post-workshop year at both the intervention and control NICUs using multivariable regression analyses adjusting for potential confounders. Results: Fifteen physicians were included in the study. Physicians' CR scores (2.14 vs. 2.47, p = 0.02) and SPRAT (4.14 vs. 4.50, p = 0.05) in PDA management improved after the workshops. The analyses of neonatal outcomes included 294 and 6,234 neonates in the intervention and control NICUs, respectively. Neonates' discharge mortality declined sharply at the intervention NICUs (from 15/146 to 5/148, relative risk reduction -0.67; adjusted odds ratio 0.30, 95% confidence interval 0.10 to 0.89) during the post-workshop period. The mortality reduction was much greater than that in the control NICUs (from 207/3,322 to 147/2,912, relative risk reduction -0.19; adjusted odds ratio 0.75, 95% confidence interval 0.59 to 0.95), although the difference between the intervention and control NICUs were not statistically significant. Conclusions: Overall, physicians' confidence in PDA management improved after attending guideline workshops. Face-to-face workshops by guideline developers can be a useful strategy to improve physicians' PDA management skills and, thereby, might reduce PDA-associated mortality in preterm neonates. [ABSTRACT FROM AUTHOR]

Background The International Network for Evaluating Outcomes in Neonates (iNeo) is a collaboration of population-based national neonatal networks including Australia and New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the UK. The aim of iNeo is to provide a platform for comparative evaluation of outcomes of very preterm and very low birth weight neonates at the national, site, and individual level to generate evidence for improvement of outcomes in these infants. Methods/design Individual-level data from each iNeo network will be used for comparative analysis of neonatal outcomes between networks. Variations in outcomes will be identified and disseminated to generate hypotheses regarding factors impacting outcome variation. Detailed information on physical and environmental factors, human and resource factors, and processes of care will be collected from network sites, and tested for association with neonatal outcomes. Subsequently, changes in identified practices that may influence the variations in outcomes will be implemented and evaluated using quality improvement methods. Discussion The evidence obtained using the iNeo platform will enable clinical teams from member networks to identify, implement, and evaluate practice and service provision changes aimed at improving the care and outcomes of very low birth weight and very preterm infants within their respective countries. The knowledge generated will be available worldwide with a likely global impact. [ABSTRACT FROM AUTHOR]

Objectives: To determine the feasibility of clinical trials of newly developed treatments or standardisation of existing practices to further improve outcomes among very low birth weight (VLBW) infants, a nationwide database was analysed with a two-dimensional approach using two multivariate logistic models. Design: Retrospective observational analysis. Setting: Level III perinatal centres in Japan. Participants: 15 920 VLBW infants admitted at 38 participating centres from 2003 through 2010. Outcome measures: Clinical information for the infants was collected until discharge from the centres. A multivariate logistic model identified practices and morbidities associated with mortality. Then, those which were significantly associated with mortality were analysed using a multilevel logistic model. The residues calculated by the multilevel analysis were used as an indicator of centre variation. Results: Among practices, antenatal steroids and intubation at birth showed relatively high centre variations (0.9 and 0.8) and favourable ORs (0.7 and 0.5) for mortality, while caesarean section showed a low centre variation (0.4) and a favourable OR (0.8). Sepsis and air leak showed high centre variations (0.4 and 0.4) and high ORs (3.8 and 3.4) among morbidities. Pulmonary haemorrhage, persistent pulmonary hypertension of the newborn, and intraventricular haemorrhage showed moderate variations (0.2, 0.3 and 0.2, respectively) and high ORs (5.6, 4.1 and 2.9, respectively). In contrast, necrotising enterocolitis showed the lowest variation (0.1) and a high OR (4.9). Conclusions: The two-dimensional approach has clearly demonstrated the importance of clinical trial or standardisation. The practices and morbidities with low centre variations and high ORs for mortality must be improved through clinical trials of newly introduced techniques, while standardisation must be considered for practices and morbidities with a high centre variation. Trial registration: The database was registered as UMIN000006961. [ABSTRACT FROM AUTHOR]