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IntroductionPatent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants.Methods and analysisA multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3–7 days.Intravenous indomethacin (0.1–0.3 mg/kg intravenous every 12–24 hours for a total of three doses).OutcomesThe primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment.Sites and sample sizeThe study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years.AnalysisTo examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student’s t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach.Ethics and disseminationThe study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres.Trial registration numberNCT04347720.

BackgroundTherapeutic hypothermia is standard of care for babies with moderate/severe hypoxic-ischaemic encephalopathy and is increasingly used for mild encephalopathy.ObjectiveDescribe temporal trends in the clinical condition of babies diagnosed with hypoxic-ischaemic encephalopathy who received therapeutic hypothermia.DesignRetrospective cohort study using data held in the National Neonatal Research Database.SettingNational Health Service neonatal units in England, Wales and Scotland.PatientsInfants born from 1 January 2010 to 31 December 2017 with a recorded diagnosis of hypoxic-ischaemic encephalopathy who received therapeutic hypothermia for at least 3 days or died in this period.Main outcomesPrimary outcomes: recorded clinical characteristics including umbilical cord pH; Apgar score; newborn resuscitation; seizures and treatment on day 1. Secondary outcomes: recorded hypoxic-ischaemic encephalopathy grade.Results5201 babies with a diagnosis of hypoxic-ischaemic encephalopathy received therapeutic hypothermia or died; annual numbers increased over the study period. A decreasing proportion had clinical characteristics of severe hypoxia ischaemia or a diagnosis of moderate or severe hypoxic-ischaemic encephalopathy, trends were statistically significant and consistent across multiple clinical characteristics used as markers of severity.ConclusionsTreatment with therapeutic hypothermia for hypoxic-ischaemic encephalopathy has increased in England, Scotland and Wales. An increasing proportion of treated infants have a diagnosis of mild hypoxic-ischaemic encephalopathy or have less severe clinical markers of hypoxia. This highlights the importance of determining the role of hypothermia in mild hypoxic-ischaemic encephalopathy. Receipt of therapeutic hypothermia is unlikely to be a useful marker for assessing changes in the incidence of brain injury over time.

IntroductionTherapeutic hypothermia is standard of care for infants born ≥36 weeks gestation with hypoxic ischaemic encephalopathy (HIE); consensus on optimum nutrition during therapeutic hypothermia is lacking. This results in variation in enteral feeding and parenteral nutrition (PN) for these infants. In this study, we aim to determine the optimum enteral nutrition and PN strategy for newborns with HIE during therapeutic hypothermia.Methods and analysisWe will undertake a retrospective cohort study using routinely recorded electronic patient data held on the United Kingdom (UK) National Neonatal Research Database (NNRD). We will extract data from infants born ≥36 weeks gestational age between 1 January 2008 and 31 December 2016, who received therapeutic hypothermia for at least 72 hours or died during therapeutic hypothermia, in neonatal units in England, Wales and Scotland. We will form matched groups in order to perform two comparisons examining: (1) the risk of NEC between infants enterally fed and infants not enterally fed, during therapeutic hypothermia; (2) the risk of late-onset blood stream infections between infants who received intravenous dextrose without any PN and infants who received PN, during therapeutic hypothermia. The following secondary outcomes will also be examined: survival, length of stay, breast feeding at discharge, hypoglycaemia, time to full enteral feeds and growth. Comparison groups will be matched on demographic, maternal, infant and organisational factors using propensity score matching.Ethics and disseminationIn this study, we will use deidentifed data held in the NNRD, an established national population database; parents can opt out of their baby’s data being held in the NNRD. This study holds study-specific Research Ethics Committee approval (East Midlands Leicester Central, 17/EM/0307). These results will help inform optimum nutritional management in infants with HIE receiving therapeutic hypothermia; results will be disseminated through conferences, scientific publications and parent-centred information produced in partnership with parents.Trial registration numberNCT03278847; pre-results,ISRCTN47404296; pre-results.

Background Gastro-oesophageal reflux is prevalent in preterm infants. Despite widespread use in clinical practice, there is still much controversy over the efficacy and safety of drug interventions, particularly antacid therapy. Objective To systematically review the effects of antacid therapy on preterm infants with symptoms of gastro-oesophageal reflux, and to assess the safety of these interventions. Methods We carried out an electronic search of the Cochrane central register of controlled trials (CENTRAL, The Cochrane Library), MEDLINE (1966–present), EMBASE (1980–present) and CINAHL (1982–present) as well as other online sources. Participants were preterm infants (

Background Current evidence supports progressive feeding in preterm infants. Due to lower necrotising enterocolitis risk, recent studies suggest starting total enteral feeding from birth in 30–33 weeks preterm infants. The feasibility of this practice is unclear. Aim Explore feeding practices in 30–33 weeks preterm infants. Design Prospective, multicentre, observational study recruiting 10 consecutive 30–33 weeks preterm infants from each of the eight UK hospitals. Results Eighty infants received their first feed at median of 24 hours, achieving total enteral (without intravenous nutrition) and full feeds (≥150 ml/kg/day) at median of 5 and 8 days, respectively. Eleven infants who achieved total enteral feeding within 24 hours after birth achieved full feeds earlier (p=0.02) with shorter hospital stay (p=0.009) but were also of older gestation (p=0.004). Conclusion Current early feeding approaches in 30–33 weeks preterm infants were found to be conservative. Total enteral feeding from birth is possible in these infants but further studies are needed.