Pulmonary Effects of Neonatal Hydrocortisone Treatment in Ventilator-Dependent Preterm Infants

Background/Objective. Hydrocortisone, administered to ventilated preterm neonates to facilitate extubation, has no adverse long-term effects, but short-term pulmonary effects have not been described previously. In the present study, we analyzed effects of hydrocortisone on ventilator settings and FiO2 in ventilator-dependent preterm infants. Patients and Methods. Fifty-five preterm children were included in this retrospective cohort study. Hydrocortisone was administered at a postnatal age of > 7 days to treat chronic lung disease (CLD). Ventilator settings before and after hydrocortisone administration were recorded as well as FiO2 at 36 weeks' gestational age. Presence of cerebral palsy was assessed at a mean corrected age of 24.1 months. Results. Hydrocortisone administered at a median postnatal age of 14 days significantly reduced FiO2 from a median of 0.39 to 0.30, mean airway pressure (MAP) from a median of 10.0 cm H2O to 7.6 cm H2O, and PaCO2 from a median of 53.5 mmHg to 47 mmHg. Extubation was achieved in all patients. CLD at 36 weeks was present in 11 of the 52 patients (21.1%). None developed cerebral palsy. Conclusions. Hydrocortisone was effective in reducing the FiO2, MAP, and PaCO2 and facilitated extubation. Hydrocortisone was not associated with cerebral palsy

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants.</p> <p>Methods/Design</p> <p>The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis.</p> <p>Discussion</p> <p>This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants.</p> <p>Trial registration number</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2768">NTR2768</a></p

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Hydrocortisone Treatment for Bronchopulmonary Dysplasia and Brain Volumes in Preterm Infants

OBJECTIVE: To assess whether there was an adverse effect on brain growth after hydrocortisone (HC) treatment for bronchopulmonary dysplasia (BPD) in a large cohort of infants without dexamethasone exposure. STUDY DESIGN: Infants who received HC for BPD between 2005 and 2011 and underwent magnetic resonance imaging at term-equivalent age were included. Control infants born in Geneva (2005-2006) and Utrecht (2007-2011) were matched to the infants treated with HC according to segmentation method, sex, and gestational age. Infants with overt parenchymal pathology were excluded. Multivariable analysis was used to determine if there was a difference in brain volumes between the 2 groups. RESULTS: Seventy-three infants treated with HC and 73 matched controls were included. Mean gestational age was 26.7 weeks, and mean birth weight was 906 g. After correction for gestational age, postmenstrual age at time of scanning, the presence of intraventricular hemorrhage, and birth weight z-score, no differences were found between infants treated with HC and controls in total brain tissue or cerebellar volumes. CONCLUSIONS: In the absence of associated parenchymal brain injury, no reduction in brain tissue or cerebellar volumes could be found at term-equivalent age between infants with or without treatment with HC for BPD

SUGAR-DIP trial:Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals