Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (the SToP-BPD study): Statistical analysis plan

Background: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth with short-term and long-term adverse consequences. Although the glucocorticoid dexamethasone has been proven to be beneficial for the prevention of BPD, there are concerns about an increased risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. The aim of the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (SToP-BPD) trial is to assess the efficacy and safety of postnatal hydrocortisone administration for the reduction of death or BPD in ventilator-dependent preterm infants. Methods/design: The SToP-BPD study is a multicentre, double-blind, placebo-controlled hydrocortisone trial in preterm infants at risk for BPD. After parental informed consent is obtained, ventilator-dependent infants are randomly allocated to hydrocortisone or placebo treatment during a 22-day period. The primary outcome measure is the composite outcome of death or BPD at 36 weeks postmenstrual age. Secondary outcomes are short-term effects on pulmonary condition and long-term neurodevelopmental sequelae assessed at 2 years corrected age. Complications of treatment, other serious adverse events and suspected unexpected serious adverse reactions are reported as safety outcomes. This pre-specified statistical analysis plan was written and submitted without knowledge of the unblinded data

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

Conservative treatment for patent ductus arteriosus in the preterm

BACKGROUND: A patent ductus arteriosus (PDA) is common among preterms, and prophylactic medical treatment has been advocated as the first-line approach. Conservative treatment may result in similar outcome, but without exposure to the harmful side effects of medication. A retrospective analysis revealed a ductal closure rate of 94% after conservative treatment with adjustment of ventilation (lowering the inspiratory time and increasing positive end expiratory pressure) and fluid restriction. OBJECTIVE: To study prospectively over one year the rate of PDA closure, and morbidity and mortality following conservative treatment. METHOD: Prospective study (1 January 2005 - 31 December 2005) including 30 newborns <or=30 weeks' gestation, all of whom were being ventilated and required surfactant. Echocardiography was performed 48-72 h after birth. Clinically important PDA was conservatively treated as described above. The percentage of children with PDA, ductal ligation and major complications was determined. RESULTS: Ten neonates (33%) developed a clinical important PDA. Following conservative treatment the duct closed in all neonates (100%), and none required ductal ligation or medical treatment. The rates of major complications were no higher than those reported by the Vermont Oxford Network and in the literature. CONCLUSION: The managed care plan resulted in an overall ductal closure rate of 100%. These results suggest that conservative treatment of PDA is a worthy alternative to prophylactic medical treatmen

End-of-life decisions in neonates and infants : a nationwide mortality follow-back survey

Objectives Neonatology has undergone important clinical and legal changes; however, the implications for end-of-life decision-making in seriously ill neonates to date are unknown. Our aim was to examine changes in prevalence and characteristics of end-of-life decisions (ELDs) in neonatology. Methods We performed a nationwide mortality follow-back survey in August 1999 to July 2000 and September 2016 to December 2017 in Flanders, Belgium. Data were linked to information from death certificates. For each death under the age of 1, physicians were asked to complete an anonymous questionnaire about which ELDs were made preceding death. Results The response rate was 87% in 1999-2000 (253/292) and 83% in 2016-2017 (229/276). The proportion of deaths of infants born before 26 weeks' gestation was increased (14% vs 34%, p=0.001). Prevalence of ELDs remained stable at 60%, with non-treatment decisions occurring in about 35% of all deaths. Use of medication with an explicit life-shortening intention was prevalent in 7%-10% of all deaths. In early neonatal death (27 days old), it increased from 2% to 10%. Conclusions Over a timespan of 17 year, the prevalence of neonatal ELDs has remained stable. A substantial number of deaths was preceded by the intentionally hastening of death by administrating medication. While surveying solely the physician perspective in this paper, there is a need for an open multidisciplinary debate, including, for example, nursing staff and family members, based on clinical as well as ethical and jurisdictional reflections to discuss the need for international guidelines

End-of-life decisions in neonates and infants : a nationwide mortality follow-back survey

Objectives Neonatology has undergone important clinical and legal changes; however, the implications for end-of-life decision-making in seriously ill neonates to date are unknown. Our aim was to examine changes in prevalence and characteristics of end-of-life decisions (ELDs) in neonatology. Methods We performed a nationwide mortality follow-back survey in August 1999 to July 2000 and September 2016 to December 2017 in Flanders, Belgium. Data were linked to information from death certificates. For each death under the age of 1, physicians were asked to complete an anonymous questionnaire about which ELDs were made preceding death. Results The response rate was 87% in 1999-2000 (253/292) and 83% in 2016-2017 (229/276). The proportion of deaths of infants born before 26 weeks' gestation was increased (14% vs 34%, p=0.001). Prevalence of ELDs remained stable at 60%, with non-treatment decisions occurring in about 35% of all deaths. Use of medication with an explicit life-shortening intention was prevalent in 7%-10% of all deaths. In early neonatal death (27 days old), it increased from 2% to 10%. Conclusions Over a timespan of 17 year, the prevalence of neonatal ELDs has remained stable. A substantial number of deaths was preceded by the intentionally hastening of death by administrating medication. While surveying solely the physician perspective in this paper, there is a need for an open multidisciplinary debate, including, for example, nursing staff and family members, based on clinical as well as ethical and jurisdictional reflections to discuss the need for international guidelines

Barriers to and Facilitators of End-of-Life Decision Making by Neonatologists and Neonatal Nurses in Neonates: A Qualitative Study

CONTEXT: Making end-of-life decisions (ELDs) in neonates involves ethically difficult and distressing dilemmas for health care providers. Insight into which factors complicate or facilitate this decision-making process could be a necessary first step in formulating recommendations to aid future practice. OBJECTIVES: This study aimed to identify barriers to and facilitators of the ELD-making process as perceived by neonatologists and nurses. METHODS: We conducted semistructured face-to-face interviews with 15 neonatologists and 15 neonatal nurses, recruited through four neonatal intensive care units in Flanders, Belgium. They were asked what factors had facilitated and complicated previous ELD-making processes. Two researchers independently analyzed the data, using thematic content analysis to extract and summarize barriers and facilitators. RESULTS: Barriers and facilitators were found at three distinct levels: the case-specific context (e.g., uncertainty of the diagnosis and specific characteristics of the child, parents, and health care providers, which make decision making more difficult), decision-making process (e.g., multidisciplinary consultations and advance care planning, which make decision making easier), and overarching structure (e.g., lack of privacy and complex legislation making decision making more challenging). CONCLUSION: Barriers and facilitators found in this study can lead to recommendations, some simpler to implement than others, to aid the complex ELD-making process. Recommendations include establishing regular multidisciplinary meetings to include all health care providers and reduce unnecessary uncertainty, routinely implementing advance care planning in severely ill neonates to make important decisions beforehand, creating privacy for bad-news conversations with parents, and reviewing the complex legal framework of perinatal ELD making.status: publishe

Psychological support in end-of-life decision-making in neonatal intensive care units: Full population survey among neonatologists and neonatal nurses

BACKGROUND: Moral distress and burnout related to end-of-life decisions in neonates is common in neonatologists and nurses working in neonatal intensive care units. Attention to their emotional burden and psychological support in research is lacking. AIM: To evaluate perceived psychological support in relation to end-of-life decisions of neonatologists and nurses working in Flemish neonatal intensive care units and to analyse whether or not this support is sufficient. DESIGN/PARTICIPANTS: A self-administered questionnaire was sent to all neonatologists and neonatal nurses of all eight Flemish neonatal intensive care units (Belgium) in May 2017. The response rate was 63% (52/83) for neonatologists and 46% (250/527) for nurses. Respondents indicated their level of agreement (5-point Likert-type scale) with seven statements regarding psychological support. RESULTS: About 70% of neonatologists and nurses reported experiencing more stress than normal when confronted with an end-of-life decision; 86% of neonatologists feel supported by their colleagues when they make end-of-life decisions, 45% of nurses feel that the treating physician listens to their opinion when end-of-life decisions are made. About 60% of both neonatologists and nurses would like more psychological support offered by their department when confronted with end-of-life decisions, and 41% of neonatologists and 50% of nurses stated they did not have enough psychological support from their department when a patient died. Demographic groups did not differ in terms of perceived lack of sufficient support. CONCLUSION: Even though neonatal intensive care unit colleagues generally support each other in difficult end-of-life decisions, the psychological support provided by their department is currently not sufficient. Professional ad hoc counselling or standard debriefings could substantially improve this perceived lack of support.status: publishe