Timing of Umbilical Cord Clamping for Preterm Infants Needing Resuscitation at Birth: The Opticord trial

RESEARCH QUESTION: In very preterm babies (born <32 weeks’ gestation) requiring neonatal resuscitation, is resuscitation with the umbilical cord intact for at least 3 minutes (‘intact’ group) superior to resuscitation with the umbilical cord clamped and cut during the first 60 seconds (‘clamped’ group) for survival without severe brain injury at 36 weeks’ postmenstrual age. BACKGROUND, AIMS & OBJECIVES: Deferred cord clamping has been shown to prevent the deaths of preterm infants but concerns exist around those requiring resuscitation and randomised control trials are needed to assess the benefit and harms in this group of babies. Our research question is the 2nd highest priority for neonatal research in the UK. We aim to determine the clinical and cost effectiveness of resuscitation with an intact cord. METHODS: Design: Multi--centre, two-arm, cluster randomised superiority trial Setting: Secondary & tertiary care maternity units with Level 2 or 3 neonatal intensive care units. Population: Very preterm babies <32 weeks’ gestational age requiring resuscitation at birth. Intervention: Bedside resuscitation with the umbilical cord intact for at least three minutes. Comparator: Resuscitation with the umbilical cord clamped and cut in the first 60 seconds. Primary outcome: Survival without severe brain injury at 36 weeks’ postmenstrual age (PMA). Severe brain injury defined as Grade III or IV intraventricular haemorrhage or periventricular leukomalacia. Secondary outcomes: Babies Survival at 36 weeks’ PMA, at 12- and 24-months of age corrected for prematurity (known as corrected age [CA]), Survival without moderate or severe neurodevelopmental impairment on parent-completed questionnaire at 24 months, sepsis, necrotising enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, blood transfusions, hypotension, phototherapy, exchange transfusion. Health-related quality of life (HRQoL) using the EQ-TIPS questionnaire at 12- and 24-months CA. Resource use at 6 weeks, 12- and 24 months Secondary outcomes: Mother Survival until hospital discharge, sepsis, post-partum haemorrhage, post-partum infection up to 7 days after birth Parents’ experience and satisfaction of intervention and trial and acceptability of resuscitation and cord management (6 weeks post-partum) Maternal health-related quality of life (HRQoL) and wellbeing collected using the EQ-5D-5L and ICE-CAP instruments at 6 weeks, 12- and 24-months?post-partum. Sample size: 2,422 babies from 46 sites in the UK. 10–16 international sites to realise a total sample size of 3,198–3,420. Analysis: Comparative analyses between groups will be intention-to-treat. A generalised linear mixed model will be used to compare survival without severe brain injury. Risk ratios and risk differences along with 95% confidence intervals will be presented. TIMELINES: Total 78 months (m): m1–12 set-up, m13–46 recruitment, m24 internal pilot, m55 primary and short-term outcome report, m78 follow-up report. Please see GANNT chart. IMPACT AND DISSEMINATION: Worldwide practice will be changed by the results either leading to intact cord resususcitation adoption or negating it. We will publish in peer reviewed, high impact journal and a NIHR monograph and present at national & international conferences. Social media platforms & websites of the trials unit, universities, collaborators, and partners including the neonatal charity Bliss will also publicise the results.