Title: Evidence-based care for preterm and sick newborn infants and their families: Cochrane partnership programme
Funder: Department of Health and Social Care

Abstract: Background In the UK, one-in-ten infants is born preterm or sick and requires neonatal care. Although outcomes for preterm or sick newborn infants have improved substantially over the past three decades, major morbidities associated with the need for prolonged invasive or intensive care remain. These include extra-uterine growth and developmental faltering secondary to nutritional deficiency, necrotising enterocolitis (NEC), and late-onset (hospital-acquired) infection. Attributable mortality for NEC and severe infection is more than 20% and these are now the most common causes of death beyond the early neonatal period for very preterm infants. NEC, infection, and nutritional insufficiency are also associated with increased rates of chronic lung disease and neuro-disability, longer durations of hospital stay, and higher (life-long) health service costs. To better prevent and treat these conditions, families and parents, clinicians and caregivers, guideline writers and policy-makers, and service-commissioners need to access high-quality evidence to guide care practices, highlight uncertainties, and inform priority setting for further research. Cochrane Reviews provide the underpinning evidence for key neonatal care practices, and have informed regional, national, and international guidelines and policy statements. Cochrane Neonatal and Cochrane Pregnancy and Childbirth provide most of the cited evidence in the World Health Organization (WHO) recommendations on care of the preterm infant. Aims and objectives The aim of this NIHR-funded programme is to extend our on-going work developing, maintaining, updating, and disseminating Cochrane reviews of the effectiveness of treatments and tests for sick and preterm newborn infants, focussing on producing and maintaining reviews of neonatal transition support, infection treatment and prevention strategies, and nutritional interventions. This programme aims to produce a suite of policy- and practice-informing systematic reviews that meet the needs of commissioners, services, and clinicians (including Cochrane “overviews”, reviews of diagnostic test accuracy (DTA) and reviews using network and individual participant data (IPD) meta-analysis) and drives improvements in care and research to improve outcomes for newborn infants and their families. Strategy The programme is being undertaken by a multidisciplinary team with extensive experience of neonatal care and research. Our strategy is to combine academic and technical expertise and resources with the views of family advocates and NHS clinicians to provide evidence of sufficient validity and utility to influence practice and service delivery. The programme of work is aligned to the priorities and needs of the British Association of Perinatal Medicine (BAPM) and Bliss (third sector support organisation for infants and families). This will set our outputs at the heart of regional and national quality improvement cycles and encourage and empower clinicians and families to promote generation and use of Cochrane reviews to inform care and research. Projected outputs 1. We will update key priority reviews of interventions and tests with major impacts on neonatal care practices and outcomes, with a focus on those reviews that support policies or guidelines, or inform research priorities, especially where the evidence-base is evolving- e.g. transition support, enteral feeding strategies, post-hospital discharge support. 2. We will produce policy and practice-informing Cochrane “overviews” that map the evidence from systematic reviews and synthesise the evidence-base across a clinical area. We will integrate the findings with the views and needs of service-providers and service-users (Bliss). Candidate topics are cognate with the “top” UK research priorities for preterm birth identified by the James Lind Alliance (JLA)-sponsored Priority Setting Partnership. These include strategies to refine neonatal delivery room care, optimise early neonatal nutrition for extremely preterm infants, promote infection control in neonatal units (particularly with regard to vascular access devices), and improve transition support and post-discharge care for infants and families. 3. We will undertake DTA reviews of key uncertainties aligned with JLA priorities. These include reviews of molecular assays for diagnosing infection, novel methods (such as measuring volatile organic compound profiles) for diagnosing NEC, and the use of biomarkers to shorten antibiotic courses for empirical treatment of well infants who are at risk of congenital infection. 4. With NIHR Complex Review Support Unit, we aim to undertake IPD meta-analyses addressing major new interventions in neonatal care where plausibility exists for differential effects in groups of infants. These include reviews of lactoferrin supplementation to explore whether any infant group is more likely to benefit with regard to preventing infection and NEC, and of early nutritional support to examine whether the long term "programming" effects differ between groups of infants (including data from trials included in existing Cochrane reviews). 5. We will undertake reviews using network meta-analysis to explore and define the relative effects of related interventions that are unfeasible to assess in direct comparisons (e.g. different types or combinations of probiotics to prevent NEC and infection, or different non-steroidal anti-inflammatory drugs to close the patent ductus arteriosus in very preterm infants). 6. In order to create more streamlined versions of reviews, we will explore creating condensed versions of reviews that could be more accessible to clinicians and guideline developers. These streamlined reviews will still apply all of the rigor and standards of Cochrane, but we will move much of the descriptive methodological text to appendices that can be linked to more detailed methodology online or printed as a shortened version. Dissemination We will extend our efforts to ensure that the findings of Cochrane reviews contribute to national and regional audit, benchmarking, and quality improvement activities including the UK National Neonatal Audit Project. We will engage with BAPM, Bliss, the NIHR Dissemination Centre (http://www.dc.nihr.ac.uk/), and the Knowledge Translation team at Cochrane Central to disseminate the key findings of Cochrane reviews to increase awareness and impact across the NHS and promote the use of our reviews in national policy documents such as BAPM Frameworks of Practice. As well as complying with the NIHR Open Access Policy, we will present practice-defining findings in national and international meetings and publish reviews, overviews and review summaries in high-impact specialty and general journals. We will publish summaries of key reviews and overviews with “friendly fronts” that present an outline of the various related reviews and link readers to the reviews of interest.

Lay abstract: Babies who are born too early (preterm), and particularly very preterm babies who are born before before 32 weeks of pregnancy, often require intensive care for several weeks after birth. Advances in care have improved survival and outcomes for preterm and sick infants substantially over the past 30 years. However, partly because of this increase in the chances of survival, infants now encounter problems associated with the need to prolonged periods of intensive care. The main problems include infections and severe bowel disorders (mainly “necrotising enterocolitis”), and these are associated with reduced intake of nutrition and problems with growth and development which may persist in the long term. The Cochrane Neonatal Group [see http://neonatal.cochrane.org/] aims to provide clinicians, and parents and their families, with reliable and useful summaries of the best evidence to guide care and further research to reduce the burden of harm due to infection and necrotising enterocolitis in preterm infants. We are undertaking a 3 years programme of work, supported by the National Institute of Health Research and in collaboration with partners in the UK Centre for Reviews and Dissemination and NHS, to produce and revise Cochrane systematic reviews in this field. The review team includes a range of clinicians, systematic review specialists, and family and infant advocates. Our strategy is to combine academic expertise and resources with the views of family advocates and NHS clinicians to provide reliable reviews with a “coal-face” perspective and an understanding of the context relevant to families, caregivers and the NHS. We will produce Cochrane Reviews that can drive quality improvement and encourage clinicians and families to use the best available evidence to inform standards of care to improve outcomes for babies and their families.

Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;3.3 NUTRITION AND CHEMOPREVENTION;7.3 MANAGEMENT AND DECISION MAKING;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH