title: Short and Long-Term Outcomes of Congenital Diaphragmatic Hernia
Creators: name: Lewis, Leonie
Publisher: name: University of Liverpool Repository
Year: 2022

description: Congenital diaphragmatic hernia (CDH) is a serious disease occurring in 1 in 3000 births. Essentially, failure of diaphragmatic closure in-utero leads to herniation of the abdominal contents into the thoracic cavity, causing lung hypoplasia and pulmonary hypertension. The current mortality rate is 30%-50% but for newborns that require ECMO support, a higher mortality rate of 60% is evident. The infants that do survive to hospital discharge may be left with complex long-term health problems, across multiple body systems. It is estimated that the prevalence of chronic lung disease (CLD) may affect up to 50% of all CDH patients. Neurological complications, such as motor and cognitive defects, and gastrointestinal morbidity, including severe gastroesophageal reflux disease (GORD) are also notable. This thesis focuses on both the short- and long-term outcomes of Congenital Diaphragmatic Hernia and consists of three main studies. Study I systematically reviews outcome reporting in observational studies and randomised controlled trials of post-natal interventions in CDH. With complex disease comes a variety of management strategies, and the need for these to be evaluated in robust clinical trials. However, no consensus currently exists on which outcomes should best be measured. This study aimed to review the selection, measurement, and reporting of outcomes in CDH. The outcomes were classified into seven domains modelled on the patient journey. The most frequent domains were ‘short-term markers of disease activity’ and outcomes relating to ‘hospital interventions and medication’. Long term outcomes were reported infrequently. There was heterogeneity in outcome reporting, primary outcomes were also variable and not always clearly stated. There is a clear need for a Core Outcome Set to standardise outcome reporting. Study II, a systematic review, focuses on short term outcomes in CDH, specifically the risk of Respiratory Syncytial Virus (RSV) bronchiolitis. Given uncertainties surrounding upcoming RSV epidemics, debate exists around whether palivizumab (RSV prophylaxis) should be given to CDH infants. This study aimed to evaluate the risk of RSV bronchiolitis hospitalisation and whether palivizumab prophylaxis modulates this risk. We included three retrospective cohort studies: A single study found CDH to be an independent risk factor for RSV hospitalisation (OR 3.30, 95% CI 2.01-4.4). Two studies compared RSV hospitalisation rates in CDH patients who had palivizumab vs those that did not. The pooled Risk Ratio was 1.11 (95% CI 0.29-4.23, p=0.88). Overall, the quality of evidence was considered poor, and one study was industry-funded. Study III considers the long-term sequelae of CDH. This study is a systematic review focusing on cardiorespiratory outcomes and health related quality of life in CDH survivors over 2 years of age. Indices of lung function, radiological outcomes, cardiopulmonary exercise testing, and health related quality of life were often reduced. Findings on the prevalence of asthma or reactive airway disease were mixed and there was some evidence of persistent pulmonary hypertension. Three papers reported late death (&gt;2 years), five due to respiratory cause, one of which was pulmonary hypertension. This thesis has highlighted that the outcomes of CDH survivors, both short and long term, should not be overlooked. Where not already available dedicated follow-up clinics for CDH survivors should be established. Further research into various aspects of CDH survivorship is required.