55,000 babies are born prematurely in the UK annually. Bleeding in the fluid spaces of the brain (ventricles) is common after prematurity; in England around 450 babies suffer from severe bleeds every year. This is the most important cause of neurological disability after prematurity. Bleeding occurs in the first week of life when the brain is developing rapidly and is most vulnerable to injury. The blood and its breakdown products in the brain fluid (cerebrospinal fluid, CSF) are toxic to the developing brain and cause scarring that blocks the flow and absorption of CSF. In about half these babies, this causes fluid build-up, or post-haemorrhagic ventricular dilatation (PHVD).

Current standard treatment of PHVD only drains CSF to reduce pressure inside the brain. Following early results and a successful pilot study at GOSH, we developed an NIHR-funded randomised national trial to analyse the impact of an operation to wash out blood inside the brain using a small endoscope. We will compare standard treatment (fluid drainage alone) with washout plus drainage of fluid.

Premature babies typically undergo an MRI scan of the brain at their expected birth time to assess their brain injury, predict the severity of their disability and see what early rehabilitation and treatment they need. In this study we will use new MRI techniques during this scan at GOSH and Alder Hey Hospital to better understand the extent of brain injury in relation to brain structure, function and brain fluid flow. We want to see whether these will show the impact of the washout procedure, tell us about how washout works, and improve prediction of the child's disability and early treatment needs. If successful, we will apply for further funding to extend these techniques to the other centres in the UK and maximise their benefit within the NHS.

Background

Post-haemorrhagic ventricular dilatation (PHVD) is the most important cause of developmental and cognitive disability after prematurity. The ENLIVEN-UK trial is an NIHR-funded multicentre national randomised study, aiming to recruit 100 neonates across 16 centres, to evaluate the impact of endoscopic lavage in addition to standard drainage of cerebrospinal fluid (CSF) at an early postnatal age. In this study we will use a set of novel MRI sequences at term-equivalent age (TEA) to assess impact of treatment and discover novel mechanisms of disease.

Objectives

1. To determine the impact of standard treatment and endoscopic lavage on brain structure and function, distribution of blood products, and CSF flow using advanced MRI techniques at TEA;
2. To assess how these new MRI techniques relate to prognosis, and add predictive value to the basic MRI scan carried out as standard of care, as defined by the 2-year structured formal evaluation within the ENLIVEN-UK trial and 6-monthly neurological examinations.

Methods

Neonates with PHVD undergoing neurosurgical treatment at Great Ormond Street Hospital (GOSH) and Alder Hey Children's Hospital (AHCH) (15 neonates in each), the majority of whom will be recruited to the ENLIVEN-UK study, will undergo additional novel MRI sequences at their TEA MRI scan. These will include Diffusion Tractography (DTI), DTI-along perivascular spaces (DTI-ALPS), quantitative susceptibility mapping (QSM) and resting state functional MRI (rs-fMRI) sequences. These images will be processed and evaluated by MR physicists and outcomes will be reviewed in the context of their (a) randomised surgical treatment and (b) formal developmental and cognitive evaluation at 2 years.

Outcomes

The use of these MR sequences in this population is novel. Any factors related to the impact of endoscopic lavage and prognostic significance will be evaluated in a wider neonatal cohort through the national network of neurosurgeons and neonatologists developed by the ENLIVEN-UK study.

Neonates with PHVD who have been referred to and/or have undergone neurosurgical treatment at Great Ormond Street Hospital (GOSH) and Alder Hey Children's Hospital (AHCH) (15 neonates in each) will be eligible for inclusion.

The majority of neonates will be recruited to the ENLIVEN-UK randomised clinical trial and involvement will not preclude recruitment to this study.

The only exclusion criteria will be lack of informed consent from the parent/carer.

Issues relating to confidentiality with MRI data