Childhood Outcomes after Perinatal Brain Injury (Data flowing to DfE)

University College London and Imperial College London (acting as joint controllers) require data for the Childhood Outcomes after Perinatal Brain Injury study. In this Data Sharing Agreement, Department for Education (DfE) will act as processors of the data. The study is funded by the National Institute for Health and Care Research (NIHR). This population-based cohort study will compare health and educational outcomes in children who experienced brain injury at or around the time of birth (perinatally) with two matched control groups (a preterm control group and a term control group). Perinatal brain injuries can have devastating consequences for children, families and society as a whole. As such, reducing the number of infants with perinatal brain injury is a current governmental priority. Over 3000 infants suffer a perinatal brain injury in England every year and in 2015 the Department of Health and Social Care (DHSC) declared a national ambition to halve the rates of perinatal brain injury by 2030.[1]

Advances in neonatal care and the adoption of innovative neonatal treatments have considerably impacted the survival of these infants. However, knowledge about childhood health and educational outcomes across the life course after perinatal brain injury, and how this has changed over time, is limited by a paucity of population-level research.

Most neonatal studies utilise a composite measure of mortality and neurodevelopmental impairment at 18-24 months as their primary outcome. It is however becoming increasingly clear that 2 year outcome measures are poorly predictive of childhood function (except for the most severely impaired) across the spectrum of neonatal conditions. [2,3] As such, there is a dearth of evidence underscoring the decisions of policymakers, the NHS, schools, healthcare professionals and parents – in their aspiration to support affected children to reach their full potential.

This retrospective UK population-based cohort study will compare health and educational outcomes in children with perinatal brain injury with two matched control groups (a preterm control group and a term control group), providing the most complete picture of how children’s lives are affected by perinatal brain injury.

The research plan to date has been shaped by detailed feedback from charity representatives and over 30 parents and ex-neonatal unit patients via the Great Ormond Street Parent Advisory Committee, the Bliss Insight and Involvement group (Bliss: for babies born premature or sick) , and the Meningitis Research Foundation. Parents, via these partner charity organisations, will continue to be involved in focus groups over the lifetime of the study in order to explore the study results and capture their thoughts on what they mean for parents and how best to communicate these results. The Patient and Public Involvement (PPI) work, undertaken in collaboration with the aforementioned charities, highlighted that evidence about the long-term impact of brain injuries (particularly the unseen impact on mental health and schooling) was a frequently overlooked parental priority. It matters to the people most affected.

A parallel study conducted by Imperial College London, [4] investigating perinatal brain injury across England has developed a robust definition for the exposure and identified a national cohort of infants of all gestational ages with perinatal brain injury born in England between January 1st 2008 and December 31st 2019 (cohort 1; n=54,733). This includes infants with hypoxic-ischemic encephalopathy (a type of brain dysfunction that occurs when the brain doesn't receive enough oxygen or blood flow for a period of time), perinatal stroke, central nervous system infections, intraventricular haemorrhage (bleeding inside or around the ventricles in the brain), white matter changes (softening of the white matter tissue within the brain seen as a complication of some babies born preterm), seizures and kernicterus (a complication of untreated jaundice damaging the brain) from the National Neonatal Research Database (NNRD). Infants with congenital: infections, encephalopathies or brain abnormalities, or with seizures from neonatal abstinence syndrome (NAS; a group of problems that occur in a newborn who was exposed to addictive opiate drugs while in the mother's womb) or hypoglycaemia (low blood sugar) will be excluded because they do not meet the DHSC definition for perinatal brain injury - i.e. they are not included in the national monitoring of this issue. Congenital conditions are pre-existing wouldn't represent perinatal injuries to the brain. NAS and hypoglycaemia are outside of the definition's scope and cannot be reliably or completely identified with the NNRD dataset. Patients who have opted out of the NNRD would also be excluded.

A matched preterm control group (<34 weeks gestation) will also be identified from the NNRD by 1:1 matching to the number of preterm infants with brain injuries in cohort 1 (cohort 2; n=24,612). NHS England will identify a term control cohort (≥34 weeks gestation) from birth registration and birth notification data matched on: sex; year of birth; birth weight; gestation (from 2015), and multiplicity. For every infant ≥34 weeks gestation in the brain injury cohort, three matched infants will be identified (cohort 3; n= 90,363).

For this study, demographics data will be disseminated for three cohorts of children created under NIC-342322-Q1N7M to flow to the Department for Education (DfE). The DfE use the demographic data provided by NHS England to extract the cohorts’ pseudonymised education data for the flow into the Office for National Statistics (ONS) Secure Research Service (SRS). NIC-342322-Q1N7M covers the provision of the cohorts into the creation of a cohort by NHS England. Demographics data is requested for the three cohorts of children under this Data Sharing Agreement (DSA), to allow linkage to the National Pupil Database (NPD) at the DfE, allowing University College London (UCL) to explore long term health and educational outcomes.

The overall proposed matched cohort includes 169,708 infants. Maximum proposed follow up would be 12 years and minimum follow up of 1 year.

Objectives:

1. To link routine national data to create a longitudinal matched cohort of children with perinatal brain injury

2. To determine childhood morbidity, mortality and academic attainment after perinatal brain injury, in England, between 2008-2020

Primary outcome:

• Neurodisability as per predefined diagnosis codes at 2 years, 5 years and 12 years during the study follow-up period (from birth to December 31st 2020)

Sources: HES APC, HES Outpatients, HES A&E, MHSDS

Secondary outcomes:

• All-cause mortality (time to day of death from any cause for each included child during the follow-up period; accounting for type of brain injury, specific treatments, geographic variation and year of birth). Source: Civil Registrations (Deaths), HES APC, HES Outpatients, HES A&E

• Mental health and behavioural conditions (first occurrence of any behavioural disorders including conduct disorder; emotional disorders such as depression and anxiety; hyperactivity disorder e.g. attention deficit hyperactivity disorder (ADHD); other disorders e.g. autism spectrum disorders, for an included child, during the study follow-up period (from birth to 31st December 2020 or death whichever occurs first)). Sources: MHSDS, HES APC, HES Outpatients

• Chronic conditions (first occurrence of any of the conditions below, for an included child, during the study follow-up period (from birth to 31st December 2020 or death whichever occurs first)). Sources: HES APC, HES Outpatients, HES A&E

Subgroups: (as per the Hardelid (chronic childhood condition coding) classification)[5]

• Infections

• Cancer and chronic blood conditions

• Cardiovascular conditions

• Respiratory conditions

• Musculoskeletal/ dermatological conditions

• Neurological conditions e.g. epilepsy

• Metabolic/ endocrine/ digestive conditions

• Renal/ genitourinary conditions

The outcomes proposed have been chosen to collectively reflect parental, researcher, clinician and policymaker priorities as evidenced in the academic literature and through UCL’s Public and Patient Involvement (PPI) work. Where possible, the outcomes are consistent with those used in previous studies and reflect the most prevalent issues affecting the population of interest.

The controllers of the NNRD (the NDAU) will send the minimum number of personal identifiers to NHS England for the infants in cohort 1 and 2; they will also send the minimum variables required for matching to create cohort 3 from the birth registration and birth notification data.

Data are requested for the people within the three cohorts in their entirety, as the large study size is necessary to have sufficient statistical power to investigate the study objectives, stratified by important factors such as the type of brain injury, gestation, and type of neurodisability.

Data requested are for the minimum data fields required for the study. Individual identifiers for the cohorts (forename, surname, sex, date of birth, unique study ID, postcodes) are required because without the linkage to the NPD under this agreement (DARS-NIC-475526-F3Z5H), the data released under DARS-NIC-342322-Q1N7M (HES, mental health and mortality data) will not be able to be linked to NPD data. The linked health data for cohorts 1-3 under DARS-NIC-342322-Q1N7M will be pseudonymised, retaining the unique study ID only, and securely transferred to the ONS Secure Research Server (SRS) for analysis. UCL do not require access to identifiable data and have not requested such access.

Organisations involved

UCL and Imperial College London will be joint data controllers. This project has been registered with the UCL Data Protection Team (registration number: Z6364106/2020/08/04 and the Imperial College London Data Protection Impact Assessment Team. At no point will UCL researchers have access to identifiable information. UCL researchers will only have access to pseudonymised data held within the ONS SRS. No data will be held by or at UCL. Imperial College London will not have access to the pseudonymised data held within the ONS SRS. They will only have access to the data which they already hold and control within the NNRD.

The NNRD is stored on Chelsea and Westminster NHS Foundation Trust servers. Imperial College London will extract data from the NNRD. Imperial College London/ Chelsea and Westminster NHS Foundation Trust will submit the NNRD cohort data to NHS England but will not be a data processor of NHS England data. The Department for Education (under this agreement) and the Office for National Statistics (ONS) (under DARS-NIC-342322-Q1N7M) will be data processors of NHS England data for the purposes of this study. These organisations will not have access to data from other organisations (or each other) that they do not already hold. The linkage to educational outcomes (NPD) will be undertaken by the Department for Education under this agreement. Identifiers will be removed from the educational outcome data (only the unique study ID number will be retained) before transfer into the ONS SRS. UCL research staff responsible for conducting the analysis for the project have completed the ONS Researcher Accreditation process, which involves specific training in the safe use of research data environments. They will sign and adhere to the ONS Accredited Researcher Declaration, and will be required to adhere to ONS data protection policies and procedures. All data to be transferred out of the SRS (the results of the analyses) will be checked by ONS staff to ensure that no individual level data, or potentially identifiable data, is transferred. Only aggregate level data with small numbers suppressed will be transferred out of the SRS system for publication.

The study has been funded as a doctoral fellowship by the National Institute for Health Research (NIHR). The NIHR has no role in the design or conduct of the study, and will not be processing or accessing any data. Two of the co-investigators/ supervisors in the study team are based at Imperial College London. They will have supervisory roles and advise upon the analysis and interpretation of results but will not have access to record level data in the ONS SRS.

The lawful basis for the data processing proposed for this study Article 6(1)(e) and Article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). The research is in the public interest it is hoped to provide the most complete picture of how children’s lives are affected by perinatal brain injury, providing essential information to answer parents’ questions accurately and in a meaningful family-centric manner.

Appropriate safeguards will be in place when processing data in accordance with Article 89(1) of the GDPR, namely the use of pseudonymisation to respect for the principle of data minimisation.

All data made available to the UCL research team will be pseudonymised using a unique study ID. Imperial College will not have any access to NHS England data. The UCL research team will not have access to individual identifiable data at any stage.

The proposed study has been subject to favourable independent review by a Research Ethics Committee, as well as by the Health Research Authority Confidentiality Advisory Group (CAG), which provides strong evidence that the research is in the public interest. The legal basis for the processing of personal identifiable information without consent is provided under section 251 of the NHS Act 2006, that of a medical purpose (medical research) that is in the public interest. UCL have received section 251 approval from the Health Research Authority CAG for the study.

References

1. Department of Health & Social Care. New ambition to halve rate of stillbirths and infant deaths 2015 [Available from: https://www.gov.uk/government/news/new-ambition-to-halve-rate-of-stillbirths-and-infant-deaths accessed 15th Oct 2019.

2. Marlow N. Is survival and neurodevelopmental impairment at 2 years of age the gold standard outcome for neonatal studies? Archives of Disease in Childhood-Fetal and Neonatal Edition 2015;100(1):F82-F84.

3. Marlow N. Measuring neurodevelopmental outcome in neonatal trials: a continuing and increasing challenge. Archives of Disease in Childhood-Fetal and Neonatal Edition 2013;98(6):F554-F58.

4. Gale C, Statnikov Y, Jawad S, et al. Neonatal brain injuries in England: population-based incidence derived from routinely recorded clinical data held in the National Neonatal Research Database. Arch Dis Child Fetal Neonatal Ed 2018;103(4):F301-F06. doi: 10.1136/archdischild-2017-313707

5. Wijlaars, L.P., Gilbert, R. and Hardelid, P., 2016. Chronic conditions in children and young people: learning from administrative data. Arch Dis Child, 101(10), pp.881-885.

The study will involve the following data processing and linkage steps:

1. Infants meeting the Department of Health definition for perinatal brain injury will be identified within the National Neonatal Research Database (NNRD) (cohort 1, n = 54,733). This database contains care data for all neonates admitted to NHS neonatal units across England, Wales and Scotland. Its population coverage is internationally unique with 100% coverage since 2012 and high representative coverage since 2008. The premature infants (< 34 weeks gestation) in cohort 1 will be matched to a comparator group of infants within the NNRD (cohort 2, n = 24,612).

2. The pseudonymised neonatal care data for cohort 1 and 2 will be transferred to the ONS Secure Research Service (SRS) by Imperial College London.

3. Under DARS-NIC-342322-Q1N7M, the NNRD will transfer the minimum identifiers for the NNRD cohorts (1 and 2) to NHS England (NHS number, date of birth, sex and postcode at birth). The NNRD will also provide the birth weight, gestation (from 2015), and multiplicity status (i.e. twins, triplets etc) for the remaining children with gestation time > 34 weeks in cohort 1 to NHS England.

4. The un-matched infants in cohort 1 with perinatal brain injury will be matched in a 1:3 ratio, by NHS England, to a comparator group of infants, identified from Birth Notifications and Civil Registrations (Births) data to create a ‘term’ control cohort (cohort 3, n = 90,363) (DARS-NIC-342322-Q1N7M).

5. All 3 cohorts will be linked to Civil Registrations (Deaths), Hospital Episode Statistics (HES) Admitted Patient Care (APC), HES Accident and Emergency (A&E), HES Outpatients and the Mental Health Services Data Set (MHSDS) up to December 31st 2020, by NHS England. The pseudonymised health outcomes and analysis covariates from the Births products for the three cohorts will be transferred from NHS England to the ONS SRS (DARS-NIC-342322-Q1N7M).

6. Under this Data Sharing Agreement (DARS-NIC-475526-F3Z5H), a file containing a list of personal identifiers (forename, surname, date of birth, sex, and postcodes) for linkage to the National Pupil Database (NPD) will be transferred from NHS England to the Department for Education (DfE). The NPD contains detailed information on the educational attainment, special educational needs and attendance of children at state schools across England between the ages of 5-18 years. A logic model, designed to maximise the chance of a reliable postcode match (given the variation over time), will be used. After linkage, all identifiers will be removed (only the unique study ID number will be retained) and these pseudonymised educational data will also be securely transferred for storage within the ONS SRS.

Identifiable information transferred to the DfE for matching will be controlled through secure access arrangements in line with DfE policy. Access is limited to a team of qualified (permanent DfE staff) data engineers employed on the maintenance and production of the National Pupil Database (NPD). All DfE staff accessing this data are cleared to levels in line with departments vetting protocols and have Baseline Personnel Security Standard (BPSS), Disclosure and Barring Service (DBS) and Level 2 Non-Police Personnel Vetting (NPPV) check clearance. The DfE uses Microsoft Azure cloud hosting for the storage and processing of data, applying a combination of software and hardware controls which meet the ISO27001 standards and the Government Security Policy Framework. The Department’s use of Microsoft Azure hosting has approval from the Cabinet Office and meets all the relevant guidelines for holding and processing personal and restricted data. This includes ensuring the systems comply with Data Protection Legislation and other relevant legislative obligations that apply to data rated at OFFICIAL-SENSITIVE.

Microsoft Limited Azure supply Cloud Services for the DfE and are therefore listed as a processor. They supply support to the system, but do not access data. Therefore, any access to the data held under this agreement would be considered a breach of the agreement. This includes granting of access to the database(s) containing the data. Microsoft Limited Azure servers are located within the EEA.

UCL researchers will only have access to pseudonymised data held within the ONS SRS under DARS-NIC-342322-Q1N7M. In order to access any data in the ONS SRS, all researchers will need to be ONS accredited and undergo data protection and confidentiality training. No data will be held by or at UCL. There will be no requirement or attempt to re-identify participants. Indeed, this would not be possible for UCL.

UCL research staff responsible for conducting the analysis for the project will complete the ONS Researcher Accreditation process, which involves specific training in the safe use of research data environments. They will sign and adhere to the ONS Accredited Researcher Declaration, and will be required to adhere to ONS data protection policies and procedures. All data to be transferred out of the SRS (the results of the analyses) will be checked by ONS staff to ensure that no individual level data, or potentially identifiable data, is transferred. Only aggregate level data with small number suppression will be transferred out of the SRS system for publication.

Data retention

The linkage keys used for the health and educational linkages will be securely held by NHS England and the Department for Education respectively. These will be retained for the duration of the agreement should further linkage be required (this will be requested separately to this version of the DSA). Only the pseudonymised dataset will be retained within ONS SRS to facilitate analysis by the UCL research team.

Academic outputs are hoped to include high-impact peer reviewed publications, and international conference presentations. Findings are expected to be submitted for publication in high impact general medical journals, such as the New England Journal of Medicine, the British Medical Journal, and JAMA Pediatrics. The study results are intended to be presented at international conferences such as the Royal College of Paediatrics and Child Health annual conference, the Kings Fund annual conference, and the Paediatric Academic Societies meeting in the USA.

Publications will be Open Access as per UCL policy, and freely available both on journal websites and via the UCL webpage. Outputs will contain only aggregate level data with small numbers suppressed in line with National Neonatal Research Database (NNRD), NHS England, Office for National Statistics (ONS) and Department for Education (DfE) policy and guidance. All data will be stored within the ONS secure research service (SRS) and all outputs from this server undergo independent checks by ONS staff to ensure outputs meet regulations and could not be deemed identifiable in any way.

Dissemination of the research findings to the public (parents who have children with a perinatal brain injury) are intended to be facilitated through existing collaborations with the Neonatal Data Analysis Unit (NDAU), BLISS (the charity for babies born sick or premature) and the Meningitis Research Foundation. UCL are also looking to also create an infographic/ information leaflet to improve communication of prognosis after perinatal brain injury between doctors and parents. Public dissemination is intended to include production of lay research reports publicised on the NDAU, BLISS, UCL and Meningitis Research Foundation websites. Research regarding neonatal outcomes has attracted a high level of media interest, and it is anticipated that this will be the case for the proposed study. UCL are acutely aware of the potential harmful effect of inaccurate or sensational reporting of research findings in this sensitive area, and the confusion and anxiety this can cause for affected families. UCL are planning to work closely with BLISS and Imperial College London to co-ordinate press releases and ensure that information is conveyed accurately and responsibly. BLISS and the Meningitis Research Foundation are also expected to publicise findings to their followers and the general public through their social media channels.

UCL will commence analysing the data as soon as it has been made available in the ONS SRS. It is anticipated that the process of data analysis, interpretation and report writing will take approximately 36 months, with papers submitted for publication in mid to late 2024.

This population study is hoped to provide the most complete picture of how children’s lives are affected by perinatal brain injury, providing essential information to answer parents’ questions accurately and in a meaningful family-centric manner. This information is intended to reshape clinical practice and facilitate optimum service planning within the NHS, to meet the needs of these children and their families through to adulthood, and ultimately improve their future health outcomes. An understanding of the sequelae of perinatal brain injury, specifically how and when children are affected, is expected to inform enhanced developmental surveillance across the NHS and enable the design of targeted multidisciplinary interventions to support children as needed. For example, premature infants (prone to inattention) can benefit from delayed school entry, Special Educational Needs (SEN) support, and educational packages raising awareness amongst educators of these specific challenges.

Stakeholder meeting with a view to impacting policy:

One of the project supervisors has a strong track record in bringing together key stakeholders on the issue of perinatal brain injury. Stakeholder meetings have previously been arranged with representatives from the Department of Health and Social Care, NHS Improvement, NHS England, neonatal doctors and nurses, and parent representatives; to discuss how perinatal brain injury should be defined in research. This project intends to utilise these existing connections to maximise the impact of this work.

UCL is looking to hold a stakeholder meeting in the final year of the fellowship, inviting representatives with whom the research team have established relationships, from the Department of Health and Social Care, the Department of Education, NHS England, BLISS, Meningitis Research Foundation, neonatal doctors and nurses, and parent representatives. It is planned that a Professor of Human Development from Oxford University with considerable experience in shaping social and education policy globally will be invited to join the stakeholder meeting, as well as a psychologist with considerable experience in designing educational interventions for preterm infants. The study results are intended to be discussed in this meeting alongside how these findings should shape policy and practice going forward. UCL are additionally anticipating to create an action plan to determine an effective strategy to disseminate this information to teachers and other professionals within the education sector, in collaboration with our stakeholders. This is hoped to ensure wide-spread awareness across the education sector, and that long-lasting sustainable measures are in place/ planned to support current and future children with perinatal brain injury, beyond completion of this fellowship.

Anticipated impact on neonatal care, society and NHS services:

Impact on neonatal care

• Equip healthcare professionals with reliable information to counsel families (target date 2024).

• Communication aids will facilitate meaningful family-centred conversations on the neonatal unit (target date 2024)

• Help prepare families for their child’s future and understanding what additional support may be needed (long-term)

• Encourage healthcare professionals to consider the long-term impact of various neonatal care decisions (long-term)

Impact on the NHS and policymakers

• Help those involved in shaping policy, resource planning and service provision to make informed decisions about how to most effectively support these children whilst maximising the efficiency of services (target date 2024-25)

• UCL findings are intended to inform national guidelines on follow-up after brain injury (target date 2024-25)

Impact on schooling and policymakers

• Equip parents with important information about the academic impact of brain injuries to help them plan their child’s future and support them with their educational needs (long-term)

• Provide key information and education to teachers about how they can support children with perinatal brain injuries (long-term)

• Help the Department for Education in determining resource allocation and the provision of additional educational support (long-term)

Outputs expected late 2024-2025. There are therefore no yielded benefits to date.