4-year PhD Studentship: Evaluating the impact of Magnesium Sulphate fetal neuroprotection on cerebral palsy rates in England

Around 10% of very preterm births in developed countries result in Cerebral Palsy (CP),1representing a significant burden for affected individuals, families,2 and healthcare services. Since 2015, NICE recommends administration of magnesium sulphate (MgSO4) in very preterm deliveries as a core part of maternity care.3 Data from other countries indicated that antenatal MgSO4 may reduce CP risk by ~30% when given to women at risk of preterm birth4. This would imply that ~200 cases annually might be avoidable in England by consistent administration of MgSO4.5

However, by 2017 only 64% of eligible women were receiving MgSO4,6 while high regional variation (49%-78%) was also observed, indicating health inequalities. 6 The National “Prevention of Cerebral Palsy in Preterm labour” (PReCePT) Programme (NPP) was rolled out in 2018 to increase MgSO4 use to 85% by 2020. Recent work has indicated that this programme was effective and cost-effective7. However, the implicit assumptions that (1) the administration of MGSO4 does indeed have comparable effects as reported elsewhere, and (2) that increased uptake from NPP will reduce CP incidence, remain untested. Addressing these important gaps in knowledge that require addressing for optimizing maternity care and reduce burden on affected individuals and families, as well as healthcare services.

Aims and objectives

This PhD aims to investigate both assumptions, and in addition will assess the impact of the Covid-19 pandemic on the NPP and incidence rates of CP. It has Three objectives:

Objective 1: To evaluate whether the administration of MgSO4 to mothers reduce the probability of CP in pre-term babies.

Objective 2: To determine whether the introduction of NPP in England has led to a reduction in CP rates.

Objective 3: To assess whether the administration of MGSO4 to mothers of preterm babies changed during the Covid-19 pandemic, and whether this has resulted in an increase of CP in the community.

Methodology

The project will link data from the UK National Neonatal Research Database (NNRD) to the national GP dataset (Clinical Practice Research Datalink (CPRD)) or collaborate with OpenSafely for the years 2012-2021. There is currently no Cerebral Palsy (CP) register in England, and cases of suspected CP at age 2 will be determined through the use, and possible modification, of previously developed screening algorithms.

Objective 1: newborns in England whose mothers were administered MGSO4 will be propensity score matched to comparable newborns whose mothers did not receive MGSO4. Odds of developing CP of exposed (mother received MGSO4) relative to unexposed ( not administered MGSO4) will be calculated using multi-level multivariable logistic regression.

Objective 2: interrupted timeseries analysis will be conducted with the timepoint of participation in PreCEPT1 and PReCePT National Programme (NPP) for each region signifying a change in protocol, using negative binomial mixed-effects models.

Objective 3: timeseries of CP from ‘genetic’, ‘perinatal hypoxia’, or ‘preterm’ causes will be separately analysed using interrupted timeseries analyses incorporating national and regional pandemic measures and the PreCePT programme.

Of particular interest are the impact of NPP on health inequalities, and stratified analyses by deprivation level and ethnicities will be conducted in all analyses.

How to apply for this project

This project will be based in Bristol Medical School - Population Health Sciences in the Faculty of Health Sciences at the University of Bristol.

Please visit the Faculty of Health Sciences website for details of how to apply