Title: Investigating gender mortality differences in children admitted to UK Paediatric Intensive Care Units.
Funder: Health Education England

Abstract: Background Child and infant mortality is an important indicator of child health and overall development in countries. Under circumstances where boys and girls have the same access to resources such as food and medical care, boys have higher mortality rates than girls during childhood. In the UK most childhood deaths occur within Paediatric Intensive Care Units (PICUs). We carried out an analysis of more than 86,000 infants across the UK from 2005-2015 to investigate mortality among the sexes. We found that girls had a significantly higher mortality than boys in PICU. We also found that PICU admission rates for boys are higher than girls and this has been observed by other studies. When analysing mortality in PICU, we must also consider Length of PICU stay (LOS). We know that there is a positive association between LOS in PICU and mortality and data on LOS are very difficult to model. To obtain valid inference we need an accurate statistical model for these data. Aim The primary aim is to explain the higher mortality rate for girls in PICU. Research questions Why do infant girls have a higher mortality rate than infant boys in PICU? Is this the case for older children? Is this the case after discharge from PICU? Why do boys have higher admission rates to PICU? Should the Paediatric Index of Mortality (PIM) be adjusted for sex? Is there a better way of modelling the mortality data for PICU? How should we analyse data on length of stay in PICU?Objectives Objectives for Questions 1-4 Attempt to explain the higher mortality rate for girls in PICU and the higher admission rate for boys using factors outside of PICU such as maternal and perinatal factors. Study the life trajectory of children who leave PICU alive.Objectives for Question 5 Adjust the PIM score to account for sexObjectives for Questions 6-7 Conduct a methodological exploration to derive a more accurate statistical model for joint mortality and LOS dataMethods 1. Data linkage (Questions 1-4) We will use data from PICANet on children of all ages and admitted between 2010 and 2018. We will link this data to inpatient maternity data from Hospital Episode Statistics to obtain information on maternal and perinatal characteristics to try and explain the difference in mortality and admission rates between the sexes. We will link the PICANet data to mortality record from the Office of National Statistics to study the life trajectory of children who are discharged from PICU. 2. Reassessment of PIM (Question 5) This is a reanalysis of the data obtained for Part 1 of this project. PIM score from Part 1 will be recalculated by accounting for sex. 3. Methodological exploration (Questions 6-7) This is a statistical modelling study using the available data to develop a more accurate model for mortality and length of stay (LOS) in PICU. To our knowledge this is the first attempt in the literature to explain the sex mortality differences by linking PICU data to external databases.

Lay abstract: Aim The overall aim is to explain the higher mortality rate for girls compared to boys when admitted to Paediatric Intensive Care Units (PICU) in the UK Background Every year more than 20,000 children are admitted to PICUs in the UK. Previous small studies have highlighted that baby girls may have higher mortality rates than baby boys in PICU. In 2017 we completed an analysis of all babies (0-12 months old) who were admitted to PICUs over an 11-year period. We obtained anonymous records for 68,000 babies and compared the rates of death between girls and boys during their admission to PICU. We discovered that girls had higher death rates than boys. This is different to what is seen in the general population where boys have higher death rates than girls for children of all ages. We carefully examined whether this difference could be due to differences in age, disease severity, infections, and a number of other factors. None of the factors could explain why girls died more than boys in PICU. We now want to examine these findings in greater detail as this could have implications for the care of critically ill children generally. We also know that boys are more likely to be admitted to PICU than girls. This has been observed every year by the Paediatric Intensive Care Audit Network (PICANet). So far there has been no explanation offered for this observation. We would like to attempt to understand why more boys are admitted to PICU, yet more girls die in PICU. Design and methods We will use national PICANet data for all ages of children admitted to PICU. These data are routinely collected in every PICU, they will be anonymised, and we will seek permission to use them. Next, we will link data from PICANet to routinely collected maternity data.We will consider factors such as age and ethnicity, and whether maternal characteristics such as mother's age can explain any differences. We will then link these data to death records for those who are discharged alive from PICU to see if the difference in death rates between girls and boys persists after they leave the PICU. If we can find a plausible explanation for girls having higher death rates than boys, then we may be able to identify possible strategies to reduce such differences in future. Any findings will be carefully considered by specialist commissioners and professionals through the Paediatric Intensive Care Society (PICS). Patient and public involvement (PPI) I presented this proposal to a Parent and Carer Advisory Group (PCAG) meeting arranged by the Clinical Research Network PPI officer. The parents commented on the plain English summary and provided answers to some questions I posed to them. Two parents agreed to be members of a small panel to support this project throughout its progress. I also attended a PPI session by INVOLVE who commented on the proposal and showed much interest in the research topic. Benefits to Patients We will be able to better understand factors associated with admission and death in PICU. We intend to suggest ways to enable better health planning which might reduce PICU admission and mortality rates Understanding risk factors for admission and mortality will allow better understanding of causes of life-threatening conditions, and therefore ways for prevention. We can identify who is in most need of out-of-hospital care and direct NHS resources to meet their needsDissemination We will disseminate this work through PICANet and PICS. We will submit manuscripts to peer reviewed journals, and issue newsletters to PCAG and disseminate to other interested parents via PCAG.

Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE