Is there a sex difference in mortality rates in Paediatric Intensive Care Units: A Systematic Review

Introduction Mortality rates in infancy and childhood are lower in females than males. However, for children admitted to Paediatric Intensive Care Units (PICU), mortality has been reported to be lower in males, although males have higher admission rates. This female mortality excess for the subgroup of children admitted in intensive care is not well understood. To address this, we carried out a systematic literature review to summarise the available evidence. Our review studies the differences in mortality between males and females aged 0 to <18 years, while in a PICU, to examine whether there was a clear difference (in either direction) in PICU mortality between the two sexes, and, if present, to describe the magnitude and direction of this difference. Methods and analysis Any studies that directly or indirectly reported the rates of mortality in children admitted to intensive care by sex were eligible for inclusion. The search strings were based on terms related to the population (those admitted into a paediatric intensive care unit), the exposure (sex), and the outcome (mortality). We used the search databases MEDLINE, Embase, and Web of Science as these cover relevant clinical publications. We assessed the reliability of included studies using a modified version of the risk of bias in observational studies of exposures (ROBINS-E) tool. We considered estimating a pooled effect if there were at least three studies with similar populations, periods of follow-up while in PICU, and adjustment variables. Results We identified 124 studies of which 114 reported counts of deaths by males and females which gave a population of 278,274 children for analysis, involving 121,800 (44%) females and 156,474 males (56%). The number of deaths and mortality rate for females were 5,614 (4.61%), and for males 6,828 (4.36%). In the pooled analysis, the odds ratio of female to male mortality was 1.06 [1.01 to 1.11] for the fixed effect model, and 1.10 [1.00 to 1.21] for the random effects model. Conclusion Overall, males have a higher admission rate to PCU, and a lower overall mortality in PICU. Systematic review registration PROSPERO database reference number CRD42020203009. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement OA ICA-CDRF-2018-04-ST2-049 National Institute for Health and Care Research https://www.fundingawards.nihr.ac.uk/award/ICA-CDRF-2018-04-ST2-049 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files. * HES : Hospital Episode Statistics. 2 ONS : Office of National Statistics. 2 PICU : Paediatric Intensive Care Unit. 1–6, 8, 10, 22–25 PIM : Paediatric Index of Mortality. 10 PRISMA-P : Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. 3 R&D : Research and Development. 38