Identification of novel genetic, neurobiological and radio-anatomical biomarkers for risk stratification of sudden unexpected death in infancy and early childhood: the BIOMINRISK study protocol

Abstract

Introduction: The BIOMINRISK project is a national French study aimed at identifying novel biomarkers associated with sudden unexpected death in infancy (SUDI) through a multidisciplinary approach encompassing three key components of intrinsic vulnerability to SUDI: genetic, neurobiological and radio-anatomical. A better understanding of the pathophysiological mechanisms underlying SUDI may enhance the personalisation of prevention strategies and contribute to reducing its incidence.

Methods and analysis: We will analyse data from 250 children under the age of 2 included in the national SUDI registry (the OMIN registry) since 2020 for which biological samples and medical imaging data will have been collected from 15 participating French hospitals. Our investigations will focus on three axes: (1) genetic: we will conduct whole genome sequencing family trio analyses to identify novel variants and genes associated with sudden infant death syndrome (SIDS) by examining SIDS cases along with their two parents; (2) neurobiological: a case-control study will be performed to investigate the roles of various neuromodulators-including serum serotonin, blood butyrylcholinesterase and cerebrospinal fluid orexin-in the arousal regulation in children who have died from SUDI. We will recruit 250 living age-matched and sex-matched controls who will undergo blood tests and lumbar punctures as part of their routine care and (3) radio-anatomical: a case-control study will explore the potential anatomical predisposition to SUDI by assessing upper airway narrowness. We will compare the osseous structures of the upper airways (nasal fossae, hard palate) using geometric morphometrics on CT images. Recruitment of 250 living age-matched and sex-matched controls who have undergone brain CT scans, including facial bones, will be conducted.

Ethics and dissemination: The study has received ethics approval for all three axes. Results will be published in international peer-reviewed journals and presented at national and international conferences.

Trial registration number: NCT06244433.

Keywords: Cot death; Death, Sudden, Cardiac; GENETICS; Neurobiology; PUBLIC HEALTH; Paediatric radiology.

Figure 1. Study schedule of enrolment, examinations and assessments. SIDS, sudden infant death syndrome; SUDI: sudden unexpected death in infancy.