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Background: Hearing loss in newborns and children is a public health concern, due to high prevalence and negative effects on their development. Early detection and intervention of childhood hearing loss may mitigate these negative effects. Population-based newborn hearing screening programs have been established worldwide to identify children at risk for congenital hearing loss and to follow children at risk for late onset or progressive hearing loss. This article presents the protocol for a systematic review that aims to review the risk factors associated with permanent hearing loss in children, including congenital, early, or late onset. Risk factors associated with progressive hearing loss will be investigated as a secondary aim. Methods: Scientific literature from the following databases will be investigated: MEDLINE, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), Embase, and CINAHL. The primary outcome is a permanent bilateral or unilateral hearing loss with congenital onset or onset during childhood (birth to 18 years). The secondary outcome is progressive hearing loss. Studies must report data on risk factors associated with permanent hearing loss; risk factors may be present at birth or later and result in immediate or delayed hearing loss. Randomized controlled trials, quasi-experimental studies, nonrandomized comparative and non-comparative studies, and case series will be included. The risk of bias will be assessed using the Qualitative Assessment Tool for Quantitative Studies (McMaster University). If aggregation of data is possible for a subsection of studies, we will pool data using meta-analysis techniques. If aggregation of data is not possible, a qualitative synthesis will be presented. We will assess the quality and strength of the overall body of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Discussion: The resulting information will inform the update of a provincial audiological surveillance protocol for the Ontario Infant Hearing Program and will be applicable to early hearing detection and intervention (EHDI) programs worldwide. Systematic review registration: We have registered the protocol in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018104121.