Phenotyping healthcare use before pediatric-onset multiple sclerosis, including by sex and age: A matched cohort study

BACKGROUND: Little is known about the prodrome in pediatric-onset multiple sclerosis (POMS), especially potential age and sex differences. OBJECTIVE: To compare annual hospitalization and physician visit rates overall, and for physician visits, examine sex- and age-group (<12, 12-15, 16 to <18 years) differences, up to 18 years pre-first demyelinating event (pre-index) in 451 POMS and 1420 matched non-multiple sclerosis (MS) individuals. METHOD: Using Ontario administrative data (1991-2020), we estimated rate ratios (RRs) by visit-related diagnosis, sex, and age using over-dispersed-Poisson models. RESULTS: The POMS cohort showed elevated rates by year 1 pre-index ("year -1"), for ill-defined, other-health-contact, mental-, and respiratory-related hospitalizations (RRs ⩾ 3.6). Elevated physician visits began at year -14 for respiratory (RRs ⩾ 1.3), year -13 for endocrine (RRs ⩾ 2.4) and injury-related (RRs ⩾ 1.2), year -12 for ill-defined (RRs ⩾ 1.3), and year -11 for nervous system (RRs ⩾ 4.0) and mental-related (RRs ⩾ 2.0). Nervous system visits showed the largest sex-gap; males with (vs without) MS had elevated RRs from year -12 and females from year -6; both peaked the year pre-index (males: RR = 47.2; 95% confidence interval (CI): 17.3-128.3; females: RR = 17.0; 95% CI: 8.9-32.3). Among 12- to 15-year-olds, elevated rates were sustained for respiratory-related (from year -12, except year -5), injury-related, and ill-defined (from year -13); (all RR ⩾ 1.3), while findings were more sporadic in the other age groups. CONCLUSION: Findings suggest prolonged, organ-specific healthcare use pre-POMS, with some sex- and age-related differences indicating pre-onset disease heterogeneity.