Association of clinical and social factors with risk of fracture in children with atopic dermatitis

Children with atopic dermatitis (AD) have multiple risk factors for accidental fractures, injuries that can lead to significant morbidity and mortality. However, little is known about the factors that mediate the relationship between AD and fracture in children.Our purpose was to examine the association of AD with fracture and to identify potential mediating factors.This retrospective cohort study examined children with and without AD from a longitudinal matched cohort database of 353,040 children registered in the national health insurance service and participated in the national health-screening program of Korea. We defined AD using medical claims and medication prescription records. We investigated accidental fracture events between the index date and the end of follow-up in a propensity score-matched cohort. Pre-specified subgroup analyses considered fractures in four different regions of the body. The mediating effects of 10 possible clinical factors (including the use of antihistamines and systemic corticosteroids) and social factors (including nutritional status and parental safety awareness) were determined.There were 145,704 participating children, 20% with AD and 49% girls. Fractures occurred in 6,652 of the children with AD (23%, mean age: 64.6 ± 29.2 months) and in 24,698 of the control group (21%, mean age 65.0 ± 28.9 months). Children with AD had an 8% greater risk of fracture events overall (adjusted relative risk [aRR]: 1.08, 95% CI: 1.05-1.10). In subgroup analysis, AD was related to increased rates of skull and facial bone fracture (aRR: 1.09, 95% CI: 1.04-1.14), for trunk including vertebrae (aRR: 1.58, 95% CI: 1.22- 2.05), and for distal limbs (aRR: 1.11, 95% CI: 1.07-1.15). However, the relationship with proximal limb fracture was insignificant. Duration of systemic corticosteroid prescription was the largest mediating factor, followed by duration of antihistamine prescription, and infant feeding practices. In particular, the duration of systemic corticosteroid prescription was significantly associated with fracture events (incidence: 20.1% at the 25th percentile and 23.6% at the 75th percentile; difference: 3.4% [95% CI: 2.8-4.0%]).Children with AD were related to increased fracture events. The key factors with mediating effects were systemic use of corticosteroid and antihistamine. Infant feeding practices had weaker mediating effects.