Mutual Risk Factors for Pediatric Autoimmune Diseases in Different Stages of Childhood: A register-based longitudinal study using the Finnish Health in Teens (Fin-HIT) cohort

For unknown reasons, the incidences of many chronic pediatric autoimmune diseases have been increasing in the past decade, placing long-term burdens on families and healthcare systems. To prevent the rising numbers of these diseases, it is important to find their potential risk factors.

The general aim of this study was to search for mutual environmental factors that might contribute to overall development of pediatric autoimmune diseases, represented by type 1 diabetes (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD). These diseases were chosen due to their chronic nature and similarities in their pathogenesis. The specific aim was to estimate the likelihood of developing autoimmune diseases after exposures to potential environmental risk factors at different stages of childhood.

This register-based longitudinal study utilized The Finnish Health in Teens (Fin- HIT) cohort – a nationwide prospective cohort to address health behaviors of Finnish children and adolescents, comprising over 11,000 children (born 2000-2005) without specific exclusion criteria. The participants were recruited through schools, and baseline data collection was performed in 2011–2014. At school, the participants were asked to answer a questionnaire on their dietary habits, and their height, weight, and waist circumference were measured in a standardized way by trained fieldworkers.

The children in the Fin-HIT cohort were followed-up for a median of 16.6 years through national health registers. Data on autoimmune diagnoses (DM, JIA, and IBD) from birth until the end of the follow-up were obtained from the Special Reimbursement Register, and data on thyroxin (as an indicator for AIT diagnosis) and outpatient antibiotic purchases were obtained from the Drug Purchase Register. Both of these registers are maintained by the Social Insurance Institution (i.e KELA). Maternal and perinatal data were obtained from the Medical Birth Register maintained by the Finnish Institute for Health and Welfare.

By the end of the follow-up, 245 (2.2%) children received primary diagnosis, of which 102 were DM, 61 were AIT, 54 were JIA, and 28 were IBD. Nine children also had a secondary diagnosis (7 were AIT, 1 was JIA, and 1 was IBD), comprising a total of 254 diagnoses. The incidence for each diagnosis per 100,000 children/year were 106.1 for DM, 46.0 for AIT, 55.0 for JIA, and 23.7 for IBD.

Children who developed studied autoimmune diseases were compared with those who did not. The analyzed risk-factor variables were: (1) maternal and perinatal factors (including gestational age and mode of delivery); (2) frequency and types of antibiotic exposures throughout childhood; and (3) dietary patterns (including eating habits and the consumption frequencies of sugary products, fruit, and vegetables), overweight (based on BMI categories), and central obesity (present when weight to height ratio was ≥0.5) of school-aged children. The likelihood of developing an autoimmune disease was estimated using Odds Ratio (OR).

Preterm birth (
Conclusions: Preterm birth, exposures to macrolides, and central obesity in school- aged children were identified as shared risk factors for pediatric autoimmune diseases in this study. The detailed mechanism on how these potential risk factors are related to the development of autoimmune diseases warrants further studies.