Maternal weight and hypertension as risk factors for juvenile idiopathic arthritis: a prospective population-based pregnancy cohort study

OBJECTIVES: The intrauterine environment may influence childhood immune-mediated disease risk. We investigated whether maternal prepregnancy body mass index (BMI), gestational weight gain (GWG) or hypertensive disorders during pregnancy (HDP) were associated with juvenile idiopathic arthritis (JIA) in children and whether genetic susceptibility modified associations. METHODS: We linked the Norwegian Mother, Father and Child Cohort Study (MoBa) to the Norwegian Patient Registry to identify children with JIA. Logistic regression estimated adjusted ORs (aORs) for associations with BMI, GWG and HDPs. Causal mediation analyses assessed whether hypertension mediated the GWG-JIA association. In a genotyped subsample, we tested interactions between exposures and a JIA Polygenic Risk Score (PRS). RESULTS: Among 78 901 eligible children, 265 developed JIA (genotyped subsample: 192 JIA/44 053 non-JIA). By the end of follow-up, all children were ≥14 years old and 85% were ≥16 years old. Maternal prepregnancy BMI was not associated with JIA. Each 1 SD (~6 kg) increase in GWG was associated with modestly higher odds of JIA (aOR 1.12, 95% CI 1.00 to 1.26), particularly among women with prepregnancy obesity (aOR 1.40, 95% CI 1.10 to 1.77). Maternal hypertension and pre-eclampsia were associated with higher JIA risk (aOR 1.43, 95% CI 1.02 to 1.99 and aOR 1.61, 95% CI 1.10 to 2.37). Hypertension did not mediate the GWG-JIA association (p>0.05). Among children with lower PRS, maternal obesity was associated with a lower JIA risk (aOR 0.37, 95% CI 0.17 to 0.80). CONCLUSION: Higher GWG and HDPs were independently associated with increased JIA risk. Genetic susceptibility may modify associations with maternal BMI, supporting a role for pregnancy health in JIA development.