Mothers with rheumatoid arthritis (RA) diagnosed before delivery may be more likely to have offspring with autism spectrum disorder (ASD), according to results of a prospective population-based cohort study published in Psychological Medicine.
Rheumatoid arthritis is diagnosed in 0.5% to 1% of women of childbearing age. Maternal RA diagnosed before giving birth has been associated with complications during pregnancy, as well as certain neurologic and developmental disorders in offspring.
Researchers assessed the association between maternal RA diagnosed before delivery and risk for ASD in their children.
Children born alive in Sweden from 1995 to 2015 were included in the study and followed-up with until 2017, with clinical diagnoses of both mothers and offspring as reported in the National Patient Register (NPR). Mothers with arthralgia in the absence of RA were included in a control group to examine specific disease pathways based on the presence or absence of joint inflammation and autoimmunity. Relationships between maternal RA and ASD in offspring were assessed, as well as the role of familial factors and serostatus.
A total of 1,507,537 children were included in the study cohort. Of these, 3629 were born to mothers diagnosed with RA before delivery. Overall, 70 (1.94%) of these children were diagnosed with ASD after birth. Of children born to mothers without RA, 28,892 (1.92%) were later diagnosed with ASD. Offspring of mothers diagnosed with RA were more likely to be born prematurely.
Maternal RA diagnosed before giving birth was associated with increased risk of delivering offspring with ASD (hazard ratio [HR], 1.43; 95% CI, 1.11-1.84). Offspring of fathers (HR, 0.88; 95% CI, 0.51-1.51) and maternal sisters (HR, 1.20; 95% CI, 0.86-1.68) diagnosed with RA before delivery were not at increased risk for ASD.
In the control group, 240 children born to mothers with arthralgia were diagnosed with ASD (incidence rate [IR], 281 per 100,000 person-years). The relative risk for offspring ASD in mothers with arthralgia diagnosed before and after delivery were 1.41 (95% CI, 1.24-1.60) and 1.36 (95% CI, 1.27-1.44), respectively.
Seronegative RA was also associated with increased risk for ASD (HR, 1.61; 95% CI, 1.12-2.30).
Study imitations include statistical precision occurring mostly in subgroups, despite a sample size of the general public; and data on disease activity and prenatal medication use were not available.
The study authors concluded, “The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA.”
Yin W, Norrbäck M, Levine SZ, et al. Maternal rheumatoid arthritis and risk of autism in the offspring. Psychol Med. Published online April 24, 2023. doi:10.1017/S0033291723000855