Maternal rheumatoid arthritis and risk of autism in the offspring
Weiyao Yin1,2, Mattias Norrbäck3, Stephen Z Levine4
1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Insights
Maternal Rheumatoid Arthritis (RA) before delivery is linked to a higher risk of Autism Spectrum Disorder (ASD) in children. This association, particularly with seronegative RA, suggests non-autoimmune pathways may also contribute to ASD risk.
Area of Science:
- Reproductive Health
- Neurodevelopmental Disorders
- Immunology
Background:
- Maternal Rheumatoid Arthritis (RA) is suspected to elevate offspring Autism Spectrum Disorder (ASD) risk via inflammation/autoimmunity, though the link remains uncertain.
- A prospective, population-based cohort study was designed to investigate the association between maternal RA and ASD in offspring.
Purpose of the Study:
- To examine the association between maternal Rheumatoid Arthritis (RA) and the risk of Autism Spectrum Disorder (ASD) in offspring.
- To explore potential underlying mechanisms by comparing RA with arthralgia, a condition lacking inflammation/autoimmunity.
Main Methods:
- A Swedish cohort study included children born between 1995-2015, with follow-up through 2017.
- ASD and RA diagnoses were confirmed via the National Patient Register.
- Cox regression analysis, adjusted for confounders, quantified the association, examining RA serostatus, etiological subgroups, and timing of exposure. A negative control group (arthralgia) was used to explore mechanisms.
Main Results:
- Maternal RA before delivery was associated with an increased risk of offspring ASD (HR=1.43, 95% CI 1.11-1.84).
- The association was particularly notable for seronegative RA (HR=1.61, 95% CI 1.12-2.30).
- Maternal arthralgia showed a similar increased risk for offspring ASD (HR=1.41, 95% CI 1.24-1.60), while paternal RA and RA diagnosed after delivery did not show a significant association.
Conclusions:
- Maternal RA diagnosed before delivery is associated with an increased risk of offspring ASD in Sweden.
- The similar risk observed with maternal arthralgia suggests that factors beyond autoimmunity/inflammation, potentially acting independently or jointly with RA, may influence ASD risk.
Background:
Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD.
Methods:
We included all children born alive in Sweden from 1995 to 2015, followed up through 2017. Diagnoses of ASD and RA were clinically ascertained from National Patient Register. We quantified the association by hazard ratios (HR) and two-sided 95% confidence intervals (CI), from Cox regression after detailed adjustment for potential confounders. We examined RA serostatus, etiological subgroups and the timing of exposure. To closer examine the underlying mechanism for the association, we included a negative control group for RA, arthralgia, with similar symptomology as RA but free from inflammation/autoimmunity.
Results:
Of 3629 children born to mothers with RA, 70 (1.94%) were diagnosed with ASD, compared to 28 892 (1.92%) of 1 503 908 children born to mothers without RA. Maternal RA before delivery was associated with an increased risk of offspring ASD (HR = 1.43, 95% CI 1.11-1.84), especially for seronegative RA (HR = 1.61, 95% CI 1.12-2.30). No similar association was observed for paternal RA, maternal sisters with RA, or RA diagnosed after delivery. Maternal arthralgia displayed as high risks for offspring ASD as did maternal RA (HR = 1.41, 95% CI 1.24-1.60).
Conclusions:
In Sweden, maternal RA before delivery was associated with an increased risk of offspring ASD. The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA.
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