Maternal systemic autoimmune rheumatic diseases were associated with a higher hazard of childhood mental disorder diagnoses, including anxiety disorders and several neurodevelopmental disorders, in a nationwide retrospective cohort study published in Lupus Science & Medicine.
Investigators analyzed nearly 2 million singleton live births in Taiwan from 2004 to 2015 using the Taiwan Maternal and Child Health Database linked with the Taiwanese Birth Registry, Death Registry, catastrophic illness records, and national health insurance claims. The analysis included 3,907 offspring born to mothers with systemic autoimmune rheumatic diseases (SARDs) and 1,946,061 born to mothers without autoimmune rheumatic diseases.
Maternal SARDs included systemic lupus erythematosus (SLE), rheumatoid arthritis, primary Sjogren’s syndrome, idiopathic inflammatory myositis, systemic sclerosis, and systemic vasculitis. Maternal diagnoses were restricted to those approved for catastrophic illness certificates prior to delivery. Approval required clinical and laboratory information and review based on classification criteria for each disease. Childhood mental disorders were identified by at least 1 relevant diagnosis in an inpatient record or at least 2 diagnoses in outpatient records.
Investigators used Cox proportional hazards models adjusted for maternal age, maternal and paternal psychiatric history, maternal tobacco use, parity, urbanicity of residence, family income, birth sex, and birth cohort year. Investigators also performed causal mediation and sensitivity analyses.
During follow-up through the end of 2021, childhood mental disorders were diagnosed in 774 offspring (20%) of mothers with SARDs and 306,907 offspring (16%) of mothers without SARDs. Maternal SARDs were associated with a 30% higher adjusted hazard of childhood mental disorders. Higher hazards were observed among offspring of mothers with SLE, primary Sjogren’s syndrome, idiopathic inflammatory myositis, and systemic sclerosis. Adjusted analyses did not show statistically significant associations for rheumatoid arthritis or systemic vasculitis.
Maternal SARDs were also associated with higher hazards of anxiety disorders and neurodevelopmental disorders overall, including intellectual disability, attention-deficit/hyperactivity disorder, specific learning disorders, and motor disorders. The investigators did not detect an association with autism spectrum disorder.
Mediation analyses suggested that low birth weight partly mediated the association between maternal SARDs and childhood mental disorders, with an estimated 19% mediated. Associations were attenuated following additional adjustment for antirheumatic medication prescriptions during pregnancy.
The investigators noted that they lacked data on maternal SARD disease activity during pregnancy and several potential confounders, including maternal obesity and alcohol consumption. Maternal smoking data were unavailable, and diagnoses and medication prescriptions related to nicotine dependence were used as a proxy for tobacco use, which may have underestimated the true prevalence of smoking. Misclassification of maternal SARD diagnoses was possible despite the use of critical illness certificate-related diagnoses, and using claims data to identify childhood mental disorders may also have underestimated their incidence. Residual confounding from maternal genetics, lifestyle, and environmental factors also could not be excluded, and causality had not been established.
“Our findings suggest the need for monitoring [mental disorders] in offspring born to mothers with SARDs in clinical practice with multidisciplinary care,” wrote lead author Ya-Chun Huang of the Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine at National Cheng Kung University Hospital, College of Medicine in Tainan City, Taiwan, and colleagues.
Disclosures: The study was funded by the US National Institutes of Health, Alex’s Lemonade Stand Foundation, Taiwan National Science and Technology Council, National Science and Technology Council, and National Health Research Institutes. Full disclosures can be found in the published study.
Source: Lupus Science & Medicine
