Maternal Autoimmune Disease Linked to Higher Risk of Mental Disorders in Offspring

Hua He, MD, PhD

The prevalence of autoimmune disease surpasses 5% and yields a high burden. Most autoimmune diseases are more common in women during their childbearing years.

Maternal immune activation during pregnancy is associated with higher risks of several mental disorders that present in offspring during childhood. However, there's little known about the relationship between maternal autoimmune disease and the mental health of offspring during and after childhood.

Investigators explored this relationship by conducting a population-based nationwide cohort study. The team was led by Hua He, MD, PhD, Developmental and Behavioral Pediatric Department and Child Primary Care Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.

Reviewing the Data

The main outcome was mental disorders, defined by hospital diagnoses, in offspring. Categories included any mental disorder, organic disorders, substance use disorders, schizophrenia, mood disorders, neurotic disorders, obsessive-compulsive disorder (OCD), eating disorders, personality disorders, intellectual disability, developmental disorders, childhood autism, behavioral disorders, attention-deficit hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) or conduct disorder (CD).

Data for the study were obtained from Danish national registers and analyses were performed from March 2020-September 2021. Investigators identified 2,272,472 live-born singletons born in Denmark from 1978-2015 from the Danish Medical Birth Registry.

After the exclusion of 18,239 infants due to death or emigration the final cohort total was 2,254,234 births with 38,916,359 person-years. An infant was considered to be prenatally exposed to maternal autoimmune disease if they were born to a mother diagnosed with autoimmune disease before childbirth.

Categorizing Risk

Ultimately, results showed that prenatal exposure to maternal autoimmune diseases was linked to increased risks of mental disorders in offspring. An association between the presence of maternal type 1 diabetes and rheumatoid arthritis during pregnancy and mental health in offspring up to early adulthood was revealed in the data.

The follow-up period in this cohort study lasted up to 38 years. Offspring who had any exposure to maternal autoimmune diseases had a 16% higher risk of a mental disorder diagnosis compared with the unexposed offspring.

When investigators classified autoimmune diseases by organ system, they discovered that children had an increased risk of mental disorders for most system types, but the highest risk was observed for primary biliary cirrhosis.

"The 5 most common maternal autoimmune diseases associated with the overall risk of mental disorders in offspring were type 1 diabetes (HR, 1.24; 95% CI, 1.18-1.30), rheumatoid arthritis (HR, 1.25; 95% CI, 1.14-1.38), systemic lupus erythematosus (HR, 1.34; 95% CI, 1.13-1.60), multiple sclerosis (HR, 1.21; 95% CI, 1.08-1.36), and psoriasis vulgaris (HR, 1.24; 95% CI,1.14-1.36)," investigators wrote.

The study "Association of Maternal Autoimmune Diseases With Risk of Mental Disorders in Offspring in Denmark" was published in JAMA Network Open.