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CME / ABIM MOC / CE

Are Maternal Autoimmune Disorders Linked to Mental Illness in Children?

  • Authors: News Author: Heidi Splete; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 6/10/2022
  • THIS ACTIVITY HAS EXPIRED FOR CREDIT
  • Valid for credit through: 6/10/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for pediatricians, psychiatrists, rheumatologists, family medicine and primary care clinicians, nurses, physician assistants, and other members of the health care team for women with autoimmune disorders and their children, who may be at risk for mental illness.

The goal of this activity is for learners to be better able to describe the association between maternal autoimmune diseases before childbirth and risk for mental disorders among offspring up to early adulthood, based on a population-based nationwide cohort study using data from Danish national registers on singletons born in Denmark from 1978 to 2015 with up to 38 years of follow-up.

Upon completion of this activity, participants will:

  • Assess the association between maternal autoimmune diseases before childbirth and risk for mental disorders among offspring up to early adulthood, based on a Danish population-based nationwide cohort study
  • Evaluate the clinical implications of the association between maternal autoimmune diseases before childbirth and risk for mental disorders among offspring up to early adulthood, based on a Danish population-based nationwide cohort study
  • Outline implications for the healthcare team


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News Author

  • Heidi Splete

    Freelance writer, Medscape

    Disclosures

    Heidi Splete has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Stocks, stock options, or bonds: AbbVie (former)

Editor/Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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CME / ABIM MOC / CE

Are Maternal Autoimmune Disorders Linked to Mental Illness in Children?

Authors: News Author: Heidi Splete; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED FOR CREDIT

CME / ABIM MOC / CE Released: 6/10/2022

Valid for credit through: 6/10/2023, 11:59 PM EST

processing....

Clinical Context

Prevalence of autoimmune diseases exceeds 5%, and these diseases carry a high morbidity burden. Most autoimmune diseases are more common in women of reproductive age. Animal studies suggest that maternal immune activation can trigger changes in brain morphology, abnormal neurotransmitter activity, and behavioral deficits in offspring, implicating intrauterine exposure to immunologic insults in the pathophysiology of mental disorders.

Empirical evidence suggests links between certain maternal autoimmune diseases, including type 1 diabetes and rheumatoid arthritis, and specific mental disorders in offspring, including autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD).

Study Synopsis and Perspective

Mental disorders were significantly more likely in children whose mothers had 1 of 5 common autoimmune diseases, a new study has found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as ADHD, but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been "scattered and limited," which "hampered an overall understanding" of the link, Fei Li, MD, the corresponding author of the study, told Medscape Medical News.

Dr Li, from Shanghai Jiao Tong University School of Medicine, in China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks for mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country's National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR], 1.16), with an incidence of 9.38 vs 7.91 per 1000 person-years, the researchers report.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.24), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19) systems.

The 5 autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.35), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk for childhood autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers write.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk for obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, the authors add.

The study findings were limited by several factors, including the lack of data on the potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers note. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria during the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and the ability to consider a range of confounders, the researchers say.

"This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring's mental disorders from childhood through early adulthood," Dr Li told Medscape Medical News.

For clinicians, Dr Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

"Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well," she said.

Pay Early Attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said that previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history--problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr Jay, who was not involved in the research.

"It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options," Dr Jay added.

The authors have reported no relevant financial relationships.

JAMA Netw Open. April 15, 2022.[1]

Study Highlights

  • This population-based nationwide cohort study used data from Danish national registers on 2,254,234 singletons born in Denmark from 1978 to 2015 with up to 38 years of follow-up.
  • Median age at follow-up was 16.7 (interquartile range, 10.5-21.7) years, and 51.28% were male.
  • Maternal autoimmune diseases diagnosed before or during pregnancy were determined from the Danish National Patient Register, and mental disorders in children from hospital diagnoses.
  • 2.26% of infants were born to mothers with autoimmune diseases before childbirth.
  • These had increased risk for overall mental disorders compared with participants without prenatal exposure to autoimmune disease (HR, 1.16; 95% confidence interval [CI], 1.13-1.19; incidence, 9.38 vs 7.91 per 1000 person-years).
  • For autoimmune disease classified by affected organ system, HR was 1.19 for the skin, 1.19 for the endocrine, 1.17 for the nervous, 1.24 for the connective tissue, 1.11 for the gastrointestinal, and 1.10 for the blood systems.
  • The 5 maternal autoimmune diseases most commonly associated with mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.
  • Overall risk in offspring was Increased for most specific autoimmune diseases, but varied (eg, primary biliary cirrhosis: HR, 3.07 [95% CI, 1.75-5.41]; multiple sclerosis, HR, 1.21 [95% CI, 1.08-1.36]).
  • Increased risks for overall mental disorders in offspring occurred in different age groups for maternal type 1 diabetes (aged 1-5 years: HR, 1.35 [95% CI, 1.17-1.57]; 6-18 years: HR, 1.24 [95% CI, 1.15-1.33]; >18 years: HR, 1.19 [95% CI, 1.09-1.30]) and rheumatoid arthritis (1-5 years: HR, 1.42 [95% CI, 1.16-1.74]; 6-18 years: HR, 1.19 [95% CI, 1.05-1.36]; >18 years: HR, 1.28 [95% CI, 1.02-1.60]).
  • After exposure to any maternal autoimmune disease, risk was increased for organic mental disorders (HR, 1.54; 95% CI, 1.21-1.94), schizophrenia (HR, 1.35; 95% CI, 1.21-1.51), obsessive-compulsive disorder (HR, 1.42; 95% CI, 1.24-1.63), mood disorders (HR, 1.12; 95% CI, 1.04-1.21), childhood autism (HR, 1.21; 95% CI, 1.08-1.36], ADHD (HR, 1.19; 95% CI, 1.12-1.26), and intellectual disability (HR, 1.19; 95% CI, 1.07-1.34).
  • The investigators concluded that prenatal exposure to most autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis, was associated with modestly increased risks for overall and type-specific mental disorders in offspring, which varied according to different subtypes of maternal autoimmune diseases and specific mental disorders.
  • Maternal type 1 diabetes and rheumatoid arthritis during pregnancy were associated with offspring's mental health up to early adulthood.
  • Offspring of mothers with autoimmune diseases may benefit from long-term surveillance for a wide spectrum of mental disorders, especially offspring of mothers with type 1 diabetes and rheumatoid arthritis.
  • If these findings are confirmed in future studies, they may have important implications for early screening and appropriate intervention for children at high risk for mental disorders.
  • Varied risk for most specific autoimmune diseases may reflect differences in pathogenicity or degree of autoimmunity and/or statistical variance because of small numbers of events.
  • Potential mechanisms may include genetic risk factors shared by autoimmune diseases and mental disorders.
  • Alternatively, mothers with disturbed autoimmunity before giving birth may transfer autoantibodies to the fetus during pregnancy, activating the child's immune system and altering normal brain development.
  • The finding that children born to mothers with autoimmune diseases diagnosed before childbirth had a higher risk for mental disorders would support the maternal transmission hypothesis suggested by previous animal research.
  • Previous studies suggested that women with autoimmune disease have increased risk for obstetric complications such as preterm birth, which may increase risk for mental disorders in the child.
  • However, in analyses restricted to term births, risk for mental disorders remained increased, suggesting that the associations cannot be explained entirely by this hypothesis.
  • Further studies are needed to clarify the underlying mechanisms, including potential transfer of maternal antibodies to the fetus.
  • Study strengths were use of a population-based registry, large sample size, and ability to consider a range of confounders.
  • Study limitations include lack of data on the potential exacerbation of autoimmune disease activity during pregnancy; potential detection bias, as mothers with chronic autoimmune disease may use health care more frequently; and advances in medical care and changes in diagnostic criteria during the long study, which may have affected exposures and outcomes.
  • In addition, the study could not assess the risk for mental disorders in late adulthood because maximum follow-up was 38 years, and absence of information from primary care and the delayed inclusion of outpatient records might have resulted in underestimation of the associations.

Clinical Implications

  • Prenatal exposure to most autoimmune diseases was associated with modestly increased risks for overall and type-specific mental disorders in offspring.
  • If these findings are confirmed in future studies, they may have important implications for early screening and appropriate intervention for children at high risk for mental disorders.
  • Implications for the Health Care Team: Offspring of mothers with autoimmune diseases may benefit from long-term surveillance for a wide spectrum of mental disorders.

 

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