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The impact of lupus on the next generation

BY NICOLA GARRETT

 

Children born to mothers with systemic lupus erythematosus are not at greater risk of a rheumatic autoimmune disease but may be at increased risk of autoimmune diseases not rheumatic in origin, data from a population-based registry study shows.

Autoimmune diseases tend to cluster in families, suggesting a common genetic predisposition and shared environmental factors, Julie Couture, MD, a pediatric rheumatologist at the Hospital for Sick Children in Toronto, and her colleagues, wrote in Arthritis & Rheumatology (doi: 10.1002/art.40570).

However, few have researched the subject and published study results have been conflicting, largely because of their small sample size.

 

“More robust data could be valuable when counseling families, and to prompt further study on the contributions of genetic, environmental, and in utero factors contributing to autoimmune diseases susceptibility,” Dr. Couture and her colleagues wrote.

The team analyzed data from the Offspring of SLE Mothers Registry (OSLER), involving 719 children born to 509 mothers with SLE and an average disease duration of 3.7 years. They matched the data to 5,824 control mothers with SLE who had 8,493 children.

Both groups of mothers had similar demographic characteristics but those with SLE were less likely to be white, had more comorbidities, and experienced substantially more obstetrical complications, such as preterm births and caesarean sections.

Compared with control children, SLE offspring were exposed to drugs more in utero, particularly corticosteroids and antimalarials.

 

After an average follow-up of just over 9 years, results showed that, compared with controls, children born to mothers with SLE had similar records of rheumatic diagnoses (0.14% of children; 95% confidence interval, 0.01-0.90 vs. 0.19% of children; 95% CI, 0.11-0.32).

In a multivariate analysis, the adjusted SLE effect estimate was “inconclusive” for rheumatic autoimmune diseases (odds ratio, 0.71; 95% CI, 0.11-4.82).

However, the authors observed a “trend toward” more nonrheumatic autoimmune diseases in the offspring of mothers with SLE versus controls (1.11%; 95% CI, 0.52-2.27 vs. 0.48%; 95% CI 0.35-0.66). And, in multivariate analysis, SLE offspring had greater than twofold increased risk of nonrheumatic autoimmune diseases, compared with control children (OR, 2.30; 95% CI, 1.06-5.03).

 

When researchers repeated the multivariate analysis after they had controlled for maternal history of nonrheumatic autoimmune diseases, the effect estimates were similar to that of the primary analysis (OR 2.33; 95% CI, 1.04- 5.19).

Crohn’s disease (n = 4; 0.56% of SLE offspring and n = 16; 0.19% of control children) and type 1 diabetes (n = 3; 0.42% of SLE offspring and n = 19; 0.22% of control children) were the most frequently observed diseases in both groups of children.

The observed link was not completely explained by such variables as preterm birth and caesarean section, which have been linked to an increased risk of autoimmune diseases like type 1 diabetes, Dr. Couture and her colleagues said.  For example, when they adjusted for caesarean births, the effect estimates remained similar (OR, 2.27; 95% CI, 1.02 -5.06).

However, the authors cautioned that, while they observed a trend toward more nonrheumatic diseases in SLE offspring, compared with the general population, the absolute numbers were small.

 

When researchers repeated the multivariate analysis after they had controlled for maternal history of nonrheumatic autoimmune diseases, the effect estimates were similar to that of the primary analysis (OR 2.33; 95% CI, 1.04- 5.19).

Crohn’s disease (n = 4; 0.56% of SLE offspring and n = 16; 0.19% of control children) and type 1 diabetes (n = 3; 0.42% of SLE offspring and n = 19; 0.22% of control children) were the most frequently observed diseases in both groups of children.

The observed link was not completely explained by such variables as preterm birth and caesarean section, which have been linked to an increased risk of autoimmune diseases like type 1 diabetes, Dr. Couture and her colleagues said.  For example, when they adjusted for caesarean births, the effect estimates remained similar (OR, 2.27; 95% CI, 1.02 -5.06).

However, the authors cautioned that, while they observed a trend toward more nonrheumatic diseases in SLE offspring, compared with the general population, the absolute numbers were small.

“The occurrence of autoimmune diseases in children born to women with SLE is uncommon, and the vast majority of offspring do not have any autoimmune disease, as far as we have been able to study them,” they added.

Nevertheless, a better understanding of the maternal programming of the fetal immune system could “potentially help explain the increased risk of nonrheumatic autoimmune diseases in SLE offspring.”

Further research is warranted to investigate the relative contribution of genetic factors, shared environmental exposures, as well as in utero exposure to inflammation and maternal autoantibodies, according to the authors, who added that observational studies had shown that rheumatic autoimmune diseases were rarer in childhood and follow-up of OSLER (Offspring of SLE Mothers Registry) offspring into adulthood would be helpful.

Nicola Garrett is a freelance reporter for MDedge News.