番茄社区

SAN DIEGO -- Children born to mothers with systemic lupus erythematosus have twice the risk for autism spectrum disorders (ASD) as those whose mothers are unaffected, a Canadian researcher reported here.

In multivariate analyses that adjusted for potential confounders, offspring of mothers with lupus had a hazard ratio for ASD of 2.31 (95% CI 1.03-5.16), which was "substantial" and statistically significant, according to Evelyne Vinet, MD, of McGill University in Montreal.

"However, the absolute risk is small, at 1.4% versus 0.6%, and women with lupus shouldn't be alarmed," she said during a press briefing at the annual meeting of the American College of Rheumatology.

The rationale for undertaking this study came from recent experimental evidence suggesting that in animal models, in utero exposure to autoantibodies such as N-methyl-D-aspartate receptor antibodies and antiphospholipid antibodies, as well as to cytokines such as interleukin 6, was associated with changes in brain development and behavioral abnormalities.

In addition, some small studies have suggested a possible link between maternal lupus and problems such as learning disabilities and dyslexia in their children.

To examine the possibility of a link between maternal lupus and ASD, Vinet and colleagues analyzed data from the Offspring of Systemic Lupus Erythematosus mothers Registry (OSLER).

This database includes all women who have been hospitalized or referred to a physician for lupus between 1989 and 2009.

Controls were chosen from a Quebec universal healthcare administrative database, and data from a public drug plan were analyzed to identify possible effects of in utero drug exposure.

In this analysis, 509 women and 719 children were matched with 5,824 matched maternal controls and 8,493 control children. Mean follow-up was 9 years.

Comparisons of mothers with lupus and controls found no significant differences for race or ethnicity or education level.

In addition, obstetrical complications including preterm birth, infants being small for gestational age, or gestational diabetes weren't significantly different between the two groups.

In the subsample of women included in the public drug registry, there were 18 cases of ASD, 16 of which had not been exposed to any medications during pregnancy. One case had been exposed to a corticosteroid and one control had been exposed to an anticonvulsant.

Limitations of the study included the possibility of unmeasured confounders such as smoking and obesity and a lack of information about potentially important autoantibodies such as anti-DNA and antiphospholipid antibodies.

"Further research is needed on the role of lupus-related antibodies such as N-methyl-D-aspartate receptor antibodies, and more experience will be needed about medication exposures," Vinet concluded.

Work on the role of antibodies and autoimmunity has already been pioneered by , and colleagues from the Feinstein Institute for Medical Research in Manhasset, N.Y., Vinet noted in her presentation.

Recently, Diamond's group

"We found that among 3,000 women with autistic kids, 10% had brain-reactive antibodies, and the mothers also were more likely to have anti-nuclear antibodies and autoimmune disease," Diamond told 番茄社区.

"Those brain-reactive antibodies don't harm the mother herself unless there is an insult to her blood-brain barrier, but fetal brains don't have a fully formed blood-brain barrier, so in the second trimester those antibodies can cross the placenta and may adversely affect the developing fetal brain," she explained.

She and her colleagues have been experimenting with giving brain-reactive autoantibodies to mice, with the goal of identifying potential decoy antigens that might be able to provide protection to the developing brain in humans.

"The potential for changes in practice [is] so clear," she observed.

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