Children born to mothers with lupus have twice the risk of autism spectrum disorders

According to research presented this week at the American College of Rheumatology Annual Meeting in San Diego, children born to mothers with lupus may be at twice the risk of autism spectrum disorders than those born to mothers without the disease.

Systemic lupus erythematosus, also called SLE or lupus, is a chronic inflammatory disease that can affect the skin, joints, kidneys, lungs, nervous system, and/or other organs of the body. The most common symptoms include skin rashes and arthritis, often accompanied by fatigue and fever. Lupus occurs mostly in women, typically developing in individuals in their twenties and thirties - prime child-bearing age.

Recent experimental studies suggest exposure to a mother's antibodies and cytokines while in the womb are important risk factors for autism spectrum disorders (commonly called ASD). Interestingly, women with lupus display autoantibodies and cytokines, which — when studied in animals — have been shown to alter fetal brain development and induce behavioural irregularities in offspring.

Despite these studies, no studies have specifically assessed the risk of ASD in children of women with lupus, and researchers recently aimed to determine if children born to these mothers might have an increased risk of ASD when compared to children born to mothers without lupus.

"A handful of small studies suggest an increased risk of learning disabilities in children born to women with lupus. However, no study has specifically assessed the risk of ASD in offspring of mothers with lupus, explains Evelyne Vinet, MD, FRCPC; assistant professor, Department of Rheumatology; McGill University Health Centre, Montreal; and lead investigator in the study. "We undertook this study because women with lupus often ask: 'Will my disease affect the future health of my children?' By providing evidence to answer this relevant question, our study will help clinicians to appropriately counsel women with lupus who are planning a pregnancy."

The Offspring of Systemic Lupus Erythematosus mothers Registry ( OSLER) is a large, Canadian, population-based cohort which includes all women who have had one or more hospitalizations for childbirth after lupus diagnosis as identified through health care databases between the years of 1989 and 2009. Using OSLER, Dr. Vinet's team compared 719 children born to 509 mothers with lupus to 8,493 children born to 5,824 randomly-selected women without the disease.

The average age of mothers in the study was just over 30 years, and the average time of follow up for the children in the study was just over nine years. Dr. Vinet's team matched each mother with lupus to at least four women without the disease, based on their age and the year they delivered their children. The researchers also took into consideration each mother's demographics, sex and birth order of the children delivered, and obstetrical complications.

Dr. Vinet's team discovered that children born to mothers with lupus had more ASD diagnoses compared to the children born to mothers without the disease (1.4 percent vs. 0.6 percent, respectively). Additionally, the researchers found that children born to mothers with lupus might be diagnosed with ASD earlier in life - with an average of 3.8 years at the time of diagnosis (compared to 5.7 years in children born to mothers without lupus).

Finally, Dr. Vinet's team looked at whether medications taken during pregnancy potentially played a role in ASD diagnosis in this study. They looked at a smaller group of 1,925 children, whose mothers had public drug coverage, and found exposures to medications during pregnancy were rare. In fact, in the 18 ASD cases observed in offspring of lupus mothers with public drug coverage, none of the children were exposed to antimalarials, antidepressants, or immunosuppressants during pregnancy. And, only one child born to a mother with lupus and another born to a mother without the disease were exposed to corticosteroids and anticonvulsants, respectively.

"The findings from this study suggest that, although the absolute risk is relatively small, when compared to children from the general population, children born to women with lupus have a two-fold increased risk of autism spectrum disorders," says Dr. Vinet. "Hopefully, this study will prompt further research on the potential role of lupus-related autoantibodies, such as N-methyl-D-aspartate receptor antibodies, in ASD. In the meantime, women with lupus who are contemplating a pregnancy should discuss with their physician to ideally plan the pregnancy at a time of low disease activity and review the safety of their medications."