Potential New Risk Factors for Tourette's, Tics Identified

Deborah Brauser

January 16, 2014

Inadequate maternal weight gain, cannabis use during pregnancy, and birth order have been identified as 3 new potential risk factors for Tourette syndrome and chronic tic disorders in children, new research shows.

A prospective study of 6090 children from the prospective Avon Longitudinal Study of Parents and Children (ALSPAC) showed that less than adequate maternal weight gain during pregnancy and being born first were significantly associated with Tourette syndrome in the offspring by the age of 13 or 14 years.

In addition, maternal cannabis use was significantly associated with chronic tic disorders in children.

All of these risk factors are newly reported pregnancy-related associations for these disorders.

The investigators also found that, as reported in other studies, alcohol use during pregnancy was significantly linked to increased risk for Tourette syndrome.

"I think this study is novel and important because it looked at people before the time that they were born all the way through. So we didn't have the biases that often come from recall," lead author Carol A. Mathews, MD, professor of psychiatry at the University of California–San Francisco and member of the Medical Advisory Board for the Tourette Syndrome Association, told Medscape Medical News.

Dr. Mathews added that although the findings need to be replicated, clinicians should monitor pregnancies for these risk factors if either parent has Tourette syndrome or if there is a family history of the disorder.

"I think the number 1 take-away is to use caution. And if there is a family history, pay a little more attention to the mother-fetal environment," she said.

The study was published in the January issue of the British Journal of Psychiatry.

Unexplained Etiology

Tourette syndrome is a phenomenologically heterogeneous neuropsychiatric disorder comprising multiple motor and vocal tics that begin in early childhood and persist for at least a year. It has a prevalence of 0.3% to 0.8%, whereas chronic tic disorder has a prevalence of 1% to 3%.

The investigators note that previous research examining nongenetic risk factors for these disorders have been conflicting or unclear.

Dr. Carol Mathews

"We know that Tourette syndrome has a very strong genetic component, with 60% due to genetic factors. But that leaves about 40% that is left unexplained," said Dr. Mathews.

"Environmental risk factors are hard to look at because there are millions and millions of potentials out there. But for these neurodevelopmental disorders, it seems pretty clear that one of the strongest candidates for these types of risk factors is the pre- and perinatal exposures," she said.

The ongoing ALSPAC study first enrolled 14,541 pregnant women who resided in the United Kingdom city of Avon and who had delivery dates between April 1991 and December 1992. Questionnaires asking about their offspring's health were mailed periodically.

A primary objective of the study was to determine whether potential risk factors identified for Tourette's in previous studies ― including maternal prenatal smoking and alcohol use, excessive vomiting during pregnancy, complications of delivery, low birth weight, and young gestational age at birth ― could be validated.

Investigators evaluated data from maternal questionnaires, obstetric records, and pediatric medical records for 6090 children.

The primary outcome measures were diagnoses of Tourette syndrome and either Tourette syndrome or chronic tic disorder (grouped together as Tourette syndrome/chronic tic disorder) based on criteria from the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition, Text Revision (DSM-IV-TR) when the children were 13 or 14 years old, as well as tic-related information from maternal questionnaires.

A total of 50 of the teens had Tourette syndrome, and 72 had chronic tic disorder.

Novel Risk Factors

Results showed that the most significant risk factor for development of the disorders was inadequate weight gain during pregnancy (adjusted odds ratio [OR], 9.70; 95% confidence interval [CI], 2.71 - 34.73; P < .0001 for Tourette syndrome only and OR, 3.18; 95% CI, 1.52 - 6.65; P = .002 for Tourette syndrome/chronic tic disorder).

"It's hard to know why this is. We would just say to monitor pregnancies and do everything that we could to ensure that mothers do gain adequate weight," said Dr. Mathews.

"We're not saying mothers with inadequate weight gain will have children with Tourette syndrome. It increases the odds, but the risk to begin with is very low."

In addition, parity (second or later born vs first born) was associated with Tourette syndrome/chronic tic disorder (P = .02), and drinking more than 2 units of alcohol per week during the last 2 months of pregnancy was associated with Tourette syndrome only (P = .03).

Maternal use of cannabis during the last 2 months of pregnancy was significantly associated with both disorders (P = .001 and P = .03, respectively).

However, Dr. Mathews noted caution about this finding. "There were not many people using cannabis in this study, so I'm a little bit less excited about this."

No significant association was found between the disorders and the previously reported risk factors of prenatal maternal smoking, low birth weight, or gestational age.

"This study suggests several potentially modifiable environmental risk factors," write the investigators.

However, they note that the 3 novel factors of maternal inadequate weight gain, parity, and maternal cannabis use need to be further studied in other cohorts.

Surprise Finding

In an accompanying editorial, Daniel A. Gorman, MD, and Elia Abi-Jaoude, MD, both from the University of Toronto, Canada, note that it was surprising that only 1 of the previously identified risk factors ― alcohol use during pregnancy ― was associated with Tourette's and chronic tic disorders.

The editorialists point out that the patterns of associations identified does not suggest an obvious overall mechanism by which environmental risk factors exert their effects. They add that by suggesting that a number of previous associations may be mistaken, the results "bring us a little closer to the truth" about the etiology of Tourette's and chronic tic disorders.

The study authors have not reported any relevant financial relationships.

Br J Psychiatry. 2014;204:40-45, 6-8. Full article, Editorial

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