Early Life Factors Influence Risk for Pediatric-Onset Multiple Sclerosis

Maternal illness during pregnancy and parental exposure to pesticides were associated with increased risk for pediatric multiple sclerosis.

VANCOUVER, British Columbia — Results from new research suggest that maternal illness and pesticide-related environmental exposure contribute to risk of pediatric-onset multiple sclerosis (MS), whereas cesarean-section delivery was associated with reduced risk.

The study was presented at the 2016 annual meeting of the American Academy of Neurology (AAN).

Jennifer S. Graves, MD, PhD, a study investigator with the University of California, San Francisco, told Neurology Advisor that early life, including embryogenesis, is a particularly vulnerable time for environmental effects.

“Various forms of stress, toxins, or infectious exposures may alter the immune system in this vulnerable period, leading to disruption of normal immune system development, including self-tolerance, and promote autoimmunity,” she said.

This led Dr Graves and fellow researchers to conduct the present case-control study in which children with MS or clinically isolated syndrome were compared with healthy controls. The children were enrolled at 16 centers that participated in the US Network of Pediatric MS Centers.

Parents completed a comprehensive environmental questionnaire that assessed pregnancy and perinatal factors. The treating neurologist established the case status, which was confirmed by a panel of 3 pediatric MS specialists.

Dr Graves and colleagues utilized multivariable logistic regression analyses to examine the association of environmental factors with case status after adjusting for sex, race, ethnicity, and socioeconomic status.

In all, researchers received questionnaire responses from 275 eligible cases (median age, 15.7 years; 62% female) and 437 healthy controls (median age, 14.5 years; 54% female).

Multivariable analysis indicated that maternal illness during pregnancy increased the likelihood of having MS by 2-fold (95% confidence interval [CI], 1.16-4.19; P=.02), whereas a cesarean-section birth was associated with a 57% reduction (95% CI, 0.21-0.88; P=.02).

“Cesarean section may be protective against MS onset in childhood; this was not an expected result, but may fit with recent data regarding the potential role of gut microorganisms in MS risk,” Dr Graves said. “This risk factor may be more relevant in childhood-onset disease [given the] proximity of the factor to the onset of the disease in this population.”

After adjustment for maternal illness and cesarean-section delivery, there were no associations between MS risk and maternal age, tobacco smoke exposure, maternal body-mass index, and breastfeeding.

In a separate analysis adjusting for sex, race, ethnicity, and socioeconomic status, the researchers found that having a father who worked in a gardening-related occupation (odds ratio [OR]=2.03; 95% CI, 1.07-3.84; P=.03) or any use in household or pesticide-related products (OR=2.56; 95% CI, 1.03-6.37; P=.04) increased the risk for having pediatric MS.

“Pesticides may contribute to MS risk,” Dr Graves said. “Further work is needed to confirm this result, to identify specific agents, and to identify a mechanism by which to explain this association.”

Click here for more coverage from the 68th Annual Meeting of the American Academy of Neurology, April 15-21, 2016, in Vancouver, British Columbia, Canada.


Graves J, Chitnis T, Weinstock-Guttman B, et al. Maternal illness in pregnancy and perinatal exposure to pesticides are associated with risk for pediatric onset MS. Presented at: The 68th Annual Meeting of the American Academy of Neurology; April 15-21, 2016; Vancouver, British Columbia, Canada. Abstract I15.012.