Dataset Information

Maternal and Perinatal Exposures Are Associated With Risk for Pediatric-Onset Multiple Sclerosis.

ABSTRACT: OBJECTIVE:To determine if prenatal, pregnancy, or postpartum-related environmental factors are associated with multiple sclerosis (MS) risk in children. METHODS:This is a case-control study of children with MS or clinically isolated syndrome and healthy controls enrolled at 16 clinics participating in the US Network of Pediatric MS Centers. Parents completed a comprehensive environmental questionnaire, including the capture of pregnancy and perinatal factors. Case status was confirmed by a panel of 3 pediatric MS specialists. Multivariable logistic regression analyses were used to determine association of these environmental factors with case status, adjusting for age, sex, race, ethnicity, US birth region, and socioeconomic status. RESULTS:Questionnaire responses were available for 265 eligible cases (median age 15.7 years, 62% girls) and 412 healthy controls (median age 14.6, 54% girls). In the primary multivariable analysis, maternal illness during pregnancy was associated with 2.3-fold increase in odds to have MS (95% confidence interval [CI] 1.20-4.21, P = .01) and cesarean delivery with 60% reduction (95% CI 0.20-0.82, P = .01). In a model adjusted for these variables, maternal age and BMI, tobacco smoke exposure, and breastfeeding were not associated with odds to have MS. In the secondary analyses, after adjustment for age, sex, race, ethnicity, and socioeconomic status, having a father who worked in a gardening-related occupation (odds ratio [OR] 2.18, 95% CI 1.14-4.16, P = .02) or any use in household of pesticide-related products (OR 1.73, 95% CI 1.06-2.81, P = .03) were both associated with increased odds to have pediatric MS. CONCLUSION:Cesarean delivery and maternal health during pregnancy may influence risk for pediatric-onset MS. We report a new possible association of pesticide-related environmental exposures with pediatric MS that warrants further investigation and replication.

SUBMITTER: Graves JS

PROVIDER: S-EPMC5369674 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Maternal and Perinatal Exposures Are Associated With Risk for Pediatric-Onset Multiple Sclerosis.

Graves Jennifer S JS Chitnis Tanuja T Weinstock-Guttman Bianca B Rubin Jennifer J Zelikovitch Aaron S AS Nourbakhsh Bardia B Simmons Timothy T Waltz Michael M Casper T Charles TC Waubant Emmanuelle E

Pediatrics 20170401 4

<h4>Objective</h4>To determine if prenatal, pregnancy, or postpartum-related environmental factors are associated with multiple sclerosis (MS) risk in children.<h4>Methods</h4>This is a case-control study of children with MS or clinically isolated syndrome and healthy controls enrolled at 16 clinics participating in the US Network of Pediatric MS Centers. Parents completed a comprehensive environmental questionnaire, including the capture of pregnancy and perinatal factors. Case status was confi ...[more]

PMID: 28562303

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Project description:ImportancePediatric-onset multiple sclerosis (PoMS) is associated with significant cognitive and physical disability. Whether this disability translates into differences in educational achievements and earnings is unknown.ObjectiveTo evaluate the association between PoMS and educational level and income throughout adulthood.Design, setting, and participantsA prospective register-based cohort study of individuals with PoMS and a population-based matched reference cohort was conducted using nationwide microdata from linked registers in Sweden from January 1, 1990, to December 31, 2016; analyses were completed from May 1, 2019, to September 1, 2020. Of 772 persons with PoMS identified in the Swedish MS registry, 485 had an onset during the period from 1980 to 2014 and had socioeconomic data available. The general population reference cohort without multiple sclerosis (MS) (n = 4850) was randomly selected from the full Swedish population, matched 10:1 on age, sex, and country of birth.ExposurePediatric-onset MS, diagnosed by a neurologist, with onset before 18 years of age.Main outcomes and measuresHighest educational level (elementary school, high school, or university) was assessed using logistic regression. Income, measured as the mean annual earnings from paid work in US dollars, was compared using Tobit models, and net annual sickness absence and disability pension days were compared using zero-inflated negative binomial regression. Earnings and days receiving disability benefits were compared within 4 age periods (19-24, 25-34, 35-44, and 45-54 years).ResultsThe median age of the cohort with PoMS (n = 485) and the matched reference cohort (n = 4850) in 2016 was 32 years (interquartile range, 26-40 years), and most participants were women (348 [71.8%] in the PoMS cohort and 3480 [71.8%] in the matched reference cohort). Persons with PoMS were less likely than persons in the matched reference cohort to attend university (odds ratio, 0.80 [95% CI, 0.66-0.97]) and had significantly lower annual earnings than the reference cohort, ranging from -$1618 (95% CI, -$2558 to -$678) in the youngest age period to -$10 683 (95% CI, -$18 187 to -$3178) in the eldest. Persons with PoMS received higher rates of disability benefits, as sickness absence days in the youngest age period (rate ratio, 3.06 [95% CI, 2.08-4.52]) and disability pension days in the oldest age period (rate ratio, 1.43 [95% CI, 1.11-1.85]).Conclusions and relevanceThis study suggests that having PoMS is associated with less educational achievement, lower earnings, and greater use of disability benefits throughout the working-age life span. As adults, persons with PoMS never earned as much as their counterparts without MS, and they exhibited a heavier reliance on disability benefits.

Project description:BackgroundWe previously reported a relationship between air pollutants and increased risk of pediatric-onset multiple sclerosis (POMS). Ozone is an air pollutant that may play a role in multiple sclerosis (MS) pathoetiology. CD86 is the only non-HLA gene associated with POMS for which expression on antigen-presenting cells (APCs) is changed in response to ozone exposure.ObjectivesTo examine the association between county-level ozone and POMS, and the interactions between ozone pollution, CD86, and HLA-DRB1*15, the strongest genetic variant associated with POMS.MethodsCases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. County-level-modeled ozone data were acquired from the CDC's Environmental Tracking Network. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS was assessed by logistic regression. Interactions between tertiles of ozone level and the GG genotype of the rs928264 (G/A) single nucleotide polymorphism (SNP) within CD86, and the presence of DRB1*15:01 (DRB1*15) on odds of POMS were evaluated. Models were adjusted for age, sex, genetic ancestry, and mother's education. Additive interaction was estimated using relative excess risk due to interaction (RERI) and attributable proportions (APs) of disease were calculated.ResultsA total of 334 POMS cases and 565 controls contributed to the analyses. County-level ozone was associated with increased odds of POMS (odds ratio 2.47, 95% confidence interval (CI): 1.69-3.59 and 1.95, 95% CI: 1.32-2.88 for the upper two tertiles, respectively, compared with the lowest tertile). There was a significant additive interaction between high ozone tertiles and presence of DRB1*15, with a RERI of 2.21 (95% CI: 0.83-3.59) and an AP of 0.56 (95% CI: 0.33-0.79). Additive interaction between high ozone tertiles and the CD86 GG genotype was present, with a RERI of 1.60 (95% CI: 0.14-3.06) and an AP of 0.37 (95% CI: 0.001-0.75) compared to the lowest ozone tertile. AP results indicated that approximately half of the POMS risk in subjects can be attributed to the possible interaction between higher county-level ozone carrying either DRB1*15 or the CD86 GG genotype.ConclusionsIn addition to the association between high county-level ozone and POMS, we report evidence for additive interactions between higher county-level ozone and DRB1*15 and the CD86 GG genotype. Identifying gene-environment interactions may provide mechanistic insight of biological processes at play in MS susceptibility. Our work suggests a possible role of APCs for county-level ozone-induced POMS risk.

Dataset Information

Maternal and Perinatal Exposures Are Associated With Risk for Pediatric-Onset Multiple Sclerosis.

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Maternal and Perinatal Exposures Are Associated With Risk for Pediatric-Onset Multiple Sclerosis.

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