. 2014 Nov 18;83(21):1923-9.

doi: 10.1212/WNL.0000000000001001. Epub 2014 Oct 22.

Protective environmental factors for neuromyelitis optica

Jennifer Graves¹, Siri Grandhe², Kelley Weinfurtner², Lauren Krupp², Anita Belman², Tanuja Chitnis², Jayne Ness², Bianca Weinstock-Guttman², Mark Gorman², Marc Patterson², Moses Rodriguez², Tim Lotze², Gregory Aaen², Ellen M Mowry², John W Rose², Timothy Simmons², T Charles Casper², Judith James², Emmanuelle Waubant²; US Network of Pediatric Multiple Sclerosis Centers

Collaborators, Affiliations

Collaborators

US Network of Pediatric Multiple Sclerosis Centers:
Jayne Ness, Yolanda Harris, Mark Gorman, Leslie Benson, Gregory Aaen, Tanuja Chitnis, J Moses Rodriguez, Lauren Krupp, Anita Belman, Tim Lotze, Bianca Weinstock-Guttman, O Farooq, Emmanuelle Waubant, Jennifer Graves, T Charles Casper, John Rose, Shelly Roalstad, Tyler Hunt, Cody Olsen, Timothy Simmons, Wendy Weber

Affiliations

¹ From the Department of Neurology (J.G., K.W., E.W.), University of California, San Francisco; Virginia Commonwealth Medical School (S.G.); Lourie Center for Pediatric MS (L.K., A.B.), Stony Brook Children's Hospital, NY; Partners MS Center (T.C.), Massachusetts General Hospital for Children, Harvard Medical School; UAB Center for Pediatric Onset Demyelinating Disease (J.N.), Children's Hospital of Alabama; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric Multiple Sclerosis and Related Diseases Program (M.G.), Boston Children's Hospital, MA; Mayo Clinic's Pediatric MS Center (M.P., M.R.), Rochester, MN; Blue Bird Circle Multiple Sclerosis Center (T.L.), Texas Children's Hospital, Houston; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Multiple Sclerosis Center (E.M.M.), Johns Hopkins University, Baltimore, MD; Department of Pediatrics (J.W.R., T.S., T.C.C.), University of Utah, Salt Lake City; Oklahoma Medical Research Foundation (J.J.), Oklahoma City; and Department of Pediatrics (E.W.), UCSF Benioff Children's Hospital. Jennifer.Graves@ucsf.edu.
² From the Department of Neurology (J.G., K.W., E.W.), University of California, San Francisco; Virginia Commonwealth Medical School (S.G.); Lourie Center for Pediatric MS (L.K., A.B.), Stony Brook Children's Hospital, NY; Partners MS Center (T.C.), Massachusetts General Hospital for Children, Harvard Medical School; UAB Center for Pediatric Onset Demyelinating Disease (J.N.), Children's Hospital of Alabama; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric Multiple Sclerosis and Related Diseases Program (M.G.), Boston Children's Hospital, MA; Mayo Clinic's Pediatric MS Center (M.P., M.R.), Rochester, MN; Blue Bird Circle Multiple Sclerosis Center (T.L.), Texas Children's Hospital, Houston; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Multiple Sclerosis Center (E.M.M.), Johns Hopkins University, Baltimore, MD; Department of Pediatrics (J.W.R., T.S., T.C.C.), University of Utah, Salt Lake City; Oklahoma Medical Research Foundation (J.J.), Oklahoma City; and Department of Pediatrics (E.W.), UCSF Benioff Children's Hospital.

PMID: 25339213
PMCID: PMC4248458
DOI: 10.1212/WNL.0000000000001001

Protective environmental factors for neuromyelitis optica

Jennifer Graves et al. Neurology. 2014.

. 2014 Nov 18;83(21):1923-9.

doi: 10.1212/WNL.0000000000001001. Epub 2014 Oct 22.

Authors

Collaborators

US Network of Pediatric Multiple Sclerosis Centers:
Jayne Ness, Yolanda Harris, Mark Gorman, Leslie Benson, Gregory Aaen, Tanuja Chitnis, J Moses Rodriguez, Lauren Krupp, Anita Belman, Tim Lotze, Bianca Weinstock-Guttman, O Farooq, Emmanuelle Waubant, Jennifer Graves, T Charles Casper, John Rose, Shelly Roalstad, Tyler Hunt, Cody Olsen, Timothy Simmons, Wendy Weber

Affiliations

¹ From the Department of Neurology (J.G., K.W., E.W.), University of California, San Francisco; Virginia Commonwealth Medical School (S.G.); Lourie Center for Pediatric MS (L.K., A.B.), Stony Brook Children's Hospital, NY; Partners MS Center (T.C.), Massachusetts General Hospital for Children, Harvard Medical School; UAB Center for Pediatric Onset Demyelinating Disease (J.N.), Children's Hospital of Alabama; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric Multiple Sclerosis and Related Diseases Program (M.G.), Boston Children's Hospital, MA; Mayo Clinic's Pediatric MS Center (M.P., M.R.), Rochester, MN; Blue Bird Circle Multiple Sclerosis Center (T.L.), Texas Children's Hospital, Houston; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Multiple Sclerosis Center (E.M.M.), Johns Hopkins University, Baltimore, MD; Department of Pediatrics (J.W.R., T.S., T.C.C.), University of Utah, Salt Lake City; Oklahoma Medical Research Foundation (J.J.), Oklahoma City; and Department of Pediatrics (E.W.), UCSF Benioff Children's Hospital. Jennifer.Graves@ucsf.edu.
² From the Department of Neurology (J.G., K.W., E.W.), University of California, San Francisco; Virginia Commonwealth Medical School (S.G.); Lourie Center for Pediatric MS (L.K., A.B.), Stony Brook Children's Hospital, NY; Partners MS Center (T.C.), Massachusetts General Hospital for Children, Harvard Medical School; UAB Center for Pediatric Onset Demyelinating Disease (J.N.), Children's Hospital of Alabama; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric Multiple Sclerosis and Related Diseases Program (M.G.), Boston Children's Hospital, MA; Mayo Clinic's Pediatric MS Center (M.P., M.R.), Rochester, MN; Blue Bird Circle Multiple Sclerosis Center (T.L.), Texas Children's Hospital, Houston; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Multiple Sclerosis Center (E.M.M.), Johns Hopkins University, Baltimore, MD; Department of Pediatrics (J.W.R., T.S., T.C.C.), University of Utah, Salt Lake City; Oklahoma Medical Research Foundation (J.J.), Oklahoma City; and Department of Pediatrics (E.W.), UCSF Benioff Children's Hospital.

PMID: 25339213
PMCID: PMC4248458
DOI: 10.1212/WNL.0000000000001001

Abstract

Objective: To determine whether early environmental factors, such as cesarean delivery, breastfeeding, and exposure to smoking or herpes viruses, are associated with neuromyelitis optica (NMO) risk in children.

Methods: This is a case-control study of pediatric NMO, multiple sclerosis (MS), and healthy subjects. Early-life exposures were obtained by standardized questionnaire. Epstein-Barr virus, cytomegalovirus, and herpes simplex virus 1 antibody responses were determined by ELISA. Multivariate logistic regression models were used to adjust for age at sampling, sex, race, and ethnicity.

Results: Early-life exposures were obtained from 36 pediatric subjects with NMO, 491 with MS, and 224 healthy controls. Daycare (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.14, 0.78; p < 0.01) and breastfeeding (OR 0.42, 95% CI 0.18, 0.99; p = 0.05) were associated with lower odds of having NMO compared with healthy subjects. Cesarean delivery tended to be associated with 2-fold-higher odds of NMO compared with having MS/clinically isolated syndrome (OR 1.98, 95% CI 0.88, 4.59; p = 0.12) or with being healthy (OR 1.95, 95% CI 0.81, 4.71; p = 0.14). Sera and DNA were available for 31 subjects with NMO, 189 with MS, and 94 healthy controls. Epstein-Barr virus, herpes simplex virus 1, cytomegalovirus exposure, and being HLA-DRB1*15 positive were not associated with odds of having NMO compared with healthy subjects.

Conclusions: Exposure to other young children may be an early protective factor against the development of NMO, as previously reported for MS, consistent with the hypothesis that infections contribute to disease risk modification. Unlike MS, pediatric NMO does not appear to be associated with exposures to common herpes viruses.

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Conflict of interest statement

J. Graves was supported by the Foundation for Consortium of Multiple Sclerosis Centers and the NIH Bridging Interdisciplinary Research Careers in Women's Health programs (5K12HD052163) during this work. She has been a one-time advisory board participant for EMD Serono. S. Grandhe and K. Weinfurtner report no disclosures relevant to the manuscript. L. Krupp is supported by the National MS Society, NIH, Robert and Lisa Lourie Foundation, Department of Defense. She has received honoraria, consulting payments, grant support, or royalties from Biogen, MedImmune, Novartis, Teva Neuroscience, Sanofi-Aventis, and EMD Serono. A. Belman reports no disclosures relevant to the manuscript. T. Chitnis has served as a consultant for Biogen Idec, Teva Neurosciences, Novartis, Sanofi-Aventis, and has received grant support from NIH, National MS Society, Guthy-Jackson Charitable Foundation, CMSC and Merck-Serono, and Novartis. J. Ness reports no disclosures relevant to the manuscript. B. Weinstock-Guttman received honoraria for serving in advisory boards and educational programs from Teva Pharmaceuticals, Biogen Idec, Novartis, Acorda EMD Serono, Novartis, Genzyme, and Sanofi. She also received support for research activities from the NIH, National Multiple Sclerosis Society, National Science Foundation, Department of Defense, EMD Serono, Biogen Idec, Teva Neuroscience, Novartis, Acorda, Genzyme, and the Jog for the Jake Foundation. M. Gorman, M. Patterson, M. Rodriguez, T. Lotze, and G. Aaen report no disclosures relevant to the manuscript. E. Mowry is supported by the National MS Society and the NIH. She receives free medication for a randomized control trial from Teva Neuroscience. J. Rose has research funding from Teva Neuroscience and Biogen. He is a member of the Medical Advisory Board for the DECIDE trial, which is funded by Biogen and AbbVie. T. Simmons reports no disclosures relevant to the manuscript. T. Casper has been supported by the National MS Society and the NIH (R01NS071463). He is an ad hoc consultant for Biovest International, Inc. J. James reports no disclosures relevant to the manuscript. E. Waubant is funded by the National MS Society, the NIH, and the Race to Erase MS. She has received honorarium from Teva Neuroscience and Genzyme for 2 educational lectures, and is an ad hoc consultant for Actelion, Sanofi-Aventis, and Roche. She is on an advisory board for a clinical trial of Novartis. Go to Neurology.org for full disclosures.

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Protective environmental factors for neuromyelitis optica

Collaborators

Affiliations

Protective environmental factors for neuromyelitis optica

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

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Grants and funding

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Full Text Sources

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