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American Journal of Epidemiology Advance Access originally published online on March 25, 2008
American Journal of Epidemiology 2008 167(11):1281-1286; doi:10.1093/aje/kwn056
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Maternal Age, Exposure to Siblings, and Risk of Amyotrophic Lateral Sclerosis

Fang Fang1, Freya Kamel2, Dale P. Sandler2, Pär Sparén1 and Weimin Ye1

1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
2 National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC

Correspondence to Dr. Fang Fang, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77 Stockholm, Sweden (e-mail: fang.fang{at}ki.se).

Received for publication September 11, 2007. Accepted for publication February 15, 2008.

Between 1987 and 2005, the authors conducted a nested case-control study based on the Swedish Multi-Generation Register to investigate whether early life exposures, namely, maternal age at delivery and exposure to siblings, are associated with an increased risk of amyotrophic lateral sclerosis (ALS). The study comprised 768 ALS cases and five controls per case matched by birth year and gender. Odds ratios and their corresponding 95% confidence intervals for ALS were estimated by conditional logistic regression modeling. Low maternal age (≤20 years) and high maternal age (≥41 years) were both associated with higher risk of ALS (odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.1, 2.0 and OR = 1.7, 95% CI: 1.1, 2.4, respectively). The relative risk of ALS increased slightly with increasing number of younger siblings (OR = 1.1, 95% CI: 1.0, 1.1; p = 0.02). Children whose first younger sibling was born after the age of 6 years had the greatest relative risk (OR = 1.8, 95% CI: 1.2, 2.7). Exposure to older siblings was not associated with the risk of ALS. Although the strength of the observed associations was modest, these results provided further support for the theory that early life exposures might contribute to the disease pathogenesis.

amyotrophic lateral sclerosis; maternal age; risk; siblings


Abbreviations: ALS, amyotrophic lateral sclerosis; CI, confidence interval; ICD, International Classification of Diseases; OR, odds ratio


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