Dr. Mayes has received consulting fees, speaking fees, and/or honoraria from Actelion, United Therapeutics, and Gilead (less than $10,000 each).
Separate influences of birth order and gravidity/parity on the development of systemic sclerosis
Article first published online: 28 JAN 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis Care & Research
Volume 62, Issue 3, pages 418–424, March 2010
How to Cite
Cockrill, T., del Junco, D. J., Arnett, F. C., Assassi, S., Tan, F. K., McNearney, T., Fischbach, M., Perry, M. and Mayes, M. D. (2010), Separate influences of birth order and gravidity/parity on the development of systemic sclerosis. Arthritis Care Res, 62: 418–424. doi: 10.1002/acr.20096
- Issue published online: 25 FEB 2010
- Article first published online: 28 JAN 2010
- Accepted manuscript online: 28 JAN 2010 12:00AM EST
- Manuscript Accepted: 15 OCT 2009
- Manuscript Received: 15 JUN 2009
- National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grant Numbers: N01-AR-02251, R01-AR-055258, IP50-AR-44888, IP50-AR-054144
- The University Clinical Research Center by the University of Texas Health Science Center at Houston. Grant Numbers: M01-RR-02558, UL1-RR-024148
- The University of Texas Medical Branch. Grant Numbers: M01-RR-00073, U54-RR-026141
- Clinical and Translational Science Award. Grant Numbers: M01-RR-01346, UL1-RR-025767
Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma).
Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister.
Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06–1.50 for birth order 2–5; OR 2.22, 95% CI 1.57–3.15 for birth order 6–9; and OR 3.53, 95% CI 1.68–7.45 for birth order 10–15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8).
Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility.