Separate influences of birth order and gravidity/parity on the development of systemic sclerosis.
OBJECTIVE
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).


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Cockrill
Tonya
T
University of Texas Health Science Center at Houston, TX 77030, USA.
del Junco
Deborah J
DJ
Arnett
Frank C
FC
Assassi
Shervin
S
Tan
Filemon K
FK
McNearney
Terry
T
Fischbach
Michael
M
Perry
Marilyn
M
Mayes
Maureen D
MD
D000328:Adult; D001722:Birth Order; D016022:Case-Control Studies; D005260:Female; D020073:Gravidity; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010298:Parity; D011247:Pregnancy; D012042:Registries; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000209:etiology*; D012801:Sibling Relations
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