title: Separate influences of birth order and gravidity/parity on the development of systemic sclerosis.
abstract: 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.
authors.affiliation: University of Texas Health Science Center at Houston, TX 77030, USA.
authors.forename: Tonya
authors.initials: T
authors.lastname: Cockrill
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: del Junco
authors.forename: Frank C
authors.initials: FC
authors.lastname: Arnett
authors.forename: Shervin
authors.initials: S
authors.lastname: Assassi
authors.forename: Filemon K
authors.initials: FK
authors.lastname: Tan
authors.forename: Terry
authors.initials: T
authors.lastname: McNearney
authors.forename: Michael
authors.initials: M
authors.lastname: Fischbach
authors.forename: Marilyn
authors.initials: M
authors.lastname: Perry
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
mesh_terms: 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
references.citation: Immunol Res. 2008;40(2):97-113
references.pmid: 18213524
references.citation: J Rheumatol. 1988 Feb;15(2):202-5
references.pmid: 3361530
references.citation: Arthritis Rheum. 2003 Oct;48(10):2989-90
references.pmid: 14558107
references.citation: Ann Rheum Dis. 2005 Jun;64(6):845-8
references.pmid: 15550532
references.citation: Rheum Dis Clin North Am. 1996 Nov;22(4):751-64
references.pmid: 8923594
references.citation: J Obstet Gynaecol Res. 2009 Apr;35(2):191-202
references.pmid: 19335792
references.citation: Lancet. 1998 Feb 21;351(9102):559-62
references.pmid: 9492775
references.citation: Arthritis Rheum. 1963 Feb;6:70-4
references.pmid: 13930588
references.citation: Arthritis Rheum. 2008 Nov 15;59(11):1661-4
references.pmid: 18975360
references.citation: Ann Rheum Dis. 1988 Jun;47(6):441-4
references.pmid: 3382262
references.citation: Ann Rheum Dis. 2002 Apr;61(4):346-50
references.pmid: 11874839
references.citation: Cell Immunol. 1985 Aug;94(1):73-84
references.pmid: 4016962
references.citation: Cell Immunol. 2007 Jul;248(1):12-7
references.pmid: 17920574
references.citation: J Rheumatol. 1992 Oct;19(10):1575-9
references.pmid: 1464871
references.citation: J Am Acad Dermatol. 1992 Jan;26(1):49-55
references.pmid: 1732335
references.citation: J Reprod Immunol. 2008 Jan;77(1):14-22
references.pmid: 17561268
references.citation: Am J Epidemiol. 2004 Jan 15;159(2):162-6
references.pmid: 14718218
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):705-8
references.pmid: 8570620
references.citation: J Rheumatol. 2001 Mar;28(3):509-13
references.pmid: 11296950
references.citation: Immunology. 2004 Jul;112(3):352-63
references.pmid: 15196202
references.citation: Arthritis Rheum. 2002 Feb;46(2):451-6
references.pmid: 11840448
references.citation: Arthritis Rheum. 1980 May;23(5):581-90
references.pmid: 7378088
references.citation: JAMA. 2004 Mar 3;291(9):1127-31
references.pmid: 14996783
references.citation: J Reprod Immunol. 2000 Jul;47(2):197-206
references.pmid: 10924751
references.citation: BMC Psychiatry. 2004 Nov 27;4:41
references.pmid: 15566576
references.citation: Br J Rheumatol. 1994 Jun;33(6):598-9
references.pmid: 8205416
references.citation: J Reprod Immunol. 2001 Oct-Nov;52(1-2):77-84
references.pmid: 11600179