{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T20:19:09Z","timestamp":1778703549542,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,1,28]],"date-time":"2010-01-28T00:00:00Z","timestamp":1264636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>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\u2010term effects that permit fetal survival as well as longer\u2010term effects that could influence late\u2010onset 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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case\u2010sibling 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\u2010affected and one unaffected sister.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u20131.50 for birth order 2\u20135; OR 2.22, 95% CI 1.57\u20133.15 for birth order 6\u20139; and OR 3.53, 95% CI 1.68\u20137.45 for birth order 10\u201315). 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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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\u2010associated events, including but not limited to microchimerism, plays a role in SSc susceptibility.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.20096","type":"journal-article","created":{"date-parts":[[2010,1,28]],"date-time":"2010-01-28T15:03:49Z","timestamp":1264691029000},"page":"418-424","source":"Crossref","is-referenced-by-count":35,"title":["Separate influences of birth order and gravidity\/parity on the development of systemic sclerosis"],"prefix":"10.1002","volume":"62","author":[{"given":"Tonya","family":"Cockrill","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah J.","family":"del Junco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank C.","family":"Arnett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shervin","family":"Assassi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filemon K.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry","family":"McNearney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Fischbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilyn","family":"Perry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen D.","family":"Mayes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,2,25]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2004.01925.x"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780060108"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/33.6.598"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11297"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.9.1127"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.4.346"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)08357-8"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(01)00116-4"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(92)70005-Z"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(85)90086-3"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.2.705"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh027"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10178"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24198"},{"key":"e_1_2_7_16_2","first-page":"509","article-title":"Relationship between parity and clinical and biological features in patients with systemic sclerosis","volume":"28","author":"Launay D","year":"2001","journal-title":"J Rheumatol"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"e_1_2_7_18_2","first-page":"202","article-title":"Scleroderma (systemic sclerosis): classification, subsets and pathogenesis","volume":"15","author":"Leroy EC","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_7_19_2","first-page":"268","volume-title":"Biostatistical genetics and genetic epidemiology","author":"Gauderman WJ","year":"2002"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-4-41"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471722146"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-857X(05)70299-4"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(00)00054-1"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2007.05.006"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0756.2008.00963.x"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2007.04.007"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-007-8005-x"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.029314"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.47.6.441"},{"key":"e_1_2_7_30_2","first-page":"1575","article-title":"Reproductive function prior to disease onset in women with scleroderma","volume":"19","author":"Englert H","year":"1992","journal-title":"J Rheumatol"}],"container-title":["Arthritis Care &amp; 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