{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T08:07:45Z","timestamp":1777104465218,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,5,13]],"date-time":"2013-05-13T00:00:00Z","timestamp":1368403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>This study examines gene\u2013environment interaction between the <jats:italic>MTHFR<\/jats:italic> C667T polymorphism and folic acid in the etiology of orofacial clefts (OFC). We used a pooled\u2010analytical approach on four studies that used similar methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We used logistic regression to analyze the pooled sample of 1149 isolated cases and 1161 controls. Fetal and maternal <jats:italic>MTHFR<\/jats:italic> C677T genotypes, and maternal periconceptional exposure to smoking, alcohol, vitamin containing folic acid and folic acid supplements were contrasted between the cleft types [non\u2010syndromic clefts lip or without cleft palate (CL(P)) and non\u2010syndromic cleft palate (CP)] and control groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>There was a reduced risk of CL(P) with maternal folic acid use (<jats:italic>p<\/jats:italic>\u2009=\u20090.008; OR\u2009=\u20090.70, 95% CI: 0.65\u20130.94) and with supplements containing folic acid (<jats:italic>p<\/jats:italic>\u2009=\u20090.028, OR\u2009=\u20090.80, 95% CI: 0.65\u20130.94). Maternal smoking increased the risk of both CL(P) (<jats:italic>p<\/jats:italic>\u2009&lt;\u200910 <jats:italic>e\u2212<\/jats:italic>3; OR\u2009=\u20091.62, 95% CI: 1.35\u20131.95) and CP (<jats:italic>p<\/jats:italic>\u2009=\u20090.028; OR\u2009=\u20091.38, 95% CI: 1.04\u20131.83). No significant risk was observed with either maternal or fetal <jats:italic>MTHFR<\/jats:italic> C677T genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>This individual participant data (IPD) meta\u2010analysis affords greater statistical power and can help alleviate the problems associated with aggregate\u2010level data\u2010sharing. The result of this IPD meta\u2010analysis is consistent with previous reports suggesting that folic acid and smoking influence OFC outcomes. <jats:italic>Birth Defects Research (Part A) 97:509\u2010514, 2013<\/jats:italic>. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23133","type":"journal-article","created":{"date-parts":[[2013,5,13]],"date-time":"2013-05-13T11:45:15Z","timestamp":1368445515000},"page":"509-514","source":"Crossref","is-referenced-by-count":41,"title":["Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: An individual participant data pooled\u2010analysis"],"prefix":"10.1002","volume":"97","author":[{"given":"Azeez","family":"Butali","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Little","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Community Medicine University of Ottawa  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Chevrier","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de Recherche M\u00e9dicale Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvian","family":"Cordier","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de Recherche M\u00e9dicale Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regine","family":"Steegers\u2010Theunissen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Erasmus Medical Center 3000 DR Rotterdam The Netherlands"},{"name":"Department of Epidemiology Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astanand","family":"Jugessur","sequence":"additional","affiliation":[{"name":"Division of Epidemiology Norwegian Institute of Public Health N\u20100403 Oslo Norway"},{"name":"Craniofacial Research Murdoch Childrens Research Institute Royal Children's Hospital 3052 Parkville Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bola","family":"Oladugba","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Nigeria Nsukka Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Mossey","sequence":"additional","affiliation":[{"name":"Dundee Dental School and Hospital University of Dundee  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20595"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32162"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31462"},{"key":"e_1_2_5_5_1","first-page":"CD007950","article-title":"Effects and safety of periconceptional folate supplementation for preventing birth defects","author":"De\u2010Regil LM","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyq139"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwr194"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr106"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.96"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2011.01810.x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyn098"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2009.01577.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwg097"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.3399\/bjgp12X652328"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm262"},{"key":"e_1_2_5_17_1","first-page":"213","article-title":"Tobacco smoking and oral clefts: a meta\u2010analysis","volume":"82","author":"Little J","year":"2004","journal-title":"Bull World Health Organ"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1597\/06-150.1"},{"key":"e_1_2_5_19_1","first-page":"428","article-title":"Folate and clefts of the lip and palate\u2014a UK\u2010based case\u2013control study. 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