{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:14:40Z","timestamp":1785798880177,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T00:00:00Z","timestamp":1440633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The aim of present study was to check the possible association of potential parental environmental exposures and maternal supplementation intake with the risk of nonsyndromic orofacial clefting (NSOC). A retrospective study comprised 499 cases and 480 controls was conducted in Heilongjiang Province. Chi-square analysis and unconditional multiple logistic regression were used in the study. The results showed that maternal history of fever and the common cold without fever (ORCL\/P = 3.11 and 5.56, 95%CI: 1.67\u20135.82 and 2.96\u201310.47, ORCPO = 3.31 and 8.23, 95%CI: 1.58\u20136.94 and 4.08\u201316.95), paternal smoking and alcohol consumption (ORCL\/P = 2.15 and 5.04, 95%CI: 1.37\u20133.38 and 3.00\u20138.46, ORCPO = 1.82 and 4.40, 95%CI: 1.06\u20133.13 and 2.50\u20137.74), maternal exposure to organic solvents, heavy metals, or pesticides (ORCL\/P = 6.07, 5.67 and 5.97, 95%CI: 1.49\u201324.76, 1.34\u201324.09 and 2.10\u201316.98, ORCPO = 10.65, 7.28 and 3.48, 95%CI: 2.54\u201344.67, 1.41\u201337.63 and 1.06\u201311.46) and multivitamin use during the preconception period (ORCL\/P = 0.06, 95%CI: 0.02\u20130.23, ORCPO = 0.06, 95%CI: 0.01\u20130.30) were associated with cleft lip or without cleft palate (CL\/P) and cleft palate only (CPO). Maternal history of skin disease and negative life events  (ORCL\/P = 12.07 and 1.67, 95%CI: 1.81\u201380.05 and 1.95\u20132.67) were associated with CL\/P. Some potential parental hazardous exposures during the periconception period and maternal use of multivitamins during the preconception period were associated with risk of NSOC.<\/jats:p>","DOI":"10.3390\/nu7095328","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T10:03:37Z","timestamp":1440669817000},"page":"7172-7184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Association of Parental Environmental Exposures and Supplementation Intake with Risk of Nonsyndromic Orofacial Clefts: A Case-Control Study in Heilongjiang Province, China"],"prefix":"10.3390","volume":"7","author":[{"given":"Yanru","family":"Hao","sequence":"first","affiliation":[{"name":"Department of Oral Maxillofacial Surgery, The First Affiliated Hospital, Harbin Medical University, 122 Youzheng Street, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subao","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Harbin Children's Hospital, 57 Youyi Road, Daoli District,  Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Oral Maxillofacial Surgery, The First Affiliated Hospital, Harbin Medical University, 122 Youzheng Street, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Mi","sequence":"additional","affiliation":[{"name":"Department of Oral Maxillofacial Surgery, The First Affiliated Hospital, Harbin Medical University, 122 Youzheng Street, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Maxillofacial Surgery, The First Affiliated Hospital, Harbin Medical University, 122 Youzheng Street, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Oral Maxillofacial Surgery, The First Affiliated Hospital, Harbin Medical University, 122 Youzheng Street, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"An","sequence":"additional","affiliation":[{"name":"Department of Oral Maxillofacial Surgery, The First Affiliated Hospital, Harbin Medical University, 122 Youzheng Street, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Medical Administration, The Second Affiliated Hospital, Harbin Medical University,  246 Xuefu Road, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deshu","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The Fourth Affiliated Hospital, Harbin Medical University,  37 Yiyuan Street, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ydbio.2006.07.042","article-title":"Molecular control of secondary palate development","volume":"301","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/oxfordjournals.epirev.a017947","article-title":"Genetic epidemiology of birth defects: Nonsyndromic cleft lip and neural tube defects","volume":"19","author":"Mitchell","year":"1997","journal-title":"Epidemiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000337464","article-title":"Epidemiology of oral clefts 2012: An international perspective","volume":"16","author":"Mossey","year":"2012","journal-title":"Front. Oral Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"R73","DOI":"10.1093\/hmg\/ddh052","article-title":"Genetics of cleft lip and palate: Syndromic genes contribute to the incidence of non-syndromic clefts","volume":"13","author":"Stanier","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","first-page":"1152","article-title":"Development of the upper lip: Morphogenetic and molecular mechanisms","volume":"235","author":"Jiang","year":"2006","journal-title":"Dev. Dyn. Off. Publ. Am. Assoc. Anat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0301-2115(02)00358-5","article-title":"Nutrient-gene interactions in early pregnancy: A vascular hypothesis","volume":"106","author":"Steegers","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/(SICI)1096-9926(199605)53:5<309::AID-TERA5>3.0.CO;2-W","article-title":"Review of the role of potential teratogens in the origin of human nonsyndromic oral clefts","volume":"53","author":"Wyszynski","year":"1996","journal-title":"Teratology"},{"key":"ref_8","first-page":"13","article-title":"The use of birth defect registries for etiological research: A review","volume":"5","author":"Reefhuis","year":"2002","journal-title":"Community Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1034\/j.1399-0004.2002.610402.x","article-title":"Gene\/environment causes of cleft lip and\/or palate","volume":"61","author":"Murray","year":"2002","journal-title":"Clin. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/bdra.20285","article-title":"Periconceptional health and lifestyle factors of both parents affect the risk of live-born children with orofacial clefts","volume":"76","author":"Krapels","year":"2006","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_11","first-page":"551","article-title":"Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants","volume":"58","author":"Shaw","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/01.jom.0000214466.06076.07","article-title":"Maternal residential proximity to waste sites and industrial facilities and oral clefts in offspring","volume":"48","author":"Brender","year":"2006","journal-title":"J. Occup. Environ. Med. Am. Coll. Occup. Environ. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/bdra.20177","article-title":"Maternal diseases and isolated orofacial clefts in hungary","volume":"73","author":"Metneki","year":"2005","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1365-3016.2009.01025.x","article-title":"Risk factors for oral clefts: A population-based case-control study in Shenyang, china","volume":"23","author":"Wang","year":"2009","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/00001648-199511000-00003","article-title":"Paternal occupation and risk of birth defects in offspring","volume":"6","author":"Schnitzer","year":"1995","journal-title":"Epidemiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.annepidem.2007.04.008","article-title":"Parent\u2019s occupation and isolated orofacial clefts in Norway: A population-based case-control study","volume":"17","author":"Nguyen","year":"2007","journal-title":"Ann. Epidemiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1136\/oem.54.4.223","article-title":"Congenital malformations and maternal occupation: A registry based case-control study","volume":"54","author":"Bianchi","year":"1997","journal-title":"Occup. Environ. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1542\/peds.92.4.559","article-title":"Association of the common cold in the first trimester of pregnancy with birth defects","volume":"92","author":"Zhang","year":"1993","journal-title":"Pediatrics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/bdra.20277","article-title":"Review: Hyperthermia and fever during pregnancy","volume":"76","author":"Edwards","year":"2006","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/(SICI)1096-9926(199811)58:5<209::AID-TERA8>3.0.CO;2-Q","article-title":"Teratogen update: Gestational effects of maternal hyperthermia due to febrile illnesses and resultant patterns of defects in humans","volume":"58","author":"Graham","year":"1998","journal-title":"Teratology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/00001648-200207000-00019","article-title":"Maternal fever, multivitamin use, and selected birth defects: Evidence of interaction?","volume":"13","author":"Botto","year":"2002","journal-title":"Epidemiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1096-9926(199801)57:1<1::AID-TERA1>3.0.CO;2-6","article-title":"Maternal illness, including fever and medication use as risk factors for neural tube defects","volume":"57","author":"Shaw","year":"1998","journal-title":"Teratology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/aje\/kwm146","article-title":"Maternal periconceptional alcohol consumption and risk of orofacial clefts","volume":"166","author":"Romitti","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.ijporl.2011.02.018","article-title":"Parental exposures and risk of nonsyndromic orofacial clefts in offspring: A case-control study in Greece","volume":"75","author":"Mirilas","year":"2011","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_25","first-page":"183","article-title":"The effect of teratogens on maternal corticosterone levels and cleft incidence in A\/J mice","volume":"12","author":"Hansen","year":"1992","journal-title":"J. Craniofac. Genet. Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1016\/j.brainres.2009.08.057","article-title":"Altered gene expression in neural crest cells exposed to ethanol in vitro","volume":"1305","author":"Wentzel","year":"2009","journal-title":"Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1097\/01.ede.0000259986.85239.87","article-title":"Maternal stressful life events and risks of birth defects","volume":"18","author":"Carmichael","year":"2007","journal-title":"Epidemiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/ppe.12123","article-title":"Maternal stressors and social support as risks for delivering babies with structural birth defects","volume":"28","author":"Carmichael","year":"2014","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1097\/PRS.0000000000000778","article-title":"Parental health and social support in the first trimester of pregnancy and the risk of oral clefts: A questionnaire-based, case-control study","volume":"135","author":"Ma","year":"2015","journal-title":"Plast. Reconstruct. Surg."},{"key":"ref_30","first-page":"141","article-title":"Involvement of glucocorticoids in the development of the secondary palate","volume":"13","author":"Salomon","year":"1979","journal-title":"Differ. Res. Biol. Divers."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/tera.1420260306","article-title":"Vitamin B6 reduces cortisone-induced cleft palate in the mouse","volume":"26","author":"Yoneda","year":"1982","journal-title":"Teratology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/1096-9926(200102)63:2<79::AID-TERA1013>3.0.CO;2-3","article-title":"Maternal multivitamin use and orofacial clefts in offspring","volume":"63","author":"Itikala","year":"2001","journal-title":"Teratology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1542\/peds.104.6.e66","article-title":"Dose-dependent effect of folic acid on the prevention of orofacial clefts","volume":"104","author":"Czeizel","year":"1999","journal-title":"Pediatrics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/S1701-2163(16)32685-8","article-title":"Pre-conceptional vitamin\/folic acid supplementation 2007: The use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies","volume":"29","author":"Wilson","year":"2007","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/j.1753-4887.2011.00425.x","article-title":"Vitamin A and clefting: Putative biological mechanisms","volume":"69","author":"Ackermans","year":"2011","journal-title":"Nutr. Rev."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/7\/9\/5328\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:47:29Z","timestamp":1760215649000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/7\/9\/5328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,27]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2015,9]]}},"alternative-id":["nu7095328"],"URL":"https:\/\/doi.org\/10.3390\/nu7095328","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,27]]}}}