{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:36:36Z","timestamp":1760060196434,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: There is a need to search for risk factors of CL\/P, which is the most common facial congenital deformity due to its multifactorial etiology. This study aimed to assess the possible external factors influencing the occurrence of non-syndromic CL\/P. Methods: Retrospective\u2013prospective case record analysis was performed with a sample of 224 consecutively treated patients. The data were obtained from medical records and questionnaires completed by children\u2019s parents. Results: Factors that may have potentially increased the risk of CL\/P were as follows: advanced paternal age (p = 0.014), mother experiencing an infection in the first trimester of pregnancy (p &lt; 0.001), maternal passive smoking (p = 0.001) and stress during the first trimester of pregnancy (p = 0.003). Where mothers were treated with folic acid in the first trimester of pregnancy, in the whole sample the risk of a CL\/P in newborns was reduced (p = 0.007). Advanced paternal age was unrelated to the occurrence of isolated CL, and stress did not increase the risk of isolated CP etiology. Maternal folic acid intake in the first trimester of pregnancy did not influence CLP occurrence. Conclusions: In a group of children from Southeastern Poland, the occurrence of CL\/P was related to advanced maternal age and maternal external risk factors, such as infections, passive tobacco smoking and severe stress during the first trimester of pregnancy. Maternal folic acid intake during the first trimester reduced the risk of CL and CP. Due to the observational nature of the study, the above conclusions should be interpreted as a potential effect.<\/jats:p>","DOI":"10.3390\/jcm14165682","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T14:32:36Z","timestamp":1754922756000},"page":"5682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Etiology of Cleft Lip and\/or Cleft Palate in Southeastern Poland Based on Current Observational Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6240-1297","authenticated-orcid":false,"given":"Margareta","family":"Budner","sequence":"first","affiliation":[{"name":"Department of Plastic Reconstructive and Microsurgery, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5027-8584","authenticated-orcid":false,"given":"Patrycja","family":"Korulczyk","sequence":"additional","affiliation":[{"name":"Medical Simulation Center, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3654-3042","authenticated-orcid":false,"given":"Agnieszka","family":"Lasota","sequence":"additional","affiliation":[{"name":"Department of Jaw Orthopedics, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","unstructured":"(2011). IPDTOCWorking Group Prevalence at birth of cleft lip with or without cleft palate: Data from the International Perinatal Database of Typical Oral Clefts (IPDTOC). Cleft Palate Craniofac J., 48, 66\u201381.","DOI":"10.1597\/09-217"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101e","DOI":"10.1097\/01.PRS.0000164494.45986.91","article-title":"The Spectrum of Orofacial Clefting","volume":"115","author":"Eppley","year":"2005","journal-title":"Plast Reconstr Surg"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.molmed.2011.07.007","article-title":"Breakthroughs in the genetics of orofacial clefting","volume":"17","author":"Mangold","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14364","DOI":"10.1038\/ncomms14364","article-title":"Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity","volume":"8","author":"Yu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1002\/ajmg.c.31381","article-title":"Genetics of cleft lip and cleft palate","volume":"163","author":"Leslie","year":"2013","journal-title":"Am. J. Med. Genet. Part. C Semin. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1597\/12-088","article-title":"Classifying common oral clefts: A new approach after descriptive registration","volume":"51","author":"Luijsterburg","year":"2014","journal-title":"Cleft Palate Craniofac. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cps.2013.12.003","article-title":"Classification, epidemiology, and genetics of orofacial clefts","volume":"41","author":"Watkins","year":"2014","journal-title":"Clin. Plast. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1597\/15-029","article-title":"Subphenotyping and Classification of Orofacial Clefts: Need for Orofacial Cleft Subphenotyping Calls for Revised Classification","volume":"53","author":"McBride","year":"2016","journal-title":"Cleft Palate Craniofac J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/10556656211057368","article-title":"Classifica-tion Systems of Cleft Lip, Alveolus and Palate: Results of an International Survey","volume":"60","author":"Houkes","year":"2023","journal-title":"Cleft Palate Craniofac J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrg2933","article-title":"Cleft lip and palate: Understanding genetic and environmental in-fluences","volume":"12","author":"Dixon","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.12688\/f1000research.9503.1","article-title":"Genetic factors influencing risk to orofacial clefts: Today\u2019s challenges and tomorrow\u2019s opportunities","volume":"5","author":"Beaty","year":"2016","journal-title":"F1000Research"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.ajhg.2016.02.014","article-title":"A genome-wide association study of nonsyndromic cleft palate identifies an etiologic missense variant in GRHL3","volume":"98","author":"Leslie","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1002\/ajmg.a.36691","article-title":"Rare functional variants in genome-wide association identified candidate genes for nonsyndromic clefts in the African population","volume":"164A","author":"Butali","year":"2014","journal-title":"Am. J. Med. Genet A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/bdra.23391","article-title":"Association between polymorphisms at the GREM1 locus and the risk of nonsyn-dromic cleft lip with or without cleft palate in the Polish population","volume":"103","author":"Mostowska","year":"2015","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_16","first-page":"513","article-title":"Cleft Lip and\/or Palate in Infants Prenatally Exposed to Opioids","volume":"59","author":"Louw","year":"2021","journal-title":"Cleft Palate Craniofacial J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1177\/1055665620956869","article-title":"Environmental Risk Factors for Nonsyndromic Cleft Lip and\/or Cleft Palate in Xin-jiang Province, China: A Multiethnic Study","volume":"58","author":"Hong","year":"2021","journal-title":"Cleft Palate Craniofac J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"\u00c1cs, M., Cavalcante, B.G.N., B\u0103n\u0103rescu, M., Wenning, A.S., Hegyi, P., Szab\u00f3, B., Harnos, A., Gerber, G., and Varga, G. (2024). Maternal factors increase risk of orofacial cleft: A meta-analysis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-79346-7"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1597\/11-299","article-title":"Epidemiology of orofacial clefts in the East of ireland in the 25-year period 1984\u20132008","volume":"51","author":"McDonnell","year":"2014","journal-title":"Cleft Palate Craniofac J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.annepidem.2015.05.003","article-title":"Parental age and the risk of isolated cleft lip: A registry-based study","volume":"25","author":"Berg","year":"2015","journal-title":"Ann Epidemiol."},{"key":"ref_21","first-page":"578","article-title":"Analysis of Environmental Exposures for Nonsyndromic Cleft Lip and\/or Palate: A Case-Control Study","volume":"51","author":"Hsieh","year":"2022","journal-title":"Iran J Public Health."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/01.ede.0000158745.84019.c2","article-title":"Parent\u2019s age and the risk of oral clefts","volume":"16","author":"Bille","year":"2005","journal-title":"Epidemiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jdent.2011.10.002","article-title":"Parental age as a risk factor for non-syndromic oral clefts: A meta-analysis","volume":"40","author":"Herkrath","year":"2012","journal-title":"J. Dent."},{"key":"ref_24","unstructured":"United States Department of Health and Human Services (2014). The Health Consequences of Smoking\u201450 Years of Progress. A Report of the Surgeon General, United States Department of Health and Human Services, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1177\/10556656211040015","article-title":"Maternal Cigarette Smoking and Cleft Lip and Palate: A Systematic Review and Meta-Analysis","volume":"59","author":"Fell","year":"2022","journal-title":"Cleft Palate Craniofac J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1177\/1055665618774019","article-title":"Proportion of Orofacial Clefts Attributable to Recognized Risk Factors","volume":"56","author":"Raut","year":"2019","journal-title":"Cleft Palate Craniofac J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.oooo.2016.08.007","article-title":"Maternal active smoking and risk of oral clefts: A meta-analysis","volume":"122","author":"Zhang","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sabbagh, H.J., Hassan, M.H.A., Innes, N.P.T., Elkodary, H.M., Little, J., and Mossey, P.A. (2015). Passive smoking in the etiology of non-syndromic orofacial clefts: A systematic review and meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116963"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ijom.2012.10.008","article-title":"Current concepts on the effect of environmental factors on cleft lip and palate","volume":"42","author":"MendozaMendoza","year":"2013","journal-title":"Int. J. Oral. Maxillofac. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7172","DOI":"10.3390\/nu7095328","article-title":"Association of Parental Environmental Exposures and Supplementation Intake with Risk of Nonsyndromic Orofacial Clefts: A Case-Control Study in Hei-longjiang Province, China","volume":"7","author":"Hao","year":"2015","journal-title":"Nutrients"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Heydari, M.H., Sadeghian, A., Khadivi, G., Mustafa, H.J., Javinani, A., Nadjmi, N., and Khojasteh, A. (2024). Prevalence, trend, and associated risk factors for cleft lip with\/without cleft palate: A national study on live births from 2016 to 2021. BMC Oral Health., 24.","DOI":"10.1186\/s12903-023-03797-z"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s004310050850","article-title":"Folic acid for the prevention of congenital anomalies","volume":"157","author":"Hall","year":"1998","journal-title":"Eur. J. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e34419","DOI":"10.1097\/MD.0000000000034419","article-title":"Cleft lip and palate risk factors among otorhinolaryngology: Head and neck surgery patients in two hospitals","volume":"102","author":"Hmadieh","year":"2023","journal-title":"Medicine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.sdentj.2023.02.004","article-title":"Maternal stress as a risk factor for non-syndromic oro-facial clefts: Systematic review and meta-analysis","volume":"35","year":"2023","journal-title":"Saudi Dent. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/cga.12496","article-title":"Associated congenital anomalies and syndromes of 248 infants with orofacial clefts born between 2011 and 2014 in the Japan environment and children\u2019s study","volume":"63","author":"Sato","year":"2023","journal-title":"Congenit. Anom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.arcped.2012.07.002","article-title":"\u00c9pid\u00e9miologie des fentes labio-palatines: Exp\u00e9rience du Registre de malformations cong\u00e9nitales d\u2019Alsace entre 1995 et 2006 [Epidemiology of orofacial clefts (1995\u20132006) in France (Congenital Malfor-mations of Alsace Registry)]","volume":"19","author":"Doray","year":"2012","journal-title":"Arch Pediatr."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"D\u0105browska, J., Biedziak, B., Bogdanowicz, A., and Mostowska, A. (2023). Identification of Novel Risk Variants of Non-Syndromic Cleft Palate by Targeted Gene Panel Sequencing. J. Clin. Med., 12.","DOI":"10.3390\/jcm12052051"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/16\/5682\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:25:02Z","timestamp":1760034302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/16\/5682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":37,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["jcm14165682"],"URL":"https:\/\/doi.org\/10.3390\/jcm14165682","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,8,11]]}}}