Regional differences in birth prevalence of cleft lip and/or palate in Sweden – a register study of all children born in Sweden between 2000 and 2020

Authors

  • Måns Cornefjord Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden; Department of Plastic and Reconstructive Surgery, Skåne University Hospital, Malmö, Sweden https://orcid.org/0000-0003-4281-8858
  • Karin Källén Institution of Clinical Sciences, Department of Obstetrics and Gynecology, Centre of Reproduction Epidemiology, Tornblad Institute, Lund University, Lund, Sweden https://orcid.org/0000-0001-5765-2630
  • Kristina Klintö Division of Speech Language Pathology, Phoniatrics and Audiology, Department of Clinical Sciences in Lund, Lund University, Sweden; Division of Speech Language Pathology, Department of Otorhinolaryngology, Skåne University Hospital, Malmö, Sweden https://orcid.org/0000-0002-7044-9386
  • Mia Stiernman Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden; Department of Plastic and Reconstructive Surgery, Skåne University Hospital, Malmö, Sweden https://orcid.org/0000-0002-2563-7679
  • Anna-Paulina Wiedel Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden; Department of Oral and Maxillofacial Surgery, Skåne University Hospital, Malmö, Sweden https://orcid.org/0000-0001-6088-1143
  • Magnus Becker Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden; Department of Plastic and Reconstructive Surgery, Skåne University Hospital, Malmö, Sweden https://orcid.org/0000-0002-1915-1736

DOI:

https://doi.org/10.2340/jphs.v60.44798

Keywords:

Cleft lip and palate, cleft lip, cleft palate, birth prevalence, incidence, Sweden, cleft types, trends, regional differences, geographical differences

Abstract

The birth prevalence of cleft lip and/or palate (CL/P) varies globally, and regional differences have previously been observed within Sweden. Updated data on CL/P birth prevalence is needed and has been requested nationally and internationally. This study investigated regional differences and temporal trends in the birth prevalences of CL/P and specific cleft subtypes across Sweden’s six health care regions (HC regions) from 2000 to 2020. Using data from the Swedish Medical Birth Register and the National Register of Congenital Anomalies (coverage 97–99%), the study included 2,230,771 children. Variables included were year and region of birth, and cleft diagnoses: cleft lip and/or palate (CL/P), cleft palate without cleft lip (CP), cleft lip with/without cleft palate (CL ± P), bilateral cleft lip with/without cleft palate (BCL ± P), and unilateral/bilateral cleft lip and palate (UCLP, BCLP). Poisson regression models were used to assess regional differences and trends. The Stockholm HC region had the lowest prevalence for all cleft types except CP. The Northern HC region had a higher CP prevalence, while clefts involving the lip (CL ± P, BCL ± P) were more common in the Southeastern and Southern HC regions. Declining trends were observed in at least two regions for all cleft types except CP. CL/P, CL ± P, and BCL ± P showed decreasing prevalence in three regions. The findings confirm some previously reported regional patterns, including a higher CP birth prevalence in northern Sweden. Potential explanations for the regional differences include genetic variation, differences in attitude towards pregnancy termination, socioeconomic factors, and exposure to other risk factors, but need further examination.

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References

Panamonta V, Pradubwong S, Panamonta M, et al. Global birth prevalence of orofacial clefts: a systematic review. J Med Assoc Thai. 2015;98 Suppl 7:S11–S121.

Mossey PA, Little J, Munger RG, et al. Cleft lip and palate. Lancet. 2009;374(9703):1773–1785. https://doi.org/10.1016/S0140-6736(09)60695-4 DOI: https://doi.org/10.1016/S0140-6736(09)60695-4

Murray JC. Gene/environment causes of cleft lip and/or palate. Clin Genet. 2002;61(4):248–256. https://doi.org/10.1034/j.1399-0004.2002.610402.x DOI: https://doi.org/10.1034/j.1399-0004.2002.610402.x

Croen LA, Shaw GM, Wasserman CR, et al. Racial and ethnic variations in the prevalence of orofacial clefts in California, 1983–1992. Am J Med Genet. 1998;79(1):42–47. https://doi.org/10.1002/(SICI)1096-8628(19980827)79:1<42::AID-AJMG11>3.0.CO;2-M DOI: https://doi.org/10.1002/(SICI)1096-8628(19980827)79:1<42::AID-AJMG11>3.0.CO;2-M

Taritsa IC, Ledwon JK, Bajaj A, Gosain AK. 12-Year Trends of Orofacial Clefts in the United States: High-lighting Racial/Ethnic Differences in Prevalence of Cleft Lip and Cleft Palate. Cleft Palate Craniofac J. 2025 May;62(5):820-828. https://doi.org/10.1177/10556656241227033. Epub 2024 Jan 30. DOI: https://doi.org/10.1177/10556656241227033

Msamati BC, Igbigbi PS, Chisi JE. The incidence of cleft lip, cleft palate, hydrocephalus and spina bifida at Queen Elizabeth Central Hospital, Blantyre, Malawi. Cent Afr J Med. 2000;46(11): 292–296. https://doi.org/10.4314/cajm.v46i11.8572 DOI: https://doi.org/10.4314/cajm.v46i11.8572

Iregbulem LM. The incidence of cleft lip and palate in Nigeria. Cleft Palate J. 1982;19(3):201–205.

Zucchero TM, Cooper ME, Maher BS, et al. Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate. N Engl J Med. 2004;351(8):769–780. https://doi.org/10.1056/NEJMoa032909 DOI: https://doi.org/10.1056/NEJMoa032909

Setó-Salvia N, Stanier P. Genetics of cleft lip and/or cleft palate: association with other common anomalies. Eur J Med Genet. 2014;57(8):381–393. https://doi.org/10.1016/j.ejmg.2014.04.003 DOI: https://doi.org/10.1016/j.ejmg.2014.04.003

Mitchell LE, Risch N. Mode of inheritance of nonsyndromic cleft lip with or without cleft palate: a reanalysis. Am J Hum Genet. 1992;51(2):323–332.

Wyszynski DF, Zeiger J, Tilli MT, et al. Survey of genetic counselors and clinical geneticists regarding recur-rence risks for families with nonsyndromic cleft lip with or without cleft palate. Am J Med Genet. 1998;79(3):184–190. https://doi.org/10.1002/(SICI)1096-8628(19980923)79:3<184::AID-AJMG6>3.0.CO;2-N DOI: https://doi.org/10.1002/(SICI)1096-8628(19980923)79:3<184::AID-AJMG6>3.0.CO;2-N

Grosen D, Chevrier C, Skytthe A, et al. A cohort study of recurrence patterns among more than 54,000 rela-tives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance. J Med Genet. 2010;47(3):162–168. https://doi.org/10.1136/jmg.2009.069385 DOI: https://doi.org/10.1136/jmg.2009.069385

Källén K. Maternal smoking and orofacial clefts. Cleft Palate Craniofac J. 1997;34(1):11–16. https://doi.org/10.1597/1545- 1569_1997_034_0011_msaoc_2.3.co_2 DOI: https://doi.org/10.1597/1545-1569_1997_034_0011_msaoc_2.3.co_2

Martelli DR, Coletta RD, Oliveira EA, et al. Association between maternal smoking, gender, and cleft lip and palate. Braz J Otorhinolaryngol. 2015;81(5):514–519. https://doi.org/10.1016/j.bjorl.2015.07.011 DOI: https://doi.org/10.1016/j.bjorl.2015.07.011

Wyszynski DF, Duffy DL, Beaty TH. Maternal cigarette smoking and oral clefts: a meta-analysis. Cleft Palate Craniofac J. 1997;34(3):206–210. https://doi.org/10.1597/1545-1569_ 1997_034_0206_mcsaoc_2.3.co_2 DOI: https://doi.org/10.1597/1545-1569_1997_034_0206_mcsaoc_2.3.co_2

Abrishamchian AR, Khoury MJ, Calle EE. The contribution of maternal epilepsy and its treatment to the etiol-ogy of oral clefts: a population based case-control study. Genet Epidemiol. 1994;11(4):343–351. https://doi.org/10.1002/gepi.1370110404 DOI: https://doi.org/10.1002/gepi.1370110404

Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: pro-spective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62(6):385–392. https://doi.org/10.1002/1096-9926(200012)62:6<385::AID-TERA5>3.0.CO;2-Z DOI: https://doi.org/10.1002/1096-9926(200012)62:6<385::AID-TERA5>3.3.CO;2-Q

Brentlinger PE. Folic acid antagonists during pregnancy and risk of birth defects. N Engl J Med. 2001;344(12):933–934; author reply 4–5. https://doi.org/10.1056/NEJM200103223441212 DOI: https://doi.org/10.1056/NEJM200103223441212

Cedergren M, Källén B. Maternal obesity and the risk for orofacial clefts in the offspring. Cleft Palate Crani-ofac J. 2005;42(4):367–371. https://doi.org/10.1597/04-012.1 DOI: https://doi.org/10.1597/04-012.1

Movva VC, Spangler B, Young AJ, et al. A retrospective review of the association between maternal body mass index and the risk of congenital anomalies. Congenit Anom (Kyoto). 2024;64(1):17–22. https://doi.org/10.1111/cga.12544 DOI: https://doi.org/10.1111/cga.12544

Ahmed Sakran K, Mutahar Abotaleb B, Khaled Al-Rokhami R, et al. Analysis of environmental exposures for nonsyndromic cleft lip and/or palate: a case-control study. Iran J Public Health. 2022;51(3):578–586. https://doi.org/10.18502/ijph.v51i3.8934 DOI: https://doi.org/10.18502/ijph.v51i3.8934

Johnson CY, Little J. Folate intake, markers of folate status and oral clefts: is the evidence converging? Int J Epidemiol. 2008;37(5):1041–1058. https://doi.org/10.1093/ije/dyn098 DOI: https://doi.org/10.1093/ije/dyn098

Clark JD, Mossey PA, Sharp L, et al. Socioeconomic status and orofacial clefts in Scotland, 1989 to 1998. Cleft Palate Craniofac J. 2003;40(5):481–485. https://doi.org/10.1597/1545-1569_2003_040_0481_ssaoci_2.0.co_2 DOI: https://doi.org/10.1597/1545-1569(2003)040<0481:SSAOCI>2.0.CO;2

Lupo PJ, Danysh HE, Symanski E, et al. Neighborhood-based socioeconomic position and risk of oral clefts among offspring. Am J Public Health. 2015;105(12):2518–2525. https://doi.org/10.2105/AJPH.2015.302804 DOI: https://doi.org/10.2105/AJPH.2015.302804

Figueiredo JC, Ly S, Magee KS, et al. Parental risk factors for oral clefts among Central Africans, Southeast Asians, and Central Americans. Birth Defects Res A Clin Mol Teratol. 2015;103(10):863–879. https://doi.org/10.1002/bdra.23417 DOI: https://doi.org/10.1002/bdra.23417

Mbuyi-Musanzayi S, Kayembe TJ, Kashal MK, et al. Non-syndromic cleft lip and/or cleft palate: Epidemiology and risk factors in Lubumbashi (DR Congo), a case-control study. J Craniomaxillofac Surg. 2018;46(7):1051–1058. https://doi.org/10.1016/j.jcms.2018.05.006 DOI: https://doi.org/10.1016/j.jcms.2018.05.006

Cornefjord M, Källén K, Klintö K, Stiernman M, Wiedel AP, Becker M. Birth prevalence of cleft lip and/or pal-ate - a register study of all children born in Sweden years 2000-2020. J Plast Surg Hand Surg. 2025 Jun 3;60:120-126. https://doi.org/10.2340/jphs.v60.43739. DOI: https://doi.org/10.2340/jphs.v60.43739

Hagberg C, Larson O, Milerad J. Incidence of cleft lip and palate and risks of additional malformations. Cleft Palate Craniofacial J. 1998;35(1):40–45. https://doi.org/10.1597/1545-1569_1998_035_0040_ioclap_2.3.co_2 DOI: https://doi.org/10.1597/1545-1569(1998)035<0040:IOCLAP>2.3.CO;2

Beckman L, Myrberg N. The incidence of cleft lip and palate in Northern Sweden. Hum Hered. 1972;22(5):417–422. https://doi.org/10.1159/000152519 DOI: https://doi.org/10.1159/000152519

Chetpakdeechit W, Mohlin B, Persson C, et al. Cleft extension and risks of other birth defects in children with isolated cleft palate. Acta Odontol Scand. 2010;68(2):86–90. https://doi.org/10.3109/00016350903258003 DOI: https://doi.org/10.3109/00016350903258003

Lokal_Profil. A map of the health care regions and municipalities of Sweden [Internet]. 2010 [cited 2025 Aug 18]. Available from: https://commons.wikimedia.org/wiki/File:SWE-Map_Sjukv%C3%A5rdsregioner-kommuner.svg

World Health Organization. International statistical classification of diseases and related health problems 10th revision (ICD-10) [Internet]. 2016 [cited 2025 Apr 03]. Available from: https://icd.who.int/browse10/2016/en

Sweden S. Befolkningstäthet i Sverige [Internet]. 2025 [cited 2025 Apr 09]. Available from: https://www.scb.se/hitta-statistik/sverige-i-siffror/manniskorna-i-sverige/befolkningstathet-i-sverige/?

Sweden S. Varied development in gross regional domestic product (GRDP) in 2022 [Internet]. 2024 [cited 2025 Apr 09]. Availa-ble from: https://www.scb.se/en/finding-statistics/statistics-by-subject-area/national-accounts/national-accounts/regional-accounts/pong/statistical-news/regional-accounts-2022/

Sweden S. Utrikes födda i Sverige [Internet]. 2025 [cited 2025 Apr 10]. Available from: https://www.scb.se/hitta-statistik/sverige-i-siffror/manniskorna-i-sverige/utrikes-fodda- i-sverige/#utrikes-fodda-per-region

Calzolari E, Bianchi F, Rubini M, et al. Epidemiology of cleft palate in Europe: implications for genetic research. Cleft Palate Craniofac J. 2004;41(3):244–249. https://doi.org/10.1597/02-074.1 DOI: https://doi.org/10.1597/02-074.1

Rintala AE. Epidemiology of orofacial clefts in Finland: a review. Ann Plast Surg. 1986;17(6):456–459. https://doi.org/10.1097/00000637-198612000-00004 DOI: https://doi.org/10.1097/00000637-198612000-00004

Rahimov F, Nieminen P, Kumari P, et al. High incidence and geographic distribution of cleft palate in Finland are associated with the IRF6 gene. Nat Commun. 2024;15(1):9568. https://doi.org/10.1038/s41467-024-53634-2 DOI: https://doi.org/10.1038/s41467-024-53634-2

Clementi M, Tenconi R, Bianchi F, et al. Evaluation of prenatal diagnosis of cleft lip with or without cleft pal-ate and cleft palate by ultrasound: experience from 20 European registries. EUROSCAN study group. Prenat Diagn. 2000;20(11):870–875. https://doi.org/10.1002/1097-0223(200011)20:11<870::AID-PD940>3.0.CO;2-J DOI: https://doi.org/10.1002/1097-0223(200011)20:11<870::AID-PD940>3.0.CO;2-J

Guichoud Y, El Ezzi O, de Buys Roessingh AS. Cleft lip and palate antenatal diagnosis: A Swiss University Center performance analysis. Diagnostics. 2023;13:1–10. https://doi.org/10.3390/diagnostics13152479 DOI: https://doi.org/10.3390/diagnostics13152479

Dixon MJ, Marazita ML, Beaty TH, et al. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet. 2011;12(3):167–178. https://doi.org/10.1038/nrg2933 DOI: https://doi.org/10.1038/nrg2933

Additional Files

Published

2025-10-21

How to Cite

Cornefjord, M., Källén, K., Klintö, K., Stiernman, M., Wiedel, A.-P., & Becker, M. (2025). Regional differences in birth prevalence of cleft lip and/or palate in Sweden – a register study of all children born in Sweden between 2000 and 2020. Journal of Plastic Surgery and Hand Surgery, 60(1), 196–203. https://doi.org/10.2340/jphs.v60.44798

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Original Research Articles