a presentation on the epidemiology of orofacial clefts including information about classification, prevalence and etiological factors

1. Epidemiology of Orofacial Clefts(OFC) Abdullah Marghalani, BDS MSD(c) Umm Al-Qura University, Faculty of Dentistry

3. Present at birth

5. Congenital Birth Defects From an epidemiological perspective, congenital birth defects are difficult to study: Individual conditions are relatively rare Fetus is exposed to an array of genetic and environmental factors They represent birth prevalence, not the true incidence of the disease

6. Orofacial Cleft Cleft lip with or without cleft palate Cleft palate

7. Cleft lip without cleft palate

8. Cleft lip with cleft palate

9. Cleft palate

10. Classification Tessier’s classification Veau’s classification Davis and Ritchie classification Kernahan and Stark classification

11. Tessier’s classification Craniomaxillofacial clefting classification It includes numbered clefts from 0 (midline cleft of the lip and nose) to 30 (a mandibular cleft) Commonly used by surgeons Cleft no. 0= median cleft lip Cleft no. 1, 2, and 3= unilateral and bilateral cleft lip

12. Veau’s classification(1931) Group I (A) - Defects of the soft palate only Group II (B) - Defects involving the hard palate and soft palate Group III (C) - Defects involving the soft palate to the alveolus, usually involving the lip Group IV (D) - Complete bilateral clefts Thornton J.B., Nimer S., Howard P.S. The incidence, classification, etiology, and embryology of oral clefts. (1996) Seminars in orthodontics, 2 (3), pp. 162-168.

13. Davis and Ritchie classification(1922) Group I Pre-alveolar process cleft (Lip cleft; alveolar process normal) Unilateral. Right. Left. Complete. Incomplete. Bilateral. Right : Complete ; incomplete. Left : Complete ; incomplete Median (rare). Complete. Incomplete. Group II Post-alveolar process cleft (Palate cleft; alveolar process normal) Soft palate (The uvula only or the entire soft palate, may be cleft) Hard palate. (May be notch only, or cleft may extend to the anterior palatine foramen, in addition to the soft palate) . J.S. Davis and H.P. Ritchie, Classification of congenital clefts of the lip and palate, JAMA79 (1922), pp. 1323–1327

14. Davis and Ritchie classification(1922) Group III Alveolar process cleft Unilateral. Right: Complete; incomplete. Left: Complete; incomplete Bilateral. Right : Complete ; incomplete. Left : Complete; incomplete Median (rare). Complete. Incomplete. Clefts of the lip and palate are usually associated in this group J.S. Davis and H.P. Ritchie, Classification of congenital clefts of the lip and palate, JAMA79 (1922), pp. 1323–1327

15. Kernahan and Stark classification This system provides a graphic classification scheme using a Y-configuration, which can be divided into 9 areas: Areas 1 and 4 - Lip Areas 2 and 5 - Alveolus Areas 3 and 6 - Palate between the alveolus and the incisive foramen Areas 7 and 8 - Hard palate Area 9 - Soft palate

16. Orofacial clefts OFC: Non-syndromic Syndrome related: Chromosal abnormality: Trisomy 13 Trisomy 18 Single gene disorders: Van der Woude syndrome Stickler syndrome

17. Etiological factors Genetic factors(30 different candidate genes have been identified in different types of clefting) Environmental factors: Maternal smoking Maternal alcohol use Maternal nutrition Drugs Demographic factors: Maternal age Gender Race

19. Maternal smoking Meta-analysis of 24 case-control and cohort studies from 1966-2002, they found smoking is associated with CL±P(OR=1.34;95%CI:1.25-1.44) and CP(OR=1.2;95%CI:1.10-1.35) Little J, Cardy A, Munger RG. Tobacco smoking and oral clefts: a meta analysis. Bull World Health Organ. 2004b;82:213–218.

20. Maternal Alcohol Use Multi-center case-control study done in Europe(1989-1992) looking for an association between alcohol consumption in the 1st trimester and CP Multivariate analysis showed: Increased risk for CP with alcohol consumption(OR=2.28; 95%CI:1.02-5.09) Christine L. et al Tobacc and Alcohol Use During Pregnancy and Risk of Oral Clefts. 2000;90(3):415-419

21. Maternal Alcohol Use Case-control study in California Gary et al found that mothers’ consumption of alcohol during the period of 1 month before through 3 months after pregnancy for at least once weekly Associated with CL±P (OR=3.4; 95%CI:1.1-9.7) Gary S., Edward L. Maternal periconceptional alcohol consumption and risk for Orofacial clefts. 1999. The Journal of Pediatrics. 134(3):298-303

22. Maternal Nutrition Folic acid Vitamin A Zinc Yazdy M, Honein M, Rasmussen S, Frias J. Priorities for Future Public Health Research in Orofacial Clefts. Cleft Palate-Crainofacial Journal, 2007;44:351-357

23. Folic acid Meta-analysis of 17 studies: Five prospective studies: Folic acid is protective for OFC (RR= 0.55;95% CI:0.32-0.95) 12 case-control studies: Folic acid is protective for OFC (RR= 0.78;95% CI:0.71-0.85) Badovinac R L [et al.] Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: a meta-analysis . /Birth Defects Research. .Jan 2007. - 1 : Vol. 79. - pp. 8-15.

24. Drugs Antiepileptic corticosteroids Benzodiazepines In Carmichael et al study(2007), using the NBDPS data, they found that maternal periconceptional corticosteroids use associated with increased risk of CLP (OR=1.7) but not CP(OR=0.5) Yazdy M, Honein M, Rasmussen S, Frias J. Priorities for Future Public Health Research in Orofacial Clefts. Cleft Palate-Crainofacial Journal, 2007;44:351-357

25. Maternal age Using the NBDPS, the birth prevalence of CLP was lower among mothers aged 30-34 compared to mothers aged 25-29(PR=0.8; 95%CI:0.7-0.9) Genisca AE, Frıas JL, Broussard CS, Honein MA, Lammer EJ, Moore CA, Shaw GM, Murray JC, Yang W, Rasmussen SA, National Birth Defects Prevention Study. 2009. Orofacial clefts in the National Birth Defects Prevention Study, 1997–2004. Am J Med Genet Part A 149A:1149–1158.

26. National Birth Defect Prevention Study(NBDPS) The NBDPS is an ongoing, population-based, multi-site, case-control study of major birth defects, including orofacial clefts Data on infants with birth defects are collected through population-based birth defects surveillance systems in ten sites: Arkansas, California, Centers for Disease Control and Prevention, Atlanta, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah

27. Prevalence Orofacial clefts affect approximately 6,800 births in the United States annually Center for Disease Control and Prevention,2006

28. Prevalence of orofacial cleft National Birth Defects Prevention Study (NBDPS)

29. Prevalence The NBDPS data are consistent with other studies showing that: CL±P are less prevalent among females(PR=0.7; 95% CI:0.6-0.8) CP is more prevalent among females(PR=1.2; 95%CI: 1.1-1.4) Birth prevalence of all types of orofacial clefts is lower among non-Hispanic Blacks when compared to non-Hispanic Whites National Birth Defects Prevention Study (NBDPS)

30. laterality In CLP: Unilateral was two times more prevalent than bilateral involvement In CL: Unilateral was ten times more prevalent than bilateral involvement Involvement was most often Left sided in CL and CLP National Birth Defects Prevention Study (NBDPS)

31. Cleft Palate National Birth Defects Prevention Study (NBDPS)

32. Additional defects Genisca AE, Frıas JL, Broussard CS, Honein MA, Lammer EJ, Moore CA, Shaw GM, Murray JC, Yang W, Rasmussen SA, National Birth Defects Prevention Study. 2009. Orofacial clefts in the National Birth Defects Prevention Study, 1997–2004. Am J Med Genet Part A 149A:1149–1158.

33. Prenatal Diagnosis Improved ultrasound equipment and experience has made the diagnosis possible Parental counseling Bender P. Genetics of Cleft Lip and Palate. Journal of Pediatric Nursing. 2000;15:242-249

34. Prenatal Diagnosis Using the NBDPS data, a study was conducted to determine how frequently OFC are diagnosed prenatally: Of 522 cases of CLO, 106 cases were detected prenatally(20.3%) Of 978 cases of CLP, 326 cases were detected prenatally (33.3%) Of 798 cases of CPO, 2 cases were detected prenatally (0.3%) Johnson C., Honein M., Hobbs C., Rasmussen S., and the National Birth Defects Prevention Study, 1998-2004. Prenat Diagn 2009;29:833-839

35. References Yazdy M, Honein M, Rasmussen S, Frias J. Priorities for Future Public Health Research in Orofacial Clefts. Cleft Palate-Crainofacial Journal, 2007;44:351-357 Center for Disease Control and Prevention. Improved National Prevalence Estimates for 18 Selected Major Birth Defects-United States, 1999-2001. MMWR.2006;45:1301-1332 National Birth Defects Prevention Study (NBDPS) Genisca AE, Frıas JL, Broussard CS, Honein MA, Lammer EJ, Moore CA, Shaw GM, Murray JC, Yang W, Rasmussen SA, National Birth Defects Prevention Study. 2009. Orofacial clefts in the National Birth Defects Prevention Study, 1997–2004.Am J Med Genet Part A 149A:1149–1158. Krapels I., Keers C., Muller M., Theunissen R. Nutrition and Genes in the Development of Orofacial Clefting. Nutrition Reviews;64:280-288 Huang WY, Winn DM, Brown LM, et al. Alcohol concentration and risk of oral cancer in Puerto Rico. Am J Epidemiol 2003;157:881–887. Thornton J.B., Nimer S., Howard P.S. The incidence, classification, etiology, and embryology of oral clefts. (1996) Seminars in orthodontics, 2 (3), pp. 162-168.

36. Thornton J.B., Nimer S., Howard P.S. The incidence, classification, etiology, and embryology of oral clefts. (1996) Seminars in orthodontics, 2 (3), pp. 162-168. J.S. Davis and H.P. Ritchie, Classification of congenital clefts of the lip and palate, JAMA 79 (1922), pp. 1323–1327 Whitaker L., Pashayan H., Reichman J. A Propsed new classificatopn of crainfacial anomalies. Cleft Palate Journal July 1981;18(3):161-176 Honein M., Rasmussen S., Reefhuis J., Romitti P., Lammer E., Sun L., and Correa A. Maternal Smoking and Enviromental Tobacco Smoke Exposure and the Risk for Orofacial Clefts. Epidemiology 2007;18:226-233 Honein M., Rasmussen S., Reefhuis J., Romitti P., Lammer E., Sun L., and Correa A. Maternal Smoking and Enviromental Tobacco Smoke Exposure and the Risk for Orofacial Clefts. Epidemiology 2007;18:226-233 Christine L. et al Tobacc and Alcohol Use During Pregnancy and Risk of Oral Clefts. 2000;90(3):415-419 Gary S., Edward L. Maternal periconceptional alcohol consumption and risk for Orofacial clefts. 1999. The Journal of Pediatrics. 134(3):298-303 Genisca AE, Frıas JL, Broussard CS, Honein MA, Lammer EJ, Moore CA, Shaw GM, Murray JC, Yang W, Rasmussen SA, National Birth Defects Prevention Study. 2009. Orofacial clefts in the National Birth Defects Prevention Study, 1997–2004. Am J Med Genet Part A 149A:1149–1158.