Maternal Risk Factors Associated with the Development of Cleft Lip and Cleft Palate in Mexico: A Case-Control Study

Document Type : Original


1 Department of Perinatology, The Women's Hospital, Secretariat of Health, 80127, Culiacan, Sinaloa, Mexico.

2 CIASaP, School of Medicine, Autonomous University of Sinaloa, 80246, Culiacan, Sinaloa, Mexico

3 Research Department, The Women's Hospital, Secretariat of Health, 80127, Culiacan, Sinaloa, Mexico

4 Department of Internal Medicine, Gulf Coast Medical Center, Panama City, 32405, Florida, USA.

5 Faculty of Biological and Chemical Sciences, Autonomous University of Sinaloa, 80000 Culiacán, SIN, Mexico.


Cleft lip and palate, the most common developmental deformity, is seen worldwide and the etiology involves a combination of genetic and environmental factors. The purpose of this study was to determine the maternal risk factors associated with the development of cleft lip and cleft palate.
Materials and Methods:
We conducted a case control study at the Women’s Hospital in Culiacan, Mexico. Medical records were analyzed, including patients who delivered babies with and without cleft lip and cleft palate from January 2010 to December 2015. Multiple variables were analyzed, including gestational age, weight at birth, the use of folic acid and multivitamins during pregnancy, smoking, alcohol abuse, the use of recreational drugs, history of sexually transmitted infections, marital status, socioeconomic status, education, and nutritional status.
We found that the maternal risk factors with the strongest association for the development of cleft lip and cleft palate were the following: patients who were not taking folic acid during pregnancy [OR 3.27, 95% CI 1.32-8.09], P=0.00; patients who were not taking vitamin supplementation during pregnancy [OR 2.6, 95% CI 1.19-7.27], P=0.02; smoking during pregnancy [OR 2.05, 95% CI 1.23-3.41], P=0.01; and alcohol abuse during pregnancy [OR 1.90, 95% CI 1.17-3.08], P=0.03.
The main risk factors associated with the development of cleft lip and cleft palate in a Mexican population at the Women’s hospital in Culiacan, Sinaloa, Mexico were smoking, alcohol abuse, and patients not taking folic acid and multivitamins during pregnancy.


Main Subjects

1. Diewert VM. Development of human craniofacial morphology during the late embryonic and early fetal periods. American journal of orthodontics. 1985;88(1):64-76.
2. Harville EW, Wilcox AJ, Lie RT, Vindenes H, Abyholm F. Cleft lip and palate versus cleft lip only: are they distinct defects? American journal of epidemiology. 2005;162(5):448-53.
3. Burg ML, Chai Y, Yao CA, Magee W, Figueiredo JC. Epidemiology, Etiology, and Treatment of Isolated Cleft Palate. Frontiers in physiology. 2016;7:67.
4. Chung KC, Kowalski CP, Kim HM, Buchman SR. Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip/palate. Plastic and reconstructive surgery. 2000;105(2):
5. Mills JL, Molloy AM, Parle-McDermott A, Troendle JF, Brody LC, Conley MR, et al. Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate. Birth defects research Part A, Clinical and molecular teratology. 2008;82(9):636-43.
6. Mossey PA, Shaw WC, Munger RG, Murray JC, Murthy J, Little J. Global oral health inequalities: challenges in the prevention and management of orofacial clefts and potential solutions. Advances in dental research. 2011;23(2):247-58.
7. Hook EB. Congenital malformations worldwide: A report from the international clearinghouse for birth defect monitoring systems. American Journal of Human Genetics. 1992;51(4):919-20.
8. García RG, Navarro RL. Incidencia de labio y paladar hendido en México: 2003-2006. Revista ADM. 2008;65(6):309-13.
9. Boulet SL, Grosse SD, Honein MA, Correa-Villasenor A. Children with orofacial clefts: health-care use and costs among a privately insured population. Public health reports. 2009;124(3):
10. Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet. 2009;374(9703):1773-85.
11. Bille C, Skytthe A, Vach W, Knudsen LB, Andersen AM, Murray JC, et al. Parent's age and the risk of oral clefts. Epidemiology. 2005;16(3):311-6.
12. Acs N, Banhidy F, Puho E, Czeizel AE. Maternal influenza during pregnancy and risk of congenital abnormalities in offspring. Birth defects research Part A, Clinical and molecular teratology. 2005; 73(12):989-96.
13. Norma Oficial Mexicana, NOM-017-SSA2-2012, para la vigilancia epidemiológica, diario oficial de la federación. Available online at: May 30, 2016). 2013.
14. Kutbi H, Wehby GL, Moreno Uribe LM, Romitti PA, Carmichael S, Shaw GM, et al. Maternal underweight and obesity and risk of orofacial clefts in a large international consortium of population-based studies. International journal of epidemiology. 2017;46(1):190-9.
15. Goh YI, Bollano E, Einarson TR, Koren G. Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. Journal of obstetrics and gynaecology Canada . 2006; 28(8): 680-9.
16. Wilcox AJ, Lie RT, Solvoll K, Taylor J, McConnaughey DR, Abyholm F, et al. Folic acid supplements and risk of facial clefts: national population based case-control study. Bmj. 2007; 334 (7591):464.
17. Cisneros Domínguez G, Bosch Núñez AI. Alcohol, tabaco y malformaciones congénitas labio- alveolopalatinas.MEDISAN.2014;18(9):1293-7.
18. Torres E, Otero L. Factores etiológicos asociados con la fisura labio palatina no sindrómicas [internet].[Consultado 1 nov 2011].http://recursostic.
19. Dirección General de Epidemiología (DGE), Anuarios de Morbilidad, Secretaria de Salud. Last accessed 01 Jun 2016, http://www. epidemiologia.
20. Campaña H, López Camelo JS. Epidemiología del labio leporino en Sudamérica. Revista Argentina de Antropología Biológica 2001;3(2).
21. Gonzalez-Farias F, Cisneros Estrada X, Fuentes Ruiz C, Diaz Gonzalez G, Botello AV. Pesticides distribution in sediments of a tropical coastal lagoon adjacent to an irrigation district in northwest Mexico. Environmental technology. 2002;23 (11): 1247-56.
22. Yang W, Carmichael SL, Roberts EM, Kegley SE, Padula AM, English PB, et al. Residential agricultural pesticide exposures and risk of neural tube defects and orofacial clefts among offspring in the San Joaquin Valley of California. American journal of epidemiology. 2014;179(6):740-8.
23. Benedetti D, Nunes E, Sarmento M, Porto C, Dos Santos CE, Dias JF, et al. Genetic damage in soybean workers exposed to pesticides: evaluation with the comet and buccal micronucleus cytome assays. Mutation research. 2013;752(1-2):28-33.