Epidemiology of cleft lip with or without cleft palate in Thais

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Abstract

Background

Oral clefts, including cleft lip (CL), CL with cleft palate (CL/CP), and cleft palate only (CPO), are among the most common birth defects, and if left untreated can cause significant morbidity. Causes are complex and involve both genetic and environmental factors. Several studies have demonstrated the highest prevalence of oral clefts being in Asian, white, and African populations. However, there have been very few epidemiological studies of oral clefts in Thais.

Objectives

To describe the epidemiology and factors associated with oral clefts in Thais.

Methods

This retrospective case-control observational study included individuals from numerous regions in Thailand. We reviewed data regarding 784 patients with an oral cleft collected in questionnaires as part of the Thai nationwide Smart Smile and Speech Project from 2006 to 2014. Data regarding patients with oral clefts were analyzed, and compared with data regarding 187 unaffected controls.

Results

Of 784 cases, CL/CP accounted for 59.8%, CPO 21.9%, and CL 18.3%. A family history of oral clefts was detected in all 3 types (P < 0.001). Maternal use of any drugs or herbal medicine not prescribed by physicians during pregnancy in cases of CPO (P = 0.049) and maternal consumption of alcohol during pregnancy in cases of CL/CP (P = 0.047) were significantly higher than that by mothers of controls.

Conclusions

CL/CP is the most common type of oral cleft. A family history of oral clefts, and maternal consumption of alcohol or nonprescribed drugs are positively associated with oral clefts in Thais.

Abstract

Background

Oral clefts, including cleft lip (CL), CL with cleft palate (CL/CP), and cleft palate only (CPO), are among the most common birth defects, and if left untreated can cause significant morbidity. Causes are complex and involve both genetic and environmental factors. Several studies have demonstrated the highest prevalence of oral clefts being in Asian, white, and African populations. However, there have been very few epidemiological studies of oral clefts in Thais.

Objectives

To describe the epidemiology and factors associated with oral clefts in Thais.

Methods

This retrospective case-control observational study included individuals from numerous regions in Thailand. We reviewed data regarding 784 patients with an oral cleft collected in questionnaires as part of the Thai nationwide Smart Smile and Speech Project from 2006 to 2014. Data regarding patients with oral clefts were analyzed, and compared with data regarding 187 unaffected controls.

Results

Of 784 cases, CL/CP accounted for 59.8%, CPO 21.9%, and CL 18.3%. A family history of oral clefts was detected in all 3 types (P < 0.001). Maternal use of any drugs or herbal medicine not prescribed by physicians during pregnancy in cases of CPO (P = 0.049) and maternal consumption of alcohol during pregnancy in cases of CL/CP (P = 0.047) were significantly higher than that by mothers of controls.

Conclusions

CL/CP is the most common type of oral cleft. A family history of oral clefts, and maternal consumption of alcohol or nonprescribed drugs are positively associated with oral clefts in Thais.

Oral clefts including cleft lip (CL), CL with a cleft palate (CL/CP), and cleft palate alone (CPO) are among the most common congenital malformations of the oral cavity. The prevalence of oral clefts is about 1-2 per 1,000 live births worldwide [1]. The highest prevalence has been reported in Asians, followed by white people of western European ancestry, and Africans [1, 2]. The prevalence of oral clefts in Thais is around 1.1-2.4 per 1,000 live births [3, 4]. If left untreated, individuals with oral clefts experience significant morbidity such as malnutrition because of feeding problems [5, 7]. In addition, multiple specialists are required for the appropriate management of patients with oral clefts from infancy to adolescence. Financial and psychosocial issues are also major concerns in families with members affected by oral clefts [8, 10]. Several studies have attempted to determine risk factors including genetic, maternal, and other environmental factors contributing to the occurrence of oral clefts [5, 11-14]. These studies were conducted in the hope that strategies could be implemented to reduce the incidence of oral clefts. There have been a few studies reporting the risk factors for oral clefts in Thais. These were conducted in selected regions of the northeastern and southern parts of Thailand [5, 15, 16]. We conducted a retrospective case-control observational study to describe the nationwide epidemiological characteristics and determine other factors that may have contributed to the occurrence of oral clefts. Based on the timing of embryogenesis and epidemiology, CPO has been considered a separate entity from CL and CL/CP; we therefore classified oral clefts into CL, CL/CP, and CPO [17, 18].

Materials and methods

Study design

After approval by the institutional review board of the Faculty of Medicine, Chulalongkorn University (certificates of approval Nos. 471/2008 and 493/2013, and institutional review board approval Nos. 216/51 and 227/56), we reviewed data regarding 784 patients with an oral cleft and their mothers as collected in questionnaires as a part of the Smart Smile and Speech Project during 2006-2014 as approved by the Thai Ministry of Public Health, and regarding a group of control patients consisting of 187 unrelated children without oral clefts who had attended King Chulalongkorn Memorial Hospital. The questionnaires had been completed by physicians or trained project assistants after obtaining written informed signed consent from the participants (including patients, controls, and their mothers) as appropriate, consent from a parent or legal guardian where the participant was less the age of consent, and assent from participants where appropriate (usually older than 7 years), in accordance with the Declaration of Helsinki and its contemporary revisions.

Participants

All patients with oral clefts had been examined by pediatricians and pediatric surgeons, and were divided into three groups (CL, CL/CP, and CPO). The patients were from 40 provinces across Thailand and control patients without oral clefts had attended King Chulalongkorn Memorial Hospital (Table 1).

Data analysis

We retrospectively reviewed data regarding demographics, maternal use of any drugs or herbal medicine not prescribed by physicians, tobacco and alcohol consumption more than once a week during pregnancy, and family medical history. Categorical data between the case and control groups were compared using a chi-square test. All data were analyzed using IBM SPSS Statistics for Windows, version 22 (IBM Corp, Armonk, NY, USA). P < 0.05 was considered significant.

Results

Of 784 patients with an oral cleft, CL/CP was the most common type (59.8%) followed by CPO 21.9% and CL 18.3%. The proportion of affected female patients with CPO was 53.5% and CL 53.2%. By contrast, a higher proportion of male patients with CL/CP were noted (58.3%). Compared with the control group, there was a significant difference in family history of oral clefts in CL, CPO, and CL/CP (P < 0.001) and in maternal use of nonprescribed medications during pregnancy in CPO (P = 0.049), and maternal consumption of alcohol during pregnancy in CL/CP (P = 0.047) (Table 2).

Table 1

Number of patients with oral clefts from various regions of Thailand

CL, cleft lip; CPO, cleft palate only; CL/CP, CL and cleft palate

Region of ThailandCLCPOCL/CP
Northern3945128
Northeastern2940142
Western--1
Central204172
Southern4838116
Unidentified7810
Total (n = 784)143172469
Table 2

Characteristics of patients with oral clefts and unaffected controls

VariableTotalCL (n = 143)CPO (n = 172)CL/CP (n = 469)Control (n = 187)
1. Sex
 Male50067 (46.9%)75 (46.6%)262 (58.3%)96
 Female44176 (53.2%)86 (53.5%)188 (41.8%)91
PaP = 0.42P = 0.38P = 0.11
2. Nonprescribed drug use during pregnancy
 No use847124 (87.9%)148 (86.1%)403 (87.6%)172
 Use11217 (12.1%)24 (14.0%)57 (12.4%)14
PaP = 0.17P = 0.049*P = 0.07
3. Smoking during pregnancy
 No smoking942139 (99.3%)169 (98.8%)451 (98.3%)183
 Smoking131 (0.7%)2 (1.2%)8 (1.7%)2
PaP = 0.73P = 0.94P = 0.54
4. Alcohol consumption during pregnancy
 None924134 (97.8%)167 (98.2%)439 (95.9%)184
 More than once per week273 (2.2%)3 (1.8%)19 (4.2%)2
PaP = 0.42P = 0.58P = 0.047*
5. Family history of oral clefts
 Positive15826 (19.3%)30 (18.8%)98 (22.3%)4
 Negative758109 (80.7%)130 (81.2%)342 (77.7%)177
PaP <0.001P < 0.001P <0.001

Discussion

We describe some epidemiological characteristics of patients with oral clefts in a large sample size from all parts of Thailand. The most common type of oral clefts was CL/CP 469/784 (59.8%). This finding is consistent with previous studies in Japanese and Chinese populations. However, the proportions differed from those in populations with African ancestry [9, 19, 20]. Several studies found that CLO was the most common type of cleft in populations with African ancestry [10, 19, 21]. We found that oral clefts were more frequent in male patients (male/ female; 500/441) as consistent with previous reports [22,23].

The present study revealed a significantly greater use of nonprescribed drugs by mothers during pregnancy associated with patients with CPO (P = 0.049) and maternal alcohol consumption during pregnancy associated with CL/CP (P = 0.047). Maternal use of medications during pregnancy was associated with an increased risk of having children with oral clefts in a population from Kosovo [24], while an association between maternal consumption of alcohol and oral clefts was found in populations from Spain [13] and Brazil [11, 12].

We found that a proportion of patients with oral clefts had other family members affected (19.2% in CL, 18.8% in CPO, and 22.3% in CL/CP). A previous study of a population from the southern region of Thailand [25] showed that 17.7% of patients with oral cleft had a family history of oral clefts.

In conclusion, CL/CP is the most common type of oral cleft in the Thai population. Consistent with other populations studied by others, some significant epidemiological and genetic factors, including maternal use of nonprescribed medications and consumption of alcohol during pregnancy, and family history of oral clefts tended to be associated with a higher prevalence of oral clefts.

Acknowledgments

We thank the medical staff of the Thai Red Cross Society and the provincial hospitals for collecting data. This work was supported by the Thailand Research Fund, the Chulalongkorn Academic Advancement into its 2nd Century Project, Birth Defects Association (Thailand), and Thai Health Promotion Foundation.

Conflict of interest statement: The authors declare that there is no conflict of interest in this research.

References

  • 1

    Watkins SE, Meyer RE, Strauss RP, Aylsworth AS. Classification, epidemiology, and genetics of orofacial clefts. Clin Plast Surg. 2014; 41:149-63.

  • 2

    Tolarova MM, Cervenka J. Classification and birth prevalence of orofacial clefts. Am J Med Genet. 1998; 75:126-37.

  • 3

    Pradubwong S, Pongpagatip S, Prathanee B, Thanawirattananit P, Ratanaanekchai T, Chowchuen B. The treatment of 4-5 year-old patients with cleft lip and cleft palate in Tawanchai Center: follow-up. J Med Assoc Thai. 2012; 95 Suppl 11:S135-40.

  • 4

    Voraphani N, Siriwan P, Shotelersuk V. Pedigree analysis study of oral cleft patient in Thailand. Chula Ped J. 2004; 4:21-5.

  • 5

    Mutarai T, Ritthagol W, Hunsrisakhun J. Factors influencing early childhood caries of cleft lip and/or palate children aged 18 to 36 months in southern Thailand. Cleft Palate Craniofac J. 2008; 45:468-72.

  • 6

    Bessell A, Hooper L, Shaw WC, Reilly S, Reid J, Glenny AM. Feeding interventions for growth and development in infants with cleft lip, cleft palate or cleft lip and palate. The Cochrane Database of Systematic Reviews. 2011: CD003315.

  • 7

    Wan T, Wang G, Yang Y. The nutrition status of mild form Pierre Robin sequence before cleft palate repair: an analysis of 34 cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014; 118:43-6.

  • 8

    Blanco R, Colombo A, Suazo J. Maternal obesity is a risk factor for orofacial clefts: a meta-analysis. Br J Oral Maxillofac Surg. 2015; 53:699-704.

  • 9

    Dai L, Zhu J, Mao M, Li Y, Deng Y, Wang Y, et al. Time trends in oral clefts in Chinese newborns: data from the Chinese National Birth Defects Monitoring Network. Birth Defects Res A Clin Mol Teratol. 2010; 88:41-7.

  • 10

    Elliott RF, Jovic G, Beveridge M. Seasonal variation and regional distribution of cleft lip and palate in Zambia. Cleft Palate Craniofac J. 2008; 45:533-38.

  • 11

    Bezerra JF, Oliveira GH, Soares CD, Cardoso ML, Ururahy MA, Neto FP, et al. Genetic and non-genetic factors that increase the risk of non-syndromic cleft lip and/or palate development. Oral diseases. 2015; 21:393-99.

  • 12

    Leite IC, Koifman S. Oral clefts, consanguinity, parental tobacco and alcohol use: a case-control study in Rio de Janeiro, Brazil. Braz Oral Res. 2009; 23:31-7.

  • 13

    Molina-Solana R, Yanez-Vico RM, Iglesias-Linares A, Mendoza-Mendoza A, Solano-Reina E. Current concepts on the effect of environmental factors on cleft lip and palate. Int J Oral Maxillofac Surg. 2013; 42:177-84.

  • 14

    Lieff S, Olshan AF, Werler M, Strauss RP, Smith J, Mitchell A. Maternal cigarette smoking during pregnancy and risk of oral clefts in newborns. Am J Epidemiol. 1999; 150:683-94.

  • 15

    Wichajarn K, Panamonta O, Pradubwong S, Panamonta M, Weraarchakul W, Chowchuen B. Prevalence and type of associated syndromes in patients with cleft lip and cleft palate who received the treatment in Tawanchai Center until 4-5 years of age. J Med Assoc Thai. 2014; 97 Suppl 10:S105-9.

  • 16

    Pisek A, Pitiphat W, Chowchuen B, Pradubwong S. Oral health status and oral impacts on quality of life in early adolescent cleft patients. J Med Assoc Thai. 2014; 97 Suppl 10:S7-16.

  • 17

    Koillinen H, Lahermo P, Rautio J, Hukki J, Peyrard- Janvid M, Kere J. A genome-wide scan of nonsyndromic cleft palate only (CPO) in Finnish multiplex families. J Med Genet. 2005; 42:177-84.

  • 18

    Brito LA, Meira JG, Kobayashi GS, Passos-Bueno MR. Genetics and management of the patient with orofacial cleft. Plast Surg Int. 2012:782821. doi: 10.1155/2012/782821.

  • 19

    Manyama M, Rolian C, Gilyoma J, Magori CC, Mjema K, Mazyala E, et al. An assessment of orofacial clefts in Tanzania. BMC Oral Health. 2011; 11:5.

  • 20

    Natsume N, Kawai T, Kohama G, Teshima T, Kochi S, Ohashi Y, et al. Incidence of cleft lip or palate in 303738 Japanese babies born between 1994 and 1995. Br J Oral Maxillofac Surg. 2000; 38:605-7.

  • 21

    Spritz RA, Arnold TD, Buonocore S, Carter D, Fingerlin T, Odero WW, et al. Distribution of orofacial clefts and frequent occurrence of an unusual cleft variant in the Rift Valley of Kenya. Cleft Palate Craniofac J. 2007; 44:374-77.

  • 22

    Kianifar H, Hasanzadeh N, Jahanbin A, Ezzati A. Cleft lip and palate: a 30-year epidemiologic study in north-east of Iran. Iran J Otorhinolaryngol. 2015; 27: 35-41.

  • 23

    Natsume N, Kawai T, Ogi N, Yoshida W. Maternal risk factors in cleft lip and palate: case control study. Br J Oral Maxillofac Surg. 2000; 38:23-25.

  • 24

    Salihu S, Krasniqi B, Sejfija O, Heta N, Salihaj N, Geci A, et al. Analysis of potential oral cleft risk factors in the Kosovo population. Int J Surg. 2014; 99:161-5.

  • 25

    Jaruratanasirikul S, Chichareon V, Pattanapreechawong N, Sangsupavanich P. Cleft lip and/or palate: 10 years experience at a pediatric cleft center in Southern Thailand. Cleft Palate Craniofac J. 2008; 45:597-602

Footnotes

a

chi-square test

a

chi-square test

*

P < 0.05

a

chi-square test

a

chi-square test

*

P < 0.05

a

chi-square test

1

Watkins SE, Meyer RE, Strauss RP, Aylsworth AS. Classification, epidemiology, and genetics of orofacial clefts. Clin Plast Surg. 2014; 41:149-63.

2

Tolarova MM, Cervenka J. Classification and birth prevalence of orofacial clefts. Am J Med Genet. 1998; 75:126-37.

3

Pradubwong S, Pongpagatip S, Prathanee B, Thanawirattananit P, Ratanaanekchai T, Chowchuen B. The treatment of 4-5 year-old patients with cleft lip and cleft palate in Tawanchai Center: follow-up. J Med Assoc Thai. 2012; 95 Suppl 11:S135-40.

4

Voraphani N, Siriwan P, Shotelersuk V. Pedigree analysis study of oral cleft patient in Thailand. Chula Ped J. 2004; 4:21-5.

5

Mutarai T, Ritthagol W, Hunsrisakhun J. Factors influencing early childhood caries of cleft lip and/or palate children aged 18 to 36 months in southern Thailand. Cleft Palate Craniofac J. 2008; 45:468-72.

6

Bessell A, Hooper L, Shaw WC, Reilly S, Reid J, Glenny AM. Feeding interventions for growth and development in infants with cleft lip, cleft palate or cleft lip and palate. The Cochrane Database of Systematic Reviews. 2011: CD003315.

7

Wan T, Wang G, Yang Y. The nutrition status of mild form Pierre Robin sequence before cleft palate repair: an analysis of 34 cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014; 118:43-6.

8

Blanco R, Colombo A, Suazo J. Maternal obesity is a risk factor for orofacial clefts: a meta-analysis. Br J Oral Maxillofac Surg. 2015; 53:699-704.

9

Dai L, Zhu J, Mao M, Li Y, Deng Y, Wang Y, et al. Time trends in oral clefts in Chinese newborns: data from the Chinese National Birth Defects Monitoring Network. Birth Defects Res A Clin Mol Teratol. 2010; 88:41-7.

10

Elliott RF, Jovic G, Beveridge M. Seasonal variation and regional distribution of cleft lip and palate in Zambia. Cleft Palate Craniofac J. 2008; 45:533-38.

11

Bezerra JF, Oliveira GH, Soares CD, Cardoso ML, Ururahy MA, Neto FP, et al. Genetic and non-genetic factors that increase the risk of non-syndromic cleft lip and/or palate development. Oral diseases. 2015; 21:393-99.

12

Leite IC, Koifman S. Oral clefts, consanguinity, parental tobacco and alcohol use: a case-control study in Rio de Janeiro, Brazil. Braz Oral Res. 2009; 23:31-7.

13

Molina-Solana R, Yanez-Vico RM, Iglesias-Linares A, Mendoza-Mendoza A, Solano-Reina E. Current concepts on the effect of environmental factors on cleft lip and palate. Int J Oral Maxillofac Surg. 2013; 42:177-84.

14

Lieff S, Olshan AF, Werler M, Strauss RP, Smith J, Mitchell A. Maternal cigarette smoking during pregnancy and risk of oral clefts in newborns. Am J Epidemiol. 1999; 150:683-94.

15

Wichajarn K, Panamonta O, Pradubwong S, Panamonta M, Weraarchakul W, Chowchuen B. Prevalence and type of associated syndromes in patients with cleft lip and cleft palate who received the treatment in Tawanchai Center until 4-5 years of age. J Med Assoc Thai. 2014; 97 Suppl 10:S105-9.

16

Pisek A, Pitiphat W, Chowchuen B, Pradubwong S. Oral health status and oral impacts on quality of life in early adolescent cleft patients. J Med Assoc Thai. 2014; 97 Suppl 10:S7-16.

17

Koillinen H, Lahermo P, Rautio J, Hukki J, Peyrard- Janvid M, Kere J. A genome-wide scan of nonsyndromic cleft palate only (CPO) in Finnish multiplex families. J Med Genet. 2005; 42:177-84.

18

Brito LA, Meira JG, Kobayashi GS, Passos-Bueno MR. Genetics and management of the patient with orofacial cleft. Plast Surg Int. 2012:782821. doi: 10.1155/2012/782821.

19

Manyama M, Rolian C, Gilyoma J, Magori CC, Mjema K, Mazyala E, et al. An assessment of orofacial clefts in Tanzania. BMC Oral Health. 2011; 11:5.

20

Natsume N, Kawai T, Kohama G, Teshima T, Kochi S, Ohashi Y, et al. Incidence of cleft lip or palate in 303738 Japanese babies born between 1994 and 1995. Br J Oral Maxillofac Surg. 2000; 38:605-7.

21

Spritz RA, Arnold TD, Buonocore S, Carter D, Fingerlin T, Odero WW, et al. Distribution of orofacial clefts and frequent occurrence of an unusual cleft variant in the Rift Valley of Kenya. Cleft Palate Craniofac J. 2007; 44:374-77.

22

Kianifar H, Hasanzadeh N, Jahanbin A, Ezzati A. Cleft lip and palate: a 30-year epidemiologic study in north-east of Iran. Iran J Otorhinolaryngol. 2015; 27: 35-41.

23

Natsume N, Kawai T, Ogi N, Yoshida W. Maternal risk factors in cleft lip and palate: case control study. Br J Oral Maxillofac Surg. 2000; 38:23-25.

24

Salihu S, Krasniqi B, Sejfija O, Heta N, Salihaj N, Geci A, et al. Analysis of potential oral cleft risk factors in the Kosovo population. Int J Surg. 2014; 99:161-5.

25

Jaruratanasirikul S, Chichareon V, Pattanapreechawong N, Sangsupavanich P. Cleft lip and/or palate: 10 years experience at a pediatric cleft center in Southern Thailand. Cleft Palate Craniofac J. 2008; 45:597-602

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