DISCUSIÓN

Discussion of the article "Prevalence of cleft lip and palate and risk indicators: Study of the reference population of Felix Bulnes University Hospital, Santiago de Chile"

Discusión del artículo "Prevalencia de fisura labiopalatina e indicadores de riesgo: Estudio de la población atendida en el Hospital Clínico Félix Bulnes de Santiago de Chile"

José Luis López Cedrún

Jefe de Servicio. Servicio de Cirugía Oral y Maxilofacial. Hospital Juan Canalejo. La Coruña, España

We read with interest the article in which the authors retrospectively study the incidence and etiopathogenesis of congenital cleft lip and/or palate in the reference population of a Chilean hospital. The findings were similar to those of other western areas with regard to the proportion of cleft lip, cleft palate, and complete cleft, as well as the prevalence of the deformity. The risk indicators observed are related to maternal age younger than 20 years, first pregnancy, a high degree of Amerindian ethnicity, and family history. Other factors that are associated, but not statistically significant, are habits (tobacco and alcohol use), exposure to oral contraceptives, radiation, and agricultural chemicals, and chronic diseases such as diabetes, hypertension, and stress.

Some of the factors mentioned have already been documented. The high incidence of cleft lip and/or palate in Native American populations is known, which confirms the risk observed in this study. The documented incidence is similar to that of a recent study of a Bolivian population (1.23/1000 live births).¹

Among environmental factors, a maternal smoking habit has been found in many studies with a consistent, moderate, and statistically significant association.^2,3 Lorente et al.⁴ find an association of cleft palate with alcohol as well as tobacco. However, these authors do not observe an association of cleft palate with smoking after adjusting for the alcohol dose.

As regards maternal age, an epidemiologic study made in the Czech Republic also reports an association of the deformity with maternal age around 15 years and another peak frequency in women more than 35 years old.⁵ Most studies made before the 1970s report an association with older maternal age. After this date, the literature shows both positive and negative associations with older age. A more recent meta-analysis finds no significant correlation between cleft lip and/or palate and maternal age, although the incidence is slightly greater in women more than 40 years old or less than 25 years old. This suggests the influence of other factors, such as undetected chromosomal anomalies, paternal age, racial distribution in some populations, and habits.⁶

As the authors of this study indicate, the greater risk in mothers younger than 20 years old is related with first pregnancy and other risk factors (low social status, smoking and alcohol use). It is known that there is a higher risk of nonchromosomal congenital anomalies and certain specific deformities in lower social strata.⁷ They also report a high familial recurrence of the disease and the initial unawareness of the existence of affected relatives.

A greater risk of disease was found in parents dedicated to farming activities in contact with chemical agents, but the findings were not statistically significant, probably due to sample size. A study conducted in Valencia, Spain showed an association of certain deformities (including clefts) and the involvement of mothers in farming activities in the month before conception and the first trimester of pregnancy; this association was not observed in fathers.⁸ A study in California (EE.UU.) of this environmental factor finds no relation with exposure to chemical agents,⁹ but it is relevant that the study population is involved intensively in industrialized agriculture in this region.

An interesting aspect of the present study was the association of the disease with winter conceptions, probably related to the use of drugs to fight respiratory diseases that are more prevalent at that time of year. The authors also document an association with drugs like oral contraceptives and tranquilizers.

Other genetic factors have been studied in the literature with less convincing results. A variation in several loci that may interact with environmental factors and condition disease risk has been proposed. For instance, Mitchell et al.¹⁰ studied the locus of the alpha receptor of retinoic acid, which is involved in the specific cellular response to retinoic acid and may be implicated in the risk of disease via interaction with vitamin A. This study,¹⁰ which was conducted in a Danish population, found no evidence of risk of orofacial clefts and the receptor cited, possibly because maternal multivitamin supplements protected against this risk. The authors claim¹⁰ that adequate vitamin A levels are required for the normal development of the primary palate. Genetic factors have been examined using modern genetic technologies on specific candidates in search of mutations, but no molecular base that explains the formation of orofacial clefts has been detected. The findings in syndromic patients have been positive and in the future this may help us to clarify the etiopathogenesis of nonsyndromic cases.¹¹

In support of the conclusions of the authors of the present paper and others, it seems that the etiology of congenital cleft lip and/or palate is complex. Genetic factors participate with diverse interactions with environmental factors, thus implying a multifactorial origin. Since it has been not been possible so far to prevent more than a small percentage of deformities, knowledge of any risk factor is relevant. Risk factor analysis in specific populations is important for that reason. In our area, due to the homogeneity of the population, Eurocleft is a major opportunity to participate in a multicenter analysis with a large enough number of cases to ensure sufficient statistical power for valid conclusions.

Bibliografía

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