External factors
These are factors such as environment, alcohol consumption, drug use, etc. CLP is known to be influenced by environmental risk factors. Consequently, a multifactorial model of inheritance is favored in which genetic risk factors of small individual impact may interact with environmental covariates (Dixon, M.J., Marazita, M.L., Beaty, T.H. & Murray, J.C. (2011). The etiology of both cleft lip with or without cleft palate (CLP) and isolated cleft palate (CP) is thought to be multifactorial, with both genetic and environmental factors playing a role. However, it is clear that environmental factors also play a role and an important area of future research will be to unravel interactions that occur between candidate genes and environmental factors during early development of the embryo (Cobourne, 2004).
It is logical to state that the true etiology relevant to these conditions cannot be treated in isolation, but it should be remembered that intrauterine enviremental (in utero) factors will influence foetal development in combination with the individual genetic background of the embryo (Cobourne, 2004).
Alcohol consumption: The present study found an association between oral clefts and smoking and, although not conclusive, supports an association of oral cleft with alcohol (Bille et al., 2007) Results on alcohol intake during pregnancy are much more diverse, possibly because alcohol intake during pregnancy varies substantially over time and between populations. Also maternal alcohol can have an increased incidence on birth defects (Cobourne, 2004). Another study about the influence of alcohol consumption, suggested as a risk factor for the development of a cleft, is ‘binge’ drinking. Binge drinking is known as high doses of alcohol in short periods of time. This binge drinking will also increase the risk of CLP during birth (Dixon, M.J., Marazita, M.L., Beaty, T.H. & Murray, J.C. (2011).
Smoking: The present study found an association between oral clefts and smoking and, although not conclusive, supports an association of oral cleft with alcohol (Bille et. al., 2007) The etiology of both defects is thought to be multi-factorial with genes playing an important role . Among environmental risk factors the only consistently replicated finding is a modest effect of smoking . Maternal cigarette smoking, leading to embryonic hypoxia, has been associated with an increased incidence of non-syndromic CLP. The evidence for association is far from overwhelming. There is some suggestion that the risk of clefting associated with maternal smoking can be increased in infants carrying the cleft associated TGF mutation. Potential synergism between these two factors has also been refuted.
Folic acid antagonists: Nutritional status of pregnant mothers with respect to incidences of clefting , folic acid supplementation is an method of reducing CLP incidence. Folic acid helps stimulating the development of the nervous system. There is conclusive evidence for maternal folate supplementation in the prevention of neural tube defects and it may predispose to orofacial clefting. (Medical research council, 1991 ; Cobourne, 2004). Recent research has shown that there are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Not only the effect of the folic acid supplements is usefull on the individual and the family, but also usefull is the low cost of the supplements.
More factors: At the time, there is a lot of research on influences that provoke CLP during pregnancy. For example: hyperthermia, stress, obesity, occupational exposures and infection. On a lot of these examples there are small results of being an influence on provoking CLP during pregnancy. To be sure about these facts there has to be done more research. By now there is to less evidence to say that these factors may have harmful effects on a relatively rare disorder such as clefting (Dixon et al., 2011).