Factors of influence

CLP: Cleft Lip and Palate affects approximately 1/700 live births, with wide variability across geographic origin, racial and ethnic groups, as well as environmental exposures and socioeconomic status. In general, Asian and Amerindian populations have the highest reported birth prevalence rates, often as high as 1/500, European-derived populations have intermediate prevalence rates at about 1/1000, and African-derived populations have the lowest prevalence rates at about 1/2500. These observations suggest the relative contribution of individual susceptibility genes may vary across different populations. The frequency of CLP also differs by sex and laterality: there is a 2:1 male to female ratio for clefts involving the lip and approximately a 1:2 male to female ratio for clefts of the palate only; and there is a 2:1 ratio of left to right sided clefts among unilateral cleft lip cases (Dixon, M.J., Marazita, M.L., Beaty, T.H. & Murray, J.C. (2011).
 

Internal factors
The internal facors will be explained first. Internal factors are factors that are ‘inside’ the body. 

In most cases, the cause of a cleft in babies is not clear. Cleft can occur through an combination of predisposition factors and external disturbances in the period between 6 and 12 weeks. We order the causes of clefts into three groups:
1. A disorder in pregnancy
2. Genetic factors
3. A combination of both.

A disorder in pregnancy
Until the sixth a ninth week of pregnancy every baby has a sided cleft lip and cleft jaw. All babies also have up to the ninth a twelfth week a palate cleft. Normally the various parts grow together. When this process is incompletely, then there will remain gaps. 

Genetic factors
This means a disorder in the construction of the child:
- created at the moment of conception. Something similar occurs. For example, a chromosome (genetic material) deviation. Usually there are more congenital abnormalities present, and/ or
- Through one or both parents is the predisposition to cleft passed. Cleft is for example in one of both parents, and/or one or more family members.

A combination of factors
The most common cause of a cleft is a combination of predisposing factors and predisposing factors in pregnancy. Cleft often occurs by more than one factor: we call it multifactorial (Ackersmans-Swart, 2013)

Beside these factors there are 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).