Further investigations are needed to identify new gene-environment associations. Most of the reported risk factors in reviewed papers are weak. However, we have to note that multiple risk factors contribute the CL/P etiology, therefore the effect of each factor is rather small. Poor maternal nutritional status leads to many complications, in both the short and long term.

The first few weeks of embryo development are particularly sensitive to changes in the maternal environment reflecting changes in the external world. Although most factors appear to explain very little of the population burden of CL/P, maternal nutritional factors do appear to substantially contribute to the complex etiologies of CL/P. There are buy Enzalutamide very few exposures for which the available information is sufficient to make fully evidence-based recommendations regarding the clinical management of teratogenic risks in humans. Nevertheless, physicians must advise pregnant women about identified potential risks [88] and the reviewed papers delivered some new data regarding what constitutes a healthy diet and lifestyle during pregnancy. Experiments with livestock species show that sound nutritional

management LDK378 ic50 at key stages in the reproductive process provides an acceptable and effective way to improve the reproductive outcome, not only in terms of the number of offspring born, but also in terms of their physiological well-being and viability [89]. The overarching principles of nutrition are believed to be similar among mammals [89]. If a type of diet has been used for a “long time” without adverse effects being reported, does this represent good evidence that it is safe to use in periconceptional period? Less potent teratogens and unhealthy diet patterns may remain undetected for long periods. Phenytoin was used from 1938 as an antiepileptic drug, while its teratogenic effects were only suggested 30 years after its introduction to the market Baricitinib and supported in 1973 [90]. Very often physicians simply tell women to eat “a healthy diet” and gain appropriate weight during pregnancy. However,

to achieve this, they need to show direction to do so properly [91]. Prospective parents should discuss important health behaviors that may affect a pregnancy such as vitamin and micronutrient intake, lifestyle, and occupation with their medical care provider. Until now, conclusive evidence was provided for periconceptional folate and the prevention of neural tube defects [14]. The information from the reviewed research reports regarding the homeostasis of trace elements [22, 25], citrulline [26], and lipid-soluble vitamins [19, 20] is somewhat limited and preliminary. However, it could be useful while preparing some reasonable guidelines for prospective parents, who wish to minimize their chances of having a baby with CL/P.