Folate deficiency Inadequate levels of folate (vitamin B9) and vitamin B12 during pregnancy have been found to lead to increased risk of<unk> s. Although both are part of the same biopathway, folate deficiency is much more common and therefore more of a concern. Folate is required for the production and maintenance of new cells, for DNA synthesis and RNA synthesis. Folate is needed to carry one carbon groups for methylation and nucleic acid synthesis. It has been hypothesized that the early human embryo may be particularly vulnerable to folate deficiency due to differences of the functional enzymes in this pathway during embryogenesis combined with high demand for post translational methylations of the cytoskeleton in<unk>  cells during<unk> <unk>  closure. Failure of post-translational methylation of the cytoskeleton, required for differentiation has been implicated in<unk> s. Vitamin B12 is also an important receptor in the folate biopathway such that studies have shown deficiency in vitamin B12 contributes to risk of<unk> s as well. There is substantial evidence that direct folic supplementation increases blood serum levels of bioavailable folate even though at least one study have shown slow and variable activity of dihydrofolate reductase in human liver. A diet rich in natural folate (350 μg/d) can show as much increase in plasma folate as taking low levels of folic acid (250 μg/d) in individuals However a comparison of general population outcomes across many countries with different approaches to increasing folate consumption has found that only general food fortification with folic acid reduces<unk> s. While there have been concerns about folic acid supplementation being linked to an increased risk for cancer, a systematic review in 2012 shows there is no evidence except in the case of prostate cancer which indicates a modest reduction in risk. There have been studies showing the relationship between<unk> s, folate deficiency and the difference of skin pigmentation within human populations across different latitudes. There are many factors that would influence the folate levels in human bodies: (i) the direct dietary intake of folic acid through fortified products, (ii) environmental agents such as UV radiation. In concern with the latter, the UV radiation-induced folate photolysis has been shown via in vitro and in vivo studies to decrease the folate level and implicate in etiology of<unk> s not only in humans but other amphibian species. Therefore, a protection against the UV radiation-induced photolysis of folate is imperative for the evolution of human populations living in tropical regions where the exposure to UV radiation is high over the year. One body natural adaptation is to elevate the concentration of melanin inside the skin. Melanin works as either an optical filter to disperse the incoming UV radiation rays or free radical to stabilize the hazardous photochemical products. Multiple studies have demonstrated the highly melanized integument as a defense against folate photolysis in Native Americans or African Americans correlates with lower occurrence of<unk> s in general. Genetic deficiencies As reported by Bruno Reversade and colleagues, the inactivation of the NUAK2 kinase in humans leads to anencephaly. This fatal birth<unk>  is believed to arise as a consequence of impaired HIPPO signalling. Other genes such as TRIM36 have also been associated with anencephaly in humans. Gene-environment interaction A deficiency of folate itself does not cause<unk> s. The association seen between reduced<unk> s and folic acid supplementation is due to a gene-environment interaction such as vulnerability caused by the C677T Methylenetetrahydrofolate reductase (MTHFR) variant. Supplementing folic acid during pregnancy reduces the prevalence of<unk> s by not exposing this otherwise sub-clinical mutation to aggravating conditions. Other potential causes can include folate antimetabolites (such as methotrexate), mycotoxins in contaminated corn meal, arsenic, hyperthermia in early development, and radiation. Maternal obesity has also been found to be a risk factor for<unk> s. Studies have shown that both maternal cigarette smoking and maternal exposure to secondhand smoke increased the risk for<unk> s in offspring. A mechanism by which maternal exposure to cigarette smoke could increase<unk>  risk in offspring is suggested by several studies that show an association between cigarette smoking and elevations of homocysteine levels. Cigarette smoke during pregnancy, including secondhand exposure, can increase the risk of<unk> s. All of the above may act by interference with some aspect of normal folic acid metabolism and folate linked methylation related cellular processes as there are multiple genes of this type associated with<unk> s. Other Folic acid supplementation reduces the prevalence of<unk> s by approximately 70% of<unk> s indicating that 30% are not folate-dependent and are due to some cause other than alterations of methylation patterns. Multiple other genes related to<unk> s exist which are candidates for folate insensitive<unk> s. There are also several syndromes such as Meckel syndrome, and Triploid Syndrome which are frequently accompanied by<unk> s that are assumed to be unrelated to folate metabolism
Neural tube defect
Birth defect
Congenital limb deformities
Craniofacial abnormality
Vocal cord dysfunction
Neonatal sepsis
Perinatal asphyxia
Renal hypoplasia