In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo begin to change shape and form the neural tube.

[3] The number of deaths in the US each year due to neural tube defects also declined from 1,200 before folate fortification was started to 840.

Open NTDs include anencephaly, encephaloceles, hydranencephaly, iniencephaly, schizencephaly, and the most common form, spina bifida.

Infants born with this condition lack the main part of the forebrain and are usually blind, deaf and display major craniofacial anomalies.

[10] Despite the wide range in its implications, encephaloceles are most likely to be caused by improper separation of the surface ectoderm and the neuroectoderm after the closure of the neural folds in the fourth week of gastrulation.

[16] Theories regarding the causes of hydrancephaly include: Iniencephaly is a rare neural tube defect that results in extreme bending of the head to the spine.

[27] 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.

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.

Melanin works as either an optical filter to disperse the incoming UV radiation rays or free radical to stabilize the hazardous photochemical products.

The association seen between reduced neural tube defects 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 NTDs by not exposing this otherwise sub-clinical mutation to aggravating conditions.

[36] Other potential causes can include folate antimetabolites (such as methotrexate), mycotoxins in contaminated corn meal, arsenic, hyperthermia in early development, and radiation.

[42] Cigarette smoke during pregnancy, including secondhand exposure, can increase the risk of neural tube defects.

[43] 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 neural tube defects.

[50][51] Incidence of neural tube defects has been shown to decline through maintenance of adequate folic acid levels prior to and during pregnancy.

[52] In 1996, the United States Food and Drug Administration published regulations requiring the addition of folic acid to enriched breads, cereals, flour and other grain products.

[53] Similar regulations made it mandatory to fortify selected grain products with folic acid in Canada by 1998.

[54] During the first four weeks of pregnancy (when most women do not even realize that they are pregnant), adequate folate intake is essential for proper operation of the neurulation process.

[64][65] Individuals who have previously given birth to a child with a neural tube defect and are trying to conceive again may benefit from a supplement containing 4.0 mg daily, following advice provided by their doctor.

[63] In Canada, guidelines on folic acid intake when trying to conceive is based on a risk assessment of how likely they are to experience a neural tube defect during pregnancy.

Medium risk individuals would also include those taking medications that can interfere with folate absorption such as anticonvulsants, metformin, sulfasalazine, triamterene, and trimethoprim.

[62] If the pregnancy is low risk to develop a neural tube defect then the recommendation for that individual is 0.4 mg daily until 4–6 weeks postpartum or however long breastfeeding lasts.

Aggressive surgical management has improved survival and the functions of infants with spina bifida, meningoceles and mild myelomeningoceles.

Fetal surgery in utero before 26 weeks gestation has been performed with some hope that there is benefit to the outcome including a reduction in Arnold–Chiari malformation and thereby decreases the need for a ventriculoperitoneal shunt but the procedure is very high risk for both mother and baby and is considered extremely invasive with questions that the positive outcomes may be due to ascertainment bias and not true benefit.

[69] Prevalence rates of NTDs at birth used to be a reliable measure for the actual number of children affected by the diseases.

[70] While maternal age may not have a huge impact, mothers that have a body mass index greater than 29 double the risk of their child having an NTD.