Neural tube defect - wikipedia Neural tube defect Neural tube defect Illustration of a child with spina bifida, the most common NTD Specialty Medical genetics Neural tube defects ( NTDs ) are a group of birth defects in which an opening in the spinal cord or brain remains from early in human development. In the 3rd week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo begin to change shape and form the neural tube. When the neural tube does not close completely, an NTD develops. Specific types include : spina bifida which affects the spine, anencephaly which results in little to no brain, encephalocele which affects the skull, and iniencephaly which results in severe neck problems. NTDs are one of the most common birth defects, affecting over 300,000 births each year worldwide. For example, spina bifida affects approximately 1,500 births annually in the USA, or about 3.5 in every 10,000 ( 0.035 % of US births ), which has decreased from around 5 per 10,000 ( 0.05 % of US births ) since folate fortification of grain products was started. 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. Contents 1 Types 1.1 Anencephaly 1.2 Encephaloceles 1.3 Hydranencephaly 1.4 Iniencephaly 1.5 Spina bifida 1.5. 1 Spina bifida cystica 1.5. 2 Spina bifida occulta 2 Cause 2.1 Folate deficiency 2.2 Gene - environment interaction 2.3 Other 3 Diagnosis 4 Prevention 5 Treatment 6 Epidemiology 7 References 8 External links Types There are two types of NTDs : open, which are more common, and closed. Open NTDs occur when the brain and / or spinal cord are exposed at birth through a defect in the skull or vertebrae ( back bones ). Examples of open NTDs are anencephaly, encephaloceles, hydranencephaly, iniencephaly, schizencephaly, and spina bifida. Rarer types of NTDs are called closed NTDs. Closed NTDs occur when the spinal defect is covered by skin. Common examples of closed NTDs are lipomyelomeningocele, lipomeningocele, and tethered cord. Anencephaly Anencephaly ( without brain ) is a neural tube defect that occurs when the head end of the neural tube fails to close, usually during the 23rd and 26th days of pregnancy, resulting in an absence of a major portion of the brain and skull. Infants born with this condition are born without the main part of the forebrain -- the largest part of the cerebrum -- and are usually blind, deaf and unconscious. The lack of a functioning cerebrum will ensure that the infant will never gain consciousness. Infants are either stillborn or usually die within a few hours or days after birth. Encephaloceles Encephaloceles are characterized by protrusions of the brain through the skull that are sac - like and covered with membrane. They can be a groove down the middle of the upper part of the skull, between the forehead and nose, or the back of the skull. Encephaloceles are often obvious and diagnosed immediately. Sometimes small encephaloceles in the nasal and forehead are undetected. Hydranencephaly Hydranencephaly is a condition in which the cerebral hemispheres are missing and instead filled with sacs of cerebrospinal fluid. Iniencephaly Iniencephaly is a rare neural tube defect that results in extreme bending of the head to the spine. The diagnosis can usually be made on antenatal ultrasound scanning, but if not will undoubtedly be made immediately after birth because the head is bent backwards and the face looks upwards. Usually the neck is absent. The skin of the face connects directly to the chest and the scalp connects to the upper back. The infant will usually not survive more than a few hours. Spina bifida Spina bifida is further divided into two subclasses, spina bifida cystica and spina bifida occulta. Spina bifida cystica This includes meningocele and myelomeningocele. Meningocele is less severe and is characterized by herniation of the meninges, but not the spinal cord, through the opening in the spinal canal. Myelomeningocele involves herniation of the meninges as well as the spinal cord through the opening. Spina bifida occulta In this type of neural tube defect, the meninges do not herniate through the opening in the spinal canal. By definition, spina bifida occulta means hidden split spine. The most frequently seen form of spina bifida occulta is when parts of the bones of the spine, called the spinous process, and the neural arch appear abnormal on a radiogram, without involvement of the spinal cord and spinal nerves. The risk of recurrence in those who have a first degree relative ( a parent or sibling ) is 5 -- 10 times greater compared to the general population. Cause Folate deficiency Inadequate levels of folate ( vitamin B9 ) and vitamin B12 during pregnancy have been found to lead to increased risk of NTDs. 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 neural cells during neural tube closure. Failure of post-translational methylation of the cytoskeleton, required for differentiation has been implicated in neural tube defects. Vitamin B is also an important receptor in the folate biopathway such that studies have shown deficiency in vitamin B contributes to risk of NTDs 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 neural tube defects. 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. Gene - environment interaction A deficiency of folate itself does not cause neural tube defects. 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. 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 NTDs. Studies have shown that both maternal cigarette smoking and maternal exposure to secondhand smoke increased the risk for neural tube defects in offspring. A mechanism by which maternal exposure to cigarette smoke could increase NTD 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 neural tube defects. 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. Other Folic acid supplementation reduces the prevalence of neural tube defects by approximately 70 % of neural tube defects indicating that 30 % are not folate - dependent and are due to some cause other than alterations of methylation patterns. Multiple other genes related to neural tube defects exist which are candidates for folate insensitive neural tube defects. There are also several syndromes such as Meckel syndrome, and Triploid Syndrome which are frequently accompanied by neural tube defects that are assumed to be unrelated to folate metabolism Diagnosis Tests for neural tube defects include ultrasound examination and measurement of maternal serum alpha - fetoprotein ( MSAFP ). Second trimester ultrasound is recommended as the primary screening tool for NTDs, and MSAFP as a secondary screening tool. This is due to increased safety, increased sensitivity and decreased false positive rate of ultrasound as compared to MSAFP. Amniotic fluid alpha - fetoprotein ( AFAFP ) and amniotic fluid acetylcholinesterase ( AFAChE ) tests are also used to confirming if ultrasound screening indicates a positive risk. Often, these defects are apparent at birth, but acute defects may not be diagnosed until much later in life. An elevated MSAFP measured at 16 -- 18 weeks gestation is a good predictor of open neural tube defects, however the test has a very high false positive rate, ( 2 % of all women tested in Ontario, Canada between 1993 and 2000 tested positive without having an open neural tube defect, although 5 % is the commonly quoted result worldwide ) and only a portion of neural tube defects are detected by this screen test ( 73 % in the same Ontario study ). MSAFP screening combined with routine ultrasonography has the best detection rate although detection by ultrasonography is dependent on operator training and the quality of the equipment. Prevention 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. It is important to note that 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. Therefore, women who could become pregnant are advised to eat foods fortified with folic acid or take supplements in addition to eating folate - rich foods to reduce the risks of serious birth defects. In Canada, mandatory fortification of selected foods with folic acid has been shown to reduce the incidence of neural tube defects by 46 %. Women who may become pregnant are advised to get 400 micrograms of folic acid daily. Women who have previously given birth to a child with a neural tube defect may benefit from a supplement containing 4.0 mg / 5.0 mg in the UK mg daily, following advice provided by their doctor. Treatment As of 2008, treatments of NTDs depends on the severity of the complication. No treatment is available for anencephaly and infants usually do not survive more than a few hours. Aggressive surgical management has improved survival and the functions of infants with spina bifida, meningoceles and mild myelomeningoceles. The success of surgery often depends on the amount of brain tissue involved in the encephalocele. The goal of treatment for NTDs is to allow the individual to achieve the highest level of function and independence. Fetal surgery in utero before 26 weeks gestation has been performed with some hope that there is benefit to the final 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. Further, this surgery is not a cure for all problems associated with a neural tube defect. Other areas of research include tissue engineering and stem cell therapy but this research has not been used in humans. Epidemiology. Deaths from neural tube defects per million persons in 2012 0 -- 0 1 -- 1 2 -- 3 4 -- 6 7 -- 10 11 -- 15 16 -- 20 21 -- 28 29 -- 69 Neural tube defects resulted in 71,000 deaths globally in 2010. It is unclear how common the condition is in low income countries. References ^ Jump up to : `` Neural Tube Defects ( NTDs ) : Condition Information ''. National Institute of Child Health and Human Development, U.S. National Institutes of Health. 2017. Retrieved 30 November 2017. Jump up ^ National Center on Birth Defects and Developmental Disabilities ( 2012 ). `` Neural Tube Defects ( Annual Report ) '' ( PDF ). US Centers for Disease Control and Prevention. ^ Jump up to : `` Spina Bifida - Data and Statistics ''. National Center on Birth Defects and Developmental Disabilities, US Centers for Disease Control and Prevention. 12 October 2016. 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Jump up ^ Zaganjor, Ibrahim ; Sekkarie, Ahlia ; Tsang, Becky L. ; Williams, Jennifer ; Razzaghi, Hilda ; Mulinare, Joseph ; Sniezek, Joseph E. ; Cannon, Michael J. ; Rosenthal, Jorge ( 2016 - 04 - 11 ). `` Describing the Prevalence of Neural Tube Defects Worldwide : A Systematic Literature Review ''. PLoS ONE. 11 ( 4 ). doi : 10.1371 / journal. pone. 0151586. ISSN 1932 - 6203. PMC 4827875. PMID 27064786. External links Classification ICD - 10 : Q00, Q01, Q05 ICD - 9 - CM : 740, 741, 742 OMIM : 182940 301410 MeSH : D009436 DiseasesDB : 8926 External resources eMedicine : neuro / 244 ped / 2805 `` Neural Tube Defects ''. MedlinePlus. U.S. National Library of Medicine. St. Joseph 's Hospital and Medical Center Fetal Care Center Preventing Neural Tube Birth Defects : A Prevention Model and Resource Guide : Centre for Disease Control and Prevention ( CDC ) hide Congenital malformations and deformations of nervous system ( Q00 -- Q07, 740 -- 742 ) Brain Neural tube defect Anencephaly Acephaly Acrania Acalvaria Iniencephaly Encephalocele Chiari malformation Other Microcephaly Congenital hydrocephalus Dandy -- Walker syndrome other reduction deformities Holoprosencephaly Lissencephaly Microlissencephaly Pachygyria Hydranencephaly Septo - optic dysplasia Megalencephaly Hemimegalencephaly CNS cyst Porencephaly Schizencephaly Polymicrogyria Bilateral frontoparietal polymicrogyria Spinal cord Neural tube defect Spina bifida Rachischisis Other Currarino syndrome Diastomatomyelia Syringomyelia Retrieved from `` https://en.wikipedia.org/w/index.php?title=Neural_tube_defect&oldid=842552303 '' Categories : Congenital disorders of nervous system Animal developmental biology Hidden categories : Infobox medical condition ( new ) All articles with unsourced statements Articles with unsourced statements from November 2017 Talk Contents About Wikipedia Deutsch עברית Nederlands Polski ไทย Türkçe Edit links This page was last edited on 23 May 2018, at 05 : 24. 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Question: when do neural tube defects occur during pregnancy
Answer: the 3rd week