Neural tube defect

Last updated
Neural tube defect
Spina-bifida.jpg
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 spine or cranium remains from early in human development. 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. When the neural tube does not close completely, an NTD develops.

Contents

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. [1]

NTDs are one of the most common birth defects, affecting over 300,000 births each year worldwide. [2] For example, spina bifida affects approximately 1,500 births annually in the United States, or about 3.5 in every 10,000 (0.035% of US births), [1] [3] which has decreased from around 5 per 10,000 (0.05% of US births) since folate fortification of grain products was started. [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. [4]

Types

There are two classes 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 (spinal column). Open NTDs include anencephaly, encephaloceles, hydranencephaly, iniencephaly, schizencephaly, and the most common form, spina bifida. Closed NTDs occur when the spinal defect is covered by skin. Types of closed NTDs include lipomeningocele, lipomyelomeningocele, and tethered cord. [5]

Anencephaly

Anencephaly (without brain) is a severe neural tube defect that occurs when the anterior-most end of the neural tube fails to close, usually during the 23rd and 26th days of pregnancy. This results in an absence of a major portion of the brain and skull. Infants born with this condition lack the main part of the forebrain and are usually blind, deaf and display major craniofacial anomalies. The lack of a functioning cerebrum will prevent the infant from even gaining consciousness. Infants are either stillborn or usually die within a few hours or days after birth. [6] For example, anencephaly in humans can result from mutations in the NUAK2 kinase. [7]

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. [8] Due to the range in its location, encephaloceles are classified by the location as well as the type of defect it causes. Subtypes include occipital encephalocele, encephalocele of the carnival vault, and nasal encephaloceles (frontoethmoidal encephaloceles and basal encephaloceles), with approximately 80% of all encephaloceles occurring in the occipital area. [9] Encephaloceles are often obvious and diagnosed immediately. Sometimes small encephaloceles in the nasal and forehead are undetected. [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. [11]

Hydranencephaly

Hydranencephaly is a condition in which the cerebral hemispheres are missing and instead filled with sacs of cerebrospinal fluid. People are born with hydranencephaly, but most of the time, the symptoms appear in a later stage. Newborns with hydrancephaly can swallow, cry, sleep and their head is in proportion to their body. [12] However, after a few weeks, the infants develop increased muscle tone and irritability. After a few months, the brain start to fill with cerebrospinal fluid (hydrocephalus). This has several consequences. Infants start to develop problems with seeing, hearing, growing, and learning. The missing parts of the brain and the amount of cerebrospinal fluid can also lead to seizures, spasm, problems with regulating their body temperature, and breathing and digestion problems. Besides problems in the brain, hydranencephaly can also be seen on the outside of the body. Hydrocephalus leads to more cerebrospinal fluid in the brain, which can result in an enlarged head. [13] [14]

The cause of hydranencephaly is not clear. Hydranencephaly is a result of an injury of the nervous system or an abnormal development of the nervous system. The neural tube closes in the sixth week of the pregnancy, [15] so hydranencephaly develops during these weeks of the pregnancy. The cause of these injuries/development is not clear. [16]

Theories regarding the causes of hydrancephaly include:

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. Individuals with iniencephaly generally die within a few hours after birth. [17]

Spina bifida

Spina bifida is further divided into two subclasses, spina bifida cystica and spina bifida occulta. [18]

Causes

Folate deficiency

Inadequate levels of folate (vitamin B9) and vitamin B12 during pregnancy have been found to lead to increased risk of NTDs. [23] [24] Although both are part of the same biopathway, folate deficiency is much more common and therefore more of a concern. [23] [24] 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. [25] Failure of post-translational methylation of the cytoskeleton, required for differentiation has been implicated in neural tube defects. [26] Vitamin B12 is also an important receptor in the folate biopathway such that studies have shown deficiency in vitamin B12 contributes to risk of NTDs as well. [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. [28] [29] 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 [30] 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. [31] 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. [32]

There have been studies showing the relationship between NTDs, 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 NTDs 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 NTDs in general. [33] [34]

Genetic deficiencies

As reported by Bruno Reversade and colleagues, the inactivation of the NUAK2 kinase in humans leads to anencephaly. [7] This fatal birth defect is believed to arise as a consequence of impaired HIPPO signalling. [7] Other genes such as TRIM36 have also been associated with anencephaly in humans. [35]

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. [36] Other potential causes can include folate antimetabolites (such as methotrexate), mycotoxins in contaminated corn meal, arsenic, hyperthermia in early development, and radiation. [37] [38] [39] Maternal obesity has also been found to be a risk factor for NTDs. [40] Studies have shown that both maternal cigarette smoking and maternal exposure to secondhand smoke increased the risk for neural tube defects in offspring. [41] 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. [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. [44]

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. [45] Multiple other genes related to neural tube defects exist which are candidates for folate insensitive neural tube defects. [44] 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 [46]

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. [47] This is due to increased safety, increased sensitivity and decreased false positive rate of ultrasound as compared to MSAFP. [47] Amniotic fluid alpha-fetoprotein (AFAFP) and amniotic fluid acetylcholinesterase (AFAChE) tests are also used to confirming if ultrasound screening indicates a positive risk. [48] 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). [49] 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. [50] [51]

Prevention

Incidence of neural tube defects has been shown to decline through maintenance of adequate folic acid levels prior to and during pregnancy. This is achieved through dietary sources and supplementation of folic acid. [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. Therefore, any individuals 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. [55] [56] [57] In Canada, mandatory fortification of selected foods with folic acid had been shown to reduce the incidence of neural tube defects by 46% compared to incidence prior to mandatory fortification. [58] However, relying on eating a folate-rich diet alone is not recommended for preventing neural tube defects when trying to conceive because a regular diet usually does not contain enough folate to reach pregnancy requirements. [59] [60] All individuals who have the ability to become pregnant are advised to get 400 micrograms of folic acid daily. [61] [62] This daily 400 mcg dose of folic acid can be found in most multivitamins advertised as for women. [63] Higher doses can be found in pre-natal multivitamins but those doses may not be necessary for everyone. [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. Risk is divided into high, moderate, and low risk categories. [62] High risk would include those that had a past experience with neural tube defects, either themselves or during another pregnancy. [62] Medium risk individuals are those with certain conditions that put them at higher risk for experiencing a neural tube defect. These include having a first or second degree relative or partner with a history of neural tube defects, having a gastrointestinal condition that affects normal absorption patterns, advanced kidney disease, kidney dialysis, alcohol over-use, or had another pregnancy resulting in a congenital abnormality that was folate sensitive. Medium risk individuals would also include those taking medications that can interfere with folate absorption such as anticonvulsants, metformin, sulfasalazine, triamterene, and trimethoprim. [62] Low risk would include everyone else that do not fall into either medium or high risk categories. Recommendations on when to start folic acid supplementation for all individuals looking to become pregnant is at least three months preconception. [60] [62] If an individual is in the high risk category, the recommended dose is 4–5 mg of folic acid daily until 12 weeks gestation and then decrease to 0.4–1 mg until 4–6 weeks postpartum or for however long breastfeeding lasts. [62] If an individual is in the medium risk category, the recommended dose is 1 mg of folic acid daily until 12 weeks gestation and then they can either continue at 1 mg or decrease to 0.4 mg daily until 4–6 weeks postpartum or however long breastfeeding lasts. [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. [62] All dose recommendations and risk assessment should be done with the advice of a qualified health care provider. [61]

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. [66] 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 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. [67]

Epidemiology

Deaths from neural tube defects per million persons in 2012 .mw-parser-output .div-col{margin-top:0.3em;column-width:30em}.mw-parser-output .div-col-small{font-size:90%}.mw-parser-output .div-col-rules{column-rule:1px solid #aaa}.mw-parser-output .div-col dl,.mw-parser-output .div-col ol,.mw-parser-output .div-col ul{margin-top:0}.mw-parser-output .div-col li,.mw-parser-output .div-col dd{page-break-inside:avoid;break-inside:avoid-column} .mw-parser-output .legend{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .legend-color{display:inline-block;min-width:1.25em;height:1.25em;line-height:1.25;margin:1px 0;text-align:center;border:1px solid black;background-color:transparent;color:black}.mw-parser-output .legend-text{} 0-0 1-1 2-3 4-6 7-10 11-15 16-20 21-28 29-69 Neural tube defects world map-Deaths per million persons-WHO2012.svg
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. [68] It is unclear how common the condition is in low income countries. [69]

Prevalence rates of NTDs at birth used to be a reliable measure for the actual number of children affected by the diseases. [70] However, due to advances in technology and the ability to diagnose prenatally, the rates at birth are no longer reliable. [70] Measuring the number of cases at birth may be the most practical way, but the most accurate way would be to include stillbirths and live-births. [70] Most studies that calculate prevalence rates only include data from live births and stillborn children and normally exclude the data from abortions and miscarriages. [70] Abortions are a huge contributing factor to the prevalence rates; one study found that in 1986 only a quarter of the pregnancies with an identified NTD were aborted, but that number had already doubled by 1999. [70] Through this data, it is clear that excluding data from abortions could greatly affect the prevalence rates. This could also possibly explain why prevalence rates have appeared to drop. If abortions are not being included in the data but half of the identified cases are being aborted, the data could show that prevalence rates are dropping when they actually are not. However, it is unclear how much of an impact these could have on prevalence rates due to the fact that abortion rates and advances in technology vary greatly by country. [70]

There are many maternal factors that also play a role in prevalence rates of NTDs. [70] These factors include things like maternal age and obesity all the way to things like socioeconomic status along with many others. [70] Maternal age has not been shown to have a huge impact on prevalence rates, but when there has been a relationship identified, older mothers along with very young mothers are at an increased risk. [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. [70] Studies have also shown that mothers with three or more previous children show moderate risk for their next child having an NTD. [70]

Related Research Articles

<span class="mw-page-title-main">Folate</span> Vitamin B9; nutrient essential for DNA synthesis

Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division. As the human body cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements.

<span class="mw-page-title-main">Spina bifida</span> Birth defect of the spinal cord

Spina bifida /ˌspaɪnə ˈbɪfɪdə/ is a birth defect in which there is incomplete closing of the spine and the membranes around the spinal cord during early development in pregnancy. There are three main types: spina bifida occulta, meningocele and myelomeningocele. Meningocele and myelomeningocele may be grouped as spina bifida cystica. The most common location is the lower back, but in rare cases it may be in the middle back or neck.

<span class="mw-page-title-main">Anencephaly</span> Neural tube defect involving absence of much of the brain, skull and scalp

Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day following conception. Strictly speaking, the Greek term translates as "without a brain", but it is accepted that children born with this disorder usually only lack a telencephalon, the largest part of the brain consisting mainly of the cerebral hemispheres, including the neocortex, which is responsible for cognition. The remaining structure is usually covered only by a thin layer of membrane—skin, bone, meninges, etc., are all lacking. With very few exceptions, infants with this disorder do not survive longer than a few hours or days after birth.

<span class="mw-page-title-main">Iniencephaly</span> Rare neural tube defect characterised by fusion of the occiput with the spine

Iniencephaly is a rare type of cephalic disorder characterised by three common characteristics: a defect to the occipital bone, spina bifida of the cervical vertebrae and retroflexion of the head on the cervical spine. Stillbirth is the most common outcome, with a few rare examples of live birth, after which death invariably occurs within a short time.

<span class="mw-page-title-main">Birth defect</span> Condition present at birth regardless of cause

A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part and functional disorders in which problems exist with how a body part works. Functional disorders include metabolic and degenerative disorders. Some birth defects include both structural and functional disorders.

<span class="mw-page-title-main">Prenatal testing</span> Testing for diseases or conditions in a fetus

Prenatal testing is a tool that can be used to detect some birth defects at various stages prior to birth. Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of the zygote, embryo, or fetus, either before gestation even starts or as early in gestation as practicable. Screening can detect problems such as neural tube defects, chromosome abnormalities, and gene mutations that would lead to genetic disorders and birth defects, such as spina bifida, cleft palate, Down syndrome, trisomy 18, Tay–Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, and fragile X syndrome. Some tests are designed to discover problems which primarily affect the health of the mother, such as PAPP-A to detect pre-eclampsia or glucose tolerance tests to diagnose gestational diabetes. Screening can also detect anatomical defects such as hydrocephalus, anencephaly, heart defects, and amniotic band syndrome.

<span class="mw-page-title-main">Nutrition and pregnancy</span> Nutrient intake and dietary planning undertaken before, during and after pregnancy

Nutrition and pregnancy refers to the nutrient intake, and dietary planning that is undertaken before, during and after pregnancy. Nutrition of the fetus begins at conception. For this reason, the nutrition of the mother is important from before conception as well as throughout pregnancy and breastfeeding. An ever-increasing number of studies have shown that the nutrition of the mother will have an effect on the child, up to and including the risk for cancer, cardiovascular disease, hypertension and diabetes throughout life.

<span class="mw-page-title-main">Encephalocele</span> Neural tube defect in which the brain protrudes out of the skull

Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during fetal development. Encephaloceles cause a groove down the middle of the skull, or between the forehead and nose, or on the back side of the skull. The severity of encephalocele varies, depending on its location.

Neurodevelopmental disorders are a group of conditions that begin to emerge during childhood. According to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) published in 2013, these conditions generally appear in early childhood, usually before children start school, and can persist into adulthood. The key characteristic of all these disorders is that they negatively impact a person's functioning in one or more domains of life depending on the disorder and deficits it has caused. All of these disorders and their levels of impairment exist on a spectrum, and affected individuals can experience varying degrees of symptoms and deficits, despite having the same diagnosis.

<span class="mw-page-title-main">Fetal surgery</span> Growing branch of maternal-fetal medicine

Fetal surgery also known as antenatal surgery, prenatal surgery, is a growing branch of maternal-fetal medicine that covers any of a broad range of surgical techniques that are used to treat congenital abnormalities in fetuses who are still in the pregnant uterus. There are three main types: open fetal surgery, which involves completely opening the uterus to operate on the fetus; minimally invasive fetoscopic surgery, which uses small incisions and is guided by fetoscopy and sonography; and percutaneous fetal therapy, which involves placing a catheter under continuous ultrasound guidance.

Food fortification or enrichment is the process of adding micronutrients to food. It can be carried out by food manufacturers, or by governments as a public health policy which aims to reduce the number of people with dietary deficiencies within a population. The predominant diet within a region can lack particular nutrients due to the local soil or from inherent deficiencies within the staple foods; the addition of micronutrients to staples and condiments can prevent large-scale deficiency diseases in these cases.

<span class="mw-page-title-main">Folate deficiency</span> Abnormally low level of folate (vitamin B9) in the body

Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. This may result in a type of anemia in which red blood cells become abnormally large and is a late finding in folate deficiency and folate deficiency anemia is the term given for this medical condition. Signs of folate deficiency are often subtle. Symptoms may include feeling tired, heart palpitations, shortness of breath, feeling faint, open sores on the tongue, loss of appetite, changes in the color of the skin or hair, irritability, and behavioral changes. Temporary reversible infertility may occur. Folate deficiency anemia during pregnancy may give rise to the birth of low weight birth premature infants and infants with neural tube defects.

Vitamin B<sub>12</sub> deficiency Disorder resulting from low blood levels of vitamin B12

Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have few or absent symptoms. In moderate deficiency, feeling tired, headaches, soreness of the tongue, mouth ulcers, breathlessness, feeling faint, rapid heartbeat, low blood pressure, pallor, hair loss, decreased ability to think and severe joint pain and the beginning of neurological symptoms, including abnormal sensations such as pins and needles, numbness and tinnitus may occur. Severe deficiency may include symptoms of reduced heart function as well as more severe neurological symptoms, including changes in reflexes, poor muscle function, memory problems, blurred vision, irritability, ataxia, decreased smell and taste, decreased level of consciousness, depression, anxiety, guilt and psychosis. If left untreated, some of these changes can become permanent. Temporary infertility, reversible with treatment, may occur. A late finding type of anemia known as megaloblastic anemia is often but not always present. In exclusively breastfed infants of vegan mothers, undetected and untreated deficiency can lead to poor growth, poor development, and difficulties with movement.

A multiple of the median (MoM) is a measure of how far an individual test result deviates from the median. MoM is commonly used to report the results of medical screening tests, particularly where the results of the individual tests are highly variable.

<span class="mw-page-title-main">Folate receptor 1</span> Protein-coding gene in the species Homo sapiens

Folate receptor 1 is a protein that in humans is encoded by the FOLR1 gene.

<span class="mw-page-title-main">MTRR (gene)</span> Protein-coding gene in the species Homo sapiens

Methionine synthase reductase, also known as MSR, is an enzyme that in humans is encoded by the MTRR gene.

<span class="mw-page-title-main">Rachischisis</span> Neural tube defect in which the spinal cord is exposed

Rachischisis is a developmental birth defect involving the neural tube. This anomaly occurs in utero, when the posterior neuropore of the neural tube fails to close by the 27th intrauterine day. As a consequence the vertebrae overlying the open portion of the spinal cord do not fully form and remain unfused and open, leaving the spinal cord exposed. Patients with rachischisis have motor and sensory deficits, chronic infections, and disturbances in bladder function. This defect often occurs with anencephaly.

The MOMS Trial was a clinical trial that studied treatment of a birth defect called myelomeningocele, which is the most severe form of spina bifida. The study looked at prenatal and postnatal surgery to repair this defect. The first major phase concluded that prenatal surgery had strong, long-term benefits and some risks.

Sir Nicholas John Wald FRS, FRCP, FMedSci, qualified in medicine from University College London in 1967. He is currently honorary professor of preventive medicine, University College London, honorary professor, Population Health Research Institute, St George's, University of London, visiting professor, University of Oxford, and honorary consultant and adjunct professor, Brown University, Rhode Island. He was professor of environmental and preventive medicine from 1983 to 2019 at Barts and The London School of Medicine and Dentistry. He was co-founder and director of the Wolfson Institute of Preventive Medicine.

The rostral neuropore or anterior neuropore is a region corresponding to the opening of the embryonic neural tube in the anterior portion of the developing prosencephalon. The central nervous system develops from the neural tube, which initially starts as a plate of cells in the ectoderm and this is called the neural plate, the neural plate then undergoes folding and starts closing from the center of the developing fetus, this leads to two open ends, one situated cranially/rostrally and the other caudally. Bending of the neural plate begins on day 22, and the cranial neuropore closes on day 24. giving rise to the lamina terminalis of the brain.

References

  1. 1 2 "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.
  2. ↑ National Center on Birth Defects and Developmental Disabilities (2012). "Neural Tube Defects (Annual Report)" (PDF). US Centers for Disease Control and Prevention.
  3. 1 2 "Spina Bifida - Data and Statistics". National Center on Birth Defects and Developmental Disabilities, US Centers for Disease Control and Prevention. 12 October 2016. Retrieved 29 November 2017.
  4. ↑ National Center on Birth Defects and Developmental Disabilities. "Folic Acid – Birth Defects Count". US Centers for Disease Control and Prevention. Retrieved 13 May 2014.
  5. ↑ Avagliano, Laura; Massa, Valentina; George, Timothy M.; Qureshy, Sarah; Bulfamante, Gaetano; Finnell, Richard H. (2019-11-15). "Overview on Neural tube defects: from development to physical characteristics". Birth Defects Research. 111 (19): 1455–1467. doi:10.1002/bdr2.1380. ISSN   2472-1727. PMC   6511489 . PMID   30421543.
  6. ↑ CDC (2019-12-04). "Facts about Craniosynostosis | CDC". Centers for Disease Control and Prevention. Retrieved 2022-11-28.
  7. 1 2 3 Bonnard, Carine; Navaratnam, Naveenan; Ghosh, Kakaly; Chan, Puck Wee; Tan, Thong Teck; Pomp, Oz; Ng, Alvin Yu Jin; Tohari, Sumanty; Changede, Rishita; Carling, David; Venkatesh, Byrappa (2020-12-07). "A loss-of-function NUAK2 mutation in humans causes anencephaly due to impaired Hippo-YAP signaling". The Journal of Experimental Medicine. 217 (12). doi:10.1084/jem.20191561. ISSN   1540-9538. PMC   7953732 . PMID   32845958.
  8. ↑ "Encephaloceles | National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 2022-11-28.
  9. ↑ Abdel-Aziz, Mosaad; El-Bosraty, Hussam (2010). ""Nasal encephalocele: Endoscopic excision with anesthetic consideration"". International Journal of Pediatric Otorhinolaryngology. 74 (8): 869–873. doi:10.1016/j.ijporl.2010.04.015. PMID   20554034 . Retrieved 2020-11-19.
  10. ↑ "Encephaloceles Information Page". NIH. National institute of Neurological Disorders and Stroke. Retrieved September 15, 2017.
  11. ↑ Broekman, Marike; Hoving, Eelco (2008). ""Nasal encephalocele in a child with Beckwith-Wiedemann syndrome"". Journal of Neurosurgery. 6 (1): 485–7. doi:10.3171/PED/2008/1/6/485. PMID   18518702 . Retrieved 2020-11-19.
  12. ↑ Pavone, Piero; Praticò, Andrea D; Vitaliti, Giovanna; Ruggieri, Martino; Rizzo, Renata; Parano, Enrico; Pavone, Lorenzo; Pero, Giuseppe; Falsaperla, Raffaele (2014-10-18). "Hydranencephaly: cerebral spinal fluid instead of cerebral mantles". Italian Journal of Pediatrics. 40: 79. doi: 10.1186/s13052-014-0079-1 . ISSN   1824-7288. PMC   4421920 . PMID   25326191.
  13. ↑ "Hydranencephaly Information Page". National Institute of Neurological Disorders and Stroke. 2019-03-27.
  14. ↑ "Hydranencephaly". NORD (National Organization for Rare Disorders). Retrieved 2020-05-12.
  15. ↑ "Fetal development: What happens during the first trimester?". Mayo Clinic. Retrieved 2020-05-12.
  16. ↑ Sandoval, Jose I.; De Jesus, Orlando (2022), "Hydranencephaly", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   32644417 , retrieved 2022-11-28
  17. ↑ Korostyshevskaya, Alexandra; Gornostaeva, Alyona; Volkov, Rem; Yarnykh, Vasily (2020-11-19). "Iniencephaly: radiologic and pathomorphologic perinatal observation". Radiology Case Reports. 16 (1): 201–204. doi:10.1016/j.radcr.2020.11.003. ISSN   1930-0433. PMC   7689276 . PMID   33294089.
  18. ↑ Brea, Cristina M.; Munakomi, Sunil (2022), "Spina Bifida", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   32644691 , retrieved 2022-11-28
  19. 1 2 Le, Tao; Bhushan, Vikas; Vasan, Neil (2010). First Aid for the USMLE Step 1: 2010 (20th ed.). McGraw-Hill. p.  127. ISBN   978-0-07-163340-6.
  20. ↑ Saladin, Kenneth (2010). Anatomy and Physiology: The Unity of Form and Function . McGraw-Hill. p.  485. ISBN   978-0-07-352569-3.
  21. ↑ Pittman, T (2008). "Spina bifida occulta". Journal of Neurosurgery. Pediatrics. 1 (2): 113. doi:10.3171/PED/2008/1/2/113. PMID   18352777.
  22. ↑ "Spina Bifida Occulta (for Parents) - Nemours KidsHealth". kidshealth.org. Retrieved 2022-11-28.
  23. 1 2 Molloy, A. M.; Kirke, P. N.; Troendle, J. F.; Burke, H.; Sutton, M.; Brody, L. C.; Scott, JM; Mills, JL (2009). "Maternal Vitamin B-12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification". Pediatrics. 123 (3): 917–23. doi:10.1542/peds.2008-1173. PMC   4161975 . PMID   19255021.
  24. 1 2 De-Regil, Luz Maria; Peña-Rosas, Juan Pablo; Fernández-Gaxiola, Ana C.; Rayco-Solon, Pura (2015-12-14). "Effects and safety of periconceptional oral folate supplementation for preventing birth defects". The Cochrane Database of Systematic Reviews. 2015 (12): CD007950. doi:10.1002/14651858.CD007950.pub3. ISSN   1469-493X. PMC   8783750 . PMID   26662928.
  25. ↑ Bjorklund N, Gordon R (2006). "A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton". Int. J. Dev. Biol. 50 (2–3): 135–41. doi: 10.1387/ijdb.052102nb . PMID   16479482.
  26. ↑ Akchiche; et al. (2012). "Homocysteinylation of neuronal proteins contributes to folate deficiency-associated alterations of differentiation, vesicular transport, and plasticity in hippocampal neuronal cells". The FASEB Journal. 26 (10): 3980–92. doi: 10.1096/fj.12-205757 . PMID   22713523. S2CID   30113330.
  27. ↑ Li, F.; Watkins, D.; Rosenblatt, D. S. (2009). "Vitamin B-12 and birth defects". Molecular Genetics and Metabolism. 98 (1–2): 166–72. doi:10.1016/j.ymgme.2009.06.004. PMID   19586788.
  28. ↑ Anderson C.; et al. (2013). "Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase C677T genotype: results from a crossover trial". Mol. Nutr. Food Res. 57 (4): 637–44. doi:10.1002/mnfr.201200108. PMC   4132693 . PMID   23456769.
  29. ↑ Bailey SW, Ayling JE (Sep 2009). "The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake". Proc Natl Acad Sci U S A. 106 (36): 15424–29. Bibcode:2009PNAS..10615424B. doi: 10.1073/pnas.0902072106 . PMC   2730961 . PMID   19706381.
  30. ↑ Brouwer, I. A.; Van Dusseldorp, M.; West, C. E.; Meyboom, S.; Thomas, C. M.; Duran, M.; Van Het Hof, K. H.; Eskes, T. K.; Hautvast, J. G.; Steegers-Theunissen, R. P. (1999). "Dietary Folate from Vegetables and Citrus Fruit Decreases Plasma Homocysteine Concentrations in Humans in a Dietary Controlled Trial". J. Nutr. 129 (6): 1135–39. doi: 10.1093/jn/129.6.1135 . PMID   10356077.
  31. ↑ International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? BMJ 2005;330:571
  32. ↑ Wein, TN; Pike, E; Wisløff, T; Staff, A; Smeland, S; Klemp, M (12 January 2012). "Cancer risk with folic acid supplements: a systematic review and meta-analysis". BMJ Open . 2 (1): e000653. doi:10.1136/bmjopen-2011-000653. PMC   3278486 . PMID   22240654. Open Access logo PLoS transparent.svg
  33. ↑ Jablonski, Nina G.; Chaplin, George (2010-05-11). "Human skin pigmentation as an adaptation to UV radiation". Proceedings of the National Academy of Sciences. 107 (Supplement 2): 8962–8968. Bibcode:2010PNAS..107.8962J. doi: 10.1073/pnas.0914628107 . ISSN   0027-8424. PMC   3024016 . PMID   20445093.
  34. ↑ "Evolution of Human Skin Coloration — Department of Anthropology". anth.la.psu.edu. Retrieved 2020-05-16.
  35. ↑ Singh, Nivedita; Kumble Bhat, Vishwanath; Tiwari, Ankana; Kodaganur, Srinivas G.; Tontanahal, Sagar J.; Sarda, Astha; Malini, K. V.; Kumar, Arun (2017-03-15). "A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family". Human Molecular Genetics. 26 (6): 1104–1114. doi: 10.1093/hmg/ddx020 . ISSN   1460-2083. PMID   28087737.
  36. ↑ Yan, L; Zhao, L; Long, Y; Zou, P; Ji, G; Gu, A; Zhao, P (October 3, 2012). "Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies". PLOS ONE. 7 (10): e41689. Bibcode:2012PLoSO...741689Y. doi: 10.1371/journal.pone.0041689 . PMC   3463537 . PMID   23056169. Open Access logo PLoS transparent.svg
  37. ↑ Neural Tube Defects at eMedicine
  38. ↑ Suarez, L.; Brender, J. D.; Langlois, P. H.; Zhan, F. B.; Moody, K. (2007). "Pregnant women taking medication for epilepsy have a higher chance of having a child with a neural tube defect. Maternal exposures to hazardous waste sites and industrial facilities and risk of neural tube defects in offspring". Annals of Epidemiology. 17 (10): 772–77. doi:10.1016/j.annepidem.2007.05.005. PMID   17689262.
  39. ↑ Zhou, F. C.; Fang, Y.; Goodlett, C. (2008). "Peptidergic Agonists of Activity-Dependent Neurotrophic Factor Protect Against Prenatal Alcohol-Induced Neural Tube Defects and Serotonin Neuron Loss". Alcoholism: Clinical and Experimental Research. 32 (8): 1361–71. doi:10.1111/j.1530-0277.2008.00722.x. PMC   2758042 . PMID   18565153.
  40. ↑ Huang, Hai-Yan; Chen, Hong-Lin; Feng, Li-Ping (March 2017). "Maternal obesity and the risk of neural tube defects in offspring: A meta-analysis". Obesity Research & Clinical Practice. 11 (2): 188–197. doi:10.1016/j.orcp.2016.04.005. ISSN   1871-403X. PMID   27155922.
  41. ↑ Wang, M; Wang, ZP; Gong, R; Zhao, ZT (January 2014). "Maternal smoking during pregnancy and neural tube defects in offspring: a meta-analysis". Child's Nervous System. 30 (1): 83–89. doi:10.1007/s00381-013-2194-5. PMID   23760473. S2CID   40996359.
  42. ↑ Suarez, Lucina; Ramadhani, Tunu; Felkner, Marilyn; Canfield, Mark A.; Brender, Jean D.; Romitti, Paul A.; Sun, Lixian (2011). "Maternal Smoking, Passive Tobacco Smoke, and Neural Tube Defects". Birth Defects Research. Part A, Clinical and Molecular Teratology. 91 (1): 29–33. doi:10.1002/bdra.20743. ISSN   1542-0752. PMC   6034638 . PMID   21254356.
  43. ↑ Meng, Xin; Sun, Yanxin; Duan, Wenhou; Jia, Chongqi (2018). "Meta-analysis of the association of maternal smoking and passive smoking during pregnancy with neural tube defects". International Journal of Gynecology & Obstetrics. 140 (1): 18–25. doi:10.1002/ijgo.12334. ISSN   1879-3479. PMID   28963797. S2CID   20885736.
  44. 1 2 Greene ND, Stanier P, Copp AJ (October 2009). "Genetics of human neural tube defects". Hum. Mol. Genet. 18 (R2): R113–29. doi:10.1093/hmg/ddp347. PMC   2758708 . PMID   19808787.
  45. ↑ "Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group". Lancet. 338 (8760): 131–37. 1991. doi:10.1016/0140-6736(91)90133-a. PMID   1677062. S2CID   14225812.
  46. ↑ Rose, N, Mennuti, M, Glob. Fetal Neural Tube Defects: Diagnosis, Management, and Treatment libr. women's med., ( ISSN   1756-2228) 2009; doi : 10.3843/GLOWM.10224
  47. 1 2 Wilson, R. Douglas; Audibert, Francois; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Cartier, Lola; Chitayat, David; Gagnon, Alain; Johnson, Jo-Ann (October 2014). "Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects". Journal of Obstetrics and Gynaecology Canada. 36 (10): 927–939. doi: 10.1016/s1701-2163(15)30444-8 . PMID   25375307.
  48. ↑ Milunsky A, Alpert E (1984). "Results and benefits of a maternal serum alpha-fetoprotein screening program". JAMA. 252 (11): 1438–42. doi:10.1001/jama.252.11.1438. PMID   6206249.
  49. ↑ Summer Maternal Serum Screening in Ontario Using the Triple Marker Test J Med Screen September 2003 vol. 10 no. 3 107–11.
  50. ↑ Boyd, PA; Devigan, C.; Khoshnood, B.; Loane, M.; Garne, E.; Dolk, H. (2008). "Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down's syndrome". BJOG: An International Journal of Obstetrics and Gynaecology. 115 (6): 689–696. doi:10.1111/j.1471-0528.2008.01700.x. PMC   2344123 . PMID   18410651.
  51. ↑ Norem et.al Routine Ultrasonography Compared With Maternal Serum Alpha-fetoprotein for Neural Tube Defect Screening Obstetrics & Gynecology: October 2005 Vol 106:4 pp. 747–52
  52. ↑ De Wals, Philippe; Tairou, Fassiatou; Van Allen, Margot I.; Uh, Soo-Hong; Lowry, R. Brian; Sibbald, Barbara; Evans, Jane A.; Van den Hof, Michiel C.; Zimmer, Pamela; Crowley, Marian; Fernandez, Bridget (2007-07-12). "Reduction in Neural-Tube Defects after Folic Acid Fortification in Canada". New England Journal of Medicine. 357 (2): 135–142. doi: 10.1056/NEJMoa067103 . ISSN   0028-4793. PMID   17625125.
  53. ↑ Daly S, Mills JL, Molloy AM, Conley M, Lee YJ, Kirke PN, Weir DG, Scott JM (1997). "Minimum effective dose of folic acid for food fortification to prevent neural-tube defects". Lancet. 350 (9092): 1666–69. doi:10.1016/S0140-6736(97)07247-4. PMID   9400511. S2CID   39708487.
  54. ↑ Ray, Joel G. (2004-06-01). "Folic Acid Food Fortification in Canada". Nutrition Reviews. 62 (6): 35–39. doi: 10.1111/j.1753-4887.2004.tb00072.x . PMID   15298446.
  55. ↑ Greene, ND; Stanier, P; Copp, AJ (2009). "Genetics of human neural tube defects". Human Molecular Genetics. 18 (R2): R113–29. doi:10.1093/hmg/ddp347. PMC   2758708 . PMID   19808787.
  56. ↑ Milunsky A, Jick H, Jick SS, Bruell CL, MacLaughlin DS, Rothman KJ, Willett W (1989). "Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects". Journal of the American Medical Association. 262 (20): 2847–52. doi:10.1001/jama.262.20.2847. PMID   2478730.
  57. ↑ Goh, YI; Koren, G (2008). "Folic acid in pregnancy and fetal outcomes". J. Obstet. Gynaecol. 28 (1): 3–13. doi:10.1080/01443610701814195. PMID   18259891. S2CID   28654601.
  58. ↑ De Wals P, Tairou F, Van Allen MI, et al. (2007). "Reduction in neural-tube defects after folic acid fortification in Canada". N Engl J Med. 357 (2): 135–42. doi: 10.1056/NEJMoa067103 . PMID   17625125.
  59. ↑ Naithani, Manisha; Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti (2016). "Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine". Scientifica. 2016: 1–5. doi: 10.1155/2016/1520685 . ISSN   2090-908X. PMC   4811260 . PMID   27064332.
  60. 1 2 Canada, Health (2009-04-28). "Prenatal Nutrition Guidelines for Health Professionals - Folate Contributes to a Healthy Pregnancy". www.canada.ca. Retrieved 2021-12-01.
  61. 1 2 Canada, Public Health Agency of (2018-01-05). "Folic acid and neural tube defects". www.canada.ca. Retrieved 2022-02-27.
  62. 1 2 3 4 5 6 7 8 Wilson, R. Douglas; Genetics Committee; Wilson, R. Douglas; Audibert, François; Brock, Jo-Ann; Carroll, June; Cartier, Lola; Gagnon, Alain; Johnson, Jo-Ann; Langlois, Sylvie; Murphy-Kaulbeck, Lynn (June 2015). "Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies". Journal of Obstetrics and Gynaecology Canada. 37 (6): 534–552. doi: 10.1016/s1701-2163(15)30230-9 . ISSN   1701-2163. PMID   26334606.
  63. 1 2 Centers for Disease Control (11 September 1992). "Recommendations for the Use of Folic Acid to Reduce the Number of Cases of Spina Bifida and Other Neural Tube Defects". Morbidity and Mortality Weekly Report. 41 (RR-14): 001.
  64. ↑ CDC (2021-04-19). "Folic Acid". Centers for Disease Control and Prevention. Retrieved 2022-02-27.
  65. ↑ Canada, Health (2009-04-28). "Prenatal Nutrition Guidelines for Health Professionals - Folate Contributes to a Healthy Pregnancy". www.canada.ca. Retrieved 2022-02-27.
  66. ↑ Copp, Andrew J.; Stanier, Philip; Greene, Nicholas D. E. (2013). "Neural tube defects – recent advances, unsolved questions and controversies". Lancet Neurology. 12 (8): 799–810. doi:10.1016/S1474-4422(13)70110-8. ISSN   1474-4422. PMC   4023229 . PMID   23790957.
  67. ↑ Sutton, Leslie N. (2008). "Fetal surgery for neural tube defects". Best Practice & Research Clinical Obstetrics & Gynaecology. 22 (1): 175–188. doi:10.1016/j.bpobgyn.2007.07.004. PMC   2293328 . PMID   17714997.
  68. ↑ Lozano, R (Dec 15, 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. hdl: 10536/DRO/DU:30050819 . PMC   10790329 . PMID   23245604. S2CID   1541253.
  69. ↑ 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): e0151586. Bibcode:2016PLoSO..1151586Z. doi: 10.1371/journal.pone.0151586 . ISSN   1932-6203. PMC   4827875 . PMID   27064786.
  70. 1 2 3 4 5 6 7 8 9 10 11 Frey, Lauren; Hauser, W. Allen (2003). "Epidemiology of Neural Tube Defects". Epilepsia. 44 (s3): 4–13. doi: 10.1046/j.1528-1157.44.s3.2.x . ISSN   1528-1167. PMID   12790881.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.