470:
shown to reduce the incidence of neural tube defects by 46% compared to incidence prior to mandatory fortification. 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. All individuals who have the ability to become pregnant are advised to get 400 micrograms of folic acid daily. This daily 400 mcg dose of folic acid can be found in most multivitamins advertised as for women. Higher doses can be found in pre-natal multivitamins but those doses may not be necessary for everyone. 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. 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. High risk would include those that had a past experience with neural tube defects, either themselves or during another pregnancy. 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
451:). 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.
498:. 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. 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. 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. 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. All dose recommendations and risk assessment should be done with the advice of a qualified health care provider.
596:
practical way, but the most accurate way would be to include stillbirths and live-births. Most studies that calculate prevalence rates only include data from live births and stillborn children and normally exclude the data from abortions and miscarriages. 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. 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.
529:
205:
the location as well as the type of defect it causes. Subtypes include occipital encephalocele, encephalocele of the cranial vault, and nasal encephaloceles (frontoethmoidal encephaloceles and basal encephaloceles), with approximately 80% of all encephaloceles occurring in the occipital area. Encephaloceles are often obvious and diagnosed immediately. Sometimes small encephaloceles in the nasal and forehead are undetected. 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.
221:
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.
189:(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. For example, anencephaly in humans can result from mutations in the
336:(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.
2012:
1806:
345:
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.
32:
327:
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
600:
there has been a relationship identified, older mothers along with very young mothers are at an increased risk. 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. Studies have also shown that mothers with three or more previous children show moderate risk for their next child having an NTD.
507:
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 outcome including a reduction in
220:
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. However, after a few weeks, the infants
204:
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. Due to the range in its location, encephaloceles are classified by
595:
Prevalence rates of NTDs at birth used to be a reliable measure for the actual number of children affected by the diseases. However, due to advances in technology and the ability to diagnose prenatally, the rates at birth are no longer reliable. Measuring the number of cases at birth may be the most
426:
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
344:
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
506:
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
326:
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
224:
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, so hydranencephaly develops during these weeks of the pregnancy. The cause of these
599:
There are many maternal factors that also play a role in prevalence rates of NTDs. These factors include things like maternal age and obesity all the way to things like socioeconomic status along with many others. Maternal age has not been shown to have a huge impact on prevalence rates, but when
464:
published regulations requiring the addition of folic acid to enriched breads, cereals, flour and other grain products. Similar regulations made it mandatory to fortify selected grain products with folic acid in Canada by 1998. During the first four weeks of pregnancy (when most women do not even
253:
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
469:
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. In Canada, mandatory fortification of selected foods with folic acid had been
339:
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
409:
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
335:
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
2042:
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
277:. 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.
459:
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. In 1996, the United States
519:
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.
478:, 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
292:
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
3649:
2598:
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).
284:. In this type of neural tube defect, the meninges do not herniate through the opening in the spinal canal. The most frequently seen form of spina bifida occulta is when parts of the bones of the spine, called the
385:(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
3535:
3512:
3030:
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).
3132:
2963:
2538:"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"
794:
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).
3642:
2781:
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".
126:
affects approximately 1,500 births annually in the United States, 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
3635:
414:
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
1602:"Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase C677T genotype: results from a crossover trial"
1518:"Homocysteinylation of neuronal proteins contributes to folate deficiency-associated alterations of differentiation, vesicular transport, and plasticity in hippocampal neuronal cells"
3329:
Zaganjor, Ibrahim; Sekkarie, Ahlia; Tsang, Becky L.; Williams, Jennifer; Razzaghi, Hilda; Mulinare, Joseph; Sniezek, Joseph E.; Cannon, Michael J.; Rosenthal, Jorge (2016-04-11).
254:
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.
2648:
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".
2270:
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".
3033:"Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies"
1708:
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).
991:
Pavone, Piero; Praticò, Andrea D; Vitaliti, Giovanna; Ruggieri, Martino; Rizzo, Renata; Parano, Enrico; Pavone, Lorenzo; Pero, Giuseppe; Falsaperla, Raffaele (2014-10-18).
130:
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.
2447:
Wilson, R. Douglas; Audibert, Francois; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Cartier, Lola; Chitayat, David; Gagnon, Alain; Johnson, Jo-Ann (October 2014).
377:
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
2416:
1910:
Singh, Nivedita; Kumble Bhat, Vishwanath; Tiwari, Ankana; Kodaganur, Srinivas G.; Tontanahal, Sagar J.; Sarda, Astha; Malini, K. V.; Kumar, Arun (2017-03-15).
3264:"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"
2902:"Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine"
515:
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
2080:"Peptidergic Agonists of Activity-Dependent Neurotrophic Factor Protect Against Prenatal Alcohol-Induced Neural Tube Defects and Serotonin Neuron Loss"
1961:"Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies"
1368:"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"
2585:
2127:
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".
418:
metabolism and folate linked methylation related cellular processes as there are multiple genes of this type associated with neural tube defects.
3923:
2170:
Wang, M; Wang, ZP; Gong, R; Zhao, ZT (January 2014). "Maternal smoking during pregnancy and neural tube defects in offspring: a meta-analysis".
232:
blockage in the carotid artery: some researchers think that a blockage of the carotid artery leads to the under-/no development of the brain.
241:
environmental toxins: during the pregnancy, a woman can be exposed to environmental toxins that may have effect on the health of the infant.
1749:
International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working?
1092:
340:
through fortified products, (ii) environmental agents such as UV radiation. In concern with the latter, the UV radiation-induced folate
3488:
174:. Closed NTDs occur when the spinal defect is covered by skin. Types of closed NTDs include lipomeningocele, lipomyelomeningocele, and
1710:"Dietary Folate from Vegetables and Citrus Fruit Decreases Plasma Homocysteine Concentrations in Humans in a Dietary Controlled Trial"
405:
in early development, and radiation. Maternal obesity has also been found to be a risk factor for NTDs. Studies have shown that both
3484:
1651:"The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake"
1477:"A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton"
592:
Neural tube defects resulted in 71,000 deaths globally in 2010. It is unclear how common the condition is in low income countries.
642:
3834:
665:. National Center on Birth Defects and Developmental Disabilities, US Centers for Disease Control and Prevention. 12 October 2016
238:
infections: during the pregnancy, a woman can develop an infection in the uterus what can lead to problems with the neural tube.
707:
Avagliano, Laura; Massa, Valentina; George, Timothy M.; Qureshy, Sarah; Bulfamante, Gaetano; Finnell, Richard H. (2019-11-15).
2373:"Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group".
2213:
Suarez, Lucina; Ramadhani, Tunu; Felkner, Marilyn; Canfield, Mark A.; Brender, Jean D.; Romitti, Paul A.; Sun, Lixian (2011).
3928:
1288:
1255:
3558:
382:
3085:"Recommendations for the Use of Folic Acid to Reduce the Number of Cases of Spina Bifida and Other Neural Tube Defects"
3477:
1050:
920:
528:
322:
during pregnancy have been found to lead to increased risk of NTDs. Although both are part of the same biopathway,
2900:
Naithani, Manisha; Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti (2016).
1886:
3786:
1366:
Molloy, A. M.; Kirke, P. N.; Troendle, J. F.; Burke, H.; Sutton, M.; Brody, L. C.; Scott, JM; Mills, JL (2009).
619:
508:
3627:
435:
which are frequently accompanied by neural tube defects that are assumed to be unrelated to folate metabolism
2488:
Milunsky A, Alpert E (1984). "Results and benefits of a maternal serum alpha-fetoprotein screening program".
175:
2991:
331:
is also an important receptor in the folate biopathway such that studies have shown deficiency in vitamin B
461:
378:
146:. Open NTDs occur when the brain and/or spinal cord are exposed at birth through a defect in the skull or
3809:
1418:
De-Regil, Luz Maria; Peña-Rosas, Juan Pablo; Fernández-Gaxiola, Ana C.; Rayco-Solon, Pura (2015-12-14).
876:
851:
2586:
Routine
Ultrasonography Compared With Maternal Serum Alpha-fetoprotein for Neural Tube Defect Screening
512:
3743:
1247:
1241:
3133:"Prenatal Nutrition Guidelines for Health Professionals - Folate Contributes to a Healthy Pregnancy"
2964:"Prenatal Nutrition Guidelines for Health Professionals - Folate Contributes to a Healthy Pregnancy"
2011:
1805:
796:"A loss-of-function NUAK2 mutation in humans causes anencephaly due to impaired Hippo-YAP signaling"
622:. National Institute of Child Health and Human Development, U.S. National Institutes of Health. 2017
427:
are candidates for folate insensitive neural tube defects. There are also several syndromes such as
3572:
1280:
1420:"Effects and safety of periconceptional oral folate supplementation for preventing birth defects"
465:
realize that they are pregnant), adequate folate intake is essential for proper operation of the
366:
2424:
765:
640:
92:
1339:
3791:
3469:
1148:
Korostyshevskaya, Alexandra; Gornostaeva, Alyona; Volkov, Rem; Yarnykh, Vasily (2020-11-19).
406:
369:
signalling. Other genes such as TRIM36 have also been associated with anencephaly in humans.
3331:"Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review"
1912:"A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family"
1748:
1272:
3342:
1972:
1832:
1662:
683:
217:
2025:
1068:
8:
3717:
3658:
3539:
3084:
1273:
3346:
3298:
1976:
1836:
1666:
80:, specialized cells on the dorsal side of the embryo begin to change shape and form the
3888:
3801:
3767:
3373:
3330:
3311:
3239:
3214:
3190:
3157:
2936:
2901:
2841:
2758:
2733:
2709:
2692:
2673:
2562:
2537:
2398:
2350:
2325:
2303:
2247:
2214:
2195:
2104:
2079:
1995:
1960:
1863:
1820:
1789:
1762:
1685:
1650:
1626:
1601:
1547:
1452:
1419:
1392:
1367:
1182:
1149:
1027:
992:
828:
795:
741:
708:
516:
265:
is further divided into two subclasses, spina bifida cystica and spina bifida occulta.
3279:
3173:
3049:
3032:
2661:
2465:
2449:"Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects"
2448:
3757:
3583:
3448:
3440:
3378:
3360:
3303:
3288:
3244:
3195:
3177:
3062:
3054:
2941:
2923:
2882:
2833:
2798:
2763:
2714:
2665:
2630:
2622:
2567:
2553:
2505:
2470:
2420:
2390:
2386:
2355:
2295:
2287:
2252:
2234:
2187:
2152:
2144:
2109:
2095:
2060:
2000:
1941:
1933:
1868:
1850:
1794:
1731:
1690:
1631:
1582:
1539:
1498:
1457:
1439:
1397:
1321:
1317:
1284:
1251:
1214:
1187:
1169:
1125:
1032:
1014:
967:
963:
896:
833:
815:
746:
728:
448:
432:
341:
323:
44:
3612:
3552:
3548:
3544:
2845:
2677:
2402:
2307:
2199:
2056:
1551:
1476:
3893:
3430:
3368:
3350:
3315:
3293:
3283:
3275:
3234:
3226:
3185:
3169:
3044:
2931:
2913:
2872:
2825:
2790:
2753:
2745:
2704:
2657:
2612:
2557:
2549:
2497:
2460:
2428:
2382:
2345:
2337:
2279:
2242:
2226:
2179:
2136:
2099:
2091:
2052:
1990:
1980:
1923:
1858:
1840:
1784:
1776:
1721:
1680:
1670:
1621:
1613:
1574:
1529:
1488:
1447:
1435:
1431:
1387:
1379:
1313:
1177:
1161:
1022:
1004:
959:
888:
823:
807:
736:
720:
685:
662:
274:
69:
49:
3435:
3418:
3230:
3107:
3777:
3577:
3355:
1985:
1761:
Wein, TN; Pike, E; Wisløff, T; Staff, A; Smeland, S; Klemp, M (12 January 2012).
1565:
Li, F.; Watkins, D.; Rosenblatt, D. S. (2009). "Vitamin B-12 and birth defects".
892:
475:
428:
354:
285:
213:
159:
2523:
1780:
1763:"Cancer risk with folic acid supplements: a systematic review and meta-analysis"
1578:
1165:
3829:
3820:
3796:
3662:
3657:
3615:
2140:
1206:
1117:
709:"Overview on Neural tube defects: from development to physical characteristics"
479:
471:
386:
167:
76:
remains from early in human development. In the third week of pregnancy called
3588:
2829:
2183:
1417:
1009:
3917:
3898:
3762:
3738:
3712:
3444:
3364:
3181:
3158:"Neural tube defects – recent advances, unsolved questions and controversies"
3058:
2927:
2794:
2626:
2536:
Boyd, PA; Devigan, C.; Khoshnood, B.; Loane, M.; Garne, E.; Dolk, H. (2008).
2501:
2291:
2238:
2148:
1937:
1854:
1443:
1173:
1018:
819:
732:
487:
201:
155:
119:
104:
65:
3529:
3525:
3521:
1845:
1726:
1709:
1675:
947:
365:. This fatal birth defect is believed to arise as a consequence of impaired
3872:
3867:
3815:
3733:
3705:
3485:
Preventing Neural Tube Birth
Defects: A Prevention Model and Resource Guide
3452:
3382:
3307:
3248:
3199:
3066:
2945:
2918:
2886:
2861:"Reduction in neural-tube defects after folic acid fortification in Canada"
2837:
2767:
2718:
2634:
2601:"Reduction in Neural-Tube Defects after Folic Acid Fortification in Canada"
2571:
2474:
2359:
2299:
2256:
2191:
2156:
2113:
2064:
2004:
1959:
Yan, L; Zhao, L; Long, Y; Zou, P; Ji, G; Gu, A; Zhao, P (October 3, 2012).
1945:
1872:
1798:
1735:
1694:
1635:
1617:
1586:
1543:
1502:
1461:
1401:
1383:
1325:
1218:
1191:
1129:
1036:
971:
900:
837:
750:
495:
411:
402:
390:
262:
250:
171:
163:
123:
112:
88:
77:
2802:
2669:
2509:
2394:
1493:
877:""Nasal encephalocele: Endoscopic excision with anesthetic consideration""
852:"Encephaloceles | National Institute of Neurological Disorders and Stroke"
3850:
3687:
3670:
3473:
2877:
2860:
2749:
2617:
2600:
2341:
1928:
1911:
1534:
1517:
811:
491:
466:
444:
362:
316:
289:
270:
186:
151:
96:
81:
2816:
Goh, YI; Koren, G (2008). "Folic acid in pregnancy and fetal outcomes".
2432:
2319:
2317:
1147:
641:
National Center on Birth
Defects and Developmental Disabilities (2012).
3772:
2283:
2230:
415:
394:
3504:
3029:
724:
3700:
3607:
2314:
2030:
1150:"Iniencephaly: radiologic and pathomorphologic perinatal observation"
483:
3263:
993:"Hydranencephaly: cerebral spinal fluid instead of cerebral mantles"
1767:
948:""Nasal encephalocele in a child with Beckwith-Wiedemann syndrome""
147:
84:. When the neural tube does not close completely, an NTD develops.
3219:
Best
Practice & Research Clinical Obstetrics & Gynaecology
2215:"Maternal Smoking, Passive Tobacco Smoke, and Neural Tube Defects"
122:, affecting over 300,000 births each year worldwide. For example,
3695:
3156:
Copp, Andrew J.; Stanier, Philip; Greene, Nicholas D. E. (2013).
2219:
Birth
Defects Research. Part A, Clinical and Molecular Teratology
1887:"Evolution of Human Skin Coloration — Department of Anthropology"
684:
National Center on Birth
Defects and Developmental Disabilities.
398:
73:
3566:
3563:
2524:
Maternal Serum
Screening in Ontario Using the Triple Marker Test
1707:
3516:
2858:
2417:
Fetal Neural Tube Defects: Diagnosis, Management, and Treatment
1909:
308:
31:
2588:
Obstetrics & Gynecology: October 2005 Vol 106:4 pp. 747–52
2212:
39:
Illustration of a child with spina bifida, the most common NTD
3328:
2446:
1093:"Fetal development: What happens during the first trimester?"
990:
358:
190:
108:
100:
2542:
BJOG: An International Journal of Obstetrics and Gynaecology
532:
Deaths from neural tube defects per million persons in 2012
3082:
706:
1821:"Human skin pigmentation as an adaptation to UV radiation"
793:
2899:
2535:
2041:
1340:"Spina Bifida Occulta (for Parents) - Nemours KidsHealth"
927:. National institute of Neurological Disorders and Stroke
2597:
1365:
228:
Theories regarding the causes of hydrancephaly include:
2859:
De Wals P, Tairou F, Van Allen MI, et al. (2007).
1055:
National Institute of Neurological Disorders and Stroke
2780:
2725:
1275:
Anatomy and Physiology: The Unity of Form and Function
881:
International Journal of Pediatric Otorhinolaryngology
2647:
1474:
447:
and measurement of maternal serum alpha-fetoprotein (
3494:
2272:
International Journal of Gynecology & Obstetrics
1760:
874:
1564:
620:"Neural Tube Defects (NTDs): Condition Information"
1819:Jablonski, Nina G.; Chaplin, George (2010-05-11).
16:Group of birth defects of the brain or spinal cord
3155:
3083:Centers for Disease Control (11 September 1992).
3078:
3076:
2731:
2526:J Med Screen September 2003 vol. 10 no. 3 107–11.
2323:
3915:
2169:
2077:
1818:
1115:
677:
648:. US Centers for Disease Control and Prevention.
1825:Proceedings of the National Academy of Sciences
1213:, Treasure Island (FL): StatPearls Publishing,
1124:, Treasure Island (FL): StatPearls Publishing,
1073:NORD (National Organization for Rare Disorders)
875:Abdel-Aziz, Mosaad; El-Bosraty, Hussam (2010).
688:. US Centers for Disease Control and Prevention
372:
3073:
2990:Canada, Public Health Agency of (2018-01-05).
2487:
2324:Greene ND, Stanier P, Copp AJ (October 2009).
2269:
2084:Alcoholism: Clinical and Experimental Research
1958:
1239:
945:
3643:
2126:
1240:Le, Tao; Bhushan, Vikas; Vasan, Neil (2010).
1116:Sandoval, Jose I.; De Jesus, Orlando (2022),
657:
655:
3037:Journal of Obstetrics and Gynaecology Canada
2453:Journal of Obstetrics and Gynaecology Canada
2078:Zhou, F. C.; Fang, Y.; Goodlett, C. (2008).
1648:
1204:
614:
612:
2783:Journal of the American Medical Association
1599:
1424:The Cochrane Database of Systematic Reviews
1304:Pittman, T (2008). "Spina bifida occulta".
1235:
1233:
1205:Brea, Cristina M.; Munakomi, Sunil (2022),
3650:
3636:
3489:Centers for Disease Control and Prevention
3416:
3112:Centers for Disease Control and Prevention
770:Centers for Disease Control and Prevention
652:
381:such as vulnerability caused by the C677T
30:
3434:
3372:
3354:
3297:
3287:
3238:
3189:
3048:
2935:
2917:
2876:
2757:
2732:Greene, ND; Stanier, P; Copp, AJ (2009).
2708:
2693:"Folic Acid Food Fortification in Canada"
2616:
2561:
2464:
2349:
2246:
2103:
1994:
1984:
1927:
1862:
1844:
1788:
1725:
1684:
1674:
1625:
1533:
1492:
1451:
1391:
1181:
1026:
1008:
827:
789:
787:
785:
740:
609:
2815:
2129:Obesity Research & Clinical Practice
1515:
1230:
946:Broekman, Marike; Hoving, Eelco (2008).
527:
357:and colleagues, the inactivation of the
3835:Bilateral frontoparietal polymicrogyria
3417:Frey, Lauren; Hauser, W. Allen (2003).
3255:
3215:"Fetal surgery for neural tube defects"
2734:"Genetics of human neural tube defects"
2326:"Genetics of human neural tube defects"
1303:
1270:
1264:
348:
115:which results in severe neck problems.
3924:Congenital disorders of nervous system
3916:
3412:
3261:
3212:
3130:
3025:
3023:
3021:
3019:
3017:
3015:
3013:
3011:
2989:
2985:
2983:
2961:
2957:
2955:
1246:(20th ed.). McGraw-Hill. p.
782:
443:Tests for neural tube defects include
3631:
3419:"Epidemiology of Neural Tube Defects"
3410:
3408:
3406:
3404:
3402:
3400:
3398:
3396:
3394:
3392:
3089:Morbidity and Mortality Weekly Report
2442:
2440:
1413:
1411:
1361:
1359:
913:
643:"Neural Tube Defects (Annual Report)"
511:and thereby decreases the need for a
2992:"Folic acid and neural tube defects"
1243:First Aid for the USMLE Step 1: 2010
800:The Journal of Experimental Medicine
766:"Facts about Craniosynostosis | CDC"
663:"Spina Bifida - Data and Statistics"
302:
3105:
3008:
2980:
2952:
2690:
1306:Journal of Neurosurgery. Pediatrics
763:
383:methylenetetrahydrofolate reductase
225:injuries/development is not clear.
150:(spinal column). Open NTDs include
13:
3661:malformations and deformations of
3389:
2710:10.1111/j.1753-4887.2004.tb00072.x
2437:
1408:
1356:
1051:"Hydranencephaly Information Page"
686:"Folic Acid – Birth Defects Count"
208:
14:
3940:
3478:U.S. National Library of Medicine
3462:
1649:Bailey SW, Ayling JE (Sep 2009).
1600:Anderson C.; et al. (2013).
1567:Molecular Genetics and Metabolism
921:"Encephaloceles Information Page"
196:
2554:10.1111/j.1471-0528.2008.01700.x
2096:10.1111/j.1530-0277.2008.00722.x
2010:
1804:
118:NTDs are one of the most common
3787:Agenesis of the corpus callosum
3322:
3206:
3149:
3124:
3099:
2893:
2852:
2809:
2774:
2684:
2641:
2605:New England Journal of Medicine
2591:
2578:
2529:
2516:
2481:
2409:
2366:
2263:
2206:
2163:
2120:
2071:
2057:10.1016/j.annepidem.2007.05.005
2035:
2018:
1952:
1903:
1879:
1812:
1754:
1742:
1701:
1642:
1593:
1558:
1509:
1468:
1332:
1297:
1198:
1141:
1109:
1085:
1061:
1043:
984:
939:
523:
257:
245:
138:There are two classes of NTDs:
127:
1516:Akchiche; et al. (2012).
1475:Bjorklund N, Gordon R (2006).
1436:10.1002/14651858.CD007950.pub3
868:
844:
757:
700:
634:
269:Spina bifida cystica includes
181:
99:which results in little to no
1:
3436:10.1046/j.1528-1157.44.s3.2.x
3280:10.1016/S0140-6736(12)61728-0
3231:10.1016/j.bpobgyn.2007.07.004
3174:10.1016/S1474-4422(13)70110-8
3131:Canada, Health (2009-04-28).
3050:10.1016/s1701-2163(15)30230-9
2962:Canada, Health (2009-04-28).
2662:10.1016/S0140-6736(97)07247-4
2466:10.1016/s1701-2163(15)30444-8
997:Italian Journal of Pediatrics
603:
454:
142:, which are more common, and
3929:Animal developmental biology
3356:10.1371/journal.pone.0151586
2387:10.1016/0140-6736(91)90133-a
1986:10.1371/journal.pone.0041689
893:10.1016/j.ijporl.2010.04.015
501:
462:Food and Drug Administration
438:
379:gene-environment interaction
373:Gene-environment interaction
216:is a condition in which the
170:, and the most common form,
7:
3753:other reduction deformities
2691:Ray, Joel G. (2004-06-01).
2415:Rose, N, Mennuti, M, Glob.
1831:(Supplement 2): 8962–8968.
1781:10.1136/bmjopen-2011-000653
1579:10.1016/j.ymgme.2009.06.004
1166:10.1016/j.radcr.2020.11.003
397:in contaminated corn meal,
280:Spina bifida occulta means
68:in which an opening in the
10:
3945:
3262:Lozano, R (Dec 15, 2012).
3213:Sutton, Leslie N. (2008).
2141:10.1016/j.orcp.2016.04.005
513:ventriculoperitoneal shunt
509:Arnold–Chiari malformation
407:maternal cigarette smoking
361:kinase in humans leads to
3881:
3858:
3849:
3726:
3678:
3669:
3598:
3498:
2830:10.1080/01443610701814195
2184:10.1007/s00381-013-2194-5
1271:Saladin, Kenneth (2010).
1010:10.1186/s13052-014-0079-1
297:
43:
38:
29:
24:
3739:Congenital hydrocephalus
2795:10.1001/jama.262.20.2847
2738:Human Molecular Genetics
2502:10.1001/jama.252.11.1438
1916:Human Molecular Genetics
1655:Proc Natl Acad Sci U S A
1318:10.3171/PED/2008/1/2/113
964:10.3171/PED/2008/1/6/485
421:
133:
87:Specific types include:
1846:10.1073/pnas.0914628107
1676:10.1073/pnas.0902072106
1279:. McGraw-Hill. p.
952:Journal of Neurosurgery
2381:(8760): 131–37. 1991.
2172:Child's Nervous System
2045:Annals of Epidemiology
1618:10.1002/mnfr.201200108
1384:10.1542/peds.2008-1173
1154:Radiology Case Reports
713:Birth Defects Research
589:
445:ultrasound examination
3792:Septo-optic dysplasia
3744:Dandy–Walker syndrome
3470:"Neural Tube Defects"
3289:10536/DRO/DU:30050819
2419:libr. women's med., (
1727:10.1093/jn/129.6.1135
1494:10.1387/ijdb.052102nb
531:
307:Inadequate levels of
2919:10.1155/2016/1520685
2878:10.1056/NEJMoa067103
2618:10.1056/NEJMoa067103
1535:10.1096/fj.12-205757
812:10.1084/jem.20191561
349:Genetic deficiencies
235:inherited condition.
218:cerebral hemispheres
128:folate fortification
3718:Chiari malformation
3347:2016PLoSO..1151586Z
2818:J. Obstet. Gynaecol
2433:10.3843/GLOWM.10224
2026:Neural Tube Defects
1977:2012PLoSO...741689Y
1837:2010PNAS..107.8962J
1667:2009PNAS..10615424B
1606:Mol. Nutr. Food Res
58:Neural tube defects
3889:Currarino syndrome
3860:Neural tube defect
3802:Hemimegalencephaly
3768:Microlissencephaly
3680:Neural tube defect
3599:External resources
3274:(9859): 2095–128.
3106:CDC (2021-04-19).
2750:10.1093/hmg/ddp347
2342:10.1093/hmg/ddp347
2284:10.1002/ijgo.12334
2231:10.1002/bdra.20743
1929:10.1093/hmg/ddx020
764:CDC (2019-12-04).
590:
517:ascertainment bias
282:hidden split spine
107:which affects the
91:which affects the
25:Neural tube defect
3911:
3910:
3907:
3906:
3845:
3844:
3758:Holoprosencephaly
3625:
3624:
2697:Nutrition Reviews
2656:(9092): 1666–69.
1522:The FASEB Journal
1481:Int. J. Dev. Biol
1290:978-0-07-352569-3
1257:978-0-07-163340-6
1118:"Hydranencephaly"
1069:"Hydranencephaly"
856:www.ninds.nih.gov
725:10.1002/bdr2.1380
719:(19): 1455–1467.
433:triploid syndrome
324:folate deficiency
303:Folate deficiency
64:) are a group of
55:
54:
19:Medical condition
3936:
3894:Diastomatomyelia
3856:
3855:
3676:
3675:
3652:
3645:
3638:
3629:
3628:
3496:
3495:
3481:
3457:
3456:
3438:
3414:
3387:
3386:
3376:
3358:
3326:
3320:
3319:
3301:
3291:
3259:
3253:
3252:
3242:
3210:
3204:
3203:
3193:
3162:Lancet Neurology
3153:
3147:
3146:
3144:
3143:
3128:
3122:
3121:
3119:
3118:
3103:
3097:
3096:
3080:
3071:
3070:
3052:
3027:
3006:
3005:
3003:
3002:
2987:
2978:
2977:
2975:
2974:
2959:
2950:
2949:
2939:
2921:
2897:
2891:
2890:
2880:
2856:
2850:
2849:
2813:
2807:
2806:
2778:
2772:
2771:
2761:
2729:
2723:
2722:
2712:
2688:
2682:
2681:
2645:
2639:
2638:
2620:
2595:
2589:
2582:
2576:
2575:
2565:
2533:
2527:
2520:
2514:
2513:
2485:
2479:
2478:
2468:
2444:
2435:
2413:
2407:
2406:
2370:
2364:
2363:
2353:
2321:
2312:
2311:
2267:
2261:
2260:
2250:
2210:
2204:
2203:
2167:
2161:
2160:
2124:
2118:
2117:
2107:
2075:
2069:
2068:
2039:
2033:
2022:
2016:
2015:
2014:
2008:
1998:
1988:
1956:
1950:
1949:
1931:
1922:(6): 1104–1114.
1907:
1901:
1900:
1898:
1897:
1883:
1877:
1876:
1866:
1848:
1816:
1810:
1809:
1808:
1802:
1792:
1758:
1752:
1751:BMJ 2005;330:571
1746:
1740:
1739:
1729:
1705:
1699:
1698:
1688:
1678:
1661:(36): 15424–29.
1646:
1640:
1639:
1629:
1597:
1591:
1590:
1562:
1556:
1555:
1537:
1513:
1507:
1506:
1496:
1472:
1466:
1465:
1455:
1430:(12): CD007950.
1415:
1406:
1405:
1395:
1363:
1354:
1353:
1351:
1350:
1336:
1330:
1329:
1301:
1295:
1294:
1278:
1268:
1262:
1261:
1237:
1228:
1227:
1226:
1225:
1202:
1196:
1195:
1185:
1145:
1139:
1138:
1137:
1136:
1113:
1107:
1106:
1104:
1103:
1089:
1083:
1082:
1080:
1079:
1065:
1059:
1058:
1047:
1041:
1040:
1030:
1012:
988:
982:
981:
979:
978:
943:
937:
936:
934:
932:
917:
911:
910:
908:
907:
872:
866:
865:
863:
862:
848:
842:
841:
831:
791:
780:
779:
777:
776:
761:
755:
754:
744:
704:
698:
697:
695:
693:
681:
675:
674:
672:
670:
659:
650:
649:
647:
638:
632:
631:
629:
627:
616:
585:
579:
573:
567:
561:
555:
549:
543:
537:
275:myelomeningocele
50:Medical genetics
34:
22:
21:
3944:
3943:
3939:
3938:
3937:
3935:
3934:
3933:
3914:
3913:
3912:
3903:
3877:
3841:
3778:Hydranencephaly
3722:
3665:
3656:
3626:
3621:
3620:
3594:
3593:
3507:
3468:
3465:
3460:
3415:
3390:
3341:(4): e0151586.
3327:
3323:
3260:
3256:
3211:
3207:
3154:
3150:
3141:
3139:
3129:
3125:
3116:
3114:
3104:
3100:
3081:
3074:
3028:
3009:
3000:
2998:
2988:
2981:
2972:
2970:
2960:
2953:
2898:
2894:
2857:
2853:
2814:
2810:
2789:(20): 2847–52.
2779:
2775:
2744:(R2): R113–29.
2730:
2726:
2689:
2685:
2646:
2642:
2596:
2592:
2583:
2579:
2534:
2530:
2521:
2517:
2496:(11): 1438–42.
2486:
2482:
2459:(10): 927–939.
2445:
2438:
2414:
2410:
2372:
2371:
2367:
2336:(R2): R113–29.
2330:Hum. Mol. Genet
2322:
2315:
2268:
2264:
2211:
2207:
2168:
2164:
2125:
2121:
2076:
2072:
2040:
2036:
2023:
2019:
2009:
1957:
1953:
1908:
1904:
1895:
1893:
1891:anth.la.psu.edu
1885:
1884:
1880:
1817:
1813:
1803:
1759:
1755:
1747:
1743:
1706:
1702:
1647:
1643:
1598:
1594:
1573:(1–2): 166–72.
1563:
1559:
1528:(10): 3980–92.
1514:
1510:
1487:(2–3): 135–41.
1473:
1469:
1416:
1409:
1364:
1357:
1348:
1346:
1338:
1337:
1333:
1302:
1298:
1291:
1269:
1265:
1258:
1238:
1231:
1223:
1221:
1203:
1199:
1146:
1142:
1134:
1132:
1114:
1110:
1101:
1099:
1091:
1090:
1086:
1077:
1075:
1067:
1066:
1062:
1049:
1048:
1044:
989:
985:
976:
974:
944:
940:
930:
928:
919:
918:
914:
905:
903:
873:
869:
860:
858:
850:
849:
845:
792:
783:
774:
772:
762:
758:
705:
701:
691:
689:
682:
678:
668:
666:
661:
660:
653:
645:
639:
635:
625:
623:
618:
617:
610:
606:
588:
587:
583:
581:
577:
575:
571:
569:
565:
563:
559:
557:
553:
551:
547:
545:
541:
539:
535:
526:
504:
480:anticonvulsants
476:kidney dialysis
457:
441:
429:Meckel syndrome
424:
387:antimetabolites
375:
355:Bruno Reversade
353:As reported by
351:
334:
330:
320:
314:
305:
300:
286:spinous process
260:
248:
214:Hydranencephaly
211:
209:Hydranencephaly
199:
184:
160:hydranencephaly
136:
20:
17:
12:
11:
5:
3942:
3932:
3931:
3926:
3909:
3908:
3905:
3904:
3902:
3901:
3896:
3891:
3885:
3883:
3879:
3878:
3876:
3875:
3870:
3864:
3862:
3853:
3847:
3846:
3843:
3842:
3840:
3839:
3838:
3837:
3830:Polymicrogyria
3826:
3825:
3824:
3823:
3821:Schizencephaly
3818:
3805:
3804:
3799:
3797:Megalencephaly
3794:
3789:
3783:
3782:
3781:
3780:
3775:
3770:
3765:
3760:
3749:
3748:
3747:
3746:
3736:
3730:
3728:
3724:
3723:
3721:
3720:
3715:
3710:
3709:
3708:
3703:
3698:
3693:
3684:
3682:
3673:
3667:
3666:
3663:nervous system
3655:
3654:
3647:
3640:
3632:
3623:
3622:
3619:
3618:
3603:
3602:
3600:
3596:
3595:
3592:
3591:
3580:
3569:
3555:
3532:
3508:
3503:
3502:
3500:
3499:Classification
3493:
3492:
3482:
3464:
3463:External links
3461:
3459:
3458:
3388:
3321:
3254:
3225:(1): 175–188.
3205:
3168:(8): 799–810.
3148:
3123:
3098:
3072:
3043:(6): 534–552.
3007:
2979:
2951:
2892:
2851:
2808:
2773:
2724:
2683:
2640:
2611:(2): 135–142.
2590:
2577:
2548:(6): 689–696.
2528:
2515:
2480:
2436:
2408:
2365:
2313:
2262:
2205:
2162:
2135:(2): 188–197.
2119:
2090:(8): 1361–71.
2070:
2051:(10): 772–77.
2034:
2017:
1971:(10): e41689.
1951:
1902:
1878:
1811:
1775:(1): e000653.
1753:
1741:
1720:(6): 1135–39.
1700:
1641:
1592:
1557:
1508:
1467:
1407:
1355:
1344:kidshealth.org
1331:
1296:
1289:
1263:
1256:
1229:
1207:"Spina Bifida"
1197:
1160:(1): 201–204.
1140:
1108:
1084:
1060:
1042:
983:
938:
912:
887:(8): 869–873.
867:
843:
781:
756:
699:
676:
651:
633:
607:
605:
602:
582:
576:
570:
564:
558:
552:
546:
540:
534:
533:
525:
522:
503:
500:
472:kidney disease
456:
453:
440:
437:
423:
420:
374:
371:
350:
347:
332:
328:
318:
312:
304:
301:
299:
296:
295:
294:
278:
259:
256:
247:
244:
243:
242:
239:
236:
233:
210:
207:
202:Encephaloceles
198:
197:Encephaloceles
195:
183:
180:
168:schizencephaly
156:encephaloceles
135:
132:
53:
52:
47:
41:
40:
36:
35:
27:
26:
18:
15:
9:
6:
4:
3:
2:
3941:
3930:
3927:
3925:
3922:
3921:
3919:
3900:
3899:Syringomyelia
3897:
3895:
3892:
3890:
3887:
3886:
3884:
3880:
3874:
3871:
3869:
3866:
3865:
3863:
3861:
3857:
3854:
3852:
3848:
3836:
3833:
3832:
3831:
3828:
3827:
3822:
3819:
3817:
3814:
3813:
3812:
3811:
3807:
3806:
3803:
3800:
3798:
3795:
3793:
3790:
3788:
3785:
3784:
3779:
3776:
3774:
3771:
3769:
3766:
3764:
3763:Lissencephaly
3761:
3759:
3756:
3755:
3754:
3751:
3750:
3745:
3742:
3741:
3740:
3737:
3735:
3732:
3731:
3729:
3725:
3719:
3716:
3714:
3713:Encephalocele
3711:
3707:
3704:
3702:
3699:
3697:
3694:
3691:
3690:
3689:
3686:
3685:
3683:
3681:
3677:
3674:
3672:
3668:
3664:
3660:
3653:
3648:
3646:
3641:
3639:
3634:
3633:
3630:
3617:
3614:
3610:
3609:
3605:
3604:
3601:
3597:
3590:
3586:
3585:
3581:
3579:
3575:
3574:
3570:
3568:
3565:
3561:
3560:
3556:
3554:
3550:
3546:
3542:
3541:
3537:
3533:
3531:
3527:
3523:
3519:
3518:
3514:
3510:
3509:
3506:
3501:
3497:
3490:
3486:
3483:
3479:
3475:
3471:
3467:
3466:
3454:
3450:
3446:
3442:
3437:
3432:
3428:
3424:
3420:
3413:
3411:
3409:
3407:
3405:
3403:
3401:
3399:
3397:
3395:
3393:
3384:
3380:
3375:
3370:
3366:
3362:
3357:
3352:
3348:
3344:
3340:
3336:
3332:
3325:
3317:
3313:
3309:
3305:
3300:
3295:
3290:
3285:
3281:
3277:
3273:
3269:
3265:
3258:
3250:
3246:
3241:
3236:
3232:
3228:
3224:
3220:
3216:
3209:
3201:
3197:
3192:
3187:
3183:
3179:
3175:
3171:
3167:
3163:
3159:
3152:
3138:
3137:www.canada.ca
3134:
3127:
3113:
3109:
3102:
3095:(RR-14): 001.
3094:
3090:
3086:
3079:
3077:
3068:
3064:
3060:
3056:
3051:
3046:
3042:
3038:
3034:
3026:
3024:
3022:
3020:
3018:
3016:
3014:
3012:
2997:
2996:www.canada.ca
2993:
2986:
2984:
2969:
2968:www.canada.ca
2965:
2958:
2956:
2947:
2943:
2938:
2933:
2929:
2925:
2920:
2915:
2911:
2907:
2903:
2896:
2888:
2884:
2879:
2874:
2871:(2): 135–42.
2870:
2866:
2862:
2855:
2847:
2843:
2839:
2835:
2831:
2827:
2823:
2819:
2812:
2804:
2800:
2796:
2792:
2788:
2784:
2777:
2769:
2765:
2760:
2755:
2751:
2747:
2743:
2739:
2735:
2728:
2720:
2716:
2711:
2706:
2702:
2698:
2694:
2687:
2679:
2675:
2671:
2667:
2663:
2659:
2655:
2651:
2644:
2636:
2632:
2628:
2624:
2619:
2614:
2610:
2606:
2602:
2594:
2587:
2581:
2573:
2569:
2564:
2559:
2555:
2551:
2547:
2543:
2539:
2532:
2525:
2519:
2511:
2507:
2503:
2499:
2495:
2491:
2484:
2476:
2472:
2467:
2462:
2458:
2454:
2450:
2443:
2441:
2434:
2430:
2426:
2422:
2418:
2412:
2404:
2400:
2396:
2392:
2388:
2384:
2380:
2376:
2369:
2361:
2357:
2352:
2347:
2343:
2339:
2335:
2331:
2327:
2320:
2318:
2309:
2305:
2301:
2297:
2293:
2289:
2285:
2281:
2277:
2273:
2266:
2258:
2254:
2249:
2244:
2240:
2236:
2232:
2228:
2224:
2220:
2216:
2209:
2201:
2197:
2193:
2189:
2185:
2181:
2177:
2173:
2166:
2158:
2154:
2150:
2146:
2142:
2138:
2134:
2130:
2123:
2115:
2111:
2106:
2101:
2097:
2093:
2089:
2085:
2081:
2074:
2066:
2062:
2058:
2054:
2050:
2046:
2038:
2032:
2028:
2027:
2021:
2013:
2006:
2002:
1997:
1992:
1987:
1982:
1978:
1974:
1970:
1966:
1962:
1955:
1947:
1943:
1939:
1935:
1930:
1925:
1921:
1917:
1913:
1906:
1892:
1888:
1882:
1874:
1870:
1865:
1860:
1856:
1852:
1847:
1842:
1838:
1834:
1830:
1826:
1822:
1815:
1807:
1800:
1796:
1791:
1786:
1782:
1778:
1774:
1770:
1769:
1764:
1757:
1750:
1745:
1737:
1733:
1728:
1723:
1719:
1715:
1711:
1704:
1696:
1692:
1687:
1682:
1677:
1672:
1668:
1664:
1660:
1656:
1652:
1645:
1637:
1633:
1628:
1623:
1619:
1615:
1612:(4): 637–44.
1611:
1607:
1603:
1596:
1588:
1584:
1580:
1576:
1572:
1568:
1561:
1553:
1549:
1545:
1541:
1536:
1531:
1527:
1523:
1519:
1512:
1504:
1500:
1495:
1490:
1486:
1482:
1478:
1471:
1463:
1459:
1454:
1449:
1445:
1441:
1437:
1433:
1429:
1425:
1421:
1414:
1412:
1403:
1399:
1394:
1389:
1385:
1381:
1378:(3): 917–23.
1377:
1373:
1369:
1362:
1360:
1345:
1341:
1335:
1327:
1323:
1319:
1315:
1311:
1307:
1300:
1292:
1286:
1282:
1277:
1276:
1267:
1259:
1253:
1249:
1245:
1244:
1236:
1234:
1220:
1216:
1212:
1208:
1201:
1193:
1189:
1184:
1179:
1175:
1171:
1167:
1163:
1159:
1155:
1151:
1144:
1131:
1127:
1123:
1119:
1112:
1098:
1094:
1088:
1074:
1070:
1064:
1057:. 2019-03-27.
1056:
1052:
1046:
1038:
1034:
1029:
1024:
1020:
1016:
1011:
1006:
1002:
998:
994:
987:
973:
969:
965:
961:
957:
953:
949:
942:
931:September 15,
926:
922:
916:
902:
898:
894:
890:
886:
882:
878:
871:
857:
853:
847:
839:
835:
830:
825:
821:
817:
813:
809:
805:
801:
797:
790:
788:
786:
771:
767:
760:
752:
748:
743:
738:
734:
730:
726:
722:
718:
714:
710:
703:
687:
680:
664:
658:
656:
644:
637:
621:
615:
613:
608:
601:
597:
593:
530:
521:
518:
514:
510:
499:
497:
493:
489:
488:sulfasalazine
485:
481:
477:
473:
468:
463:
452:
450:
446:
436:
434:
430:
419:
417:
413:
408:
404:
400:
396:
392:
388:
384:
380:
370:
368:
364:
360:
356:
346:
343:
337:
325:
321:
310:
291:
287:
283:
279:
276:
272:
268:
267:
266:
264:
255:
252:
240:
237:
234:
231:
230:
229:
226:
222:
219:
215:
206:
203:
194:
192:
188:
179:
177:
176:tethered cord
173:
169:
165:
161:
157:
153:
149:
145:
141:
131:
129:
125:
121:
120:birth defects
116:
114:
110:
106:
105:encephalocele
102:
98:
94:
90:
85:
83:
79:
75:
71:
67:
66:birth defects
63:
59:
51:
48:
46:
42:
37:
33:
28:
23:
3873:Rachischisis
3868:Spina bifida
3859:
3816:Porencephaly
3808:
3752:
3734:Microcephaly
3706:Iniencephaly
3679:
3606:
3582:
3571:
3557:
3534:
3511:
3429:(s3): 4–13.
3426:
3422:
3338:
3334:
3324:
3271:
3267:
3257:
3222:
3218:
3208:
3165:
3161:
3151:
3140:. Retrieved
3136:
3126:
3115:. Retrieved
3111:
3108:"Folic Acid"
3101:
3092:
3088:
3040:
3036:
2999:. Retrieved
2995:
2971:. Retrieved
2967:
2909:
2905:
2895:
2868:
2865:N Engl J Med
2864:
2854:
2821:
2817:
2811:
2786:
2782:
2776:
2741:
2737:
2727:
2703:(6): 35–39.
2700:
2696:
2686:
2653:
2649:
2643:
2608:
2604:
2593:
2584:Norem et.al
2580:
2545:
2541:
2531:
2518:
2493:
2489:
2483:
2456:
2452:
2411:
2378:
2374:
2368:
2333:
2329:
2278:(1): 18–25.
2275:
2271:
2265:
2225:(1): 29–33.
2222:
2218:
2208:
2178:(1): 83–89.
2175:
2171:
2165:
2132:
2128:
2122:
2087:
2083:
2073:
2048:
2044:
2043:offspring".
2037:
2024:
2020:
1968:
1964:
1954:
1919:
1915:
1905:
1894:. Retrieved
1890:
1881:
1828:
1824:
1814:
1772:
1766:
1756:
1744:
1717:
1713:
1703:
1658:
1654:
1644:
1609:
1605:
1595:
1570:
1566:
1560:
1525:
1521:
1511:
1484:
1480:
1470:
1427:
1423:
1375:
1371:
1347:. Retrieved
1343:
1334:
1309:
1305:
1299:
1274:
1266:
1242:
1222:, retrieved
1210:
1200:
1157:
1153:
1143:
1133:, retrieved
1121:
1111:
1100:. Retrieved
1096:
1087:
1076:. Retrieved
1072:
1063:
1054:
1045:
1000:
996:
986:
975:. Retrieved
958:(1): 485–7.
955:
951:
941:
929:. Retrieved
924:
915:
904:. Retrieved
884:
880:
870:
859:. Retrieved
855:
846:
803:
799:
773:. Retrieved
769:
759:
716:
712:
702:
690:. Retrieved
679:
667:. Retrieved
636:
624:. Retrieved
598:
594:
591:
524:Epidemiology
505:
496:trimethoprim
458:
442:
425:
412:homocysteine
403:hyperthermia
391:methotrexate
376:
352:
338:
306:
281:
263:Spina bifida
261:
258:Spina bifida
251:Iniencephaly
249:
246:Iniencephaly
227:
223:
212:
200:
185:
172:spina bifida
164:iniencephaly
143:
139:
137:
124:spina bifida
117:
113:iniencephaly
89:spina bifida
86:
78:gastrulation
61:
57:
56:
3851:Spinal cord
3688:Anencephaly
3474:MedlinePlus
2906:Scientifica
2824:(1): 3–13.
1097:Mayo Clinic
669:29 November
626:30 November
586: 29–69
580: 21–28
574: 16–20
568: 11–15
492:triamterene
467:neurulation
363:anencephaly
293:population.
290:neural arch
271:meningocele
187:Anencephaly
182:Anencephaly
152:anencephaly
97:anencephaly
82:neural tube
3918:Categories
3773:Pachygyria
3659:Congenital
3584:DiseasesDB
3142:2022-02-27
3117:2022-02-27
3001:2022-02-27
2973:2021-12-01
1896:2020-05-16
1372:Pediatrics
1349:2022-11-28
1312:(2): 113.
1224:2022-11-28
1211:StatPearls
1135:2022-11-28
1122:StatPearls
1102:2020-05-12
1078:2020-05-12
977:2020-11-19
906:2020-11-19
861:2022-11-28
775:2022-11-28
604:References
562: 7–10
455:Prevention
416:folic acid
395:mycotoxins
342:photolysis
311:(vitamin B
288:, and the
3701:Acalvaria
3613:neuro/244
3608:eMedicine
3445:1528-1167
3423:Epilepsia
3365:1932-6203
3182:1474-4422
3059:1701-2163
2928:2090-908X
2627:0028-4793
2425:1756-2228
2292:1879-3479
2239:1542-0752
2149:1871-403X
2031:eMedicine
1938:1460-2083
1855:0027-8424
1444:1469-493X
1174:1930-0433
1019:1824-7288
820:1540-9538
733:2472-1727
556: 4–6
550: 2–3
544: 1–1
538: 0–0
502:Treatment
484:metformin
439:Diagnosis
389:(such as
317:vitamin B
148:vertebrae
45:Specialty
3810:CNS cyst
3692:Acephaly
3616:ped/2805
3453:12790881
3383:27064786
3335:PLOS ONE
3308:23245604
3299:10790329
3249:17714997
3200:23790957
3067:26334606
2946:27064332
2887:17625125
2846:28654601
2838:18259891
2768:19808787
2719:15298446
2678:39708487
2635:17625125
2572:18410651
2475:25375307
2427:) 2009;
2403:14225812
2360:19808787
2308:20885736
2300:28963797
2257:21254356
2200:40996359
2192:23760473
2157:27155922
2114:18565153
2065:17689262
2005:23056169
1965:PLOS ONE
1946:28087737
1873:20445093
1799:22240654
1768:BMJ Open
1736:10356077
1695:19706381
1636:23456769
1587:19586788
1552:30113330
1544:22713523
1503:16479482
1462:26662928
1402:19255021
1326:18352777
1219:32644691
1192:33294089
1130:32644417
1037:25326191
972:18518702
901:20554034
838:32845958
751:30421543
193:kinase.
3696:Acrania
3578:D009436
3374:4827875
3343:Bibcode
3316:1541253
3240:2293328
3191:4023229
2937:4811260
2912:: 1–5.
2803:2478730
2759:2758708
2670:9400511
2563:2344123
2522:Summer
2510:6206249
2395:1677062
2351:2758708
2248:6034638
2105:2758042
1996:3463537
1973:Bibcode
1864:3024016
1833:Bibcode
1790:3278486
1714:J. Nutr
1686:2730961
1663:Bibcode
1627:4132693
1453:8783750
1393:4161975
1183:7689276
1028:4421920
829:7953732
742:6511489
399:arsenic
74:cranium
3567:301410
3564:182940
3451:
3443:
3381:
3371:
3363:
3314:
3306:
3296:
3268:Lancet
3247:
3237:
3198:
3188:
3180:
3065:
3057:
2944:
2934:
2926:
2885:
2844:
2836:
2801:
2766:
2756:
2717:
2676:
2668:
2650:Lancet
2633:
2625:
2570:
2560:
2508:
2473:
2423:
2401:
2393:
2375:Lancet
2358:
2348:
2306:
2298:
2290:
2255:
2245:
2237:
2198:
2190:
2155:
2147:
2112:
2102:
2063:
2003:
1993:
1944:
1936:
1871:
1861:
1853:
1797:
1787:
1734:
1693:
1683:
1634:
1624:
1585:
1550:
1542:
1501:
1460:
1450:
1442:
1400:
1390:
1324:
1287:
1254:
1217:
1190:
1180:
1172:
1128:
1035:
1025:
1017:
1003:: 79.
970:
899:
836:
826:
818:
806:(12).
749:
739:
731:
692:13 May
584:
578:
572:
566:
560:
554:
548:
542:
536:
494:, and
431:, and
315:) and
309:folate
298:Causes
144:closed
111:, and
3882:Other
3727:Other
3671:Brain
3491:(CDC)
3312:S2CID
2842:S2CID
2674:S2CID
2399:S2CID
2304:S2CID
2196:S2CID
1548:S2CID
646:(PDF)
449:MSAFP
422:Other
367:HIPPO
359:NUAK2
191:NUAK2
134:Types
109:skull
101:brain
93:spine
70:spine
3589:8926
3573:MeSH
3559:OMIM
3540:9-CM
3449:PMID
3441:ISSN
3379:PMID
3361:ISSN
3304:PMID
3245:PMID
3196:PMID
3178:ISSN
3063:PMID
3055:ISSN
2942:PMID
2924:ISSN
2910:2016
2883:PMID
2834:PMID
2799:PMID
2764:PMID
2715:PMID
2666:PMID
2631:PMID
2623:ISSN
2568:PMID
2506:PMID
2490:JAMA
2471:PMID
2421:ISSN
2391:PMID
2356:PMID
2296:PMID
2288:ISSN
2253:PMID
2235:ISSN
2188:PMID
2153:PMID
2145:ISSN
2110:PMID
2061:PMID
2001:PMID
1942:PMID
1934:ISSN
1869:PMID
1851:ISSN
1795:PMID
1732:PMID
1691:PMID
1632:PMID
1583:PMID
1540:PMID
1499:PMID
1458:PMID
1440:ISSN
1428:2015
1398:PMID
1322:PMID
1285:ISBN
1252:ISBN
1215:PMID
1188:PMID
1170:ISSN
1126:PMID
1033:PMID
1015:ISSN
968:PMID
933:2017
897:PMID
834:PMID
816:ISSN
747:PMID
729:ISSN
694:2014
671:2017
628:2017
273:and
140:open
62:NTDs
3553:742
3549:741
3545:740
3536:ICD
3530:Q05
3526:Q01
3522:Q00
3513:ICD
3431:doi
3369:PMC
3351:doi
3294:PMC
3284:hdl
3276:doi
3272:380
3235:PMC
3227:doi
3186:PMC
3170:doi
3045:doi
2932:PMC
2914:doi
2873:doi
2869:357
2826:doi
2791:doi
2787:262
2754:PMC
2746:doi
2705:doi
2658:doi
2654:350
2613:doi
2609:357
2558:PMC
2550:doi
2546:115
2498:doi
2494:252
2461:doi
2429:doi
2383:doi
2379:338
2346:PMC
2338:doi
2280:doi
2276:140
2243:PMC
2227:doi
2180:doi
2137:doi
2100:PMC
2092:doi
2053:doi
2029:at
1991:PMC
1981:doi
1924:doi
1859:PMC
1841:doi
1829:107
1785:PMC
1777:doi
1722:doi
1718:129
1681:PMC
1671:doi
1659:106
1622:PMC
1614:doi
1575:doi
1530:doi
1489:doi
1448:PMC
1432:doi
1388:PMC
1380:doi
1376:123
1314:doi
1281:485
1248:127
1178:PMC
1162:doi
1023:PMC
1005:doi
960:doi
925:NIH
889:doi
824:PMC
808:doi
804:217
737:PMC
721:doi
717:111
393:),
72:or
3920::
3611::
3587::
3576::
3562::
3551:,
3547:,
3543::
3528:,
3524:,
3520::
3517:10
3487::
3476:.
3472:.
3447:.
3439:.
3427:44
3425:.
3421:.
3391:^
3377:.
3367:.
3359:.
3349:.
3339:11
3337:.
3333:.
3310:.
3302:.
3292:.
3282:.
3270:.
3266:.
3243:.
3233:.
3223:22
3221:.
3217:.
3194:.
3184:.
3176:.
3166:12
3164:.
3160:.
3135:.
3110:.
3093:41
3091:.
3087:.
3075:^
3061:.
3053:.
3041:37
3039:.
3035:.
3010:^
2994:.
2982:^
2966:.
2954:^
2940:.
2930:.
2922:.
2908:.
2904:.
2881:.
2867:.
2863:.
2840:.
2832:.
2822:28
2820:.
2797:.
2785:.
2762:.
2752:.
2742:18
2740:.
2736:.
2713:.
2701:62
2699:.
2695:.
2672:.
2664:.
2652:.
2629:.
2621:.
2607:.
2603:.
2566:.
2556:.
2544:.
2540:.
2504:.
2492:.
2469:.
2457:36
2455:.
2451:.
2439:^
2397:.
2389:.
2377:.
2354:.
2344:.
2334:18
2332:.
2328:.
2316:^
2302:.
2294:.
2286:.
2274:.
2251:.
2241:.
2233:.
2223:91
2221:.
2217:.
2194:.
2186:.
2176:30
2174:.
2151:.
2143:.
2133:11
2131:.
2108:.
2098:.
2088:32
2086:.
2082:.
2059:.
2049:17
2047:.
1999:.
1989:.
1979:.
1967:.
1963:.
1940:.
1932:.
1920:26
1918:.
1914:.
1889:.
1867:.
1857:.
1849:.
1839:.
1827:.
1823:.
1793:.
1783:.
1771:.
1765:.
1730:.
1716:.
1712:.
1689:.
1679:.
1669:.
1657:.
1653:.
1630:.
1620:.
1610:57
1608:.
1604:.
1581:.
1571:98
1569:.
1546:.
1538:.
1526:26
1524:.
1520:.
1497:.
1485:50
1483:.
1479:.
1456:.
1446:.
1438:.
1426:.
1422:.
1410:^
1396:.
1386:.
1374:.
1370:.
1358:^
1342:.
1320:.
1308:.
1283:.
1250:.
1232:^
1209:,
1186:.
1176:.
1168:.
1158:16
1156:.
1152:.
1120:,
1095:.
1071:.
1053:.
1031:.
1021:.
1013:.
1001:40
999:.
995:.
966:.
954:.
950:.
923:.
895:.
885:74
883:.
879:.
854:.
832:.
822:.
814:.
802:.
798:.
784:^
768:.
745:.
735:.
727:.
715:.
711:.
654:^
611:^
490:,
486:,
482:,
474:,
401:,
333:12
329:12
319:12
178:.
166:,
162:,
158:,
154:,
103:,
95:,
3651:e
3644:t
3637:v
3538:-
3515:-
3505:D
3480:.
3455:.
3433::
3385:.
3353::
3345::
3318:.
3286::
3278::
3251:.
3229::
3202:.
3172::
3145:.
3120:.
3069:.
3047::
3004:.
2976:.
2948:.
2916::
2889:.
2875::
2848:.
2828::
2805:.
2793::
2770:.
2748::
2721:.
2707::
2680:.
2660::
2637:.
2615::
2574:.
2552::
2512:.
2500::
2477:.
2463::
2431::
2405:.
2385::
2362:.
2340::
2310:.
2282::
2259:.
2229::
2202:.
2182::
2159:.
2139::
2116:.
2094::
2067:.
2055::
2007:.
1983::
1975::
1969:7
1948:.
1926::
1899:.
1875:.
1843::
1835::
1801:.
1779::
1773:2
1738:.
1724::
1697:.
1673::
1665::
1638:.
1616::
1589:.
1577::
1554:.
1532::
1505:.
1491::
1464:.
1434::
1404:.
1382::
1352:.
1328:.
1316::
1310:1
1293:.
1260:.
1194:.
1164::
1105:.
1081:.
1039:.
1007::
980:.
962::
956:6
935:.
909:.
891::
864:.
840:.
810::
778:.
753:.
723::
696:.
673:.
630:.
313:9
60:(
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
