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Neural Tube Defects

The brain is the key working mechanism of the body that supports every part working together and keeping you alive. Even if someone can still breathe after the brain is dead, all organs in the body systems will gradually cease and eventually, the heart will stop beating, which demonstrates the huge role that the brain plays in the regulation of the body (Wijdicks). This article will be introducing and discuss the formation of Neural Tube Defects, the two most common defects that could form during embryogenesis, the possible causes for NTDs, and future research directions.

As the brain originally develops from the embryo, there is a group of cells that interacts and contributes to the formation of all organs and tissues of the body, and this group of cells is known as germ layers. The 3 germ layers are ectoderm, endoderm, and mesoderm, each of them further develops into different parts of the body. Among the 3 germ layers, the ectoderm is the one that gives rise to the neural tube and neural crest, which forms the brain, spinal and peripheral nerves. After 15 to 20 days, ectoderm will turn to neuroectoderm, where the central part will become the central nervous system that is made up of the brain and spinal cord, and the peripheral part will become the peripheral nervous system and receives information from body parts and sends instructions from the brain to the limbs. “The development and closure of the neural tube are completed 28 days after the conception” (Imbard et al.).

During this process of neural tube formation, Neural Tube Defects (NTD) could happen when the neural tube closure fails. Failure during neural tube closure can occur in different locations and stages during the developmental axis formation, resulting in distinct malformations. When the tube doesn’t close at the posterior neuropore, spina bifida would arise. This happens when the lumbar cord joins the sacral cord and the spinal cord protrudes through an incompletely fused spine, thus externalized like a ‘tail’ (Fletcher and Brei). The protruding part interferes with spinal cord functions and may lead to paralysis since it hinders the flow of cerebrospinal fluid. Furthermore, this extra length and weight of the ‘tail’ pulls on the brain. In more severe cases, it may even pull the cerebellum out. Depending on the size and the location of the lesion, interruption of the spinal cord could cause levels of paralysis of the legs, incontinence of urine and feces, anesthesia of the skin, and abnormalities of hips, knees, and feet (Northrup and Volcik). Likewise, the intellectual disability caused by spina bifida ranges from mild to severe depending on the size and location of the opening of the “tail” and whether the nerves are affected (Centers for Disease Control and Prevention). Surprisingly, the mortality rate of infants with spina bifida from a study of 1,533 liveborn infants was 4.4%. The study also shows that maternal obesity and overweight are associated with a high risk of mortality of infants (15.7%) compared with normal-weight mothers, which proves “the importance of maternal weight prior to spina bifida” (Pace et al.).

On the other hand, anencephaly, which forms when the spine doesn’t close at the anterior neuropore, will be much more serious than spina bifida. Anencephaly is characterized by the absence of the brain hemisphere and cranial arch, which are the upper parts of the neural tube that forms the forebrain and cerebrum (Salari et al.). There isn’t enough skin and bone to cover and thus the brain disintegrates. The diagnosis of anencephaly is confirmed by a physical examination of their looks. For example, the common features of anencephaly babies are a “frog-like appearance, short neck, bulging eyes, and large eyes” (Salari et al.). Unlike spina bifida which has a relatively low risk of mortality, anencephaly occurs in 1.0 - 4.7 per 1,000 births (Oumer et al.), and the mortality rate is 100% in utero, at birth or a few hours after birth (Munteanun et al.). Due to the lack of cerebrum of the brain, infants with anencephaly are incapable of having consciousness and have a feeling of pain, although may still have reflex actions such as respiration and occasionally sound and touch (Machado et al.). It is important to remember that anencephaly is lethal and there’s no chance of survival under this condition, due to the severe brain malformation that is present.

The Neural Tube Defects such as anencephaly and spina bifida are a result of both environmental, nutrition and parental genetic factors. The most common environmental influences are when the mother takes in harmful substances or experiences obesity or other diseases such as diabetes during pregnancy. A research conducted by comparing 2,755 Atlanta Area women who gave birth to an infant without birth defect with another group of Atlanta Area women who gave birth to an infant with anencephaly or spina bifida. After adjusting all other compounding variables that could have an impact on the research result, the researchers found that obese women had almost twice the risk of having an infant with NTDs (Watkins et al.). Exposure to some airborne chemicals such as polyvinyl chloride and toxic wastes can also be dangerous for the mother and the newborn baby (Theriault et al.; Uzych). Furthermore, nutritional risk factors such as the folate status also play roles in the presence of Neural Tube Defects. The deficiency of folic acid is associated with the increased risk of NTD. Deficiency of maternal vitamin B12 is also a known risk of NTD, as vitamin B12 is a cofactor of the enzyme methionine synthase, an important component of one-carbon metabolism in charge of converting homocysteine to methionine (Finnell et al.). Different meta-analysis studies all over the world with different races and populations, involving Canadian, United States, Chinese, and Tunisian, have all demonstrated that low vitamin B12 status is a risk factor of NTD. For the genetic risk factors for NTDs, human epidemiological studies have shown a strong correlation between monozygotic twins (7.7%) compared to like sex or dizygotic twins (4.0%; Finnell et al.; Shaw et al.; Wallingford et al.; Blencowe et al.). “A well documented over 240 genes, whose mutation cause NTDs in the mouse, support the likelihood that numerous gene defects contribute to NTDs” (Finnell et al.). However, it is important to note that there’s currently no indication of clinically actionable NTD candidate genes that would directly lead to the NTDs.

In the past decades, our clinical understanding and treatment for Neural Tube Defects (NTDs) has improved significantly and has seen a remarkable accumulation of clinical and experimental data in search of the causes and preventive measures of neural tube malformations such as an increase in folic acid. Yet, we still develop a limited knowledge of the morphologic and molecular bases of normal development of human neural tubes. In future research studies, the area of study may be focused on the possible interaction or combinations of gene-nutrient-environment interactions, prenatal medical and surgical modification of NTD and effective preventive strategies. Studies of survivors from spina bifida could also be worth attention since there’s almost no literature published about later adult ages (Webb).


Centers for Disease Control and Prevention. "Facts about Anencephaly." Centers for Disease Control and Prevention, 16 Dec. 2022,,part%20of%20the%20neural%20tube. Accessed 9 May 2023.

---. "What is Spina Bifida?" Centers for DIsease Control and Prevention, 3 Sept. 2020,,cord%20and%20nerves%20are%20affected. Accessed 16 May 2023.

Cleveland Clinic. "Anencephaly." Cleveland Clinic, 18 Aug. 2020, Accessed 9 May 2023.

Finnell, Richard H., et al. "Gene Environment Interactions in the Etiology of Neural Tube Defects." Frontiers in Genetics, vol. 12, 10 May 2021,

Fletcher, Jack M., and Timothy J. Brei. "Introduction: Spina Bifida-A Multidisciplinary Perspective." Developmental Disabilities Research Reviews, vol. 16, no. 1, 2010, pp. 1-5,

Jaquier, M., et al. "Spontaneous Pregnancy Outcome after Prenatal Diagnosis of Anencephaly." BJOG: An International Journal of Obstetrics and Gynaecology, vol. 113, no. 8, Aug. 2006, pp. 951-53,

Machado, Isabela Nelly, et al. "Anencephaly: Do the Pregnancy and Maternal Characteristics Impact the Pregnancy Outcome?" ISRN Obstetrics and Gynecology, vol. 2012, 19 Jan. 2012, pp. 1-5,

Munteanu, Octavian, et al. "The Etiopathogenic and Morphological Spectrum of Anencephaly: A Comprehensive Review of Literature." Romanian Journal of Morphology and Embryology, vol. 61, no. 2, 2020, pp. 335-43,

Northrup, Hope, and Kelly A. Volcik. "Spina Bifida and Other Neural Tube Defects." Current Problems in Pediatrics, vol. 30, no. 10, Nov. 2000, pp. 317-32,

Oumer, Mohammed, et al. "Prevalence of Anencephaly in Africa: A Systematic Review and Meta-analysis." Scientific Reports, vol. 11, no. 1, 9 Dec. 2021,

Pace, Nelson D., et al. "Survival of Infants with Spina Bifida and the Role of Maternal Prepregnancy Body Mass Index." Birth Defects Research, vol. 111, no. 16, 19 July 2019, pp. 1205-16,

Salari, Nader, et al. "Global Prevalence of Congenital Anencephaly: A Comprehensive Systematic Review and Meta-analysis." Reproductive Health, vol. 19, no. 1, 17 Oct. 2022,

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