Neural tube defects, or NTDs, are a group of severe birth defects in which the brain and spinal cord are malformed and lack the protective encasement of soft tissue and bone. They are called neural tube defects because they develop out of a tube formed in the early embryo by the closure of the outer germ layer of tissue. This tube later develops into the brain and spinal cord.
Description
Incomplete formation and protection of the brain or spinal cord with bony and soft tissue coverings that occur during the fourth week of embryo formation are known collectively as neural tube defects. These lesions may occur anywhere in the midline of the head or spine. Neural tube defects are among the most common serious birth defects, but they vary considerably in their severity. In some cases, the brain or spinal cord is completely exposed; in some cases it is protected by a tough membrane (meninges); and in other cases it is covered by skin.
Spina bifida is a congenital defect that accounts for about two-thirds of all neural tube defects. Its name comes from two Latin words that mean "cloven backbone." The spinal defect may appear anywhere from the neck to the buttocks. In its most severe form, termed "spinal rachischisis," the entire spinal canal is open, exposing the spinal cord and nerves. More commonly, the defect appears as a localized mass on the back that is covered by skin or by the meninges.
Anencephaly, the second most common neural tube defect, accounts for about one-third of cases. Two major subtypes occur. In the most severe form, all of the skull bones are missing and the brain is exposed in its entirety. The second form, in which only a part of the skull is missing and a portion of the brain exposed, is termed "meroacrania."
Encephaloceles are the least common form of neural tube defects, comprising less than 10% of the total. With encephaloceles, a portion of the skull bones is missing, leaving a bony hole through which the brain and brain coverings herniate, or protrude abnormally. Encephaloceles occur in the midline from the base of the nose to the junction of the skull and neck. As with spina bifida, the severity of encephaloceles varies greatly. At the mildest end of the spectrum, an encephalocele may appear as only a small area of faulty skin development with or without any underlying skull defect. At the severe end of the spectrum, most
of the brain may be herniated outside of the skull into a skin-covered sac.
Genetic profile
Most neural tube defects (80–90%) occur as isolated events. In the United States and Canada, NTDs occur in the Caucasian population in about 1.5 of every 1,000 live births. Neural tube defects of this variety are believed to arise through the combined influence of genetic and environmental forces. This multifactorial causation presumes that one or more predisposing genes collaborate with one or more environmental influences to result in the birth defect. Poor nutrition is believed to be an environmental risk factor; hereditary defects in the absorption and utilization of folic acid are presumptive genetic predisposing factors. After a couple has one infant with a neural tube defect, the risk of recurrence is 3–5%. After the birth of two infants affected with neural tube defects, the risk increases to 8–10%. A parent with a multifactorial NTD has a 3–4% chance of having a child with an NTD.
When neural tube defects occur concurrently with other malformations, there is a greater likelihood of an underlying specific genetic or environmental cause. Genetic causes include chromosome aberrations and single gene mutations. Environmental causes include maternal diabetes mellitus, exposure to prolonged hyperthermia, and taking seizure medications during the early months of pregnancy.
Demographics
Neural tube defects occur worldwide. It appears that the highest prevalence (about one in 100 pregnancies) exists in certain northern provinces in China; an intermediate prevalence (about one in 300–500 pregnancies) has been found in Ireland and in Central and South America; the lowest prevalence (fewer than one in 2,000 pregnancies) has been found in the Scandinavian countries. In the United States, the highest prevalence tends to occur in the Southeast. Worldwide there has been a steady downward trend in prevalence rates over the past 50–70 years.
Causes and symptoms
Because of the incorrect development of the spinal cord and nerves, a number of consequences are commonly seen in spina bifida. As a rule, the nerves below the level of the defect develop in an abnormal manner and fail to function, resulting in paralysis and loss of sensation below the level of the spinal lesion. Since most defects occur in the lumbar region, the lower limbs are paralyzed and lack normal sensation. Furthermore, the bowel and bladder have inadequate nerve connections, leading to the inability to control bladder and bowel function. Sexual function is likewise impaired. Hydrocephaly, which is an abnormal accumulation of fluid within the ventricles or cavities of the brain, develops in most of these infants either before or after surgical repair of the spine defect.
In anencephaly, the brain is destroyed by its exposure during intrauterine life. Most infants with anencephaly are stillborn or die within the first few days or weeks after birth.
Infants with encephaloceles have variable neurologic impairments depending on the extent of brain involvement. When only the brain covering is involved, the individual may escape any adverse effect. When the brain is involved in the defect, however, impairments of the special senses such as sight and hearing, as well as cognitive impairments, commonly result.
Diagnosis
At birth, the diagnosis of a neural tube defect is usually obvious based on external findings. Prenatal diagnosis may be made with ultrasoundexamination after 12–14 weeks of pregnancy. Screening of pregnancies can be carried out at 16 weeks by testing the mother's blood for the level of alpha-fetoprotein. Open neural tube defects leak this fetal chemical into the surrounding amniotic fluid, a small portion of which is absorbed into the mother's blood.
Treatment
No treatment is available for anencephaly. Aggressive surgical and medical management has improved survival and function of infants with spina bifida. Surgery closes the defect, providing protection against injury and infection. Walking may be achieved with orthopedic devices. A common complication that may occur before or after surgical correction is the accumulation of excessive cerebral spinal fluid (hydrocephaly) in the major cavities within the brain. Hydrocephaly is usually treated with the placement of a mechanical shunt, which allows cerebral spinal fluid from the ventricles to drain into the circulation or into another body cavity. A number of medical and surgical procedures have been used to protect the urinary system. Encephaloceles are usually repaired by surgery soon after birth. The success of surgery often depends on the amount of brain tissue involved in the encephalocele.
It has been found that 400 mcg of folic acid taken for two to three months prior to conception and two to three months following conception protects the fetus against most neural tube defects. While there are a number of foods (green leafy vegetables, legumes, liver, orange juice) that are good sources of natural folic acid, synthetic folic acid is available in over-the-counter multivitamins and a number of fully fortified breakfast cereals.
In addition, a population-wide increase in folic acid intake has been achieved through the fortification of enriched cereal grain flours since January 1998, a measure authorized by the U.S. Food and Drug Administration. The increased blood levels of folic acid in the general population achieved in recent years has likely resulted from the synergy of dietary, supplementation, and fortification sources.
Prognosis
The prognosis for infants with anencephaly is grim; they are usually stillborn or die within the first days of life. In contrast, 80–90% of infants with spina bifida survive with surgery. Paralysis below the level of the defect, including an inability to control bowel and bladder function, and hydrocephaly are complications experienced by most infants who survive. Intellectual function, however, is normal in most cases.
The prognosis for infants with encephaloceles varies considerably. Small encephaloceles may cause no disability whether surgical correction is performed or not. Infants with larger encephaloceles may have residual impairment of vision, hearing, nerve function, and intellectual capacity.
Health care team roles
Pediatricians, family physicians, obstetricians, or nurse midwives usually diagnose previously unknown neural tube defects at birth. Testing maternal blood for alpha-fetoproteins can often diagnose neural tube defects. Surgeons often repair neural tube defects. Physical therapists, social workers, and counselors may provide ongoing care to children with neural tube defects and their families. Support groups are often helpful to these families.
Prevention
Taking folic acid supplements (400 mcg per day) from two to three months prior to conception and the first trimester of pregnancy offers some protection against many neural tube defects. Pregnant women should be advised to avoid certain medications and recreational drugs, especially some anticonvulsants and hallucinogens.
KEY TERMS
Anencephaly—Absence of all or a portion of the bones of the skull.
Embryo—An organism during an early development period when organs and other specialized structures are being formed. In humans, the embryonic period is considered to be the first eight weeks after conception.
Encephalocele—A hole in the bony covering of the spinal cord through which portions of the brain, spinal cord or meninges may herniate.
Folic acid—A water-soluble vitamin that is essential to the formation of purine and thymine in the body. A deficiency of folic acid causes a form of anemia.
Herniate—To protrude abnormally through an opening in bone or surrounding tissues.
Hydrocephaly—An abnormal accumulation of cerebrospinal fluid in the cavities of the brain.
Meninges—The three-layered membrane that covers the brain and spinal cord.
Neural tube—A tube that forms in the early embryo when the outer germ layer of tissue (ectoderm) closes. The neural tube develops into the spinal cord and the brain.
Spinal rachischisis—A lack of covering over the entire spinal canal, exposing the spinal cord and nerves.
BOOKS
Adams, Raymond D, Maurice Victor, and Allan Ropper. Adams' and Victor's Principles of Neurology, 6th ed. New York: McGraw-Hill, 1997.
Cunningham, F. Gary, et al. Williams Obstetrics, 21st ed. New York: McGraw-Hill, 2001.
Elias, Sherman, Joe Leigh Simpson, and Allan T. Bombard. "Amniocentesis and Fetal Blood Sampling." In Genetic Disorders in the Fetus: Diagnosis, Prevention, and Treatment, 5th ed., edited by Aubrey Milunsky. Baltimore, MD: Johns Hopkins University Press, 1998.
Haslam, Robert H. A. "Neural tube defects." In Nelson Textbook of Pediatrics, 16th ed., edited by Richard E. Behrman et al. Philadelphia: Saunders, 2000.
"Multifactorial Inheritance." Chapter 286 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.
Rapp, Rayna. Testing Women, Testing the Fetus: The Social Impact of Amniocentesis in America. New York: Routledge, 2000.
Shannon, Joyce B. "Amniocentesis and chorionic villus sampling (CVS)." In Health Reference Series, Medical Tests Sourcebook., ed. Joyce B. Shannon. Detroit, MI, Omniographics, Inc., 1999.
PERIODICALS
Gelabert-Gonzalez M, Cutrin-Prieto JM, Garcia-Allut A. "Spinal arachnoid cyst without neural tube defect." Children's Nervous System 17, no. 3 (2001): 179-181.
Gross SM, Caufield LA, Kinsman SL, Ireys HT. "Inadequate folic acid intakes are prevalent among young women with neural tube defects." Journal of American Dietetic Association 101, no. 3 (2001): 342-345.
Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. "Neural tube defects in relation to use of folic acid antagonists during pregnancy." American Journal of Epidemiology 153, no. 10 (2001): 961-968.
Richter B, Stegmann K, Roper B, Boddeker I, Ngo ET, Koch MC. "Interaction of folate and homocysteine pathway genotypes evaluated in susceptibility to neural tube defects (NTD) in a German population." Journal of Human Genetics 46, no. 3 (2001): 105-109.
van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ. "Folate, homocysteine and neural tube defects: An overview." Experimental Biology and Medicine (Maywood) 226, no. 4 (2001): 243-270.
Viner-Brown SI, Cain R, Simon PR. "Open neural tube defects among newborns in Rhode Island." Medicine and Health in Rhode Island 84, no. 4 (2001): 138-139.
ORGANIZATIONS
American Academy of Neurology. 1080 Montreal Avenue, St. Paul, MN 55116. (651) 695-1940. Fax: (651) 695-2791. <http://www.aan.com>. info@aan.org.
American Academy of Pediatrics. 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (847) 434-4000. Fax: (847) 434-8000. <http://www.aap.org/default.htm>. kidsdoc@aap.org.
American Association for Clinical Chemistry. 2101 L Street, NW - Suite 202, Washington, DC 20037-1558. (800) 892-1400 or (202) 857-0717. Fax: (202) 887-5093. <http://www.aacc.org>. info@aacc.org.
American Board of Obstetrics and Gynecology. 2915 Vine Street Suite 300, Dallas, TX 75204. (214) 871-1619. Fax:(214) 871-1943. <http://www.abog.org>. info@abog.org.
American College of Obstetricians and Gynecologists. 409 12th St., S.W., PO Box 96920, Washington, DC 20090-6920. <http://www.acog.org>.
American Society for Reproductive Medicine. 1209 Montgomery Highway, Birmingham, AL 35216-2809.(205) 978-5000. <http://www.asrm.com>.
