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Neural tube defects: anencephaly and spina bifida

  • NTDs arise from failures in the development and closure of the neural tube during the first 6 weeks of gestation, leading to damage to the spinal cord or to the brain, and to nerves.
  • There are two main types of neural tube defect (NTD):
    • anencephaly (a lethal form where much of the brain skull and scalp are missing)
    • spina bifida (where one or more vertebrae are not fully formed and allow the contents of the spinal canal to pouch out from the vertebra posteriorly).
  • Both main types of NTD are equally common, and usually follow a multifactorial inheritance pattern, although both occur slightly more frequently in female infants than males.
  • The severity of the NTD differs between individuals and depends on the location of the lesion and whether the overlying skin remains intact.
  • Spina bifida most commonly occurs in the lumbosacral region, and usually may be classified as:
    • a meningocele (when only the membranes around the spinal cord protrude out from the vertebra forming a fluid-filled sac)
    • a myelomeningocele (when the spinal cord itself also protrudes). The lesions can be open to the exterior, or can present as closed (where the membranes are intact and may also be covered by the skin).
  • Some rarer types of NTD include:
    • encephalocele (outpouching of the brain and/or its membranes through a skull defect, usually at the occiput)
    • rachischisis (spina bifida involving an extensive length of the spine)
    • diastematomyelia (division of the lower part of the spinal cord longitudinally, often associated with a bony vertebral spur).
  • Common symptoms from spina bifida include weakness and paralysis of the legs, difficulties in bowel and bladder control, hydrocephalus and some learning disabilities.
  • The birth incidence of NTDs in the British Isles has declined to less than 0.1%, probably owing mainly to a combination of improved maternal nutrition and the administration of folic acid supplement before and during pregnancy. Also, most lesions can be detected antenatally on routine mid-trimester ultrasound scan, or following raised 2nd trimester maternal serum alphafetoprotein, giving informed prenatal choice for the parents.
  • Excepting lethal presentations, open lesions resulting from the condition are surgically closed as soon as possible in neonates, as this optimises outcome.
  • Spina bifida occulta, involving minor incomplete posterior fusion of a vertebra, and sometimes associated with additional features on the overlying skin, is a common benign finding in the general population on X-ray of the lower back. It is present in up to 5-10% of the general population, and does not confer any known increased genetic risk for spina bifida in offspring.

Clinical features

  • Anencephaly is a lethal condition. The forebrain fails to develop, and the brain is exposed due to a large section of the skull being missing, resulting in stillbirth, or in death within the first few hours after birth.
  • With spina bifida, the most common symptoms include weakness or paralysis of the legs, difficulties in bowel and bladder control, hydrocephalus (present in 90% of children with a lumbosacral myelomeningocele), and some learning disability. The bladder problems often lead to recurrent urinary infections and kidney damage.
  • With spina bifida, life expectancy may be reduced, depending on the severity of the lesion and the complications.
  • In the general population, 5-10% of people are found on X-ray of the lower back to have minor incomplete posterior fusion of a vertebra, and sometimes associated with a hairy patch or dimple on the overlying skin. Referred to as ‘spina bifida occulta’, this is a common benign finding, and is not thought to confer any increased genetic risk for NTD in offspring.

Diagnosis

  • Postnatally, for most forms of NTD the diagnosis is obvious at birth
  • Prenatal detection is now mostly achieved by mid-trimester detailed fetal ultrasonography, with more accurate delineation if necessary by fetal MRI scan to assist prediction of likely clinical severity and complications. Mild defects may be difficult to detect.
  • Although most fetuses with an open NTD result in a raised level (>2.5 MoM) of 2nd trimester (16-week) maternal serum alphafetoprotein (MSAFP), this is more often raised for other reasons. Due to assay interference, MSAFP is also unreliable in mothers taking valproate, which is noteworthy since 1st trimester fetal exposure to valproate does confer a slightly higher risk for NTD.
  • Currently, there is no reliable 1st trimester maternal serum marker for NTD.

Genetic basis

  • Most NTDs show multifactorial inheritance. However, they may also be seen as a feature in some chromosome or rare single gene disorders, usually in combination with other malformations.
  • A positive family history of NTD significantly increases the genetic recurrence risk (eg. typically up to around 4% where one parent or a previous child has NTD).
  • Certain health problems in the mother, or the medication used for their treatment, are known also to confer an increased susceptibility for a fetus to have a NTD. These include maternal diabetes, obesity, folate deficiency, or folate-antagonist anticonvulsants prescribed for epilepsy.
  • Studies of genes involved in the folate pathway to find any common variation which is associated sufficiently strongly with differences in susceptibility to NTD to be applied in any clinical setting, have been disappointing.

Clinical management

  • In non-lethal presentations, open spina bifida lesions are usually surgically closed as soon as possible following birth.
  • Accompanying hydrocephalus usually also requires neurosurgical management.
  • Regular multidisciplinary follow-up assessment is required, particularly for the urinary tract and spine.
  • Longer term counselling support and learning support may be required.
  • In order to minimise the chance for a fetus to have a NTD, all women contemplating pregnancy are advised to take supplementary folate as 400 mcg of folic acid daily from at least one month before embarking upon a pregnancy until three months after the date of the last menstrual period.
  • Research has shown that for women at known increased genetic risk of having a child with a NTD the recommended supplementary folate dose of 5mg daily reduces the risk of NTD occurrence in their children by as much as 70%.

Genetic testing

  • As NTDs can occur as one manifestation of some congenital malformation syndromes, karyotyping, clinical genetic referral, and/or appropriate gene tests should be considered if a baby presents with other congenital anomalies (eg. renal cysts, polydactyly, or syndactyly) in addition to a NTD.

 

This information is intended for educational use and was current in February 2014. For clinical management, it is recommended that local guidelines and protocols are used.