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Neural tube defects

Last updated: January 23, 2025

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Neural tube defects (NTDs) are the most common congenital malformations of the central nervous system (CNS). They develop between the 3rd and 4th weeks of pregnancy and are often caused by folate deficiency. Most commonly, a deficiency in folate results in improper closure of the neural tube in the embryo, mainly at the caudal or cranial ends. The formation of defects at the caudal end is more common and is known as spina bifida. Spina bifida may occur without any apparent clinical features (spina bifida occulta) or manifest with protrusion of the meninges and, potentially, the spinal cord (myelomeningocele) through a gap in the vertebrae. Myelomeningoceles predominantly cause symptoms of sensory and motor function loss, such as bladder dysfunction and paraplegia. NTDs at the cranial end can cause cranial fissure malformations; the most severe manifestation of this, anencephaly, is incompatible with life. The diagnosis of NTDs is often established during pregnancy via ultrasound and detection of elevated alpha-fetoprotein levels in the maternal serum or amniotic fluid. Treatment involves prophylactic administration of antibiotics and rapid surgical closure of the defect to avoid CNS infections. Supplementation with folic acid is an important preventative measure; because of the high rate of unplanned pregnancies, daily folic acid is recommended for all individuals capable of pregnancy. For individuals with a personal, family, or partner history of NTD, a higher folic acid dose is recommended.

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Definitionstoggle arrow icon

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Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

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Etiologytoggle arrow icon

Most NTDs are isolated malformations with multifactorial etiology; they are more likely to occur when risk factors are present.

Risk factors for neural tube defects [4][5]

Fetal causes

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Spinal defects (subtypes of spina bifida) [6]
Condition Description Clinical features

Diagnosis

Closed spinal dysraphism
Spina bifida occulta
  • Most commonly affects the lower lumbar or sacral region
  • Often asymptomatic (may be an incidental finding in imaging)
  • Possible symptoms at the level of the vertebral defect:
    • Lumbar skin dimple
    • Collection of fat
    • Patch of hair
Lipomyelomeningocele
  • Often asymptomatic
  • Subcutaneous mass in the lumbar or sacral region
  • Possibly skin dimple and/or patch of hair
Lipomeningocele
Open spinal dysraphism
Meningocele
Myelomeningocele
Myeloschisis (rachischisis)
  • Portions of the neural tube completely fail to fuse, leading to bare, exposed neural tissue without coverage of meninges, bones, or skin.
  • Most severe subtype
Myelocele
  • Parts of the spinal cord (without meningeal coverage) herniate through the vertebral bone defect.

Cranial defects [6]
Condition Description Clinical features Diagnosis
Anencephaly
Encephalocele
  • Brain tissue herniates through occipital or frontal bone defect.
  • Covered by skin
  • Malformations and neurological deficits that vary in severity
  • Lethal in severe cases
  • Normal AFP (usually not elevated)
Acrania
  • Incompatible with life

The most common NTDs are spina bifida and anencephaly.

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Diagnosistoggle arrow icon

Prenatal period [1]

AFP is only elevated in open NTDs.

Postnatal period [1]

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Differential diagnosestoggle arrow icon

Tethered cord syndrome [7][8]

Congenital dermal sinus

The differential diagnoses listed here are not exhaustive.

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Treatmenttoggle arrow icon

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Preventiontoggle arrow icon

Counseling on modifiable risk factors for NTD and folic acid supplementation is a routine part of preconception care and prenatal care.

Management of modifiable risk factors for NTD

Folic acid supplementation in pregnancy [4][5][12]

Folic acid supplementation reduces the risk of neural tube defects. [4]

Standard prevention [5][12][13]

  • Recommended for all individuals capable of pregnancy
  • Advise oral folic acid 0.4–0.8 mg once daily, continued until 12 weeks' gestation. [5][12][13]
  • For individuals planning pregnancy who are not already taking folic acid, recommend starting ≥ 4 weeks before trying to conceive. [4]

Because of the high rate of unplanned pregnancies, the USPSTF recommends that all individuals capable of pregnancy take a folic acid supplement. [5]

Checking serum vitamin B12 levels to rule out an undiagnosed vitamin B12 deficiency anemia is not required before starting folic acid supplementation. [14]

Prevention for high-risk individuals [4][14]

  • Individuals with any of the following have an increased risk of pregnancy affected by NTD:
    • Previous pregnancy with NTD from either the birthing parent or partner
    • Partner history of NTD
    • Personal history of NTD
  • A standard dose of oral folic acid (0.4–0.8 mg PO daily) is recommended throughout reproductive life. [12]
  • A high dose of oral folic acid (4 mg daily) is recommended from 3 months before conception until 12 weeks' gestation. [4][14]

There is limited evidence for the efficacy of reducing NTDs with higher doses of folic acid in individuals with diabetes, maternal obesity, genetic disorders, and epilepsy (including individuals on antiepileptics). [4]

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