What is NTD (Neural Tube Defect)?

Neural Tube Defects (NTDs)

Neural tube defects (NTDs) are a group of serious birth defects that affect the developing nervous system, including anencephaly, spina bifida, and encephalocele, occurring within the first month of conception when the neural tube fails to close properly. 1

Types of Neural Tube Defects

• Anencephaly: Partial or complete absence of skull bones with minimal remnant of brain tissue. Almost always fatal before or shortly after birth. 1

• Spina Bifida: Failure of vertebral arches to close over an open neural tube, exposing the spinal cord and nerves. Compatible with survival but typically causes moderate to severe physical disabilities and occasionally cognitive impairment. While most cases are open, 10-15% are closed (covered by skin). 1

• Encephalocele: Protrusion of brain tissue and/or covering membranes through the skull, most often in the occipital region. 1

Epidemiology and Impact

• The birth frequency of NTDs is approximately 1-2 per 1,000 births globally, with an estimated 214,000-322,000 affected pregnancies annually worldwide. 1, 2

• At least 90-95% of NTDs occur in women without a prior family history of this disorder. 1

• NTDs are the second most common major congenital anomaly after cardiac malformations. 3, 4

• Prevalence varies by geographic region, race, and environmental factors, with disproportionately higher rates in developing countries. 2, 3

Pathophysiology and Timing

• NTDs occur within the first 28 days after conception, often before pregnancy is recognized. 1, 5

• "Open" NTDs result from failure of primary neurulation, while "closed" NTDs are typically disorders of secondary neurulation. 6

• "Herniation" NTDs involve exteriorization of meninges with or without neural tissue through pathological openings in the skull or vertebral column. 6

Risk Factors

• Maternal folate insufficiency before and during early pregnancy is the most common preventable risk factor. 5, 2

• Other risk factors include:

  • Genetic factors (over 200 mutant genes cause NTDs in mice)
  • Previous pregnancy affected by NTD
  • Pre-pregnancy diabetes
  • Exposure to certain medications (e.g., valproic acid)
  • Maternal nutritional status 2, 6

Prevention

• Folic acid supplementation has been shown to reduce both occurrence and recurrence of NTDs by 40-100%. 1, 5

• For women without prior history of NTD-affected pregnancy:

  • 400 μg (0.4 mg) of folic acid daily throughout reproductive years 1, 5

• For women with prior history of NTD-affected pregnancy:

  • 4 mg of folic acid daily, starting at least 1 month (preferably 3 months) before conception and continuing through the first trimester 5
  • This higher dose has been shown to reduce recurrence risk by approximately 70% 5

• Prevention strategies include:

  • Daily supplements
  • Multivitamins containing folic acid
  • Consumption of foods fortified with folic acid
  • Combination of these approaches 1, 5

• Mandatory folic acid fortification of staple foods (implemented in about 60 countries) is considered safe, economical, and effective for primary prevention of NTDs. 2

Clinical Implications

• Outcomes depend on the level and extent of the lesion. 3, 4

• Management options include prenatal screening and diagnosis, with the possibility of fetal surgery for some cases to improve outcomes. 3, 4

• Unlike many other congenital abnormalities, primary prevention of NTDs is possible with adequate folic acid intake. 3, 4

Neural tube defects represent a significant cause of infant mortality and lifelong disability, but their occurrence can be substantially reduced through appropriate folic acid supplementation before and during early pregnancy.