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Neural Tube Defects: Definitions, Key Clinical Findings and Management


Approximately 3 to 4 weeks after fertilization, the neural plate folds, creating the neural tube. There are multiple factors, environmental as well a genetic, that go in to ensuring a full closure. When this process is not fully completed, neural tube defects (NTD) result. Folic acid supplementation decreases the risk for failed closure. ACOG recommends that folic acid, 400 micrograms, should be offered to all women “capable of becoming pregnant” starting at least 1 month before pregnancy (see ‘Related ObG Topics’ for more on folic acid recommendations).

Types and Definitions


  • Anencephaly
    • Failure of cephalic fusion
    • Abnormal clinical findings: Brain | Skull | Skin
  • Exencephaly
    • Failure of scalp/skull formation
    • Abnormal clinical findings: Exteriorization of brain
  • Encephalocele
    • Complete failure of skull formation
    • Abnormal clinical findings: Brain extrusion
  • Iniencephaly
    • Failure of cervical/upper thoracic vertebrae closure
    • Abnormal clinical findings: Brain | Thorax | Diaphragm | Lungs | Heart | Retroflexed spine

Spina Bifida – Failure of Spinal/Caudal Closure

  • Myelomeningocele
    • Abnormal clinical findings: Exposure of cord and meninges
    • Lumbosacral most common
  • Meningocele
    • Abnormal clinical findings: Exposure of meninges
  • Spina Bifida Occulta
    • Vertebral defect without spinal cord or meningeal exposure

Complex – Severe

  • Holorachischisis
    • Entire spinal cord exposed
  • Craniorachischisis
    • Anencephaly and additional NTD (usually affecting cervical-thoracic region)


Clinical Findings

75% of infants with myelomeningocele survive to early adulthood with modern therapies


  • Ventriculomegaly (hydrocephalus)
    • Can be treated with ventriculoperitoneal shunt placement
    • Placement often in first year of life, with many requiring revisions
  • Arnold–Chiari malformation (herniation of the cerebellar tonsils and distal medulla oblongata into the foramen magnum / spinal canal
    • Risk of severe neurologic morbidity or mortality
  • Intellectual delay
    • Intelligence dependent on level/type of the NTD, Arnold-Chiari malformation, hydrocephalus


  • Ability to walk dependent on level of NTD
    • L4 level or lower have better function

Bladder function

  • Myelomeningocele commonly associated with neurogenic bladder
    • Not related to vertebral defect level
    • May result in chronic renal dysfunction, with related morbidity and mortality

Bowel function

  • Most patients with open (no skin covering) NTDs will have bowel dysfunction and fecal incontinence

Note: Approximately 30% of individuals with NTD will have severe, life-threatening latex allergy

Screening and Diagnosis

Elevated MSAFP 

  • Screening test only
  • Differential diagnosis
    • Incorrect dating | Multiple Gestation | Fetal demise
  • ≥2.5 MoM (15 to 20 weeks): Detection rates as follows (1to 3% false positive rate)
    • Anencephaly: >95%
    • Open NTD: 65% to 80%
  • Increased risk for adverse events like IUGR and fetal demise
  • According to the ACOG guideline, with modern ultrasound and recommendation for universal second trimester anatomy exam, MSAFP screening “is less important”
  • ACMG released an updated guideline on open neural tube defects that includes the role of MSAFP in prenatal care that includes the following points
    • Since quality ultrasound and prenatal care are not uniform, there is still a role for MSAFP screening
    • MSAFP screening can identify
      • Incorrectly dated pregnancies | Multiple gestations | Other anatomic abnormalities | Rare maternal conditions (e.g., liver cancer)
    • Follow up recommendations for elevated MSAFP are consistent with management guidelines below
    • It is important to consider a priori risk for NTD that may be elevated due to factors such as
      • Personal or family history of NTD use | Diabetes | Medications (e.g., valproate)


  • 2D ultrasound can be considered diagnostic
    • 3D ultrasound not superior for diagnosis but may provide further anatomic detail
  • Optimal timing: 18 to 22 weeks, but earlier if indicated due to high risk or abnormal MSAFP
  • First-trimester
    • NTD can be diagnosed in the first trimester but less sensitive and should not replace standard second trimester ultrasound

Fetal MRI

  • To be used in conjunction with ultrasonography as indicated, particularly for diagnostic confirmation
  • MRI should not be used for
    • Routine NTD screening following ultrasound diagnosis
    • Primary NTD screening modality


  • Specifically for NTD Diagnosis
    • Reserve for acetylcholinesterase measurement if closed vs open NTD is inconclusive on ultrasound
  • ACOG recommends amniocentesis using microarray in the setting of fetal anomalies

Antepartum and Intrapartum Management

  • Refer to MFM unit with additional multidisciplinary support including genetics, pediatric neurosurgical and neonatology expertise
    • Outcomes likely superior if delivery occurs in high-risk, tertiary centers
  • Offer detailed sonography including fetal echocardiography
  • Individualize counseling
  • Increased antenatal fetal surveillance is not recommended
  • Delivery
    • Plan for term delivery but individualize (e.g., increasing hydrocephalus)
    • Cesarean section for breech presentation
    • ACOG states “Because it is not clear whether or how significantly the neurologic outcome is affected by the method of delivery in these infants, decisions about the timing and route of delivery should be made individually in consultation with personnel with experience and knowledge of NTDs”

Fetal Surgery

ACOG recommends that “utero repair is an option for women who meet appropriate criteria… only in an established fetal therapy center”


  • Management of Myelomeningocele Study (MOMS) RCT
  • Participants
    • 19w0d to 25w6d
    • Upper border T1-S1 with Arnold–Chiari malformation
  • 12-month follow-up
  • Results
    • 158 patients
    • Lower incidence of composite outcome of fetal or neonatal death or need for shunt placement
      • 68% vs 98% | RR, 0.70; 97.7% CI, 0.58 to 0.84
    • Lower incidence of hindbrain herniation
      • 64% vs 96% | RR, 0.67; 95% CI, 0.56 to 0.81
    • Higher level of function, two or more levels better than expected, including ambulation without devices or orthotics
    • No difference in cognitive test scores

Maternal and neonatal risks

  • Planned cesarean required due to uterine rupture risk
  • Preterm birth
    • <35 weeks: 50%
    • <30 weeks: 11%
  • Other risks include
    • PROM | Oligohydramnios | Dehiscence | Transfusion
  • Endoscopic repair has been reported and may improve outcomes

Learn More – Primary Sources:

ACOG Practice Bulletin 187: Neural Tube Defects

ACMG Policy Statement on folic acid and neural tube defects

Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)