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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)

NICHD Study Update: Does Prenatal Surgery of Myelomeningocele Improve Motor Development Beyond 2 Years Follow-Up?


  • The initial report of the NICHD prenatal myelomeningocele study demonstrated improvement in the following   
    • Decreased hindbrain herniation and consequent need for shunting and improved distal neurologic function 
  • Long-term outcomes have confirmed shunting benefit but data on neurologic and motor function outcomes were lacking  
  • Farmer et al. (Am J Obstet Gynecol., 2018) report the 30-month outcomes for the entire cohort of patients randomized to either prenatal or postnatal repair of myelomeningocele 


  • Follow-up analyses of NICHD sponsored Management of Myelomeningocele Study 
  • Women had been randomly assigned to undergo 
    • Standard postnatal repair 
    • Prenatal repair at <26 weeks gestation 
  • Primary outcome of the study was a composite of mental development and motor function outcome at 30 days  
  • Secondary outcomes 
    • Independent ambulation and the Bayley Sales of Infant Development (2nd edition) 
  • Effects and Subgroups
    • Fetal leg movements 
    • Ventricle size 
    • Presence of hindbrain herniation 
    • Gender  
    • Location of the myelomeningocele lesion 
  • Within the prenatal surgery group only, these and other baseline parameters were evaluated as predictors of 30-month motor and cognitive outcomes 
  • Researchers also assessed if the presence or absence of a shunt at 1 year was associated with 30-month motor outcomes 


  • Data from 183 subjects were analyzed  
  • Prenatal repair improved the primary outcome  
    • Composite score of mental development and motor function was 199.4 ± 80.5 vs 166.7 ± 76.7 (P=.004) 
  • Prenatal surgery resulted in improvements in the secondary outcomes of 
    • Independent ambulation (44.8% vs 23.9%, P=.004) 
    • Self-care score (20.8 vs 19.0, P=.006) 
    • Mean Bayley Scales of Infant Development, psychomotor development index (17.3% vs 15.1%, P=.03) 
  • Prenatal surgery did not affect cognitive development at 30 months 
  • Boys demonstrated slightly better improvement in functional level and psychomotor development index 
  • Independent ambulation was associated with 
    • Patients receiving prenatal surgery 
    • The presence of in utero ankle, knee, and hip movement 
    • Absence of a sac over the lesion and a myelomeningocele lesion ≤L3  
  • Postnatal motor function showed no correlation with either prenatal ventricular size or postnatal shunt placement 


  • The full cohort data of 30-month cognitive development and motor function supported previous findings 
  • Prenatal surgery of myelomeningocele improved motor function, mental development, independent ambulation, self care score 
  • Indicators of independent ambulation were identified including presence of in utero joint movement and absence of sac over the lesion and a lesion ≤L3.  
  • Future research should focus on longer-term follow up to school age  
  • This study did not use fetoscopic methods, which also awaits further research  
    • Primary benefit of fetoscopy would be to avoid requirement for cesarean section
  • The ACOG / SMFM Committee Opinion states

Open maternal–fetal surgery for myelomeningocele repair has been demonstrated to improve a number of important pediatric outcomes at the expense of procedure-associated maternal and fetal risks.

Women with pregnancies complicated by fetal myelomeningocele who meet established criteria for in utero repair should be counseled in nondirective fashion regarding all management options, including the possibility of open maternal–fetal surgery.

Interested candidates for fetal myelomeningocele repair should be referred for further assessment and consultation to a fetal therapy center that offers this intervention and possesses the expertise, multi-disciplinary team, services, and facilities to provide detailed information regarding maternal–fetal surgery and the intensive care required for patients who choose to undergo open maternal–fetal surgery.  

Learn More – Primary Sources: 

The Management of Myelomeningocele Study: full cohort 30-month pediatric outcomes.

ACOG SMFM Committee Opinion 720: Maternal–Fetal Surgery for Myelomeningocele

NTDs and Pregnancy – Folic Acid Recommendations


ACOG guidance provides the latest update on neural tube defects (NTDs) including recommendations related to screening, management and delivery. The USPSTF has reaffirmed its recommendation that folic acid supplementation prevents NTDs in offspring. Evidence of potential harms to mother or infant is no greater than small.


    • All women who are planning or capable of pregnancy should take a daily supplement containing 0.4 to 0.8 mg (400 to 800 µg) of folic acid
    • Approximately 50% of pregnancies in the US are unplanned so it is best to already be on folic acid prior to pregnancy
  • ACMG
    • Daily folic acid intake of 400 µg (0.4 mg) is recommended in all women of child-bearing age
      • If planning pregnancy, start at least 4 weeks prior to planned conception
    • Women at High risk: 4,000 µg (4 mg) of daily folic acid supplementation at least 12 weeks prior to conception
      • Then continue with 400 µg (0.4 mg) after 12 weeks gestation

Note: ACMG highlights that folic acid supplementation reduces risk but not entirely prevent NTDs even among women who are fully compliant

  • ACOG, CDC, AAFP, AAP, Health and Medicine Division of the National Academies (formerly the Institute of Medicine), US Public Health Service, American Academy of Neurology
    • Women who are capable of becoming pregnant should take at least 0.4 mg (400 µg) of folic acid daily
  • ACOG, CDC, and several other organizations
    • Women with a history of neural tube defects, or has a partner with an NTD or a partner who has had a child with an NTD or other high-risk factors take 4 mg (4000 μg) of folic acid daily

Note: While USPSTF focuses on prevention of NTD, other organizations also stress the prevention of other birth defects such as heart defects, urinary tract anomalies and oral facial clefts

High risk factors include the following

  • Patient has a previously NTD-affected pregnancy
  • Patient herself is affected
  • Patient with a first- or second-degree relative with a NTD
  • Diabetes mellitus type 1
  • Obesity
  • Particular antiseizure medications (eg, valproic acid)

NOTE: Folic acid may not prevent NTDs in diabetic pregnancies, especially if not well controlled | Likewise regarding obesity and antiepileptic medications may also be folate-resistant

Learn More – Primary Sources:

USPSTF Statement: Folic Acid Supplementation for the Prevention of Neural Tube Defects

ACOG Practice Bulletin 187: Neural Tube Defects

ACOG Committee Opinion 720: Maternal–Fetal Surgery for Myelomeningocele

ACMG Policy Statement on folic acid and neural tube defects

ACMG Focused Revision: Policy statement on folic acid and neural tube defects

CDC Recommendations for the Use of Folic Acid to Reduce the Number of Cases of Spina Bifida and Other Neural Tube Defects

SOGC Guideline 410: Prevention, Screening, Diagnosis, and Pregnancy Management for Fetal Neural Tube Defects

Locate a Genetic Counselor or Genetics services:

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Maternal Fetal Medicine Specialist Locator-SMFM