Prenatal vs Postnatal Spina Bifida Repair and the Impact on Neurodevelopmental Impairment

BACKGROUND AND PURPOSE:

• Inversetti et al. (Ultrasound in Obstetrics & Gynecology, 2018) compared the impact of prenatal vs postnatal spina bifida repair on childhood neurodevelopment

METHODS:

• Systematic review and meta-analysis
• Included the following studies
  • Those that assessed neurological outcome of infants with spina bifida repaired prenatally vs postnatally
  • RCTs and non-randomized prospective controlled studies
• Primary outcome: Neurodevelopmental impairment at 1-year old or later
• Secondary outcomes
  • Preterm birth
  • Need for ventriculoperitoneal (VP) shunt by 12 months of age
  • Absence of signs of hindbrain herniation at the first postnatal MRI evaluation
  • Independent ambulation evaluated at 30 months

RESULTS:

• 2 studies included in systematic review and meta-analysis
  • 213 total children
  • 14 to 53 months of age
• Neurodevelopment
  • Assessed with Bayley Scales of Infant Development II (BSID-II) mental development index
  • Corrected for age
• Neurodevelopmental impairment was similar between children who went through prenatal (23.8%) and postnatal repair (27.8%)
• Risk of preterm birth was higher in the prenatal cohort (P < 0.0001)
  • Odds ratio (OR) 17.62 (95% CI, 7.60–40.87)
• The need for VP shunt placement by 12 months was lower in the prenatal group (P < 0.0001)
  • 41.3% vs 83.0%
  • OR 0.14 (95% CI, 0.08–0.26)
• Need for a shunt was lower in the prenatal group vs postnatal group (P < 0.0001)
  • 41.3% vs 83.0%
  • OR 0.14 (95% CI, 0.08-0.26)
• Neurodevelopmental impairment was not different between those children that did and did not have a shunt (prenatal RCT study only)
• Hindbrain herniation (MRI) was lower in prenatal vs postnatal group (P < 0.0001)
  • 0% vs 4.5%
  • OR 9.45 (95% CI, 3.12–28.64)
• Independent ambulation at 30 months was higher in the prenatal vs postnatal group (P = 0.003)
  • 37.6% vs 18.9%
  • OR 2.59 (95% CI, 1.39–4.86)

CONCLUSION:

• There was no difference in risk of neurodevelopmental impairment when comparing prenatal to postnatal spina bifida repair
• While preterm birth was higher in prenatal repair group, hindbrain herniation rate was reduced and independent ambulation was increased

Learn more – Primary Sources:

Neurodevelopmental outcome of children with spina bifida aperta repaired prenatally vs postnatally: systematic review and meta-analysis

Neural Tube Defects: Definitions, Key Clinical Findings and Management

WHAT IS IT?

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

Cranial

• 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)

KEY POINTS:

Clinical Findings

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

CNS

• 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

Ambulation

• 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)

Ultrasound

• 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

Amniocentesis

• 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”

Benefits

• 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

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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)