• Nathan Riley, MD

Obgyno Wino Podcast Episode 97 - Neural Tube Defects

"Most people don’t grow up. It’s too damn difficult. What happens is most people get older. That’s the truth of it. They honor their credit cards, they find parking spaces, they marry, they have the nerve to have children, but they don’t grow up. Not really. They get older. But to grow up costs the earth, the earth. It means you take responsibility for the time you take up, for the space you occupy. It’s serious business. And you find out what it costs us to love and to lose, to dare and to fail. And maybe even more, to succeed." — Maya Angelou

2020 Côtes-du-Rhône Rouge Famille Perrin

PB #187, Published December 2017

Five Pearls

1. NTDs comprise a wide range of conditions, from asymptomatic spina bifida occulta to anencephaly, which more often than not results in early neonatal death if the baby survives pregnancy.

2. Folic acid supplementation reduces risk for NTD. 400 mcg is recommended for all women. 4 mg is recommended for women with history of NTD in prior pregnancy.




Embryology and epidemiology

- the neural tube forms when a sheet of neuroepithelial cells rolls into a tube

- occurs 3-4 weeks after conception

- begins in the cervical region then extends caudally and cranially

- 0.55 per 10,000 lives births in the U.S. are affected by anencephaly (2.5 per 10,000 live births + stillbirths + terminations)

Etiologies and risk factors for neural tube defects (NTDs)

- etiology is multifactorial but risk is reduced through folic acid supplementation

- anticonvulsant medication use (e.g. carbamazepine and valproic acid) increases the risk

- maternal hyperthermia (e.g. sauna, hot tub, or fever) is associated with higher risk

- pregestational diabetes and obesity are independent risk factors

- some aneuploidies are associated with NTDs: T13, T18, and triploidy

- there are also a few single gene disorders and microdeletions such as 22q11.1 (formerly DiGeorge syndrome) which carry higher risk

- specific gene polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene may be associated with NTDs but data is mixed

- if NTD affected prior child, risk of next pregnancy being affected is 3% (risk if 10% if two siblings were affected)

- risk of NTD is increased if 2nd or 3rd degree relative is affected, but absolute risk remains <1%


Clinical consequences

- wide spectrum of these disorders

- spina bifida occulta, for example, is usually completely asymptomatic (vertebrae and not completely closed)

- when CNS is directly affected, swallowing difficulties may manifest as polyhydramnios (which can be associated with preterm contractions and labor)

- anencephaly and more severe forms of spina bifida is commonly associated with persistent breech

- most infants with myelomeningocele die without surgical intervention, but with surgery, 75% survive to early adulthood

- size and location of hydrocephalus has great clinical importance and may require ventriculoperitoneal shunting

- Arnold-Chiari malformation: brain matter pushed into the spinal canal due to increased intracranial pressure, associated w/ spina bifida (4 types of chiari malformations)

- if this malformation is not rectified, long-term neurologic damage can result

- motor dysfunction can also be present to varying degrees depending on level of defect

- scoliosis is common w/ spina bifida (50%)

- lower urinary tract dysfunction is very common in NTDs, especially w/ myelomeningocele

- long-term voiding dysfunction results in hydronephrosis and renal dysfunction

- innervation issues with anus/rectum also commonly lead to constipation/fecal incontinence

- 1/3 of people w/ open NTDs have an allergy to latex

- as a result of all of these issues...NTDs are very expensive medically speaking due to long-term specialized care needs

Folic acid supplementation can reduce risk of NTDs

- every women is recommended 400 mcg daily of folic acid supplementation

- if history of NTD in prior pregnancy, higher dose of 4 mg daily is recommended through at least the 12th wga

- this higher dose reduces risk by >70% of NTD in subsequent pregnancy

- we aren't sure why folic acid is related to NTDs

- roughly 30% of NTDs aren't prevented even with folic acid supplementation

- higher doses of folic acid unfortunately do not reliably prevent NTDs in diabetes, obesity, or in women taking medications that interfere with folic acid metabolism (e.g. anticonvulsants)

- folic acid is non-toxic to the mom or fetus

Note: the additional folic acid should be consumed from separate supplements not by loading up on multivitamins, as many of the fat soluble vitamins in multivitamins can be toxic in high quantities.

Screening for NTDs consists of serum biomarkers and ultrasound (US)

- maternal serum fetal alpha protein (MSAFP, for short)

- AFP is produced in the liver and yolk sac, and if detected in high levels in mom's blood, it may be suggestive of an open NTD

- MSAFP levels are measured multiples of the median (MoM)

- 65-80% detection rate for open NTDs; 95% detection rate for ancephaly if levels are 2.5 MoM or greater

- MSAFP elevations are also not specific to NTDs: can be increased in multi-fetal gestation, fetal abdominal wall defects, placental issues, fetal nephrosis, or fetal demise

- great for screening tool, but fetal anatomy survey remains the definitive way to detect NTDs (much greater sensitivity: 95% versus 75%)

- formal anatomy survey is recommended for all women at 18-22 wga

- different head shapes or the presence of ventriculomegaly can also indicate open NTDs

Source: Neuroimaging Clinics

- if there remains any doubt, amniocentesis to check for acetylcholinesterase can help clarify open versus closed NTD

- 3D US isn't great for clarifying the details of NTD

So you've diagnosed what?

- refer to Maternal Fetal Medicine asap when an US report or serum screening reveals any abnormalities

- once the diagnosis is fairly clear, a shared decision making process should ensue ideally involving a transdisciplinary approach (see my episode on Perinatal Palliative Care for more)


- fortunately, it's not a decision born by you, so provide counseling and then support her in her decision

- one of the first pieces of information that should be collected once a diagnosis is suspected is to confirm through amniocentesis with chromosomal microarray: if NTD is associated with a genetic disorder, this may have distinct implications for prognosis and management options

- anencephaly is incompatible with long-term survival; therefore, some patients may want to terminate such a pregnancy

- outcomes of open spina bifida are highly variable

- in-utero surgical correction of some defects is possible and even recommended

- if significant hydrocephalus is suspected, ventriculoperitoneal shunting may be warranted soon after birth, and pediatric neurosurgery should be included in prenatal meetings to help guide decision-making

- serial ultrasound may be helpful throughout to monitor fetal growth and progression/resolution of hydrocephalus

- antenatal surveillance isn't helpful, as the presence of a NTD doesn't predispose pregnancy to greater risk for placental insufficiency

C-section is not necessary for most NTDs

- most of these kiddos deliver at term unless there is a maternal or obstetrics complications prompting earlier delivery

- if an in-utero surgery was performed, then same recommendations apply as patients with history of prior cesarean delivery by classical incision (higher risk of uterine rupture than a low transverse cesarean incision)

- if the nervous system isn't fully intact (e.g. anencephaly, myelomeningocele), breech presentation is common, and c-section is recommended (esp if the head is enlarged due to hydrocephalus)

- vaginal birth is still probably the best mode of delivery for a cephalic baby even with meningomyelocele

Source: Texas Children's

Fetal surgery for NTD

- neurological damage ensues with open NTDs that expose nervous tissue to amniotic fluid, which causes inflammation and damage

- another issue is that a large-enough open defect permits a decompression of the spinal canal and cranium such that the brain contents herniate down into the spinal canal (Arnold-Chiari malformation)

- closure of the defect may therefore improve long-term outcomes

- amniocentesis with chromosomal microarray should be conducted as an important piece of information pertaining to prognosis and conceivable outcomes

- counseling on the pro/cons of such a surgery is complicated and should be provided by trained fetal surgeons as a part of serial multi-disciplinary meetings from the time of diagnosis

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