Neural tube defect Flashcards
Closure of the neural tube begins at the___ region and extends cranially and caudally
cervical
Failure of neural tube closure at the ___ end results in anencephaly, and failure of closure at the___ end results in myelomeningocele or spina bifida.
cranial; caudal
- What’s the malformation for anencephaly?
- List the secondary consequences of anencephaly.
- Can anencephaly baby live?
- Failure of the fusion of the cephalic portion of neural folds; absence of all or part of brain, skull, and skin.
- Secondary consequences of anencephaly include absent or partial development of the forebrain with degeneration of the exposed neural tissue, incomplete development of the calvarium, and abnormal facial features, including cleft palate and abnormalities of the auricular area.
- Typically, anencephalic infants are stillborn, or survive only a few hours or days after delivery.
What’s the malformation for Exencephaly?
Failure of scalp and skull formation; exteriorization of abnormally formed brain
What’s the malformation for Encephalocele?
Failure of complete skull formation; extrusion of brain tissue into membranous sac
What’s the malformation for Iniencephaly?
Defect of cervical and upper thoracic vertebrae; with abnormalities of the associated vertebrae, retroflexion of the upper spine, defects of the thoracic cage, and abnormalities in development of the diaphragm, lungs, and heart
What’s the malformation for spinal bifida?
What are some associated anatomic changes?
List the team members that manage pregnancies complicated by spina bifida.
Failure of fusion of caudal portion of neural tube, usually of 3-5 contiguous vertebrae; spinal cord or meninges, or both, exposure to amniotic fluid.
Talipes equinovarus (clubfoot) and scoliosis are also commonly associated with spina bifida.
maternal–fetal medicine, neonatology, pediatric neurosurgery, and genetics
What’s the malformation for Meningocele and myelomenigocele?
What are some associated anatomic changes?
Both are from failure of fusion of caudal portion of neural tube;
- Meningocele: meninges exposed
- myelomenigocele: meninges and neural tissue exposed
- the lumbosacral regions are most commonly affected.
Associated anatomic changes include hydrocephalus, abnormal head shape, decreased biparietal diameter or head circumference, and Arnold–Chiari or Chiari type II malformation (herniation of the hindbrain)
What’s the malformation for myeloschisis?
Failure of fusion of caudal portion of neural tube; flattened mass of neural tissue exposed
What’s the malformation for Holorachischisis?
Failure of fusion of vertebral arches; entire spinal cord exposed
What’s the malformation for craniorachischisis?
coexisting anencephaly and open neural tube defect, often in the cervical-thoracic region
NTDs account for as many as ___ of neonatal deaths associated with congenital abnormalities in low-income settings
29%
Prevalence for spina bifida, per 10,000 live births and per 10,000 live births, stillbirths, or terminations?
the prevalence was 3.40 per 10,000 live births and 4.41 per 10,000 live births, stillbirths, or terminations
What are the general category for NTDs?
multifactorial, or attributed to a complex combination of genetic and environmental factors. Family history
List examples for specific environmental exposures factors associated with NTDs
- certain medications;
- maternal medical conditions (DM, obesity);
- geographic and ethnic associations (highest in Hispanic population) –> reflect a combination of genetic predispositions, dietary practices, and environmental exposures.
- genetic etiologies, including chromosomal abnormalities and single gene disorders
- fungal toxin fumonisin
- maternal hypertermia
To produce a NTD, the external influence must be present during the first ___ days of development, when the neural tube is forming.
28
What kind of medications increase the risk of NTDs? Also give some specific examples
- Medications that interfere with, or deplete, folic acid
- The antiepileptic medication carbamazepine has been associated with an increased risk of spina bifida. Valproic acid, an antiepileptic medication used also for treatment of bipolar and personality disorders, has been associated with a 10-fold to 20-fold increased risk of NTDs
- diphenylhydantoin, aminopterin,
Valproic acid, an antiepileptic medication used also for treatment of bipolar and personality disorders, has been associated with a __ fold increased risk of NTDs
10 to 20 fold
Maternal febrile illness during the first trimester may increase the risk of NTDs by as much as ____ fold
3
a ___ fold increased risk of anencephaly for women with history of hot tub use during early pregnancy
1.7
What maternal conditions are associated with increased risk of NTDs?
- Pregestational diabetes
- Maternal obesity
___ fold increased risk of NTDs for obese women
- __-fold increased risk for severely obese women (defined as a BMI greater than or equal to 38 or more than 243 pounds)
- 7
3. 1
List specific genetic conditions that are associated with NTDs?
- Trisomy 13, trisomy 18, and triploidy are associated with NTDs.
- Some genetic syndromes associated with single gene disorders or chromosomal microdeletions, such as 22q11.2 deletion syndrome and Waardenburg syndrome
List the general gene classes that are implicated in NTDs
genes related to
- folate metabolism;
- planar cell polarity genes, which are involved in cell movement during neural tube closure;
- and genes involved in the development of cilia that are essential for cell signaling
What does methylenetetrahydrofolate reductase (MTHFR) gene encode for?
cytoplasmic enzyme involved in the conversion of homocysteine to methionine
- routine screening for MTHFR status is not recommended.
what is C677T?
Polymorphism in C677T have been associated with a higher frequency of NTDs in some populations
The risk of having a fetus with an NTD when there is an affected sibling, a second-degree relative, or a third-degree relative is ___%, __%, and __%, respectively. With two affected siblings, the risk is ___%
The risk of having a fetus with an NTD when there is an affected sibling, a second-degree relative, or a third-degree relative is 3.2%, 0.5%, and 0.17%, respectively. With two affected siblings, the risk is 10%
Polyhydramnios can occur as a result of impaired fetal swallowing especially with ___ and __ -level spinal lesions and those lesions associated with aneuploidy,
Polyhydramnios can occur as a result of impaired fetal swallowing especially with anencephaly and higher-level spinal lesions and those lesions associated with aneuploidy
Breech presentation is common at term with ___ and ___.
Breech presentation is common at term with anencephaly and spina bifida.
What do you worry about in NTD baby with polyhydramnios?
uterine overdistention and increased risk of preterm contractions, umbilical cord prolapse, and placental abruption
List some prognostic factors for infants with NTDs
Size and location of the lesion and the presence of hydrocephalus
Intelligence in NTDs is correlated with ___ and the presence of ___
Intelligence is correlated with the level of the spinal disruption and the presence of hydrocephalus
patients with motor level dysfunction at the ___ level or below have better physical function than those patients with higher-level lesions.
Additionally, although scoliosis occurs in about __% cases with spina bifida, it is not associated with decreased physical capability
patients with motor level dysfunction at the L4 level or below have better physical function than those patients with higher-level lesions. Additionally, although scoliosis occurs in about one half of cases with spina bifida, it is not associated with decreased physical capability
Clinical consequence of NTDs
- Intelligence, cognitive deficits
- Ambulation, motor function
- Impaired function of the bowel and bladder
- At least one third of individuals with an NTD have a severe allergy to latex and can have life-threatening reactions after exposure
At least ___% of individuals with an NTD have a severe allergy to latex and can have life-threatening reactions after exposure
1/3
At least ___% of NTDs are not prevented by folic acid supplementation
30%
Folic acid is involved in ___ metabolism, which includes synthesis of ___ and ___ for DNA replication and methyl group transfer to macromolecules. Many folate-dependent reactions are important for cell growth and proliferation, crucial processes during neural tube formation
Folic acid is involved in one-carbon metabolism, which includes synthesis of purines and pyrimidines for DNA replication and methyl group transfer to macromolecules. Many folate-dependent reactions are important for cell growth and proliferation, crucial processes during neural tube formation
Supplementation ___ of folic acid supplementation daily for low risk women should begin at least ___ before pregnancy and continue through the first ___ weeks of pregnancy.
Women at high risk of NTDs should take ___ of folic acid daily. The daily supplement should be initiated ___ before pregnancy and continued until ___ of gestational age. Following the recommended supplementation in this high-risk group may reduce risk by as much as ___%
400 micrograms
1 month
first 12 weeks
4 mg (4,000 micrograms)
3 months
first 12 weeks
70%
It has been estimated that between ____% of NTDs could be prevented by folic acid supplementation
16% and 58%
List the criteria to say that women is at high risk for NTDs
- With histories of previous pregnancies affected with NTDs,
- women who are affected with an NTD themselves
- a partner who is affected
- a partner with a previous affected child.
Antiepileptic medication use during pregnancy, particularly valproate, also has been associated with folate-resistant NTDs. For these patients, the benefit of high-dose folic acid therapy has not been definitively proved, and recent guidelines for women on antiepileptic medications do not recommend higher doses of prepregnancy folate supplementation
!!
Can you over dose on folic acid?
The risks of higher levels of folic acid supplementation are believed to be minimal. Folic acid is considered nontoxic even at very high doses because it is water soluble and rapidly excreted in the urine.
- Could mask the symptoms of pernicious anemia and delay treatment
What’s the maximum dose for vitamin A?
5,000 international units per day
Alpha-fetoprotein is a glycoprotein that is secreted by the ___ and ___ , and fetal serum concentrations are ___ times those of amniotic fluid
Alpha-fetoprotein is a glycoprotein that is secreted by the fetal yolk sac and liver, and fetal serum concentrations are 150–200 times those of amniotic fluid
When should you be checking for Maternal serum alpha-fetoprotein (MSAFP) ?
What’s abnormal MSAFP?
The detection rate is expected to be greater than ___% for anencephaly and between __% and __% for open NTDs.
False positive rate of MSAFP?
What can make false positive MSAFP?
- between 15 weeks and 18 weeks of gestation
- MSAFP is elevated to 2.5 multiples of the median or greater
- The detection rate is expected to be greater than 95% for anencephaly and between 65% and 80% for open NTDs
- false positive rates of 1–3%
- inaccurate gestational dating and association with other conditions, such as multiple gestation, fetal abdominal wall defects, fetal nephrosis, fetal demise, and placental conditions that increase risk of adverse events later in pregnancy
- MSAFP is not usually increased with closed NTDs,
Is the presence of typical findings on two-dimensional ultrasonography is considered diagnostic of an NTD?
Is 3D US better than 2D?
What are Amniocentesis with measurement of acetylcholinesterase for?
yes
no
- differentiate open NTDs from closed NTDs in cases that are not straightforward
When is the optimal time for second trimester US?
18–22 weeks
What’s the US findings for anencephaly, spina bifida? What are some associated findings for open spinal bifida?
Anencephaly: the absence of a fetal cranium and significant facial dysmorphology.
Spina bifida:
- primary findings: abnormal posterior vertebral arches and a protuberant myelomeningocele sac for open and closed NTDs, although these may not be as evident with closed spinal abnormalities.
- Associated findings of open spina bifida are seen at 18–22 weeks of gestation in more than 95% of cases, including an abnormal skull shape (the “lemon sign”), an abnormal cerebellum and posterior fossa (the “banana sign”), and ventriculomegaly
Once an NTD is suspected or detected, now what?
MFM consult in collaboration with neonatology, pediatric neurosurgery, and genetics
- to discuss the nature of the lesion and the range of expected outcomes
- to define the location and size of the lesion, to ascertain whether secondary findings such as hydrocephalus are present, and to determine whether the fetus has other structural abnormalities.
- genetic evaluation by amniocentesis for chromosomal microarra. Measurement of amniotic fluid acetylcholinesterase. Fetal MRI. serial ultrasound examination may be considered for monitoring fetal growth, head size, and progression of hydrocephalus, if present.
pregnancy termination, expectant management with neonatal surgical repair, and in utero fetal repair for appropriate candidates.
What is the optimal timing and mode of delivery of a fetus with a neural tube defect? A special consideration in the delivery and care of infants with an NTD?
- Delivery at term unless there is a maternal or obstetric complication that requires early delivery.
- A late-preterm to early-term delivery is indicated if in utero fetal surgery has been performed because of the high risk of uterine rupture, similar to patients with a previous classical cesarean delivery.
- Rapidly increasing ventriculomegaly also may prompt delivery before term so that a ventriculoperitoneal shunt can be placed.
- Planned CS for breech.
- The best delivery route for the fetus with a normal head size in cephalic presentation remains controversial. Vaginal delivery does not adversely affect neonatal outcome with meningomyelocele.
- the use of latex-free gloves because individuals with an NTD are at risk of developing a severe, potentially life-threatening allergy to latex
What’s the “two-hit hypothesis. for neurologic damage in myelomeningocele? Why fetal surgery?
The “first hit” is the primary developmental abnormality that causes the open spina bifida; the “second hit” is a combination of the inflammation to the spinal cord from exposure to amniotic fluid and direct trauma to the exposed cord
The rationale for fetal surgery is that damage to the exposed spinal cord is progressive with advancing gestation. Therefore, early repair of the lesion, in utero, can reduce damage from the second hit and, thus, improve clinical outcomes.
When is fetal surgery for NTDs performed?
19 0/7 weeks and 25 6/7 weeks.
What’s the benefit of fetal surgery for NTDs?
Children who had prenatal surgery were more likely to have a level of function that was two or more levels better than expected and were more likely to be able to walk without devices or orthotics. There were no differences between the groups with regard to cognitive test scores
Risks for fetal surgery for NTDs
- General anesthesia risk for the fetal repair
- Risk of CS
- Risks of uterine rupture, all future pregnancies require cesarean delivery before labor.
