Handbook of Genetic Counseling/Neural Tube Defects

< Handbook of Genetic Counseling

Neural Tube Defects

(History of)

Introduction

Discuss the reason for referral
Elicit prior knowledge about neural tube defects/spina bifida
- Discuss severity of affected sibling & elicit feelings toward sibling's NTD
Assess concerns and set goals for the session.
Provide overview of topics for counseling session
- Pregnancy & family history
- Address risk for NTD for this pregnancy
- Introduce testing options for NTDs

Client & Partner Information

Discuss why it's important to get pregnancy, personal, and family history.
- Explain that it is a way to identify other potential risk factors
- Use examples: seizure medication, diabetes, >1 family member with NTD, etc.
Go over pregnancy history:
- How has the pregnancy been going?
- G1P0? Any stillbirths? Spontaneous or elective abortions?
- Was the pregnancy planned? If so, how long did it take to become pregnant?
- LMP? EDC?
- Any bleeding?
- Any illnesses during the pregnancy?
  - Infection, cold, rash, fever?
- Any chronic illnesses?
- Any exposures during the pregnancy?
  - X-rays, smoking, alcohol, recreational drugs?
- Medications:
  - Currently?
  - Earlier in the pregnancy?
Personal background:
- Occupation?
- Do you have a religious preference?
- Psychosocial assessment
  - Financial, insurance concerns?
  - Support system?
- Information about the father:
  - Name, age, occupation?
  - Any exposures?
  - Any chronic illnesses?

Elicit History

Construct pedigree:
- Abnormal # miscarriages, stillbirths, infant deaths?
- Previous children with chromosome abnormality, Down syndrome, birth defects, mental retardation?
- Obtain detailed information about sister's NTD
- Any other people in family affected with NTD?
- Consanguinity? Ethnicity? Other concerns/risk factors?

What are Neural Tube Defects?

NTDs are serious birth defects that involve incomplete development of the brain, spinal cord, and/or protective coverings for these organs
The cause of NTDs is not completely understood, but involves both environmental and genetic factors (multifactorial inheritance)
Sometimes NTDs can occur as part of a larger chromosomal or malformation syndrome (like Meckel syndrome where other malformations such as cleft lip, cleft palate, polydactyly, renal cystic disease and eye defects may be seen)
There are three types of NTDs:
- Anencephaly
  - Infants born with anencephaly have underdeveloped brains, incomplete skulls, and usually survive only a few hours after birth
- Encephalocele
  - Infants have a hole in the skull through which brain tissue protrudes; most affected infants do not survive or are severely mentally retarded.
- Spina bifida
  - This is the most common NTD affecting approximately 1/1000 newborns in the U.S.
  - It results from the failure of the spine to close properly during the first month of pregnancy. The precise cause of this defect is not completely understood.
  - There are three types of spina bifida. In order of increasing severity, they are:
    - Spina bifida occulta
      - Includes individuals with a spinal defect associated with a pigmented or hairy patch of skin as well as individuals with absence of one or two vertebral arches.
      - The first group shows an increased incidence of NTDs in offspring and siblings, but the second group (which is about 5% of the population) shows no evidence of any increased risk.
      - This form of spina bifida usually has no symptoms.
    - Meningocele
      - This is the rarest form of spina bifida in which a cyst or lump consisting of membranes surrounding the spinal cord pokes through the open part of the spine.
      - The cyst can be removed by surgery, allowing for normal development.
    - Myelomenigocele
      - This is the most severe form of spina bifida where the protruding cyst contains membranes surrounding the spinal canal, nerve roots of the spinal cord, and often the spinal cord itself.
      - Or there may be no cyst, but a fully exposed section of the spinal cord and nerves.
      - Surgery to close the back is generally performed within 24 hours after birth to reduce the risk for infection and to preserve the existing function in the spinal cord.
      - Individuals with more severe spina bifida usually have paralysis and need surgeries and other extensive medical care.
      - The severity of the paralysis is determined by the spinal nerves that are involved. In general, the higher the cyst on the back, the more severe the paralysis.
      - Often, children need to use crutches, braces, or wheelchairs due to mobility deficits.
      - The condition can also cause bowel and bladder complications.
  - Some children with spina bifida have learning problems. They may have difficulty paying attention, expressing or understanding language, organizing, and grasping reading and mathematical concepts.
  - Hydrocephalus can accompany severe spina bifida
    - This is an accumulation of fluid in the brain
    - Is it controlled by a surgical procedure called "shunting" where the fluid that builds up in the brain is redirected into the abdominal cavity
  - Children with spina bifida may be more prone to developing latex allergies
Recent studies show that folic acid, a water-soluble B vitamin, is one factor that may reduce the risk of having a baby with a NTD.
- A vitamin with 400 micrograms (mcg) of folic acid every day is recommended for most women. This is the same as 0.4 milligrams (mg).
- If a woman is at an increased risk of having a baby with a NTD, it is recommended that she take a higher dose of folic acid. This should be 4000 mcg of folic acid for 1-3 months before becoming pregnant. This is the same as 4.0 mg.
- Taking folic acid will not guarantee a healthy baby.
Birth defects such as NTDs can occur in any family.
Be aware that the patient may feel guilty if she did not take folic acid before her pregnancy.

Quote Risks

Spina bifida is usually an isolated birth defect.
- 95% of babies with NTDs are born to parents with no family history of the disorder.
- The incidence of a NTD in the population is 1/200 - 1/1000 (This is 0.1% - 0.5%).
When NTDs do appear to run in the family, it does not follow any particular pattern of inheritance.
Women with certain chronic health problems like diabetes and seizure disorders (treated with certain anticonvulsant medications have an increased risk of having a baby with a NTD. This risk is approximately 1/100 (MOD)
If one sibling is affected, the recurrence risk is approximately 2-5% based on the population incidence (Harper).
State the risk in both ways (2% risk of abnormality = 98% chance of healthy baby)

Discuss the Screening Options for NTDs

Maternal Serum Screening, level II ultrasound, & amniocentesis are three testing options that may tell you if your baby is at an increased risk for a NTD.

Maternal Serum Screening

What is it?
- A blood test that measures three different substances in the mother's blood
  - Alpha-fetoprotein (AFP)
  - Human chorionic gonadotropin (hCG)
  - Unconjugated estriol (uE3)
- It is routinely offered between 14 and 22 weeks of pregnancy
  - Most accurate when done between 16-18 weeks
- It is NOT a diagnostic test; it is a screening test
- It is a way to identify pregnancies at increased risk of certain abnormalities
  - It is NOT an absolute diagnosis of a problem
- Women who are shown to be at a higher risk are then offered diagnostic testing
  - Level II Ultrasound
  - Amniocentesis
What can it tell me?
- Triple screen suggests an increased risk for certain abnormalities in the fetus such as ONTDs.
  - It also can indicate if there's an increase risk for Down Syndrome or Trisomy 18
  - We have no reasons to suspect these may be an issue in the pregnancy, but the test will provide this information.
What can it NOT tell me?
- Triple screen cannot confirm that your baby has a NTD or other defect
- It also cannot predict an increased risk for all birth defects
  - Other trisomies, mental retardation, cleft lip, etc. are not included in screen.
What does the procedure involve?
- The screening test is done with a routine maternal blood draw.
How do the markers work?
- Alpha-fetoprotein (AFP):
  - This is the marker primarily used to detect ONTDs
  - It is a protein made by the fetal liver
  - AFP is excreted into the fetal urine and amniotic fluid from where it is transferred across the placenta into the maternal blood.
  - It is not known what AFP does
  - It is present in higher concentrations when there is an ONTD because more AFP leads out into the amniotic fluid
  - It is present in lower concentrations with Down syndrome for unknown reasons.
- Human chorionic gonadotropin (hCG):
  - This is the "pregnancy hormone" used in pregnancy tests
  - Is it produced by the placenta
  - The concentration is higher in Down syndrome for unknown reasons.
- Unconjugated estriol (uE3):
  - UE3 is the most sensitive marker for Trisomy 18 (lower with Trisomy 18)
  - It is a steroid produced by the fetus and placenta
  - May be lower in Down syndrome for unknown reasons.
- MoM (Multiple of the Median):
  - This is the ratio of the marker level in the client to the median marker level
  - It allows us to compare your marker levels to the general population of pregnant women
  - A computer program takes into account all of your specific circumstances and calculates your MoM
  - 1.0 MoM is the expected value
  - If 2.0 MoM, then your concentrations are twice as high as expected
  - No one has a perfect 1.0 MoM
What does a "Screen Positive" test result mean?
- The test results are analyzed for patterns
- There are specific patterns of the three marker levels associated with an ONTD, Down Syndrome, or Trisomy 18
  - ONTD = High AFP
  - Down Syndrome = Low AFP, High hCG, Low uE3
  - Trisomy 18 = Low AFP, Low hCG, Low uE3
- 5-10% of women who undergo Triple Screen get abnormal results
- Only 3-5% of them will have an affected baby
- For ONTDs:
  - Only the AFP marker is used
  - If the concentration is >2.5 MoM, the result is screen positive for ONTD
  - The incidence of ONTD is 1-2 in 1000 fetuses
- For Down syndrome:
  - If the risk figure is over 1 in 270, the result is screen positive for DS
  - HCG is the most sensitive marker for DS
  - The incidence of DS is 1 in 660 newborns
- For Trisomy 18:
  - If the risk figure is over 1 in 100, the result is screen positive for TRI 18
  - UE3 is the most sensitive marker for Trisomy 18
  - The incidence of Trisomy 18 is 3 in 1,000 newborns
Why might I have a "Screen Positive" result?
- The fetus has either an ONTD, DS, or Trisomy 18
- The fetus has a different chromosome abnormality or birth defect
- The variation in the level of the marker or markers is normal
- The gestational age is incorrect
  - Underestimated in ONTDs (She is farther than she thought)
  - Overestimated in DS (She is not as far along as she thought)
- There are multiple pregnancies (affects NTDs and DS results)
- Fetal demise (for NTD and Tri 18)
- Other causes of (+) for NTD:
  - Abdominal wall defect
  - Feto-maternal bleeding
  - Finnish nephrosis (kidney disease)
- Other causes of (+) for Trisomy 18:
  - X-linked icthyosis (scale-like skin due to steroid sulfatase deficiency)
What does a "Screen Negative" test result mean?
- The pregnancy does not appear to be at an increased risk for ONTD, DS, or TRI 18
- This does NOT guarantee that the child will not have a birth defect
How Accurate is this test?
- The detection rate is a measure of how sensitive the test is
  - This is the chance of getting a screen (+) when the fetus is actually affected
  - There is a 60% overall detection rate
  - This means that 60 out of 100 affected pregnancies will be found by this test
- The false (+) rate is the chance of getting a (+) when the pregnancy is unaffected
  - There is a 5% overall false (+) rate
  - 5 out of 100 unaffected pregnancies will screen (+)
  - Of 100 women with normal babies, 5 will screen (+)
- More specifically:
  - For ONTD:
    - Detection rate is 85%
    - False (+) rate is 1-3%
  - For DS:
    - Detection rate is 60-65%
    - False (+) rate is 5%
    - Higher detection rate and false (+) rate for women over age 35
  - For Trisomy 18:
    - Detection rate is 60-80%
    - False (+) rate is ~0.5%
How do I follow up on a "Screen Positive" result?
- For NTD:
  - Confirm gestational age with ultrasound
  - Offer genetic counseling, ultrasound, and amniocentesis (to measure AFP)
  - If AFP is <3.0 MoM and client is <22 weeks, may repeat triple screen
  - If AFP is >3.0 MoM or client is >22 weeks, offer level II ultrasound and/or amniocentesis
- For Down Syndrome or Trisomy 18:
  - Confirm gestational age with ultrasound
  - Offer genetic counseling, ultrasound, and amniocentesis
  - DO NOT repeat screen unless initial screen was done before 14 weeks
- Unexplained screen (+) results may be associated with an increased risk for 3rd trimester complications
  - These pregnancies should be monitored more closely

Level II Ultrasound

At 18-20 weeks, a high resolution, targeted ultrasound examination can be done to carefully and specifically examine the baby's spine.
This is noninvasive and may provide reassurance but cannot be used as a diagnostic tool.
- If no evidence of a NTD is seen, it cannot be guaranteed that the baby does not have a NTD.

Amniocentesis

If the triple screen results indicate an increased risk for a NTD, one may choose to have an amniocentesis, which is a more invasive, but more diagnostic test.
What is it?
- Procedure used to obtain a small sample of fluid from the fluid-filled sac that surrounds the fetus
- Performed at 15 weeks gestation or later
  - 15-18 weeks is optimal because it leaves the patient with options
  - 22 weeks is probably the latest it can be done leaving the option of elective abortion
- Amniotic fluid contains the fetus's urine as well as other cells from the skin, throat, and digestive tract
- Fluid is studied in the lab for abnormalities
What can it tell me?
- Amnio can detect certain abnormalities in the fetus.
  - Chromosome abnormalities
  - NTDs (Spina Bifida)
- It can determine the sex of the baby.
What can it NOT tell me?
- Amnio cannot detect all birth defects or mental retardation.
  - For example, congenital heart defects, cleft lip & palate cannot be seen.
  - Also the severity of the defect cannot be known from amnio.
Exactly what does the procedure involve?
- Show figure of amniocentesis.
- You will lie down on your back with hands behind your head.
- Your abdomen will be cleaned with alcohol or iodine.
- A local anesthetic may be applied to your stomach.
- Ultrasound will be used to locate the position of the baby and the placenta and to find a safe spot for the needle.
- A long, thin needle will be inserted through the skin, into the uterus.
- The first few cc's of fluid will be discarded because they probably contain contamination from your cells.
- Then a small amount (about 1-2 tablespoons) of fluid is removed and the needle is withdrawn.
- The procedure itself usually takes ~5 minutes.
- The baby will quickly replace the fluid that is removed.
- The baby's heartbeat will be monitored by ultrasound.
- Fluid will be sent to the lab and results are available in 1-2 weeks.
- There is a small possibility of lab error or lack of cell growth
  - In this case, the procedure would have to be done again.
What will it feel like?
- If an anesthetic is used, you may not feel the needle enter the skin, but you will still feel it enter the uterus.
- This is described as a sharp pain, like a menstrual cramp that usually lasts a few seconds.
- You may also feel some cramping after the procedure.
- You should avoid strenuous activity for 24 hours after the procedure.
- Call your doctor immediately if you experience abdominal pain or cramps, vaginal bleeding, leakage of clear fluid from the vagina, fever, or anything else unusual.
  - Approximately 2% of women experience light bleeding or spotting.
What are the risks?
- The risk of miscarriage is between 1/400 and 1/200.
- This means that the added risk for pregnancy loss attributable to the procedure is 0.5% or less.
- There is a risk of uterine infection but this is less than 1 in 1,000
- There is a remote chance that birth defects can be caused by the amnio (0.1%).
- There are special considerations for mothers who are Rh negative. They need to take RhoGam after the amnio procedure.

Offer Resources

Spina Bifida Association of America

www.sbaa.org

1-800-621-3141

March of Dimes information on Spina Bifida, Amniocentesis, Folic Acid, and Maternal blood screening

www.modimes.org

1-888-MODIMES

Reporting of the Results

If they are having a procedure, discuss how they would like to receive the results
- Appointment, phone call, etc.
- Who will contact them?
Discuss the options: elective abortion, adoption, etc.

References

Harper, Peter. Practical Genetic Counseling. Fourth Edition, p. 177-180.
Foundation for Blood Research. Spring 2000 Genetics Quarterly newsletter for providers.
www.modimes.org
www.sbaa.org

Notes

The information in this outline was last updated in 2002.

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