Genetic Testing Risk Factors Reviewed

Diagnosis of Birth Defects

Birth defects can occur in 3 to 5 % of all pregnancies and it is generally recommended that all pregnant women be offered some type of screening during their pregnancy. This early diagnosis is critical as it allows the physicians and the parents enough time to assess the severity of the condition and discuss possible alternatives of managing the pregnancy. In some cases treatment can be applied during pregnancy or immediately following the delivery. In other cases the defect is so severe that pregnancy termination may be an option.

Specific tests are now available to diagnose most birth defects early in pregnancy and to determine which test is best suited for an individual woman, a physician has to assess her specific risk. It is also important to recognize, however,  that most birth defects occur in woman who have no known risk factors. Although women over the age of 35 carry a higher risk of birth defects, the majority of children with birth defects are born to women under 35 due to the fact that this age groups bears more children. This younger group has not received proper attention in the past but with the advent of non-invasive testing, these women can now be screened quite safely.

Risk Factors for birth defects:

• Mother’s age: Women over the age of 35 are at higher risk for both structural defects (i.e. heart defects) and chromosomal defects (i.e. Down’s Syndrome) birth defects. Younger women under the age of 20 have a higher risk of structural defects but not chromosomal defects.
• Father’s age: Children of older fathers have a higher incidence of birth defects as well. In these instances the abnormalities are more subtle (autism, attention deficit disorder) and often difficult to diagnose before birth.
• A history of a child with birth defects or a chromosomal problem.
• A family history of birth defects or chromosomal problems.

Couples who fall into the high-risk group should be scrutinized more closely.

Diagnostic Tests

1. Non-invasive tests (ultrasound and blood work) now allow for early detection of pregnancies at risk for birth defects and chromosomal abnormalities. However, more invasive testing such as amniocentesis and chorion villous sampling are used to reach a conclusive diagnosis. The non-invasive tests are therefore used to assess the woman’s risk and determine if the more invasive testing is needed. This relative risk is then used to determine whether amniocentesis is indicated. In this way, invasive procedures can be avoided in many circumstances. It also allows for safe screening for women who are not considered to be at risk based on their age and history.
2. Invasive testing: Amniocentesis and chorion sampling. Both allow for accurate and reliable diagnosis of chromosomal defects but are also associated with a small but distinct risk of harming an otherwise normal pregnancy.

Non-Invasive Testing:

1. Sequential Screening: This is a two part-screening test that is used to detect the following conditions.
   • Downs syndrome,
   • Trisomy 18,
   • Neural tube defects,
   • Abdominal wall defects, and other rare abnormalities.
   • The principle of this form of testing is to use several variables and measurements to assess the risk. The mother’s age, biochemical markers (blood tests), and ultrasound are used to determine the relative risk of birth defects. This approach increases the accuracy of detection.

   The sequential screen has 2 parts:

   1. Between the 11^th and 14^th week of pregnancy an ultrasound examination of the thickness of the fold on the baby’s neck, called Nuchal Translucency. The ultrasound exam and a blood test checking levels of two hormones markers, free B-HCG and pregnancy associated plasma protein (PAPP-A) are combined to improve the diagnostic accuracy. The combination of the tests allows Down’s Syndrome to be diagnosed over 80% of the time.
   2. Between 15 and 22 weeks measurements of the mother’s blood for another marker, AFP (alpha feto-protein) can increase the rate of detection of chromosomal abnormalities to over 90% and the neural tube defects to about 80%.
2. Second Trimester Ultrasound: In the second trimester the baby’s systems have developed sufficiently for a careful ultrasound examination to allow detection of structural defects. Some of the structural defects are isolated (neural tube defects such as spina-bifida and anencephaly), and some are associated with chromosomal abnormalities—i.e. children with Down’s syndrome have a higher incidence of developmental heart and bowel disorders.

The optimal time for testing is between the 16^th and the 20^th week of pregnancy. An abnormal ultrasound then prompts more invasive testing to determine whether a chromosomal disorder is present as well.

Invasive Testing: Amniocentesis and Chorion Villous Sampling

1. Amniocentesis
   Amniocentesis involves aspiration of a small amount of the fluid, which surrounds the baby. The fluid contains fetal cells, which can be analyzed for chromosomal, and biochemical defects. A needle is guided by ultrasound through the abdominal wall and into the fetal sac. A small amount of fluid is then aspirated.

   The test carries a low risk of pregnancy loss (1:300). Additional risks include fetal injury, infection, fetal bleeding, premature rupture of the membranes, and premature birth. The risk of these complications is also low.

   Amniocentesis is generally performed between the 14^th and 16^th week of pregnancy. Early amniocentesis (between 11 and 13 weeks) can be performed but carries a considerably higher risk of complications. It is therefore only done in special cases.

2. Chorionic Villous Sampling (CVS)
   This procedure involves removing a small tissue sample from the developing placenta. It is performed between the 10^th and 12^th week. The sample is obtained using a needle and can be performed either through the abdomen (similar to amniocentesis) or vaginally through the cervix.

   Once obtained the tissue can then be analyzed for chromosomal defects.

   The advantage is CVS is that it can be done earlier than an amniocentesis. An early diagnosis allows for earlier and safer termination of pregnancy, if desired.

   The risk of CVS is similar to that of mid-trimester amniocentesis.

   However, alpha-fetoprotein assay still has to be performed at the usual time since, unlike amniocentesis—the protein cannot be measured at this time.

Summary:

Advancements in diagnostic testing lead to more accurate diagnosis of birth defects.

The improvement in the non-invasive tests allows:

1. Testing of younger women considered to have an overall low risk of birth defects, and
2. In older women who want to avoid the need for invasive testing and in those whose risk for birth defects appears to be low.

A team approach to the diagnosis and treatment of birth defect is essential. A genetic counselor, a perinatologist, a neonatologist and a psychological counselor can help the pregnant woman and her partner make informed decisions regarding the management of the pregnancy. The implications of the defect need to be reviewed with the couple along with the potential for treatment before and after birth.

In cases of severe defects the possibility of pregnancy termination should be discussed.

The emotional impact of these decisions for the parents cannot be overemphasized. Short term and long term follow up is essential.

This entry was posted on Monday, December 28th, 2009 at 10:42 pm and is filed under Infant Safety. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.