Prenatal Screening

First Trimester Prenatal Screening Tests

Genetic testing for Cystic Fibrosis

Cystic Fibrosis (CF) is one of the most common life-threatening autosomal recessive conditions.  American College of Obstetrics and Gynocology (ACOG) recommends to offer CF testing to all patients.  This test screens for  the most common mutations, but not all.  A patient only needs to have this test performed once as this gene does not change.

First trimester screening for Downs Syndrome and Trisomy 18 may be obtained in two ways.

1. Nuchal translucency testing (AKA First Look, First trimester Screen, NT) is a combination of fetal ultrasound and maternal blood testing performed during the first trimester of pregnancy. This screening process can help to determine the risk of the fetus having certain birth defects. Screening tests may be used alone or in combination with other tests.  There are two parts of this screening:

• ultrasound test for fetal nuchal translucency (NT)- Nuchal translucency screening uses an ultrasound test to examine the area at the back of the fetal neck for increased fluid.
• two maternal serum (blood) tests- The blood tests measure two substances found in the blood of all pregnant women:
  • pregnancy-associated plasma protein screening (PAPP-A)– a protein produced by the placenta in early pregnancy. Abnormal levels are associated with an increased risk for chromosome abnormality.
  • human chorionic gonadotropin (hCG) – a hormone produced by the placenta in early pregnancy. Abnormal levels are associated with an increased risk for chromosome abnormality.

When used together as first trimester screening tests, nuchal translucency screening and maternal blood tests have a greater ability to determine if the fetus might have a birth defect, such as Down’s Syndrome, trisomy 18 or trisomy 13.

2.    Non-Invasive Cell-Free DNA-  A sample of maternal blood is collected via venipuncture to obtain a random analysis of circulating cell-free DNA to determine the risk of aneuploidies such as Trisomy 21 (Down’s Syndrome), Trisomy 18 (Edward’s Syndrome) and Trisomy 13 (Patau’s syndrome).  Genetic disorders involving the sex chromosomes can also be determined.  This test can be performed as early as 10 weeks gestation but does not include an ultrasound.

There is certain criteria that must be met in order for this test to be performed.  If these criteria are not met the accuracy of the results actually decreases.  See  our Health on Heels blog entry titled What price will you pay to determine your baby’s gender at 10 weeks gestation?  for more information regarding the accuracy of this test if such criteria are not met:

1. Advanced Maternal Age (AMA)-  maternal age at least 35 years old at time of birth, and/or
2. A personal history of previous pregnancy with Trisomy 21, 18, or 13, and/or
3. An abnormal prenatal screen (first or second trimester)

If the results of these first trimester screening tests are abnormal, genetic counseling is recommended. Additional testing such as chorionic villus sampling or amniocentesis may be needed for accurate diagnosis.

Second Trimester Prenatal Screening Tests

Second trimester prenatal screening may include several blood tests, called multiple markers. These markers provide information about a woman’s risk of having a baby with certain genetic conditions or birth defects. Screening is usually performed by taking a sample of the mother’s blood between the 15th and 20th weeks of pregnancy (16th to 18th is ideal). The multiple markers include:

• alpha-fetoprotein screening (AFP) – a blood test that measures the level of alpha-fetoprotein in the mothers’ blood during pregnancy. AFP is a protein normally produced by the fetal liver and is present in the fluid surrounding the fetus (amniotic fluid), and crosses the placenta into the mother’s blood. The AFP blood test is also called MSAFP (maternal serum AFP).
• Abnormal levels of AFP may signal the following:
  • open neural tube defects (ONTD) such as spina bifida
  • Down syndrome
  • other chromosomal abnormalities
  • defects in the abdominal wall of the fetus
  • twins – more than one fetus is making the protein
  • a miscalculated due date, as the levels vary throughout pregnancy
• hCG – human chorionic gonadotropin hormone (a hormone produced by the placenta)
• estriol – a hormone produced by the placenta
• inhibin – a hormone produced by the placenta

Abnormal test results of AFP and other markers may indicate the need for additional testing. Usually an ultrasound is performed to confirm the dates of the pregnancy and to look at the fetal spine and other body parts for defects. An amniocentesis may be performed to assess for elevated amniotic fluid levels of AFP and other chemicals which may indicate the presence of spina bifida.   Multiple marker screening is not diagnostic. It is only a screening test to determine who in the population should be offered additional testing for their pregnancy. Rarely, there can be “false positive” results, indicating a problem when the fetus is actually healthy. Even more rare, there can also be “false negative” results, indicating a no abnormality when the fetus actually does have a health problem.   When a woman has both first and second trimester screening tests performed, the ability of the tests to detect an abnormality is greater than using just one screening independently. Over 80 percent of fetuses affected with Down Syndrome can be detected when both first and second trimester screening are used.

What is an amniocentesis?

An amniocentesis is a procedure used to obtain a small sample of the amniotic fluid that surrounds the fetus to diagnose chromosomal disorders and open neural tube defects (ONTDs) such as spina bifida. There is a small risk of miscarriage associated with amniocentesis which must be balanced with the risk of an abnormality and the patient’s desires. Testing is available for other genetic defects and disorders depending on the family history and availability of laboratory testing at the time of the procedure. An amniocentesis is generally offered to women between the 15th and 20th weeks of pregnancy who are at increased risk for chromosome abnormalities, such as women who are over age 35 years of age at delivery, or those who have had an abnormal maternal serum screening test, indicating an increased risk for a chromosomal abnormality or neural tube defect.

How is an amniocentesis performed?

An amniocentesis is a procedure that involves inserting a thin needle through the mother’s abdomen into the amniotic sac to withdraw a small sample of the amniotic fluid for examination. The amniotic fluid contains cells shed by the fetus, which contain genetic information. Although specific details of each procedure vary slightly, generally, an amniocentesis follows this process:

• The woman’s abdomen is cleansed with an antiseptic.
• The physician may/may not give a local anesthetic to numb the skin.
• Ultrasound is used to help guide a hollow needle into the amniotic sac.
• A small sample of fluid is withdrawn for laboratory analysis.
• Strenuous activities should be avoided for 24 hours following an amniocentesis.
• Women may feel some cramping during or after the amniocentesis.

Women with twins or other multiples need sampling from each amniotic sac, in order to study each baby. Depending on the position of the baby, placenta, amount of fluid, or patient’s anatomy, sometimes the amniocentesis cannot be performed. The fluid is sent to a genetics laboratory so that the cells can grow and be analyzed. Alpha-fetoprotein, a protein made by the fetus that is present in the fluid, is also measured to rule out an open neural tube defect, such as spina bifida. Results are usually available in about 10 days to two weeks, depending on the laboratory.

Chorionic villus sampling (CVS) is a prenatal test that involves taking a sample of some of the placental tissue. This tissue contains the same genetic material as the fetus and can be tested for chromosomal abnormalities and some other genetic problems. Testing is available for other genetic defects and disorders depending on the family history and availability of laboratory testing at the time of the procedure. In comparison to amniocentesis (another type of prenatal test), CVS does not provide information on neural tube defects such as spina bifida. For this reason, women who undergo CVS also need a follow-up blood test between 16 to 18 weeks of their pregnancy, to screen for neural tube defects.

• CVS may be offered to women who are at increased risk for chromosomal abnormalities or have a family history of a genetic defect that is testable from the placental tissue. CVS is usually performed between the 10th and 12th weeks of pregnancy. Although exact methods can vary, the procedure involves inserting a small tube called a catheter through a woman’s vagina and into her cervix and usually follows this process. Another method is transabdominal CVS, which involves inserting a needle through the woman’s abdomen and into her uterus to sample the placental cells.
• Ultrasound is used to guide the catheter (for transvaginal CVS) or needle (for transabdominal CVS) into place near the placenta.
• Tissue is removed using a syringe on the other end of the catheter.
• Women may feel some cramping during and after the CVS procedure.
• The tissue samples are sent to a genetic laboratory to grow and be analyzed. Results are usually available in about 10 days to two weeks, depending on the laboratory.

Women with twins or other multiples usually need sampling from each placenta. However, because of the complexity of the procedure, and positioning of the placentas, CVS is not always feasible or successful with multiples. Some women may not be candidates for CVS or may not obtain results that are 100 percent accurate, and may therefore require a follow-up amniocentesis. In some cases there is an active vaginal infection such as herpes or gonorrhea, which will prohibit the procedure. Other times the physician obtains a sample that does not have enough tissue to grow in the laboratory, such that results are incomplete or inconclusive.