Common Prenatal Genetic Testing

What is prenatal genetic testing?
Who should have prenatal testing?
What is maternal serum screening?
What is ultrasound?
What is chorionic villus sampling (CVS)?
What is amniocentesis?

Back to Top

What is prenatal genetic testing?
Prenatal genetic testing generally refers to tests that are done during pregnancy to either screen for or diagnose a birth defect. The main goal of prenatal genetic testing is to provide families with information to make informed choices about pregnancy and reproduction, and to assist the woman's physician in providing the best care and management for her pregnancy.¹

Some prenatal genetic tests are screening tests. Screening tests cannot diagnose a birth defect, but only determine if the fetus has a high or low risk for a particular problem. One example is maternal serum screening.¹ LabCorp offers a maternal serum screening test called AFP X-tra that identifies pregnancies at increased risk for open neural tube defects, Down syndrome, and trisomy 18. The blood test is a screening test and does not provide a final diagnosis.

Other prenatal tests are diagnostic and can diagnose certain fetal problems with a high degree of accuracy.^2-4  Amniocentesis is an example of a prenatal diagnostic test performed on amniotic fluid (fluid surrounding the developing baby during pregnancy). As the fetus grows and sheds cells, those cells can be found in the amniotic fluid and can be used to study the chromosomes. This test identifies fetal chromosome abnormalities. If, for example, an extra chromosome 21 is seen, a diagnosis of Down syndrome is made.

References

1. Jorde LB, Carey JC, Bamshad MJ, White RL. Medical Genetics. 2nd ed. St. Louis, Mo: Mosby Inc; 1999.
2. American College of Obstetricians and Gynecologists. Maternal Serum Screening. Educational Bulletin. 1996; September (228):3,5-8.
3. March of Dimes Birth Defects Foundation. Amniocentesis. White Plains, NY: March of Dimes Birth Defects Foundation; 1994.
4. Centers for Disease Control and Prevention. Chorionic Villus Sampling and Amniocentesis: Recommendations for Prenatal Counseling. MMWR. 1995; 44(no. RR-9):1-11.

Back to Top

Who should have prenatal testing?
Certain types of prenatal screening are available to all pregnant women. Generally, all pregnant women are offered maternal serum screening, such as AFP Tetra, a test that can identify pregnancies at risk for open neural tube defects , Down syndrome, and trisomy 18.

The American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics (ACMG) recommend that carrier screening be offered to all couples when at least one member of the couple is Caucasian and pregnant or considering pregnancy.¹

In general, genetic testing is offered to couples or individuals identified as being at risk for a particular genetic problem. Some of the risk factors that health care providers consider in deciding who should be offered testing include family history, medical history, and ethnicity. Examples include, but are not limited to^2-4

• Women 35 or older who are pregnant or are planning to become pregnant
• Abnormal ultrasound findings
• Couples who are close blood relatives, such as first cousins
• Women who have a condition, such as diabetes, that can be associated with an increased risk of fetal problems
• Ethnicity
• Unexplained or multiple miscarriages
• Family history of an inherited condition, mental retardation or birth defects
• Positive maternal serum screening, such as AFP Tetra

References

1. American College of Obstetricians and Gynecologists, American College of Medical Genetics. Preconception and Prenatal Carrier Screening for Cystic Fibrosis: Clinical and Laboratory Guidelines. Washington, DC: ACOG; Oct 2001
2. Ledbetter DH. Prenatal Cytogenetics: Indications, Accuracy, and Future Directions. Essentials of Prenatal Diagnosis. In: Simpson JL, Elias S, eds. Essentials of Prenatal Diagnosis. New York, NY: Churchill Livingstone; 1993;9:165-166.
3. March of Dimes Birth Defects Foundation. Genetic Counseling.
4. Baker DL, Schuette JL, Uhlmann WR, eds. A Guide to Genetic Counseling. New York, NY: John Wiley & Sons, Inc.

Back to Top

What is maternal serum screening?
Maternal serum screening refers to testing performed on a pregnant woman's blood for the purpose of determining if her developing fetus may have an increased risk of having an open neural tube defect (ONTD), Down syndrome, or trisomy 18. Proteins that are produced by the developing placenta and baby enter the mother's blood. The most commonly tested proteins are AFP (alpha-fetoprotein), hCG (human chorionic gonadotropin), uE3 (unconjugated estriol), and DIA (dimeric inhibin A). By measuring the levels of these proteins in the blood, tests determine if a woman has a high or low risk of having a baby with Down syndrome, trisomy 18, or an open neural tube defect. These tests determine the risk a developing baby may have one of these conditions; however, the maternal serum screening tests are not diagnostic. If a maternal serum screening test is positive, meaning an increased chance for a fetal problem, the woman's health care provider may suggest additional diagnostic testing.

There are three types of maternal serum screening tests. The detection rates for these tests are listed in the table below.

Back to Top

What does it mean if my maternal serum screening test is negative?
A negative test result significantly reduces the risk the baby may have one of the fetal problems screened for by the maternal serum test. (See table above for the available tests and what they screen). Because this test is only a screen it cannot completely rule out the possibility of these problems.

Does a positive maternal serum screening test result mean that my baby has a birth defect?
No. Maternal serum screening is a screening test; it cannot diagnose problems with the baby or pregnancy. The test identifies those women who are more likely to have a baby with an open neural tube defect, Down syndrome, or trisomy 18. Normally, if a test result is positive additional testing may be offered.

What other tests are available if my maternal serum screening test is positive?
Follow-up options are determined privately between a woman and her physician. In general, most women with positive test results are offered genetic counseling, ultrasound, and amniocentesis.

References

1. American College of Obstetricians and Gynecologists. Maternal Serum Screening. Educational Bulletin. 1996; September (228):3,5-8.
2. Haddow JE, Palomaki GE, Knight GJ, Foster DL, Neveux LM. Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A. J Med Screen. 1998; 5(3):115-119.

Back to Top

What is ultrasound?
Ultrasound examination (See figure 1 below.) is a noninvasive procedure that uses pulsed sound waves to create a picture of the developing fetus. The sound waves are reflected off of the fetus in patterns that can depict soft tissues, such as skin and muscle, and hard tissues like bone. The reflected sound waves are displayed on a monitor, creating an image of the fetus. Ultrasound is the most commonly used method to view the fetus. In the second trimester of pregnancy, ultrasound detects 30% to 50% of all major birth defects, such as developmental problems in the limbs, spine and abdomen. Detection rates vary for individual conditions. Ultrasound may detect fetal problems associated with a chromosome abnormality, but the ultrasound does not view the fetal chromosomes or genes.

figure 1

Ultrasound examination

Reference

Jorde LB, Carey JC, Bamshad MJ, White RL. Medical Genetics. 2nd ed. St. Louis, Mo: Mosby Inc; 1999.

Back to Top

What is chorionic villus sampling (CVS)?
Chorionic villus sampling (CVS) is a diagnostic procedure performed during pregnancy to diagnose chromosome abnormalities, some inherited disorders, and certain birth defects in an unborn baby (fetus).^1-3 CVS is most commonly offered when a woman is at an advanced maternal age (35 years and older at time of delivery) because of the increased chance of a fetal chromosome problem.^1,2,4

CVS may also be offered if an inherited genetic (gene) problem that can be diagnosed prenatally is identified in the family.^{1, 3,4} Performed between 10 and 12 weeks of pregnancy (first trimester), CVS can be done in a doctor's office, hospital, or out-patient clinic.^1-4 Ultrasound is used to guide the procedure. Depending on the location of the placenta, CVS will be performed in one of two ways. A thin needle is either inserted through the abdomen or a specially designed catheter is passed through the vagina and a piece of placenta, approximately the size of a few grains of rice, is removed. The placenta contains cells generated by the baby. Approximately 99% of fetal chromosome abnormalities can be diagnosed.^1-3 Unlike amniocentesis, CVS is not able to provide information about open neural tube defects.¹ The risk of miscarriage or serious complication from the test is approximately 1/200 to 1/100 (0.5% - 1.0%)^1,2,4 Controversy exists about the risk of fetal limb defects as a result of the test, though most physicians and researchers feel that if the test is done at 10 weeks of gestation or later, there is little risk of fetal limb defects. Additionally, in approximately 1.0% to 2.0% of CVS cases, follow-up by amniocentesis is needed to clarify results.^2,3

* A rapid way to determine some chromosome problems is called FISH.

References

1. March of Dimes Birth Defects Foundation. Chorionic Villus Sampling (CVS). White Plains, NY: March of Dimes Birth Defects Foundation; 1994.
2. Nussbaum RL, MacInnes RR, Willard HF, Boerkel CF. Thompson and Thompson: Genetics in Medicine. 6th ed. Philadelphia, Pa: W.B. Saunders; 2001.
3. Kuller JA. Chorionic villus sampling. In Kuller JA, Chescheir NC, Cefalo RC, eds. Prenatal Diagnosis and Reproductive Genetics. St Louis, Mo: Mosby; 1996.
4. Centers for Disease Control and Prevention. Chorionic villus sampling and amniocentesis: Recommendations for prenatal counseling. MMWR. 1995; 44(Nº RR-9):1-11.

Back to Top

What is amniocentesis?
Amniocentesis is an important test in prenatal diagnosis.^1-3 This test is primarily used to diagnose fetal chromosome problems.^2,3,4 Amniocentesis can also help diagnose open fetal defects, such as open spina bifida, or abdominal wall defects, and some inherited problems if identified in your family.^1-4

Amniocentesis is performed on amniotic fluid (the fluid that surrounds the fetus), usually between 16 and 18 weeks of pregnancy (second trimester).^1-3 As the fetus grows and sheds cells, those cells can be found floating in the amniotic fluid and used to study the chromosomes.^1-3 Amniocentesis detects about 99% of fetal chromosome abnormalities.¹ In addition to chromosome analysis, traditional amniocentesis also measures amniotic fluid AFP (alpha fetoprotein). If the amniotic fluid AFP level is elevated, the same fluid sample will then be analyzed for AChE (acetylcholinesterase). By analyzing both amniotic fluid AFP and AChE, more than 98% of open neural tube defects, such as spina bifida, can be detected.⁴

A thin needle is inserted through the mother's abdomen (under ultrasound guidance) into the amniotic sac, and a small amount of amniotic fluid is removed.¹ Most women do not find amniocentesis to be painful. They usually report feeling a pinch at the surface of the skin. A small number of women experience uncomfortable cramping during the test.¹ Traditional amniocentesis increases the risk of miscarriage by approximately 0.5% (1/200).^1,2,4

References

1. March of Dimes Birth Defects Foundation. Amniocentesis. White Plains, NY: March of Dimes Birth Defects Foundation; 1994.
2. Centers for Disease Control and Prevention. Chorionic Villus Sampling and Amniocentesis: Recommendations for Prenatal Counseling. MMWR. 1995; 44(no. RR-9):1-11.
3. Nussbaum RL, McInnes RR, Williard HF, Boerkoel CF. Thompson and Thompson: Genetics in Medicine. Philadelphia, Pa: W.B. Saunders; 2001.
4. Cabaniss ML. Amniocentesis. In Kuller JA, Chescheir NC, Cefalo RD, eds. Prenatal Diagnosis and Reproductive Genetics. St. Louis, Mo: Mosby; 1996:chap 18.