Prenatal genetic testing gives parents-to-be information about whether their baby has certain genetic disorders before birth. Many prenatal genetic tests are available. Prenatal screening tests can tell you the chances that your unborn baby will have a type of genetic disorder called aneuploidy and a few additional disorders. Prenatal diagnostic tests can tell you whether your baby actually has certain disorders. Both screening and diagnostic testing are offered to all pregnant women. This pamphlet focuses on prenatal screening tests and explains:

  • types of genetic disorders
  • prenatal testing options
  • types of genetic screening tests
  • screening test results and what they mean
  • what to consider when deciding whether to have prenatal genetic testing

Overview of Genetic Disorders

Genetic disorders are caused by changes in a person’s genes or chromosomes. Aneuploidy is a condition in which there are missing or extra chromosomes. Inherited disorders are caused by changes in gene called mutations. Inherited disorders include sickle cell disease, cystic fibrosis, Tay-Sachs disease, and many others. In most cases, both parents must carry the same gene to have an affected child.

Genes and Chromosomes

A gene is a small piece of hereditary material called DNA. Genes come in pairs and are located on chromosomes. Chromosomes also come in pairs. Most cells have 23 pairs of chromosomes for a total of 46 chromosomes. Sperm and egg cells each have 23 chromosomes. During fertilization, when the egg and sperm join, the two sets of chromosomes come together.

A baby’s sex depends on the sex chromosomes it gets. Egg cells contain only an X chromosome. Sperm cells can carry an X chromosome or a Y chromosome. A combination of XX results in a girl and XY results in a boy.

What Is Aneuploidy?

Aneuploidy is a condition in which there are missing or extra chromosomes. In a trisomy, there is an extra chromosome. In a monosomy, a chromosome is missing. Examples include the following:

  • Down syndrome – Most cases caused by an extra chromosome 21 (trisomy 21)
  • Trisomy 13 (Patau syndrome) – Caused by an extra chromosome 13
  • Trisomy 18 (Edwards syndrome) – Caused by an extra chromosome 18
  • Turner syndrome – Caused by a missing or altered X chromosome

Although any woman at any age can have a child with an aneuploidy, the risk increases as a woman ages.

Prenatal Testing Options

There are two general types of prenatal tests for genetic disorders: 1. screenings tests and 2. diagnostic tests. Screening tests can tell you your risk of having a baby with certain disorders. They include carrier screening and prenatal genetic screening tests:

  • Carrier screening is done on parents (or those just thinking about becoming parents) using a blood or tissue sample swabbed from inside the cheek. Also called “gene testing”, these tests are used to find out whether a person carries a gene for certain inherited disorders. Carrier screening can be done before or during pregnancy.
  • Prenatal genetic screening tests of the pregnant woman’s blood and findings from ultrasound exams can screen the unborn baby for aneuploidy; defects of the brain and spine called neural tube defects; and some defects of the abdomen, heart and facial features. This article focuses on these tests.

Prenatal diagnostic tests can tell you, with as much certainty as possible, whether the baby has an aneuploidy or a specific inherited disorder for which you request testing. These tests are done on cells from the unborn baby or placenta obtained through amniocentesis or chorionic villus sampling (CVS). The cells can be analyzed in different ways. Diagnostic tests carry a very small risk of pregnancy loss.

Types of Genetic Screening Tests

The screening tests offered to you depend on which tests are available in your area, how far along you are in your pregnancy, and your health care professional’s assessment of which tests best fit your needs. Any woman of any age, regardless of risk factors, can choose to have diagnostic testing instead of or in addition to screening tests.

Timing needs to be considered when having prenatal screening tests. With first-trimester testing, you have more options and more time to think about what an abnormal screening test result may mean for you and your family. With second-trimester testing, there is less time and fewer options.

Not all types of tests are covered by insurance companies. It is a good idea to check with your insurance company before you have any of these tests. If your company does not cover a test, you will have to pay for it yourself.

First-Trimester Screening

First-trimester screening includes a test of the pregnant woman’s blood and an ultrasound exam. Both tests usually are performed together and are done between 10 weeks and 13 weeks of pregnancy:

  • The blood test measures the level of two substances.
  • The ultrasound exam, called a nuchal translucency screening, measures the thickness of a space at the back of the developing baby’s neck. An abnormal nuchal translucency measurement means there is an increased risk that the baby has Down syndrome or other type of aneuploidy. It also is linked to physical defects of the heart, abdominal wall, and skeleton.

Second-Trimester Screening

Second-trimester screening includes the following tests:

  • The “quad” or “quadruple” blood test measures the levels of four different substances in your blood. The quad test screens for Down syndrome, trisomy 18, and neural tube defects. It is done between 15 weeks and 22 weeks of pregnancy. A blood test that measures three substances (“triple screen”) and five substances (“penta screen”) are available but are not as widely used.
  • An ultrasound exam done between 18 weeks and 20 weeks of pregnancy checks for major physical defects in the brain and spine, facial features, abdomen, heart and limbs.

Combined First- and Second-Trimester Screening

The results from first- and second-trimester tests can be combined in various ways. Combined test results are more accurate than a single test result. If you choose combined screening, keep in mind that final results often are not available until the second trimester.

First-, Second-, and Third-Trimester Screening: Cell-Free DNA Testing

Cell-free DNA is the small amount of DNA that is released from the placenta into a pregnant woman’s bloodstream. The cell-free DNA in a sample of a woman’s blood can be screened for Down syndrome, trisomy 13, trisomy 18, and problems with the number of sex chromosomes.This test can be done starting at 10 weeks of pregnancy. It takes about 1 week to get the results.

The cell-free DNA test works best for women who have an increased risk of having a baby with a chromosome disorder, such as a woman who already has a child with a chromosome disorder. For a woman at low risk of having a baby with a chromosome disorder, conventional screening remains the most appropriate choice. Cell-free DNA testing is not recommended for a woman carrying more than one baby.

The cell-free DNA test is a screening test. If a cell-free DNA test result suggests that there is an increased risk of aneuploidy, diagnostic testing with CVS or amniocentesis and an ultrasound exam for physical defects are recommended.

Screening Test Results

Results of blood screening tests for aneuploidy are reported as the level of risk that the disorder might be present:

  • A positive screening test result for aneuploidy means that your baby is at higher risk of having the disorder compared with the general population. It does not mean that your baby definitely has the disorder.
  • A negative result means that your baby is at lower risk of having the disorder compared with the general population. It does not rule out the possibility that your baby has the disorder.

Diagnostic testing with CVS or amniocentesis that gives a more definite result is an option for all pregnant women. Your obstetrician or other health care professional, such as a genetic counselor, will discuss what your screening test results mean and help you decide the next steps.

Accuracy of Prenatal Screening Tests

With any type of testing, there is a possibility of false-positive results and false-negative results. A screening test result that shows there is a problem when one does not exist is called a false-positive result. A screening test result that shows there is not a problem when one does exist is called a false-negative result. Your health care professional can give you information about the rates of false-positive and false-negative results for each test that is offered.

Deciding Whether to Have Prenatal Genetic Testing

Screening and diagnostic testing are voluntary. It is your choice whether to have prenatal testing. Your personal beliefs and values are important factors in the decision about prenatal testing.

It can be helpful to think about how you would use the results of prenatal screening tests in your pregnancy care. Remember that a positive screening test tells you only that you are at higher risk of having a baby with Down syndrome or another aneuploidy. A diagnostic test should be done if you want to know a more certain result. Some parents want to know beforehand that their baby will be born with a genetic disorder. This knowledge gives parents time to learn about the disorder and plan for the medical care that the child may need. Some parents may decide to end the pregnancy in certain situations.

Other parents do not want to know this information before the child is born. In this case, you may decide not to have follow-up diagnostic testing if a screening test result is positive. Or you may decide not to have any testing at all. There is no right or wrong answer. Your health care professional or a genetic counselor can discuss all of the testing options with you.

Finally….screening tests can assess your risk of having a baby with aneuploidy and a few additional disorders. Screening tests are part of an overall strategy of prenatal testing for genetic disorders. Talk to your obstetrician or other health care professional about which tests are right for you.

Table 1: Prenatal Screening Tests

Screening Test Description What Does It Screen For? When Is It Done During Pregnancy? Down Syndrome Detection Rate
First Trimester Screening
Blood Test Blood test for PAPP-A and hCG Down syndrome
Trisomy 13
Trisomy 18		 10-13 weeks When combined with the nuchal translucency ultrasound exam, 82-87%
Nuchal translucency (NT) test Measurement of a space at the back of the fetal neck during an ultrasound exam Down syndrome
Trisomy 13
Trisomy 18		 10-13 weeks 64-70%
Second Trimester Screening
Blood test Quad screen: Blood test for MSAFP, hCG , Estriol, and Inhibin-A Down syndrome
Trisomy 18
Neural tube defects		 15-22 weeks 81%
Ultrasound exam Ultrasound exam that checks the baby’s anatomy Major physical defects 18-20 weeks Varies with type of finding
Combined First and Second Trimester Screening
Integrated Screening Blood test for PAPP-A and an NT ultrasound exam in the first trimester, followed by quad screen in the second trimester Down syndrome
Trisomy 18
Neural tube defects		 10-13 weeks, then
15-22 weeks		 96%
Contingent sequential First-trimester combined screening result:
– High risk diagnostic test or ctDNA screening offered
– Low risk: no further testing
– Intermediate risk: second trimester screening test offered		 Down syndrome
Trisomy 18
Neural tube defects		 10-13 weeks, then
15-22 weeks		 88-94%
Stepwise sequential First-trimester combined screening result:
– Positive: cfDNA screening or diagnostic test offered
– Negative second-trimester screening test offered		 Down syndrome
Trisomy 18
Neural tube defects		 10-13 weeks, then
15-22 weeks		 95%
Screening After 10 weeks of Pregnancy
Cell-free DNA (cfDNA) test Blood test that analyzes DNA from the placenta circulating in the mother’s blood Down syndrome
Trisomy 18
Trisomy 13 (some labs); does not screen for neural tube defects		 10 weeks and later 99% in women at high risk

Abbreviations: cfDNA, cell-free DNA; hCG, human chorionic gonadotropin; MSAFP, maternal serum alpha fetoprotein, NT, nuchal translucency.; PAPP-A, pregnancy-associated plasma protein A.

Glossary

  • Amniocentesis: A procedure in which a needle is used to withdraw and test a small amount of amniotic fluid and cells from the sac surrounding the fetus.
  • Aneuploidy: Having an abnormal number of chromosomes.
  • Carrier: A person who shows no signs of a particular disorder but could pass the gene on to his or her children.
  • Cells: The smallest units of a structure in the body; the building blocks for all parts of the body.
  • Chorionic Villus sampling (CVS): A procedure in which a small sample of cells is taken from the placenta and tested.
  • Chromosomes: Structures that are located inside each cell in the body and contain the genes that determine a person’s physical makeup.
  • Cystic Fibrosis: An inherited disorder that causes problems in digestion and breathing.
  • Diagnostic Tests: Tests that look for a disease or cause of a disease.
  • DNA: The genetic material that is passed down from parents to offspring. DNA is packaged in structures called chromosomes.
  • Down Syndrome: A genetic disorder that causes abnormal features of the face and body, medical problems such as heart defects, and intellectual disability. Most cases of Down syndrome are caused by an extra chromosome 21 (trisomy 21). Many children with Down syndrome live to adulthood.
  • Genes: Segments of DNA that contain instructions for the development of a person’s physical traits and control of the processes in the body. It is the basic unit of heredity and can be passed down from parent to offspring.
  • Genetic Counselor: A health care professional with special training in genetics and counseling who can provide expert advice about genetic disorders and prenatal testing.
  • Genetic Disorders: Disorders caused by a change in genes or chromosomes.
  • Inherited Disorders: Disorders caused by a change in a gene that can be passed down from parent to children.
  • Monosomy: A condition in which there is a missing chromosome.
  • Mutations: Permanent changes in genes that can be passed on from parents to child.
  • Neural Tube Defects: Birth defects that result from incomplete development of the brain, spinal cord or their coverings.
  • Nuchal Translucency Screening: A test in which the size of a collection of fluid at the back of the fetal neck is measured by ultrasound to screen for certain birth defects; such as Down syndrome, trisomy 18, or heart defects.
  • Obstetrician: A physician who specializes in caring for women during pregnancy, labor and the post-partum period.
  • Placenta: Tissue that provides nourishment to and takes waste away from the fetus.
  • Screening Tests: Tests that look for possible signs of disease in people who do not have symptoms.
  • Sex Chromosomes: The chromosomes that determine a person’s sex. In humans, there are two sex chromosomes, X and Y. Females have two X chromosomes and males have an X and a Y chromosome.
  • Sickle Cell Disease: An inherited disorder in which red blood cells have a crescent shape, causing chronic anemia and episodes of pain. It occurs most often in African Americans.
  • Tay-Sachs Disease: An inherited birth defect that causes intellectual disability, blindness, seizures, and death, usually by age 5 years. It most commonly affect people of Eastern and Central European Jewish, Cajun, and French Canadian descent, but it can occur in anyone.
  • Trimester: One of the three 3-month periods into which pregnancy is divided.
  • Trisomy: A condition in which there is an extra chromosome.
  • Trisomy 13 (Patau Syndrome): A chromosomal disorder that causes serious problems with the brain and heart as well as extra fingers and toes, cleft palate and lip, and other defects. Most infants with trisomy 13 die within the first year of life.
  • Trisomy 18 (Edwards Syndrome): A chromosomal disorder that causes severe intellectual disability and serious physical problems such as a small head, heart defects and deafness. Most infants with trisomy 18 die before birth or within the first month of life.
  • Turner Syndrome: A condition affecting females in which there is a missing or damaged X chromosome. It causes a webbed neck, short height, and heart problems but does not usually cause developmental delays.
  • Ultrasound Exams: Tests in which sound waves are used to examine internal structures. During pregnancy, they can be used to examine the fetus.
  • X Chromosome: One of two chromosomes that determine a person’s sex. Egg cells carry only the X chromosome.
  • Y Chromosome: One of two chromosomes that determine a person’s sex. Sperm cells can carry a Y chromosome or an X chromosome.

Prenatal Test Codes

Below is a list of codes which may be helpful when confirming insurance coverage.

  • OBSTETRIC PANEL – 80055
  • SMA TESTING (spinal muscle atrophy)
    • Billed and performed by Integrated Genetics
    • Cost $875
    • CPT code 81401
  • SMA TESTING (Connecticare, Aetna, Husy patients)*
    • Billed and performed by Quest Diagnostics
    • Cost $950
    • CPT code 81401
    • *Husky patients need to be preauthorized for SMA – sent to Quest
  • CYSTIC FIBROSIS*
    • Billed through ECHN (Manchester Memorial Hospital) performed by ARUP Reference Lab
    • Cost $3,360
    • CPT code 81220
    • *Cystic Fibrosis test is covered, sent through ECHN for Husky patients
  • FRAGILE X
    • Billed through ECHN (Manchester Memorial Hospital), performed by Integrated Genetics
    • Cost $495
    • CPT Code 81243
  • FIRST TRIMESTER SCREENING
    • Performed at Hartford Hospital
    • CPT code 76813 – ultrasound
    • 99242 – MD consult
    • 36415 – venipuncture
    • Performed at UCONN
    • CPT codes 76813 – ultrasound
    • 99242 – MD consult
    • 84163 – Plasma protein-A
    • 84702 – hCG quantitative
  • GENETIC COUNSELING
    • CPT code 99404 – (preventative medicine counseling or risk factor reduction provided to an individual for at least 60 minutes by a genetic individual)
  • QUAD SCREEN
    • CPT codes 82105 (AFP serum), 82677 (Estriol), and 86336 (Inhibin A)
  • INTEGRATED SCREEN
    • CPT code 82105
  • AFP ONLY
    • CPT code 82105
  • LEVEL II ULTRASOUND
    • CPT code 76811
  • CHRONIC VILLI SAMPLI (CVS)
    • Performed and billed by Hartford Hospital
    • CPT code 59015
  • AMNIOCENTESIS
    • CPT codes 59000 (diagnostic amnio), 76946 (ultrasound guidance)
  • CELL FREE DNA
    • Performed at Hartford Hospital
    • This is an out of pocket expense
  • POSSIBLE DIAGNOSIS CODE (ICD-9)
    • V22.0 – supervision of normal first pregnancy
    • V22.1 – supervision of other normal pregnancy
    • V23.82 – AMA primigravida
    • V23.82 – AMA multigravida
    • V28.9 – unspecified antenatal screening of mother
    • V19.8 – family history of other conditions
    • 659.63 – other advanced maternal age, antepartum condition
    • 793.99 – abnormal ultrasound
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