Understanding Noninvasive Prenatal Testing for Fetal Chromosomal Abnormalities

What Are Chromosomal Abnormalities?

Chromosomes are structures inside every cell of the body. They hold our genes. Genes are messages that tell the body how to grow and develop. Genes are inherited from your mother and your father.

Most people have 23 pairs of chromosomes, which each carry thousands of genes. The first 22 pairs are called the autosomes, and are the same in males and females. The 23rd pair are the sex chromosomes – X and Y. Females usually have two X’s, and males have one X and one Y. Some people are born with an extra or missing chromosome. Having three copies of a chromosome instead of two is known as having a trisomy (tri – three, somy- chromosomes). The most common fetal trisomies are trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome). People can also be born with an extra or missing sex chromosome.

There is nothing that a parent can do to cause a chromosomal abnormality, and nothing a parent can to do prevent it. Chromosomal abnormalities happen by chance.

Who’s at Risk to Have a Baby With a Chromosomal Abnormality?

There is a small chance in any pregnancy to have a baby with a chromosome problem. Healthy women, mothers of all ages and all races can be at risk. Certain risk factors can increase the chance to have a baby with chromosomal abnormalities, including:

• Advanced maternal age
• Fetal ultrasound abnormality suggestive of aneuploidy
• Personal/family history of chromosomal abnormalities
• Positive serum screening test

What Is Trisomy 21? 

Down Syndrome

Down syndrome is a condition caused by an extra copy of chromosome 21. Children with Down syndrome have delays in both intelligence and development. Children with Down syndrome also have higher chances for certain health problems. Not everyone with Down syndrome is affected in the same way, and there is no way to determine before birth how a child may be affected.¹ Down syndrome affects about 1 in every 700 babies.^2,3 The chance to have a child with Down syndrome increases with the mother’s age, but mothers of all ages can have a child with Down syndrome and it can occur in people of all races.¹

What Is Trisomy 18?

Edward​s Syndrome

Trisomy 18, also known as Edwards syndrome, is caused by an extra copy of chromosome 18. Babies with trisomy 18 often have multiple birth defects, and many don’t survive the first few months of life. Survivors have serious health problems and typically do not walk or talk. About 1 in every 5,000 babies is born with trisomy 18.⁴

What Is Trisomy 13?

Patau Syndrome

Trisomy 13, also known as Patau syndrome, is caused by an extra copy of chromosome 13. Like babies with trisomy 18, these babies have multiple birth defects and often don’t survive the first few months of life. Survivors are profoundly intellectually and developmentally impaired. This condition is much less common than Down syndrome and occurs in about 1 in 16,000 babies.⁴

What Are Sex Chromosomal Abnormalities?

The sex chromosomes, X and Y, are associated with gender; females typically have two X chromosomes and males have an X and a Y. Abnormalities in the number of sex chromosomes do not usually cause substantial developmental and intellectual impairment. Early diagnosis can help these children get services as needed in order to reach their full potential. Overall, about 1 in every 500 babies is born with a sex chromosomal abnormality.⁵

Turner Syndrome (X)

Most girls with Turner syndrome have only one copy of the X chromosome. Many of these pregnancies are miscarried during pregnancy. Girls with Turner syndrome are usually shorter than average, have delayed or absent puberty and may be infertile. Most have normal intelligence, but some have learning difficulties. Children with Turner syndrome may also have heart or kidney defects. 

Klinefelter Syndrome (XXY)

Boys with Klinefelter syndrome have two X chromosomes and one Y. These boys tend to be taller than average, may have delayed or absent puberty and are often infertile. Most have normal intelligence, but some may have learning or psychological difficulties.

Triple X (XXX) and XYY Syndrome 

Children with these conditions may be taller than average and usually have normal intelligence. A few may have learning or psychological issues. These conditions are not associated with birth defects and may go undiagnosed. People with these conditions may have normal fertility.

Testing Options 

The American College of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women be offered a screening test for fetal chromosomal abnormalities, regardless of the woman’s age.³ Screening may be a maternal blood test done in the first trimester along with ultrasound, a maternal blood test done in the second trimester without ultrasound, or a combination of both.³

ACOG also recommends that invasive diagnostic testing, chorionic villus sampling (CVS) or genetic amniocentesis, for chromosome abnormalities should be made available to all women, regardless of age.⁶ These procedures obtain tissue/cells that allow for highly accurate diagnosis of genetic variations like trisomy 21, 18 or 13. CVS and amniocentesis are invasive and carry a small risk of causing a miscarriage.

In 2012, ACOG and the Society for Maternal-Fetal Medicine (SMFM) issued a joint committee opinion that supports noninvasive prenatal testing that uses cell-free fetal DNA for women at increased risk for having a baby with a chromosomal abnormality.⁷ ACOG also recommends that all women considering this testing have genetic counseling to better understand their options.

Noninvasive Testing for Pregnant Women at Increased Risk for Trisomy 21, 18 and 13

The MaterniT21 PLUS laboratory-developed test is a noninvasive blood test that is available for women with increased risk indicators for fetal chromosomal abnormalities. This test detects an increased amount of chromosomal 21, 18 and 13 material that is circulating in your blood.^8,9 Noninvasive prenatal testing can also provide you with information involving an abnormal amount of X or Y chromosomes.

Your health care provider can recommend the MaterniT21 PLUS test as early as 10 weeks in your pregnancy. This test is only available through your health care provider.

Why Is Prenatal Testing for Chromosomal Abnormalities Important?

Prenatal testing for chromosomal abnormalities can help determine whether your baby has certain genetic conditions. Knowing more about the health of your baby can help you, your family and your health care provider make informed decisions about your pregnancy.^1,10

With your health care provider, you can prepare medically, emotionally and financially for the birth of a child with special needs, such as arranging for delivery in a medically appropriate setting. Please discuss all your prenatal testing options with your health care provider.

References

1. Sheets KB, Crissman BG, Feist CD, Sell SL, et al. Practice guidelines for communicating a prenatal or postnatal diagnosis of down syndrome: Recommendations of the National Society of Genetic Counselors. J Genet Couns. 2011;20(5):432-441.
2. Parker SE, Mai CT, Canfield MA, Rickard R, et al. Updated national birth prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A. 2010;88:1008-1016.
3. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins. ACOG Practice Bulletin No. 77, January 2007. Screening for fetal chromosomal abnormalities. Obstet Gynecol. 109(1):217-228.
4. National Institutes of Health. 2009. Genetics Home Reference. Reviewed January 2009 from: http://ghr.nlm.nih.gov.
5. Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark, Hum. Genet. 1991;87(1):81-83.
6. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins. ACOG Practice Bulletin No. 88, December 2007. Invasive prenatal testing for aneuploidy. Obstet Gynecol. 110(6):1459-1467.
7. Committee opinion no. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol. 2012;120(6):1532-1534.
8. Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, et al. DNA sequencing of maternal plasma to detect Down syndrome: An international clinical validation study. Genet Med. 2011;13(11):913-920.
9. Palomaki GE, Deciu C, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Grody WW, Nelson SF, Canick JA. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13, as well as Down syndrome: An international collaborative study. Genet Med. 2012;14(3):296-305.
10. Skotko BG, Kishnani PS, Capone GT for the Down Syndrome Diagnosis Study Group. Prenatal diagnosis of Down syndrome: How best to deliver the news. Am J Med Genet A. 2009;149A(11):2361-2367.