Down Syndrome : Prenatal Screening and Diagnosis

by National Institute of Health

(Page 2 of 4)

Down Syndrome and Maternal Age

Researchers have established that the likelihood that a reproductive cell will contain an extra copy of chromosome 21 increases dramatically as a woman ages. Therefore, an older mother is more likely than a younger mother to have a baby with Down syndrome. However, of the total population, older mothers have fewer babies; about 75% of babies with Down syndrome are born to younger women because more younger women than older women have babies. Only about nine percent of total pregnancies occur in women 35 years or older each year, but about 25% of babies with Down syndrome are born to women in this age group.

The incidence of Down syndrome rises with increasing maternal age. Many specialists recommend that women who become pregnant at age 35 or older undergo prenatal testing for Down syndrome. The likelihood that a woman under 30 who becomes pregnant will have a baby with Down syndrome is less than 1 in 1,000, but the chance of having a baby with Down syndrome increases to 1 in 400 for women who become pregnant at age 35. The likelihood of Down syndrome continues to increase as a woman ages, so that by age 42, the chance is 1 in 60 that a pregnant woman will have a baby with Down syndrome, and by age 49, the chance is 1 in 12. But using maternal age alone will not detect over 75% of pregnancies that will result in Down syndrome.

Prenatal Screening for Down Syndrome

Prenatal screening for Down syndrome is available. There is a relatively simple, noninvasive screening test that examines a drop of the mother's blood to determine if there is an increased likelihood for Down syndrome. This blood test measures the levels of three markers for Down syndrome: serum alpha feto-protein (MSAFP), chorionic gonadotropin (hCG), and unconjugated estriol (uE3). While these measurements are not a definitive test for Down syndrome, a lower MSAFP value, a lower uE3 level, and an elevated hCG level, on average, suggests an increased likelihood of a Down syndrome fetus, and additional diagnostic testing may be desired.

Diagnostic Testing For Down Syndrome

There are several prenatal diagnostic tests that can be performed to determine the occurrence of Down syndrome. These tests include amniocentesis, chorionic villus sampling (CVS), and percutaneous umbilical blood sampling (PUBS). However, before undergoing any of these diagnostic tests, patients and their families should seek detailed genetic counseling to discuss their family history in relationship to the risks and benefits of performing these diagnostic procedures.

Amniocentesis, the removal and analysis of a small sample of fetal cells from the amniotic fluid, is widely available and involves a lower risk of miscarriage than chorionic villus sampling. However, amniocentesis cannot be done until the 14th to 18th week of pregnancy, and it usually takes additional time to determine whether the cells contain extra material from chromosome 21.

Chorionic villus sampling, conducted at 9 to 11 weeks of pregnancy, involves extracting a tiny amount of chorionic villi, tissue extensions that will eventually develop into a placenta. The tissue can be tested for the presence of extra material from chromosome 21. The villi can be obtained through the pregnant woman's abdomen or cervix. This type of sampling carries a 1-2% risk of miscarriage.

The third diagnostic method, percutaneous umbilical blood sampling or PUBS, is the most accurate method and can be used to confirm the results of CVS or amniocentesis. However, PUBS cannot be performed until later in the pregnancy, during the 18th to 22nd weeks, and carries the greatest risk of miscarriage.

New prenatal diagnostic techniques are currently being developed. The NICHD has supported the development of a new, noninvasive test performed during the first trimester of pregnancy, that samples and separates fetal cells from the mother's blood. The goal is to compare the accuracy of this type of cellular level analysis with results obtained by amniocentesis or CVS.

Researchers outside the NICHD are also developing a new method of diagnosis, called preimplantation diagnosis or blastomere analysis before implantation (BABI), which allows clinicians to detect chromosome imbalances before an embryo is implanted during in vitro fertilization. This technique would primarily be used in couples who are at risk of passing on X-linked disorders, couples who have suffered repeated terminations of pregnancy, subfertile couples, or those at risk for single gene disorders. This technique, which allows the clinician to provide a genetic diagnosis prior to implantation, has been successful so far for cystic fibrosis, Tay Sachs disease, and Lesch-Nyhan syndrome. BABI allows a couple to begin their pregnancy knowing that the fetus is unaffected with the genetic disease of concern. For couples at high risk, this procedure provides an alternative to prenatal testing in the first or second trimester.

A Diagnosis of Down Syndrome

A newborn baby with Down syndrome often has physical features the attending physician will most likely recognize in the delivery room. These may include a flat facial profile, an upward slant to the eye, a short neck, abnormally shaped ears, white spots on the iris of the eye (called Brushfield spots), and a single, deep transverse crease on the palm of the hand. However, a child with Down syndrome may not possess all of these features; some of these features can even be found in the general population.

To confirm the diagnosis, the doctor will request a blood test called a chromosomal karyotype. This involves "growing" the cells from the baby's blood for about two weeks, followed by a microscopic visualization of the chromosomes to determine if extra material from chromosome 21 is present.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.