Excerpted from A Parent's Guide to Down Syndrome: Toward a Brighter Future, Revised Edition,by Siegfried M. Pueschel, M.D., Ph.D., J.D., M.P.H., with invited contributors

Copyright © 2001 by Paul H. Brookes Publishing Co. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.

Although some forms of prenatal genetic counseling have been available since the early part of the 20th century, new techniques developed during the past few decades — including amniocentesis, chorionic villus sampling (CVS), ultrasound examinations, and various approaches to prenatal screening — have revolutionized intrauterine diagnosis of genetic and chromosome disorders. Since the introduction of these procedures, physicians and genetic counselors have been able to provide more accurate information to many prospective parents regarding the outcomes of pregnancies. Now, instead of discussing general probabilities of risk, the genetic counselor often can tell parents whether the fetus does or does not have a specific genetic syndrome or chromosome disorder such as Down syndrome.

Material Alpha-Fetoprotein Screening and the Triple/Quad Tests

In the late 1970s, prenatal maternal alpha-fetoprotein (AFP) testing became available to pregnant women. Initially, this test was used to screen unborn infants for spina bifida and other neural tube defects; mothers of infants with these congenital abnormalities usually have high AFP levels in their blood during mid-pregnancy. In the early 1980s, it was observed that low maternal AFP levels often are associated with chromosome disorders, in particular Down syndrome. Subsequently, several reports in the medical literature have described a high correlation between low maternal AFP levels and the occurrence of trisomy 21 in the fetus. Other screening tests were added during the 1980s and the 1990s. Today, most prenatal testing includes AFP, estriol, and human chorionic gonadotropin (hCG), which constitute the triple test, or AFP, estriol, hCG, and inhibin, which is called the quad test. Studies have shown that approximately 60%–80% of fetuses with Down syndrome can be identified prenatally by considering the age of the mother and administering the triple or quad test.

In addition, ultrasound examinations of the fetus's neck (nuchal thickening), a series of measurements including the length of the upper arm bone (humerus) and thigh bone (femur), and the size of the head can assist in the prenatal diagnosis of Down syndrome. During the late 1990s, investigations revealed that ultrasound examinations together with maternal age and determination of the B unit of hCG and pregnancy-associated plasma protein A (PAPP-A) during the end of the first trimester can identify approximately 80% of fetuses with Down syndrome.

Indications for Prenatal Diagnosis

Some techniques used in prenatal diagnosis have an associated risk to both the mother and the fetus; therefore, specific indications for using these procedures should be present. Currently, several factors are associated with an increased risk for having a child with Down syndrome:

1. Positive screening test. If the maternal AFP and estriol levels are low and the hCG and inhibin levels are significantly increased (specific risk levels can be calculated), indicating a high probability that the mother is carrying a fetus with Down syndrome, then further prenatal tests such as amniocentesis and ultrasound examination typically are recommended.
   
   
2. Maternal age of 35 years or older. As discussed in Chapter 3, it is widely known that the incidence of chromosome abnormalities increases with advanced maternal age. The risk of having an offspring with a chromosome abnormality doubles approximately every 21-2 years once a woman reaches 35 years of age. At the maternal age of 35 years, the risk that a pregnant woman is carrying a fetus with a chromosome abnormality is approximately 1 in 200 to 1 in 300 live births. At this age or older, the estimated risk of having an affected fetus is thought to be greater than the risk associated with amniocentesis. The risk of complications from CVS, including the possibility of miscarriage or premature birth, is slightly higher than the risk associated with amniocentesis. At the maternal age of 34 years or younger, the risk of having an affected fetus is usually less than that of miscarrying as a result of amniocentesis or CVS.
   
   
3. Paternal age of approximately 50 years or older. Although a slight paternal age effect also has been identified by some investigators, it is much smaller than the effect of the maternal age. If the father is 50 years or older, then there may be a slightly elevated risk of having an offspring with Down syndrome. Some physicians recommend prenatal screening in this situation.
   
   
4. Previous birth of a child with Down syndrome or other chromosome abnormality. Many studies have shown that if a couple has a child with Down syndrome or other chromosome abnormality, the risk of recurrence is approximately 1%. Because of the increased risk, most geneticists and genetic counselors recommend prenatal diagnosis to these families.
   
   
5. Balanced chromosome translocation in a parent. For example, if a chromosome 21 is attached to chromosome 14 (see Figure 3.10), there is a 50% chance that this parent may pass on this 14/21 translocation to an offspring. Therefore, the parent has an increased risk of having more than one child with Down syndrome. This increased risk associated with balanced chromosome translocation depends on the type of translocation, the chromosomes involved, and whether the father or the mother is the carrier. In general, the risk for a translocation carrier of having a child with Down syndrome ranges between 2% and 100%. For instance, if a parent has a 21/21 translocation and the pregnancy is carried to full term, then there is a 100% chance that the child will have Down syndrome. However, if a mother is carrying a 14/21 translocation, there is an 8% - 10% chance of having another child with Down syndrome in a future pregnancy. If the father is the carrier of such a chromosome translocation, the risk is slightly less.
   
   
6. Parents with a chromosome disorder. Although most individuals with a significant chromosome abnormality probably will not have children, some individuals with chromosome disorders may reproduce. For example, if one parent has a low-percentage mosaicism for Down syndrome (i.e., only a small percentage of his or her cells have an extra chromosome 21 and the person is otherwise "typical"), he or she will have an increased risk of producing a child with Down syndrome. If an individual with Down syndrome is able to reproduce, there is a 50% chance in each pregnancy that the newborn child will have Down syndrome. In the medical literature, there are approximately 30 documented cases of women with Down syndrome having children, whereas only one report has mentioned that a male with Down syndrome had fathered a child.

Other indications for prenatal diagnosis also exist, such as the birth of a previous child with multiple congenital anomalies, spina bifida, or a metabolic disorder or parents who are carriers of specific genetic defects; however, because these and other indications are not pertinent to Down syndrome, they are not discussed here.