It is common for couples to be screened for disorders that may occur more commonly in their particular ethnic group. People of Ashkenazi Jewish background may choose to be screened for heterozygosity for a panel of AR disorders, including Tay-Sachs disease, Niemann-Pick disease, Bloom syndrome, Canavan disease, Gaucher syndrome, cystic fibrosis, Fanconi anemia, and familial dysautonomia. People of African-American ancestry may choose to be screened for sickle cell anemia. People whose ancestors originated in the Mediterranean basin may be screened for thalassemia.
Historically, prenatal screening involved maternal serum screening for α-fetoprotein (AFP), a protein secreted during fetal life by the liver, gastrointestinal tract, and yolk sac. Some of the AFP crosses the placenta and enters the maternal circulation. Although maternal serum screening was initially used to detect high levels of AFP associated with neural tube defects (NTDs) and the disruption of fetal integument such as omphalocele or gastroschisis, low levels of AFP were found to be associated with fetal aneuploidy. Approximately 50% of fetuses with autosomal trisomies (Down syndrome, trisomy 18, trisomy 13) will be detected by low maternal serum AFP levels. Three other proteins—unconjugated estriol (uE3),inhibin A, and human chorionic gonadotropin (HCG)—were added to the maternal serum screening to create the quad screen. The addition of these compounds increased the detection rate to about 80%.
The quad screen is done in the second trimester. Duringthe first trimester, measurement of a fluid collection of the posterior neck of the developing fetus is termed nuchaltranslucency. An increase in the nuchal translucency is amarker for chromosomal anomalies as well as genetic and structural abnormalities in the fetus. This association provided a noninvasive first trimester marker. Once standardization of nuchal translucency measurements was done,the detection rate for aneuploidy approached 70%. Testing for abnormalities with two first trimester analytes, freeβ-HCG and PAPP-A (pregnancy associated plasma protein)has enhanced first trimester screening to a detection rate ofalmost 90%.
Although the risk of nondisjunction resulting in aneuploidy rises as a woman gets older (and more so for womenolder than 35 years of age), all pregnant women should beindividually counseled as to their risk for aneuploidy andother fetal abnormalities. A combination of first and second trimester screening together with the women’s age producesan individualized risk factor. It is important to emphasizethat both of these first and second trimester screening testsare just screens to identify increased risk. If this risk is high,or if there is concern about fetal anomalies from family history, ultrasound, or serum screening, then a more definitivetest, either chorionic villus sampling (CVS) or amniocentesis, is offered as further testing. Fetal cells are usually testedfor chromosomal abnormalities by cytogenetic techniques,but the use of chromosomal microarray is becoming more common. Biochemical testing for a known family history ofan inherited metabolic disorder can also be done on the fetal cells, as well as molecular screening for familial mutations forknown disorders
Historically, serum screening has required the use of invasive testing follow-up to confirm findings. Because invasive testing carries a small but real risk of pregnancy loss, many women were not willing to submit to an amniocentesis or CVS. What has been needed is a noninvasive definitive test, one in which fetal risk is negligible. Recently, the search for such a noninvasive test has been successful.
Prenatal diagnosis using cell-free fetal DNA in maternal blood offers the ability to detect trisomies in fetuses using nothing more than a sample of the mother’s blood. Although still in the research stage, this technique is being piloted in high-risk pregnancies.