Diagnostic tests for Down syndrome (Trisomy 21) are considered invasive testing procedures. Note: The American College of Obstetricians and Gynecologists (ACOG) recommends that pregnant women of all ages have the option of bypassing the screening test and choosing instead to have a diagnostic test for Down syndrome.Diagnostic tests may be offered for several reasons, including:Will be age 35 or older at deliveryAbnormal results obtained on screening tests or ultrasoundPrior child or pregnancy with a birth defect Diagnostic tests, which use a sample of fetal cells, include one or both of the following procedures:Chorionic villus sampling (CVS): CVS is usually done between 10 and 12 weeks of pregnancy. It is considered an invasive procedure since the procedure involves the collection of chorionic villus cell samples from the placenta, either via a needle insertion into the abdominal wall or a catheter in the vagina. Samples are analyzed for fetal chromosome abnormalities.Amniocentesis: Amniocentesis is performed between gestational weeks 16 and 20 and is also classified as an invasive procedure. A thin needle is placed into the abdominal wall and a sample of the amniotic fluid is collected. The sample is analyzed for fetal chromosome abnormalities. Both CVS and amniocentesis are highly accurate for diagnosing Down syndrome and/or ruling out the condition. However, because they are invasive procedures, there are risks, including miscarriage, preterm labor, infection, or injury to the fetus or mother.
|Screening Tests, continued: Maternal Serum Screening|
Maternal serum screening tests may be performed during the first and second trimester of pregnancy. These serum tests involve the measurement of specific biomarkers in the maternal blood. These five biomarkers are typically used to assess the risk for Down syndrome: Maternal Serum Alpha-fetoprotein (MS-AFP) AFP is a fetal protein that is initially produced in the fetal yolk sac and liver; by the end of the first trimester of pregnancy, most if not all of the AFP is produced by the fetal liver. The concentration of AFP peaks in fetal serum at 10-13 weeks gestation. The fetal AFP normally diffuses across the placental barrier and into the maternal circulation so that MS-AFP rises throughout pregnancy to about 250 ng/mL at 32 weeks gestation. Lower MS-AFP values may be associated with increased risk for trisomy 21 (Down syndrome) or trisomy 18 (Edwards syndrome).Unconjugated estriol (uE3-estriol) Estriol is a female sex hormone that increases during pregnancy. It is produced by the placenta and passes into the maternal bloodstream during pregnancy. Its roles during pregnancy may be linked to the proper functioning of the uterus, softening of the cervix, and assistance in the lactation process. A biologically active form of estriol called uE3-estriol increases in the maternal circulation during pregnancy by the seventh to ninth weeks of gestation and continues to increase throughout pregnancy. uE3-estriol levels in maternal serum is typically decreased in the Down syndrome pregnancy. Human chorionic gonadotropin, total or free beta subunit (beta-hCG) HCG is a glycoprotein hormone produced by the placenta during pregnancy. It is present in blood and urine around 7-13 days following fertilization of the ovum. HCG has two subunit chains, alpha and beta. The beta subunit confers its specificity. A specific smaller part of the hormone, called free beta hCG may be used as a screening test during the first trimester of pregnancy. An increase in maternal serum free beta hCG (ie, greater concentration than in other pregnancies) may indicate an increased risk for Down syndrome. Total beta-hCG is tested as part of a triple or quad screen during the second trimester of pregnancy. An increase in total beta hCG in the maternal serum is also associated with increased risk of Down syndrome.Dimeric inhibin A (DIA) Inhibins are a family of glycoproteins mainly secreted by the ovaries and testicles. The beta subunits of the inhibins exist in two forms, the A and B forms. DIA is secreted by the ovaries and is designed to inhibit the production of the hormone FSH by the pituitary gland. The level of DIA is increased in the blood of mothers of fetuses with Down syndromePregnancy Associated Plasma Protein A (PAPP-A) PAPP-A is produced by the covering of the newly fertilized egg. It is thought to be involved in local proliferative processes such as wound healing and bone remodeling. Unexplained low levels of PAPP-A in the maternal serum during pregnancy may indicate increased chance for intrauterine growth restrictions, premature delivery, preeclampsia, and stillbirth. In the first trimester, low levels of this protein are seen in Down syndrome pregnancies.In the first trimester, serum screening is typically done in combination with an ultrasound to screen for nuchal translucency. Serum screening in the first trimester usually involves the measurement of two biomarkers in the maternal serum, free beta-hCG and PAPP-A. Combining the results of these two biomarkers with an ultrasound improves the screening process. In the second trimester during weeks 16-18, maternal serum assays for 3-4 levels of biomarkers are typically performed. The screening for these biomarkers has been established as a triple or quadruple (quad) screen, since the benefit of the screening lies in the combined use of the three to four biomarkers. The biomarkers used in the screening process may include MS-AFP, uE3-estriol, total beta HCG, and DIA. Increased serum levels of MS-hCG and DIA combined with decreased levels of UE3-estriol and MS-AFP suggests an increased risk of Down syndrome. Maternal age, family history, weight, race, and diabetic status are also used to determine a numeric risk for Down syndrome. It is important to understand that for women who have positive triple or quad screening results, only a very small number of them have babies who actually have a chromosomal abnormality.