Test ID: 1STT
First Trimester Maternal Screen

Prenatal screening for Down syndrome (nuchal translucency, pregnancy-associated plasma protein A, human chorionic gonadotropin) and trisomy 18 (pregnancy-associated plasma protein A, human chorionic gonadotropin)

• NT/CRL Data for First Trimester/Sequential Maternal Screening
• First Trimester/Sequential Maternal Screening Patient Information Sheet

Immunoenzymatic Assay

Approval to send specimen for first-trimester screening is required and may take up to 5 business days to complete. Nuchal translucency (NT) measurements are only accepted from NT-certified sonographers. Do not send specimen to Mayo Medical Laboratories if the sonographer is not NT-certified or before completing the application process. To begin the application process, visit the Sonographer Approval Process page at:

http://www.MayoMedicalLaboratories.com/customer-service/forms/maternal-screening.html or complete the NT/CRL Data for First Trimester/Sequential Maternal Screening form in Special Instructions.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 1 mL

Collection Instructions: Immediately spin down.

Additional Information:

1. Blood draw and ultrasound must be completed between 10 weeks, 0 days and 13 weeks, 6 days, which corresponds to a crown-rump length (CRL) range of 31 to 80 mm.

2. Initial or repeat testing is determined in the laboratory at the time of report and will be reported accordingly. To be considered a repeat test for the patient, the testing must be within the same pregnancy and trimester, with interpretable results for the same test and both tests are performed at Mayo Clinic.

Forms: First Trimester/Sequential Maternal Screening Patient Information Sheet (Supply T593) is required in Special Instructions.

Multiple marker serum screening has become a standard tool used in obstetric care to identify pregnancies that may have an increased risk for certain birth defects such as Down syndrome and trisomy 18. Second-trimester multiple marker screening has been well established for over a decade. During 2002 through 2006, first-trimester screening has been established as an alternative option of equal or better performance compared with the best second-trimester screening programs.

The first-trimester screen is performed by measuring analytes in maternal serum that are produced by the fetus and the placenta. Additionally, the nuchal translucency (NT) measurement is a sonographic marker shown to be effective in screening fetuses for Down syndrome. A mathematical model is used to calculate a risk estimate by combining the analyte values, NT measurement, and maternal demographic information. The laboratory establishes a specific cutoff for each condition, which classifies each screen as either screen-positive or screen-negative. A screen-positive result indicates that the value obtained exceeds the established cutoff. A positive screen does not provide a diagnosis, but indicates that further evaluation should be considered.

Serum Analytes

Human chorionic gonadotropin (total beta-hCG):

hCG is a glycoprotein consisting of alpha and beta subunits. hCG is synthesized by placental cells starting very early in pregnancy and serves to maintain the corpus luteum and, hence, progesterone production during the first trimester. Thereafter, the concentration of hCG begins to fall as the placenta begins to produce steroid hormones and the role of the corpus luteum in maintaining pregnancy diminishes. Increased total hCG levels are associated with an increased risk for Down syndrome.

Pregnancy-associated plasma protein A (PAPP-A):

PAPP-A is a 187 kDA protein comprised of 4 subunits: 2 PAPP-A subunits and 2 pro-major basic protein (proMBP) subunits. PAPP-A is a metalloproteinase that cleaves insulin-like growth factor-binding protein-4 (IGFBP-4), dramatically reducing IGFBP-4 affinity for IGF1 and IGF2, thereby regulating the availability of these growth factors at the tissue level. PAPP-A is highly expressed in first-trimester trophoblasts, participating in regulation of fetal growth. Levels in maternal serum increase throughout pregnancy. Low PAPP-A levels before the 14th week of gestation are associated with an increased risk for Down syndrome and trisomy 18.

Nuchal translucency (NT):

The NT measurement, an ultrasound marker, is obtained by measuring the fluid-filled space within the nuchal region (back of the neck) of the fetus. While fetal NT measurements obtained by ultrasonography increase in normal pregnancies with advancing gestational age, Down syndrome fetuses have larger NT measurements than gestational age-matched normal fetuses. Increased fetal NT measurements can therefore serve as an indicator of an increased risk for Down syndrome.

DOWN SYNDROME

Calculated screen risks <1/230 are reported as screen negative.

Risks > or =1/230 are reported as screen positive.

TRISOMY 18

Calculated screen risks <1/100 are reported as screen negative.

Risks > or =1/100 are reported as screen positive. A numeric risk for trisomy 18 risk is provided with positive results on non-diabetic, non-twin pregnancies.

An interpretive report will be provided.

Screen-Negative:

A screen-negative result indicates that the calculated screen risk is below the established cutoff of 1/230 for Down syndrome and 1/100 for trisomy 18. A negative screen does not guarantee the absence of trisomy 18 or Down syndrome. Screen-negative results typically do not warrant further evaluation.

Screen-Positive:

When a Down syndrome risk cutoff of 1/230 is used for follow-up, the combination of maternal age, pregnancy-associated plasma protein A, human chorionic gonadotropin, and nuchal translucency has an overall detection rate of approximately 85% with a false-positive rate of 5% to 10%. In practice, both the detection rate and false-positive rate increase with age, thus detection and positive rates will vary depending on the age distribution of the screening population.

Upon receiving maternal serum screening results, all information used in the risk calculation should be reviewed for accuracy (eg, maternal date of birth, demographics, sonographic information). If any information is incorrect, the laboratory should be contacted for a recalculation of the estimated risks.

The use of these markers to screen for Down syndrome or trisomy 18 is not an approved Food and Drug Administration procedure.

This test does not screen for neural tube defects. If risk assessment for neural tube defects is desired, collect specimen between 15 weeks, 0 days and 22 weeks, 6 days for an AFP single marker screen, MAFP/81169 Alpha-Fetoprotein (AFP), Single Marker Screen, Maternal, Serum.

QUAD screening (QUAD/81149 Quad Screen [Second Trimester] Maternal, Serum) is not recommended following first-trimester screening.

Variables Affecting Marker Levels:

-All serum marker multiple of medians are adjusted for maternal weight (to account for dilution effects in heavier mothers). The estimated risk calculations and screen results are dependent on accurate information for gestation, maternal age, and weight. Inaccurate information can lead to significant alterations in the estimated risk.

-A screen-negative result does not guarantee the absence of fetal defects. A screen-positive result does not provide a diagnosis, but indicates that further diagnostic testing should be considered (an unaffected fetus may have screen-positive result for unknown reasons). In fact, given the low prevalence of Down syndrome, the majority of women with a positive screen will not have a Down syndrome fetus.

-In twin pregnancies, the risk for Down syndrome is approximated, using twin-adjusted medians. A specific risk for trisomy 18 cannot be calculated; therefore, results for trisomy 18 are reported as either screen-negative or screen-positive. Risks for triplets and higher multiples cannot be calculated.

-Each center offering maternal serum screening to patients should establish a standard screening protocol, which provides pre- and post-screening education and appropriate follow-up for screen-positive results.

-Nuchal translucency (NT) measurements must be obtained from a trained and certified sonographer. NT quality indicators will be monitored on a regular basis. Institutions will be contacted if there is ongoing deviation in the quality indicators.

1. Malone FD, Canick JA, Ball RH, et al: First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med 2005 Nov 10;353(19):2001-2011

2. Screening for fetal chromosomal abnormalities. ACOG Practice Bulletin No. 77. American College of Obstetricians and Gynecologists. Obstet Gynecol 2007;109:217–27

3. Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A: SURUSS in Perspective. Semin Perinatol 2005;29:225-235

The first-trimester screen for trisomy 21 and trisomy 18 includes pregnancy-associated plasma protein A (PAPP-A), total human chorionic gonadotropin (ThCG), and nuchal translucency measurement. Analyte values are compared to median values at a given gestational age and multiple of the median (MoM) results obtained. The MoM results are used in a multivariate algorithm that includes the mother's age to derive risk factors for Down syndrome and trisomy 18. An interpretive report is provided. The Beckman Access ThCG assay is an automated 2-site, mouse monoclonal antibody-based immunoenzymatic sandwich assay with paramagnetic separation and chemiluminescent detection. Testing is performed using the Beckman Coulter DxI. (Beckman Coulter Assay Manual, Access Total HCG, Reference 387302, Lot 419063, Version 2.1, 2004). The Access PAPP-A (RUO) assay is a two-site immunoenzymatic sandwich assay. Testing is performed using the Beckman Coulter DxI. (Package insert: Beckman Coulter Access PAPP-A [RUO[, Beckman Coulter, Inc., Fullerton CA 2009)

Monday through Friday; 5 a.m.-5 p.m., Saturday; 6 a.m.-1 p.m.

81508-Fetal congenital abnormalities, biochemical assays of two proteins (PAPP-A, hCG [any form]), utilizing maternal serum, algorithm reported as a risk score