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Test Catalog

Test ID: 1STT1    
First Trimester Maternal Screen, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Prenatal screening for Down syndrome and trisomy 18

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 (trisomy 21) and trisomy 18 (Edward syndrome). Since early 2000s first-trimester screening has been established as an alternative option of equal or better performance when compared to second-trimester screening programs.

 

The first-trimester screen is performed by measuring analytes human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum that are produced by the fetus and the placenta. Additionally, the nuchal translucency (NT) measurement, a sonographic marker shown to be effective in screening fetuses for Down syndrome and trisomy 18, is included in the risk calculation. A mathematical model is used to calculate a risk estimate by combining serum concentrations to hCG and PAPP-A, 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.

 

Human Chorionic Gonadotropin (Total Beta-hCG)

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. Low levels of hCG are associated with an increased risk for trisomy 18.

 

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 and trisomy 18.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

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.

Interpretation Provides information to assist in interpretation of the test results

Screen-Negative:

A screen-negative result indicates that the calculated 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 first trimester maternal screen has an overall detection rate of approximately 85% with a false-positive rate of 5%. 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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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. 

 

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.

 

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

 

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.

-In twin pregnancies, the risk for Down syndrome is calculated using twin-adjusted medians. Risks for triplets and higher multiples cannot be calculated.

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

Clinical Reference Recommendations for in-depth reading of a clinical nature

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. American College of Obstetricians and Gynecologists: Practice Bulletin No. 163: Screening for Fetal Aneuploidy. Obstet Gynecol 2016 May;127(5):e123-137

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

4. Yarbrough ML, Stout M, Gronowski AM: Ch 69 Pregnancy and Its Disorders. In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Sixth edition. Edited by N Rafai, AR Horvath, CT Wittwer. Elsevier, 2018, pp 1655-1696

Special Instructions Library of PDFs including pertinent information and forms related to the test