Maternal Serum Screen, First Trimester

Test Summary

Clinical Use

•	Prenatal (first trimester) risk assessment for Down syndrome and trisomy 18

Clinical Background
Prenatal testing for Down syndrome and trisomy 18 risk assessment is routinely offered to pregnant women in the second trimester of pregnancy. First-trimester screening, however, is advantageous in that:

1.	negative results can reduce maternal anxiety earlier in the pregnancy;
2.	positive results can lead to earlier diagnosis; and
3.	when pregnancy termination is elected, there is more privacy and reduced maternal morbidity.

Studies have shown similar detection rates, at a constant false-positive rate, for first- and second-trimester screening tests. The American College of Obstetricians and Gynecologists (ACOG) now considers first-trimester screening a reasonable option.¹

This first-trimester maternal serum screening test includes maternal age, pregnancy-associated plasma protein-A (PAPP-A), invasive trophoblast antigen (ITA), and nuchal translucency (NT). PAPP-A is a placental protein generally present in lower concentrations in Down syndrome-affected pregnancies relative to unaffected pregnancies. ITA is a hyperglycosylated form of human chorionic gonadotropin (hCG) that is produced by cytotrophoblasts during embryonic implantation and trophoblast invasion of the uterine wall. Levels tend to be increased in Down syndrome-affected pregnancies. NT is an ultrasonographic measurement of a fluid-filled space at the back of the fetal neck. NT tends to be elevated in cases of fetal aneuploidy. Palomaki and colleagues showed that this screening test is equivalent to the PAPP-A, free-ß hCG, and NT combination for Down syndrome screening (see Table).²

Down Syndrome Detection Rates (DR)²

		DR (%) *
Age, PAPP-A, ITA, NT	84
Age, PAPP-A, free-ß hCG, NT	84
Age, PAPP-A, ITA	68
Age, PAPP-A, free-ß hCG	68
* At a 5% false-positive rate.

Individuals Suitable for Testing

•	Women in their first trimester of pregnancy who are carrying only one fetus

Specimen Requirements

•

2 mL refrigerated serum; 1.0 mL minimum

•

Provide maternal date of birth; expected date of delivery, derived by ultrasound crown-rump length (CRL) measurement (11.0 to 13.9 weeks' gestation preferred; 9.0 to 13.9 weeks accepted; if gestation age is <10.0 weeks, NT will not be used to calculate risk); maternal weight (lb) at time of sample collection; race; insulin-dependent diabetes status; number of fetuses; NT measurement (mm, as measured by a certified ultrasonographer) at time of sample collection; and sample collection date.

	Unacceptable:
	1.	samples from women carrying more than one fetus (e.g., twins, triplets, etc.)
	2.	last menstrual period (LMP)-based gestational age

Method

•	PAPP-A: enzyme immunoassay (EIA).
•	ITA: immunochemiluminescence assay (ICMA).
•	The multiple of the median (MoM) is calculated for PAPP-A, ITA, and NT.
•	PAPP-A and ITA MoM values are adjusted for maternal weight.
•	Down syndrome risk is based on all 3 MoM values, combined with the maternal age at time of delivery. Expected detection rate is 84% at a 5% false-positive rate.2
•	Trisomy 18 risk is based on maternal age, PAPP-A, and NT. Expected detection rate is 75% at a 0.5% false-positive rate.3
•	If the NT measurement is not provided, the Down syndrome risk will be based on age, PAPP-A, and ITA, and the trisomy 18 risk will be based on age and PAPP-A.
•	Neural tube defect (NTD) risk is not provided. For NTD risk, order a second-trimester (16-18 weeks' gestation) AFP test.
•	Aliases: Maternal SCR, 1st Trimester; MSS, 1st Trimester; Down Syndrome and Trisomy 18 Screen
•	CPT Codes:* 84163, 82397

Reference Range

Down syndrome risk	<1:270
Trisomy 18 risk	<1:100

Interpretive Information
Women with a risk <1:270 (Down syndrome) or <1:100 (trisomy 18) are considered at low risk of carrying an affected fetus. Since this is a screening test, such risks cannot guarantee the birth of an unaffected baby.

Women with a risk >1:270 (Down syndrome) or >1:100 (trisomy 18) are considered at increased risk of carrying an affected fetus. Genetic counseling and possible diagnostic testing are recommended.

Since inaccurate gestational age and NT measurements can substantially impact risk assessment, ultrasound confirmation is strongly suggested. Risks can be recalculated if necessary; call 1-800-642-4657, ext. 4455.

* The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed.

Polymerase chain reaction (PCR) is performed pursuant to a license agreement with Roche Molecular Systems, Inc.

References
¹ ACOG Committee Opinion #296: first-trimester screening for fetal aneuploidy. Obstet Gynecol. 2004;104:215-217.
² Palomaki GE, Knight GJ, Neveux LM, et al. Maternal serum invasive trophoblast antigen (ITA) and first trimester Down syndrome screening. Clin Chem. Submitted.
³ Tul N, Spencer K, Noble P, et al. Screening for trisomy 18 by fetal nuchal translucency and maternal serum free ß-hCG and PAPP-A at 10-14 weeks of gestation. Prenat Diagn. 1999;19:1035-1042.
⁴ Weinans MJN, Sancken U, Pandian R, et al. Invasive trophoblast antigen (hyperglycosylated hCG) as a first-trimester serum marker for Down's syndrome. In: Weinans M, ed. Operationalization of First Trimester Maternal Serum Screening for Down's Syndrome. Wageningen: Ponsen & Looyen BV; 2004:111-122.
⁵ Wald NJ, Rodeck C, Hackshaw AK, et al. First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). J Med Screen. 2003;10:56-104.
⁶ Strom CM, Palomaki GE, Knight GJ, et al. Maternal urine invasive trophoblastic antigen (ITA) is a useful marker for Down syndrome detection in the 1st trimester [abstract]. Amer J Hum Genet. 2001;69:664.
⁷ Weinans MJ, Butler SA, Mantingh A, Cole LA. Urinary hyperglycosylated hCG in first trimester screening for chromosomal abnormalities. Prenat Diagn. 2000;20:976-978.
⁸ Cuckle HS, Shahabi S, Sehmi IK, et al. Maternal urine hyperglycosylated hCG in pregnancies with Down syndrome. Prenat Diagn. 1999;19:918-920.
⁹ Cole LA, Shahabi S, Oz UA, et al. Urinary screening tests for fetal Down syndrome: II. Hyperglycosylated hCG. Prenat Diagn. 1999;19:351-359.
¹⁰ Cole LA, Omrani A, Cermik D, et al. Hyperglycosylated hCG, a potential alternative to hCG in Down syndrome screening. Prenat Diagn. 1998;18:926-933.

< Back to previous page