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Integrated Screen

Integrated Screen

Test Summary

Integrated Screen

Including the Integrated, Serum Integrated, and Sequential Integrated Screens

  

Clinical Use

  • Prenatal screening for Down syndrome, trisomy 18, and open neural tube defects (NTDs)

Clinical Background

Prenatal screening is routinely offered for Down syndrome, trisomy 18, and NTDs. Screening for NTDs is based on alpha-fetoprotein (AFP) alone, whereas Down syndrome and trisomy 18 risk assessments are based on multiple marker combinations that include maternal age and 2 or more of the following: pregnancy-associated plasma protein A (PAPP-A), nuchal translucency (NT), AFP, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and dimeric inhibin A (DIA; Down syndrome only).1-4

While screening has previously been offered in either the first or second trimester, the introduction of integrated screening that combines the results of markers measured in both the first and second trimesters has increased the detection rate (DR) for Down syndrome while lowering the number of false positives, thus reducing the necessity for invasive testing (ie, chorionic villus sampling [CVS] or amniocentesis).1,5,6 Separate screening tests in both trimesters, however, are not recommended due to a higher overall false-positive rate (FPR).1

There are a number of approaches to integrated screening (Table). One is the Integrated Screen, which combines the results of NT and PAPP-A measured in the first trimester with additional markers measured in the second trimester. Patient-specific risks are reported only after all markers have been measured. The Serum Integrated Screen is the same as the Integrated Screen, except NT measurement is not used. Although the Serum Integrated Screen has a lower detection rate than the Integrated Screen, it is the test of choice when an accurate NT measurement is not available.1

Another approach is the Sequential Integrated Screen in which NT, PAPP-A, and hCG are measured in the first trimester (part 1 of the test). Only elevated risks for Down syndrome or trisomy 18 are reported after part 1; patients with elevated risk can be referred immediately for diagnostic testing. Such patients should be followed up with a separate maternal serum AFP test to determine NTD risk because they do not undergo second-trimester screening (part 2 of the test). When first-trimester results are negative, risks are not reported after part 1; rather, the concentrations of additional markers are measured in the second trimester. When this second part of the test is complete, markers from part 1 and part 2 are combined to provide risk estimates for Down syndrome and trisomy 18. AFP is used to report NTD risk. The Stepwise Sequential Integrated Screen is similar to the Sequential Integrated Screen except that all risks are reported after part 1, whether elevated or not. Both screens enable earlier diagnosis for patients with a first-trimester elevated risk while maintaining a high detection rate.1

Table. Comparison of the Integrated Prenatal Screening Tests

Test Sampling Time
(Weeks' Gestation)
Markers Included Results Reported Down Syndrome
DR, %

Trisomy 18

DR, %7

Open Spina Bifida DR, % (1-3% FPR)2

Integrated Screen

Risk reported after
part 2

92 (3% FPR)8

NG

65-80

Part 1

9.0-13.9a

PAPP-A, NT

NA

NA

NA

Part 2

15.0-22.9b

AFP, hCG,
uE3, DIA

NA

NA

NA

Serum Integrated Screen

Risk reported after
part 2

88 (6% FPR)8

~90c

65-80

Part 1

9.0-13.9 PAPP-A NA NA NA

Part 2

15.0-22.9b

AFP, hCG,
uE3, DIA

NA

NA

NA

Sequential Integrated Screen

Elevated risks reported after part 1. Patients offered diagnostic testing.

Patients with normal risk proceed to part 2. All risks reported
after part 2.

92 (4% FPR)9

NG

65-80

Part 1

Part 2

10.0-13.9

15.0-22.9b

PAPP-A

hCG, NT

AFP, hCG,
uE3, DIA

NA

NA

NA

NA

NA

NA

Stepwise Sequential Integrated Screen

All risks reported after part 1 (whether elevated or not). Patients with elevated risk offered diagnostic testing.

Patients with normal risk proceed to part 2. All risks reported after part 2.

92 (4% FPR)9

NG

65-80

Part 1

Part 2

10.0-13.9

15.0-22.9b

PAPP-A,

hCG, NT

AFP, hCG,
uE3, DIA

NA

NA

NA

NA

NA

NA

DR, detection rate; FPR, false positive rate; PAPP-A, pregnancy-associated plasma protein A; NT, nuchal translucency; AFP, alpha-fetoprotein; hCG, human chorionic gonadotropin; uE3, unconjugated estriol; DIA, dimeric inhibin A; NG, not given; NA, not applicable.
a Blood samples are accepted from 9.0 weeks gestation; however, NT measurement must be performed from 10.0 to 13.9 weeks’ gestation.
b The best time for sample collection for part 2 is 16 to 18 weeks; however, samples collected from 14 to 22.9 weeks are accepted. Open neural tube defect risk may not be available for samples collected before 15 weeks’ gestation.
c FPR equals the Down syndrome FPR plus 0.1%.

Individuals Suitable for Testing

  • Women in their first trimester of pregnancy

Method

  • PAPP-A, AFP, hCG, uE3, DIA: marker-specific immunoassays

  • Multiple of the median (MoM): calculated for all markers; race-specific medians used for PAPP-A, AFP, hCG, uE3, and DIA; sonographer-specific medians used for NT when possible

  • MoM adjustments: maternal weight, all markers; insulin dependent diabetes, AFP only

  • NTD risk: based on AFP MoM

  • Down syndrome risk: based on maternal age at time of delivery and NT, PAPP-A, AFP, hCG, uE3, and DIA MoM values

  • Trisomy 18 risk:

   Based on maternal age and MoM values for PAPP-A, NT, AFP, hCG, and uE3

   Based on maternal age and MoM values for PAPP-A and NT in first part of Sequential Integrated

Screen or Stepwise Sequential Integrated Screen

Interpretive Information

Women with a risk below the cut-off are considered screen negative and not at increased risk of carrying an affected fetus. A negative screen does not guarantee the birth of an unaffected baby.

Women with a risk above the cut-off are considered screen positive and at increased risk of carrying an affected fetus. Additionally, women who have had a previously affected pregnancy (Down syndrome, trisomy 18, or NTD) are at increased risk regardless of the test results. Genetic counseling and possible diagnostic testing are recommended in all of these cases.

Inaccurate gestational age and NT measurements can influence risk assessment. Ultrasound estimation of gestational age is strongly suggested. Risks can be recalculated if necessary; call 866-GENEINFO.

References

  1. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. 2007;109:217-227.

  2. Bradley LA, Palomaki GE, McDowell GA; ONTD Working Group. Technical standards and guidelines: Prenatal screening for open neural tube defects. Genet Med. 2005;7:355-369.

  3. Palomaki GE, Lambert-Messerlian GM, Canick JA. A summary analysis of Down syndrome markers in the late first trimester. Adv Clin Chem. 2007;43:177-210.

  4. Norem CT, Schoen EJ, Walton DL, et al. Routine ultrasound compared with maternal serum alpha-fetoprotein for neural tube defect screening. Obstet Gynecol. 2005;106:747-752.

  5. Canick JA, Lambert-Messerlian GM, Palomaki GE, et al; First and Second Trimester Evaluation of Risk (FASTER) Trial Research Consortium. Comparison of serum markers in first-trimester Down syndrome screening. Obstet Gynecol. 2006;108:1192-1199.

  6. 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.

  7. Palomaki GE, Neveux LM, Knight GJ, et al. Maternal serum-integrated screening for trisomy 18 using both first- and second-trimester markers. Prenatal Diag. 2003;23:243-247.

  8. Wald NJ, Rodeck C, Hackshaw AK, et al. SURUSS in perspective. BJOG. 2004;111:521-531.

  9. Wald NJ, Rudnicka AR, Bestwick JP. Sequential and contingent prenatal screening for Down syndrome. Prenat Diagn. 2006;26:769-777.
     

*This test is performed using a kit that has not been approved or cleared by the FDA. The analytical performance characteristics of this test have been determined by Quest Diagnostics Nichols Institute. This test should not be used for diagnosis without confirmation by other medically established means.

Content reviewed 06/2013
 
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* The tests listed by specialist are a select group of tests offered. For a complete list of Quest Diagnostics tests, please refer to our Directory of Services.