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

• Identify pregnancies at high risk for trisomy 18

Prenatal screening is routinely offered for Down syndrome and NTDs and is accompanied by a risk assessment for trisomy 18. 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).^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], amniocentesis).^1,5,6 Separate screening tests in both trimesters, however, is 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 that 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. Though 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). If risk positive for Down syndrome or trisomy 18, the risks are reported and the patient can be referred immediately for diagnostic testing. Note, however, that such patients will not receive a NTD screen result 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 concentration 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. Thus, the Sequential Integrated Screen enables earlier diagnosis for patients with a first trimester elevated risk while maintaining a high detection rate.¹

• Women in their first trimester of pregnancy

Part 1: 2 mL refrigerated serum; 1 mL minimum
Part 2: 3 mL refrigerated serum; 1 mL minimum

Provide maternal date of birth, expected date of delivery, maternal weight (lb) at time of sample collection, race, insulin-dependent diabetes status, number of fetuses, NT measurement (mm) as determined by a currently certified ultrasonographer at time of sample collection, ultrasonographer’s certification number, and sample collection date. Individual ultrasonographer NT data will be submitted to the certifying agency (FMF or NTQR).

Gestational age determined by ultrasound is preferred; however, last menstrual period (LMP)-based gestational age is accepted for the serum integrated screen.

Unacceptable: samples from women carrying more than 2 fetuses (triplets, etc).

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

• Multiple of the median (MoM): calculated for all markers, except maternal age; 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

  • CPT codes*:

• CPT codes*:  

  • Integrated and Serum Integrated Screens: 84702, 82105, 84163**, 82677, 86336

  • Sequential Integrated Screen: 84163** and 84702 (part 1); or 84702, 82105, 82677 and 86336 (part 2)

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 1-866-GENEINFO.