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Penta Screen

Penta Screen

Test Summary

Penta Screen

  

Clinical Use

  • Prenatal risk assessment for neural tube defects (NTD), Down syndrome, and trisomy 18

Clinical Background

Prenatal screening is routinely offered for NTD, Down syndrome, and trisomy 18 risk assessment. NTD risk assessment is based on alpha-fetoprotein (AFP) alone, whereas Down syndrome and trisomy 18 risk assessments are based on multiple marker combinations that may include maternal age, AFP, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and dimeric inhibin A (DIA). In this screening test, we include an additional marker: hyperglycosylated hCG (h-hCG).

Multiple studies have demonstrated the utility of h-hCG in Down syndrome screening.1-12 h-hCG is a hyperglycosylated form of 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. As shown in Table 1, the addition of h-hCG improves screening sensitivity (ie, detection rate). Based on previous experience,13 the improvement in sensitivity gained from an additional marker should lead to a lower false-positive rate in clinical practice. Thus, the number of amniocenteses required for follow-up of  “positive” test results may be reduced.

Table 1. Down Syndrome Detection Rates (DRs) Obtained from Various Screening Tests12

Test Name Alias Markers Included DR, %a
Triple Screen Maternal Serum Screen 3 Age, AFP, hCG, uE3 72
Quad Screen Maternal Serum Screen 4 Age, AFP, hCG, uE3, DIA 79
Penta Screen Maternal Serum Screen 5 Age, AFP, hCG, uE3, DIA, h-hCG 83
a Detection rate at a 5% false-positive rate.

Individuals Suitable for Testing

  • Women in their second trimester of pregnancy (16 to 18 weeks’ gestation preferred; 14.0 to 22.9 weeks accepted, but risk of NTD not provided for samples collected prior to 15.0 weeks)

Method

  • AFP, hCG, uE3, DIA, h-hCG: marker-specific immunoassays

  • The multiple of the median (MoM) is calculated for all markers. Race-specific medians are used for AFP, hCG, uE3, and DIA.

  • MoM adjustments: maternal weight (all markers); insulin-dependent diabetes (AFP only)

  • NTD risk is based on the AFP MoM. The singleton pregnancy detection rates are 88% for anencephaly and 79% for open spina bifida (false-positive rate, 3%).14

  • Down syndrome risk is based on MoM values of all 5 markers and maternal age at time of delivery. The singleton pregnancy detection rate is 83% at a 5% false-positive rate.12

  • Trisomy 18 risk is based on maternal age and AFP, hCG, and uE3 MoMs. The singleton pregnancy detection rate is 60% at a 0.2% false-positive rate.15

  • Aliases: Maternal Serum Screen 5 (MSS 5), invasive trophoblast antigen (ITA, h-hCG)

Reference Range

Table 2. Cut-off Used to Define a Normal Screen

Disorder Normal Screen

Neural tube defect

<2.50 AFP MoM (singleton pregnancy)

<1.90 AFP MoM (insulin-dependent diabetic)

<4.00 AFP MoM (twins)

<3.50 AFP MoM (insulin-dependent diabetic, twins)

<4.50 AFP MoM (triplets)

Down syndrome

Risk <1:270

Trisomy 18

Risk <1:100

Interpretive Information

Women with values above the cut-off listed in Table 2 are considered at increased risk of carrying an affected fetus. Inaccurate patient information can substantially affect risk assessment. Risks can be recalculated using corrected patient information; call 800-642-4657, ext. 4455.

Normal Risk for NTD

Normal levels do not ensure birth of a normal infant; AFP screening has a false-negative rate of 8% for anencephaly and 38% for spina bifida.16 Closed NTD will not be detected in most cases.

Increased Risk for NTD

Ultrasonography is recommended to confirm the gestational age or detect the presence of twins or anencephaly. When the gestational age is <19 weeks and an increased AFP MoM of 2.5 but <3.5 is still unexplained, repeat blood sampling and AFP measurement are recommended to confirm the elevation. Repeat blood sampling is not recommended when 1) the Down syndrome or trisomy 18 risk is elevated; 2) the AFP MoM is 2.5 and the gestational age is advanced (19 weeks); or 3) the AFP MoM is 3.5. Follow-up for abnormal AFP results includes genetic counseling, level II or III ultrasound examination, and consideration of amniocentesis for chromosome and AFP analysis. Following these procedures, an unexplained maternal serum AFP elevation indicates an increased risk for obstetrical complications, including rupture of membranes and premature labor, intrauterine growth retardation, and stillbirth.

Increased Risk for Down Syndrome

Obtaining a repeat blood specimen is contraindicated unless the gestational age was <14 weeks at the time of the first blood draw. Ultrasonography will provide a more accurate estimation of the gestational age and may resolve the increased risk. If not, genetic counseling and cytogenetic analysis of amniotic fluid cells are recommended. Approximately 2% of pregnancies at increased risk would be expected to have an affected fetus.

Increased Risk for Trisomy 18

One in 10 pregnancies at increased risk would be expected to have an affected fetus.15 Genetic counseling and cytogenetic studies of amniotic fluid cells are recommended.

References

  1. Bahado-Singh R, Shahabi S, Karaca M, et al. The comprehensive midtrimester test: high-sensitivity Down syndrome test. Am J Obstet Gynecol. 2002;186:803-808.

  2. Bahado-Singh RO, Oz U, Shahabi S, et al. Comparison of urinary hyperglycosylated human chorionic gonadotropin concentration with the serum triple screen for Down syndrome detection in high-risk pregnancies. Am J Obstet Gynecol. 2000;183:1114-1118.

  3. Bahado-Singh RO, Oz UA, Kovanci E, et al. A high sensitivity alternative to “routine” genetic amniocentesis: Multiple urinary analytes, nuchal thickness and age. Am J Obstet Gynecol. 1999;180:169-173.

  4. Bahado-Singh RO, Oz UA, Shahabi S, et al. Urine hyperglycosylated hCG plus ultrasound biometry for detection of Down syndrome in the second trimester in a high-risk population. Obstet Gynecol. 2000;95:889-894.

  5. 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.

  6. Cole LA, Shahabi S, Oz UA, et al. Hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen) immunoassay: a new basis for gestational Down syndrome screening. Clin Chem. 1999;45:2109-2119.

  7. Cole LA, Shahabi S, Oz UA, et al. Urinary screening tests for fetal Down syndrome: II. Hyperglycosylated hCG. Prenat Diagn. 1999;19:351-359.

  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. Palomaki GE, Knight GJ, Roberson MM, et al. Invasive trophoblast antigen (hyperglycosylated human chorionic gonadotropin) in second-trimester maternal urine as a marker for Down syndrome: preliminary results of an observational study on fresh samples. Clin Chem. 2004;50:182-189.a

  10. Pandian R, Cole LA, Palomaki GE. Second-trimester maternal serum invasive trophoblast antigen: a marker for Down syndrome screening. Clin Chem. 2004;50:1433-1435.a

  11. 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.

  12. Palomaki GE, Neveux LM, Knight GJ, et al. Maternal serum invasive trophoblast antigen (hyperglycosylated hCG) as a screening marker for Down syndrome during the second trimester. Clin Chem. 2004;50:1804-1808.a

  13. Haddow JE, Palomaki GE, Knight GF, et al. Second trimester screening for Down’s syndrome using maternal serum dimeric inhibin A. J Med Screen. 1998;5:115-119.

  14. Wald NJ, Cuckle H, Brock JH, et al. Maternal serum alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Lancet. 1977;1:1323-1332.

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

  16. 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.
     

a This study was funded in part by Quest Diagnostics; however, Quest Diagnostics did not participate in the data analysis or influence the conclusions reached by the authors.

Content reviewed 06/2013

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