BIOCHEMICAL MARKERS USED IN

NUCHAL TRANSLUCENCY SCREENING  

 

  1. Serum free b-hCG levels -
  2. Serum PAPP-A (pregnancy associated plasma protein-A) levels. There is a low correlation between free b-hCG levels and PAPP-A levels. This allows the two markers to be simultaneously evaluated and probably achieves a higher degree of detection than either used independently (1). The level of PAPP-A in maternal blood normally increases with gestation. The lower the PAPP-A, the higher the risk for trisomy 21. Again, for a given gestation, each PAPP-A level represents a factor that is multiplied by the background risk to calculate the new risk

 

 

free b-hCG levels

PAPP-A levels

Down Syndrome

Increased

Decreased

Trisomy 18

Decreased

Decreased

Triploidy /
Normal fetuses

Increased
or decreased

Increased


   

 

 

Detection rates for trisomy 21 using NT measurement and

maternal serum beta hCG and PAPP-A

Ref

Predicted sensitivity for

Trisomy 21 (%)

False-positive rate (%)

Gestational age

wks

1

87

5

9-13

3

80

5

10-14

4

89

5

10-14

5

85

3.3

10-14

6

84.6

5

10-14

7

87.5

4.5

10-14

 

 

 

  3. Triple screen test (maternal serum screening)

                              –   Detection rate using NT measurement and triple test was 95% with a screen-positive rate of 7.2% (7).

·         Detection rate based on maternal age – 47% with a screen positive rate of 11% (8).

·         Detection rate based on NT at 10-14 wks (using cut-off of 95th centile) – 80% detection rate with a screen-positive rate of about 8% (9).

-          Out of 4130 pregnancies, 12 cases of Down syndrome were observed (0.28%) (10).

o       7/12 (58%) had a NT of 3 mm or more.

o       6/10 (60%) ofcases with available maternal serum screening had a risk of 1/250 or above.

o       4/5 Down syndrome cases had a NT of <3 mm were detected by subsequent maternal serum screening.

o       At a threshold giving 5% of positive tests, the sensitivity of NT, maternal serum screen and combined risk were 75%, 60% and 90% respectively.

 

  4. At present, the most efficient multiple marker screening test in the second trimester is known as the “quad” screen, a biochemical marker panel comprised of :

·         alpha-fetoprotein (AFP),

·         human chorionic gonadotropin (hCG),

·         unconjugated estriol,

·         inhibin-A (11).

     This combination approach yields sensitivities for Down syndrome of 67% to 76% for a 5% false-positive rate, depending on whether menstrual or sonographic dating are used (12). This   

      common method of screening has several limitations.

·         The earliest it can reliably be performed is 15 weeks gestation, limiting the choice of definitive diagnosis of aneuploidy to amniocentesis and pushing prenatal diagnosis into the latter second trimester.

·         Over 25% of Down syndrome cases are not detected with this screening approach, and the 5% false-positive rate ensures that as many as 60 amniocentesis procedures need to be performed for every single case of Down syndrome detected (13). Given the pregnancy loss rate of 1 in 200 associated with amniocentesis, about one normal fetus is lost for every three fetuses with Down syndrome detected.

 

 

 

REFERENCES
  1. Orlandi F, Damiani G, Wallahan TW et.al. First trimester screening for fetal aneuploidy: biochemistry and nuchal translucency. Ultrasound Obstet Gynecol 1997;10:381-386.
  2. Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first-trimester screening for Down’s syndrome. Ultrasound Obstet Gynecol 1997;17:821-825.
  3. Spencer K. Second trimester prenatal screening for Down’s syndrome using alpha-fetoprotein and free beta hCG: a seven year review. Br J Obstet Gynaecol 1999;106:1287-1293.
  4. De Biasio P, Siccardi M, Volpe G et.al. First-trimester screening for Down syndrome using nuchal translucency measurement with free beta-hCG and PAPP-A between 10 and 13 weeks of pregnancy – the combined test. Prenat Diagn 1999;19:360-363.
  5. deFraf IM, Pajkrt E, Bilardo CM et.al. Early pregnancy screening for fetal aneuploidy with serum markers and nuchal translucency. Prenat Diagn 1999;19:458-462.
  6. Krantz DA, Hallahan TW, Orlandi F et.al. First trimester Down syndrome screening using dried blood biochemistry and nuchal translucency. Obstet Gynecol 200;96:207-213.
  7. Schuchter K, Hafner E, Stangl G et.al. sequential screening for trisomy 21 by nuchal translucency measurement in the first trimester and maternal serum biochemistry in the second trimester in a low-risk population. Ultrasound Obstet Gynecol 2001;18:23-25.
  8. Lowry RB, Jones DC, Renwick DH, Trimble BK. Down syndrome in British Columbia, 1952-1973: incidence and mean maternal age. Teratology (United States) 1976;14:29-34.
  9. Snijders RJM, Noble P, Sebire N et.al. UK mulicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group. Lancet 1998;352:343-346.
  10. Audibert F, Dommergues M, Benattar C et.al. Screening for Down syndrome using first-trimester ultrasound and second-trimester maternal serum markers in a low-risk population: prospective longitudinal study. Ultrasound Obstet Gynecol 2001;18:26-31.
  11. Wald NJ, Densem JW, George L, Muttukrishna S, Knight PG. Prenatal screening for Down's syndrome using inhibin-A as a serum marker. Prenat Diagn 1996;16:143-53.  
  12. Wald NJ, Kennard A, Hackshaw AK, McGuire A. Antenatal screening for Down's syndrome. J Med Screen 1997;4:181-246
  13. Malone FD, Berkowitz RL, Canick JA, D'Alton ME. First trimester screening for aneuploidy: research or standard of care? Am J Obstet Gynecol 2000;182:490-6.