The Serum Integrated Test

According to recommendations for laboratory screening for congenital anomalies in the first and second trimester of pregnancy dated April 19, 2006 (Czech Society of Clinical Biochemistry, Czech Gynecological and Obstetrical Society, Society for Medical Genetics, Czech Nuclear Medicine Society and Reference Laboratory for clinical biochemistry of the Ministry of Health) PaPP – A testing is approved within the scope of the Procedure Price List of Notice 493/2005, however, it has to be done in screening centers which perform a minimum of 1000 examination per one year. The only center in the South Bohemian region which fulfills the condition is OKB Medipont Ltd. – Center for Medical Genetics Ltd.. The system of combining the first- and second-trimester screening is based on an agreement between the laboratory, gynaecologists and geneticists.

In compliance with the newest international trends in screening for Down syndrome, since January 1, 2007 CMG has been doing the serum integrated test (PaPP – A testing in the first trimester, AFP, HCG, uE3 testing in the second trimester). The test is in accordance with a new recommendations of the American College of Obstetricians and Gynecologists (January 2007), Royal College of Obstetricians and Gynaecologists (July 2003), Department of Health of the United Kingdom (April 2007) and Society of Obstetricians and Gynaecologists of Canada (March 2007), regarding screening for fetal chromosomal aberrations in fetuses. These recommendations are based on Evidence Based Medicine (EBM).

According to the American College of Obstetricians and Gynecologists , Royal College of Obstetricians and Gynaecologists and Society of Obstetricians and Gynaecologists of Canada four tests in the following order are recommended for screening for chromosomal aberrations:

1. integrated test (PaPP – A test and NT measurement in the first trimester, AFP, HCG,uE3 test in the second trimester)
   • detection rate 92 % the most effective test
2. serum integrated test (PaPP – A test in the first trimester, AFP, HCG, uE3 test in the second trimester)
   • detection rate 90 % (the best option in case it is impossible to obtain NT measurement by an accredited sonographer in population)
3. first-trimester test (PaPP – A, freebeta HCG test, NT measurement)
   • detection rate 83 %
4. quadruple test in the second trimester (triple test in the CR + inhibin)
   • detection rate 81%
   • (in the CR done as the triple test for AFP, HCG, uE3) – for women who come in the second trimester

Advantages of the serum integrated test as compared to the combined first-trimester test:

1. it is a population test (it is possible to do it to the majority of pregnant women in the CR)
2. it has a higher detection rate - 90% (versus 83% of the first-trimester test)
3. it speeds up the diagnosis of open neural tube defects (includes the AFP test !!!), the AFP test is not included in the first-trimester test which means that an eventual neural tube defect is detected only by an ultrasound at 20 – 22 weeks gestation. Based on higher AFP levels the integrated test detects a neural tube defect as early as at 16 weeks gestation (according to V. Gregor, MD in the CR only 3 % of neural tube defects were detected in the first trimester in the last 10 years).
4. in case it is possible to obtain the NT measurement by an accredited sonographer (in South Bohemia only in CMG), the best option is the integrated test which has a detection rate of 92%, and includes the AFP test
5. 5. our collection of PaPP- A is at 10+0 – 11+3, the second collection from 14+0, (80% of our patients have collections of AFP, HCG uE3 between 14+0 and 14+5), so the result of the test is available only a few days later than the result of the first-trimester test

The test has a low false-positive rate (5%) and in case of patients with a lower PaPP-A level under 0,35 MoM can be followed by NT scan in our accredited center.In case of a high risk (higher than 1:30 – approx. 1 woman out of 200) it is possible to speed up the process of getting a diagnosis with chorionic villus sampling– CVS in CMG. In case of patients with a lower risk we do the complete integrated test (2 -3 % of women have PaPP – A less than 0,35 MoM).

Conclusion: the serum integrated test in the first and second trimester – the most effective method of screening for Down syndrome in the whole population increases the detection rate of Down syndrome in the whole population speeds up the diagnosis – based on low PaPP-A it detects a part of pathologies in the whole population as early as in the first trimester, detects open neural tube defects already at 16 weeks gestation decreases the number of invasive procedures (false-positive rate of 5% in contrast to 9% of the triple test in the second trimester) in Southern Bohemia the test is covered by health insurance for all pregnant women

The serum integrated test – integration of biochemical parameters of the first and second trimester – solution algorithm:

1st blood sampling:
PaPP – A collected at 10+0 - 11+3

2nd blood sampling:
AFP, HCG, E3 + age from 14+0