Guide to integrated screening – the best method for detecting Down syndrome in the whole population

Determination of an exact fetal age is crucial for the screening result.

The serum integrated test in the first and second trimester consists of collecting two blood samples for biochemical testing:

1st blood sample for PaPP – A in the first trimester – the most effective blood samples are collected within weeks 10+0 – 11+3 according to an ultrasound scan

2nd blood sample for AFP, HCG, uE3 in the second trimester – 4 weeks later, from 14+0 as usual

• the result of the test is obtained by an integration of both steps and will be released by the screening center only after the sample from the second trimester is examined!!!
• there will be no result after the first step (PaPP – A alone is invalid), there will only be our recommendation for the second blood sample to be collected in the second trimester and an application form with our stamp as a doctor-geneticist. A patient will fill out the form (date of sample collection, ultrasound scan, weight) as usual
• It is important to remember to come for the second blood test, the triple test (HCG, AFP, uE3). It is necessary to do the triple test for every patient from14+0 ( PaPP – A testing alone is invalid)
• if a patient comes later or if the first step (a blood sample for PaPP-A testing) is not done it doesn’t matter – there will be the usual blood sample collected for AFP, HCG, uE3 testing in the second trimester from 14+0 as had been done previously!!!

Serum Integrated Test:

• 1st blood sample collection in the first trimester – PaPP - A testing – from 10+0 till 11+3, the sooner the better in 4 weeks
• 2nd blood sample collection in the second trimester - HCG, AFP, E3 testing - from 14+0, integration in CMG

TEST RESULT

The result of the serum integrated test is available in the same stage of pregnancy as 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 detection rate is higher than the one of the first-trimester test 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 as early as at 16 weeks gestation (in contrast to the first-trimester test which doesn’t detect it!!) decreases the number of invasive procedures (false-positive rate of 5% in contrast to 9% of the triple test in the second trimester) the result of the serum integrated test is available in the same stage of pregnancy as the result of the first-trimester test

Starting January 1st, 2007, the following health insurance companies fully cover the PaPP – A test in the South Bohemian region only if done by the OKB Medipont Ltd screening center - Center for Medical Genetics Ltd:

VZP, VoZP, OZP, ZPMV, ČNZP

The test is covered by all health insurance companies as stated above; therefore it is available for all patients.

Benefits of the first- and second-trimester serum integrated test

• the most effective method of screening for Down syndrome applicable to the whole population
• the test also detects spina bifida, abdominal wall defects, anencephaly
• a test with increased AFP levels signify possible pregnancy complications in the third trimester
• high detection rate also in younger age groups *1,2 (as opposed to the first trimester test – there the detection rate is higher for older women)
• this is a so-called population test (as opposed to selected patients for the first trimester test)
• safe invasive method – amniocentesis (at highly professional centers the risk of miscarriage after amniocentesis is not statistically higher compared to other pregnancies)

Dependence of Down syndrome detection on the week of pregnancy in which the PaPP – A test is done in the first trimester

Week of pregnancy	10	11	12	13
PaPP – A detection rate	58%	45%	35%	27%

1st blood sample collection: the most effective PaPP – A testing is within 10+0 – 11+3 weeks gestation

2nd blood sample collection in the second trimester - AFP, HCG, E3: exactly 4 weeks (14+0…)

In case it is a patient’s explicit wish it is possible to supplement the serum integrated with an NT scan done by a sonographer accredited by FMF London (at present the only accredited sonographer in Southern Bohemia is Dr. David Čutka). This kind of a test is called the integrated test. In CMG it will be possible to have the NT scan done for a fee (an NT scan done by a non-accredited sonographer cannot be included in the integrated test for both software and medical reasons).

Recommendations valid in the Great Britain, USA and Canada (from 2/2007)

According to recommendations of the American Congress of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynaecologists (RCOG) and the Society of Obstetricians and Gynaecologists of Canada (SOGC), following the principles of Evidence Based Medicine there are four tests for screening for chromosomal aberrations:

1. integrated test – 92% detection rate, the most effective test
2. serum integrated test - 90% detection rate (in case it is not possible for an accredited sonographer to do the NT scan in population)
3. first-trimester test – 83% detection rate
4. quadruple test (triple test + inhibin) – 81% detection rate (in the Czech Republic it is called the triple test – AFP, HCG, uE3)

In the South Bohemian region, since January 2007 there has been implemented a full-area screening for chromosomal aberrations – the serum integrated test. The test is available for all 7000 pregnant women only in the Medical Genetics Center Ltd - OKB Medipont Ltd. By a patient’s request our accredited sonographer can perform the NT scan and we can do the integrated test. We are able to do any kind of prenatal testing should a patient require. Prenatal screening gives many options; however, it is necessary to focus on what can be done locally. In case it is possible to do multiple tests it is advisable to give patient detailed information on all screening options.

March 2007

Karel Čutka, MD, David Čutka, MD

References:

1. Wald NJ, Rodeck C,Hackshaw AK, Walters J, Chitty L, Mackinson AM. First and second trimester antenatal screening for Down´s syndrome: the results of Serum, Urine and Ultrasound Screening Study (SURUSS). Health Technology Assessment 2003;7:24-27
2. Malone F, Canick JA, Ball RH, Nyberg DA, Comstock CH, Buckowski R, et al. First-trimester or second-trimester screening, or both, for Down´s syndrome. First and Second-Trimester Evaluation of Risk (FASTER) Research Consortium. N Engl J Med 2005;353:2001-11.
3. ACOG Practice Bulletin No.77. Screening for Fetal Chromosomal Abnormalities Obstet gynecol 2007;109:217-227
4. Model of best practice for providing Down´s Syndrome screening services, Department of Health, www.dh.gov.uk
5. Antenatal Screening for Down Syndrome. Royal College of Obstetricians and Gynaecologists.
   http://www.rcog.org.uk/resources/public/pdf/down_syndrome_screening.pdf