Εδω υπάρχει η απόλυτη σύγχηση . Οταν εμφανίζεται υψηλου κινδυνου αποτελεσμα μετα απο μια αυχενικη διαφανεια η αλφα τεστ δευτερου τριμηνου ολοι ξαφνικα αναρωτιουνται πιο εινα το οριο για να συστησουν ληψη χοριακης λαχνης ή αμνιοκεντηση . Κατω παραθετω την επισημη αποψη του fmf, την αποψη του NHS Fetal Anomaly Screening Programme και τον κλασικο τροπο αντιμετωπισης του αλφα τεστ (τριπλο β τριμηνου ) που ολοι ειχαμε συνηθισει το 1/300 που τελικα ηταν 1/270.
Η ΠΡΟΤΑΣΗ ΤΟΥ FMF ΓΙΑ ΤΑ CUT OFF ΣΤΟ ΠΡΩΤΟ ΤΡΙΜΗΝΟ
1 ) Εαν χρησιμοποιησουμε ως ως cut off level το κλασικο 1/300 θα εχουμε μια ευαισθησια περι 92 % με 5 % ψευδως θετικα ( θεωρητικα τα ψευδως θετικα αυξανουν υπερμρτρα με την ηλικα της ασθενους και κυριως πανω απο τα 38 ετη .Αρα το 5% μπορει να ειναι αφροιστικά 8 % η και 12 % . [ the increasing false-positive rate associated with first trimester NT plus serum screening in women 38 years of age and older (false-positive rate 16% at
38 years) 108 Spencer K. Age related detection and false positive rates when
screening for Down’s syndrome in the first trimester using fetal
nuchal translucency and maternal serum free beta-hCG and
PAPP-A. BJOG 2001; 108: 1043–1046.} ]
2) Μπορουμε να χρησιμοποιησουμε ως cut off level το 1/100 αρκει για το ενδιαμεσο group ( the intermediate-risk category, with a risk estimate of between 1 in 101 and 1 in 1000,) να κανουμε
1 ) χρήση των επικουρικών δεικτών δηλαδή του ρινικού οστού /τριγλωχινασ βαλβίδας και κυρίως του φλεβωδη πόρου . Έτσι θα εχουμε περιπου την ιδια ευαισθησία ( ισως καλυτερη περι 94 % ) αλλά με 2-3 % ψευδως θετικα .
2) Ή να συστήσουμε το FREE FETAL DNA TEST μετα από το COMBINED SCREENING (AGE , NT, PAPPA-BHCG)
ΣΕ ΚΙΝΔΥΝΟ ΜΕΓΑΛΥΤΕΡΟ 1/ 10 ΣΥΣΤΕΙΝΟΥΜΕ ΛΗΨΗ ΤΡΟΦΟΒΛΑΣΤΗΣ
ΣΕ ΚΙΝΔΥΝΟ ΜΕΤΑΞΥ 1/10 ΚΑΙ 1/ 1000 ΣΥΣΤΕΙΝΟΥΜΕ ΤΟ NIPT TEST
ΣΕ ΚΙΝΔΥΝΟ ΜΙΚΡΟΤΕΡΟ ΤΟΥ 1/ 1000 ΔΕΝ ΚΑΝΟΥΜΕ ΤΙΠΟΤΑ ΚΑΙ ΠΑΡΑΠΕΜΠΟΥΜΕ ΤΗΝ ΓΥΝΑΙΚΑ ΣΤΟ Β ΕΠΙΠΕΔΟΥ
UOG 2005 Mar;25(3):221-6.
Multicenter study of first-trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk-orientated two-stage first-trimester screening.
Nicolaides KH, Spencer K, Avgidou K, Faiola S, Falcon O.
First-trimester combined screening for trisomy 21 was carried out in 75 821 singleton pregnancies with live fetuses at 11 + 0 to 13 + 6 gestational weeks. The detection and false-positive rates for different risk cut-offs were calculated. To examine the potential impact of an individual risk-orientated two-stage approach to first-trimester screening it was assumed that, after first-trimester combined screening, chorionic villus sampling (CVS) would be performed in all patients with a risk estimate of 1 in 100 or more and in none of those with a risk estimate of less than 1 in 1000. Those in the intermediate-risk category, with a risk estimate of between 1 in 101 and 1 in 1000, would have further assessment of risk by first-trimester ultrasound examination to determine presence/absence of the nasal bone, presence/absence of tricuspid regurgitation or normal/abnormal Doppler velocity waveform in the ductus venosus, and CVS would be performed if their adjusted risk became 1 in 100 or more. RESULTS The estimated risk for trisomy 21 was 1 in 300 or greater in 5.2% of normal pregnancies, in 92.6% of those with trisomy 21, in 88.5% of those with trisomy 18 or 13 and in 85.6% of those with other chromosomal defects. The detection rates for trisomy 21 were about 75% and 80% for respective false-positive rates of 1% and 2%.
In the proposed individual risk-orientated two-stage screening for a risk cut-off of 1 in 100 the total false-positive rate would vary with the method used for the second stage of screening from 2.1% for absence of the nasal bone to 2.7% for increased impedance in the ductus venosus and 2.7% for tricuspid regurgitation and the respective detection rates would be 92.0%, 94.2% and 91.7%.
First-trimester combined screening for trisomy 21 is associated with a detection rate of about 90% for a false-positive rate of 5%. Individual risk-orientated two-stage screening for trisomy 21 can potentially identify, in the first trimester of pregnancy, more than 90% of affected fetuses for a false-positive rate of 2-3%.
3) Εαν κανουμε τον ορμονικο ελεγχο στις 9-10εβδομαδες και στις 12 εβδομαδες μαζι με την αυχενικη διαφανεια μετραμε και το PIV στον φλεβωδη πορο . Με την καινουργια εκδοση του προγραμματος Αstraia μπορουμε να συνυπολογίσουμε στον τελικο κίνδυνο μαζί με την αυχενική/papp-a fbhcg και το ΡΙ του φλεβωδη πορου. Θετουμε ως fixed cut off το 1/100. Αυτο σημαινει οτι για γυναικες με ρισκο > 1/100 συστήνουμαι αμμεσα ληψη χοριακης λαχνης. Τις υπολοιπες γυναικες δηλαδη για αυτές με κίνδυνο < 1/100 δεν κάνουμε τίποτα . Με αυτόν τον τρόπο η ευαισθησια του τεστ μπορει να φτασει το 93,5% με 2 % ψευδως θετικα .
fetal diagn ther
2012;31(4):221-9. doi: 10.1159/000337322. Epub 2012 May 17.
A mixture model of ductus venosus pulsatility index in screening for aneuploidies at 11-13 weeks' gestation.
Maiz N, Wright D, Ferreira AF, Syngelaki A, Nicolaides KH.
. In screening for trisomy 21 by maternal age, NT and biochemistry at a risk cutoff of 1 in 100, the detection rate was 89.7% and false positive rate was 2.74%; with addition of DV PIV, the values were 93.5 and 1.63%, respectively.
Measurement of DV PIV improves the performance of first-trimester combined test for aneuploidies.
Η ΠΡΟΤΑΣΗ ΤΟΥ FMF ΓΙΑ ΤΡΙ 18 ΚΑΙ ΤΡΙ 13 ΣΤΟ ΠΡΩΤΟ ΤΡΙΜΗΝΟ
A first trimester trisomy 13/trisomy 18 risk algorithm combining fetal nuchal translucency thickness, maternal serum free beta-hCG and PAPP-A.
Kevin Spencer, Kypros H Nicolaides
Endocrine Unit, Clinical Biochemistry Department, Harold Wood Hospital, Gubbins Lane, Romford RM3 0BE, UK.
Prenatal Diagnosis (impact factor: 2.11). 11/2002; 22(10):877-9. DOI:10.1002/pd.420 1 Bookmark
This study examines 45 cases of trisomy 13 and 59 cases of trisomy 18 and reports an algorithm to identify pregnancies with a fetus affected by trisomy 13 or 18 by a combination of maternal age fetal nuchal translucency (NT) thickness, and maternal serum free beta-hCG and PAPP-A at 11-14 weeks of gestation. In this mixed trisomy group the median MoM NT was increased at 2.819, whilst the median MoMs for free beta-hCG and PAPP-A were reduced at 0.375 and 0.201 respectively. We predict that with the use of the combined trisomy 13 and 18 algorithm and a risk cut-off of 1 in 150 will for a 0.3% false positive rate allow 95% of these chromosomal defects to be identified at 11-14 weeks. Such algorithms will enhance existing first trimester screening algorithms for trisomy 21.
It is well established that the biochemical pattern in pregnancies affected by trisomies 13 or 18 are different from that of trisomy 21 in that free β-hCG levels are reduced and that the low levels of PAPP-A are carried through into the second trimester (Spencer et al., 1999b). It is therefore not Copyright possible to create an algorithm which will distinguish between trisomies 13 and 18. However, the construction of a combined algorithm would allow clear identification of at-risk pregnancies. Using our combined algorithm we predict that at a 1 in 150 risk cut-off 95% of cases could be identified for an invasive testing rate of 0.3%. This compares well with the 90% detection for a 5% false positive rate achieved retrospectively (Spencer et al.,1999a) and prospectively (Spencer et al., 2000b) for trisomy 21. We believe this simple algorithm would benefit and enhance screening procedures in the first trimester.
ΚΛΑΣΙΚΗ ΣΧΟΛΗ ΣΤΑ ΤΕΣΤ Β ΤΡΙΜΗΝΟΥ ΤΡΙΠΛΟ ALPHA ΤΕΣΤ
A patient-specific risk for Down syndrome is calculated using the levels of MSAFP/hCG/uE3/DIA as well as the maternal age at delivery. Approximately 4-5% of patients screened will have an increased risk for Down syndrome and will be offered further diagnostic testing such as ultrasound and amniocentesis. Currently, we recommend genetic counseling and the consideration of amniocentesis if the patient's Down syndrome risk is equal to or greater than 1 in 270. This cut-off risk is specific to our Screening Program and was chosen to create the lowest false positive rate
while optimizing our detection rate. We continue to monitor our Program's screening sensitivity and specificity, and for this reason, the cut-off risk may change over time. The current detection rate for Down syndrome using the WFUSM Maternal Serum Screening Program is 75-80% with a false-positive rate of 5%. Of note, approximately one half of our samples with an increased Down syndrome risk are based on incorrect gestational dating.
Literature reports suggest that low levels of maternal serum AFP, hCG and uE3 are associated with an increased risk for Trisomy 18, and that a patient-specific risk for Trisomy 18 can be calculated using maternal age in conjunction with AFP, hCG and uE3 values. The current detection rate for
Trisomy 18 using the WFUSM Maternal Serum Screening Program is approximately 90%, with a Revised 7/10 5 false-positive rate of 0.2%. Patients with a risk for Trisomy 18 equal to or greater than 1 in 100 will be offered the option of amniocentesis.
OI ΑΓΓΛΟΙ ΠΡΑΚΤΙΚΟΙ Σ Ε ΟΛΑ ΠΡΩΤΕΙΝΟΥΝ ΕΝΑ ΕΝΙΑΙΟ CUT OFF LEVEL 1/150 ΚΑΙ ΓΙΑ ΤΟ ΠΡΩΤΟ ΚΑΙ ΓΙΑ ΤΟ ΔΕΥΤΕΡΟ ΤΡΙΜΗΝΟ
NHS Fetal Anomaly Screening Programme
First trimester screening for Τ21 T18 and T13 syndromes
National draft policy proposal
Online consultation event
Current screening strategy
Screening for T21 is currently offered to all pregnant women in England in accordance with policy recommendations from the Department of Health and it is the only approved national policy which relates to fetal anomaly screening before 14 weeks of pregnancy.(6;7) Specific targets set out are set out by the NHS Fetal Anomaly Screening Programme (NHS FASP), one of several screening programmes working under the auspices of the UK National Screening Committee (UK NSC). The aim of T21 screening is to identify those women who have a risk of more than the ‘cut off’ value of 1 in 150 of having an affected baby at term. All services providing a T21 screening programme are expected to reach a ≥90% or greater detection rate (DR) for a ≤2% or less screen positive rate (SPR) using the ‘Combined Screening’ programme at 1 in 150 ‘at term’.i
Reform in this area should include the following:
a. All pregnant women should be offered the Combined Test which can screen for T21, T18 and T13 set at a cut off value of 1 in 150 ‘at term’.
b. A second trimester policy for a T18 (but not T13) single risk from Quadruple Screening at a cut off value of 1 in 150 ‘at term’ should become an additional part of existing T21 screening programme (BUT only where the Combined Screening Test cannot be performed or for women who book in the second trimester of pregnancy).
c. Women should be offered CVS in the first instance if they have a high risk (screen positive) composite single risk for T18/T13. Amniocentesis should be undertaken if a woman has been unable to participate in Combined Screening. Both procedures carry approximately a 1% risk of procedure related loss.iii
d. The type of laboratory analysis provided will depend on the indication for referral.
e. Placental tissue /amniotic fluid should be analysed in accordance with recommendations of the Association of Clinical Genetics (ACC) standards and guidelines.(25)
Benefits to women
f. First trimester Combined Screening is an effective way to screen for T18 and T13. In addition, it is possible to detect major malformations associated with these conditions such as: exomphalos, holoprosencephaly and megacystis when performing ultrasound assessment (fetal CRL and NT measurements) for the Combined Test in the first trimester.
g. Given the choice, women may wish to know whether their pregnancy may be affected by one of these conditions in order to prepare themselves emotionally and make an informed decision at an earlier time in pregnancy.
Policy summary Timeline to be agreed
As part of the first trimester Combined Screening programme incorporating an ultrasound examination and a maternal serum blood sample for measurement of:
Free-beta human chorionic gonadotrophin (free-βhCG)
Sonographic measurement of the fetal CRL (range 45.0mm to 84.0mm)
Sonographic measurement of the fetal Nuchal translucency
Or for those where Combined Screening cannot be undertaken or present later in pregnancy, Quadruple Screening should be offered (without Inhibin A). A maternal serum blood sample should be taken for biochemical analysis of:
Intact (total) or free-βhCG
The mid-trimester fetal anomaly scan should also be offered and undertaken from:
18 weeks, 0 days to 20 weeks, 6 days
Core screening standard: Timeframe to be agreed
For T21, T18 and T13 screening programme a 90% DR with an overall SPR of 2.2%
For T18 and T13 greater than >90% DR, for equal to, or less than ≤0.2%iv
1 in 150 cut off value at term for T21, T18 and T13 across both trimesters
Confirmatory testing for higher risk results
Chorionic villus sampling (CVS) under direct continuous ultrasound guidance for a ‘higher risk’ (screen positive) first trimester serum screening result
Amniocentesis under direct continuous ultrasound guidance for those who present later in pregnancy with a ‘higher risk’ (screen positive) result from Quadruple Screening or are found to have abnormal ultrasound findings. Confirmatory analysis