Diagnostic performance and costs of contingent screening models for trisomy 21 incorporating non-invasive prenatal testing (original) (raw)
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Journal of Maternal-fetal & Neonatal Medicine, 2017
Analysis of cell-free DNA in maternal blood has been proposed as a novel screening method for evaluation of aneuploidies. The higher performance of this technique in screening of trisomies compared to all currently available methods would lead to widespread use of this technique in clinical settings. In total, 1,066,829 singleton pregnancies referred to Nilou Clinical Laboratory were screened for chromosomal trisomies during a period of 12 years. First-trimester screening (FTS), Triple and Quad markers of second-trimester screening (STS) as well as integrated results have been obtained from 444,515, 34,984, 560,857 and 26,473 singleton pregnancies respectively. Non-invasive prenatal test (NIPT) using cfDNA was applied in 3500 pregnant women. Risk cutoffs, detection rates (DRs) and false positive rates (FPRs) were assessed for combinations of screening strategies to identify the most efficient strategy for contingent cfDNA testing. Contingent screening including FTS and NIPT offer to 20% of cases would lead to detection of 98% of fetuses with trisomy 21 at a total invasive testing rate of 1.1%. Contingent screening including STS and NIPT offer to 9.0% of cases would lead to detection of 95.5% of fetuses with trisomy 21 at a total invasive testing rate of 4.5%. Contingent screening including FTS or STS and cfDNA testing are efficient strategies for screening of trisomy 21.
First-trimester combined screening for trisomy 21 at 7-14 weeks' gestation
Ultrasound in Obstetrics and Gynecology
In each case the patient-specific risk for trisomy 21 was estimated by multiplying the individual maternal age-related risk by the LR for fetal NT according to the mixture model8 and the combined LR for maternal serum free β-hCG and PAPP-A. Crude, standardized and model-based detection rates and false-positive rates were obtained by taking the proportion of cases with risks above a given risk threshold. The crude performance of screening refers to the observed values in our dataset. Standardized performance of screening was estimated after adjustments to take into account the maternal age distribution of pregnancies in England and Wales in 2000–20029. Model-based estimates of screening performance were derived by examining simulated data from 500 000 unaffected pregnancies and 500 000 trisomy 21 pregnancies with the maternal age distribution of pregnancies in England and Wales in 2000–2002, fetal NT distributions according to the mixture model and log MoM free β-hCG and log MoM PAPP...
Prospective validation of first-trimester combined screening for trisomy 21
Ultrasound in Obstetrics and Gynecology, 2009
Objective To examine the performance of the new algorithm in screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A).
Ultrasound in Obstetrics & Gynecology, 2013
Objective To define risk cut-offs with corresponding detection rates (DR) and false-positive rates (FPR) in screening for trisomy 21 using maternal age and combinations of first-trimester biomarkers in order to determine which women should undergo contingent maternal blood cell-free (cf) DNA testing. (DV-PIV) at 11 + 0 to 13 + 6 weeks' gestation and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and alpha-fetoprotein (AFP) at 8 + 0 to 13 + 6 weeks. Estimates of risk cutoffs, DRs and FPRs were derived for combinations of biomarkers and these were used to define the best strategy for contingent cfDNA testing.
Comparison between disclosure and non-disclosure approaches for trisomy 21 screening tests
Human Reproduction, 2002
BACKGROUND: First-trimester nuchal translucency (NT) and second-trimester triple test (TT) are common screening programmes for trisomy 21. The aim of this study was to compare disclosure and non-disclosure approaches of combining those tests. METHODS: Likelihood ratios of both NT and TT tests, among 508 normal and 23 trisomy 21-affected pregnancies, were used for calculating population-adjusted risks. Disclosure approach incorporated all cases which, by either NT or TT, exhibited a risk ≥1:250 whereas non-disclosure approach generated a new integrated figure ≥1:250. RESULTS: Among women aged ≤34 years, the disclosure and nondisclosure approaches were associated with false positive rates of 4.3 and 1.1%, detection rates of 76.4 and 61.2%, positive predictive value (PPV) of 1:53 and 1:17, and false negative rate of 1:3129 and 1:1985 respectively. CONCLUSIONS: The disclosure approach resulted in considerably higher detection rates. The non-disclosure approach, however, was four times better regarding the number of invasive procedures required to detect one case of trisomy 21. However, the positive predictive value associated with the disclosure policy was still much more beneficial than that obtained in women aged ജ37 years, who are routinely referred to fetal karyotyping.
Ultrasound in Obstetrics and Gynecology, 2002
Objective To evaluate the performance of a one-stop clinic for assessment of risk (OSCAR) for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free β -human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation. Method Screening for trisomy 21 was carried out by OSCAR in 15 030 singleton pregnancies with live fetuses at 11-14 weeks. The estimated risk for trisomy 21 was calculated, and the women were counseled regarding this risk and the option of invasive testing or expectant management. Follow-up of the outcome of all pregnancies was carried out. The detection and false-positive rates for different risk cut-offs were calculated. Results Fetal NT and maternal serum free β -hCG and PAPP-A were successfully measured in all cases. Pregnancy outcome, including karyotype results or the birth of a phenotypically normal baby, was obtained from 14 383 cases. The median maternal age of these cases was 34 (range 15-49) years and in 6768 (47.1%) the age was 35 years or greater. The median gestation at screening was 12 (range 11-14) weeks and the median fetal crown-rump length was 64 (range 45-84) mm. The estimated risk for trisomy 21 based on maternal age, fetal NT and maternal serum free β -hCG and PAPP-A was 1 in 300 or greater in 6.8% (967 of 14 240) normal pregnancies, in 91.5% (75 of 82) of those with trisomy 21 and in 88.5% (54 of 61) of those with other chromosomal defects. For a fixed false-positive rate of 5% the respective detection rates of screening for trisomy 21 by maternal age alone, maternal age and serum free β -hCG and PAPP-A, maternal age and fetal NT, and by maternal age, fetal NT and maternal serum biochemistry were 30.5%, 59.8%, 79.3% and 90.2%, respectively. Conclusion Screening for trisomy 21 by a combination of maternal age, fetal NT and maternal serum biochemistry at 11-14 weeks can be provided in an OSCAR setting and is associated with a detection rate of about 90% for a false-positive rate of 5%.
Journal of Maternal-Fetal and Neonatal Medicine, 2014
Objective: To compare the policy of prenatal diagnosis versus first trimester screening of trisomy 21 among pregnant women of advanced age. Methods: A retrospective study was conducted on patients aged 35 divided in two groups: patients who requested first trimester combined test and only in case of screen-positive result underwent invasive testing (group A); patients undergoing chorionic villous sampling or amniocentesis as first investigation (group B). The following outcome variables were compared: antenatal detection of trisomy 21, occurrence of trisomy 21 at birth, miscarriage rate, hospitals' costs. Results: 4527 women were included. Of these, 534 (11.80%) underwent T21 screening whereas 3993 (88.20%) requested primary invasive testing. In group A, 64 combined test were positive (11.99%) and 8 trisomy 21 cases were diagnosed (1.50%); the loss of euploid fetuses after invasive procedure was 4.55% (2/44). No false-negative case was observed. In group B 57 cases of trisomy 21 were diagnosed (1.43%), and pregnancy loss rate of chromosomally normal fetuses was 0.45% (17/3806). The estimated cost was, respectively, 67.720E for the primary screening versus 1.996.500E for direct prenatal diagnosis. Conclusion: First trimester screening of trisomy 21 is highly accurate and cost saving among women 35.
The Australian & New Zealand journal of obstetrics & gynaecology, 2016
To provide data on how screen-positive and detection rates of first trimester prenatal screening for fetal Down syndrome vary with changes in the risk cut-off and maternal age to inform contingency criteria for publicly funded noninvasive prenatal testing. First trimester screening and diagnostic data were collected for all women attending for first trimester fetal aneuploidy screening in Western Australia between 2005 and 2009. Prenatal screening and diagnostic data were linked to pregnancy outcomes, including data from the Midwives' Notification System and the Western Australian Registry of Developmental Anomalies. The prevalence of Down syndrome and performance of screening by risk cut-off and/or for women >35 years were analysed. The current screening risk cut-off of 1:300 has screen-positive and detection rates of 3.5% and 82%. The screen-positive rate increases by 0.7-0.8% for each 100 point change in risk, up to 19.2% at 1:2500 (96% detection rate). Including all women...