08860297500V3.

Elecsys free βhCG

cobas e 411
08860297190 08860297500 100 cobas e 601
cobas e 602

English Test principle

System information Sandwich principle. Total duration of assay: 18 minutes.
For cobas e 411 analyzer: test number 690 ▪ 1st incubation: 10 µL of sample, biotinylated monoclonal βhCG‑specific
For cobas e 601 and cobas e 602 analyzers: Application Code antibodies, and a monoclonal free βhCG‑specific antibody labeled with a
Number 033 ruthenium complexa) react to form a sandwich complex.
Please note ▪ 2nd incubation: After addition of streptavidin-coated microparticles, the
complex becomes bound to the solid phase via interaction of biotin and
The measured free βhCG value of a patient’s sample can vary depending streptavidin.
on the testing procedure used. The laboratory finding must therefore ▪ The reaction mixture is aspirated into the measuring cell where the
always contain a statement on the free βhCG assay method used. microparticles are magnetically captured onto the surface of the
Free βhCG values determined on patient samples by different testing electrode. Unbound substances are then removed with
procedures cannot be directly compared with one another and could be ProCell/ProCell M. Application of a voltage to the electrode then induces
the cause of erroneous medical interpretations. If there is a change in the chemiluminescent emission which is measured by a photomultiplier.
free βhCG assay procedure used while monitoring therapy, then the ▪ Results are determined via a calibration curve which is instrument-
free βhCG values obtained upon changing over to the new procedure specifically generated by 2‑point calibration and a master curve provided
via the reagent barcode or e‑barcode.
must be confirmed by parallel measurements with both methods.
a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy) )
Intended use Reagents - working solutions
Immunoassay for the in vitro quantitative determination of free βhCG The reagent rackpack is labeled as F‑BHCG.
(free β‑subunit of human chorionic gonadotropin) in human serum. This
assay is intended for the use as one component in combination with other M Streptavidin-coated microparticles (transparent cap), 1 bottle, 6.5 mL:
parameters to evaluate the risk of trisomy 21 (Down syndrome) during the Streptavidin-coated microparticles 0.72 mg/mL; preservative.
first trimester of pregnancy. Further testing is required for diagnosis of
chromosomal aberrations. R1 Anti-βhCG-Ab~biotin (gray cap), 1 bottle, 9 mL:
The electrochemiluminescence immunoassay “ECLIA” is intended for use Biotinylated monoclonal anti‑βhCG antibody (mouse) 3.5 mg/L;
on cobas e immunoassay analyzers. phosphate buffer 40 mmol/L, pH 6.8; preservative.
Summary R2 Anti-free βhCG-Ab~Ru(bpy) (black cap), 1 bottle, 10 mL:
Human chorionic gonadotropin (hCG) is a glycoprotein hormone (~37 kDa) Monoclonal anti‑free βhCG antibody (mouse) labeled with ruthenium
composed of 2 noncovalently linked subunits – the α- and β‑chain (~15 and complex 1.6 mg/L; phosphate buffer 40 mmol/L, pH 7.0; preservative.
22 kDa respectively). The protein is produced by trophoblast tissue; it
serves to maintain the corpus luteum during the early weeks of pregnancy Precautions and warnings
and it stimulates progesterone production.1,2,3,4 For in vitro diagnostic use for health care professionals. Exercise the
Naturally, hCG appears only in blood and urine of pregnant women. The normal precautions required for handling all laboratory reagents.
concentration of hCG rises exponentially in the first trimester of pregnancy Infectious or microbial waste:
to peak around 9th week of gestation.5 Subsequently, the hormone level Warning: handle waste as potentially biohazardous material. Dispose of
decreases between gestational weeks ~10‑16 to approximately one‑fifth of waste according to accepted laboratory instructions and procedures.
peak concentration and remains at this level until term. In non‑pregnant
women, hCG can be produced by trophoblastic and non‑trophoblastic Environmental hazards:
tumors and germ cell tumors with trophoblastic components.2,3,4,5,6 Apply all relevant local disposal regulations to determine the safe disposal.
The serum of pregnant women mainly contains intact hCG. However, minor Safety data sheet available for professional user on request.
fraction of α- and β‑subunits circulate in an unbound form. The proportion of This kit contains components classified as follows in accordance with the
free βhCG averages ~1 % compared to intact hCG. As a result of the Regulation (EC) No. 1272/2008:
protein degradation process, additional hCG variants can be detected in
blood and urine (e.g. nicked hCG, nicked βhCG, β core fragment).
However, only the intact hormone is biologically active.3,7
Free βhCG in combination with serum pregnancy‑associated plasma
protein A (PAPP‑A) and the sonographic determination of nuchal
translucency (NT) identifies women at an increased risk of carrying a fetus Warning
affected with Down syndrome during the first trimester (week 8‑14) of
pregnancy.8,9,10 Using this marker combination, detection rates of up to H317 May cause an allergic skin reaction.
70 % (serum markers only) and 90 % (combined with NT) have been
described at a false positive rate of 5 %.11,12,13 Prevention:
When the sonographic examination also includes the presence of the nasal P261 Avoid breathing mist or vapours.
bone, the detection rate was found to reach 97 %.14
Based on the maternal age, the risk for having a Down syndrome P272 Contaminated work clothing should not be allowed out of
pregnancy can be calculated using a specific algorithm.9,15,16 the workplace.
Based on the risk assessment thus obtained, Non-Invasive Prenatal Testing
(NIPT) based on circulating cell-free fetal DNA may be indicated.17,18,19,20 P280 Wear protective gloves.
Women found to have increased risk of aneuploidy with 1st trimester
screening should be offered genetic counselling and the option of Chorionic Response:
Villus Sampling (CVS) or amniocentesis.21
P333 + P313 If skin irritation or rash occurs: Get medical
advice/attention.

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Elecsys free βhCG

P362 + P364 Take off contaminated clothing and wash it before reuse. ▪ 11706802001, AssayCup, 60 x 60 reaction cups
Disposal: ▪ 11706799001, AssayTip, 30 x 120 pipette tips
▪ 11800507001, Clean‑Liner
P501 Dispose of contents/container to an approved waste
For risk calculation of trisomy 21:
disposal plant.
▪ 08860173190, Elecsys PAPP‑A, 100 tests
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590 ▪ 04854101200, PAPP‑A CalSet, for 4 x 1.0 mL
Avoid foam formation in all reagents and sample types (specimens, ▪ A suitable software
calibrators and controls). Additional materials for cobas e 601 and cobas e 602 analyzers:
Reagent handling ▪ 04880340190, ProCell M, 2 x 2 L system buffer
The reagents in the kit have been assembled into a ready‑for‑use unit that ▪ 04880293190, CleanCell M, 2 x 2 L measuring cell cleaning
cannot be separated. solution
All information required for correct operation is read in from the respective ▪ 03023141001, PC/CC‑Cups, 12 cups to prewarm ProCell M and
reagent barcodes. CleanCell M before use
Storage and stability ▪ 03005712190, ProbeWash M, 12 x 70 mL cleaning solution for run
Store at 2‑8 °C. finalization and rinsing during reagent change
Do not freeze. ▪ 12102137001, AssayTip/AssayCup, 48 magazines x 84 reaction
Store the Elecsys reagent kit upright in order to ensure complete cups or pipette tips, waste bags
availability of the microparticles during automatic mixing prior to use. ▪ 03023150001, WasteLiner, waste bags
Stability: ▪ 03027651001, SysClean Adapter M
Additional materials for all analyzers:
unopened at 2‑8 °C up to the stated expiration date
▪ 11298500316, ISE Cleaning Solution/Elecsys SysClean,
after opening at 2‑8 °C 12 weeks 5 x 100 mL system cleaning solution
on the analyzers 4 weeks Assay
Specimen collection and preparation For optimum performance of the assay follow the directions given in this
document for the analyzer concerned. Refer to the appropriate operator’s
Only the specimens listed below were tested and found acceptable. manual for analyzer‑specific assay instructions.
Serum collected using standard sampling tubes or tubes containing Resuspension of the microparticles takes place automatically prior to use.
separating gel. Read in the test-specific parameters via the reagent barcode. If in
Do not use plasma. exceptional cases the barcode cannot be read, enter the 15-digit sequence
Stable for 25 hours at 15‑25 °C, 8 days at 2‑8 °C, 12 months at -20 °C of numbers.
(± 5 °C). The samples may be frozen 3 times. Bring the cooled reagents to approximately 20 °C and place on the reagent
The sample types listed were tested with a selection of sample collection disk (20 °C) of the analyzer. Avoid foam formation. The system
tubes that were commercially available at the time of testing, i.e. not all automatically regulates the temperature of the reagents and the
available tubes of all manufacturers were tested. Sample collection systems opening/closing of the bottles.
from various manufacturers may contain differing materials which could Calibration
affect the test results in some cases. When processing samples in primary Traceability: This method has been standardized against the International
tubes (sample collection systems), follow the instructions of the tube Reference Preparation of Chorionic Gonadotrophin β subunit from the
manufacturer. National Institute for Biological Standards and Control (NIBSC),
Centrifuge samples containing precipitates before performing the assay. code 75/551.
Do not use heat‑inactivated samples. Every Elecsys reagent set has a barcoded label containing specific
Do not use samples and controls stabilized with azide. information for calibration of the particular reagent lot. The predefined
Ensure the samples, calibrators and controls are at 20‑25 °C prior to master curve is adapted to the analyzer using the relevant CalSet.
measurement. Calibration frequency: Calibration must be performed once per reagent lot
Due to possible evaporation effects, samples, calibrators and controls on using fresh reagent (i.e. not more than 24 hours since the reagent kit was
the analyzers should be analyzed/measured within 2 hours. registered on the analyzer).
Calibration interval may be extended based on acceptable verification of
Materials provided calibration by the laboratory.
See “Reagents – working solutions” section for reagents. Renewed calibration is recommended as follows:
Materials required (but not provided) ▪ after 12 weeks when using the same reagent lot
▪ 04854080200, free βhCG CalSet, for 4 x 1.0 mL ▪ after 7 days when using the same reagent kit on the analyzer
▪ 08740062190, PreciControl Maternal Care, for 6 x 3.0 mL ▪ as required: e.g. quality control findings outside the defined limits
▪ 11732277122, Diluent Universal, 2 x 16 mL sample diluent or Quality control
03183971122, Diluent Universal, 2 x 36 mL sample diluent
For quality control, use PreciControl Maternal Care.
▪ General laboratory equipment
In addition, other suitable control material can be used.
▪ cobas e analyzer Controls for the various concentration ranges should be run individually at
Additional materials for the cobas e 411 analyzer: least once every 24 hours when the test is in use, once per reagent kit, and
▪ 11662988122, ProCell, 6 x 380 mL system buffer following each calibration.
▪ 11662970122, CleanCell, 6 x 380 mL measuring cell cleaning The control intervals and limits should be adapted to each laboratory’s
solution individual requirements. Values obtained should fall within the defined
limits. Each laboratory should establish corrective measures to be taken if
▪ 11930346122, Elecsys SysWash, 1 x 500 mL washwater additive values fall outside the defined limits.
▪ 11933159001, Adapter for SysClean If necessary, repeat the measurement of the samples concerned.

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Elecsys free βhCG

Follow the applicable government regulations and local guidelines for automatically by the analyzers or manually). The concentration of the
quality control. diluted sample must be ≥ 15 IU/L.
Calculation After manual dilution, multiply the result by the dilution factor.
The analyzer automatically calculates the analyte concentration of each After dilution by the analyzers, the software automatically takes the dilution
sample (either in IU/L, mIU/mL or ng/mL). into account when calculating the sample concentration.
Conversion factors: IU/L x 1 = mIU/mL Expected values and clinical performance
The following results were obtained with the Elecsys free βhCG assay:
IU/L x 1 = ng/mL
1. Reference range study using a panel of samples from 251 healthy non-
mIU/mL x 1 = ng/mL pregnant female donors (Roche study No. R04P026)
Limitations - interference All results were below the lower detection limit of < 0.1 IU/L.
The effect of the following endogenous substances and pharmaceutical 2. Performance evaluation study of the Elecsys free βhCG assay and the
compounds on assay performance was tested. Interferences were tested Elecsys PAPP‑A assay in first trimester trisomy 21 risk assessment (Roche
up to the listed concentrations and no impact on results was observed. study No. B05P020 and Roche study No. CIM 000950)22
Measurements with the Elecsys free βhCG assay and the Elecsys PAPP‑A
Endogenous substances assay were conducted in 6 clinical centers in Belgium, Switzerland,
Compound Concentration tested Denmark, England and Germany. For the first trimester 4746 free βhCG
values were available (gestational weeks 8+0 to 13+6). Median values were
Bilirubin ≤ 428 µmol/L or ≤ 25 mg/dL estimated for each day of the respective gestational age by regression of
the calculated medians per day (for details refer to the software SsdwLab).
Hemoglobin ≤ 0.621 mmol/L or ≤ 1000 mg/dL The table below shows the number of single values available for each week
Intralipid ≤ 1500 mg/dL and the median predicted by the regression function for the middle day of
the respective week (week n+3). Gestational age was calculated from
Biotin ≤ 4912 nmol/L or ≤ 1200 ng/mL ultrasound crown-to-rump length (CRL) according to Robinson.23
Rheumatoid factors ≤ 1000 IU/mL
Gestational week 8+0 to 9+0 to 10+0 11+0 12+0 13+0
IgG ≤ 7.0 g/dL 8+6 9+6 to to to to
Criterion: For concentrations ≤ 10 IU/L the deviation is ≤ 1.0 IU/L. For 10+6 11+6 12+6 13+6
concentrations > 10 IU/L the deviation is ≤ 10 %. Number of 178 302 465 805 1557 1439
There is no high-dose hook effect at free βhCG concentrations up to samples
800 IU/L.
Pharmaceutical substances Median value at 70.7 75.5 57.3 42.8 34.5 29.5
In vitro tests were performed on 18 commonly used pharmaceuticals. No the middle of the
interference with the assay was found. week (IU/L)
In rare cases, interference due to extremely high titers of antibodies to Each laboratory should investigate the transferability of the expected values
analyte‑specific antibodies, streptavidin or ruthenium can occur. These to its own patient population and if necessary determine its own reference
effects are minimized by suitable test design. ranges.
For diagnostic purposes, the results should always be assessed in For prenatal testing it is recommended that the median values be re-
conjunction with the patient’s medical history, clinical examination and other evaluated periodically.
findings.
Clinical performance data
Limits and ranges In total, 2629 samples from clinical routine with known outcome were
Measuring range examined. 107 out of the 2629 samples were from pregnancies with
0.1‑190 IU/L (defined by the Limit of Blank and the maximum of the master confirmed Down syndrome. All samples were measured in parallel with
curve). Values below the Limit of Blank are reported as < 0.1 IU/L. Values FMF (Fetal Medicine Foundation) certified PAPP‑A and free βhCG tests.
above the measuring range are reported as > 190 IU/L (or up to 1900 IU/L Risk calculation was performed using a commercial software. This software
for 10‑fold diluted samples). makes use of an algorithm described by Palomaki et al.24 by means of the
mathematical calculations for Gaussian multivariate distribution as already
Lower limits of measurement published.25 Risk analysis is based on maternal age, nuchal translucency as
Limit of Blank, Limit of Detection and Limit of Quantitation well as on the results of the biochemical parameters, corrected by different
Limit of Blank = 0.1 IU/L factors such as maternal weight, smoking and ethnic background of the
pregnant woman.
Limit of Detection = 0.3 IU/L
Individual risk calculation
Limit of Quantitation = 0.5 IU/L
The calculation of a woman’s individual risk of carrying a single fetus
The Limit of Blank, Limit of Detection and Limit of Quantitation were affected by trisomy 21 was assessed without consideration of nuchal
determined in accordance with the CLSI (Clinical and Laboratory Standards translucency (NT) data to demonstrate the performance of the biochemical
Institute) EP17‑A2 requirements. methods. Maternal weight and smoking behavior were taken into account
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of as correction factors. Concordance of risk analysis compared to a
analyte‑free samples over several independent series. The Limit of Blank competitor method was examined using the cutoff value established in the
corresponds to the concentration below which analyte‑free samples are participating laboratory.26,27
found with a probability of 95 %. It is the responsibility of the user to choose the cutoff which will apply for
The Limit of Detection is determined based on the Limit of Blank and the further procedures.
standard deviation of low concentration samples. The Limit of Detection Concordance analysis data
corresponds to the lowest analyte concentration which can be detected
(value above the Limit of Blank with a probability of 95 %). A. Concordance analysis in unaffected pregnancies (n = 2522)
The Limit of Quantitation is the lowest analyte concentration that can be Cutoff 5 % FPR* Risk > cutoff (Roche**) Risk < cutoff (Roche**)
reproducibly measured with an intermediate precision CV of ≤ 20 %.
Risk > cutoff 109 (4.32 %) 18 (0.71 %)
Dilution
(competitor***)
Samples with free βhCG concentrations above the measuring range can be
diluted with Diluent Universal. The recommended dilution is 1:10 (either

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Cutoff 5 % FPR* Risk > cutoff (Roche**) Risk < cutoff (Roche**) Method comparison
Risk < cutoff 17 (0.67 %) 2378 (94.3 %) A comparison of the Elecsys free βhCG assay, 04854071200 (y) with a
commercially available free βhCG assay (x) using human sera gave the
(competitor***) following correlations:
In 2522 unaffected samples the Roche methods correctly classified Number of samples measured: 3373
2396 samples (specificity: 95.0 %) in comparison to 2395 (specificity:
95.0 %) correctly classified by the competitor methods. Passing/Bablok28 Linear regression
B. Detection rate in confirmed trisomy 21 pregnancies (n = 107) y = 0.944x - 2.74 y = 0.994x - 4.84
Cutoff 5 % FPR* Risk > cutoff (Roche**) Risk < cutoff (Roche**) τ = 0.902 r = 0.976
Risk > cutoff 86 (80.4 %) 0 The sample concentrations were between 4.96 and 187 IU/L.
(competitor***) Analytical specificity
Risk < cutoff 4 (3.74 %) 17 (15.9 %) Cross-reactivity against intact hCG < 0.05 %. No cross-reactivity against
(competitor***) hCGα chain and TSH detectable.
In 107 affected samples the Roche methods showed a detection rate of References
84.1 % (90/107) in comparison to 80.4 % (86/107) obtained with the 1 Berger P, Sturgeon C, Bidart JM, et al. The ISOBM TD-7 Workshop on
competitor methods. hCG and Related Molecules. Tumor Biol 2002;23:1-38.
* FPR = False positive rate 2 Sturgeon CM, McAllister EJ. Analysis of hCG: clinical applications and
** Combination of results from the Elecsys free βhCG assay and the Elecsys PAPP‑A assay assay requirements. Ann Clin Biochem 1998;35:460-491.
*** Combination of results from the competitor's free βhCG and PAPP‑A methods 3 Cole LA. Immunoassay of human chorionic gonadotropin, its free
subunits, and metabolites. Clin Chem 1997;43(12):2233-2243.
Specific performance data
Representative performance data on the analyzers are given below. 4 Alfthan H, Stenman UH. Pathophysiological importance of various
Results obtained in individual laboratories may differ. molecular forms of human choriogonadotropin. Mol Cell Endocrinol
1996;125:107-120.
Precision
5 Berry E, Aitken DA, Crossley JA, et al. Analysis of maternal serum
Precision was determined using Elecsys reagents, pooled human sera and alpha-fetoprotein and free beta human chorionic gonadotrophin in the
controls in a protocol (EP05‑A3) of the CLSI (Clinical and Laboratory first trimester: implications for Down’s syndrome screening. Prenat
Standards Institute): 2 runs per day in duplicate each for 21 days (n = 84). Diagn 1995;15(6):555-565.
The following results were obtained:
6 Marcillac I, Troalen F, Bidart JM, et al. Free Human Chorionic
cobas e 411 analyzer Gonadotropin β Subunit in Gonadal and Nongonadal Neoplasms.
Cancer Res 1992;52:3901-3907.
Repeatability Intermediate
precision 7 Kardana A, Cole LA. Polypeptide Nicks Cause Erroneous Results in
Assays of Human Chorionic Gonadotropin Free β-Subunit. Clin Chem
Sample Mean SD CV SD CV 1992;38(1):26-33.
IU/L IU/L % IU/L % 8 Canick JA, Lambert-Messerlian GM, Palomaki GE, et al. Comparison of
Human serum 1 0.517 0.012 2.3 0.019 3.7 Serum Markers in First-Trimester Down Syndrome Screening. Obstet &
Gynecol 2006;108(5):1192-1199.
Human serum 2 9.09 0.182 2.0 0.422 4.6
9 Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks.
Human serum 3 9.29 0.230 2.5 0.467 5.0 Prenat Diagn 2011:31(1);7-15.
Human serum 4 89.7 2.05 2.3 3.95 4.4 10 Spencer K, Crossley JA, Aitken DA, et al. Temporal changes in
maternal serum biochemical markers of trisomy 21 across the first and
Human serum 5 181 3.45 1.9 8.96 5.0 second trimester of pregnancy. Ann Clin Biochem 2002;39:567-576.
PCb) Maternal Care 1 15.6 0.409 2.6 0.524 3.4 11 Wald NJ, Rodeck C, Hackshaw AK, et al. First and second trimester
PC Maternal Care 2 51.3 1.25 2.4 1.68 3.3 antenatal screening for Down’s syndrome: the results of the Serum,
Urine and Ultrasound Screening Study (SURUSS). J Med Screen
PC Maternal Care 3 103 2.37 2.3 2.97 2.9 2003;10(2):56-104.
b) PC = PreciControl 12 Malone FD, Canick JA, Ball RH, et al. First-Trimester or Second-
Trimester Screening, or Both, for Down’s Syndrome. N Engl J Med
cobas e 601 and cobas e 602 analyzers 2005;353(19):2001-2011.
Repeatability Intermediate 13 Nicolaides KH, Spencer K, Avgidou K, et al. Multicenter study of first-
precision trimester screening for trisomy 21 in 75821 pregnancies: results and
estimation of the potential impact of individual risk-orientated two-stage
Sample Mean SD CV SD CV first-trimester screening. Ultrasound Obstet Gynecol 2005;25:221-226.
IU/L IU/L % IU/L %
14 Cicero S, Bindra R, Rembouskos G, et al. Integrated ultrasound and
Human serum 1 0.484 0.014 3.0 0.024 4.9 biochemical screening for trisomy 21 using fetal nuchal translucency,
absent fetal nasal bone, free β-hCG and PAPP-A at 11 to 14 weeks.
Human serum 2 8.23 0.234 2.8 0.339 4.1 Prenat Diagn 2003;23:306-310.
Human serum 3 8.41 0.218 2.6 0.380 4.5 15 Kagan KO, Wright D, Baker A, et al. Screening for trisomy 21 by
Human serum 4 81.8 1.84 2.2 2.96 3.6 maternal age, fetal nuchal translucency thickness, free beta-human
chorionic gonadotropin and pregnancy-associated plasma protein-A.
Human serum 5 174 4.50 2.6 7.79 4.5 Ultrasound Obstet Gynecol 2008;31:618-624.
PC Maternal Care 1 15.4 0.258 1.7 0.594 3.8 16 Ghaffari S, Tahmasebpour AR, Jamal A, et al. First-trimester screening
PC Maternal Care 2 51.1 0.774 1.5 2.05 4.0 for chromosomal abnormalities by integrated application of nuchal
translucency, nasal bone, tricuspid regurgitation and ductus venosus
PC Maternal Care 3 103 1.54 1.5 4.16 4.0 flow combined with maternal serum free β-hCG and PAPP-A: a 5-years
prospective study. Ultrasound Obstet Gynecol 2012;39:528-534.

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17 Nicolaides KH, Syngelaki A, Poon LC, et al. First-Trimester Contingent
Screening for Trisomies 21, 18 and 13 by Biomarkers and Maternal
Blood Cell-Free DNA Testing. Fetal Diagn Ther 2014;35:185-192.
Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305 Mannheim
18 Russo ML, Blakemore KJ. A historical and practical review of first www.roche.com
trimester aneuploidy screening. SeminFetal & Neonatal Medicine 2014 +800 5505 6606
19(3):183-187.
19 Evans MI, Sonek JD, Hallahan TW, et al. Cell-free fetal DNA screening
in the USA: a cost analysis of screening strategies. Ultrasound Obstet
Gynecol 2015;45(1):74-83.
20 Wright D, Wright A, Nicolaides KH. A unified approach to risk
assessment for fetal aneuploidies. Ultrasound Obstet Gynecol
2015;45(1):48-54.
21 ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No.
77. Obstet Gynecol 2007;109(1):217-227.
22 Tørring N, Aulesa C, Eiben B, et al. Performance characteristics of
Elecsys free βhCG and PAPP-A for first trimester trisomy 21 risk
assessment in gestational weeks 8+0 to 14+0. LaboratoriumsMedizin
2016:40(1);21–29.
23 Robinson HP, Fleming JEE. A critical evaluation of sonar “crown-rump
length” measurements. Br J Obstet Gynaecol 1975;82:702-710.
24 Palomaki GE, Haddow JE. Maternal serum α-fetoprotein, age, and
Down syndrome risk. Am J Obstet Gynecol 1987;156:460-463.
25 Reynolds TM, Penney MD. The mathematical basis of multivariate risk
screening: with special reference to screening for Down’s syndrome
associated pregnancy. Ann Clin Biochem 1989;27:452-458.
26 Bray I, Wright DE, Davies C, et al. Joint estimation of Down syndrome
risk and ascertainment rates: A meta-analysis of nine published data
sets. Prenat Diagn 1998;18:9-20.
27 Benn PA. Advances in prenatal screening for Down syndrome: I.
General principles and second trimester testing. Clin Chim Acta
2002;323:1-16.
28 Bablok W, Passing H, Bender R, et al. A general regression procedure
for method transformation. Application of linear regression procedures
for method comparison studies in clinical chemistry, Part III.
J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.
For further information, please refer to the appropriate operator’s manual for
the analyzer concerned, the respective application sheets and the Method
Sheets of all necessary components (if available in your country).
A point (period/stop) is always used in this Method Sheet as the decimal
separator to mark the border between the integral and the fractional parts of
a decimal numeral. Separators for thousands are not used.
Any serious incident that has occurred in relation to the device shall be
reported to the manufacturer and the competent authority of the Member
State in which the user and/or the patient is established.
The Summary of Safety & Performance Report can be found here:
https://ec.europa.eu/tools/eudamed
Symbols
Roche Diagnostics uses the following symbols and signs in addition to
those listed in the ISO 15223‑1 standard (for USA: see dialog.roche.com for
definition of symbols used):
Contents of kit
Analyzers/Instruments on which reagents can be used
Reagent
Calibrator
Volume for reconstitution
GTIN Global Trade Item Number

COBAS, COBAS E, ELECSYS and PRECICONTROL are trademarks of Roche. INTRALIPID is a trademark of
Fresenius Kabi AB.
All other product names and trademarks are the property of their respective owners.
Additions, deletions or changes are indicated by a change bar in the margin.
© 2022, Roche Diagnostics

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