Delta‐NT or NT MoM: which is the most appropriate method for calculating accurate patient‐specific risks for trisomy 21 in the first trimester?

Spencer, Kevin; Bindra, Renu; Nix, A. B. J.; Heath, V.; Nicolaides, Kypros H.

doi:10.1002/uog.186

Cited by 122 publications

(108 citation statements)

References 18 publications

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“…All scans were carried out by sonographers who had obtained The Fetal Medicine Foundation Certificate of Competence in the 11 +0 to 13 +6 week scan (www.fetalmedicine.com). Patient-specific risks were calculated by a multivariate approach using biochemical population parameters outlined in a previous study (Spencer et al, 1999), LRs based on delta NT outlined in a previous study (Spencer et al, 2003b) and the gestational age-related risk of trisomy 21 at the time of screening . Data on pregnancy outcome were obtained from the cytogenetics laboratories, the National Chromosomal Anomaly Register, the patients themselves, their general practitioners or the maternity units in which they delivered.…”

Section: Methodsmentioning

confidence: 99%

“…To take account of gestational variation of foetal NT, we expressed the measured foetal NT as the difference from the normal median NT (Snijders et al, 1998;Spencer et al, 2003a) at the measured CRL, this being the delta NT. The delta NT approach has been shown to be more appropriate than the conventional MoM approach for handling NT data and calculating patient-specific risks (Spencer et al, 2003b).…”

Section: Methodsmentioning

confidence: 99%

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Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Spencer

Cowans²,

Nicolaides³

2007

Prenatal Diagnosis

183

113

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Background Low levels of pregnancy associated plasma protein-A (PAPP-A) have been previously shown to be associated with pregnancies that subsequently develop pre-eclampsia. The objective of this study was to establish the relative risk for pre-eclampsia at various PAPP-A levels as an aid to counselling and follow up of pregnancies.Methods Maternal serum PAPP-A and free ß-human chorionic gonadotropin (ß-hCG) levels at 11 to 13 weeks of gestation from 224 singleton pregnancies that subsequently developed pre-eclampsia were compared to those from 47 770 normal singleton pregnancies resulting in live births after 37 weeks with birth weight greater than or equal to the 10th centile of normal for gestation. In all cases, the measured PAPP-A and free ß-hCG levels were expressed as multiple of the median (MoM). The association between metabolite levels and the incidence of pre-eclampsia was assessed by comparing the relative incidence at a number of MoM cut-offs and at various centiles. At various marker levels, the likelihood ratio for pre-eclampsia was also calculated. ResultsIn the pre-eclampsia group the median PAPP-A MoM was significantly reduced (0.772 MoM, p < 0.0001) whilst the median free β-hCG MoM was not different from controls (0.981 MoM, p = 0.26). With decreasing levels of PAPP-A, the likelihood ratio for pre-eclampsia increased. At the 5th centile of normal (PAPP-A MoM 0.415) the odds ratio was increased 4-fold and at this cut-off 15% of cases of pre-eclampsia would be identified. ConclusionsThe graphical presentation of a likelihood ratio curve for pre-eclampsia at any PAPP-A MoM level is likely to be useful in counselling women with low levels of PAPP-A and a normal karyotype. Use of low levels of PAPP-A for selecting women for further follow-up with uterine artery Doppler may further improve the clinical discrimination.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Spencer

Cowans²,

Nicolaides³

2007

Prenatal Diagnosis

183

113

View full text Add to dashboard Cite

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“…The small ticks labeled "a," "b," and "c" to the right of the log SD plot indicate estimates for this parameter, reported from three large published datasets. 15 are all based on NT MoM levels using either sonographer-specific medians 5,12,15 or a single set of medians with strict adherence to a specified methodology. 15 These three estimates are higher than 86%, 76%, and 69% of the computed standard deviations for the 140 assessed sonographers, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…15 are all based on NT MoM levels using either sonographer-specific medians 5,12,15 or a single set of medians with strict adherence to a specified methodology. 15 These three estimates are higher than 86%, 76%, and 69% of the computed standard deviations for the 140 assessed sonographers, respectively. Table 3 summarizes the number of sonographers who are outside of the target range for one or more of the quality assessment parameters, stratified by laboratory.…”

Section: Methodsmentioning

confidence: 99%

Quality assessment of routine nuchal translucency measurements: a North American laboratory perspective

Palomaki

Neveux

Donnenfeld³

et al. 2008

Genetics in Medicine

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Purpose: To assess nuchal translucency measurements that were performed as part of routine prenatal screening for Down syndrome. Methods: Collect ultrasound measurements of nuchal translucency and crown rump length provided by individual sonographers over a 6-month period to six North American prenatal screening laboratories, along with the laboratory's nuchal translucency interpretation in multiples of the median. For sonographers with 50 or more observations, compute three nuchal translucency quality measures (medians, standard deviations, and slopes), based on epidemiological monitoring. Results: Altogether, 23,462 nuchal translucency measurements were submitted by 850 sonographers. Among the 140 sonographers (16%) who submitted more than 50 observations, 76 (54%) were found to have all three quality measures in the target range. These 140 sonographers collectively accounted for 14,210 nuchal translucency measurements (61%). The most common single measure to be out of range was nuchal translucency multiples of the median, found for 29 of the 140 sonographers (21%). Nuchal translucency (NT) is defined as the collection of fluid behind the fetal neck occurring in the first trimester of pregnancy. 1-3 When measured and interpreted correctly, it is the most discriminatory marker for Down syndrome that has been reported in a routine setting. Univariately, NT measurements can identify about 60% of Down syndrome pregnancies in the first trimester at a 5% false-positive rate. 4 Detection increases to between 80% and 85%, when NT is combined with first trimester biochemical measurements of pregnancyassociated plasma protein-A (PAPP-A) and human chorionic gonadotropin (the intact, total, or free-␤ subunit forms). 4 When NT measurements are incorporated into the integrated test (NT and PAPP-A measurements in the first trimester) and the quadruple test (␣-fetoprotein, unconjugated estriol, human chorionic gonadotropin and dimeric inhibin-A in the second trimester), 85-90% detection is achievable at a false-positive rate of 2% or less. 5,6 Acquiring the skill to properly measure NT requires specialized training and oversight. 7 Recognizing this, several national and international programs have been established to train and qualify sonographers, and also to assess their ability to consistently and accurately quantify the NT thickness. 8 -11 The hands-on performance training is usually evaluated through still images submitted to one, or a panel of, expert sonographers. Several research trials using NT measurements have shown that such training, although necessary, is not sufficient to assure reproducibility of absolute measurements among sonographers. For example, both the Serum, Urine and Ultrasound Screening Study (SURUSS) 5 and First and Second Trimester Evaluation of Risk (FASTER) study 12 found that use of sonographer-specific reference data (medians) resulted in improved screening performance.In the current study, information was sought from screening laboratories regarding how they deal with NT measurements

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“…At the Harold Wood Hospital, King George Hospital and the Fetal Medicine Centre chorionicity was recorded in twin pregnancies by the identification of the lambda sign in dichorionic twins (Monteagudo et al, 1994;Sepulveda et al, 1996Sepulveda et al, , 1997. Patient-specific risks were calculated by a multivariate approach using biochemical population parameters outlined in a previous study (Spencer et al, 1999), likelihood ratios based on delta NT outlined in a previous study (Spencer et al, 2003a) and the gestational age-related risk of trisomy 21 at the time of screening . Data on pregnancy outcome were obtained from the cytogenetics laboratories, the National Chromosomal Anomaly Register, the patients themselves, their general practitioners or the maternity units in which they delivered.…”

Section: Methodsmentioning

confidence: 99%

Screening for trisomy 21 in twin pregnancies in the first trimester: an update of the impact of chorionicity on maternal serum markers

2008

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Objective To examine the distribution of first-trimester biochemical markers of aneuploidy in twin pregnancies, and to assess whether there are differences in the distributions between monochorionic and dichorionic twins.Methods Maternal serum-free β-hCG and PAPP-A were measured between 11 + 0 and 13 + 6 weeks as part of a routine first-trimester screening program in conjunction with fetal nuchal translucency (NT) performed at two sites. Data from twin pregnancies were extracted from the fetal databases along with information on the chorionicty. The individual marker concentrations were expressed as weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM using data from singleton pregnancies as the reference. The overall medians were compared to those in singleton pregnancies and between monochorionic and dichorionic twins.Results Data was available from 1914 sets of twins. Of these, 1214 had information with respect to chorionicity, with 1024 being dichorionic and 190 being monochorionic. The overall median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM amongst twin pregnancies were 2.023 for free β-hCG (sd log 10 MoM = 0.2611 and 2.121 for PAPP-A (sd log 10 MoM = 0.2255)-both medians were significantly greater than the medians in singleton pregnancies (1.00 MoM). In the case of monochorionic and dichorionic twins the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected, free β-hCG MoM's were not significantly different (1.983 v 2.041), however for PAPP-A the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM in monochorionic twins was significantly lower than in dichorionic twins (1.756 v 2.250) whilst the sd log 10 MoM's were not significantly different (0.2185 v 0.2167).Conclusion Screening in twin pregnancies requires adjustment of the calculated MoM to account for the presence of two fetuses. In general, for free β-hCG, this should be by dividing the observed corrected MoM by 2.023. For PAPP-A two different factors are required −2.192 in dichorionic twins and 1.788 in monochorionic twins.

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Delta‐NT or NT MoM: which is the most appropriate method for calculating accurate patient‐specific risks for trisomy 21 in the first trimester?

Abstract: Objective To assess whether in screening for trisomy 21 by nuchal translucency (NT) the delta or the multiples of the median (MoM)

Cited by 122 publications

References 18 publications

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Quality assessment of routine nuchal translucency measurements: a North American laboratory perspective

Screening for trisomy 21 in twin pregnancies in the first trimester: an update of the impact of chorionicity on maternal serum markers

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