Article

A first trimester trisomy 13/trisomy 18 risk algorithm combining fetal nuchal translucency thickness, maternal serum free ?-hCG and PAPP-A

Endocrine Unit, Clinical Biochemistry Department, Harold Wood Hospital, Gubbins Lane, Romford RM3 0BE, UK.
Prenatal Diagnosis (Impact Factor: 3.27). 10/2002; 22(10):877-9. DOI: 10.1002/pd.420
Source: PubMed

ABSTRACT 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.

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Available from: Kevin Spencer, Mar 14, 2014
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    • "These findings are consistent with previous reports in relation to fetal size that suggest independence between CRL measurements and PAPP-A levels (Smith et al., 1998); however, no studies have addressed the relationship between PAPP-A and first trimester growth rate as measured by CRL. In our study all babies were chromosomally normal, although in the case of some chromosomal abnormalities both the first trimester growth rate and PAPP-A levels tend to be low (Spencer and Nicolaides, 2002). It has been known for several years that low PAPP-A levels are associated with a higher likelihood of a baby being born SGA with birthweight <10th percentile (Pihl et al., 2008) and adverse pregnancy outcome (Ong et al., 2000; Smith et al., 2002, 2006; Krantz et al., 2004; Spencer et al., 2008). "
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    ABSTRACT: We sought to define the relationship between first trimester fetal growth, pregnancy-associated plasma protein A (PAPP-A) levels and birthweight. Two-hundred and one women with repeat first trimester crown-rump length (CRL) measurements were included. In 194, the first trimester PAPP-A value was known and in 169 there was complete data including birthweight. Fetal growth curves were derived using functional linear discriminant analysis (FLDA) and growth compared between those with < 10th percentile, 10th to 90th and > 90th percentile PAPP-A multiple of median (MoM) levels and birthweight percentiles. Median maternal age was 35 years, gestation at PAPP-A sampling and of first scan was 11 weeks. Median delivery gestation was 40 weeks and birthweight 3425 g. There was no association between first trimester fetal CRL growth and either PAPP-A MoM percentile or birthweight percentile. There was a significant positive correlation between PAPP-A MoM and birthweight percentile (p = 0.0004). First trimester fetal growth rate is not related to birthweight percentile or first trimester PAPP-A levels. Irrespective of gestation, a low PAPP-A is associated with delivery of a smaller baby, and a high PAPP-A with a larger baby.
    Prenatal Diagnosis 09/2010; 30(9):873-8. DOI:10.1002/pd.2578 · 3.27 Impact Factor
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    • "All scans were carried out by sonographers who had obtained the Fetal Medicine Foundation certificate of competence in the 11–14 weeks' scan (www.fetalmedicine.com).The maternal serum-free β-hCG and PAPP-A were measured using the Kryptor analyser (Brahms AG, Berlin) and the performance of this assay has been described previously Spencer et al., 1999). Patient-specific risks were calculated by a multivariate approach using population parameters established in large-scale retrospective studies and prospective studies (Snijders et al., 1998; Spencer et al., 1999) and the maternal age and gestational-related risk of Trisomy 21 at the time of screening (Snijders et al., 1999) or for Trisomy 13/18 (Spencer and Nicolaides, 2002). Women with a risk of greater than 1 : 300 for Trisomy 21 or 1 : 100 for Trisomy 13/18 were offered invasive testing to determine the fetal karyotype. "
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    ABSTRACT: ADAM12s is a placenta-derived glycoprotein that is involved in growth and differentiation, and has been shown to be a potential first-trimester and second-trimester marker of Trisomy 21 and other aneuploides. Maternal ADAM12s concentrations show a considerable temporal variation with gestational age and here we study the levels at 11-13 weeks of gestation to establish the effectiveness or otherwise at a time when other established markers are used. Samples collected as part of routine first-trimester screening were retrieved from storage. In total, 46 samples from pregnancies with Trisomy 21 were identified and collected between 11 and 13 weeks of gestation-of these 83% had been identified by combined first-trimester screening. A series of 414 gestational age-matched samples collected during the same period formed the control group. ADAM12s was measured by a new DELFIA assay incorporating two monoclonals (6E6 and 8F8). Results were expressed as weight-corrected multiples of the median (MoM). The median MoM ADAM12s rose from 0.914 at 11 weeks to 1.032 at 13 weeks. Combining the data from this study and other published studies suggests that ADAM12s is unlikely to be of much additional value when screening for Trisomy 21 in the period 11-13 weeks. More studies are required looking at the potential of ADAM12s prior to 10 weeks.
    Prenatal Diagnosis 05/2008; 28(5):422-4. DOI:10.1002/pd.1994 · 3.27 Impact Factor
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    • "All scans were carried out by sonographers who had obtained the Fetal Medicine Foundation certification of competence in the 11 to 14 week scan (www.fetalmedicine.com). Patientspecific risks were calculated by a multivariate approach using population parameters established in large-scale retrospective studies and prospective studies (Snijders et al., 1998; Spencer et al., 1999; Spencer et al., 2003b) and by the maternal age and gestational-related risk of either trisomy 21 at the time of screening (Snijders et al., 1999) or trisomy13/18 (Spencer and Nicolaides, 2002). Women with a risk of greater than 1 : 300 for trisomy 21, or 1 : 100 for trisomy 13/18 were offered invasive testing to determine the foetal karyotype. "
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    ABSTRACT: To assess whether the maternal serum ADAM12s concentrations are altered in the first and second trimester of pregnancies complicated by rare aneuploides. ADAM12s was measured by a semi-automated time-resolved immunofluorometric assay in a series of 60 first-trimester cases with trisomy 13, 78 first-trimester cases with Turner's syndrome, 38 first-trimester cases with triploidy and 24 first-trimester cases with sex aneuploidy-the cases were compared with the data from 389 first-trimester controls. In the second trimester, a smaller number of 6, 7, 2 and 13 cases, respectively, were compared with the data from 341 controls. All data were expressed as multiple of the median (MoM) and corrected for maternal weight. Correlation with previously analysed markers (PAPP-A, free beta-hCG and delta NT) was performed. The first-trimester median MoM ADAM12s was significantly lower than 1.0 in all types of rare aneuploidy with the possible exception of triploidy type II. A significant positive correlation with gestational age was reported for trisomy 13 and Turner's syndrome. ADAM12s was not significantly correlated with any other first-trimester marker. In the second trimester, ADAM12s values were marginally increased in these rare aneuploidies. ADAM12s has already been shown to be a possible early first- and second-trimester marker of trisomies 21 and 18. Our data also show the possibility of levels of this marker being altered in the first and second trimester of pregnancies with rare aneuploidies. This may be a useful addition to screening strategies in the future.
    Prenatal Diagnosis 12/2007; 27(13):1233-7. DOI:10.1002/pd.1885 · 3.27 Impact Factor
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