A first-trimester Trisomy 13/Trisomy 18 risk algorithm combining fetal nuchal translucency thickness, maternal serum free β-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


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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    • "In this study, it was found that PP13 levels are significantly lower in trisomy 18 and 13 pregnancies. In these trisomies serum levels of PAPP-A and fβ-hCG are also largely decreased (Spencer and Nicolaides, 2002) which is not necessarily the case in pregnancies complicated by PE. Therefore, addition of PP13 to the current screening test could be valuable to make a proper distinction between normal, aneuploid and PE pregnancies. "
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    ABSTRACT:  To investigate the predictive value of maternal serum pregnancy-associated plasma protein A (PAPP-A), free β subunit of human chorionic gonadotrophin (fβ-hCG), placental protein 13 (PP13), placental growth factor (PlGF) and a desintegrin and metalloproteinase 12 (ADAM12), for first-trimester identification of early-onset pre-eclampsia.   Nested case-control study.   Routine first-trimester screening for trisomy 21 in the Netherlands.   Eighty-eight women who developed pre-eclampsia or haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 34 weeks of gestation and 480 controls.   PP13, PlGF and ADAM12 were measured in stored first-trimester serum, previously tested for PAPP-A and fβ-hCG. All marker levels were expressed in multiples of the gestation-specific normal median (MoMs). Model predicted detection rates for fixed false-positive rates were obtained for statistically significant markers alone and in combination.   Development of pre-eclampsia or HELLP syndrome.  PP13 and PlGF were reduced in women with pre-eclampsia, with medians 0.68 MoM and 0.73 MoM respectively (P < 0.0001 for both). PAPP-A was reduced (median 0.82 MoM, P < 0.02) whereas ADAM12 and fβ-hCG did not differ between control women and those with pre-eclampsia. In pre-eclampsia complicated by a small-for-gestational-age fetus, all markers except fβ-hCG had lower values, compared with pregnancies involving fetuses of normal weight. The model-predicted pre-eclampsia detection rate for a combination of PP13 and PlGF was 44% and 54%, respectively, for a fixed 5% and 10% false-positive rate.  This study demonstrates that PP13 and PlGF in the first-trimester might be promising markers in risk assessment for early pre-eclampsia/HELLP syndrome but for an adequate screening test additional characteristics are necessary.
    BJOG An International Journal of Obstetrics & Gynaecology 10/2010; 117(11):1384-9. DOI:10.1111/j.1471-0528.2010.02690.x · 3.45 Impact Factor
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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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