ADAM 12 as a second‐trimester maternal serum marker in screening for Down syndrome

Abstract

Background ADAM 12 is a placenta-derived glycoprotein that is involved in growth and differentiation. The maternal serum concentration of ADAM 12 is a potential first-trimester maternal serum marker of Down syndrome (DS). Here we examine the potential of ADAM 12 as a second-trimester maternal serum marker of DS. Materials and MethodsThe concentration of ADAM 12 was determined in gestational week 14-19 in 88 DS pregnancies and 341 matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and the distribution of log 10 MoM ADAM 12 values in DS pregnancies and controls determined. Correlations with alpha-fetoprotein (AFP) and free β-human chorionic gonadotrophin (free β-hCG) were established and used to model the performance of maternal serum screening with ADAM 12 in combination with other second-trimester serum markers. ResultsThe ADAM 12 maternal serum concentration was significantly increased with a median MoM of 1.85 and a mean log 10 MoM (SD) of 0.268 (0.2678) compared to a mean log 10 MoM (SD) of 0.013 (0.4318) in controls. ADAM 12 correlated with maternal weight and ethnicity (with the serum concentration increased in Afro-Caribbeans), but neither with maternal age nor gestational age, and only marginally with AFP (r(DS) = 0.078, r(controls) = 0.093) and free β-hCG (r(DS) = 0.073, r(controls) = 0.144. The increase in detection rate-for a false positive rate of 5%-by adding ADAM 12 to the double test (AFP + free β-hCG) was 4%, similar to that of adding uE3 to the double test.Conclusion ADAM 12 is an efficient second-trimester marker for DS. Further studies should be conducted to determine whether it may be a useful additonal or alternative marker to those currently used in the secondtrimester.

ADAM12 as a marker of trisomy 18 in the first and second trimester of pregnancy

“…The low ADAM12 results confirm the early observations of Laigaard et al [17] who demonstrated in a small series of 10 cases that prior to 55 days, levels of ADAM12 were less than the detection limit of the assay and increased as the gestational age increased. This mirrors the temporal pattern that has been described for ADAM12 in pregnancies with trisomy 21 [19,20], and is similar to that described for PAPP-A [31,32], which like ADAM12 is another IGFBP protease [13,33]. However the temporal pattern is unlike that seen for PAPP-A in trisomy 18 when the low levels of PAPP-A in the first trimester are even further reduced in the second trimester [6,34,35].…”

“…In a larger series of first trimester cases [19] and a similar larger series of second trimester cases [20] with trisomy 21 it has been confirmed that first trimester levels of ADAM12 are reduced and that the reduction is more pronounced in earlier gestation. Discrimination appears best around 8-10 weeks, decreasing slightly at 12-14 weeks, and then as ADAM12 levels increase in trisomy 21, discrimination improves yet again at around 16 weeks.…”

“…In the second trimester some 12 cases of trisomy 18 detected by second trimester screening were available. As a control group we used gestational agematched data from the 389 first trimester and the 341 second trimester samples published as part of previous studies and which were analyzed in the same batches as the trisomy 18 samples [19,20]. In all first trimester cases, gestational age at sample collection (median controls ¼ 85 days; median cases ¼ 83.9 days) was determined by CRL measurement.…”

Maternal Serum ADAM-12 as a Potential Marker for Different Adverse Pregnancy Outcomes

“…Later studies, using a new DELFIA platform (PerkinElmer Life Sciences, Turku, Finland), supported these early results, placing the discriminatory power of ADAM-12 greatest prior to 10 weeks' gestation [21][22][23][24][25] . In the second trimester, ADAM-12 levels were found to be increased in trisomy-21 pregnancies [26,27] .…”

A disintegrin and metalloproteinase-12 (ADAM12): Function, roles in disease progression, and clinical implications

“…These include various cancers [27,51,52,53,54,55,56,57,58,59], liver fibrogenesis [60], cardiac hypertrophy [61], and asthma [62]. There is also evidence to suggest that increases in ADAM12 are associated with adverse outcomes in pregnancy [63,64,65], and that it may also be used as a first [66] or second [67,68] trimester screen for Down syndrome, although these data are considerably more debated. Given these, it is suggested that discerning the molecular basis of the ADAM12 assisted disease progression would lead to improved selection of therapeutic options and possibly individualized therapy of patients.…”