First trimester screening for trisomy 21 in gestational week 8-10 by ADAM12-S as a maternal serum marker

Abstract

BackgroundA disintegrin and metalloprotease 12 (ADAM12-S) has previously been reported to be significantly reduced in maternal serum from women with fetal aneuploidy early in the first trimester and to significantly improve the quality of risk assessment for fetal trisomy 21 in prenatal screening. The aim of this study was to determine whether ADAM12-S is a useful serum marker for fetal trisomy 21 using the mixture model.MethodIn this case control study ADAM12-S was measured by KRYPTOR ADAM12-S immunoassay in maternal serum from gestational weeks 8 to 11 in 46 samples of fetal trisomy 21 and in 645 controls. Comparison of sensitivity and specificity of first trimester screening for fetal trisomy 21 with or without ADAM12-S included in the risk assessment using the mixture model.ResultsThe concentration of ADAM12-S increased from week 8 to 11 and was negatively correlated with maternal weight. Log MoM ADAM12-S was positively correlated with log MoM PAPP-A (r = 0.39, P < 0.001), and with log MoM free beta hCG (r = 0.21, P < 0.001). The median ADAM12-S MoM in cases of fetal trisomy 21 in gestational week 8 was 0.66 increasing to approx. 0.9 MoM in week 9 and 10. The use of ADAM12-S along with biochemical markers from the combined test (PAPP-A, free beta hCG) with or without nuchal translucency measurement did not affect the detection rate or false positive rate of fetal aneuploidy as compared to routine screening using PAPP-A and free β-hCG with or without nuchal translucency.ConclusionThe data show moderately decreased levels of ADAM12-S in cases of fetal aneuploidy in gestational weeks 8-11. However, including ADAM12-S in the routine risk does not improve the performance of first trimester screening for fetal trisomy 21.

First‐trimester maternal serum ADAM12‐s and PAPP‐A levels are altered in pregnancies conceived after assisted reproduction techniques (ART)

“…Several studies have described a positive correlation between the ADAM12‐s and PAPP‐A levels in the first trimester . In this study, we also found a strong positive correlation between MoM levels of PAPP‐A and ADAM12‐s in spontaneous pregnancies, which supports the previous studies.…”

Predicting first trimester pregnancy outcome: derivation of a multiple marker test

“…Some pathophysiologic conditions of pregnancy such as hypertensive disorders and aneuploidy may impact biomarker interpretation. (33-35) In addition, some markers, such as progesterone, may have altered expression in a pregnancy resulting from assisted reproduction. Our study demonstrated that prediction was independent of gestational age; however, it is possible that having data from one additional point of care, such as additional serum data from another time point (i.e.…”

Biomarkers for ectopic pregnancy and pregnancy of unknown location

“…A case control study of patients with EP and viable IUPs demonstrated that a level≤48.49ml/mL was 97% sensitivity and 37% specific for EP, suggesting promising utility as a marker of extra-uterine location. However, ADAM-12 has also been explored as a marker of aneuploidy, and as such, its performance amidst a cohort including abnormal IUPs must be considered (44, 45). Others have attempted to validate ADAM-12 and found that it did not discriminate EP from all other outcomes when including treated persisted PULs, spontaneously resolving PULs, and probable EPs (AUC 0.65, p>0.05) but when restricting the analysis to well defined PUL outcomes, it had slightly better diagnostic potential (AUC 0.66, p<0.05) (46).…”

“…Alternatively, including gestational age independent markers like certain microRNAs may be helpful (52). Second, one must consider the impact of other pathophysiologic processes of pregnancy such as hypertensive disorders and aneuploidy and how these may impact biomarker interpretation (24, 32, 44, 45, 120). In addition, some markers, such as progesterone, may have altered expression in a pregnancy resulting from assisted reproduction.…”