Maternal Serum Disintegrin and Metalloprotease Protein-12 in Early Pregnancy as a Potential Marker of Adverse Pregnancy Outcomes

Abstract

ObjectivesThe aim of this study was to determine whether the concentration of disintegrin and metalloprotease protein12 (ADAM12) in first trimester maternal serum can be used as a marker for first-trimester complete spontaneous abortions, missed abortions, ectopic pregnancies and hydatidiform moles.MethodsThe maternal serum concentrations of ADAM12 were measured in the range of 5–9+6 weeks of gestation using an automated AutoDelfia immunoassay platform in 9 cases of complete spontaneous abortion, 27 cases of missed abortions, 56 cases of ectopic pregnancies, 12 cases of hydatidiform moles, and 100 controls. Logistic regression analysis was used to determine significant factors for predicting adverse pregnancy outcomes in early pregnancy. Screening performance was assessed using receiver operating characteristic curves.ResultsTwo hundred and four women were enrolled in the study. In the control group, the level of ADAM12 increased with gestational age. The median ADAM12 levels in the spontaneous abortion (0.430 MoM), ectopic pregnancy (0.460 MoM) and hydatidiform mole (0.037 MoM) groups were lower than that in the control group, while the median ADAM12 level in the missed abortion group (1.062 MoM) was not significant from the controls (1.002 MoM). Logistic regression analysis demonstrated that the level of ADAM12 in maternal serum facilitated the detection of ectopic pregnancies (OR = 0.909; 95% CI = 0.841∼0.982) and complete spontaneous abortion (OR = 0.863; 95% CI = 0.787∼0.946).ConclusionsIn complete spontaneous abortion and ectopic pregnancy, ADAM12 maintained at low levels in early pregnancies, and there were significant differences compared to normal pregnancies. ADAM12 is a promising marker for the diagnosis of complete spontaneous abortion and ectopic pregnancy in symptomatic women, and under certain conditions, ADAM12 can diagnose ectopic pregnancy and spontaneous abortion before an ultrasonographic detection of the conditions.

A disintegrin and metalloproteinase 12 (ADAM12) localizes to invasive trophoblast, promotes cell invasion and directs column outgrowth in early placental development

“…Although there is no clear evidence for the involvement of ADAM12 during human implantation and decidualizion, reduced levels of ADAM12 in serum of women with ectopic pregnancies indicate its possible involvement in blastocyst implantation 126,127 . It has also been suggested that ADAM17, which is highly expressed in the receptive-phase human endometrium, might facilitate blastocyst implantation by mediating MUC1 ectodomain release 128 .…”

Using dynein heavy chain 5 and creatine kinase levels in cervical fluid and blood for early diagnosing of ectopic pregnancy

“…Several biomarkers have been evaluated for the early detection of an ectopic pregnancy, 3,18 but the studies could not achieve high sensitivity and specificity for diagnosing an ectopic pregnancy. As a result, some investigators evaluated embryo or trophoblast associated proteins, such as pregnancy associated plasma protein‐A (PAPP‐A), a disintegrin and metalloprotease‐12 (ADAM‐12) and Activin A for diagnosis 18–20 . The general weakness of PAPP‐A and ADAM‐12 is that these markers are also reduced in incomplete abortus cases, and the power for these markers to distinguish between an ectopic pregnancy and an incomplete abortus was low 20 .…”

Biomarkers of Ectopic Pregnancy-Present and Future

“…ADAM-12 was found to be significantly decreased in patients with EP when compared to viable IUP in a cohort of 199 patients [48]. Horne et al observed that when measured in isolation, ADAM-12 levels had limited value as a diagnostic biomarker for EP [49], whereas Yang et al observed low levels of ADAM12 in complete spontaneous abortion and ectopic pregnancy compared to normal pregnancies [50]. Overall, this promising new marker still requires large prospective cohorts for validation.…”