Are Serum Protein Biomarkers Derived from Proteomic Analysis Useful in Screening for Trisomy 21 at 11–13 Weeks?

Abstract

Objective: The aim of this study is to identify potential biomarkers for fetal trisomy 21 from previous publications using proteomic techniques and examine the potential value of such biomarkers in early screening for this aneuploidy. Methods: This was a case-control study of 25 pregnancies with fetal trisomy 21 and 50 euploid controls undergoing first-trimester screening for aneuploidies by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free β-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A). The maternal serum concentrations of afamin, apolipoprotein E, clusterin, ceruloplasmin, epidermal growth factor, fetuin-A, pigment epithelium-derived factor glycoprotein and transthyretin were determined using an ELISA and compared in the euploid and trisomy 21 groups. Results: In pregnancies with fetal trisomy 21, the median maternal age, fetal NT thickness and serum free β-hCG were increased, whereas serum PAPP-A was decreased. However, there were no significant differences between cases and controls in any of the biomarkers. Conclusion: Proteins identified as potential biomarkers for trisomy 21 using proteomic techniques have not been found to be useful in early screening for this aneuploidy.

The vitamin E-binding protein afamin increases in maternal serum during pregnancy

“…Recently, afamin was identified as a potential biomarker for trisomy 21 by proteomic comparative analysis of plasma from pregnant women [36]. However, this finding was not confirmed in a later study comparing 25 women pregnant with trisomy-affected babies and 50 euploid healthy pregnancies [36].…”

“…The previously reported abundance of afamin in human follicle fluid suggests the importance of afamin for oocyte development, maturation and hence fertility in general, most likely due to its vitamin E-carrying property [6]. Recently, afamin was identified as a potential biomarker for trisomy 21 by proteomic comparative analysis of plasma from pregnant women [36]. However, this finding was not confirmed in a later study comparing 25 women pregnant with trisomy-affected babies and 50 euploid healthy pregnancies [36].…”

Maternal serum protein profile and immune response protein subunits as markers for non‐invasive prenatal diagnosis of trisomy 21, 18, and 13

“…Among full autosomal trisomy, only trisomy 21, 18, and 13 are capable of postnatal survival and are susceptible to a spectrum of diseases including cancer . In the last two decades, several biochemical and biophysical traits have been identified that led to considerable improvement in the non‐invasive screening for such trisomies . Current practice relying on combined maternal serum testing using different markers, such as alphafetoprotein, β ‐human chorionic gonadotropin, and unconjugated oestriol yields a 69% detection rate, which can be increased to approximately 80–85% by adding use of ultrasound markers, such as thickened nuchal fold .…”

“…The current practice of using single protein biomarkers will most likely give way to the use of multiplexed biomarkers, as they promise better sensitivity and specificity . Use of proteomics platform to mine deep into the plasma proteome has resulted in the identification of several target candidate markers for Down syndrome (DS) . In silico approaches using data mining techniques have also been used to identify proteins other than those previously reported as well as associated with chromosome 21 .…”

Fetuin A Concentration in the Second Trimester Amniotic Fluid of Fetuses with Trisomy 21 Appears to Be Lower: Phenotypic Considerations

“…We hypothesized that levels of fetuin A in amniotic fluid might differ between pregnancies with DS and euploid pregnancies and that presence or absence of features in the DS group may potentially be associated with the metabolic actions of fetuin A. Fetuin A, which has been studied in maternal serum as a potential novel marker in prenatal diagnosis of trisomy 21 in the first trimester, has not been found to differ significantly in levels between euploid and aneuploid pregnancies [10]. The focus of our study is to elucidate a number of metabolic pathways in trisomy 21 rather than add new information to the already studied field of prenatal diagnosis.…”