Analytical Comparison of Pregnancy-Associated Plasma Protein-A (PAPP-A) Immunoassays for Biochemical Determination of Gestational Age.

Abstract

Accurate pregnancy dating is critical for maternal and child health and for counseling on safe and effective abortion methods. While last menstrual period and first trimester ultrasound are often used together to determine gestational age (GA), they have limited accuracy and availability, respectively. Prior studies have shown that pregnancy-associated plasma protein-A (PAPP-A) increases exponentially during pregnancy and has the potential to serve as a biochemical marker of GA. We aimed to analyze the relationship between sonographically determined GA and serum PAPP-A concentration measured by different immunoassays and to derive cutoff levels informative for the 70 days GA commonly recommended limit for medical abortion in outpatient settings. We compared technical characteristics of 4 commercially available PAPP-A immunoassays and tested 120 maternal serum samples (GA range: 34-231 days) along with contrived pool samples and traceable quality controls. These characteristics included area under the receiver operator characteristic (AUROC) plot, sensitivity and specificity based on cutoffs defined by the Youden Index, and likelihood ratios. All 4 immunoassays had sensitivities and specificities ≥80%, and AUROC values ranging from 0.948 to 0.968. Marked differences among absolute PAPP-A values were noted depending on immunoassay. PAPP-A cutoff values at 70 days GA for each individual immunoassay were established along with procedural recommendations that increase equivalence among immunoassays. Maternal serum PAPP-A levels correlated strongly with GA despite differences in immunoassay formats and absolute data output. Serum PAPP-A has biomarker potential for future development of a point-of-care test aimed at increasing access to medical abortion.