A technical and clinical evaluation of the new ThermoFisher BRAHMS unconjugated estriol and inhibin-A assays and their use in second trimester Down syndrome screening

Abstract

To evaluate second-trimester Down syndrome screening performance of the new ThermoFisher BRAHMS GOLD unconjugated estriol (uE3) and inhibin-A assays. Serum samples were analyzed for levels of uE3 and inhibin-A using the ThermoFisher BRAHMS GOLD immunoanalyzer and compared to other platforms. Levels were transformed to multiples of the median (MoM) in unaffected pregnancies. Log₁₀ MoM distributions in unaffected and Down syndrome pregnancies were assessed for central tendency (mean) and dispersion (SD). Empirical and estimated screening performances were determined. Correlation between BRAHMS and AutoDELFIA^® uE3 and inhibin-A were 0.63 and 0.97, respectively, the respective mean difference was 31.3% [95%CI 50.2% to −112.8%] and −23.3% [95%CI −41.9% to −4.7%]. Passing–Bablok indicated significant systematic (−2.78 [95%CI −3.57 to −2.04]) and proportional bias (1.30 [95%CI 1.15 to −1.47]) between uE3 assays and significant proportional bias (0.71[95%CI 0.65–0.78]) between inhibin-A assays. The uE3 and inhibin-A log₁₀ MoM distribution mean [SD] in unaffected and Down syndrome pregnancies were 0.0024 [SD = 0.2341] and −0.0001 [SD = 0.2078], and −0.2028 [SD = 0.2495] and 0.3645 [SD = 0.2576], respectively. The new BRAHMS uE3 and inhibin-A assays had an 81–83% detection rate for Trisomy21 for a 5% false-positive rate. The new BRAHMS assays achieved the expected screening performance provided the risk estimation model is adjusted to account for the higher BRAHMS uE3 MoM measurement distribution variance.

Keywords:

• BRAHMS
• Compact Plus
• GOLD
• second trimester
• Down syndrome
• inhibin-A
• unconjugated estriol
• detection rate
• false-positive rate

Correction Statement

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Authors’ contributions

All authors contributed to obtaining the data, data analysis and writing of the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

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