First‐trimester pre‐eclampsia biomarker profiles in Asian population: a multicenter cohort study

OBJECTIVES: To: (i) evaluate the applicability of the European-derived biomarker multiple of median (MoM) formulae for the risk assessment of preterm preeclampsia (PE) across seven Asian populations spanning the East, Southeast and South Asian regions of the continent; (ii) perform a quality assurance (QA) assessment of the biomarker measurements; and (iii) establish criteria for prospective ongoing measurement QA assessment. METHODS: This was a prospective, non-intervention, multicenter study in 4,023 singleton pregnancies at 11-13+6 weeks in 11 recruiting centers in China, Hong Kong, India, Japan, Singapore, Taiwan and Thailand. Women were screened for preterm PE between December 2016 and June 2018 and gave written informed consent to participate in the study. Maternal and pregnancy characteristics were recorded, mean arterial blood pressure (MAP), mean uterine artery pulsatility Index (UtA-PI) and maternal serum placental growth factor (PlGF) were measured in accordance with the Fetal Medicine Foundation (FMF) standardized measurement protocols. MAP, UtA-PI, and PlGF were transformed into MoMs using the FMF published formulae, which adjusted for gestation and covariates that directly affect their levels. Variations of biomarker MoM values and their dispersion (standard deviation: SD) and interval cumulative sum (CUSUM) test over time were evaluated to identify systematic measurement deviation from expected measurement distributions. RESULTS: In the total screened population, the median (95% confidence interval (CI)) MoM values of MAP, UtA-PI, and PlGF were 0.961 (0.958-0.965), 1.018 (0.996-1.030) and 0.891 (0.861-0.909), respectively. Women in this largely Asian cohort had approximately 4% and 11% lower MAP and PlGF biomarker levels, respectively, compared to those expected from normal median formulae based on a largely Caucasian population. UtA-PI and PlGF MoMs were beyond the 0.4 to 2.5 MoM range (truncation limits) in 16 (0.4%) and 256 (6.4%) pregnancies, respectively. QA assessment tools indicated that all centers had consistently lower MAP MoM values, but within 10% of the expected value. UtA-PI MoM values were within 10% of the expected value in all sites, except one. Most PlGF MoM values were systematically lower than 10% of the expected value except those derived from South Asian population, which were 37% higher. CONCLUSIONS: Owing to the anthropometric differences in Asian women, significant changes in the biomarkers for PE screening were noted, particularly MAP and PlGF, requiring Asian-specific formulae for the calculation of MoMs to be developed if reliable and consistent patient-specific risks for preterm PE are to be reported. We have also demonstrated the importance and need for regular quality assessment of biomarker values. This article is protected by copyright. All rights reserved.