P Chaemsaithong1, D Sahota1, R K Pooh2, M Zheng3, R Ma4, N Chaiyasit5, K Koide6, S W Shaw7, S Seshadri8, M Choolani9, T Panchalee10, P Yapan10, W S Sim11, A Sekizawa6, Y Hu3, A Shiozaki12, S Saito12, T Y Leung1, L C Poon1. 1. Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR. 2. CRIFM Clinical Research Institute of Fetal Medicine PMC, Osaka, Japan. 3. Nanjing Drum Tower Hospital, Nanjing, China. 4. First Affiliated Hospital of Kunming Medical University, Kunming, China. 5. King Chulalongkorn Memorial Hospital, Bangkok, Thailand. 6. Showa University Hospital, Tokyo, Japan. 7. Taipei Chang Gung Memorial Hospital, Taipei, Taiwan. 8. Mediscan, Chennai, India. 9. National University Hospital, Singapore. 10. Siriraj Hospital, Bangkok, Thailand. 11. KK Women's and Children's Hospital, Singapore. 12. University of Toyama University Hospital, Toyama, Japan.
Abstract
OBJECTIVES: To (i) evaluate the applicability of the European-derived biomarker multiples of the median (MoM) formulae for risk assessment of preterm pre-eclampsia (PE) in seven Asian populations, spanning the east, southeast and south regions of the continent, (ii) perform quality-assurance (QA) assessment of the biomarker measurements and (iii) establish criteria for prospective ongoing QA assessment of biomarker measurements. METHODS: This was a prospective, non-intervention, multicenter study in 4023 singleton pregnancies, at 11 to 13 + 6 weeks' gestation, 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 and mean arterial 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 published FMF formulae, derived from a largely Caucasian population in Europe, which adjust for gestational age and covariates that affect directly the biomarker levels. Variations in biomarker MoM values and their dispersion (SD) and cumulative sum tests over time were evaluated in order to identify systematic deviations in biomarker measurements from the expected distributions. RESULTS: In the total screened population, the median (95% CI) MoM values of MAP, UtA-PI and PlGF were 0.961 (0.956-0.965), 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 MoM levels, respectively, compared with those expected from normal median formulae, based on a largely Caucasian population, whilst UtA-PI MoM values were similar. 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 women in all centers had consistently lower MAP MoM values than expected, but were within 10% of the expected value. UtA-PI MoM values were within 10% of the expected value at all sites except one. Most PlGF MoM values were systematically 10% lower than the expected value, except for those derived from a South Asian population, which were 37% higher. CONCLUSIONS: Owing to the anthropometric differences in Asian compared with Caucasian women, significant differences in biomarker MoM values for PE screening, particularly MAP and PlGF MoMs, were noted in Asian populations compared with the expected values based on European-derived formulae. If reliable and consistent patient-specific risks for preterm PE are to be reported, adjustment for additional factors or development of Asian-specific formulae for the calculation of biomarker MoMs is required. We have also demonstrated the importance and need for regular quality assessment of biomarker values.
OBJECTIVES: To (i) evaluate the applicability of the European-derived biomarker multiples of the median (MoM) formulae for risk assessment of preterm pre-eclampsia (PE) in seven Asian populations, spanning the east, southeast and south regions of the continent, (ii) perform quality-assurance (QA) assessment of the biomarker measurements and (iii) establish criteria for prospective ongoing QA assessment of biomarker measurements. METHODS: This was a prospective, non-intervention, multicenter study in 4023 singleton pregnancies, at 11 to 13 + 6 weeks' gestation, 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 and mean arterial 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 published FMF formulae, derived from a largely Caucasian population in Europe, which adjust for gestational age and covariates that affect directly the biomarker levels. Variations in biomarker MoM values and their dispersion (SD) and cumulative sum tests over time were evaluated in order to identify systematic deviations in biomarker measurements from the expected distributions. RESULTS: In the total screened population, the median (95% CI) MoM values of MAP, UtA-PI and PlGF were 0.961 (0.956-0.965), 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 MoM levels, respectively, compared with those expected from normal median formulae, based on a largely Caucasian population, whilst UtA-PI MoM values were similar. 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 women in all centers had consistently lower MAP MoM values than expected, but were within 10% of the expected value. UtA-PI MoM values were within 10% of the expected value at all sites except one. Most PlGF MoM values were systematically 10% lower than the expected value, except for those derived from a South Asian population, which were 37% higher. CONCLUSIONS: Owing to the anthropometric differences in Asian compared with Caucasian women, significant differences in biomarker MoM values for PE screening, particularly MAP and PlGF MoMs, were noted in Asian populations compared with the expected values based on European-derived formulae. If reliable and consistent patient-specific risks for preterm PE are to be reported, adjustment for additional factors or development of Asian-specific formulae for the calculation of biomarker MoMs is required. We have also demonstrated the importance and need for regular quality assessment of biomarker values.