Study population
This was a prospective cohort study of Chinese women with singleton pregnancies who attended for their Hong Kong Hospital Authority Universal Down Syndrome screening test at 11-13+6weeks of gestation between December 2016 and December 2019 at the Prince of Wales Hospital, Hong Kong SAR.
Consented women underwent a structured ultrasound examination to document fetal viability, fetal NT thickness, fetal crown rump length (CRL) and absence of major fetal abnormalities. In all cases, maternal blood was drawn on the same day as the scan for determination of PAPP-A, free β-hCG and PlGF concentration levels using the BRAHMS KRYPTOR Compact Plus or Gold analysers (ThermoFisher Scientific, Hennigsdorf, Germany) at the Obstetrics Screening Laboratory of the Chinese University of Hong Kong. In addition, mean arterial pressure and uterine artery pulsatility index were documented as part of ongoing studies for risk assessment of preeclampsia.11Chaemsaithong P, Pooh RK, Zheng MM, Ma RM, Chaiyasit N, et al. Prospective evaluation of screening performance of first-trimester prediction models for preterm preeclampsia in an Asian population. Am J Obstet Gynecol 2019;221:650.e1-650.e16
Measured fetal NT, PAPP-A and free β-hCG were converted to their multiple of expected median (MoM) values using previously published expected median values in Chinese. 22Sahota DS, Leung TY, Fung TY, Chan LW, Law LW, et al. Medians and correction factors for biochemical and ultrasound markers in Chinese women undergoing first trimester screening for trisomy 21. Ultrasound Obstet Gynecol 2009;33:387-93 Gestational age at the time of screening was determined by CRL measurement using a previously published Chinese dating formula.33Sahota DS, Leung TY, Leung TN, Chan OK, Lau TK. Fetal crown-rump length and estimation of gestational age in an ethnic Chinese population. Ultrasound Obstet Gynecol 2009;33:157-60 Women were informed of their estimated term risk for trisomies 13, 18 and 21 based on their age, fetal NT, PAPP-A and free β-hCG MoM levels. Women with a term risk of 1:250 or higher were counselled and offered one of three options of fetal karyotyping after undergoing an invasive procedure (chorionic villous sampling or amniocentesis), seeking a diagnostic or non-invasive prenatal commercial test from a private specialist or opting for no further tests. Karyotype results were provided by our in-house prenatal diagnostic laboratory using either conventional karyotype or chromosomal microarray analysis.
Details on screening, follow-up management option selected, result of testing and pregnancy outcome were documented in our screening centre Laboratory Information System. Fetuses of screened pregnancies were considered to be phenotypically ‘normal’ at birth, if (1) the pregnancy was not reported as a false-negative case; (2) the fetus did not have any congenital abnormalities at birth; or (3) diagnostic test results in cases screened positive indicated that the pregnancy was euploidy (46XX/46XY) or had a karyotype considered to be a normal variant (balanced translocation, inherited maternal/paternal).
All scans were performed by midwives and doctors, accredited and annually recertified to assess the fetal NT by the Fetal Medicine Foundation (FMF, London, United Kingdom). Ultrasound providers, PAPP-A and free β-hCG MoMs were subject to internal quality assurance assessment for central tendency and dispersion using target plots.44Sahota DS, Chen M, Leung TY, et al. Assessment of sonographer nuchal translucency measurement performance—central tendency and dispersion. J Matern Fetal Neonatal Med 2011;24:812-6 Daily quality control (QC) samples with known low, intermediate and high concentrations were measured and monitored on both analysers to determine inter-and intra-day variation. In addition, the laboratory is a participant in two United Kingdom National External Quality Assurance Schemes (UKNEQAS), one for aneuploidy screening and second for quality assurance of PlGF measurements. The Screening Laboratory has previously reported a consistent detection rate of 90% for trisomy 21 affected pregnancies since it introduced the first trimester combined screening test in 2003 and that 5-6% of screened pregnancies are screened high risk.55Leung TY, Chan LW, Law LW, Sahota DS, Fung TY, et al First trimester combined screening for trisomy 21 in Hong Kong: outcome of the first 10,000 cases. J Matern Fetal Neonatal Med 2009;22:3004-, 66Sahota DS, Leung WC, To WKW, Lau ET, Leung TY. Prospective assessment of the Hong Kong Hospital Authority universal Down syndrome screening programme. Hong Kong Med J 2013;19:101-8 Women were not informed of their estimated risk for trisomy 21 based on PlGF.