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.