Ethnic-specific reference range affects the efficacy of quadruple test as a universal screening for Down syndrome in a developing country

Abstract

Objective To evaluate the efficacy of the quadruple test for potential use as a Thai national policy for Down syndrome (DS) screening and establish an accurate equation for risk estimation of Down syndrome based on gestational age, weight and the ethnic-specific reference range of our population. Methods A prospective study was conducted on singleton pregnancies at 14 to 21 weeks of gestation to evaluate the efficacy of quadruple DS screening using the automatically calculated Western European descent factor (WF) in our population and the impact of screening using a specific Thai ethnic factor as well as to establish an equation for the risk estimation of DS based on gestational age, weight and a local Thai ethnic factor to correct for the impact of ethnic factor on the screening efficacy. Results Of a total of 5,515 women, 12 cases of DS and 8 cases of other aneuploidies were found. The detection rate, false positive rate and specificity were 75.0%, 9.1% and 90.9%, respectively, by automatic calculation with the widely used WF; the screening efficacy was lower when used in Asian populations than in other studies. The best-fitted regression equation of serum quadruple screening of AFP, free β-hCG, uE3 and inhibin A was established by adjustment for gestational age (GA) in days, maternal weight and our Thai-specific ethnic reference range which was created for this study. Calculations with our Thai-specific ethnic model gave a better detection rate of 83.3%, a false positive rate of 9.6% and specificity of 90.4%. Conclusion The serum quadruple test had a lower detection rate than expected when the risk estimation was based on the WF reference range. The serum quadruple test using WF had significantly different levels when corrected with our ethnic-specific factor. Using our local ethnic specific model could increase the detection rate of DS screening in Thailand with a minimal increase in false positive rates. Our findings indicate that DS screening should be adjusted with an appropriate individual ethnic factor when used for national screening.

Utility of fetal facial markers on a second trimester genetic sonogram in screening for Down syndrome in a high-risk Thai population

“…A related study found that adding genetic sonogram screening in pregnancies identified as low risk for a Down syndrome fetus by cell-free DNA had a low positive predictive value [ 33 ]. To optimize the screening performance for Down syndrome, particularly in some developing countries in which maternal serum biomarkers are currently used but have lower detection rates than expected, such as in our setting [ 34 ], our study supports the idea of adding facial ultrasound markers in groups at moderate risk for Down syndrome to maternal serum biomarkers. As a previous study using only absent or hypoplastic nasal bone for Down syndrome screening reported a low detection rate for Down syndrome in Asian fetuses [ 35 ], adding multiple facial ultrasound markers should increase the detection rate of Down syndrome screening in our populations [ 36 ].…”

Systems Thinking Approach on Foetal Abnormalities Due to Alpha-Fetoprotein Level

“…AFP concentrations are usually greater as gestational age-progressed beyond the first trimester, but they dropped as maternal weight increases. 5 This supports the finding that maternal serum levels are affected by maternal weight-adjusted for Multiple of the Median (MoM). As a result, maternal weight adjustment for serum calculation also plays role.…”

“…Although many women with high maternal AFP do not have foetus abnormalities, there is a higher risk of obstetric problems such as premature rupture of membranes, placenta accreta, increta, and percreta. 5 According to the current studies, patients with a lower maternal body weight had higher serum AFP concentrations. AFP concentrations are usually greater as gestational age-progressed beyond the first trimester, but they dropped as maternal weight increases.…”

“…Furthermore, some recent studies have revealed that race and ethnicity have a significant impact on serum concentrations in both Down syndrome (DS) and normal foetuses throughout gestation. 5 Other studies have observed discrepancies in normative median serum levels in subgroups of the same nation or ethnicity, indicating that maternal serum quadruple markers do not have universally parameters for screening for Down syndrome in all races and ethnicities. 5 However, the variations in AFP concentrations are not strongly influenced by the maternal weight (Wald et al, 1981).…”

Study on the Effect of B-Ultrasound NT Scan in Early Pregnancy Combined with Serum Screening in Early and Middle Pregnancy for Down Syndrome

“…In the United Kingdom and the United States, it is routine for pregnant women to undergo serum screening for Down syndrome in the second trimester, either with A triple test (alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and unconjugated estriol (UE)) or with A quadruple test (with the addition of statin A) [ 6 , 7 ]. Recently, early pregnancy screening using fetal neck translucency, HCG, and pregnancy-associated plasma protein A (PAPP-A) has supplied an earlier and more effective screening method [ 8 ].…”