First-trimester Down Syndrome Screening Research Articles

The effect of cognitive behavioral counseling on anxiety and worry level of women with intermediate risk during first trimester screening for down syndrome: a randomized controlled trial: a randomized controlled trial

BackgroundAnxiety related to prenatal screening programs negatively affects maternal and child health.ObjectiveThe study aimed to determine the effect of Cognitive Behavioral Counseling on the anxiety and worry levels of women with intermediate risk during first-trimester screening for Down Syndrome.MethodsThe study was a randomized controlled trial conducted on 52 pregnant women with intermediate risk (1: 51 − 1:1500) during first-trimester screening for Down Syndrome and without additional structural anomalies that referred to three cities of Zanjan province in 2021. The eligible women were randomly assigned to intervention and control groups, with a block size of four. The intervention group received CBC in four sessions of 120 min two times a week by phone. Data were collected using Vandenberg Anxiety Questionnaire, and Cambridge Worry Questionnaire in three phases baseline, after the intervention, and 6 weeks follow-ups. Data were analyzed using independent t-test, chi-square, and repeated measures ANOVA at a 95% confidence level. (P < 0.05).ResultsIn the counselling group, the mean (SD) of a total score of anxiety before the intervention was 67.11 (20.68) which decreased to 32.50 (13.58) in six weeks after the intervention. Furthermore, the mean (SD) of a total score of worry before the intervention was 56.19 (16.76) which decreased to 32.96 (8.89) six weeks after the intervention. Based on the repeated measures ANOVA test, the mean total score of anxiety and worry were statistically significant 6 weeks after the intervention compared with the control group(p < 0.001).ConclusionBased on the study results, CBC can reduce the anxiety and worry levels of women with intermediate risk during first trimester screening for Down Syndrome.Trial registrationThe study was registered at the Iranian Registry of Clinical Trials website under the code IRCT20160608028352N8, (https://en.irct.ir/trial/49998). The first trial registration date was (29/08/2020).

First-trimester screening for Down syndrome using quadruple maternal biochemical markers.

Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency. Singleton pregnancies recruited at 11-14weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates. Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72-97%) of the cases at a false-positive rate of 13% (95% CI: 12-15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82-99%) at a false-positive rate of 4% (95% CI: 4-5%) using a 1:300 cut-off and to 100% (95% CI: 89-100%) at a false-positive rate of 6% (95% CI: 5-8%) using a 1:500 cut-off. First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%.

Follow Your Nose: Repeat Nasal Bone Evaluation in First-Trimester Screening for Down Syndrome.

Examine whether repeat nasal bone evaluation following an absent/uncertain nasal bone on first-trimester screening (FTS) improves Down syndrome (DS) screening specificity. A retrospective chart review of FTS sonograms in one center from January 2015 to January 2018 was performed. Data was extracted for those with an absent/uncertain nasal bone. Repeat evaluations were offered. Of 6780 FTS sonograms, 589 (8.7%) had an absent/uncertain nasal bone. Upon repeat exam, 268/376 (71.3%) had a present nasal bone. Compared with Black patients, patients of other ethnicities were more likely to have a present nasal bone on exam 2 (P < .00001). Of 268 patients with a present nasal bone on exam 2, 37 (13.8%) had an abnormal DS risk following exam 1; 34/37 (91.9%) normalized following nasal bone visualization, dropping the screen positive rate to 1.1%. Repeat nasal bone examination is beneficial in refining DS risk assessment and improves the specificity of FTS.

First-trimester screening versus non-invasive prenatal testing for Down syndrome at high-risk pregnant women in Hanoi Obstetrics and Gynecology Hospital, Vietnam: A cost-utility analysis

ABSTRACT Background: Non-invasive prenatal testing (NIPT) is a relatively new technology for diagnosis of fetal aneuploidies in the context of a developing country like Vietnam. Currently, first-trimester screening (FTS) is more conventional in Vietnam. NIPT is assumed to be more accurate than other maternal screening but is also more costly. The purpose of the study was to perform a cost-utility analysis comparing the FTS and NIPT for Down syndrome for high-risk pregnant women (over 35-year-old) in Vietnam. Methods: Decision tree model and probabilistic sensitivity analysis were used. Results: With the modelling population of 27,232 over 35 years of age pregnant women, FTS helps detect 218.5 cases of the fetus with Down syndrome compared with 247.2 cases when screening with NIPT. In addition, NIPT reduced 1384 false-positive cases compared to FTS. From a societal perspective, NIPT-dominated FTS. Compared to FTS, adopting an NIPT would cost an additional of USD 3,800 for each additional quality-adjusted life-year gained. Conclusions: NIPT is a cost-effective alternative to FTS for prenatal screening for Down syndrome with high-risk pregnant women. This is a very first attempt on cost-utility analysis of prenatal screening methods for Down syndrome in Vietnam and recommendations are made for future research to determine the most cost-effectiveness methods.

First-trimester serum biomarker screening for fetal Down syndrome as a predictor of preterm delivery: a population-based study

Objective: To examine the relationship between the first-trimester serum biomarker levels (pregnancy-associated plasma protein A:PAPP-A; and free beta-human chorionic gonadotropin: b-hCG) and preterm birth; and to create the predictive models for preterm birth in case of strong correlation. Methods: Secondary analysis on a large prospective database of singleton pregnancies undergoing first-trimester serum screening with complete follow-up for pregnancy outcomes. The multiples of medians (MoM) of the biomarkers were compared between the group of term and preterm/early preterm birth. Predictive models were developed based on adjusted MoMs and logistic regression analysis, and then diagnostic performances in predicting preterm birth were assessed. Results: Of 24,611 pregnancies eligible for analysis, 1908 (7.8%) and 500 (2.0%) had preterm and early preterm birth, respectively. Medians MoMs of both biomarkers were significantly lower in preterm and early preterm birth group. The predictive models were constructed. Performance in predicting preterm birth of these models yielded the area-under-ROC-curve of 0.560, 0.652, and 0.653 for b-hCG, PAPP-A, and combined biomarkers, respectively. In predicting early preterm birth, the areas-under-the-curve were found to be 0.551, 0.675, and 0.674 for b-hCG, PAPP-A, and combined biomarkers, respectively. Conclusion: The routine first-trimester serum screening of fetal Down syndrome could also be used as a tool of risk identification of preterm birth. We could take advantage of the screening by incorporating the predictive models into the Down syndrome screening software to report the preterm risk in the same test without extra effort and extra cost

First trimester screening for pre-eclampsia in Chinese pregnancies: case-control study.

To assess the potential of screening for pre-eclampsia (PE) in a Chinese population. Case-control study. Teaching hospital in Hong Kong. A total of 3330 women having a viable singleton pregnancy attending first-trimester Down-syndrome screening. Mean arterial pressure (MAP), bilateral uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF) were measured. Screening markers were transformed to multiples of the gestational median (MoM) and adjusted for maternal and pregnancy characteristics. MoM distributions in PE and non-PE pregnancies were compared with published expected values. PE screening performance was assessed using area under receiver operating curves (AUROC). PE detection rate. A total of 30 (0.9%) women developed either early (<34weeks) or late (≥34weeks) onset PE. MAP was dependent on maternal BMI, UtA-PI on fetal crown rump length, uterine artery peak systolic velocity (UtA-PSV) on maternal age and gestation, and PlGF on gestation in non-PE pregnancies. MoM distributions determined using published Fetal Medicine Foundation models deviated significantly from one for both MAP (P<0.0001) and PI (P<0.0001), but not PlGF (P=0.52) in non-PE pregnancies, whilst PlGF MoM distributions in those who developed early as opposed to late onset PE were significantly higher (P=<0.05). AUROC for any PE using multiple markers was 0.72 (95% CI: 0.64-0.81) with detection rates of 72 and 55% for early and late PE, respectively, for a 10% false positive rate. Detection rates for PE in our Chinese population were lower than the expected 90-95% even after adjusting MoM for local women's characteristics. General Research Fund (Project number 470513). Pre-eclampsia screening in the Chinese population had detection rates lower than previously published results.

Obstetric professionals\u2019 perceptions of non-invasive prenatal testing for Down syndrome: clinical usefulness compared with existing tests and ethical implications

BackgroundWhile non-invasive prenatal testing (NIPT) for fetal aneuploidy is commercially available in many countries, little is known about how obstetric professionals in non-Western populations perceive the clinical usefulness of NIPT in comparison with existing first-trimester combined screening (FTS) for Down syndrome (DS) or invasive prenatal diagnosis (IPD), or perceptions of their ethical concerns arising from the use of NIPT.MethodsA cross-sectional survey among 327 obstetric professionals (237 midwives, 90 obstetricians) in Hong Kong.ResultsCompared to FTS, NIPT was believed to: provide more psychological benefits and enable earlier consideration of termination of pregnancy. Compared to IPD, NIPT was believed to: provide less psychological stress for high-risk women and more psychological assurance for low-risk women, and offer an advantage to detect chromosomal abnormalities earlier. Significant differences in perceived clinical usefulness were found by profession and healthcare sector: (1) obstetricians reported more certain views towards the usefulness of NIPT than midwives and (2) professionals in the public sector perceived less usefulness of NIPT than the private sector. Beliefs about earlier detection of DS using NIPT were associated with ethical concerns about increasing abortion. Participants believing that NIPT provided psychological assurance among low-risk women were less likely to be concerned about ethical issues relating to informed decision-making and pre-test consultation for NIPT.ConclusionsOur findings suggest the need for political debate initially on how to ensure pregnant women accessing public services are informed about commercially available more advanced technology, but also on the potential implementation of NIPT within public services to improve access and equity to DS screening services.

Strong impact of ethnicity on effectiveness of the first trimester maternal serum screen of fetal Down syndrome

Objectives: The objective of this study is to compare the effectiveness of first-trimester maternal serum screening (MSS) for fetal Down syndrome among Thai women between the method using Caucasian reference ranges with racial factor correction (CRR-RC) and that using Thai reference ranges (TRR).Methods: A prospective database of MSS was accessed. The levels of PAPP-A and beta-hCG were calculated to determine their MoMs (multiple of medians) by two methods: (1) CRR-RC for Asian women and (2) TRR. The MoMs from both methods were used to determine the fetal risk.Results: Of 24,885 women including 36 fetuses with Down syndrome, the detection rates were significantly higher with TRR when compared with CRR-RC, 77.8 and 63.9%, respectively, p < .001. Additionally, the false-positive rates were significantly lower with TRR when compared to CRR-RC (7.5 versus 12.5%, respectively, p < .001)Conclusions: The effectiveness of MSS was much better by using our own reference ranges rather than the method of racial factor correction. The important insight is that ethnicity strongly impacts on the effectiveness that cannot be completely corrected by ethnic factor. MSS derived by the CRR-RC in other regions should be interpreted with high precaution, especially where the biophysical characteristics of the women are much different from Caucasian population.

For women of average risk, what are the best tests to screen for Down syndrome in the first trimester?

EVIDENCE-BASED ANSWER In average-risk women, the most accurate combination of traditional tests for first-trimester screening for Down syndrome is combined testing with serum pregnancyassociated plasma-protein-A (PAPP-A), free or total betahuman chorionic gonadotropin (β-hCG), ultrasonographic nuchal translucency measurement, and nasal bone ossification in combination with maternal age. Of note, nasal bone ossification is not available until 11 weeks’ gestation (SOR: A, meta-analyses of cohort and casecontrol studies). Of serum-only tests, PAPP-A and β-hCG in combination with maternal age are most accurate (SOR: A, meta-analyses of cohort and case-control studies). Cell-free DNA (cfDNA) testing has the highest sensitivity and specificity (SOR: B, single cohort study), but further evidence on cost-effectiveness is needed to support its widespread use in average-risk women (SOR: C, expert consensus).

A First-Trimester Biomarker Panel for Predicting the Development of Gestational Diabetes.

Serum markers measured early in pregnancy have been associated with the later diagnosis of gestational diabetes mellitus (GDM). This study aims to explore the performance of a panel of first-trimester biochemical markers for the prediction of GDM. A case-control study was performed that included 12 women who developed GDM and 60 controls matched for maternal and gestational age at blood collection. Levels of pregnancy-associated plasma protein A (PAPP-A), soluble endoglin, pregnancy protein 13, and adiponectin (Adipo) were measured on residual sera used in first-trimester screening for Down syndrome. Data were analyzed by nonparametric methods. A receiver operating characteristic curve was used to calculate the detection rate (DR) obtained with a panel of significant predictors for GDM. Multiples of the median values for Adipo and PAPP-A were significantly reduced in GDM cases versus matched controls. Combination of Adipo and PAPP-A yielded a DR of 63.6% at a false-positive rate of 10%. Addition of body mass index (BMI) to this panel increased DR to 72.7%. This study suggests that first-trimester screening with Adipo, PAPP-A, and BMI may effectively identify women at high risk for the development of GDM.

Risk of Fetal Loss Associated With Invasive Testing Following Combined First-Trimester Screening for Down Syndrome

Abstracted from Ultrasound Obstet Gynecol 2016;47:38–44 The risk of miscarriage after chorionic villus sampling (CVS) and amniocentesis (AC) was investigated in randomized clinical trials in the 1980s and 1990s. Studies have compared CVS with AC and found comparable risk of miscarriage after the 2 procedures.

Association of first-trimester pregnancy-associated plasma protein A levels and idiopathic preterm delivery: A population-based screening study

ObjectiveThis study aims to determine the strength of relationship between pregnancy-associated plasma protein A (PAPP-A) concentrations, using a Thai-specific reference range, and rates of idiopathic preterm delivery. Materials and methodsA retrospective cohort study was conducted on consecutive singleton pregnancies, undergoing first-trimester screening for fetal Down syndrome, between January 2007 and July 2012, at our network hospitals in the northern part of Thailand. The prospective database was assessed for the records with complete outcome information, including PAPP-A concentrations, gestational age at delivery, medical and obstetric complications, and fetal and pregnancy outcomes. Pregnancies with potential causes of preterm delivery were excluded. The recruited women were assigned to two groups; a group with normal PAPP-A levels (≥10th percentile) and a group with low PAPP-A levels (<10th percentile). The main outcome was the rate of idiopathic preterm births in the two groups. ResultsOf 6867 screened women, 3830 were available for analysis and 670 were excluded because of potential confounders. Of the remaining 3160, 302 had low PAPP-A levels and 2858 had normal PAPP-A levels. The rates of spontaneous preterm births at ≤36 weeks, ≤34 weeks, and ≤32 weeks of gestation were significantly higher in women with low PAPP-A levels (7.6% vs. 17.9%, 3.1% vs. 11.9%, and 2.2% vs. 11.9%, respectively), with a relative risk of 2.37, 3.79, and 5.41 for preterm birth, respectively. ConclusionA PAPP-A level of ≤10th percentile was significantly associated with an increased risk for idiopathic preterm birth. Therefore, pregnant women with low PAPP-A levels in the first trimester should be considered at a high risk of preterm delivery.

Risk of fetal loss associated with invasive testing following combined first-trimester screening for Down syndrome: a national cohort of 147,987 singleton pregnancies.

To assess prospectively the risk of fetal loss associated with chorionic villus sampling (CVS) and amniocentesis (AC) following combined first-trimester screening (cFTS) for Down syndrome. This was a nationwide population-based study (Danish Fetal Medicine Database, 2008-2010) including 147,987 women with singleton pregnancy who underwent cFTS. Propensity score stratification was used to assess the risk of fetal loss with and without invasive testing. Analyses were performed between 3 and 21 days after cFTS for CVS and between 28 and 42 days after cFTS for AC. Results are reported as average risk differences with 95% CIs. The risks of miscarriage and stillbirth were not higher in women exposed to CVS or AC compared with unexposed women, independent of the analysis time-point. The average effect of CVS on risk of miscarriage was -0.08% (95% CI, -0.64; 0.47) at 3 days and -0.21% (95% CI, -0.58; 0.15) at 21 days after cFTS, while the effect on risk of stillbirth was -0.18% (95% CI, -0.50; 0.13) at 3 days and -0.27% (95% CI, -0.58; 0.04) at 21 days after cFTS. Regarding the effect of AC on risk of miscarriage, the analysis at 28 days after cFTS showed an average effect of 0.56% (95% CI, -0.21; 1.33), while the effect on risk of stillbirth was 0.09% (95% CI, -0.39; 0.58) at 42 days after cFTS. Neither CVS nor AC was associated with increased risk of miscarriage or stillbirth. These findings indicate that the procedure-related risk of CVS and AC is very low.

First-trimester combined screening for trisomy 21 in women with renal disease.

To evaluate the results of first-trimester combined screening for Down syndrome in women with chronic renal disease. Fifty-five pregnant women with renal disease were compared with 110 patients matched for maternal age, maternal weight, smoking status, and gestational age. Maternal renal function was assayed at the time of the combined screening, and renal insufficiency was defined by serum creatinine >90 µmol/L and renal clearance <80 mL/min. We defined three groups: kidney disease and normal renal function (group 1), kidney disease and renal insufficiency (group 2), and a control group (group 3). The values of nuchal translucency, pregnancy-associated plasma protein A, human β-chorionic gonadotrophin (hCGβ), and false-positive rates for Down syndrome screening were compared. There were 39 (71%) and 16 (29%) cases in groups 1 and 2, respectively. Nuchal translucency and multiple of the median (MoM) pregnancy-associated plasma protein A were similar in the three groups. However, MoM hCGβ levels were higher in group 2 than in groups 1 and 3 (5.37 vs 1.1 vs 0.98 MoM, p = 0.0001). The resulting screen-positive rate was also higher in group 2 than in groups 1 and 3 (43.7% vs 10.2% vs 5.5%, p = 0.0001). Trisomy 21 first-trimester screening using hCGβ is not suitable in the case of maternal renal failure. © 2014 John Wiley & Sons, Ltd.

First-Trimester Screening for Down Syndrome with Serum Sampling at Different Gestational Ages: The Effect on Screening Performance

Introduction: The objective of this study was to evaluate the performance of first-trimester Down syndrome (DS) screening with serum sampling at different weeks of gestation. Material and Methods: We studied 35,431 singleton pregnancies (2005-2011), including 145 DS cases. Screening performance was determined in different maternal age groups with serum sampling between weeks 9 + 0 and 13 + 6. Results: No significant differences were found between the detection rates at different gestational weeks. The false-positive rate (FPR) in week 9 (6%) was comparable to the FPR in week 10 (6.5%; p = 0.214), whereas it was significantly lower compared to weeks 11 (7.2%; p = 0.007), 12 (7.4%; p = 0.003) and 13 (8.5%; p < 0.001). The odds of receiving a false-positive result was significantly increased with serum sampling in week 11 (OR 1.32, 95% CI 1.08-1.63; p = 0.008) for women ≥36 years and from week 12 onwards (OR 1.28, 95% CI 1.01-1.61; p = 0.04) for women <36 years. There were no differences in mean log₁₀ multiple of the median values of pregnancy-associated plasma protein-A, free β-human chorionic gonadotrophin or nuchal translucency between both age groups, nor in mean maternal age between the different gestational weeks in either age group. Discussion: Early serum sampling (<11 weeks) resulted in higher screening performance. The impact of the increase in the FPR was highest in women ≥36 years.

Pregnancy‐associated plasma protein A levels and neonatal complications in post‐date pregnancies

To assess the association between serum pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin (free β-hCG) in the first trimester and perinatal complications in post-date pregnancies. A total of 4948 women, who delivered after 40 gestational weeks, were included. Labour was not induced routinely until 42 weeks. Serum levels of PAPP-A and free β-hCG were determined at the first-trimester screening for Down syndrome. Neonatal complications were obtained from specific registration forms filled out by senior neonatologists. In post-date pregnancies, PAPP-A < 0.4 multiples of the median was associated with Apgar score of less than 7 at 5 min (ORadj 5.4, 95% CI 2.0-14.3), admission to the neonatal intensive care unit (ORadj 1.5, 95% CI 1.0-2.3) and newborn hypoglycaemia (ORadj 3.4, 95% CI 1.8-6.4). In small for gestation (SGA) neonates, the risk of hypoglycaemia was further increased (OR 14.6, 95% CI 3.4-58.0). Similar analyses were made with free β-hCG, but no statistically significant associations were found. Low first-trimester serum PAPP-A was associated with increased neonatal morbidity in post-date pregnancies, particularly in newborns with SGA. Thus, PAPP-A may qualify the timing of induction of labour in these pregnancies.

Comparison of combined, biochemical and nuchal translucency screening for Down syndrome in first trimester in Northern Finland

To compare the efficacy of fetal nuchal translucency screening, maternal serum screening and combined screening for Down syndrome. A prospective study. University hospital and its public health care district in Northern Finland. A total of 35,314 women participated in the first-trimester screening for Down syndrome within the public healthcare system in 2002-08. There were 95 pregnancies involving Down syndrome. Serum samples were obtained from 35,314 women, nuchal translucency was measured in 27,144 pregnancies and full combined screening was performed in those pregnancies, including 76 involving Down syndrome. The adjusted estimated risk for Down syndrome was calculated using the Perkin Elmer AutoDELFIA® time-resolved fluoroimmunoassay kit for the measurement of pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin. Nuchal translucency was measured by trained personnel in a university or district hospital. Risk cut-off figures 1:250 and 1:300 at term were used. Differences in detection rate, false-positive rate, positive and negative predictive values between nuchal translucency screening, serum screening and combined screening. Using the risk cut-off figure 1:250, the detection rates for serum screening, nuchal translucency screening and combined screening were 64.2, 64.5 and 72.4%, respectively and the false-positive rates were 7.8, 4.4 and 4.0%, respectively. Combined screening is the method of choice for Down syndrome screening in Finland.

963 Pregnancy-Associated Plasma Protein a Levels and Neonatal Complications in Post-Term Pregnancies

ObjectivesTo assess the association between serum pregnancy-associated plasma protein A (PAPP-A) measured in the first trimester and perinatal complications in post-term pregnancies.MethodsA total of 4948 singleton pregnant women, who delivered...

Health Technology Assessment and the Media: More Compatible than One May Think?

While the Health Technology Assessment (HTA) community has acknowledged the importance of public and consumer involvement in the HTA process, very few studies have examined how technology-related findings may be reported by the media to the broader public. This paper compares the content of press articles with the content of three Canadian HTA reports that respectively assess electroconvulsive therapy, first-trimester prenatal screening for Down syndrome, and prostate-specific antigen screening for prostate cancer. We qualitatively and quantitatively analyzed 186 press articles addressing the same technologies. Our results show that beyond stylistic emphasis, there is an important overlap between media coverage of these technologies and the content of HTA reports. Findings also highlight shared interests on which both researchers and journalists could build to enhance the communication of health information to the public.

Median levels of serum biomarkers of fetal Down syndrome detected during the first trimester among pregnant Thai women

ObjectiveTo develop Thai-specific medians of serum pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin (hCG) levels during the first trimester of pregnancy and to compare these values to a Caucasian-specific model for the detection of fetal Down syndrome. MethodsSerum concentrations of PAPP-A and free β-hCG were measured during the first trimester in a group of 2339 Thai women undergoing normal singleton pregnancies. ResultsThai reference ranges of PAPP-A and free β-hCG were established by gestational age (70–98days). The equation of best fit for PAPP-A was: predicted median PAPP-A level=28.767 – 0.781×(gestational age in days)+0.006×(gestational age in days)2; r=0.986. The equation of best fit for free β-hCG was: predicted median free β-hCG level=465.332×10(–0.024×gestational age in days); r=0.881. Weight-corrected models were also derived for each biomarker. The Thai-specific reference ranges gave higher positive screening rates than the Caucasian-specific model, even after weight correction (5.1% versus 4.0%). The Thai-specific models were validated in an independent group of 302 pregnant women. ConclusionEthnic group-specific medians for PAPP-A and free β-hCG should be incorporated during first-trimester screening for fetal Down syndrome.