Screening For Fetal Down Syndrome Research Articles

Performance of Serum Quad Test in Screening for Fetal Down Syndrome in a Large-Scale Unselected Population in a Developing Country.

Objective: To assess the effectiveness of Quad test in the detection of Down syndrome (DS) in routine practice among a large-scale population and to compare the effectiveness of Quad test based on the Western reference model (WM) and that based on Thai reference model (TM). Methods: Quad test was performed on 42,769 pregnancies at 14-21weeks. The fetal risk of DS derived from Quad test was automatically computed based on WM and used in evaluating the effectiveness. Also, the fetal risk was calculated based on the TM. Results: Of 39,740 women with complete follow-ups including 74 fetuses with DS, with WM, the detection and false positive rates were 81.1% and 7.2%, respectively, whereas the detection and false positive rates with TM were 87.8%, and 6.8%, respectively. According to ROC curves, the performance of Quad test based on TM was slightly but significantly better than that based on WM (AUC of 0.959 vs. 0.940, p = 0.001). Conclusion: Quad test is highly effective in service settings and suitable for developing countries and the effectiveness is even higher when based on ethnicity-specific reference model.

Combined First Trimester Screening for Fetal Down Syndrome at the Split University Hospital Center: a Seven-Year Experience

Combined First Trimester Screening for Fetal Down Syndrome at the Split University Hospital Center: a Seven-Year Experience

The Significance of Apolipoprotein E Measurement in the Screening of Fetal Down Syndrome.

Prenatal screening for Down syndrome (DS) is based on both noninvasive and invasive methods. Noninvasive, cell-free fetal DNA genetic tests are expensive, whereas biochemical methods remain imprecise. Amniocentesis is the most frequently used invasive diagnosis procedure, characterized by 99.8% diagnostic efficiency and less than 1% risk of miscarriage. The aim of this study was to evaluate the screening value of apolipoprotein E (ApoE) as a potential noninvasive biomarker for prenatal DS assessment. This study was conducted on a group of female patients who decided to undergo routine amniocentesis between the 15th and 18th week of pregnancy at the Department of Reproduction and Gynecological Endocrinology of the Medical University of Bialystok, Poland. For the purpose of this study, 20 women with DS fetuses were selected as the study group, and 20 healthy pregnant women with euploid fetus karyotypes as the control group. The plasma levels of ApoE were significantly higher in the study group compared to healthy subjects (p < 0.05). The area under the receiver operating characteristic (ROC) curve was 0.978 (p < 0.001), with the cut-off set to 1.37 mg/mL, which was characterized by 80% of sensitivity and 100% of specificity. The high sensitivity and specificity demonstrate the screening utility of maternal ApoE concentration in prenatal fetal DS screening.

Are the first-trimester levels of PAPP-A and fb-hCG predictors for obstetrical complications in diabetic pregnancy?

Objective To assess the levels of pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (fb-hCG) in cases of diabetic pregnancy, to determine whether these biomarkers can be considered significant predictors for macrosomia, preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth in mothers with different types of pregestational diabetes mellitus (DM). Methods It was a retrospective cohort study. Study groups were presented: type 1 DM (n = 100), type 2 DM (n = 50), and controls (n = 25). At 11 + 0 to 13 + 6 week’s gestation, we recorded maternal characteristics and medical history, and performed a combined test for the detection of risk of chromosomal abnormalities. To assess the performance of the markers in the prediction of the main obstetrical complications (PE, IUGR, preterm birth, and macrosomia), receiver-operating characteristic (ROC) curves were produced and area under the curves was calculated. Results The study has shown that DM is associated with a high rate of perinatal complications: PE, IUGR, macrosomia, and preterm birth. The median level of PAPP-A was significantly lower in case of type 1 DM- 0.89 (inter quartile range (IQR), 0.51–1.1), and type 2 DM-0.88 (IQR, 0.42–1.15) compared to the unaffected group 1.03 (IQR, 0.96–1.12; p = .025). There were no significant differences in the fb-hCG multiples of the normal median (MoM; p = .14) between the diabetic and unaffected groups. More significant results were obtained when calculated by percentile: in diabetic pregnancies, PAPP-A and fb-hCG MoMs values were lower in the 5–10% ranges and higher in the 95% range, compared to the control group. ROC-analysis did not show any significant data that first-trimester PAPP-A and fb-hCG serum levels are predictors for PE, IUGR, macrosomia, and preterm birth. Conclusion The routine first-trimester serum screening of fetal Down syndrome cannot be used as a tool of risk identification for PE, IUGR, macrosomia, and preterm birth in case of diabetic pregnancy.

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

Second-trimester maternal serum screening for fetal Down syndrome: As a screening test for hemoglobin Bart's disease: A prospective population-based study.

The purpose of this study is to determine the effectiveness of second-trimester maternal serum screening for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. A secondary analysis of a large prospective database (20254 pregnancies) was conducted to compare the levels of maternal serum screening, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin, and unconjugated estriol between pregnancies with Hb Bart's disease and unaffected pregnancies. The median AFP levels were much higher among affected fetuses (1.96 vs 1.12 multiple of the median; P<.001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cutoff value of 1.5 multiple of the median. The serum free beta-human chorionic gonadotropin levels were slightly, but significantly, higher in the affected pregnancies, while the serum unconjugated estriol levels were minimally, but significantly, lower among the affected pregnancies. Second-trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis.

Low maternal serum pregnancy-associated plasma protein-A as a risk factor of preeclampsia.

Low levels of pregnancy-associated plasma protein-A (PAPP-A) might be associated with abnormal placentation, leading to the development of preeclampsia during late gestation. We aimed to determine the association between low serum PAPP-A levels and rates of preeclampsia in Thai women with otherwise low-risk pregnancies. A cohort study was conducted on consecutive singleton pregnancies undergoing first trimester screening for fetal Down syndrome at a tertiary centre hospital. A prospective database was assessed for patient records, including PAPP-A levels, pregnancy outcomes and obstetrics complications. Pregnancies with potential causes of preeclampsia were excluded. Enrolled women were categorised into two groups: women with normal PAPP-A levels (≥ 10th percentile; control group); and those with low PAPP-A levels (< 10th percentile; study group). The main outcome measure was rate of preeclampsia. Of 6,887 women screened, 3,830 were available for analysis and 167 were excluded due to potential confounders. Of the remaining 3,663 women enrolled, 357 women were categorised as having low PAPP-A levels and 3,306 had normal PAPP-A levels. The prevalence of preeclampsia (8.4% vs. 2.6%) and early-onset preeclampsia (i.e. before 34 weeks of gestation) (1.1% vs. 0.1%) was significantly higher (relative risk 3.27 and 9.26, respectively) in women from the study group than in the control group. Pregnancy with PAPP-A levels < 10th percentile was significantly associated with an increased risk of preeclampsia that tended toward early development. Therefore, pregnant women with low PAPP-A levels in the first trimester should be considered to be at increased risk of preeclampsia.

Commentary on Down syndrome screening in China.

Prenatal screening for fetal Down syndrome has been widely practised in China for many years. In this special issue of BJOG, Tu et al. have published a systematic review on the performance of prenatal screening tests using biochemical and sonographic markers in Chinese women (Tu et al. BJOG 2016). Among the 78 included studies, of which most were from China, the majority (n = 64, 82%) were based on second-trimester biochemical markers. Although the pooled sensitivity and specificity for the second-trimester markers were 0.79 and 0.96, respectively, there were wide variations among individual studies. Most interestingly, 13 of the 64 second-trimester studies had a sensitivity of over 90%. Such an excellent performance has rarely been reported in studies from the non-Chinese population (Alldred et al. Cochrane Database Syst Rev 2012 Jun 13;(6):CD009925). This raised a concern over the quality of individual studies that warranted detailed analysis. In contrast, Li et al. reported in detail how to implement successfully a first-trimester combined screening (FTCS) programme for fetal Down syndrome in a resource-limited area of mainland China (Li et al. BJOG 2016). Despite the resource limitations, the author had followed strictly all the steps that were important for a successful screening programme, namely training and accreditation of staff, generation and use of local data, development of a customised cut-off and continuous quality assurance for both sonographers and biochemical assays. Specifically, the quality assurance steps included the following: (1) all sonographers were accredited by the Fetal Medicine Foundation and re-certified annually; (2) the performance of each sonographer was continuously monitored using a rolling standardised audit quality assurance report; (3) the multiple of the median values of individual biochemical markers were assessed monthly to determine the central tendency and dispersion; and (4) outcome data were followed-up. The above steps allowed early identification of deviation from expected performance for which early intervention could be initiated. Certification and quality assurance of sonographers is a particularly difficult process, requiring the support and cooperation of hospital administrators. It is interesting that in Li et al.'s study the cost of FTCS was quoted to be RMB800. Based on screening performance, noninvasive prenatal testing (NIPT) for fetal Down syndrome by cell-free DNA in maternal plasma is a far better test than FTCS, having a sensitivity and a specificity both above 99%. The cost of NIPT has come down substantially over the past 2 years. In China, NIPT is available in many major cities at a current user price most commonly between RMB2000 and 3000. It should not be long before the cost of NIPT is comparable to that of FTCS. At present, many hospitals in China are developing their own in-house NIPT platforms. This is a suboptimal move because such small hospital-based laboratories will not have enough volume to maintain a meaningful quality assurance programme. It is advisable that these screening programmes are coordinated within a region and centralised in one or a few centres where a strict quality assurance programme could be implemented. Even if NIPT has replaced conventional screening, the concept of ‘quality assurance’ as demonstrated in the study by Li et al. remains the key to the success for all screening programmes. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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.

First trimester screening cut-offs for noninvasive prenatal testing as a contingent screen: Balancing detection and screen-positive rates for trisomy 21.

To provide data on how screen-positive and detection rates of first trimester prenatal screening for fetal Down syndrome vary with changes in the risk cut-off and maternal age to inform contingency criteria for publicly funded noninvasive prenatal testing. First trimester screening and diagnostic data were collected for all women attending for first trimester fetal aneuploidy screening in Western Australia between 2005 and 2009. Prenatal screening and diagnostic data were linked to pregnancy outcomes, including data from the Midwives' Notification System and the Western Australian Registry of Developmental Anomalies. The prevalence of Down syndrome and performance of screening by risk cut-off and/or for women >35 years were analysed. The current screening risk cut-off of 1:300 has screen-positive and detection rates of 3.5% and 82%. The screen-positive rate increases by 0.7-0.8% for each 100 point change in risk, up to 19.2% at 1:2500 (96% detection rate). Including all women >35 years as screen positive would increase the screen-positive rate and detection rates to 30.2% and 97.2%. Variation in screening risk cut-off and the use of maternal age to assess eligibility for noninvasive testing could significantly impact the demand for, and cost of, the test. A contingent first trimester screening approach for risk assessment is superior to the use of a combination of screening and maternal age alone. These data will inform decisions regarding the criteria used to determine eligibility for publicly funded noninvasive prenatal testing.

Noninvasive prenatal screening by next-generation sequencing.

Noninvasive prenatal screening (NIPS) has emerged as a highly accurate method of screening for fetal Down syndrome, with a detection rate and specificity approaching 100%. Challenging the widespread use of this technology are cost and the paradigm shift in counseling that accompanies any emerging technology. The expense of the test is expected to decrease with increased utilization, and well beyond the current NIPS technology, its components (fetal genome measurements, sequencing technology, and bioinformatics) will be utilized alone or in combinations to interrogate the fetal genome. The end goal is simple: to offer patients information early in pregnancy about fetal genomes without incurring procedural risks. This will allow patients an opportunity to make informed reproductive and pregnancy management decisions based on precise fetal genomic information.

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.

FIRST AND SECOND TRIMESTER SONOGRAPHIC SCREENING FOR FETAL DOWN SYNDROME

Screening for Down syndrome is an important part of routine antenatal care and should be made available, if requested, after appropriate counselling including risks and benefits, to all pregnant women, regardless of maternal age. Prenatal screening for fetal Down syndrome and other aneuploidies has advanced significantly since its advent in the 1980s. Historically, women 35 years or older were offered prenatal genetic counselling and the option of a diagnostic test such as chorionic villus sampling or amniocentesis. With this screening approach only 20% to 30% of the fetal Down syndrome population are detected antenatally. Sonographic and maternal biochemical markers are now used in combination to screen for aneuploidies in the first and second trimesters. The most common screening method in the first trimester combines the maternal serum markers HCG and PAPP-A with the sonographic evaluation of fetal nuchal translucency thickness. Newer markers have been proposed to further refine the risk assessment for Down syndrome to maximise detection rates and minimise false positive rates. These newer first trimester markers include sonographic assessment of the fetal nasal bone (NB), the frontomaxillary facial (FMF) angle, ductus venosus (DV) Doppler and tricuspid valve regurgitation (TR).

Maternal Homocysteine Level and Markers Used in First-Trimester Screening for Fetal Down Syndrome

This study examined possible relationships between homocysteine and markers used in first-trimester screening for Down syndrome. Pregnancies were categorized into 4 groups according to quartile ranking of maternal plasma homocysteine concentration. Of the 595 pregnancies, 147 were assigned to group 1 (homocysteine level 0.6-3.5 μmol/L), 156 to group 2 (homocysteine level 3.6-4.5 μmol/L), 142 to group 3 (homocysteine level 4.6-5.6 μmol/L), and 150 pregnancies to group 4 (homocysteine level 5.7-12.6 μmol/L). No significant difference in mean nuchal translucency and mean free β-human chorionic gonadotropin (free-βhCG) multiples of the median (MoM) levels were observed. However, the mean pregnancy-associated plasma protein A (PAPP-A) MoM levels were significantly decreased in inverse relationship with homocysteine level among all 4 groups (F = 31.127, P < .001). If homocysteine is assayed as part of the first-trimester maternal serum testing, it is important to adjust for homocysteine concentration when using PAPP-A serum level for calculating the risk of fetal aneuploidy.

P11.16: Median levels of free beta-hCG and PAPP-A in the first trimester screening for Down syndrome in a Brazilian population from a private center in Rio de Janeiro

To assess whether there is a need to correct first-trimester biochemical markers (free beta-hCG and PAPP-A) in a Brazilian population from a private center in Rio de Janeiro (Perinatal Group—Laranjeiras) while screening for Down syndrome using the Fetal Medicine Foundation (FMF) algorithm. The data from 546 women undergoing first trimester combined screening for fetal Down syndrome were analyzed to derive our center population-specific medians. The observed medians were compared to those based on the original algorithm of the Fetal Medicine Foundation (FMF) in Caucasians. The median maternal serum levels of free beta-hCG and PAPP-A were similar between the target population and average Caucasians. There was no need to correct the original FMF algorithm for the Brazilian population analyzed in this study. There is no need to adjust the biochemical markers in the Brazilian population from our center in Rio de Janeiro in a first trimester screening program.

Prenatal Diagnosis in the First Trimester of Pregnancy

In the past 2 decades, the second trimester of pregnancy has been the most common time for prenatal diagnosis of fetal anomalies and chromosomal aneuploidies. More recently, screening for and diagnosis of chromosomal abnormalities are increasingly being performed in the first trimester. With improvements and technological advances in ultrasound, it is now possible to identify many fetal structural anomalies at 11 to 13 6/7 weeks' gestation. At 10 to 11 weeks' gestation, biochemical markers in serum-PAPP-A, free beta-hCG, AFP, and uE3-combined with sonographic measurement of nuchal translucency and the presence/absence of the nasal bone can achieve a Down syndrome detection rate of 97.5% at a false-positive rate of 5%. Structural anomalies of the central nervous system, and the cardiac, renal, and gastrointestinal tracts can now be diagnosed by either transabdominal or transvaginal scanning, achieving detection of up to 80% of CNS anomalies by 13 weeks' gestation. In future, the emphasis in prenatal diagnosis will likely be in the first trimester. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader should be able to explain the rationale for first trimester combined ultrasound and serum analyte screening for fetal Down syndrome, describe the fetal anatomic structures that can be seen and evaluated in the first trimester, provide patient counseling about the relative benefits of genetic amniocentesis versus chorionic villous sampling, and discuss the application of Doppler technology to the evaluation of a first trimester fetus.

Expected performance of second trimester maternal serum testing followed by a ‘genetic sonogram’ in screening of fetal Down syndrome

To assess the efficacy of screening for fetal Down syndrome through the sequential provision of second trimester maternal serum tests and fetal ultrasound (the 'genetic sonogram'). Monte Carlo modeling was used to generate typical results for second trimester serum screening. Serum test likelihood ratios were then multiplied by likelihood ratios associated with the provision of a genetic sonogram. The impact of adding the genetic sonogram on the detection rate (DR) and false-positive rate (FPR) were assessed for typical protocols that are currently in use. The effect of expanding the number of women who receive the genetic sonogram, variation in the marker frequencies in the genetic sonogram, and a multivariate Gaussian model that incorporated both serum and ultrasound measurements as continuous variables were also considered. When the genetic sonogram is offered only to those women who are screen-positive by serum testing, there can be a substantial reduction in the number of women with an indication for amniocentesis but also some loss in detection. The extent of these changes will partially depend on the serum tests and cutoff used. Providing the genetic sonogram to more women can reduce loss in detection without resulting in high amniocentesis rates. As a sequential screening tool, the genetic sonogram can be improved by incorporating markers that have a high frequency in affected pregnancies and by using ultrasound measurements as continuous variables. It should be possible to provide highly effective multistep screening protocols that maximize the benefits of both maternal serum and ultrasound while minimizing the amount of testing offered.

Patient choice in first trimester screening for fetal down syndrome

DEVEREUX SALLER, LISA PASTORE, KAREN VENTURA, LOGAN KARNS, ERIKA WERNER, University of Virginia, Obstetrics & Gynecology, Charlottesville, Virginia OBJECTIVE: Options for Down syndrome (DS) screening in the first trimester include combined first trimester screening (FTS) (nuchal translucency (NT) & first trimester serum markers) & integrated screening (Integrated) (NT, first & second trimester serum markers). We investigated patient choice & motivation regarding these screening options, theorizing that the test chosen might be predictable based on demographic characteristics. STUDY DESIGN: Patients had genetic counseling & were offered FTS or Integrated. An attempt was made to objectively describe the advantages of each test. All patients were offered a survey prior to undergoing NT. Whether completed or not, the survey was sealed in an envelope & forwarded to the study epidemiologist. Medical providers were blinded as to participation. RESULTS: Of 100 patients, 78 non-selected patients and 41 partners completed the form. 47 (60%) & chose FTS & 31 (40%) chose Integrated. There were no differences between FTS and Integrated patients in Maternal Age, genetic counselor, indication (O35yo vs. screening), educational level, working outside the home, or proximity to our medical center (p range=0.090.98). The median age in both groups was 35, however there was a significant difference in a priori age-related DS risk (Median risk: FTS 1:190 vs. Integrated 1:300, p=0.02). FTS was chosen by some of the youngest & oldest patients, yielding the same median age, but a higher median age-related risk. Reasons for choosing the screening test differ by test chosen (p!0.001). Reasons stated most frequently were: ‘‘earliest reassurance’’ (79% FTS) vs. ‘‘most information’’ (80% Integrated) and ‘‘lowest chance of needing additional diagnostic testing’’ (55% Integrated). CONCLUSION: Given the choice and objective counseling, significant percentages of patients chose each screening test. Patient choice of FTS or Integrated screening is not predictable based on demographic characteristics. Following genetic counseling, the stated reasons for choosing a particular screening test were consistent with the characteristics of that test.

Higher Median Levels of Free β-hCG and PAPP-A in the First Trimester of Pregnancy in a Chinese Ethnic Group

Objective: To study the effect of ethnic Chinese on the medians of free β-hCG and PAPP-A in the first trimester of pregnancy. Methods: The data of 943 women undergoing first trimester combined screening for fetal Down syndrome were analysed to derive the Chinese-specific medians. The calculated risk of Down syndrome based on these Chinese-specific medians was compared with that based on the original algorithm of the Fetal Medicine Foundation (FMF). Results: The maternal serum levels of multiples of median of free β-hCG and PAPP-A were significantly higher among the Chinese than among the Caucasians. The weight-adjusted gestation-specific medians were developed. Without adjustment for ethnicity, the original FMF algorithm underestimated the risk of Down syndrome by a median of 1%. Adjustment by ethnicity increased the false-positive rate by 10% (from 5.3 to 5.9%). Conclusion: Ethnic Chinese have a significantly higher maternal serum level of free β-hCG and PAPP-A in the first trimester, which could not be explained by differences in maternal weight. Adjustment for ethnicity may be necessary for these biochemical markers in a first trimester screening program.

Placental volume, as measured by 3-dimensional sonography and levels of maternal plasma cell-free fetal DNA

Measurement of cell-free fetal (cff) DNA in maternal plasma may have clinical application in prenatal screening for fetal Down syndrome and preeclampsia. Little is known regarding the tissue of origin of these fetal-derived sequences. We tested the hypothesis that if the placenta is the major contributor of cff DNA, then an increased placental volume should be associated with higher maternal plasma cff DNA levels. We enrolled 143 pregnant women who underwent first-trimester placental volume measurement using 3-dimensional ultrasonography. Cff DNA in maternal plasma on the day of the scan was quantified by real-time polymerase chain reaction (PCR) amplification of a Y-chromosome sequence. The association between measured placental volume and maternal plasma cff DNA levels was analyzed along with relevant clinical variables. The median (25th, 75th percentiles) maternal plasma cff DNA level was 16.9 genome equivalents (GE)/mL (10.8, 28.7). Raw values were adjusted for gestational age and maternal body mass index. The median (25th, 75th percentiles) placental volume was 53.2 mL (43.0, 64.7), and median placental quotient (ratio of placental volume to fetal crown-rump length) was 1 mm2 (0.8, 1.1). Based on multivariate linear regression analyses, neither of the above placental measurements showed a significant association with maternal plasma cff DNA levels (P = .43 and .43, respectively). A modest association was found between plasma cff DNA levels and gravidity (P = .03). Our data did not show a significant association between either the placental volume or placental quotient, and maternal plasma cff DNA levels. We speculate that it is the extent of placental apoptosis that primarily affects the amount of cff DNA released into the maternal circulation.