Maternal Serum Screening Research Articles

Certified Nurse-Midwives' Experiences With Provision of Prenatal Genetic Screening: A Case for Interprofessional Collaboration.

Prenatal genetic screening (GS) for the most common autosomal aneuploidies encompasses maternal serum screening (MSS) and noninvasive prenatal testing (NIPT, or cell-free fetal DNA testing). In the United States, most maternity care is provided by obstetrician-gynecologists; however, women are increasingly utilizing the services of certified nurse-midwives (CNMs). Currently, limited research exists on midwives' experiences with providing prenatal GS. Therefore, the purpose of this study was to explore CNMs' experiences in providing prenatal GS. A semistructured guide focused on MSS and NIPT was used to interview a convenience sample of 13 CNMs. Results were coded and analyzed using grounded theory to elicit overarching themes. Results were organized into 6 themes describing CNMs' prenatal GS provision: (1) clinical protocols; (2) patient education; (3) patient-CNM shared decision-making process; (4) testing initiation; (5) results delivery; and (6) follow-up coordination. Key influences on midwives' perspectives on offering prenatal GS included a noninterventionist approach to pregnancy and past experiences with false-positive MSS results. Participants had an understanding of prenatal GS that was appropriate to midwifery scope of practice. Results indicate that NIPT utilization is compatible with the midwifery philosophy of noninterventionism, although midwives had limited experiences with NIPT to date.

EP05.03: An atypical case of Turner syndrome

Turner syndrome is a genetic disease with a karyotype of 45, X or 46, XX/45, X (mosaicism). 1/2500 female live births are affected, although 15% of spontaneous miscarriages show an X monosomy and only 1% of fetuses will survive to term. Typical prenatal findings are nuchal cystic hygroma, nonimmune hydrops, and renal and cardiac abnormalities. However, neither sonography nor maternal serum screening can be considered diagnostic of Turner syndrome, and karyotype confirmation is mandatory. A 38-year-old III gravida II para presented for first trimester screening in 13 gestational weeks. The first child was born with biliar atresia and needed living liver donation at the age of 3 weeks. The 2nd child is healthy. This fetus presented with a nuchal fold of 3.3.mm, generalised edema and an early IUGR at a CRL of 55mm. The nasal bone was hypoplastic. The fetus showed hypertelorism, low set ears and a strawberry shaped head. The IT was not visible and a sacral spina bifida was detected. Besides an omphalocele, there was a congenital heart defect, suspicious for TOF with pericardial effusion, cardiomegaly, VSD, overriding aorta and suspected pulmonary stenosis. CVS was performed but probably contaminated by maternal cells. In the framework of scientific research postnatal molecular karyotyping could surprisingly confirm 45/X0 twice. In conclusion, as our case shows, Turner syndrome can present with a broad heterogenity of signs and symptoms. The wide range of prenatal features indicates that a number of different X-located genes are responsible for the complete phenotype. Nevertheless affected fetuses show a substantial number of early-onset signs that can be detected in the first trimester, i.e. cystic hygroma, fetal hydrops, cardiac defects and increased nuchal translucency and can be diagnosed in early pregnancy. The difference in the appearance of NT in each chromosomal defect may reflect the heterogeneity of causes, hence invasive diagnostics is mandatory. 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.

Avoiding Unnecessary Disparities in Care: Evaluating Noninvasive Prenatal Screening Performance via Whole Genome Sequencing Across Classes of Obesity

Purpose/AimExamine how well noninvasive prenatal screening (NIPS) performs in women across body mass index (BMI) classes.HypothesisNIPS via whole genome sequencing better serves all women, regardless of BMI, compared with traditional maternal serum screening.Significance/BackgroundNoninvasive Prenatal Screening (NIPS), increasingly offered as a first‐line aneuploidy screen, has superior performance compared with maternal serum screening (MSS). Fetal fraction (FF) is one of the many factors that influence the performance of NIPS. Low FF is associated with early gestational age, a compromised placenta (eg, from triploidy and certain aneuploidies), and high BMI. By far, the most common driver of low FF is high BMI. The most recent American College of Medical Genetics and Genomics statement recommends “offering aneuploidy screening other than NIPS in cases of significant obesity.” However, patients with high BMI constitute approximately25% of US pregnancies, creating a significant disparity in care based on weight.Methods58,639 patients who received NIPS were stratified into standard BMI classes. For each BMI group, the aggregate analytical sensitivity was calculated by summing—over the range of FF values—the product of 1) the sensitivity for a given FF and depth based on a model of whole‐genome sequencing (WGS) NIPS and 2) the BMI‐specific probability of observing a patient at that FF. Scaled sensitivities were incorporated into residual‐risk calculations to assess impact on patient results reporting.FindingsDue to downward shifts in the FF distribution, NIPS sensitivity drops as BMI increases: non‐obese analytical sensitivity for T21 is 99.5%, whereas for class III it is 94.1%. Nevertheless, even patients with class III BMI have expected T21 sensitivity in excess of that obtainable via standard MSS (92.9%). Sensitivity for T13 and T18 was also higher across the BMI spectrum for WGS‐based NIPS relative to MSS.DiscussionWGS‐based NIPS with high performance at low FF is a high‐quality aneuploidy screening option for all women, regardless of BMI. Providers can therefore offer the same high level of care to all patients, regardless of body habitus.

Exome Sequencing Identifies RET Associated Hirschsprung Disease in a Fetus with Echogenic Bowel

AbstractThis is report of a case of RET associated Hirschsprung disease in a fetus diagnosed using exome sequencing. The fetus initially presented with echogenic bowel at 16 weeks with maternal first trimester serum screen showing increased risk for Trisomy 21. Amniotic fluid karyotype, ΔF508 CFTR genotype and maternal TORCH serology were normal. Subsequent ultrasonograms showed dilated bowel loops, predominantly large bowel. Following delivery at 24 weeks, a post-mortem examination was performed. Dilated bowel was confirmed with no structural gut abnormality and no other dysmorphic finding. Histopathology revealed agangliosis confirming a diagnosis of Hirschsprung disease. Exome sequencing done on fetal DNA from amniotic fluid revealed a putative pathogenic heterozygous c.1438G > A variant in exon 7 of RET gene, which was inherited from the asymptomatic mother. This enabled genetic counseling and prenatal diagnosis in subsequent pregnancy.

A cross-sectional study on maternal anxiety levels after cytomegalovirus screening

Purpose: we aimed to estimate the anxiety levels of pregnant women following maternal serum screening for CMV infection.Materials and methods: In this case-control study conducted from April 2016 to June 2017, we enrolled all pregnant women referred to our hospital who were CMV immunoglobulin (Ig) M antibody positive (IgM-positive group, n = 51); further, those who were CMV IgG positive but IgM negative (IgM-negative group, n = 51) during the same period were included as study controls. Data were collected on patient characteristics, CMV IgM levels, and whether patients were accompanied by their partners during the first hospital visit after CMV IgM testing. The State-Trait Anxiety Inventory was used to assess anxiety levels.Results: Both groups were age matched [mean age (years): IgM-positive, 30 ± 4.2 and IgM-negative, 29.9 ± 4.6]. The mean state-anxiety score was higher in the IgM-positive group (53 ± 9.6) than in the IgM-negative group (38.5 ± 7.0, p < .05) with no between-group differences in trait-anxiety scores. Similarly, a higher number of women were accompanied by their partners in the IgM-positive group. The state-anxiety scores and CMV IgM levels were not correlated in the IgM-positive group.Conclusion: Counseling support is essential for IgM-positive pregnant women following serum screening, and the screening should be avoided if support systems are unavailable.

Death of a Fetus With Myeloproliferative Disorder and Trisomy 21

A 27-year-old woman, gravida 2, para 1, presented at 24 weeks gestation with an intrauterine death. She previously consulted with maternal-fetal medicine because of a high suspicion of trisomy 21 after abnormal maternal serum screen and cell-free DNA test results. The patient elected to have chromosomal analysis following the death of the fetus, which confirmed a trisomy 21 diagnosis. Placental pathologic findings suggested that the cause of fetal death was total occlusion of the major vessels due to the accumulation of myeloid precursor cells, a novel mechanism. This case report discusses the rare finding of myeloproliferative disorder as a cause of death of a fetus with trisomy 21.

Aiding Risk Information learning through Simulated Experience (ARISE): A Comparison of the Communication of Screening Test Information in Explicit and Simulated Experience Formats.

To determine whether the use of Aiding Risk Information learning through Simulated Experience (ARISE) to communicate conditional probabilities about maternal serum screening results for Down syndrome promotes more accurate positive predictive value (PPV) estimates and conceptual understanding of screening, compared with explicitly providing individuals with this information via numerical summary or icon array. In experiment 1, 582 participants completed an online study in which they were asked to estimate the PPV and rate their attitudes toward a screening test when information was presented in either a description (required calculation of the PPV), explicit (PPV was provided and had to be identified), or an ARISE format (PPV was inferred through experience-based learning). In experiment 2, 316 participants estimated the PPV and rated their attitudes toward screening based on information presented in either an icon array (identify the icons that represent the PPV) or ARISE format. In experiment 1, ARISE elicited the most accurate PPV estimates compared with the description and explicit formats, and both the explicit and ARISE formats led to more unfavorable attitudes toward screening. In experiment 2, both the icon array and ARISE resulted in similar PPV estimates; however, ARISE led to more negative attitudes toward screening. These findings suggest that ARISE may be superior to other formats in the communication of PPV information for screening tests. However, differences in the complexity of the formats vary and require further investigation.

Introduction of cell-free DNA screening is associated with changes in prenatal genetic counseling indications.

The introduction of cell-free DNA screening, or non-invasive prenatal testing (NIPT), for chromosome abnormalities has greatly impacted prenatal care since its introduction in late 2011. We aimed to evaluate the association between the introduction of cell-free DNA screening and indication and referral patterns for genetic counseling at a large US academic medical center by comparing the percentage of each counseling indication between the time period prior to the introduction of cell-free DNA screening (2006-2011) and following its introduction (2012-2016) using multivariable Poisson regression models. Genetic counseling indications for positive carrier screens, average risk patients, abnormal ultrasound findings, and family history indications were significantly higher following the introduction of NIPT while advanced maternal age and abnormal maternal serum screening indications dropped significantly. We also showed that the uptake of amniocentesis dropped significantly after the introduction of cell-free DNA screening, while chorionic villus sampling uptake increased. These results provide evidence that the introduction of new genetic screening technologies is associated with a shift in genetic counseling referral indications and an increased uptake in genetic screening. Additional research is needed to explore the impact of expanded testing options on the need for genetic counseling services.

Prenatal diagnosis in Finland.

In Finland the local authorities are responsible for the provision of prenatal diagnostic services for the communities or the community pays for the visits of its citizens to the larger hospitals. The local authorities have autonomy in making the policies for prenatal diagnosis, which leads to an uneven availability of the services, i.e. availability of ultrasound (US) screening, maternal serum screening, and age limits for fetal chromosome studies due to advanced maternal age. The municipalities receive Government aid for health care. In all areas, US screening and screening for fetal chromosome anomalies either by advanced maternal age only or maternal serum screening are arranged. Families with special problems are sent to five university hospitals for prenatal diagnostic services. To make possible the prenatal diagnosis of the autosomal recessive diseases belonging to the Finnish disease heritage, a special effort has been made on their molecular genetics. The uptake level of ultrasound screening is on average 90%. In cases of abnormal findings, the patients are referred to central or university hospitals for further examinations. The uptake of amniocentesis (AC) or chorionic villus sampling (CVS) due to advanced maternal age is 50-85%. The high numbers come from southern and urban parts of the country. The uptake for maternal serum screening is probably of the similar or of even higher order. In addition to the public services, private prenatal diagnosis, US, maternal serum screening, AC and CVS are available in all parts of Finland.

Prenatal diagnosis in Italy.

In Italy, there are about 560,000 births per year. The number of prenatal diagnoses (PND) performed is estimated at 80,000 examinations per year, but no official data are available regarding the distribution of the different procedures. There are no official registers, either at a national or at a regional level, concerning PND and particularly the invasive procedures (as amniocentesis, chorionic villus sampling, chordocentesis). Thanks to the direct interest of some scientific societies, such as the Italian Association of Medical Cytogenetics, the Italian Association of Medical Genetics, the Italian Society for the Study of Metabolic Hereditary Diseases and the Italian Society of Gynaecology and Obstetrics, it has been possible to identify the number and distribution of public and private structures interested in genetic counselling and prenatal diagnosis during the last decades. As to the congenital malformations, there is a regional epidemiological system of surveys (started in 1982) co-ordinated by the Epidemiological and Biostatistical Laboratory of the 'Istituto Superiore di Sanità' (National Board of Health). This institution has published data for the period between 1986 and 1990 concerning the trend of incidence for the most important malformations at birth. Cytogenetic PND in public services is allowed for the following indications: maternal age 35 and over, previous child with a chromosomal anomaly, parent with a constitutional chromosomal abnormality and abnormal findings at the ultrasound examinations. Current methods in use consist in echography, amniocentesis, chorionic villus sampling, fetal blood sampling and maternal serum screening. At the moment, new approaches to the fetal tissue sampling are, as follows: amniotic fluid filtration, transcervical cell sampling and isolation of fetal cells from maternal blood. Furthermore, areas under development are 3D sonography and first-trimester anatomic survey sonography. PND is financed by regional laws, the National Health Service and private funds. There is a current legislation on termination of pregnancy (Law 194/1978). This law permits voluntary interruption of pregnancy within the first 90 days, while it is permitted between 90 and 180 days only in cases of severe fetal anomalies and over 180 days for serious risks for the woman's life: but it is necessary to do everything to save the fetal life. No law has been issued yet on pre-implantation diagnosis. Presently, the major problems are: the unbalanced distribution of financial resources among the different regions, the irrational number and distribution of centres for PND, inadequate prenatal counselling, especially in central/southern Italy, where counselling is somehow lacking. Therefore, guidelines for appropriate prenatal counselling should be established. For the future, we believe that the best results in this field are probably related to the advances of research (there is a target programme of the Italian National Research Council called 'Genetic Engineering', which is in its fourth year of financing). This programme will hopefully be cost-effective and improve the quality of PND so that more congenital anomalies can be detected at lower expenses in the future.

Prenatal diagnosis in Switzerland.

Switzerland, with a population of slightly over 7 million, has about 83,000 births per year. There is no comprehensive national registry for prenatal diagnosis (PND) or congenital malformations. Health care is largely organised within each of the 23 countries. Whereas ultrasound screening is available to all pregnant women, the availability of other types of PND is largely determined by proximity to the university medical centres or specialised clinics. Maternal biochemical serum screening is offered by some 15-20 laboratories, and cytogenetic analyses are performed in 8. DNA-based diagnosis is essentially limited to the medical genetics departments/divisions of the 5 university medical schools. It can be estimated that slightly over 10% of gestations are monitored by invasive prenatal diagnostic techniques. The greatest challenge for the future will be the training of the medical and paramedical personnel necessary for the current and future pre- and postnatal diagnostic testing.

Prenatal diagnosis in Spain.

An overview of the national organisation of prenatal diagnosis (PND) in Spain is presented. Although PND is technically well developed and the number of prenatal services seems to be adequate, the uneven distribution between regions is reflected in a different prevalence reduction of chromosomal disorders and congenital malformations. Only about 41% or pregnant women use PND, with a wide range (14-64%) between regions. There is no national policy in PND or maternal serum screening for Down's syndrome, but local policies. As clinical genetics is not an officially recognised speciality, there is a shortage of clinical geneticists and it is difficult to organise PND activities and regulate them by law.

Cost-Effectiveness Analysis of Non-invasive Prenatal Testing for Down Syndrome in China.

There is little evidence in China regarding the cost-effectiveness of non-invasive prenatal testing (NIPT) for Down syndrome (DS). This study aims to evaluate the cost-effectiveness of NIPT and provide evidence to inform decision-making. To determine the cost-effectiveness of NIPT for DS, a decision-analytic model was developed using the TreeAge Pro software from a societal perspective in a simulated cohort of 10 000 pregnant women. Main indicators were based on field surveys from sampled hospitals in four locations in China and a literature review. The conventional maternal serum screening (CMSS) strategy, contingent screening strategy (NIPT delivered to high risk pregnant women after CMSS), and universal screening strategy could prevent 3.02, 7.53, and 9.97 DS births, respectively. NIPT would decrease unnecessary invasive procedures, resulting in fewer procedure-related miscarriages. The cost-effectiveness ratio of the contingent screening strategy was the lowest. When compared with the CMSS strategy, the incremental cost per DS birth averted by the contingent screening strategy and universal screening strategy were USD 20,160 and 352,388, respectively. One-way sensitivity analysis showed that, if the cost of NIPT could be decreased to USD 76.92, the cost-effectiveness ratio of the universal screening strategy would be lower than the CMSS strategy. Although NIPT has the merits of greater effectiveness and safety, CMSS is unlikely to be replaced by NIPT at this time because of NIPT's higher cost. Contingent screening may be an appropriate strategy to balance the effectiveness and cost factors of the new genetic testing technology.

The trends of prenatal screening and prenatal diagnosis in Taiwan from 2006 to 2015

Objective To determine the trends in the impact of combined first-trimester testing in conjunction with second-trimester maternal serum screening and non-invasive prenatal diagnosis in Taiwan from 2006 to 2015 Methods This national registry-based cohort retrospective study examined a total of 2,019,369 births from January 2006 to December 2015. In the 10-year period, the prenatal screening methods evolved from second-trimester serum test screening to the combined first-trimester test and the secondary-trimester quadruple test, followed by non-invasive cell-free DNA prenatal screening. Official policy indications were implemented for prenatal cytogenetic diagnosis among pregnant women. Personal registration numbers of women who had an amniocentesis or chorionic villus sampling (CVS) were retrieved from the Taiwan Central Cytogenetic Registry and cross-linked with the National Registry of Patients to determine the outcome of each pregnancy. The data used were provided by the Health Promotion Administration of Ministry of Health and Welfare. Results We estimated that the total number of invasive prenatal diagnoses was 410,972, and the overall rate of invasive procedures was 21.82%. The proportion of advanced maternal age (AMA) increased from 11.8% in 2006 to 24.9% in 2015. The rate of the indication for invasive prenatal diagnosis in AMA increased from 62.7% in 2006 to 91.2% in 2015. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 93.7% and 99.1% in 2015, respectively. The population prevalence's of trisomy 21, 18, and 13 were one in 739, 2920, and 10847, respectively. Discussion The amount of AMA pregnant women increased year by year, and the number of invasive procedures increased with age. However, the detection rate was also increased by the improvements in screening methods.

Down Syndrome Prediction Using a Cascaded Machine Learning Framework Designed for Imbalanced and Feature-correlated Data

Down syndrome (DS) caused by the presence of part or all of a third copy of chromosome 21 is the most common form of aneuploidy. The prenatal screening for DS is a key component of antenatal care and is recommended to be universally offered to women irrespective of age or background. The objective of this paper is to introduce a noninvasive and accurate diagnosis procedure for DS and to minimize social and financial cost of prenatal diagnosis. Recently, machine learning has received considerable attention in predictive analytics for medical problems. However, there is few its applications on DS prediction reported due to the difficulty of dealing with highly imbalanced and feature-correlated screening data. In this paper, we propose a cascaded machine learning framework designed for DS prediction based on three complementary stages: 1) pre-judgment with isolation forest technique, 2) model ensemble by voting strategy, and 3) final judgment using logistic regression approach. The experimental results show that the performance of this framework on maternal serum screening data set, when evaluated with different evaluation parameters, is superior to those of some machine learning methods. The best suggested combination of input features for DS screening is the group of alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and maternal age. In addition, our method has the potential to generate further accurate prediction for imbalanced and feature-correlated data, thereby providing a novel and effective approach for certain diseases analysis.

Maternal serum screening marker levels in twin pregnancies affected by gestational diabetes.

To investigate the levels of maternal serum screening markers in the first and second trimester twin pregnancies, which subsequently developed gestational diabetes mellitus (GDM). 145 twin pregnancies were recruited in the first trimester. Stored blood samples were retrospectively tested for pregnancy-associated plasma protein (PAPP)-A, human chorionic gonadotrophin (hCG), placental growth factor (PlGF), placental protein (PP)13, α-fetoprotein (aFP) and inhibin A. Values were expressed in multiples of the gestation-specific median (MoMs) in singletons, adjusted for maternal weight and parity, as appropriate. Twenty samples of first and second trimester were available from 11 twins who subsequently developed GDM and 219 samples from unaffected twins. The median PAPP-A level in the affected twins was 3.61 MoM compared with 2.46 MoM in unaffected twins (P < 0.001, Wilcoxon rank sum test, two tailed); significant results were found in both trimesters. The median PP13 was also increased but to a lesser extent. It was only statistically significant overall (P < 0.05) and in second trimester samples (P < 0.02). No other marker differed significantly. Logistic regression found that combining PAPP-A and maternal weight had a 55% detection rate for a 10% false-positive rate. Early prenatal marker evaluation in twin pregnancies can be also useful for predicting the risk for developing GDM and should be further investigated.

Patient decision-making and the role of the prenatal genetic counselor: An exploratory study.

Despite much theory about how genetic counseling facilitates prenatal decision-making, there are limited data regarding patients' perceptions of the process and the role of the genetic counselor (GC). Our aim in this study was to explore patients' perceptions of their prenatal genetic counseling session, with a focus on their relationship with their GC and how factors inside and outside the session influenced their decision-making about amniocentesis. We performed a qualitative study with patients who had seen a GC after maternal serum screening revealed an increased risk for aneuploidy. Semistructured interviews were transcribed verbatim, and analyzed using a constant comparative method. To complement and triangulate with these data, we used a secondary quantitative measure-the 6-item Satisfaction With Decision-making (SWD) scale, and questionnaires completed by participants' GCs. Eleven patients participated and four predominant themes emerged from our data: (1) being unprepared; (2) recognizing responsibility for decision-making; (3) the burden of responsibility; and (4) the impact of support through affirmation. Despite the underlying tension within these themes, patients reported high satisfaction with their decisions (SWD mean score=28.5/30, range: 26-30). Patients perceived their GCs to be nonbiased yet supportive in the decision-making process. Patients described feeling affirmed, but not swayed in their decision.

Improving women\u2019s knowledge about prenatal screening in the era of non-invasive prenatal testing for Down syndrome \u2013 development and acceptability of a low literacy decision aid

BackgroundAccess to information about prenatal screening is important particularly in light of new techniques such as non-invasive prenatal testing (NIPT). This study aimed to develop and examine the acceptability of a low literacy decision aid (DA) about Down syndrome screening among pregnant women with varying education levels and GPs.MethodsWe developed a DA booklet providing information about first-trimester combined testing, maternal serum screening, and NIPT. GPs and women participated in a telephone interview to examine the acceptability of the DA and measure screening knowledge before and after reading the DA. The knowledge measure was designed to assess whether women had understood the gist of the information presented in the decision aid. It comprised conceptual questions (e.g. screening tells you the chance of having a baby with Down syndrome) and numeric questions (e.g. the accuracy of different screening tests).ResultsTwenty-nine women and 18 GPs participated. Regardless of education level, most women found the booklet ‘very’ clearly presented (n = 22, 76%), and ‘very’ informative (n = 23, 80%). Overall, women’s conceptual and numeric knowledge improved after exposure to the DA, from 4% having adequate knowledge to 69%. Women’s knowledge of NIPT also improved after receiving the decision aid, irrespective of education. Most GPs found it ‘very’ clearly presented (n = 13, 72%), and that it would ‘very much’ facilitate decision-making (n = 16, 89%).ConclusionsThe DA was found to be acceptable to women as well as GPs. A comprehensive evaluation of the efficacy of the decision aid compared to standard information is an important next step. Strategies are needed on how to implement the tool in practice.

Cell-free fetal DNA versus maternal serum screening for trisomy 21 in pregnant women with and without assisted reproduction technology: a prospective interventional study

PurposeCell-free DNA (cfDNA) as a primary screening test has been available for years but few studies have addressed this option in a prospective manner. The question is of interest after reports that maternal serum screening (MSS) is less accurate for pregnancies resulting from assisted reproduction technologies (ART) than for spontaneous pregnancies (SP). MethodsA prospective interventional study was designed to address the performances of cfDNA compared with MSS in pregnancies with or without ART. Each patient was offered both MSS and cfDNA testing. The primary analysis cohort ultimately included 794 patients with a spontaneous pregnancy (SP) (n = 472) or pregnancy obtained after ART (n = 322). ResultsOverall, the false-positive rate and positive predictive value were 6.6% and 8.8% for MSS but 0% and 100% for cfDNA. MSS false-positive rate and positive predictive values were clearly poorer in the ART group (11.7% and 2.6%) than in the SP group (3.2% and 21.1%). The global rates of invasive procedures were 1.9% (15/794) with cfDNA but 8.4% (65/794) if MSS alone was proposed. ConclusioncfDNA achieved better performance than MSS in both spontaneous and ART pregnancies, thus decreasing the number of invasive procedures. Our findings suggest that cfDNA should be considered for primary screening, especially in pregnancies obtained after ART.

How to correct the impact of ethnicity on effectiveness of the second trimester maternal serum screen of fetal Down syndrome?

Objectives: To compare the performance of second trimester maternal serum screen (MSS) for fetal Down syndrome in Thai population between the conventional method using Caucasian reference ranges with ethnic factor correction (CRR-EC) and the method using specific Thai reference ranges (TRRs).Methods: A prospective database of the MSS project was accessed. The concentrations of alpha fetoprotein (AFP), beta-hCG, and uE3 were converted to their multiple of medians (MoMs) by two methods; CRR-EC for Asian women and TRR. The detection rate and false positive rate derived from the two methods were compared.Results: Of 20,229 cases, 35 women had fetal Down syndrome. The detection rates of both methods were comparable, whereas the false-positive rate of TRR was significantly lower (8.8 versus 11.7%; p < .001). The improvement was mainly caused by more accuracy of the MoMs of beta-hCG, not AFP/uE3, based on TRR.Conclusions: The effectiveness of MSS could be improved by using our own reference ranges instead of using ethnic factor correction. With TRR, the false-positive rate or the number of invasive diagnoses could be significantly decreased without compromise of the detection rate. To improve MSS performance, each population should use its own reference ranges.