Rapid non-invasive prenatal screening test for trisomy 21 based on digital droplet PCR.

Non-invasive prenatal tests for the detection of fetal aneuploidies are predominantly based on the analysis of cell-free DNA (cfDNA) from the plasma of pregnant women by next-generation sequencing. The development of alternative tests for routine genetic laboratories is therefore desirable. Multiplex digital droplet PCR was used to detect 16 amplicons from chromosome 21 and 16 amplicons from chromosome 18 as the reference. Two fluorescently labeled lock nucleic acid probes were used for the detection of reaction products. The required accuracy was achieved by examining 12 chips from each patient using Stilla technology. The plasma cfDNA of 26 pregnant women with euploid pregnancies and 16 plasma samples from pregnancies with trisomy 21 were analyzed to determine the cutoff value for sample classification. The test was validated in a blind study on 30 plasma samples from pregnant patients with a risk for trisomy 21 ranging from 1:4 to 1:801. The results were in complete agreement with the results of the invasive diagnostic procedure (sensitivity, specificity, PPV, and NPV of 100%). Low cost, and speed of analysis make it a potential screening method for implementation into the clinical workflow to support the combined biochemical and ultrasound results indicating a high risk for trisomy 21.

Effect of umbilical cord drainage after spontaneous delivery in the third stage of labor.

Umbilical cord drainage involves releasing the cord clam from the umbilical cord after separation of the newborn from the maternal end of the umbilical cord. Consequently, there is emptying of blood from the placenta. This procedure is part of the active management of the third stage of labor (TSL). OBJECTIVE: This study is intended to provide knowledge about the duration of TSL and the risk of retention of the placenta using umbilical cord drainage and the no-drainage procedure. MATERIALS AND METHODS: A prospective randomized study of the management of the third stage of labor in 600 patients. The patients were equally divided into two groups with umbilical cord drainage (300) and without umbilical cord drainage (300). TSL was actively managed by FIGO (the International Federation of Gynecology and Obstetrics) recommendations. We monitored the duration of TSL and retention of the placenta after a 30 min period. RESULTS: The mean duration of TSLwas 6.8 ± 0.4 min in the drainage group and 11.6 ± 0.8 min in the control group. We conclude that umbilical cord drainage significantly shortens the duration of TSL (P = 0.026) as well as reduces the risk of placental retention. In a group where we use the drainage of the umbilical cord, placental retention 30 min after delivery of the fetus occurred in four cases while the second set occurred in 14 cases (RR 3.62; 95% CI 1.18-11.14). CONCLUSION: We assume that during umbilical cord drainage, the collapse of thin-walled uteroplacental vessels occurs earlier causing bleeding from these vessels between the placenta and the uterine wall, and therefore, earlier separation of the placenta occurs. Of course, the drainage of the umbilical cord is only one step in the algorithm of active management at the third stage of labor according to FIGO.

Anxiety and depressive symptoms in pregnant women during the COVID-19 pandemic in the Czech Republic-Broader sociodemographic causes, connections and implications.

INTRODUCTION: Our study (part of multicentric "MindCOVID") investigates risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic in the Czech Republic. MATERIAL AND METHODS: The study used a prospective cross-sectional design. Data was collected using an online self-administered questionnaire. Standardized scales, general anxiety disorder (GAD)-7 and patient health questionnaire (PHQ)-9 were administered online. Multivariate regression analysis was employed to evaluate the relationship between sociodemographic, medical and psychological variables. RESULTS: The Czech sample included 1830 pregnant women. An increase of depressive and anxiety symptoms measured by PHQ-9 and GAD-7 in pregnant women during the COVID-19 pandemic was associated with unfavorable financial situation, low social and family support, psychological and medical problems before and during pregnancy and infertility treatment. Fear of being infected and adverse effect of COVID-19, feeling of burden related to restrictions during delivery and organization of delivery and feeling of burden related to finances were associated with worse anxiety and depressive symptoms. CONCLUSIONS: Social and emotional support and lack of financial worries are protective factors against mood disorders in pregnant women in relation to COVID-19 pandemic. In addition, adequate information about organization of delivery and additional support from healthcare professionals during the delivery are needed. Our findings can be used for preventive interventions, given that repeated pandemics in the future are anticipated.

Associations between nausea and vomiting in pregnancy, disgust sensitivity, and first-trimester maternal serum free ß-hCG and PAPP-A.

Elevated levels of nausea and vomiting in pregnancy (NVP) and disgust sensitivity have been observed in the first trimester and both are thought to have a protective function for the mother and her fetus. Their aetiology is not clear, however, with previous studies attributing elevated NVP and disgust to various factors including endocrine changes, immunological changes, and psychological variables. To date, no study has directly assessed the relationship between disgust and NVP. Here, we prospectively collected two independent samples (S1 and S2; n1 = 201, n2 = 391) of women in the first trimester of pregnancy, who completed the Index of Nausea, Vomiting, and Retching and the Disgust Scale-Revised. We also measured free ß-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum. Our results did not confirm any association between NVP and disgust; in addition, they indicate that NVP and disgust may have different proximate causes. Disgust sensitivity was significantly negatively correlated with free ß-hCG and (only in S1) with PAPP-A. In contrast, NVP was significantly positively associated with free ß-hCG levels and (only in S1) with PAPP-A. While low hCG levels seem to be an important indicator for activation of the behavioral immune system in the first trimester, increased hCG levels play a role in stronger symptoms of NVP, a result consistent with previous studies. Levels of PAPP-A are likely part of a larger network of immunological and endocrine responses and do not appear to provide sufficient information for predicting women's NVP and disgust sensitivity.

Epidermolysis in a newborn of a mother affected by covid-19 in the 3rd trimester of pregnancy.

Covid-19, caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a pandemic. Although this infection primarily presents with respiratory symptoms, the number of reported extrapulmonary manifestations, including dermatological, is also increasing. A group of pregnant women is particularly susceptible to respiratory diseases, but with regard to covid-19, there is still limited data on the course of infection in pregnancy in relation to the possibility of vertical transmission. We present the case of a 30-year-old unvaccinated patient with a history of overcoming covid-19 infections in the 7th month of pregnancy, and with persistent skin lesions. The patient gave birth to a mature newborn with epidermolytic lesions on a bullous base. In the differential dia-gnostic process, Staphylococcal scalded skin syndrome and epidermolysis bullosa were ruled out in the newborn. Considering the clinical findings and epidemiological history of the mother, we assume a possible vertical transmission of covid-19 with skin manifestation of the disease in the newborn.

Disgust sensitivity in early pregnancy as a response to high pathogen risk.

Introduction: Considered a part of the behavioral immune system (BIS), disgust sensitivity is expected to be adjusting as a response to the actual level of the environmental health risks. Methods: In this preregistered study, we tested the hypothesis that disgust sensitivity would be higher during the COVID-19 pandemic compared to the pre-pandemic period in pregnant women. In this between-subject study with a longitudinal trend design, we administered the Disgust Scale-Revised to 200 pregnant women before the pandemic and to 350 pregnant women during the pandemic. Results: We found a small but significant effect of the pandemic on disgust sensitivity, such that higher disgust sensitivity was found in women pregnant during the pandemic. This effect was stronger in primiparae, however, the interaction between parity and the pandemic period was not significant. Disgust sensitivity decreased with age. No differences in terms of nausea and vomiting were found between the women pregnant before and during the pandemic. Discussion: Our findings indicate that although BIS is presumed to function as a complex mechanism to prevent health-threatening behaviors, its activation in pregnant women during the COVID-19 pandemic is rather weak.

Risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic: Results of a web-based multinational cross-sectional study.

OBJECTIVE: To assess risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic using Mind-COVID, a prospective cross-sectional study that compares outcomes in middle-income economies and high-income economies. METHODS: A total of 7102 pregnant women from 12 high-income economies and nine middle-income economies were included. The web-based survey used two standardized instruments, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). RESULT: Pregnant women in high-income economies reported higher PHQ-9 (0.18 standard deviation [SD], P < 0.001) and GAD-7 (0.08 SD, P = 0.005) scores than those living in middle-income economies. Multivariate regression analysis showed that increasing PHQ-9 and GAD-7 scales were associated with mental health problems during pregnancy and the need for psychiatric treatment before pregnancy. PHQ-9 was associated with a feeling of burden related to restrictions in social distancing, and access to leisure activities. GAD-7 scores were associated with a pregnancy-related complication, fear of adverse outcomes in children related to COVID-19, and feeling of burden related to finances. CONCLUSIONS: According to this study, the imposed public health measures and hospital restrictions have left pregnant women more vulnerable during these difficult times. Adequate partner and family support during pregnancy and childbirth can be one of the most important protective factors against anxiety and depression, regardless of national economic status.

Outcome of a patient with Herlyn-Werner-Wunderlich syndrome treated with Balloon septostomy - pre- and postsurgical ultrasound findings.

Herlyn-Werner-Wunderlich syndrome is an unusual congenital anomaly defined by a triad of congenital defects of the female urogenital tract - homolateral renal agenesis, uterus duplex and obstructed hemi-hematometrocolpos whose etiology remains still unclear. Pelvic pain, dysmenorrhea and palpable mass due to the hematocolpos or hematometra are the most common clinical symptoms. Endometriosis is considered to be a prevalent finding in these young patients possibly explaining the pathophysiological mechanism of endometriosis as the result of retrograde menstruation. Early diagnosis and subsequent treatment are important to prevent the development of severe complications. In general, clinical and reproductive outcomes after drainage of the hematometrocolpos are reported to be satisfactory. A 13-year-old patient presented with pelvic pain and was diagnosed with OHVIRA syndrome treated with Balloon septostomy.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Fetal neck giant hemangioma associated with postnatal arising Kasabach-Merritt syndrome.

We report a prenatal ultrasound dia-gnosis of giant neck hemangioma at 30+1 weeks in a fetus resulting in the postnatal development of Kasabach-Merritt syndrome. Ultrasound scan revealed a large isoechoic mass occupying the whole neck, infiltrating the nasopharyngeal cavity, tongue, lower lip and mandible. Complex sonographic visualization with 2D and 4D was helpful in the process of parental counseling.

The reduced use of invasive procedures leads to a change of frequencies of prenatally detected chromosomal aberrations: population data from the years 2012-2016.

OBJECTIVE: The aim of the study was to analyze the results of screening for chromosomal aberrations in a population with a high rate of first-trimester screening and low rate of cell-free DNA testing. METHODS: The data were obtained from the National Registry of Congenital Anomalies of the Czech Republic. We calculated and compared the proportion of autosomal trisomies (Down, Edwards, and Patau syndrome) and of other chromosomal aberrations identified during prenatal diagnostics. RESULTS: We identified 3009 prenatally diagnosed cases of chromosomal aberrations in the 2012-2016 period. The number of major autosomal trisomies has increased from 329 cases (30.86 per 10,000 live births) in 2012 to 423 cases (37.41) in 2016 (p = 0.014). The numbers of other aberrations decreased from 246 cases (23.07 per 10,000) in 2012 to 217 cases (19.19) in 2016 (p = 0.017). The usage of invasive diagnostic procedures decreased from 1099.54 in 2012 to 622.73 in 2016 (per 10,000 live births). CONCLUSIONS: Our population-based study confirmed a decrease in prenatal detection of nonmajor chromosomal aberrations wherein a decrease of invasive testing occurred. With the introduction of cell-free DNA testing, further decrease of invasive procedures and detection of nonmajor aberrations may be expected.

Oral contraceptive use during relationship formation and current relationship satisfaction: Testing the congruency hypothesis in couples attending pregnancy and fertility clinics.

According to the congruency hypothesis, relationship satisfaction is predicted by the congruency (or non-congruency) between current use of oral contraceptives (OC) and their use during relationship formation. This is based on findings that OC may alter women's mate preferences, so that attraction to their partner may have changed in non-congruent women. Indeed, some studies find that women in a non-congruent state were less sexually satisfied with their partner, although they were more satisfied in non-sexual aspects of the relationship. However, some other studies have produced null results, calling the hypothesis into question. In this study, we tested the congruency hypothesis in two samples of pregnant women, and in two samples of couples attending a fertility clinic. In all four samples, couples completed questionnaires on relationship and sexual satisfaction and the women also reported their previous and current contraceptive use. In one sample of pregnant women, we found that women who used OC during relationship formation were more sexually satisfied with their partner compared to women who did not use OC at that time; this pattern has previously been interpreted as supporting the congruency hypothesis in view of certain similarities in hormonal profile between OC use and pregnancy. We did not find any significant effect of OC use during relationship formation on sexual and relationship satisfaction in the other sample of pregnant women, either sample attending the fertility clinic, or in the male partners of any of our samples. Our results thus provide mixed support for the congruency hypothesis. Finally, we discuss recommendations for future studies such as use of within-subject designs and more structured assessment of sexual satisfaction.

Performance of antenatal imaging to predict placenta accreta spectrum degree of severity.

INTRODUCTION: In cases of placenta accreta spectrum, a precise antenatal diagnosis of the suspected degree of invasion is essential for the planning of individual management strategies at delivery. The aim of this work was to evaluate the respective performances of ultrasonography and magnetic resonance imaging for the antenatal assessment of the severity of placenta accreta spectrum disorders included in the database. The secondary objective was to identify descriptors related to the severity of placenta accreta spectrum disorders. MATERIAL AND METHODS: All the cases included in the database for which antenatal imaging data were available were analyzed. The rates of occurrence of each ultrasound and magnetic resonance imaging descriptor were reported and compared between the Group "Accreta-Increta" (FIGO grades 1 & 2) and the Group "Percreta" (FIGO grade 3). RESULTS: Antenatal imaging data were available for 347 women (347/442, 78.5%), of which 105 were included in the Group "Accreta - Increta" (105/347, 30.2%) and 213 (213/347, 61.4%) in the Group "Percreta". Magnetic resonance imaging was performed in addition to ultrasound in 135 women (135/347, 38.9%). After adjustment for all ultrasound descriptors in multivariate analysis, only the presence of a bladder wall interruption was associated with a significant higher risk of percreta (Odds ratio 3.23, Confidence interval 1.33-7.79). No magnetic resonance imaging sign was significantly correlated with the degree of severity. CONCLUSIONS: The performance of ultrasound and magnetic resonance imaging to discriminate mild from severe placenta accreta spectrum disorders is very poor. To date, the benefit of additional magnetic resonance imaging has not been demonstrated.

When a rare condition creates a scientific society: The history of the International Society for Placenta Accreta Spectrum (IS-PAS).

Almost 10 years ago, clinicians at multiple locations all over Europe observed an increased number of antenatally undiagnosed cases of placenta accreta spectrum (PAS) resulting in significant morbidity and the occasional maternal death. Even with an improvement in antenatal imaging, the management of severe PAS remains challenging. One solution to improve understanding in rare but potentially lethal conditions is international collaboration. Consequently, a European working group was formed, which over the next few years grew into an international society, the IS-PAS. The collective goals are to develop a large shared database of cases, generate high-quality research into all aspects of PAS, and improve education of both healthcare professionals and patients. The first results of this collaboration are presented within this supplement.

Optimization of diagnostic strategy for non-invasive cell-free foetal RHD determination from maternal plasma.

BACKGROUND AND OBJECTIVES: The aim of the study was to optimize routine non-invasive prenatal detection of fetal RHD gene from plasma of RhD-negative pregnant women (the median of gestational age was 25 weeks, range 10-38) to detect RhD materno-fetal incompatibility and to avoid the redundant immunoprophylaxis. MATERIALS AND METHODS: Initially only one exon of RHD gene (exon 10) was investigated in 281 plasma samples (144 verified after delivery), in the second phase three RHD exons (5, 7, 10) were analyzed in 246 samples of plasma and maternal genomic DNA (204 verified) by real-time PCR method. Detection of Y-chromosomal sequence DYS-14 and five X-chromosomal insertion/deletion polymorphisms was used to confirm the fetal cfDNA detectability in plasma. Specific polymorphisms in RHD gene were detected by sequence-specific primer PCR in nine samples. RESULTS: When only the RHD exon 10 was tested, 2·8% of verified samples were false positive and 3·5% false negative. With three RHD exons (5, 7, 10) and maternal genomic DNA testing, only one case was false negative (0·5%). Nine samples were inconclusive due to RHD-positive results in maternal genomic DNA. These samples were analyzed for specific mutations in RHD gene. Combination of both methods for fetal cfDNA verification succeeded in 75% of tested group. CONCLUSION: Implementation of analysis of three RHD exons and maternal genomic DNA to routine practice lowers dramatically the ratio of false positive and negative results. This method enables more accurate determination of fetal RHD status with the reduction of unnecessary medical care and RhD immunoprophylaxis.

Association between latent toxoplasmosis and fertility parameters of men.

BACKGROUND: About a third of people in the world are infected with Toxoplasma gondii. This parasite has been found in the reproductive organs and semen of males of many animal species as well as humans. The effects of toxoplasmosis on sperm count, motility and morphology were confirmed in rats. A higher prevalence of toxoplasmosis has been observed in infertile men. On the other hand, no significant effect of infection on semen parameters in men was found in one already published study. OBJECTIVES: To compare the prevalence of toxoplasmosis in men with and without semen pathology and to examine in detail the possible impact of infection on semen volume, sperm count, motility and morphology. MATERIALS AND METHODS: The pre-registered cross-sectional study included 669 men who visited the Centre for Assisted Reproduction in Prague from June 2016 until June 2018. RESULTS: The incidence of fertility problems was significantly higher in the 163 Toxoplasma-infected men (48.47%) than in the 506 Toxoplasma-free men (42.29%), τ = 0.049, P = 0.029. After correction for multiple tests, we found significantly lower sperm concentration, concentration of progressively motile sperm, and concentration of non-progressively motile sperm in Toxoplasma-positive men than in Toxoplasma-negative men using partial Kendall correlation with age controlled. In addition, toxoplasmosis correlated with sperm quality in smokers but not in non-smokers. DISCUSSION AND CONCLUSION: Our results suggest that latent toxoplasmosis affects certain semen parameters (sperm count and motility), but does not seem to affect sperm morphology and semen volume. Impairment of semen parameters may be either a side effect of the presence of Toxoplasma gondii in male reproductive organs or a product of manipulation activity of the parasite aimed to increase the efficiency of the sexual route of its transmission. Tobacco smoking also appears to exacerbate the negative impact of toxoplasmosis on semen parameters.

Male-to-Female Presumed Transmission of Toxoplasmosis Between Sexual Partners.

Toxoplasmosis is one of the most widespread human parasitoses in developed countries. Sexual transmission has been confirmed in several animal species, and indirect evidence suggests it may occur in humans. We compared the seropositivity to Toxoplasma gondii in couples who visited the Center for Assisted Reproduction in Prague from June 2016 to June 2018 and analyzed various risk factors including the serological status of sexual partner. By comparing the risk factors in men and women, we tested the hypothesis of male-to-female sexual transmission of toxoplasmosis. The prevalence of toxoplasmosis in women with infected male partners (25.6%; n = 156) was higher than in women with uninfected male partners (18.2%; n = 477; P = 0.045). Therefore, a partner's seropositivity seems to be a risk factor for infection in women (n = 593; prevalence ratio = 1.418; P = 0.045) but not in men (n = 573; prevalence ratio = 1.058; P = 0.816). Our results support the hypothesis of the sexual transmission of T. gondii from men to women. The risk may seem relatively low, but transmission can occur during unprotected sexual intercourse, which may be at the time of conception. Because of the risk of congenital toxoplasmosis, a lower risk of infection than that observed in our study can represent a serious health problem.

Association between deficient cesarean delivery scar and cesarean scar syndrome.

INTRODUCTION: The aim of our study was to compare long-term morbidity after elective and emergency cesarean delivery (CD). METHODS: A prospective cohort study was conducted in 200 women delivered by CD. Ultrasound examinations were performed transvaginally at 6 weeks and 18 months after CD. Clinical data were collected at the time of CD and after 18 months. RESULTS: In the group of 200 women, 29% underwent emergency and 71% elective CD. Then, 6 weeks and 18 months after CD, a severe scar defect was present in 7% and 5%, respectively (P = .4). After 18 months of CD, 17% (34/200) of women had evidence of adhesions of the vesicouterine pouch. Severe CD scar defects were significant predictors for adhesion formation in vesicouterine pouch (OR 3.14, 95% CI, 1.54-4.74), pelvic pain (OR 1.68, 95% CI, 0.22-3.14), dysmenorrhea (OR 2.12, 95% CI, 0.74-3.50), and dyspareunia (OR 1.38, 95% CI, 0.09-2.67). Uterine scar defects detected at 6 weeks after elective CD were detectable at 18 months in only 40% of cases, whereas uterine scar defects after emergency CD were still detectable in 87% of cases. CONCLUSION: Uterine scar defects are more frequent at 18 weeks after emergency CD, than after elective CD (40% vs 87%). Women with severe scar defects have higher risk of adhesion formation, dysmenorrhea, dyspareunia, and chronic pelvic pain.

Genome-wide miRNA profiling in plasma of pregnant women with down syndrome fetuses.

Down syndrome (DS) is one of the most common causes of intellectual disability and new approaches allowing its rapid and effective prenatal detection are being explored. In this study, we investigated the diagnostic potential of plasma microRNAs (miRNAs). This study builds upon our previous study in DS placentas, where seven miRNAs were found to be significantly up-regulated. A total of 70 first-trimester plasma samples from pregnant women were included in the present study (35 samples with DS fetuses; 35 with euploid fetuses). Genome-wide miRNA profiling was performed in the pilot study using Affymetrix GeneChip™ miRNA 4.1 Array Strips (18 samples). Selected miRNAs were then analysed in the validation study using quantitative reverse transcription PCR (RT-qPCR; 52 samples). Based on the current pilot study results (12 miRNAs), our previous research on chorionic villi samples (7 miRNAs) and the literature (4 miRNAs), a group of 23 miRNAs was selected for the validation study. Although the results of the pilot study were promising, the validation study using the more sensitive RT-qPCR technique and a larger group of samples revealed no significant differences in miRNA profiles between the compared groups. Our results suggest that testing of the first-trimester plasma miRNAs is probably not suitable for non-invasive prenatal testing (NIPT). Different results could be theoretically achieved at later gestational ages; however, such a result probably would have limited use in clinical practice.

Understanding attitudes and behaviors towards cell-free DNA-based noninvasive prenatal testing (NIPT): A survey of European health-care providers.

Cell-free DNA-based noninvasive prenatal testing (cfDNA) is a relatively new screening tool that analyzes cfDNA circulating in maternal plasma to screen for aneuploidies. Since its introduction, cfDNA has been rapidly adopted by health care providers (HCPs). This rapid adoption, as well as progressive developments in the technology, requires professional societies to continuously update their guidelines to indicate the broadening scope both in terms of test indications and patient populations for whom it has become the appropriate primary test. CfDNA testing, initially applied to high-risk patients, is now largely considered an option for all patients. For HCPs, the rapid introduction of cfDNA into clinical practice has come with the requirement to stay up-to-date and accurately informed. We performed a survey to understand the current practices and views of European HCPs on the use of cfDNA. European HCPs were surveyed on several topics such as familiarity with cfDNA-based noninvasive prenatal testing (NIPT), current usage, patient counseling, test menu expansion, and future perspectives. The results of this survey demonstrate increasing usage and awareness of cfDNA-based NIPT in five European countries (UK, France, Germany, Spain and Italy). Major barriers to implementation include cost and a lack of physician education on NIPT.