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Exploring efficient and easily implementable prenatal screening strategies aims at birth defect prevention and control. However, there have been limited economic evaluations of non-invasive prenatal screening (NIPS) strategies in China. Furthermore, these studies were predominantly confined to local or geographically proximate provinces and lacked universality and representativeness. This study assesses the health economics of current prenatal screening strategies and NIPS as first-line screening programs, analyzing their efficacy to determine an optimal strategy. From the perspective of health economics, cost-effectiveness, cost-benefit, and single-factor sensitivity were conducted for five different screening strategies using a decision tree model. Among pregnant women aged < 35 years who underwent only one screening for foetal Down syndrome (DS), the detection rate, false positive rate and positive predictive value of NIPS for foetuses with DS were superior to those of the other four serological screening methods. Although applying NIPS as first-line screening method yields the highest efficacy and benefits, it currently lacks cost-effectiveness when compared to serological screening and sequential NIPS screening strategies., (© 2024. The Author(s).)

Genetic counseling (GC) following abnormal Down syndrome (DS) screening tests aims to ensure learning of complex medical concepts and discussion of counselees' personal desires. Pre-GC use of electronic learning tools (e-learning tools) can facilitate GC sessions by allowing more time for dialogue rather than learning medical and genetic concepts, enabling greater focus on the counselee's decisional, psychological, and personal needs. Few studies have investigated such tools for DS screening tests and those who have focused on screening uptake rather than abnormal results and implications. This study evaluated prenatal GC outcomes following implementation of an e-learning tool utilizing an educational animated movie for couples of varied ethnic backgrounds in northern Israel, with abnormal DS screening tests. E-learning tool impact was assessed as knowledge level, informed choices, satisfaction with the intervention and GC process, the state of anxiety and duration of the GC meeting. The 321 study participants were randomized to three groups: animation movie, booklet, and control. All participants had been asked to complete pre- and post-counseling questionnaires. Outcome scores were compared between the research groups. Results showed increased knowledge level in general among participants in the animation group; among minority participants, the highest knowledge level was in the animation group. Anxiety levels and informed choices were not statistically different among the groups. However, watching the animation, Jewish ethnicity, good level of genetic literacy, and academic degree were significant predictors of informed choice, and those who watched the animation were three times more likely to make an informed choice than the control group. Our findings suggest that this e-learning tool is efficient and acceptable for the general population. Special attention is needed for minorities with lower genetic literacy and education., (© 2023 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Objective: We present low-level mosaic trisomy 21 at amniocentesis in a pregnancy with a favorable fetal outcome., Case Report: A 38-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+21[4]/46,XY[34]. Prenatal ultrasound findings were normal. At 27 weeks of gestation, she was referred for genetic counseling, and the cultured amniocytes had a karyotype of 47,XY,+21[2]/46,XY[26]. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 30% (30/100 cells) mosaicism for trisomy 21. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 21q11.2q22.3 × 2.25, consistent with 20%-30% mosaicism for trisomy 21. The parental karyotypes were normal. The woman was advised to continue the pregnancy, and a 3510-g phenotypically normal male baby was delivered at 39 weeks of gestation. Cytogenetic analysis of the cord blood, umbilical cord and placenta revealed the karyotypes of 47,XY,+21[1]/46,XY[39], 47,XY,+21[2]/46,XY[38] and 46,XY in 40/40 cells, respectively. When follow-up at age 1 year and 2 months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY in 40/40 cells, and interphase FISH analysis on uncultured buccal mucosal cells showed 6.4% (7/109 cells) mosaicism for trisomy 21., Conclusion: Low-level mosaic trisomy 21 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To study pregnant women's subjective viewpoints on what is important when receiving information prior to decision-making regarding prenatal testing for chromosomal anomalies., Method: Data were collected using Q methodology. During January 2020-October 2021, 45 pregnant women in Sweden completed a 50-item Q sort. Statements regarding what is important when receiving information about prenatal screening and diagnosis were prioritized through ranking in a fixed sorting grid on an 11-point scale, from "most important" to "least important." Socio-demographics and coping styles were surveyed through questionnaires., Results: Three groups represented different viewpoints on what pregnant women consider important when receiving information about prenatal screening and diagnosis. Factor 1: Stepwise information and decision-making: viewing information and decision-making as a step-by-step process. Factor 2: Decision-making as a continuous process based on couple autonomy: Striving for an informed decision as a couple about tests, test results and conditions screened. Factor 3: As much information as early as possible-the importance of personal autonomy in decision-making: Prioritizing autonomous decision-making based on non-directive information early in the pregnancy., Conclusion: This study highlights the complexities involved when providing information. As shown by the differing viewpoints in this study, pregnant women's informational needs differ, making individual and personalized information preferable., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: Early morphologic ultrasound, generally carried out in case of atypical first trimester serum markers (PAPP-A and/or free hCGβ <0.30 MoM), has not been re-evaluated since the possibility of performing a cell-free fetal DNA analysis in this indication. Our objective was to evaluate the usefulness of early morphological ultrasound in case of atypical profile of serum markers performed in association with Non-Invasive Prenatal Testing (NIPT)., Methods: This was a single-center retrospective study in a tertiary maternity. Between January 2017 and December 2021, women with an atypical first trimester serum markers and low/intermediate risk for trisomy 21 (<1/50) were included. The clinical data, results of first trimester serum markers, NIPT, early morphological ultrasound and subsequent ultrasounds and other investigations (amniocentesis, pregnancy outcomes) were analyzed., Results: After exclusion of women with high-risk of trisomy 21 and lost to follow-up, 163 women were included. In 72 % of cases (117/163), women had a low risk of trisomy 21, and 39 % (59/163) had an early morphological ultrasound. Early morphological ultrasound was useful to detect severe IUGR leading to the suspicion of triploidy (3/163, 1.8 %). In all other situations, it did not allow earlier management. After analysis of the 3 triploidy cases, a collapsed profile for both serum markers was demonstrated (<0.25 MoM)., Conclusions: Systematic early morphological ultrasound in case of an atypical serum marker profile seems useless considering the performance of NIPT. An ultrasound restricted to women with both markers below 0.25 MoM would allow the early detection of triploidy., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Non-invasive prenatal testing (NIPT), which can screen for aneuploidies such as trisomy 21, is being implemented in several public healthcare systems across Europe. Comprehensive communication and information have been highlighted in the literature as important elements in supporting women's reproductive decision-making and addressing relevant ethical concerns such as routinisation. Countries such as England and France are adopting broadly similar implementation models, offering NIPT for pregnancies with high aneuploidy probability. However, we do not have a deeper understanding of how professionals' counselling values and practices may differ between these contexts., Methods: In this paper, we explore how professionals in England and France support patient decision-making in the provision of NIPT and critically compare professional practices and values. We draw on data from semi-structured interviews with healthcare professionals., Results: Both English and French professionals emphasised values relating to patient choice and consent. However, understandings and application of these values into the practice of NIPT provision differed. English interviewees placed a stronger emphasis on interpreting and describing the process of counselling patients and clinical care through a "principle" lens. Their focus was on non-directiveness, standardisation, and the healthcare professional as "decision-facilitator" for patients. French interviewees described their approach through a "procedural" lens. Their focus was on formal consent, information, and the healthcare professional as "information-giver". Both English and French professionals indicated that insufficient resources were a key barrier in effectively translating their values into practice., Conclusion: Our findings illustrate that supporting patient choice in the provision of NIPT may be held as an important value in common on a surface level, but can be understood and translated into practice in different ways. Our findings can guide further research and beneficially inform practice and policy around NIPT provision., (© 2024. The Author(s).)

Rationale: Because of the normal phenotype, carriers of specific chromosomal translocations are often diagnosed only after their development of associated malignancies, recurrent miscarriages, and reproductive difficulties. In this paper, we report primary balanced fetal chromosomal translocations by performing the necessary invasive prenatal diagnosis in couples with previous malformations coupled with prenatal testing suggesting a high risk for trisomy 21., Patient Concerns: Case 1 and Case 2 couples had malformed children, and Case 3 couples had a high risk of trisomy 21 on noninvasive preconception serological testing., Diagnosis and Intervention: A balanced chromosomal translocation diagnosis was confirmed by karyotyping of fetal cells obtained by amniocentesis., Outcomes: All 3 couples decided to continue their pregnancies after learning about the consequences of the chromosomal abnormalities. Approximately a year after the children were born, the staff of the Prenatal Diagnostic Center followed up with a phone call and found that the children physical development and intelligence were normal., Lesson: This case report reports healthy chromosomal balanced translocation newborns born to couples with poor maternal history and couples with abnormalities suggested by preconception testing, and followed up with the newborns to provide some experience in prenatal diagnosis and genetic counseling for chromosomal balanced translocations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article.

Objective: This study aimed to assess factors that influence patients' decisions in accepting prenatal diagnostic testing following genetic counseling for increased risk of fetal aneuploidy., Methods: This is a retrospective cohort study of women at increased risk of fetal aneuploidy and genetic disorders who had genetic counseling from January 2012 to December 2016 at a single academic center. Demographics, indications for genetic counseling, and rates of diagnostic testing were collected and compared between those who accepted diagnostic testing and those who chose cell free DNA. The variables were analyzed using Chi-square, Fisher's exact test, and multiple logistic regression., Result: Of the 2,373 pregnant women who underwent genetic counseling for increased risk of fetal aneuploidy and genetic disorders during the study period, 321 women had diagnostic testing (13.5%). Women at 35 years and older accepted diagnostic testing more than women younger than 35 years (20.7 vs. 11.5%, p  < 0.001). Asian women accepted diagnostic testing at 27.7% more than white, non-Hispanic Black, and Hispanic women at 18.0, 12.1, and 11.7%, respectively, p  = 0.002. Number of indications for genetic counseling influenced the likelihood of accepting diagnostic testing. Women with one indication had 11.5% acceptance of diagnostic testing, and with two and three indications, it was 17.0 and 29.2%, respectively. The commonest indication for diagnostic testing was cystic hygroma (risk ratio [RR] = 7.5, 95% confidence interval [CI]: 3.12-8.76 p  < 0.001). The relative risk of diagnostic testing for fetuses with shortened long bones, femur and humerus, thickened nuchal fold, echogenic bowel, single umbilical artery, and increased nuchal translucency were 4.0, 3.3, 3.1, 2.7, and 2.7, respectively. Abnormal serum analyte alone was associated with less acceptance of diagnostic testing (RR = 0.8, 95% CI: 0.7-0.96, p  = 0.017)., Conclusion: Age, race, ethnicity, and cumulative number of indications for genetic counseling influenced acceptance of diagnostic testing in at-risk women of fetal aneuploidy and genetic disorders., Key Points: · Genetic counseling.. · Fetal aneuploidy.. · Genetic disorders.. · Prenatal diagnostic testing. Prenatal diagnostic testing in women with increased risk of fetal aneuploidy and genetic disorders.., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: In this register-based study of pregnancies in Denmark, we assessed the associations between maternal age and the risk of fetal aneuploidies (trisomy 21, trisomy 18, trisomy 13, triploidy, monosomy X and other sex chromosome aberrations). Additionally, we aimed to disentangle the maternal age-related effect on fetal aneuploidies by cases with translocation trisomies and mosaicisms., Material and Methods: We followed a nationwide cohort of 542 375 singleton-pregnant women attending first trimester screening in Denmark between 2008 and 2017 until delivery, miscarriage or termination of pregnancy. We used six maternal age categories and retrieved information on genetically confirmed aneuploidies of the fetus and infant from the national cytogenetic register., Results: We confirmed the known associations between advanced maternal age and higher risk of trisomy 21, 18, 13 and other sex chromosome aberrations, especially in women aged ≥35 years, whereas we found no age-related associations with triploidy or monosomy X. Cases with translocation trisomies and mosaicisms did not influence the overall reported association between maternal age and aneuploidies., Conclusion: This study provides insight into the accurate risk of fetal aneuploidies that pregnant women of advanced ages encounter., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies., Methods: A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated., Results: Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction (P < 0.05)., Conclusion: It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.

Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article.

Objectives: To identify and describe threats to informed decision-making at key junctures of the Down syndrome (DS) determination experience., Methods: We conducted 32 narrative interviews with 42 participants (10 couples and 22 individuals). Participants relayed their stories of receiving their child's or a prospective child's DS determination. Interviews were recorded, transcribed verbatim, and analyzed thematically., Results: We identified the following 5 threats to informed decision-making: routinization of screening, screening for reassurance's sake, equating an openness to screening with an openness to testing and termination, misunderstanding and miscommunicating about probability, and a lack of up-to-date, accurate, neutral information., Conclusions: The results contribute to an existing body of literature on the DS determination experience with a uniquely Canadian lens. The threats outline how well-intended counselling can ultimately undermine reproductive autonomy and informed decision-making. With knowledge of how these seemingly harmless behaviours threaten informed decision-making and reproductive autonomy, care providers can modify their counselling to lessen their impact., (Copyright © 2023 The Author. Published by Elsevier Inc. All rights reserved.)

Objective To explore the clinical significance of non-invasive prenatal testing(NIPT)for fetal chromosomal abnormalities in the cases of twin pregnancy and its relationship with age and other related factors.Methods A total of 3733 women with twin pregnancy of 12-26 +6 weeks who voluntarily underwent NIPT in the Ningbo Women and Children's Hospital from January 2018 to December 2022 were selected.The results of NIPT and amniocentesis were compared and all the participants were followed up.The detection rate of chromosomal abnormalities by NIPT was calculated,and its correlations with age,gestational weeks,chorionicity,and pregnancy type were analyzed.Results Among the 3733 cases,71 cases of fetal chromosome abnormality were indicated by NIPT,including 13 cases of trisomy 21,19 cases of trisomy 18,5 cases of trisomy 13,18 cases of sex chromosome abnormality,and 16 cases of chromosome microdeletion/duplication(excluding 21,18,13,and sex chromosomes),among which 34 cases were true positive and 37 cases were false positive.The overall sensitivity,specificity,and positive predictive value(PPV)of NIPT for chromosomal abnormalities in the cases of twin pregnancy were 100%,98.99%,and 47.89%(34/71),respectively.NIPT showed the sensitivity,specificity,and PPV of 100%,99.78%,and 78.38%(29/37)for trisomy 21,18,and 13,100%,99.56%,and 16.67%(3/18)for sex chromosome abnormalities,and 100%,99.62%,and 12.5%(2/16)for chromosome microdeletion/duplication,respectively.In the age group of ≥40 years,the NIPT for chromosomal abnormalities showed the PPV of 66.67%,the sensitivity of 100%,and the misdiagnosis rate of 30%。However,the NIPT for trisomy 21,18,and 13 showed the PPV of 100%,the misdiagnosis rate of 0,and the sensitivity and specificity of 100%.In terms of grouping based on gestational weeks,the NIPT for chromosomal abnormalities showed the highest PPV(51.28%)in the women with twin pregnancy for 14-17 +6 weeks,followed by that(50.00%)in the women with twin pregnancy for 22-26 +6 weeks;the NIPT for trisomy 21,18,and 13 showed the highest PPV of 94.74% in the gestation group of 14-17 +6 weeks,followed by that(83.33%)in the gestation group of 18-21 +6 weeks.The rate of dichorionic diamniotic twins was higher in assisted pregnancies than in natural pregnancies,and NIPT showed the same detection efficiency for dichorionic diamniotic twins and monochorionic diamniotic twins and the same detection efficiency for different pregnancy types.Conclusions NIPT has high accuracy in the diagnosis of twin pregnancy and high sensitivity and high specificity for different ages and gestational weeks,especially for trisomy 21,18,and 13.NIPT is suitable for assisted pregnancy and natural pregnancy,and it is of high value in clinical application.However,extensive application needs a large population-based study.

Background: Non-invasive prenatal testing (NIPT) has been widely adopted as an approach for foetal aneuploidy screening. This study was to evaluate the performance of NIPT for foetal T21 detection in subgroups of pregnancies and the correlation between Z-score and discordant positive predictive values (PPVs)., Methods: We retrospectively reviewed the NIPT results among 22361 pregnancies undergoing combined second-trimester screening (cSTS) previously. Sixty-four cases with positive NIPT results for foetal T21 were validated by invasive prenatal diagnosis., Results: In pregnancies with cSTS-T21 low-, intermediate-, and high-risk, the PPVs at NIPT were 14.3%, 64.3%, and 86.4%, respectively. Mean Z-scores of positive NIPT cases with cSTS-T21 high- and intermediate-risk were comparable, while were higher than that of cases with pre-test low-risk. Furthermore, PPVs for positive NIPT cases at 3 < Z < 5, 5 ≤ Z < 9, and Z ≥ 9 were 16.7%, 63.2%, and 100.0%, respectively., Conclusions: This study suggested that Z-score value of positive cases might be associated with discordant PPVs for T21 screening in subgroups of pregnancies.

Aim: To investigate the detectability of noninvasive prenatal screening (NIPS) with conventional sequencing depth to detect fetal copy number variants., Methods: We performed a retrospective study in a total of 19 144 pregnant women. Their cell-free plasma DNA were assessed for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and genome-wide copy number variants by NIPS at conventional sequencing depth., Results: Three hundred seventy-four cases (2.0%, 374/19 144) with abnormal results were detected, which including 84 cases (0.4%, 84/19 144) with high risk of trisomy 21, 18, and 13, 90 cases (0.5%, 90/19 144) with high risk of sex chromosome abnormalities (SCA), and 44 cases (0.2%, 44/19 144) with high risk of other chromosome aneuploidies. One hundred fifty-six cases (0.8%, 156/19 144) with high risk of copy number variations (CNVs) were also detected. In following prenatal diagnosis, composite positive predictive value (PPV) of trisomy 21, 18, and 13 was 69.6% (48/69). The PPV of SCAs was 37.3% (19/51). And the PPVs for CNVs was detected as 51.0% (<5 Mb), 71.4% (5 Mb ≤ CNV ≤10 Mb), 56.5% (>10 Mb). Finally, a follow-up about the pregnancy outcomes were conducted for all available cases., Conclusions: NIPS yielded high PPVs for trisomy 21, 18, and 13 aneuploidies and moderate PPVs for SCAs and CNVs. The screening effectiveness was closely related to the size of CNV fragments. Larger CNVs, especially larger than 5 Mb, could be detected more accurately by NIPS in our analytic technique. Meanwhile, diagnostic confirmation by microarray analysis was highly recommended., (© 2023 Japan Society of Obstetrics and Gynecology.)

Globally it is estimated that Down syndrome occurs in 1 in 800 live births (Bull 2020). It has also been estimated that the incidence of Down syndrome occurs in 1/444 live births in the Republic of Ireland. Given the prevalence of Down syndrome births in Ireland and the fact that care is provided by the majority of parents at home, this qualitative study aimed to explore the experiences of Irish parents receiving a postnatal diagnosis of Down syndrome. A qualitative research approach was used through semi structured interviews. Eight parents of a baby diagnosed postnatally with Down syndrome participated in this study sharing their stories of their postnatal diagnosis experiences. Five overarching themes emerged using a descriptive thematic analysis; 1. prenatal screening, pregnancy and delivery; 2. how the diagnosis was delivered; 3. setting and emotional experiences; 4. moving on with the postnatal diagnosis and 5. Future recommendations from parents' perspectives. This study highlighted the importance of the need for clinicians to ensure that partners are present at the time of the disclosure, that ample time is allocated and that verbal and written communications are provided to parents using less medical jargon when delivering the postnatal diagnosis of Down syndrome. These reasonable adjustments could alleviate parental anxiety at this critical juncture in their lives. Online resources and support forums were also identified as an integral support for families on discharge from the maternity centres and in the early months and years., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21., Methods: This was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care., Results: When cut-off values of free beta subunit of human chorionic gonadotropin (free β-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively., Conclusions: The new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy., (© 2023. The Author(s).)

Background: Screening for trisomy 21 provides pregnant women with accurate risk information. Different algorithms are used to screen for trisomy 21 in South Africa (SA). The Fetal Medicine Foundation (FMF) provides software to screen for trisomy 21 in the first trimester by ultrasound or a combination of ultrasound and biochemistry (combined screening), and requires regular and stringent quality control. With αlpha software, first trimester combined screening and screening with biochemistry alone in the first or second trimester are possible. The αlpha screening requires quality control of biochemical tests, but not of ultrasound measurements. Ideally, a screening test should have a high detection and a low screen positive rate. Despite the availability of these screening programmes, only a minority of infants with trisomy 21 are detected prenatally, raising questions about the effectiveness of screening., Objectives: To determine the screen positive and detection rates of prenatal screening for trisomy 21 in the SA private healthcare system., Methods: Data from the three largest laboratories collected between 2010 and 2015 were linked with genetic tests to assess screen positive and detection rates. Biochemical screening alone with αlpha software (first or second trimester) and combined screening using either FMF or αlpha software were compared., Results: One-third of an estimated 675 000 pregnancies in private practice in the 6-year study period underwent screening. There were 687 cases of trisomy 21 in 225 021 pregnancies, with only 239 (35%) diagnosed prenatally. The screen positive rates were 11.8% for first trimester biochemistry, 7.6% for second trimester biochemistry, 7.3% for first trimester FMF software ultrasound alone, 3.7% for combined first trimester screening with FMF software, and 3.5% for combined first trimester screening with αlpha software. The detection rates for a 5% false positive rate were 63% for first trimester biochemistry, 69% for second trimester biochemistry, 95% for combined first trimester screening with FMF software and 80% for combined first trimester screening with αlpha software. Detection and confirmation rates were highest with FMF software., Conclusion: Screening with FMF software has a similar screen positive rate and better detection rate than screening with αlpha software. The low prenatal detection rate of trisomy 21 is mainly due to a low prevalence of screening. More research is needed in the SA setting to explore why screening and confirmatory testing after high-risk results are not performed in many pregnancies.

Objective: The aim of this work was to compare different local cutoff values (LCV) and inline cutoff values (ICV) in pregnant women in the second trimester at high risk for carrying fetuses with trisomy 21., Methods: This retrospective cohort study analyzed prenatal screening outcomes in pregnant women (n = 311,561). The receiver operating characteristic curve was used to evaluate the diagnostic significance of the trisomy 21 risk value, alpha-fetoprotein, and free beta human chorionic gonadotropin multiple of the median for predicting trisomy 21 risk. The cutoff value corresponding to the maximal Youden index was taken as the LCV. The screening efficiency of both cutoff values was compared., Results: The LCV cutoff value was lower than the ICV cutoff value (1/643 vs 1/270). The sensitivity increased by 19.80%, the positive predictive value decreased by 0.20%, and the false-positive rate increased by 6.50%., Conclusion: The LCV should be used to determine trisomy 21 risk, which can increase the detection rate of trisomy 21 in the second trimester., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess whether the fetal fraction (FF) has an impact on the screen-positive rate (SPR) in cell-free DNA (cfDNA) screening for trisomy 21., Methods: Retrospective analysis based on samples analyzed using the Harmony ® Prenatal Test (Roche Inc). Due to the size of the data set, we focused on the SPR, which was stratified according to the maternal age, weight, gestational age, and FF distribution., Results: The study cohort consisted of 364,881 patients, including 2614 with a high-risk-result. Median maternal and gestational ages were 34.6 years and 12.4 weeks. FF was dependent on maternal age, weight, and gestational age. SPR was 0.72% and it was independent of maternal weight but was dependent on maternal age. There was a positive but weak association between the FF and the SPR until the FF reached 20.0% (OR p = 1.021, p < 0.001, Nagelkerkes r2 = 0.001). This group included 357,800 pregnancies or 98.1% of the study population. In the group of pregnancies with a FF > 20%, the association was stronger (OR 1.099, p < 0.001, Nagelkerkes r2 = 0.042)., Conclusion: The SPR in cfDNA screening for trisomy 21 was relatively constant up to a FF of about 20%., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

The use of race in maternal serum screening is problematic because race is a social construct rather than a distinct biological classifier. Nevertheless, laboratories offering this testing are encouraged to use race-specific cutoff values for maternal serum screening biomarkers to determine the risk of fetal abnormalities. Large cohort studies examining racial differences in maternal serum screening biomarker concentrations have yielded conflicting results, which we postulate may be explained by genetic and socioeconomic differences between racial cohorts in different studies. We recommend that the use of race in maternal serum screening should be abandoned. Further research is needed to identify socioeconomic and environmental factors that contribute to differences in maternal serum screening biomarker concentrations observed between races. A better understanding of these factors may facilitate accurate race-agnostic risk estimates for aneuploidy and neural tube defects., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Historically, there has been a lack of cost-effectiveness data regarding the inclusion of universal non-invasive prenatal testing (NIPT) for trisomy 21, 18, and 13 in the benefit package of the Universal Health Coverage (UHC) in Thailand. Therefore, this study aimed to perform the cost-benefit analysis of prenatal screening tests and calculate the budget impact that would result from the implementation of a universal NIPT program. A decision-tree model was employed to evaluate cost and benefit of different prenatal chromosomal abnormalities screenings: 1) first-trimester screening (FTS), 2) NIPT, and 3) definitive diagnostic (amniocentesis). The comparison was made between these screenings and no screening in three groups of pregnant women: all ages, < 35 years, and ≥ 35 years. The analysis was conducted from societal and governmental perspectives. The costs comprised direct medical, direct non-medical, and indirect costs, while the benefit was cost-avoidance associated with caring for children with trisomy and the loss of productivity for caregivers. Parameter uncertainties were evaluated through one-way and probabilistic sensitivity analyses. From a governmental perspective, all three methods were found to be cost-beneficial. Among them, FTS was identified as the most cost-beneficial, especially for pregnant women aged ≥ 35 years. From a societal perspective, the definitive diagnostic test was not cost-effective, but the other two screening tests were. The most sensitive parameters for FTS and NIPT strategies were the productivity loss of caregivers and the incidence of trisomy 21. Our study suggested that NIPT was the most cost-effective strategy in Thailand, if the cost was reduced to 47 USD. This evidence-based information can serve as a crucial resource for policymakers when making informed decisions regarding the allocation of resources for prenatal care in Thailand and similar context., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wongkrajang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to explore the prenatal indicators in the second trimester of pregnancy and their association with chromosome abnormities (CA) to guide decisions toward invasive diagnostic procedures. Pregnant women who underwent prenatal screening and underwent amniocentesis in the second trimester in our Hospital between June 2017 and February 2019 were included in this retrospective cohort study. The reason for amniocentesis in prenatal screening and diagnoses was extracted from the charts. Finally, 3449 pregnant women were included. Of them, 181 were with CA confirmed by amniocentesis (i.e., the CA group), while 3268 were without CA (i.e., the non-CA group). Compared with the women in the non-CA group, those in the CA group were more likely to be older (30 [27,32] vs 29 [26,31], P < .001), had higher gestational weeks (20 [19,23] vs 19 [18,23], P = .008), an increased risk of advanced maternal age (AMA) (9.4% vs 2.2%, P < .001), had an increased risk of NIPT (IRN) (5.1% vs 1.9%, P < .001), had higher rates of a parental chromosome abnormality (PCA) (1.8% vs 0.9%, P = .002), and had increased risk of trisomy 21 (IRT21) (63.0% vs 45.3%, P < .001). AMA (OR = 4.22, 95% CI: 2.35-7.58, P < .001; AUC = 0.536), IRN (OR = 10.62, 95% CI: 6.66-16.94, P < .001; AUC = 0.589), PCA (OR = 4.77, 95% CI: 2.01-11.32, P < .001; AUC = 0.584), and IRT21 (OR = 0.67, 95% CI: 0.47-0.89, P = .008; AUC = 0.515) were independently associated with CA. AMA, IRN, IRT21, and PCA during the second trimester were independently associated with CA, but their predictive values for CA were relatively low. Combining those indicators may improve the predictive value., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Screening tests are recommended to identify genetic defects, chromosomal aneuploidies, and structural birth defects. Sonographic and maternal serum-based options are available for the risk assessment of aneuploidy in the first and/or second trimester. Also, invasive diagnostic methods, such as amniocentesis, are used for prenatal diagnosis, but these methods carry a tangible risk to the fetus. However, in recent years, circulating fetal nucleic acids have a promising moleculer tool in the noninvasive prenatal diagnosis of fetal chromosomal aneuploidies. In this study, we aimed to explore the usability of microRNAs (miRNAs) in this process of prenatal diagnosis., Methods: Fourteen pregnant patients who were found to be carrying fetuses with congenital anomalies were designated as the patient group; 16 pregnant women identified as being at risk of carrying children with such anomalies-but whose fetuses were later found to be anomaly-free-were assigned to control group 1; and 13 pregnant women who had been screened and who had not been identified as being at risk made up control group 2. An analysis of miRNA expression, isolated from maternal plasma and amniotic fluid samples, was performed by quantitative real-time polymerase chain reaction., Results: It was found that hsa-miR-629-5p, hsa-miR-320c, hsa-miR-21-5p, hsa-let-7c-5p, hsa-miR-98-5p, hsa-miR-486-5p, hsa-miR-4732-5p, and hsa-miR-181a-5p levels increased in the patient group's maternal plasma compared to that of the control group., Conclusion: In light of these data, we believe that miRNAs may have an important role in the noninvasive prenatal diagnosis of fetal birth defects, especially Down syndrome.

Twin pregnancy presents unique considerations for aneuploidy screening. Pre-test counseling regarding benefits, alternatives, and options for aneuploidy screening should be provided to all patients carrying twin pregnancy. This article aims to review the options for aneuploidy screening in twin pregnancy including the potential benefits and limitations., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess the value of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal microdeletion/microduplication syndromes by carrying out prenatal diagnoses for two fetuses with Xp22.31 microdeletion indicated by NIPT., Methods: Two pregnant women suspected for fetal Xp22.31 microdeletion syndrome who presented at Zaozhuang Maternal and Child Health Care Hospital on December 5, 2017 and October 15, 2020 were selected as the study subjects. Clinical data of the two women were collected, and peripheral venous blood samples were collected for NIPT testing. Amniotic fluid samples were taken for G-banding chromosomal karyotyping analysis and copy number variation sequencing (CNV-seq) for fetus 1, while G-banding chromosomal karyotyping and single nucleotide polymorphism microarray analysis (SNP array) were carried out for fetus 2. Peripheral venous blood samples of couple 1 were collected for CNV-seq to verify the origin of copy number variation ., Results: NIPT indicated that fetus 1 had harbored a 1.3 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. CNV-seq analysis verified the fetus to be seg[GRCh37]del(X)(p22.31)chrX:g.6800001&#95;7940000del, with a 1.14 Mb deletion at Xp22.31, which was derived from its mother. NIPT indicated that fetus 2 had harbored a 1.54 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. SNP array analysis indicated arr[GRCh37]Xp22.31(6458940&#95;8003247)×0, with a 1.54 Mb deletion in Xp22.31 region., Conclusion: NIPT not only has a good performance for detecting fetal trisomies 21, 18 and 13, but also has the potential for detecting chromosomal microdeletion/microduplications. For high risk fetuses indicated by NIPT, prenatal diagnosis needs to be carry out to verify the chromosomal abnormalities.

Objective: The first trimester combined risk of trisomy 21 is obtained by multiplying the risk related to maternal age by the likelihood ratios of nuchal translucency, free beta-human chorionic gonadotrophin (β-hCG) and placenta associated plasma protein-A. Beyond five multiples of the median (MoM) of β-hCG, the risk of trisomy 21 is truncated. The objective of the present study was to evaluate the evolution of the first trimester combined risk of trisomy 21 in individuals with first-trimester free-β-hCG levels between 5 and 10 MoM., Methods: We conducted a non-interventional cohort study from a 6-year database of combined first-trimester trisomy 21 screening of all individuals who underwent the screening in a French specialized medical analysis center. We included all pregnant individuals who had a serum-free β-hCG between 5 and 10 MoM. Patients for whom the status of the fetus, with or without trisomy 21, was not identified by the outcome of the pregnancy or by a karyotype result were excluded from the study. The discriminatory capacity of free-β-hCG above 5 MoM was studied by a receiver operating characteristic curve. We used an orthogonal polynomial regression to represent the evolution of likelihood ratios according to free-β-hCG in MoM., Results: Among 413 216 combined first-trimester screens of trisomy 21, 2239 (0.5%) screens met the inclusion criteria. In the selected population, 801 (35.8%) were excluded from the study because of missing fetal or neonatal status, and 46 (3.2%) fetuses out of 1438 included were diagnosed with trisomy 21. For free β-hCG values between 5 and 10 MoM, the area under the curve is 0.56 (0.46-0.65). The scatterplot of the likelihood ratio of β-hCG showed an increasing parabolic pattern: the likelihood of trisomy 21 increases with the free-β-hCG threshold., Conclusion: To override the truncated risk of trisomy 21 in case of free β-hCG values between 5 and 10 MoM, the study has allowed us to estimate the adjusted risk of trisomy 21, enabling health professionals to offer appropriate prenatal counseling., (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objectives: The concentrations of maternal serum markers for aneuploidy screening are influenced by maternal characteristics such as race, smoking, insulin dependent diabetes mellitus (IDDM), and in vitro fertilization (IVF). Accurate risk estimation requires adjustment of initial values for these characteristics. This study aims to update and validate adjustment factors for race, smoking, and IDDM., Methods: The study included singleton pregnancies that received multiple marker screening in Ontario, Canada between January 2012, and December 2018, and had their information collected in the Better Outcomes Registry & Network (BORN) Ontario. Serum markers assessed included first trimester pregnancy-associated plasma protein A (PAPP-A), free β and total human chorionic gonadotropin (hCG), placental growth factor (PlGF) and αlpha-fetoprotein (AFP); second trimester AFP, unconjugated estriol (uE3), total hCG and inhibin A. The Mann-Whitney U test was used to assess the differences in the median multiple of the median (MoM) of serum markers between study and reference groups. New adjustment factors were generated by dividing the median MoM of a particular race, individuals who smoke tobacco, or have IDDM by those of the reference groups., Results: The study included 624,789 pregnancies. There were statistically significant differences in serum marker concentrations among pregnant individuals who were Black, Asian, or First Nations compared to a White group, those who smoked compared to Non-smoking individuals, and those with IDDM compared to Non-IDDM group. New adjustment factors for race, smoking, and IDDM were validated by comparing median MoM of serum markers corrected using the current adjustment factors and new adjustment factors generated in this study., Conclusion: The adjustment factors generated in this study can adjust the effects of race, smoking, and IDDM on serum markers more accurately., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The 'expressivist objection' (EO) refers to the notion that using reproductive (genetic) technologies to prevent the birth of future would-be disabled people contain, and express, a negative valuation of life with disability. Whilst the EO has received increased attention in recent years in line with rapid technological and genomic developments, there remains scant research on how EO concerns are experienced and expressed by disabled people and their families, especially within and between impairment groups. Bringing together two studies-one with adults and family members living with genetic conditions (n = 62) and one with parents of children with Down's syndrome (n = 22)-we argue that disabled people and their families variously embrace, reject or rework the EO across contexts, and yet also frequently situate it within broad support for reproductive technologies. We present three key factors that mediate responses to the EO: (1) the nature of impairment and its integration within identity; (2) social and cultural contexts relating to disability and (3) the (individual and collective) imagined futures of disabled people. In so doing, we blend the conceptual architecture of medical sociology and disability studies, arguing that this allows us to accurately illuminate the nuanced responses of disabled people and their families., (© 2022 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for the Sociology of Health & Illness.)

On July 2021, the UK High Court of Justice heard the Case CO/2066/2020 on the application of Heidi Crowter who lives with Down's syndrome, and Máire Lea-Wilson whose son Aidan has Down's syndrome. Crowter and Lea-Wilson, with the support of the disability rights campaign, 'Don't Screen Us Out', have been taking legal action against the Secretary of State for Health and Social Care (the UK Government) for a review of the 1967 Abortion Act: the removal of section 1(1)(d) making termination of pregnancy lawful for 'severe' fetal indications detected after 24 weeks' gestation. On 23 September 2021, the High Court dismissed the claim. This action came at a time when non-invasive prenatal testing (NIPT) was introduced into the NHS England Fetal Anomaly Screening Programme for the trisomies 21, 13 and 18. The implementation of NIPT has been heavily criticised, in particular by 'Don't Screen Us Out' campaigners, for increasing fetal selection and discrimination of people living with disabilities. The case of Crowter and Lea-Wilson echoes debates in other European countries such as in France and Germany, where the introduction of NIPT in the public healthcare system has provoked equally vehement public reactions and discussions. The comparison between these three countries allows contextualising the public discourses around NIPT and the ground for termination of pregnancy in relation to different socio-cultural and political contexts. We examine how each country, and particularly England, deals with the conflict between the principles of promoting the rights of people living with disabilities and preserving women's reproductive autonomy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: This study aimed to evaluate the performance of noninvasive prenatal testing (NIPT) for detecting three common trisomies (T21, T18, and T13) in pregnant women with diverse clinical indications., Methods: Frequencies of NIPT, of high chance of having one of the three trisomies, and of confirmed trisomies were determined for women with each of seven clinical indications in a national cross-sectional survey of approximately 300 prenatal diagnosis centers. Data were collected for the period from October 1, 2016 to September 30, 2018 using the Prenatal Diagnosis Technology Management On-line Information System. The performance of NIPT for detecting the three trisomies in pregnant women with different clinical indications was assessed in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value, and the corresponding 95% confidence intervals., Results: A total of 5766 true positive cases for T21, T18, and T13 were detected among 1,854,148 samples, giving an overall detection rate of 0.31% (95% CI: 0.30%-0.32%). Most positive cases were associated with "NT thickening" (1.18%) and "advanced maternal age" (0.51%). The detection sensitivities of NIPT were 99.60% for T21, 99.14% for T18, and 100% for T13, while the corresponding specificities were 99.90%, 99.94%, and 99.95%. The corresponding PPVs were 69.77%, 47.24%, and 22.36%. NIPT showed high sensitivity and specificity, regardless of clinical indication. In contrast, PPV for three trisomies varied widely between 9.09% and 66.46% depending on the clinical indication. Across seven clinical indications, PPV ranged from 50.62% to 73.09% for T21, 20.00%-58.33% for T18, and 4.17%-47.37% for T13. The highest PPVs were 73.09% for T21 in pregnancies involving "advanced maternal age", 58.33% for T18 in pregnancies with "NT thickening", and 47.37% for T13 in pregnancies with "NT thickening"., Conclusions: NIPT shows high sensitivity and specificity for detecting T21, T18, and T13 in pregnant women with different clinical indications. However, PPV depends strongly on clinical indication, highlighting the need to strengthen education and genetic counseling about prenatal screening., (© 2023 John Wiley & Sons Ltd.)

Competing Interests: The authors declare that they have no conflict of interest.

Objective: To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations., Method: We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2., Results: Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61-9.95], I 2 of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07-6.47], I 2  = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34-14.78], I 2  = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83-134.68], I 2  = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76-2.03], I 2  = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78-9.00], I 2  = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed., Conclusion: An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Introduction: We hypothesized that children with Down syndrome who were born after the implementation of first-trimester combined screening for trisomy 13, 18, and 21 and a second-trimester ultrasound scan in Denmark would show a milder syndrome phenotype. We investigated the birth biometry, prevalence of congenital malformations, and early childhood morbidity of children with Down syndrome before and after implementation of this screening program., Material and Methods: A nationwide register-based study of all live born singletons with Down syndrome in Denmark from 1995 to 2018. In interrupted time series analyses, we studied the temporal developments in birth biometry, prevalence of congenital malformations, and early childhood morbidity related to the implementation of a national prenatal screening program., Results: We included 602 singletons with Down syndrome born before and 308 after implementation of the screening program. Z-scores of birthweight and head circumference increased over time before screening, but this temporal development changed after implementation by -0.05 (95% confidence interval [CI]: -0.11 to 0.01) and -0.05 (95% CI -0.12 to 0.02), respectively. Just after implementation, the prevalence of non-severe congenital heart disease decreased (relative change in odds 0.48 [95% CI: 0.24-0.94]). For severe congenital heart disease, atrioventricular septal defect, and non-heart malformations, this change was 1.16 (95% CI: 0.56-2.41), 0.95 (95% CI: 0.43-2.03), and 0.98 (95% CI: 0.33-2.76), respectively. For all malformations, pre-existing temporal developments did not change following implementation of screening. The implementation was associated with higher odds of admission to a neonatal intensive care unit (relative change 1.98 [95% CI: 0.76-5.26]) and an increased risk of hearing impairment (risk difference 3.4% [95% CI: -0.4% to 7.1%]). In contrast, the implementation was not associated with the incidence of hospital admissions by 2 years of age or with the probability of a thyroid disorder., Conclusions: After implementation of a national prenatal screening program, we did not observe a milder Down syndrome phenotype apart from an apparent reduction in the proportion of children with non-severe congenital heart disease; this result is, however, limited by small numbers., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

New technologies create new complexities. Since non-invasive prenatal tests (NIPTs) were first introduced, keeping pace with complexity constitutes an ongoing task for medical societies, politics, and practice. NIPTs analyse the chromosomes of the fetus from a small blood sample. Initially, NIPTs were targeted at detecting trisomy 21 (Down syndrome): meanwhile there are sequencing techniques capable of analysing the entire genome of the unborn child. These yield findings of unclear relevance for the child's future life, resulting in new responsibility structures and dilemmas for the parents-to-be.The industry's marketing strategies overemphasize the benefits of the tests while disregarding their consequences. This paper chooses the opposite path: starting with the underestimated consequences, it focuses on adverse developments and downsides. Disparities, paradoxes, and risks associated with NIPTs are illustrated, ethical conflicts described. Indications that new technologies developed to solve problems create new ones are examined. In the sense of critical thinking, seemingly robust knowledge is scrutinized for uncertainties and ambiguities. It analyses how the interplay between genetic knowledge and social discourse results in new dimensions of responsibility not only for parents-to-be, but also for decision-makers, authorities, and professional societies, illustrated by a review of different national policies and implementation programmes. As shown by the new NIPT policy in Norway, the consequences can be startling. Finally, a lawsuit in the United States illustrates how an agency can risk forfeiting its legitimation in connection with the inaccuracy of NIPTs., (© 2023. The Author(s).)

Background and Objective: Down syndrome is the most common chromosomal anomaly found among newborns. Prenatal screening can inform pregnant women and their partners of the risk of their baby having Down syndrome. The study aimed to determine the awareness and attitude of Nigerian pregnant women towards prenatal screening for Down syndrome., Methods: This was a prospective observational study among pregnant women who attended antenatal clinics at two teaching hospitals in Nigeria between January and June 2018. Data on their awareness and attitude towards Down syndrome screening were collected using a semi-structured questionnaire and analysed with SPSS version 23.0. Level of significance was set at p<0.05 and 95% confidence interval (CI)., Results: Four hundred and four women participated in the study and their mean age was 30.8±4.87 years. Overall, 65.1% were aware of Down syndrome and the media (54.4%) was their main source of information. Less than half (44.3%) of them had a positive attitude towards Down syndrome screening. Respondents with primary (AOR=0.20, 95% CI=1.175-21.687) and secondary education (AOR=0.34, 95% CI=1.494-5.867) were less likely to be aware of Down syndrome, while having a positive attitude towards Down syndrome screening (AOR=2.07, 95% CI=0.314-0.745) and being engaged in skilled occupation (AOR=3.26, 95% CI=0.135-0.697) predicted awareness. A positive attitude towards Down syndrome screening was predicted by being engaged in skilled (AOR=2.51, 95% CI=0.185-0.858) and semi-skilled (AOR=2.37, 95% CI=0.205-0.870) occupation., Conclusion: Though majority of pregnant women had good awareness of Down syndrome; however, less than half of them had a positive attitude towards the screening test. The awareness and positive attitude exhibited by the women in this study were influenced by their level of education and occupation., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2023 by West African Journal of Medicine.)

It is now well established that maternal serum markers are often abnormal in fetal trisomy 21. Their determination is recommended for prenatal screening and pregnancy follow-up. However, mechanisms leading to abnormal maternal serum levels of such markers are still debated. Our objective was to help clinicians and scientists unravel the pathophysiology of these markers via a review of the main studies published in this field, both in vivo and in vitro, focusing on the six most widely used markers (hCG, its free subunit hCGβ, PAPP-A, AFP, uE3, and inhibin A) as well as cell-free feto-placental DNA. Analysis of the literature shows that mechanisms underlying each marker's regulation are multiple and not necessarily directly linked with the supernumerary chromosome 21. The crucial involvement of the placenta is also highlighted, which could be defective in one or several of its functions (turnover and apoptosis, endocrine production, and feto-maternal exchanges and transfer). These defects were neither constant nor specific for trisomy 21, and might be more or less pronounced, reflecting a high variability in placental immaturity and alteration. This explains why maternal serum markers can lack both specificity and sensitivity, and are thus restricted to screening.

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 14-21 weeks. 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., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Chaipongpun, Wanapirak, Sirichotiyakul, Tongprasert, Srisupundit, Luewan, Traisrisilp, Jatavan, Sirilert and Tongsong.)

Objective: To investigate factors involved in the decision to decline prenatal screening with noninvasive prenatal testing (NIPT)., Method: A questionnaire study was conducted among 219 pregnant women in the Netherlands who had declined prenatal screening with NIPT (TRIDENT-2 study). Respondents were selectively recruited from three hospitals and 19 midwifery practices, primarily located in or near socioeconomically disadvantaged neighborhoods. 44.3% of the respondents were of non-Western ethnic origin and 64.4% were religious., Results: Most respondents (77.2%) found the decision to decline NIPT easy to make, and 59.8% had already made the decision before information about NIPT was offered. These respondents were more often religious, multigravida, and had adequate health literacy. The main reasons to decline NIPT were "I would never terminate my pregnancy" (57.1%) and "every child is welcome" (56.2%). For 16.9% of respondents, the out-of-pocket costs (175 euros) played a role in the decision, and the women in this group were more often nonreligious, primigravida, and had inadequate health literacy., Conclusion: The primary factors involved in the decision to decline NIPT were related to personal values and beliefs, consistent with autonomous choice. Out-of-pocket costs of NIPT hinder equal access for some pregnant women., (© 2022 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objectives: Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency., Methods: Singleton pregnancies recruited at 11-14 weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates., Results: Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72-97%) of the cases at a false-positive rate of 13% (95% CI: 12-15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82-99%) at a false-positive rate of 4% (95% CI: 4-5%) using a 1:300 cut-off and to 100% (95% CI: 89-100%) at a false-positive rate of 6% (95% CI: 5-8%) using a 1:500 cut-off., Conclusions: First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: To determine the efficacy of three different maternal screening programs (first-trimester screening [FTS], individual second-trimester screening [ISTS], and first- and second-trimester combined screening [FSTCS]) in predicting offspring with trisomy 21, trisomy 18, and neural tube defects (NTDs)., Methods: A retrospective cohort involving 108,118 pregnant women who received prenatal screening tests during the first (9-13+6 weeks) and second trimester (15-20+6 weeks) in Hangzhou, China from January-December 2019, as follows: FTS, 72,096; ISTS, 36,022; and FSTCS, 67,631 gravidas., Result: The high and intermediate risk positivity rates for trisomy 21 screening with FSTCS (2.40% and 5.57%) were lower than ISTS (9.02% and 16.14%) and FTS (2.71% and 7.19%); there were statistically significant differences in the positivity rates among the screening programs (all P < 0.05). Detection of trisomy 21 was as follows: ISTS, 68.75%; FSTCS, 63.64%; and FTS, 48.57%. Detection of trisomy 18 was as follows; FTS and FSTCS, 66.67%; and ISTS, 60.00%. There were no statistical differences in the detection rates for trisomy 21 and 18 among the 3 screening programs (all P > 0.05). The positive predictive values (PPVs) for trisomy 21 and 18 were highest with FTS, while the false positive rate (FPR) was lowest with FSTCS., Conclusion: FSTCS was superior to FTS and ISTS screening and substantially reduced the number of high risk pregnancies for trisomy 21 and 18; however, FSTCS was not significantly different in detecting fetal trisomy 21 and 18 and other confirmed cases with chromosomal abnormalities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Communicating the diagnosis of Down Syndrome to a couple of parents is never easy, whether before or after birth. As doctors, we must certainly rely on our own relational skills, but it is also necessary to be confident in some general indications, which are often overlooked in the strict hospital routine. This article is intended as a summary of the main articles published on this subject in the international literature, collecting and summarising the most important indications that have emerged in years of medical practice all over the world as well as in our personal experience. The diffusion of these guidelines is essential to help the doctor in this difficult task, on which there is often little training, and above all to guarantee to the parents the least traumatic communication possible., (© 2023. The Author(s).)

We analyzed patients with isolated, balanced complete atrioventricular septal defects. We identified 71 patients born in Nevada, between January 2008 and December 2020. We also analyzed prenatal detection rates. Of the 71, 61 (85%) had trisomy 21, 1 (1%) had CHARGE syndrome and 22q.11 deletion, and 10 (14%) had no chromosomal abnormalities. Of the 71, 67 had prenatal care, and 43/67 (64%) were prenatally diagnosed. Prenatal detection rate for 2008-2012 was 9/20 (45%) and 18/21 (86%) for 2018-2020, P = .03. Of the 71, 67 underwent surgical repair with 1 current postpulmonary artery banding and 0 surgical deaths. Of the 67, 3 (4%) had heart block. Only 1 (1.5%) patient had reoperation for a mitral valve replacement. Of the 71, 67 (94%) are alive during a 6-year average (range = 0-12 years) follow-up. In conclusion, surgical and long-term outcomes were excellent. Also, high state-wide, general population prenatal detection rates were achieved.