BACKGROUND:A false-positive cell-free DNA prenatal screening result may arise from confined placental mosaicism, however, the frequency and obstetrical ramifications of such cases are poorly understood. OBJECTIVE:This study aimed to assess the prevalence of confined placental mosaicism among pregnancies with false-positive cell-free DNA results and the associated obstetrical outcomes. STUDY DESIGN:This was a prospective, matched-cohort study with a 1:2 ratio of cases with false-positive cell-free DNA results and controls with low-risk cell-free DNA results that were matched by maternal age and body mass index. Participants were recruited between November 2022 and March 2025 at Monash Health and Monash Ultrasound for Women in Melbourne, Australia. Cytogenetic testing was conducted on 4 biopsies per placenta to investigate confined placental mosaicism. The cases and matched controls were compared using trio matching identifiers as random effect in conditional logistic regression and linear mixed-effects modelling. RESULTS:A total of 60 cases with false-positive cell-free DNA results were matched with 120 controls. Confined placental mosaicism was observed in 20 of the 60 cases (33.3%) and in none of the controls. The prevalence of confined placental mosaicism was highest among those with rare autosomal trisomy (57.9%; 11/19) and monosomy X (75.5%; 3/4) results. Confined placental mosaicism was also observed following common autosomal trisomy results (21.4%; 3/14) and subchromosomal copy number variants (15.8%; 3/19). The median birth weight percentile was significantly lower among instances of confirmed confined placental mosaicism (20.1; interquartile range, 9.9-48.5) than among matched controls (43.5; interquartile range, 17.1-66.1; P=.049); however, there were no statistically significant increases in small-for-gestational-age neonates or other adverse pregnancy outcomes. CONCLUSION:Confined placental mosaicism is a frequent contributor to false-positive cell-free DNA results, most often for monosomy X and rare autosomal trisomy results. Although the birth weight median percentiles were lower, the outcomes of cell-free DNA-detected confined placental mosaicism in this average-risk cohort were predominantly favorable. El resumen está disponible en Español al final del artículo. VIDEO ABSTRACT.
OBJECTIVE:To assess parental preferences, expectations and understanding of genome-wide cell-free DNA screening (gwNIPT) in Australia. METHOD:A cross-sectional survey study utilizing an anonymous electronic questionnaire was conducted across three participating screening services in Australia between September 2023 and November 2024. Questions pertained to respondent demographics, pre-screening counselling, and accuracy expectations of gwNIPT for various chromosomal anomalies. Statistical analyses to investigate associations between responses used Chi-squared and Fisher's exact tests, ordinal logistic regression, and the Kruskal-Wallis test. RESULTS:There were 329 survey responses recorded, of which 216 were completed (65.7%). The most frequent source of NIPT referral was a medical doctor (74.1%), and the most common duration of pre-screening counselling was 5 minutes (41.0%). Respondents showed overwhelming interest in all anomalies included in gwNIPT as well as various phenotypic outcomes including those of uncertain clinical significance. Despite this, only a minority of patients were aware that they were undergoing genome-wide screening (38.2%), and respondents did not anticipate a statistically significant difference in screening accuracy across different anomaly types (p = 0.715). CONCLUSION:Respondents undergoing gwNIPT indicated a preference to receive as much genetic information about their pregnancies as possible. Pre-screening counselling should therefore include the limitations of gwNIPT.
BACKGROUND:Post-partum haemorrhage due to uterine atony remains a leading cause of maternal mortality worldwide with a high portion occurring in under resourced settings. The risk of post-partum haemorrhage increases with prolonged duration of the third stage of labour. Early nipple stimulation promotes the early release of oxytocin, which has beneficial effects on uterine tone. Therefore, this meta-analysis evaluates the impact of early nipple stimulation on the duration of the third stage of labour and estimated blood loss. AIM:To assess whether early nipple stimulation following uncomplicated deliveries effects the duration of the third stage of labour and estimated blood loss. METHODS:A comprehensive search was conducted in PubMed, EMBASE, Cochrane, CiNAHL, Scopus and Web of Science, covering studies published up to February 5th 2024. Eligible studies included randomised control trials and observational studies involving women with singleton pregnancies and live foetuses who engaged in nipple stimulation in the third stage. Studies that reported the duration of the third stage of labour and/or estimated blood loss were included. Exclusion criteria comprised stillbirths, multiple pregnancies and the use of general anaesthesia. Data was analysed using a random-effects model. This review was registered with PROSPERO (CRD42023494605). RESULTS:Nine studies involving 789 mothers were included. Early nipple stimulation reduced blood loss and improved uterine tone. When synthetic oxytocin was not used, early nipple stimulation reduced the duration of the third stage of labour. CONCLUSION:Early nipple stimulation may be a viable alternative to uterotonics in uncomplicated deliveries, especially in low-resource settings. Further high-quality primary research is indicated to build upon the preliminary findings of this current meta-analysis.
False-positive prenatal cell-free DNA screening (cfDNA) results may arise from confined placental mosaicism (CPM). This cohort study examines the persistence of high-risk cfDNA in the third pregnancy trimester after exclusion of fetal involvement, and the concordance of these results with CPM in the postpartum placenta. Pregnant individuals receiving a false-positive primary cfDNA result were recruited from Monash Health and Monash Ultrasound for Women in Melbourne, Australia, between August 2023 and December 2024. Participants underwent genome-wide repeat cfDNA screening (r-cfDNA) after 30 + 0 weeks’ gestation. Placental samples were collected and cytogenetically analysed postpartum. This cohort included 21 individuals, of which 33.3
The introduction of noninvasive prenatal testing has resulted in substantial reductions to previously accepted false-positive rates of prenatal screening. Despite this, the possibility of false-positive results remains a challenging consideration in clinical practice, particularly considering the increasing uptake of genome-wide noninvasive prenatal testing, and the subsequent increased proportion of high-risk results attributable to various biological events besides fetal aneuploidy. Confined placental mosaicism, whereby chromosome anomalies exclusively affect the placenta, is perhaps the most widely accepted cause of false-positive noninvasive prenatal testing. There remains, however, a substantial degree of ambiguity in the literature pertaining to the clinical ramifications of confined placental mosaicism and its potential association with placental insufficiency, and consequentially adverse pregnancy outcomes including fetal growth restriction. Other causes of false-positive noninvasive prenatal testing include vanishing twin syndrome, in which the cell-free DNA from a demised aneuploidy-affected twin triggers a high-risk result, technical failures, and maternal origins of abnormal cell-free DNA such as uterine fibroids or unrecognized mosaicisms. Most concerningly, maternal malignancies are also a documented cause of false-positive screening results. In this review, we compile what is currently known about the various causes of false-positive noninvasive prenatal testing.
The performance of cell‐free DNA (cfDNA) screening for microscopic copy number variants (CNVs) is unclear.
To assess the outcomes of pregnancies at high‐risk for rare autosomal trisomies (RATs) and segmental imbalances (SIs) on cell‐free DNA (cfDNA) screening.
Background Blended teaching combines traditional in-person components (simulation-based training and clinical-based placement) with online resources. Due to the COVID-19 pandemic, we modified our Women's Health Interprofessional Learning through Simulation (WHIPLS) program - to develop core obstetric and gynaecological skills - into a blended teaching program. There is limited literature reporting the observations of blended teaching on learning. Aims To qualitatively evaluate the blended teaching program and explore how it contributes to learning. Materials and Methods This study was performed at Monash University in Melbourne, Australia. A total of 98 medical students and 39 midwifery students participated. Data were collected by written survey and analysed by authors using a thematic analysis framework. Results Students reported that in-person teaching remains a vital aspect of their curriculum, contributing an averaged 63.2% toward an individual's learning, compared with online. Five substantial themes demonstrate how students learnt and maximised education opportunities using a blended teaching program: 'low-pressure simulation environments', 'peer-assisted learning', 'haptic learning', 'scaffolded learning' and 'the impact of online discourse'. Discussion In-person teaching remains a cornerstone of obstetric and gynaecological clinical skills education, of which interprofessional simulation and clinical-based placement are key components. Teaching via online discourse alone, is not sufficient to completely replace and provide comparable learning outcomes, but certainly plays an important role to prime students' learning and to maximise in-person opportunities and resources. Our study reveals key pedagogies of a blended (online and in-person) learning program, providing further evidence to support its ongoing utility as a feasible and warranted approach to learning.
Objectives To explore student perceptions of learning and interprofessional aspects of obstetric and neonatal emergencies through online simulation-based workshops. Methods This qualitative study was conducted at Monash University, Australia. Data were obtained from six separate online Obstetric Neonatal Emergency Simulation workshops held between May 2020 and August 2021. A total of 385 students attended and were invited to participate in the study by completing an online survey two-three weeks later. Of the attendees, 144 students completed the survey (95 medical, 45 midwifery), equating to a response rate of 37%. Survey responses were downloaded from online survey platform and separated into medical and midwifery responses. Thematic analysis of data was performed using a coding framework, resulting in development of themes and subthemes. Results Main themes were adaptability, connectivism, preparedness for practice, experiential learning, learning through modelling and dynamics of online interaction. Students reported that online workshop was a useful alternative method to experience simulation-based learning, increase their readiness for clinical practice and foster positive interprofessional relationships. Consistent with existing literature evaluating similar in-person programs, midwifery students were most interested in interprofessional interaction (predominant theme: dynamics of online interaction), whilst medical students were more concerned with developing clinical skills (predominant themes: learning through modelling, experiential learning). Conclusions Online learning may be a useful and convenient way of delivering interprofessional simulation-based education during the pandemic, in remote areas and as an adjunct to in-person teaching. Future studies should evaluate the impact of online learning with a mixed methods study and in comparison, to in-person programs.
Objective To determine the proportion of major fetal structural abnormalities that can be detected before 11 gestational weeks. Methods We conducted a retrospective study of individual patient files at a tertiary provider of obstetric and gynecological ultrasound in Melbourne, Australia. All women who had a pre-cell-free DNA ultrasound with a crown-rump length of less than 45 mm and had one or more ultrasounds at a later gestation were included in the analysis. The primary outcome was the incidence of a fetal structural abnormality. Results A total of 3333 cases were included in the final analysis. Overall, 316 fetuses (9.5%) had a structural abnormality detected at any point throughout gestation, of which 86 were major structural abnormalities (2.6%). Sixteen fetal abnormalities were detected before 11 weeks of gestation, including 15 major abnormalities (17.4% of the major anomalies). All major fetal abnormalities detected before 11 gestational weeks were confirmed at later ultrasound examinations or the pregnancy did not continue (in four cases due to termination of pregnancy and in one case spontaneous miscarriage before first trimester morphology ultrasound). Conclusion Detection of fetal abnormalities is possible before 11 weeks of gestation. Early suspicion is more likely in cases of major structural abnormalities.
This study aims to determine the incidence of ultrasound findings that have the potential to change clinical management on the day of blood-sampling for non-invasive prenatal testing (NIPT). A retrospective study was conducted at a tertiary provider of obstetric and gynecological ultrasound in Melbourne, Australia. Individual patient files were reviewed, and results were collated for maternal characteristics, pre-NIPT ultrasound reports, results and test characteristics of both NIPT and diagnostic testing and genetic counselling notes. The primary outcome was a potential change in patient management due to findings detected on the pre-NIPT ultrasound. Of 6,250 pre-NIPT ultrasounds, 6,207 were included in analysis. Of these, 598 (9.6%) pregnancies had a finding on pre-NIPT ultrasound that had the potential to change patient management. The reasons for this potential change in management were detection of gestational age below ten weeks (245, 3.9%), miscarriage (175, 2.8%), demised twin (43, 0.7%), fetal edema (115, 1.9%) and major structural abnormalities (20, 0.3%). These findings were common in patients of advanced maternal age and in spontaneous conceptions. A pre-NIPT ultrasound has the potential to change clinical management in almost one in ten women. The proportion is higher in older age groups and lower in IVF conceived pregnancies.
This report describes the Obstetric and Neonatal Simulation (ONE-Sim) workshop run in a remote learning format for medical and midwifery students in an interprofessional setting during the COVID-19 pandemic. It explores the observation of students as participants in the online learning of using Personal Protective Equipment and simulation-based learning of perinatal emergency management. This was followed by their mutual interaction and reflections. This paper aims to understand the role of synchronous remote learning through simulation and its impact on interprofessional interactions. We describe the experience of medical and midwifery students with the ONE-Sim workshop, facilitated by medical (obstetric and neonatal) and midwifery educators. Formal thematic analysis will be performed as part of the ongoing study; however, initial direct observation demonstrated that students reacted positively to the online ONE-Sim workshop and engaged well with facilitators and peers. Students mutually interacted amongst themselves, shared their previous experiences, knowledge of roles as medical and midwifery practitioners and how they see themselves in those roles in a perinatal emergency setting. The initial observations demonstrate that interprofessional education delivered in an e-learning format can be useful and meaningful, and may be utilized across a number of specialties.
OBJECTIVE: Medical student interest in surgery is decreasing both internationally and in Australia. There is also a current shortage of perioperative nursing staff, and demand for both surgeons and perioperative nurses is only expected to rise. The aim of this qualitative thematic analysis is to explore: (1) medical and nursing student's influences on their perspectives on surgery, and (2) the impact of a novel, interprofessional, simulation-based workshop on medical and nursing student interest in surgery as a career. DESIGN: A paired, anonymous pre- and postworkshop written survey was completed by medical and nursing student participants before and immediately after the surgical skills workshop. Thematic analysis of the responses was performed by 2 researchers independently to identify themes and subthemes regarding the study aims. SETTING: The study was conducted at Monash Medical Centre, a tertiary care center in Melbourne, Australia. PARTICIPANTS: One hundred and seventy-six undergraduate medical and nursing students attended the workshop, consisting of 144 fourth-year medical students (enrolled in a 5-year course) and 32 second-year nursing student volunteers (enrolled in a 3-year course). RESULTS: Analysis of how students' prior surgical experiences impacted their perspective on surgery revealed 5 themes: inclusive mentors and role models, learning through active participation, feeling unwelcome or intimidated, demands of the surgical lifestyle, and personal factors that influenced interest in surgery as a career. Most students reported that the workshop had a beneficial effect on their perception of surgery as a career. Analysis of student responses found 3 themes that affected the impact of the workshop on their interest in surgery: simulated practice of technical skills, exposure to nontechnical aspects of surgery, and simulation fidelity. CONCLUSIONS: Interprofessional, simulated-based surgical skills workshops may improve medical and nursing students' perceptions of surgery as a career, and should be considered for inclusion in undergraduate medical and nursing curricula. (C) 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.
OBJECTIVE:To summarize the available evidence concerning fertility preservation techniques in the context of women with endometriosis.DATA SOURCES:We searched for studies published between 1984 and 2019 on endometriosis and Assisted Reproductive Technology outcomes. We searched MEDLINE and PubMed and performed a manual search of reference lists within identified studies.METHODS OF STUDY SELECTION:A total of 426 articles were identified, and 7 studies were eligible to be included for the systematic review. We included all published studies, excluding reviews, case reports, and animal studies.TABULATION, INTEGRATION, AND RESULTS:Despite a significant increase in the number of studies addressing fertility preservation over the study period, we found a relative lack of evidence addressing the use of fertility preservation techniques in women with endometriosis. The studies identified included 2 case reports, 1 histological science study, and 4 retrospective cohort studies.CONCLUSION:Women with endometriosis may benefit from fertility preservation techniques. However, there currently is a paucity of data in this population, especially when compared with other indications for fertility preservation. Although much knowledge can be translated from the oncofertility discipline, we have identified and discussed endometriosis-related changes to ovarian reserve and oocyte health that justify further well-designed research to confirm that fertility preservation outcomes are similar for women with endometriosis.
This study aims to determine the incidence of ultrasound findings that may change clinical management on the day of blood‐sampling for cell‐free DNA (cfDNA) screening.