Search

Objectives: Our aim was to examine the prenatal profiles of pregnancies affected by an atypical chromosomal aberration, focusing on pathogenic copy‐number variants (pCNVs). We also wanted to quantify the performance of combined first‐trimester screening (cFTS) and a second‐trimester anomaly scan in detecting these aberrations. Finally, we aimed to estimate the consequences of a policy of using non‐invasive prenatal testing (NIPT) rather than invasive testing with chromosomal microarray analysis (CMA) to manage pregnancies identified as high risk by cFTS. Methods: This was a retrospective review of the Danish Fetal Medicine Database of all pregnant women who underwent cFTS and a risk assessment for trisomy 21 between 1 January 2008 and 31 December 2018. Chromosomal aberrations diagnosed prenatally, postnatally or from fetal tissue following pregnancy loss or termination of pregnancy were identified. Chromosomal aberrations were grouped into one of six categories: triploidy; common trisomy (13, 18 or 21); monosomy X; other sex‐chromosome aberration (SCA); pCNV; and rare autosomal trisomy (RAT) or mosaicism. The prevalence of each aberration category was stratified by the individual cFTS markers and trisomy 21 risk estimate, and the size of each pCNV diagnosed by CMA was calculated. Results: We retrieved data on 565 708 pregnancies, of which 3982 (0.70%) were diagnosed with a fetal chromosomal aberration. cFTS identified 87% of the common trisomies, but it also performed well in identifying triploidies (86%), monosomy X (92%), atypical SCAs (58%) and RATs or mosaicisms (70%). pCNVs comprised 27% (n = 1091) of the chromosomal aberrations diagnosed overall, and the prevalence increased during the study period, as prenatal CMA was increasingly being performed. In pregnancies with a maternal age < 30 years, nuchal translucency (NT) thickness ≤ 95th centile, pregnancy‐associated plasma protein‐A (PAPP‐A) ≥ 1 multiple of the median, or trisomy 21 risk of ≤ 1 in 1000, the prevalence of pCNVs exceeded significantly the prevalence of trisomies 21, 18 and 13. Pregnancies affected by a pCNV had significantly increased NT and decreased levels of the maternal biomarkers PAPP‐A and β‐human chorionic gonadotropin compared with unaffected pregnancies. However, only 23% of these pregnancies screened positive on cFTS and 51% of pCNVs were not detected until after birth. Among high‐risk pregnancies, pCNVs comprised 14% of diagnosed aberrations, and when other atypical aberrations were considered, conventional NIPT (screening for trisomies 21, 18 and 13 and monosomy X) would miss 27% of all pathogenic aberrations diagnosed from invasive testing following a high‐risk cFTS result. Thus, 1 in 26 pregnancies at high risk following cFTS would be affected by a chromosomal aberration despite a normal result from conventional NIPT. In a contingent screening model using NIPT for the 'intermediate'‐risk group (trisomy 21 risk of 1 in 100–299), 50% of the aberrations would be missed. In our cohort, 79% of the pCNVs diagnosed were < 5Mb and therefore not detectable using current forms of 'genome‐wide' NIPT. Conclusions: As a by‐product of screening for trisomies 21, 18 and 13, most triploidies and the majority of atypical SCAs, RATs and mosaicisms are detected before birth. However, only 23% of pCNVs are associated with a high‐risk result according to cFTS and only half are diagnosed before birth. Replacing invasive testing with NIPT for high‐risk pregnancies would substantially decrease the first‐trimester detection of pathogenic chromosomal anomalies. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

This article discusses the identification of partial hydatidiform mole (PHM) using non-invasive single-cell sequencing of fetal circulating extravillous trophoblasts (cEVTs) isolated from maternal blood. PHM is a condition that is typically triploid and associated with risks such as pre-eclampsia and gestational trophoblastic disease. The article presents a case study where a novel cell-based non-invasive prenatal testing (CB-NIPT) platform was used to accurately diagnose PHM. The study found that the number of cEVTs recovered from maternal blood was significantly higher in the PHM case compared to healthy controls, suggesting the potential for cEVTs as an early marker for associated hypertensive disorders and pre-eclampsia. Early diagnosis of PHM is crucial for optimal management and this study demonstrates the potential of CB-NIPT technology for early blood-based detection of PHM. [Extracted from the article]

Objectives: To examine the distribution of nuchal translucency thickness (NT), free β‐human chorionic gonadotropin (β‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A) in pregnancies with a fetal 22q11.2 aberration. Furthermore, the performance of combined first‐trimester screening (cFTS) and a new risk algorithm targeting 22q11.2 deletions in detecting affected pregnancies was evaluated. Finally, prenatal malformations and pregnancy outcome were assessed. Methods: This was a nationwide registry‐based cohort study of all pregnancies that underwent prenatal screening with a due date between January 2008 and December 2018 in Denmark. All cases with a fetal 22q11.2 deletion or duplication (hg19 chr22:18.9mio‐25.0mio) diagnosed pre‐ or postnatally or following pregnancy loss or termination of pregnancy were retrieved from the Danish Cytogenetic Central Register and linked with pregnancy data from the Danish Fetal Medicine Database. Fetal and maternal characteristics, including cFTS results and pregnancy outcome, of pregnancies with any 22q11.2 deletion or duplication (LCR22‐A to ‐H) and pregnancies with a classic deletion or duplication (LCR22‐A to ‐D) diagnosed by chromosomal microarray were compared with those of a chromosomally normal reference group. A risk algorithm was developed for assessing patient‐specific risks for classic 22q11.2 deletions based on NT, PAPP‐A and β‐hCG. Detection rates and false‐positive rates at different risk cut‐offs were calculated. Results: We included data on 143 pregnancies with a fetal 22q11.2 aberration, of which 97 were deletions (54 classic) and 46 were duplications (32 classic). NT was significantly increased in fetuses with a classic deletion (mean, 1.89 mm), those with any deletion (mean, 1.78 mm) and those with any duplication (mean, 1.86 mm) compared to the reference group (mean, 1.65 mm). β‐hCG multiples of the median (MoM) was decreased in all 22q11.2 subgroups compared with the reference group (mean, 1.02) and reached significance in pregnancies with a classic deletion and those with any deletion (mean, 0.77 and 0.71, respectively). PAPP‐A MoM was significantly decreased in pregnancies with a classic duplication and those with any duplication (mean, 0.57 and 0.63, respectively), and was significantly increased in pregnancies with a classic deletion and those with any deletion (mean, 1.34 and 1.16, respectively), compared to reference pregnancies (mean, 1.01). The screen‐positive rate by cFTS was significantly increased in pregnancies with a classic deletion (13.7%), any deletion (12.5%), a classic duplication (46.9%) or any duplication (37.8%) compared to the reference group (4.5%). A risk algorithm targeting classic 22q11.2 deletions more than doubled the prenatal detection rate of classic 22q11.2 deletions, but with a substantial increase in the false‐positive rate. Structural malformations were detected in 41%, 35%, 17% and 25% of the pregnancies with a classic deletion, any deletion, classic duplication or any duplication, respectively. Pregnancy loss occurred in 40% of pregnancies with a classic deletion and 5% of those with a classic duplication diagnosed prenatally or following pregnancy loss. Conclusions: The distribution of cFTS markers in pregnancies with a classic 22q11.2 duplication resembles that of the common trisomies, with decreased levels of PAPP‐A. However, classic 22q11.2 deletions are associated with increased levels of PAPP‐A, which likely limits early prenatal detection using the current cFTS risk algorithm. The scope for improving early detection of classic 22q11.2 deletions using targeted risk algorithms based on NT, PAPP‐A and β‐hCG is limited. This demonstrates the capability, but also the limitations, of cFTS markers in detecting atypical chromosomal anomalies, which is important knowledge when designing new prenatal screening programs. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

This article describes the successful implementation of a population-based screening and assessment service for pregnant women in a remote healthcare setting in Australia. The service, called the Initial Maternity Assessment and Planning (IMAP) service, was expanded to include a remote Australian maternity healthcare setting using a co-design approach and implementation science methodology. Since its establishment in 2023, over 200 women have been seen through the service, resulting in an increase in the proportion of local women accessing first trimester ultrasound and a decrease in the number of local women not attending for antenatal care within the first trimester. This study demonstrates the feasibility of scaling up a service to improve equity of care for women in regional and remote areas. [Extracted from the article]

This article describes the establishment of the Initial Maternity Assessment and Planning Service (IMAP) in Australia, which aims to provide comprehensive and early antenatal care for women planning public maternity care. The service includes a comprehensive ultrasound assessment, screening for aneuploidy and pre-eclampsia, and a review of obstetric, medical, and personal history with a dedicated midwife. The information is collated by an obstetrician to provide early pregnancy risk stratification. This study confirms the feasibility of a redesigned approach to first trimester specialist maternity care. [Extracted from the article]

This article discusses the implementation outcomes of the Initial Maternity Assessment and Planning (IMAP) service in Australia. The IMAP service is a first trimester population-based screening and assessment service that aims to improve antenatal care. The study found that a majority of eligible women accessed the service within the recommended gestational window, and a significant proportion were allocated to low-risk community-based models of care. The findings suggest that the IMAP service has successfully improved the provision of early pregnancy care and highlights the potential benefits of a redesigned approach to first trimester specialist maternity care. [Extracted from the article]

Animal models for preeclampsia are mostly determined by the experimental induction of hypertension, proteinuria and latterly, endogenous production of anti-angiogenic factors (sFlt-1). The focus on maternal outcome measures is more immediately obvious, with comparative and sequential data of blood pressure and urine protein excretion. In non-human primates, the data concerning birthweight requires a greater number of observations and thus will be accumulated over a longer period of time and a greater number of experimental protocols. The following represents the outcome of over 20 years of experimental preeclampsia (EPE) compared with normal pregnancy outcome data in baboons. MethodsThis data represents the outcomes from 91 pregnancies over the last 25 years at the Australian National Baboon Colony. These pregnancies are attributed to females who had experimental preeclampsia (EPE) and those within the general colony. EPE was induced at day 130 (of 182 days gestation length), and in some protocols, treatments such as inhibitory RNA or placental growth factor (PlGF) were tested. All studies were approved by the institutional Animal Welfare Committee. RESULTS: The overall neonatal birthweight was 697 g ± 115 g. The average birthweight for normal males was 770 ± 105 g; and for male offspring of animals with EPE, 680 ± 113 g; for normal females was 640 ± 95 g and females from EPE pregnancies, 690 ± 43 g. There was only a significant difference in weight for females compared to males overall (p = 0.002), and there was no significant difference in birthweight for males or females subjected to EPE. Correction for treated EPE did not change the outcome. CONCLUSIONS: These data indicate that in a non-human primate model of placental dysfunction through late pregnancy acute ischaemia, there is no measurable effect on baby birthweight compared to normal pregnancy, and no impact from a number of current experimental treatment strategies., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: We showed in a phase II randomised controlled trial (RCT) that oral sildenafil citrate in term labour halved operative birth for fetal distress. We outline the protocol for a phase III RCT (can i ntrapartum S ild E nafil safely A vert the R isks of C ontraction-induced H ypoxia? (iSEARCH)) of 3200 women in Australia to assess if sildenafil citrate reduces adverse perinatal outcomes related to intrapartum hypoxia., Methods and Analysis: iSEARCH will enrol 3200 Australian women in term labour to determine whether up to three 50 mg oral doses of sildenafil citrate versus placebo reduce the relative risk of a primary composite end point of 10 perinatal outcomes potentially related to intrapartum hypoxia by 35% (from 7% to 4.55%). Secondary aims are to evaluate reductions in the relative risk of emergency caesarean section or instrumental vaginal birth for fetal distress by 25% (from 20% to 15%) and in healthcare costs. To detect a 35% reduction in the primary outcome for an alpha of 0.05 and power of 80% with 10% dropout in each arm requires 3200 women (1600 in each arm). This sample size will also yield >90% power to detect a 25% reduction for the secondary outcome of any operative birth (caesarean section or instrumental vaginal birth) for fetal distress., Ethics and Dissemination: Ethical approval for the iSEARCH RCT was granted by the Hunter New England Human Research Ethics Committee (ref no: 2020/ETH02791). Results will be disseminated through websites, peer-reviewed publications, scientific meetings and social media, news outlets, television and radio., Trial Registration Number: ACTRN12621000231842., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Preterm birth continues to be one of the most significant contributors to perinatal death. This study aims to evaluate the quality of antenatal care provided to women delivering preterm., Methods: This was a retrospective, descriptive, longitudinal review of all women who had antenatal care within a single Australian tertiary hospital and delivered spontaneously between 24 and 37 weeks of gestation, using an auditable scoring system assessing potential interventions for prevention of preterm birth. The review was limited to singleton pregnancies without fetal abnormalities delivering between January 2013 and April 2015. The audit tool was developed by reference to established 'best practice' guidance for prediction and prevention of preterm birth based on Royal Australian and New Zealand College of Obstetricians and Gynaecologists guidelines and published literature. Different pathways were assessed for women deemed either low- or high-risk at the outset of antenatal care., Results: A series of 161 pregnancies that delivered preterm (between 24 and 37 weeks' gestation) were reviewed. The quality of antenatal care was scored 'good' in 42.9% and 50% of high-risk and low-risk women, respectively. Care was scored 'adequate', with room for improvement in 51.4% and 45.2% of the two corresponding groups. The main deficiencies in care were recorded evidence of assessment of cervical length (absent in 35% of cases) and failure to screen for bacterial vaginosis in high-risk women., Conclusions: Auditing antenatal care for prevention of preterm birth allows identification of suboptimal practice allowing service improvement and potential intervention for preterm birth prevention., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. J. Hyett reports that in the past 36 months NHMRC funded grant with payments to the University of Sydney, that he is the CI on the Espresso study, a randomized controlled trial for prevention of preeclampsia funded by Australian NHMRC and that the study had no impact on this work. Furthermore, he declares that in the past 36 months payments were made to him as he has acted as a consultant to Menarini for the development of cell based NIPT (not related to this work). Also, he declares that in the past 36 months he has given a lecture for Besins Pharmaceuticals on the use of progesterone for the prevention of preterm birth that was not paid and not related to this work. In addition, he reports that in the past 36 months, he has been a trustee of the Fetal Medicine Foundation, a charity based in the UK., (© 2024 Rawashdeh H. et al.)

Objectives: To develop a semi-automated tool for measuring fetal abdominal wall thickness (AWT). To validate the software using images captured by other centers and create a nomogram for fetal AWT between 18 and 20 weeks., Methods: A semiautomated tool that measured AWT was developed using images captured at the routine 20-week morphology scan. The software was developed using digital images captured routinely during scans of low-risk women. Inter- and intraobserver reliability was assessed between manual and semi-automated measures. The tool was validated using images acquired from other centers. Linear regression and quadratic polynomials were used to create a nomogram for AWT., Results: The semi-automated tool was able to measure AWT in all images. Interoperator reliability was 0.90 and 0.97 (P < 0.05) for manual and semi-automated methods, respectively. Measurement agreement varied between three operators from moderate to excellent (0.77, 0.87, 0.92), with overall agreement being good (0.85). The tool could be successfully applied to 89% of images from other centers. A nomogram was generated for AWT measurements of fetuses at 18-20 weeks in normal, low risk mothers., Conclusion: Semi-automated measurement of AWT was feasible using images captured during the routine 20-week scan. This approach had lower inter- and intraobserver variability compared to manual measurement., (© 2024 International Federation of Gynecology and Obstetrics.)

The development and market emergence of vaginal sensors have begun to demonstrate their impact on women's healthcare. Until recently, in limited cases, these sensors have exhibited their capabilities in diagnosing and monitoring disorders of the vaginal tract during different stages of women's lives. This Perspective is a compilation of what has been accomplished so far in the landscape of vaginal sensors. The text explores the diverse types of vaginal sensor technologies, their applications, and their potential impact on women's healthcare. The review introduces the anatomy of the vagina and cervix and categorizes vaginal sensors that have been developed, highlighting the technologies and potential applications. The paper covers biomarkers of the vaginal tract and discusses their importance in maintaining the overall characteristics of the vaginal system. The text also explores the clinical implications of vaginal sensors in pregnancy monitoring, disease detection, and sexual health management. In the final step, the manuscript provides future perspectives and possibilities that can be incorporated in the emerging field of vaginal sensors.

Fetal head position significantly influences birth outcomes, with higher rates of complications observed when the fetal head is in the Occiput Posterior (OP) position compared to Occiput Transverse (OT) or Occiput Anterior (OA) positions. There is no consensus in the current literature on the precise rotational point at which the fetal occiput shifts from posterior to transverse, reducing clarity in both scientific and clinical communication. Different studies employ varying definitions of these positions, which affects management decisions. This study aims to determine if a definable threshold exists between the directly posterior and directly transverse positions that correlates with different birth outcomes, thereby proposing a consistent and clinically useful definition for OP versus OT. We analyzed ultrasound data from 570 patients at full dilatation from five previous studies, correlating the angle of the fetal occiput (noted on a clock-face) with birth outcomes. Adverse outcomes were defined as cesarean delivery, instrumental vaginal delivery, significant postpartum hemorrhage (500 ml or more), obstetric anal sphincter injury, five-minute Apgar scores <7, arterial cord pH <7, base excess less than -12, or neonatal intensive care unit admission. The analysis was conducted using SAS version 9.4. The study found a continuous relationship between the fetal occipital angle and adverse birth outcomes without a distinct threshold separating OP from OT positions. No clear inflection point was demonstrated in pregnancy outcomes between OT and OP. The relationship between the angle of occiput position and pregnancy outcomes was continuous: the closer the fetal head was to directly OP, the higher the likelihood of adverse outcomes. Given the lack of a clear cut-off and to improve consistency in future research, we recommend dividing the occiput position into four quadrants of 90 degrees each. This classification could standardize reporting and potentially improve clinical decision-making regarding fetal position during labor., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Pardey et al.)

Background: Australian rates of adverse obstetric outcomes have improved little despite guidelines recommending history-based screening and intervention. The first trimester provides a unique opportunity to predict and prevent complications, yet population-based screening has failed to be translated into broad clinical practice., Aims: This study aimed to redesign antenatal care within an Australian public healthcare centre to align with evidence-based maternity care, including population-based first-trimester screening with early initiation of preventative strategies in high-risk pregnancies., Methods: A five-phase action-process model, sharing key elements with implementation science theory, was used to explore barriers to change in antenatal care, co-design a novel service with consumers and establish a population-based antenatal pathway commencing with a multidisciplinary first-trimester screening, assessment and planning visit., Results: The case for change and associated barriers were defined from the perspective of antenatal care stakeholders. Key needs of each group were established, and solutions were created using co-design methodology, allowing the team to create a novel approach to antenatal care which directly addressed identified barriers. Implementation of the service was associated with a fall in the median gestation at first specialist maternity care provider visit from 20 to 13 weeks., Conclusions: This study confirms the feasibility of establishing a comprehensive first-trimester screening program within a public Australian healthcare setting and highlights a co-design process which places individualised assessment at the forefront of antenatal care. This framework may be applicable to most public maternity settings in Australia, with expansion aimed at providing equity of care, including in rural and remote settings., (© 2024 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)