ORCID Profile
0000-0002-9720-3562
Current Organisation
University of Melbourne
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Applied Ethics | Bioethics (human and animal) |
Bioethics | Expanding Knowledge in Philosophy and Religious Studies
Publisher: Wiley
Date: 07-10-2015
DOI: 10.1002/PD.4497
Abstract: Cytomegalovirus (CMV) is the most common cause of congenital infection with approximately 0.5% of pregnant women in developed countries seroconverting during pregnancy. In utero transmission occurs in about one third of women who develop primary infection in the first trimester, and these fetuses are at risk for adverse perinatal outcomes and long-term neurological complications. The great promise of a prenatal therapy to reduce fetal infection after maternal primary CMV infection has not been realized to date. The prediction of CMV sequelae is particularly challenging for clinicians because of the heterogeneity of the published literature, the wide spectrum of perinatal outcomes, the adjustment of fetal risk at each stage of assessment, and the variable quality of published data. Given the continued lack of a proven fetal therapy, it is timely to review the natural history of congenital CMV in the modern management era. We have analyzed the recent literature, integrated findings from multiple studies, and calculated stage-specific risks for adverse perinatal outcome to assist in counseling women with first trimester primary CMV infection.
Publisher: Wiley
Date: 30-04-2022
DOI: 10.1002/PD.6159
Abstract: We conducted a survey‐based discrete‐choice experiment (DCE) to understand the test features that drive women's preferences for prenatal genomic testing, and explore variation across countries. Five test attributes were identified as being important for decision‐making through a literature review, qualitative interviews and quantitative scoring exercise. Twelve scenarios were constructed in which respondents choose between two invasive tests or no test. Women from eight countries who delivered a baby in the previous 24 months completed a DCE presenting these scenarios. Choices were modeled using conditional logit regression analysis. Surveys from 1239 women (Australia: n = 178 China: n = 179 Denmark: n = 88 Netherlands: n = 177 Singapore: n = 90 Sweden: n = 178 UK: n = 174 USA: n = 175) were analyzed. The key attribute affecting preferences was a test with the highest diagnostic yield ( p 0.01). Women preferred tests with short turnaround times ( p 0.01), and tests reporting variants of uncertain significance (VUS p 0.01) and secondary findings (SFs p 0.01). Several country‐specific differences were identified, including time to get a result, who explains the result, and the return of VUS and SFs. Most women want maximum information from prenatal genomic tests, but our findings highlight country‐based differences. Global consensus on how to return uncertain results is not necessarily realistic or desirable.
Publisher: Wiley
Date: 10-12-2020
DOI: 10.1002/PD.5620
Abstract: The fetal fraction (FF) is a function of both biological factors and bioinformatics algorithms used to interpret DNA sequencing results. It is an essential quality control component of noninvasive prenatal testing (NIPT) results. Clinicians need to understand the biological influences on FF to be able to provide optimal post-test counseling and clinical management. There are many different technologies available for the measurement of FF. Clinicians do not need to know the details behind the bioinformatics algorithms of FF measurements, but they do need to appreciate the significant variations between the different sequencing technologies used by different laboratories. There is no universal FF threshold that is applicable across all platforms and there have not been any differences demonstrated in NIPT performance by sequencing platform or method of FF calculation. Importantly, while FF should be routinely measured, there is not yet a consensus as to whether it should be routinely reported to the clinician. The clinician should know what to expect from a standard test report and whether reasons for failed NIPT results are revealed. Emerging solutions to the challenges of s les with low FF should reduce rates of failed NIPT in the future. In the meantime, having a "plan B" prepared for those patients for whom NIPT is unsuccessful is essential in today's clinical practice.
Publisher: Springer Science and Business Media LLC
Date: 03-07-2012
Publisher: Cold Spring Harbor Laboratory
Date: 06-07-2022
DOI: 10.1101/2022.07.04.22277193
Abstract: COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. The aim of this study was to investigate the sociodemographic characteristics associated with vaccine uptake in Melbourne, Australia, and to compare perinatal outcomes by vaccination status. Retrospective multicenter cohort study in Melbourne following the national recommendations for mRNA COVID-19 vaccination during pregnancy in June 2021. Routinely collected data from all 12 public maternity hospitals in Melbourne were extracted on births ≥ 20 weeks’ gestation from 1 st July 2021 to 31 March 2022. Maternal sociodemographic characteristics were analyzed from the total birth cohort. Perinatal outcomes were compared between vaccinated and unvaccinated women for whom weeks 20-43 of gestation fell entirely within the 9-month data collection period. The primary outcome was the rate of congenital anomaly in singleton infants ≥ 20 weeks’ gestation among women vaccinated during pregnancy. Secondary perinatal outcomes including stillbirth, preterm birth (spontaneous and iatrogenic), birthweight ≤ 3 rd centile, and newborn intensive care unit admissions were examined for singleton infants ≥ 24 weeks’ gestation without congenital anomalies. We calculated the adjusted odds ratio of congenital anomalies and perinatal outcomes among vaccinated versus unvaccinated women using inverse propensity score weighting regression adjustment with multiple covariates p 0.05 was considered statistically significant. Births from 32,536 women were analyzed: 17,365 (53.4%) were vaccinated and 15,171 (47.6%) were unvaccinated. Vaccinated women were significantly more likely to be older, nulliparous, non-smoking, not requiring an interpreter, of higher socioeconomic status, and vaccinated against pertussis and influenza. Vaccination status also varied by region of birth: compared with women born in Australia, women born in South and Eastern Europe, the Middle East, Africa and Oceania had lower adjusted odds of vaccination. There was no significant increase in the rate of congenital anomalies or birth weight ≤ 3 rd centile in vaccinated women. Vaccinated women were significantly less like to have an infant with a major congenital anomaly compared with the unvaccinated group (2.4% vs 3.0%, aOR 0.72, 95%CI 0.56-0.94, p=0.02). This finding remained significant even when the analysis was restricted to women vaccinated before 20 weeks’ gestation. Vaccinated women had a significantly lower rate of stillbirth (0.2% vs 0.8%, aOR 0.18, 95%CI 0.09-0.37, P 0.001. Vaccination was associated with a significant reduction in total preterm births 37 weeks (5.1% vs 9.2%, aOR 0.60, 95% CI 0.51-0.71, p 0.001), spontaneous preterm birth (2.4% vs 4.0%, aOR 0.73 95% CI 0.56-0.96, p=0.02) and iatrogenic preterm birth (2.7% vs 5.2%, aOR 0.52, 95%CI 0.41-0.65, p 0.001). COVID-19 Vaccine coverage was significantly influenced by known social determinants of health, which is likely to influence the strong association between COVID-19 vaccination and lower risks of stillbirth and preterm birth. We did not observe any adverse impacts of vaccination on fetal growth or development. ⍰ COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. ⍰ Most of the published literature on COVID-19 vaccination in pregnancy have methodological limitations including fixed cohort bias and time-varying exposure. ⍰ We conducted this multicenter study to provide robust evidence on mRNA COVID-19 vaccination and perinatal outcomes including congenital anomalies, stillbirth, and preterm birth. ⍰ The adjusted odds of stillbirth, preterm birth, and neonatal intensive care admission were significantly reduced among infants born to COVID-19 vaccinated women compared with unvaccinated women. COVID-19 vaccination during pregnancy was not associated with an increase in congenital anomalies. ⍰ Our results conclusively demonstrate a significant reduction in both spontaneous and iatrogenic preterm birth for vaccinated women ⍰ Vaccinated women were significantly more likely to be older, nulliparous, non-smoking, not requiring an interpreter, residing in a higher socioeconomic postcode, and vaccinated against pertussis and influenza. There were also significant differences in vaccination rates by region of birth. ⍰ Our analysis confirmed a strong relationship between the COVID-19 mRNA vaccine and lower preterm births and stillbirths ⍰ In addition to its impact on reducing severe COVID-19 illness, vaccination may be a proxy for other biological and social determinants of health among our pregnant population.
Publisher: Wiley
Date: 12-2020
DOI: 10.1002/PD.5867
Publisher: Wiley
Date: 21-02-2018
DOI: 10.1002/PD.5228
Abstract: Any screening approach, including with cell-free DNA, will have an inferior detection rate compared with 100% diagnostic testing with chromosomal microarrays. Cell-free DNA-based screening, however, should not be seen as a threat to informed choice or maximising the benefits of diagnostic testing. Screening methods have become so much better that more women are now comfortable relying on such screening and do not need the certainty of a diagnostic test. This has not lead to a decline in detection of fetal chromosome abnormalities-in fact, we are now seeing historically high yields from prenatal screening. There are both economic and ethical consequences of offering universal diagnostic testing and abandoning the presumption of a normal infant in otherwise uncomplicated pregnancies. However, for some women, comprehensive information and diagnostic accuracy are important. Offering these women all options, with a careful and comprehensive explanation of the risks and benefits of each, results in outcomes that are best aligned with woman's preferences while at the same time requiring fewer diagnostic tests and lowering costs. It is one of the primary challenges of the modern era of prenatal testing to ensure that women receive sufficient information on which to make informed decisions.
Publisher: Wiley
Date: 06-2023
DOI: 10.1002/PD.6397
Abstract: Congenital cytomegalovirus (cCMV) is the most common congenital infection worldwide. cCMV can lead to severe long‐term sequelae, including neurological impairment and developmental delay. We performed a systematic review of clinical practice guidelines containing recommendations concerning serological screening for CMV during pregnancy. We performed a search of MEDLINE, Turning Research into Practice (TRIP) database and the grey literature for clinical practice guidelines or consensus statements published in the English language from Jan 2010 to June 2022. The quality of the included guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Textual synthesis was used to summarise and compare the recommendations on CMV serological screening in pregnancy. Eleven guidelines and two consensus statements were included. None recommended universal serological screening for CMV in pregnant women five recommended screening for high‐risk women (those with frequent contact with young children). The overall quality of the guidelines varied most were medium or low. Although clinical practice guidelines do not actively recommend routine serological screening in pregnancy, most did not meet standard processes for development and predated the emerging data on valaciclovir as a potential intervention. Existing recommendations are underpinned by limited, low‐level evidence, exposing the lack of robust data in this area of practice. Further high‐level evidence and methodologically robust guidelines are needed to guide clinical practice in this rapidly changing field.
Publisher: Wiley
Date: 2015
DOI: 10.1002/UOG.14699
Publisher: Wiley
Date: 06-2023
DOI: 10.1002/PD.6395
Publisher: Cold Spring Harbor Laboratory
Date: 23-07-2021
DOI: 10.1101/2021.07.22.21261008
Abstract: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to the delivery of maternity care globally and has been associated with regional changes in perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne endured one of the longest and most stringent lockdowns in 2020. This paper presents the protocol for a collaborative maternity dashboard project to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic. De-identified maternal and newborn outcomes will be collected monthly from all public maternity services in Melbourne, allowing rapid analysis of a multitude of perinatal indicators. Weekly outcomes will be displayed as run charts according to established methods for detecting non-random ‘signals’ in health care. A pre-pandemic median for all indicators will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≤ six consecutive weeks, all above or below the pre-pandemic median. Additional statistical analyses such as regression, time-series, and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests. This study has been registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976). ⍰ This project is the first clinician-led, multi-centre perinatal data collection system for metropolitan Melbourne. ⍰ It complements the state government data collection, with the significant benefits of more timely and flexible reporting of outcomes, and granular detail on emerging areas of concern. ⍰ The study relies on primary source coding of exposure and outcomes from each hospital that have not been internally validated during the study period. ⍰ Data from private maternity hospitals, containing 25% of Melbourne births, are not available. ⍰ This resource will support data-informed hospital pandemic responses through to the end of 2022.
Publisher: Public Library of Science (PLoS)
Date: 18-02-2014
Publisher: Informa UK Limited
Date: 05-05-2017
DOI: 10.1080/14767058.2016.1177815
Abstract: It is not known whether fasting affects levels of circulating placenta-specific transcripts. To assess whether a glucose load affects circulating placenta-specific transcripts. RNA was extracted from paired blood s les (fasting and 1-h post 75 g oral glucose) from 22 women. Placenta-specific genes were measured by RT-qPCR. There was no change in ADM, CSH1, PAPPA2, PSG1 or TAC3 expression between fasting and post-glucose states. However, HTRA1 decreased after glucose load. Maternal fasting state does not influence expression of the majority of placenta-specific genes but may need to be accounted for when validating biomarkers of placental disease.
Publisher: Wiley
Date: 29-01-2020
DOI: 10.1002/PD.5632
Publisher: Wiley
Date: 02-2023
DOI: 10.1002/PD.6323
Publisher: Wiley
Date: 25-08-2015
DOI: 10.1111/AJO.12396
Abstract: Numbers of invasive prenatal procedures are declining in response to improved aneuploidy screening methods. To assess current practice and attitudes of clinicians performing invasive prenatal diagnosis in regard to patient consent and safety, maintaining procedural competence and uptake of chromosomal microarrays (CMAs). Anonymous online survey of the Australian Association of Obstetrical and Gynaecological Ultrasonologists conducted in March 2015. The survey had a 45% response rate with 59 respondents from Australia. Of these, 34 were subspecialists in maternal fetal medicine or obstetric and gynaecological ultrasound. Fifty-six (95%) currently performed amniocentesis or chorionic villus s ling. Of these, 14 (25%) performed 150 annually, with most respondents (60%) proposing 10-25 amniocenteses/year as adequate activity to maintain their skills. The majority neither expected referrers to provide results of hepatitis B and HIV serology, nor followed up missing results. There was uncertainty regarding the procedure-related vertical transmission risk of HBV in women with high viral load, with most respondents stating they were either unsure of the risk (22%) or that the risk was unknown (30%). Fifty per cent of practitioners routinely ordered CMA after invasive testing all recommended CMA following a diagnosis of structural abnormality. In a period of declining testing, many Australian specialists are performing <25 procedures annually. Consideration of the potential risks of bloodborne viruses is limited. CMAs are rapidly being incorporated into clinical practice. These data have implications for patient consent and safety, and workforce training and practice.
Publisher: Wiley
Date: 08-2014
DOI: 10.1002/UOG.13418
Publisher: Springer Science and Business Media LLC
Date: 11-10-2021
DOI: 10.1186/S12887-021-02809-7
Abstract: The implementation of genomic testing in pregnancy means that couples have access to more information about their child’s genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based study will help to close this critical knowledge gap through a multidisciplinary cohort study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years. This study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old’s), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed. This study protocol describes the first Australian cohort study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy. ACTRN12620000446965p Registered on April 6, 2020.
Publisher: Wiley
Date: 02-2023
DOI: 10.1111/AJO.13645
Abstract: Little is published on cytomegalovirus (CMV) serological screening at the first antenatal visit or the contemporary CMV seroprevalence rates among the Australian pregnant population. We performed a retrospective analysis of public hospital births in a major tertiary centre ( n = 840) over a two month period. We found that 13.6% (95% confidence interval (CI) 11.4–16.1%) of women had been screened for CMV at their first antenatal visit with their general practitioner. Of these, 43.0% (95% CI 34.3–52.1%) were CMV seronegative and therefore susceptible to primary infection. Seronegative women were also more likely to have been born in an economically developed country, to live in a socio‐economically advantaged postcode and to be nulliparous. The information from this study may help guide future studies of congenital CMV risk reduction strategies.
Publisher: Wiley
Date: 12-2020
DOI: 10.1002/PD.5870
Publisher: Wiley
Date: 24-09-2018
DOI: 10.1002/PD.5352
Abstract: To examine the statewide utilisation of prenatal diagnosis (PNDx) and preimplantation genetic diagnosis (PGT-M) for single gene disorders. Population-based study of all women utilising PNDx in the Australian state of Victoria from 1977 to 2016. Single gene disorders were categorised using a systematic approach that aimed to reflect aspects of the PNDx decision-making process. Data on PGT-M for single gene disorders from 2005 to 2016 were similarly examined for comparison. Statistical significance testing was performed with χ Following an initial uptake period, annual PNDx rates for single gene disorders stabilised between 1.3 and 2.2 per 1000 births after the year 2000. The majority of PNDx (72%) was performed for disorders that primarily impair physical ability, while PNDx for adult onset conditions was rare (3%). PGT-M for single gene disorders has seen rapid growth since its introduction, and annual numbers now equal that of PNDx. In contrast to PNDx, one quarter of PGT-M tests were performed for adult onset conditions. Our population-wide analysis has demonstrated a steady demand for PNDx for single gene disorders over the past decade, in contrast to the rapidly increasing utilisation of PGT-M. PGT-M appears to be the preferred testing modality for adult onset disorders.
Publisher: Wiley
Date: 30-01-2018
DOI: 10.1111/AJO.12778
Abstract: Advances in technology can bring great benefits to human health, but their implementation may be influenced by socioeconomic factors, particularly in the field of prenatal screening for Down syndrome. To analyse screening test indications for, and diagnostic yield of, invasive prenatal diagnostic testing (PNDx) according to socioeconomic status. Retrospective analysis of population-based data on PNDx and karyotype results for 2014-2015 in the Australian state of Victoria. Women having PNDx < 25 weeks due to combined first trimester screening (CFTS), second trimester serum screening (STSS), or noninvasive prenatal testing (NIPT) results were included. PNDx data were analysed by indication and maternal Index of Relative Socio-economic Advantage and Disadvantage (IRSAD), the latter determined by postcode. There were 145 206 births in 2014-2015 1906 women underwent PNDx for the indication of CFTS (70.1%), NIPT (17.8%) or STSS (12.0%). Covariates positively associated with NIPT-indicated PNDx, compared with CFTS-indicated testing, were residence in a region of socioeconomic advantage, metropolitan status and maternal age. Women from the most advantaged regions had higher adjusted odds ratios (aOR) of NIPT-indicated testing compared with women from disadvantaged regions (aOR 5.72, 95% CI: 2.95-11.09). The diagnostic yield of PNDx increased with socioeconomic region, from 14% in the lowest IRSAD quintile to 31.2% in the highest (P < 0.0001). Population-based data reveal significant disparities in screening indications for PNDx and hence, in diagnostic yield, according to socioeconomic region. This finding may have ethical and policy implications for prenatal screening in Australia.
Publisher: Wiley
Date: 04-2019
DOI: 10.1002/UOG.19107
Abstract: To assess trends in ultrasound-indicated prenatal diagnostic testing performed over the past two decades in the Australian state of Victoria, in the context of rapidly changing practices in aneuploidy screening and chromosome analysis. This was a retrospective analysis of all ultrasound-indicated prenatal diagnostic testing (amniocentesis and chorionic villus s ling) performed in the state of Victoria between 1994 and 2016. Ultrasound indications for testing included: fetal structural abnormality, fetal death, fetal growth restriction, abnormal amniotic fluid volume, genetic 'soft marker' and unspecified ultrasound abnormality. Maternal age, indication for testing, type of diagnostic procedure, gestational age, type of chromosome analysis (G-banded karyotyping or chromosomal microarray (CMA)) and test results were obtained. Diagnostic yield (i.e. percentage of tests yielding a major abnormality) was analyzed by year, maternal age and gestational age. Statistical analysis was performed using the χ During the 23-year study period, 1 533 317 births were recorded and 16 152 diagnostic procedures were performed for the primary indication of ultrasound abnormality. In recent years, ultrasound abnormality became the most common indication for prenatal invasive testing (29.4% of diagnostic tests between 2013 and 2016) due to a steep decline in testing for other indications such as positive result on combined first-trimester screening or advanced maternal age alone. In 2016, over 95% of ultrasound-indicated procedures were performed with CMA among these, pathogenic copy number variant (CNV) was the most common (3.5%) abnormality detected, followed by trisomy 21 (2.8%). The diagnostic yield of ultrasound-indicated tests performed 20 weeks has remained stable due to increased utilization of CMA. Procedures performed for structural abnormalities < 16 weeks continue to have the highest diagnostic yield, supporting the benefits of early fetal structural assessment at 11-13 weeks. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Wiley
Date: 13-06-2018
DOI: 10.1111/AJO.12834
Abstract: Cell-free DNA screening has quickly become established in Australia as an accurate - albeit costly - prenatal screening test for trisomy 21, 18 and 13. It is also commonly used for the detection of sex chromosome abnormalities. The increasing number of prenatal screening pathways available to women has increased the complexity of pretest counselling. Concurrent advances in diagnostic testing with the widespread use of chromosomal microarrays create further challenges for the continuing education of clinicians and health consumers. This article aims to answer common clinical questions in this rapidly evolving field and complements the recently updated Royal Australian and New Zealand College of Obstetricians and Gynaecologists Statement on Prenatal Screening for Fetal Chromosome and Genetic Conditions.
Publisher: Springer New York
Date: 12-2019
DOI: 10.1007/978-1-4939-8889-1_3
Abstract: The field of prenatal screening and diagnosis has undergone enormous progress over the past four decades. Most of this period has been characterized by gradual improvements in the technical and public health aspects of prenatal screening for Down syndrome. Compared to the direct analysis of fetal cells from amniocentesis or chorionic villus s ling, noninvasive approaches using maternal blood or ultrasound have the great advantage of posing no risk of miscarriage to the pregnancy. Recent advances in molecular genetics and DNA sequencing have revolutionized both the accuracy and the range of noninvasive testing for genetic abnormalities using cell-free DNA in maternal plasma. Many of these advances have already been incorporated into clinical care, including diagnosis of fetal blood group and aneuploidy screening. The accelerated pace of these recent developments is creating not just technical and logistical challenges, but is also magnifying the ethical and public policy issues traditionally associated with this field.
Publisher: Elsevier BV
Date: 10-2022
Publisher: Elsevier BV
Date: 02-2020
Publisher: Wiley
Date: 29-06-2014
DOI: 10.1002/PD.4417
Publisher: Wiley
Date: 11-08-2015
DOI: 10.1111/AJO.12380
Abstract: In late 2012, a new screening test for fetal aneuploidy based on circulating cell-free DNA (cfDNA) became available to Australian women. The introduction of this technology in the United States has led to a reduction in invasive diagnostic procedures. Analysis of the number of amniocentesis and chorionic villus s ling (CVS) procedures performed in Australia from 1994 to 2014 shows that the introduction of cfDNA testing has been associated with the most rapid decline in invasive procedures in the last 20 years. This change has important implications for training in, and maintenance of, the procedural skills of amniocentesis and CVS.
Publisher: Wiley
Date: 06-2020
DOI: 10.1002/PD.5763
Publisher: Wiley
Date: 09-01-2020
DOI: 10.1111/AJO.13111
Abstract: Small for gestational age (SGA) is a major determinant of poor perinatal outcome. Detecting SGA at term using ultrasound is challenging and we often plan birth based on clinical assessment. To determine the incidence of SGA infants with birthweight <10th centile among women undergoing planned birth at term for suspected SGA despite a normal estimated fetal weight (EFW) on ultrasound at 35-37 weeks. We performed a retrospective study including all women with a fetal growth ultrasound at ≥35 weeks reporting an EFW ≥ 10th centile (appropriate for gestational age, AGA) who subsequently had an induction of labour or caesarean birth at ≥37 weeks due to ongoing clinical suspicion of SGA between 2012-2014. The primary outcome was the incidence of SGA newborns using customised centiles. There were 532 women who had a planned birth for clinical suspicion of SGA during the study period. Of these, 205 (38.5%) had an AGA fetus on ultrasound ≥35 weeks but were subsequently delivered because of a persisting clinical suspicion of SGA on abdominal assessment. Sixty-eight percent (n = 139/205) delivered an SGA infant. Furthermore, almost half of these SGA infants (47.5%) had a birthweight <3rd centile. Neonatal outcomes were worse for the SGA infants, with 15.1% (n = 21/205) requiring special care nursery compared to 1.5% (n = 1/205) of those AGA at birth. A reassuring ultrasound with EFW ≥10th centile in the late third trimester should not override clinical concerns of impaired fetal growth at term.
Publisher: Wiley
Date: 27-08-2023
DOI: 10.1002/PD.6217
Abstract: Prenatal screening for sex chromosome aneuploidies (SCAs) is increasingly available through expanded non‐invasive prenatal testing (NIPT). NIPT for SCAs raises complex ethical issues for clinical providers, prospective parents and future children. This paper discusses the ethical issues that arise around NIPT for SCAs and current guidelines and protocols for management. The first section outlines current practice and the limitations of NIPT for SCAs. It then outlines key guidelines before discussing the ethical issues raised by this use of NIPT. We conclude that while screening for SCAs should be made available for people seeking to use NIPT, its implementation requires careful consideration of what, when and how information is provided to users.
Publisher: Wiley
Date: 04-06-2013
DOI: 10.1002/PD.4150
Publisher: Wiley
Date: 02-2016
DOI: 10.1002/UOG.15845
Publisher: Springer Science and Business Media LLC
Date: 15-05-2020
DOI: 10.1038/S41467-020-16346-X
Abstract: Placental insufficiency can cause fetal growth restriction and stillbirth. There are no reliable screening tests for placental insufficiency, especially near-term gestation when the risk of stillbirth rises. Here we show a strong association between low circulating plasma serine peptidase inhibitor Kunitz type-1 (SPINT1) concentrations at 36 weeks’ gestation and low birthweight, an indicator of placental insufficiency. We generate a 4-tier risk model based on SPINT1 concentrations, where the highest risk tier has approximately a 2-5 fold risk of birthing neonates with birthweights under the 3 rd , 5 th , 10 th and 20 th centiles, whereas the lowest risk tier has a 0-0.3 fold risk. Low SPINT1 is associated with antenatal ultrasound and neonatal anthropomorphic indicators of placental insufficiency. We validate the association between low circulating SPINT1 and placental insufficiency in two other cohorts. Low circulating SPINT1 is a marker of placental insufficiency and may identify pregnancies with an elevated risk of stillbirth.
Publisher: Wiley
Date: 30-10-2018
DOI: 10.1002/PD.5363
Abstract: To assess the impact of non-invasive prenatal testing (NIPT) on trends in the prenatal diagnosis of sex chromosome aneuploidy (SCA) in a population with >73,000 annual births. Retrospective population-based cohort study from 1986-2016 of all women undergoing prenatal diagnosis before 25 weeks gestation in the Australian state of Victoria. Statistical significance was tested using the chi-square test for trend or proportions. There were 2,043,345 births and 842 SCA diagnoses from 1986-2016. The percentage of prenatal diagnostic tests leading to a SCA diagnosis increased significantly from 0.95% in 2010 to 2.93% in 2016 (p < 0.001) but due to a concurrent decline in testing, the annual prenatal diagnosis rate of SCA remained stable at 4.4/10,000 births. Among confirmed fetal SCAs the most common indication for testing in 1986 was advanced maternal age (63%) in 2016 it was high risk NIPT (49%). SCAs now make up an increasing proportion of prenatal diagnostic results but due to the overall decline in diagnostic testing, the prenatal prevalence as a percentage of births remained steady. The ascertainment of fetal SCA has evolved from an incidental finding after testing for increased risk of trisomy 21, to a diagnosis obtained after suspected SCA on NIPT.
Publisher: Wiley
Date: 18-12-2023
DOI: 10.1111/AJO.13638
Abstract: Prenatal screening for aneuploidy has undergone immense changes over the past two decades. In 2013 cell‐free DNA‐based non‐invasive prenatal testing (NIPT) became a new self‐funded option primarily for Down syndrome screening, but also other aneuploidies and genetic conditions. The numbers of Medicare item claims for prenatal diagnostic procedures have halved since the introduction of NIPT, while billings for serum screening fell by 40% over the same period, on a background of steady births. Australia is now observing historically low rates of prenatal diagnostic testing. These data provide an informative snapshot of historic changes in prenatal screening and diagnosis, as our sector prepares for the impending impacts of other advances in genomics on maternity care. They also highlight the need to address equity and quality issues that arise when consumers must bear the full costs of improved genomic tests in the absence of Medicare funding.
Publisher: Wiley
Date: 04-2015
DOI: 10.1111/AJO.12306
Abstract: Cell-free DNA-based non-invasive prenatal testing for aneuploidy (NIPT) is now established as the most accurate screening test for trisomy 21. This test became clinically available on a patient-funded basis in Australia and New Zealand in 2013. To investigate the clinical implementation of NIPT use by members of the Australian Association of Obstetrical and Gynaecological Ultrasonologists (AAOGU) during its first year of local availability. Email invitations with an embedded link to an anonymous online survey were sent to all 140 members of the AAOGU in December 2013. We received 54 responses to the survey (39% response rate). Two thirds of respondents were subspecialists in obstetric and gynaecological ultrasound or maternal fetal medicine. The majority of respondents had already used NIPT in their practice (94%). There was no significant difference in the proportion of respondents offering NIPT to high-risk women in private versus public practice (95 versus 82%, P = 0.14). However, inequity of access due to cost was the most common ethical issue encountered. The vast majority continued to offer an 11-13 week ultrasound in addition to NIPT. Almost all respondents (96%) were also willing to offer NIPT to low-risk women in December 2013 after appropriate genetic counselling. Non-invasive prenatal testing was introduced into clinical care by obstetric sonologists with confidence and in accordance with the current recommended guidelines. These results may help inform future prenatal screening policy and cost-effectiveness analyses.
Publisher: Wiley
Date: 15-01-2016
Publisher: Springer Science and Business Media LLC
Date: 29-10-2020
DOI: 10.1007/S00439-020-02227-2
Abstract: Cell-free DNA (cfDNA) has become widely recognized as a promising candidate biomarker for minimally invasive characterization of various genomic disorders and other clinical scenarios. However, among the obstacles that currently challenge the general progression of the research field, there remains an unmet need for unambiguous universal cfDNA nomenclature. To address this shortcoming, we classify in this report the different types of cfDNA molecules that occur in the human body based on its origin, genetic traits, and locality. We proceed by assigning existing terms to each of these cfDNA subtypes, while proposing new terms and abbreviations where clarity is lacking and more precise stratification would be beneficial. We then suggest the proper usage of these terms within different contexts and scenarios, focusing mainly on the nomenclature as it relates to the domains of oncology, prenatal testing, and post-transplant surgery surveillance. We hope that these recommendations will serve as useful considerations towards the establishment of universal cfDNA nomenclature in the future. In addition, it is conceivable that many of these recommendations can be transposed to cell-free RNA nomenclature by simply exchanging “DNA” with “RNA” in each acronym/abbreviation. Similarly, when describing DNA and RNA collectively, the suffix can be replaced with “NAs” to indicate nucleic acids.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2016
Publisher: Informa UK Limited
Date: 24-08-2017
DOI: 10.1080/14767058.2017.1367378
Abstract: Amniotic fluid (AF) cell-free RNA is a promising source of information regarding fetal physiology. Digital PCR (dPCR) is a direct approach to nucleic acid detection that reports absolute transcript copy number. The aim of this study was to compare quantification of cell-free fetal brain and lung RNA transcripts in AF by reverse transcription-qPCR (RT-qPCR) and dPCR. Prospective hospital-based study was performed in 2016-2017. Pulmonary genes were quantified in term AF s les collected at elective cesarean birth neurodevelopmental genes were measured in preterm s les (<34 weeks) obtained from women undergoing clinically-indicated amniocentesis. All 11 women in the term cohort had three lung transcripts and a reference gene successfully lified from their AF supernatant using RT-qPCR and dPCR. SFTPC was the most abundant lung transcript, present in higher concentrations than the reference gene in seven of the eleven s les. Neurodevelopmental gene transcripts in 12 preterm pregnancies were less reliably detected by both methods and were present in low copy numbers (<10 copies/μl). We observed significant positive correlations between transcript quantification by RT-qPCR and dPCR. This study confirms the presence of several potential mRNA markers of lung and brain development with dPCR and RT-qPCR, and a high correlation between the two methods. Transcripts of presumed fetal brain origin are present in very low copy numbers, which presents challenges to their feasibility as biomarkers of neurodevelopment.
Publisher: Oxford University Press (OUP)
Date: 05-10-2011
Publisher: Annual Reviews
Date: 14-01-2017
DOI: 10.1146/ANNUREV-MED-072115-033220
Abstract: Noninvasive prenatal DNA testing is the vanguard of genomic medicine. In only four years, this screening test has revolutionized prenatal care globally and opened up new prospects for personalized medicine for the fetus. There are widespread implications for increasing the scope of human genetic variation that can be detected before birth, and for discovering more about maternofetal and placental biology. These include an urgent need to develop pretest education for all pregnant women and consistent post-test management recommendations for those with discordant test results. The reduction in invasive testing has had downstream effects on specialist training and caused many countries to re-examine their national approaches to prenatal screening. Finally, the accumulating datasets of genomic information on pregnant women and their fetuses raise ethical issues regarding consent for future data mining and intellectual property.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.BPOBGYN.2007.06.004
Abstract: Fetal growth restriction remains a major cause of perinatal morbidity and mortality in modern obstetric practice. Placental insufficiency is the most common association, but is often a diagnosis of exclusion. Currently, no treatment can ameliorate or reverse established growth restriction: maximising gestational age and judicious timing of steroid administration and delivery are the primary tasks for the obstetrician. Although comprehensive surveillance of the preterm fetus now includes ductus venosus Doppler studies, its effectiveness in timing delivery has yet to be confirmed in randomised controlled trials. More basic research on the regulation of fetal growth is needed before specific therapies for established growth restriction can be developed.
Publisher: Wiley
Date: 15-08-2019
DOI: 10.1002/PD.5533
Publisher: Wiley
Date: 08-2020
DOI: 10.1002/PD.5775
Publisher: Wiley
Date: 27-01-2022
DOI: 10.1002/PD.6103
Abstract: To analyze population‐based trends in the prenatal diagnosis of sex chromosome aneuploidy (SCA) since the availability of non‐invasive prenatal testing (NIPT). Retrospective state‐wide data for all prenatal diagnoses performed weeks gestation from 2005 to 2020 in Victoria, Australia. Non‐invasive prenatal testing became locally available from 2012. The prenatal diagnosis rates of SCA as proportions of all prenatal diagnostic tests and all births were calculated. Statistical significance was assessed with the χ 2 test for trend, with p 0.05 considered significant. 46,518 amniocentesis and chorionic villus s ling were performed during the study period, detecting 617 SCAs. There was a significant increase in the rate of prenatal SCAs from 5.8 per 10,000 births in 2005 to 8.7 per 10,000 births in 2020 ( p 0.0001). This increase was predominantly due to 47,XXY cases, 91% of which were ascertained via positive NIPT for this condition in 2020. The prenatal diagnosis rate of 47,XXY significantly increased from 0.8 per 10,000 births in 2005 to 4.3 per 10,000 births in 2020 ( p 0.0001). Screening for SCAs using NIPT has directly led to an increase in their prenatal diagnosis on a population‐wide basis, especially 47,XXY. This has implications for clinician education, genetic counselling, and pediatric services.
Publisher: Wiley
Date: 03-10-2019
DOI: 10.1111/AJO.13064
Abstract: Obesity is prevalent in the Australian antenatal population, but there are scarce data on the prevalence and associated outcomes of body mass index (BMI) ≥50 kg/m To examine the prevalence and outcomes for women with BMI ≥50 kg/m Retrospective cohort study of women delivering a singleton pregnancy in a non-tertiary Victorian hospital during 2011-2016. Women >180 kg were excluded as their care was managed in a tertiary centre. Maternal and perinatal outcomes were analysed by BMI group. Statistical analysis was performed using χ Of the 18 518 births between 2011 and 2016, 99.4% had a maternal BMI recorded. The prevalence of BMI ≥50 kg/m The prevalence of severe maternal obesity in our non-tertiary setting is higher than previous national estimates. Women with BMI ≥50 kg/m
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 30-03-2021
DOI: 10.1002/PD.5932
Abstract: To conduct qualitative interviews with healthcare providers working in different countries to understand their experiences of dealing with uncertain results from prenatal chromosome microarray analysis (CMA) and exome sequencing (ES). Semi‐structured interviews with 31 healthcare providers who report or return prenatal CMA and/or ES results (clinicians, genetic counsellors and clinical scientists) in six countries with differing healthcare systems Australia (4), Denmark (5), Netherlands (6), Singapore (4), Sweden (6) and United Kingdom (6). The topic guide explored the main sources of uncertainty and their management. There was variation in reporting practices both between and across countries for variants of uncertain significance, however, there was broad agreement on reporting practices for incidental findings. There was also variation in who decides what results are reported (clinical scientists or clinicians). Technical limitations and lack of knowledge (to classify variants and of prenatal phenotypes) were significant challenges, as were turnaround times and lack of guidelines. Health professionals around the globe are dealing with similar sources of uncertainty, but managing them in different ways, Continued dialogue with international colleagues on ways of managing uncertain results is important to compare and contrast the benefits and limitations of the different approaches.
Publisher: Wiley
Date: 03-2014
DOI: 10.1002/UOG.13314
Publisher: Wiley
Date: 29-03-2022
DOI: 10.1111/AJO.13500
Abstract: Cytomegalovirus (CMV) is a preventable cause of neurodevelopmental disability. Australian guidelines recommend that pregnant women are informed about CMV to reduce their risk of infection however, less than 10% of maternity health professionals routinely provide prevention advice. The aim was to develop and evaluate the effectiveness of an eLearning course for midwives to improve knowledge and confidence about CMV. Participants undertaking the course between March and November 2020 were invited to complete an evaluation questionnaire: before the course (T1), immediately after (T2) and three months post completion (T3). A linear mixed model was used to evaluate change in participant scores P 0.05 was considered statistically significant. Midwives (316/363, 87%), midwifery students (29/363, 8%) and nurses (18/363, 5%) participated. At T1 80% indicated they had not received education about CMV. Total adjusted mean scores for questionnaires completed between T1 ( n = 363) and T2 ( n = 238) increased significantly (from 17.2 to 22.8, P 0.001). Limited available T3 scores ( n = 27) (−1.7, P 0.001), while lower than T2, remained higher than at T1 (+3.6, P 0.001). Participants’ awareness of CMV information resources improved from 10 to 97% from T1 to T2. Confidence in providing CMV advice increased from 6 to 95% between T1 and T2 ( P 0.001) and was maintained at T3. Almost all (99%) participants indicated they would recommend the course to colleagues. Participants who completed the eLearning course had significantly improved knowledge and confidence in providing advice about CMV. Programs targeting other maternity health professionals should be considered, to further support the implementation of the congenital CMV prevention guidelines.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.BPOBGYN.2017.02.007
Abstract: Our concept of nucleic acid biology has advanced dramatically over the past two decades, with a growing appreciation that cell-free DNA (cfDNA) fragments are present in all body fluids including plasma. In no other field has plasma DNA been as rapidly translated into clinical practice as in noninvasive prenatal testing (NIPT) for fetal chromosome abnormalities. NIPT is a screening test that requires confirmation with diagnostic testing, but other applications of cfDNA provide diagnostic information and do not require invasive testing. These applications are referred to as noninvasive prenatal diagnosis (NIPD) and include determination of fetal sex, blood group and some single gene disorders. As technology advances, noninvasive tests based on cell-free nucleic acids will continue to expand. This review will outline the technical and clinical aspects of NIPT and NIPD relevant to the daily practice of maternity carers.
Publisher: Wiley
Date: 29-12-2016
Publisher: Wiley
Date: 30-01-2018
DOI: 10.1111/AJO.12778
Abstract: Advances in technology can bring great benefits to human health, but their implementation may be influenced by socioeconomic factors, particularly in the field of prenatal screening for Down syndrome. To analyse screening test indications for, and diagnostic yield of, invasive prenatal diagnostic testing (PNDx) according to socioeconomic status. Retrospective analysis of population-based data on PNDx and karyotype results for 2014-2015 in the Australian state of Victoria. Women having PNDx < 25 weeks due to combined first trimester screening (CFTS), second trimester serum screening (STSS), or noninvasive prenatal testing (NIPT) results were included. PNDx data were analysed by indication and maternal Index of Relative Socio-economic Advantage and Disadvantage (IRSAD), the latter determined by postcode. There were 145 206 births in 2014-2015 1906 women underwent PNDx for the indication of CFTS (70.1%), NIPT (17.8%) or STSS (12.0%). Covariates positively associated with NIPT-indicated PNDx, compared with CFTS-indicated testing, were residence in a region of socioeconomic advantage, metropolitan status and maternal age. Women from the most advantaged regions had higher adjusted odds ratios (aOR) of NIPT-indicated testing compared with women from disadvantaged regions (aOR 5.72, 95% CI: 2.95-11.09). The diagnostic yield of PNDx increased with socioeconomic region, from 14% in the lowest IRSAD quintile to 31.2% in the highest (P < 0.0001). Population-based data reveal significant disparities in screening indications for PNDx and hence, in diagnostic yield, according to socioeconomic region. This finding may have ethical and policy implications for prenatal screening in Australia.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2019
Publisher: Wiley
Date: 03-06-2011
DOI: 10.1002/PD.2777
Publisher: Springer Science and Business Media LLC
Date: 31-08-2017
Publisher: Georg Thieme Verlag KG
Date: 28-03-2014
Abstract: Nearly two decades ago, the discovery of circulating cell-free fetal DNA in maternal blood created a paradigm shift in prenatal testing. Recent advances in DNA sequencing technology have facilitated the rapid translation of DNA-based testing into clinical antenatal care. In this review, we summarize the technical approaches and current clinical applications of noninvasive testing using cell-free DNA in maternal plasma. We discuss the impact of these tests on clinical care, outline proposed integration models, and suggest future directions for the field. The use of cell-free DNA in maternal blood for the detection of fetal rhesus D antigen status, fetal sex, and common whole chromosomal aneuploidies is now well established, although testing for aneuploidy is still considered screening and not diagnostic. Further advances in technology and bioinformatics may see future clinical applications extend to the noninvasive detection of fetal subchromosomal aneuploidy, single gene disorders, and the entire fetal genome.
Publisher: Elsevier BV
Date: 06-2017
Publisher: Wiley
Date: 16-05-2023
DOI: 10.1002/PD.6357
Abstract: What is already known about this topic? In 2015, the International Society for Prenatal Diagnosis (ISPD) published its first position statement on the use of non‐invasive prenatal testing (NIPT) to screen for aneuploidy. Widespread uptake across the globe and subsequent published research has shed new light on test performance and implementation issues. What does this study add? This new position statement replaces the 2015 statement with updated information on the current technologies, clinical experience, and implementation practices. As an international organization, ISPD recognizes that there are important population‐specific considerations in the organization of prenatal screening and diagnosis. These opinions are designed to apply to high income settings where prenatal screening for aneuploidy is an established part of antenatal care. This position statement is not a clinical practice guideline but represents the consensus opinion of the current ISPD Board based on the current state of knowledge and clinical practice.
Publisher: Elsevier BV
Date: 09-2022
Publisher: SAGE Publications
Date: 25-10-2018
Abstract: To evaluate the implementation of the 2013 Royal Australian and New Zealand College of Obstetricians and Gynaecologists ‘Management of Hepatitis B in Pregnancy’ guideline. Retrospective cohort study of the clinical management and obstetric outcomes among hepatitis B virus-positive women in a single tertiary maternity hospital. Women with viral load ,000 IU/ml were referred to a specialised clinic for consideration of tenofovir disoproxil fumarate therapy to reduce mother to child transmission. A total of 11,496 women gave birth during the study period, of which 101 (0.9%) women were hepatitis B virus positive. Viral load was measured in 99 (98%) of 101 hepatitis B virus-positive women 30 (30%) had a viral load ,000 IU/ml. Twenty-six women accepted tenofovir disoproxil fumarate of these, 23 had a successful virological response (viral load ,000 IU/ml before delivery). Adherence to updated management guidelines and patient acceptance of tenofovir disoproxil fumarate in our Australian population were high when provided in the context of a dedicated perinatal service.
Publisher: Elsevier BV
Date: 08-2018
Publisher: Wiley
Date: 11-12-2022
DOI: 10.1002/PD.6073
Abstract: The acronym 'TORCH' refers to well-recognised causes of perinatal infections: toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). A TORCH serology panel is often used to test for maternal primary infection following detection of ultrasound abnormalities in pregnancy. This review aims to estimate the diagnostic yield of maternal TORCH serology in pregnancy following fetal ultrasound abnormalities. Primary studies published since 2000 that assessed maternal TORCH serology for suspected fetal infection and included information on indications for testing, definition of positive TORCH serology results, and perinatal outcomes were included. Eight studies with a total of 2538 pregnancies were included. The main indications for testing were polyhydramnios, fetal growth restriction and hyperechogenic bowel. There were 26 confirmed cases of congenital CMV, of which 15 had multiple ultrasound abnormalities. There were no cases of congenital toxoplasmosis, rubella or HSV confirmed in any of the eight studies. The clinical utility of TORCH serology for non-specific ultrasound abnormalities such as isolated fetal growth restriction or isolated polyhydramnios is low. It is time to retire the TORCH acronym and the reflex ordering of 'TORCH' panels, as their continued use obscures, rather than illuminates, appropriate investigation for fetal ultrasound abnormalities.
Publisher: Wiley
Date: 25-06-2016
Abstract: To analyse population-based trends over the entire history of prenatal testing for aneuploidy. Retrospective analysis of state-wide data sets. Australian state of Victoria with ~70 000 annual births. All pregnant women undergoing invasive prenatal testing at <25 weeks' gestation from 1976 to 2013. Analysis of three state-wide data sets: (1) Prenatal diagnosis data set of 119 404 amniocenteses and chorionic villus s lings from 1976 to 2013 (2) central serum screening laboratory data set from 1996 to 2013 (3) government birth statistics from 1976 to 2013. Annual numbers and uptake rates of invasive prenatal tests and serum screening, indications for invasive prenatal testing, prenatal diagnoses of aneuploidy, diagnostic yield of invasive tests. Annual numbers of invasive prenatal tests climbed steadily from 1976, then declined from 2000. In 2013, the number of invasive prenatal tests was the lowest in 25 years, while the number of trisomy 21 diagnoses was the highest ever recorded. Annual uptake of serum screening climbed from 1.6 to 83% over 1996-2013. Results from 2013 showed a high diagnostic yield (15.8%) for a low rate of invasive testing (3.4% of births). Over four decades, the number of invasive procedures performed for each diagnosis of major chromosome abnormality declined from 100 to six. This study demonstrates historic reductions in the proportion of women undergoing invasive testing and dramatic improvements in diagnostic yield. Monitoring the impact of new prenatal technologies on this progress remains an important research priority. Invasive prenatal testing has reached historic lows due to dramatic improvements in Down syndrome screening.
Publisher: MDPI AG
Date: 27-08-2022
Abstract: Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase (OLAH) in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of both fetal growth restriction and preecl sia, we aimed to investigate OLAH levels and function in the human placenta. We assessed OLAH mRNA expression (qPCR) throughout pregnancy, finding placental expression increased as gestation progressed. OLAH mRNA and protein levels (Western blot) were elevated in placental tissue from cases of preterm preecl sia, while OLAH protein levels in placenta from growth-restricted pregnancies were comparatively reduced in the preecl tic cohort. OLAH expression was also elevated in placental explant tissue, but not isolated primary cytotrophoblast cultured under hypoxic conditions (as models of placental dysfunction). Further, we discovered that silencing cytotrophoblast OLAH reduced the expression of pro- and anti-apoptosis genes, BAX and BCL2, placental growth gene, IGF2, and oxidative stress gene, NOX4. Collectively, these findings suggest OLAH could play a role in placental dysfunction and may be a therapeutic target for mitigating diseases associated with this vital organ. Further research is required to establish the role of OLAH in the placenta, and whether these changes may be a maternal adaptation or consequence of disease.
Publisher: Wiley
Date: 2008
DOI: 10.1002/PD.1975
Abstract: The aim of this study was to compare the effect of mode of delivery on the postpartum clearance of cell-free fetal (cff) DNA. Women who gave birth to a single-term male infant by any mode of delivery had blood collected on three occasions: within 3 h of birth, on day 1-2 postpartum and at 2 weeks postpartum. The SRY sequence was used as a marker of cff DNA, and was detected using conventional PCR. Eighty-seven women were included in the study. There were 28 women in the elective caesarean section group and 59 in the labor group. Cell-free fetal DNA was detected in 38/87 (44%) of women within 3 h of birth. There was a significant difference between the group that labored and the group that did not (54 vs 21%, p = 0.003). Twelve percent of women who labored had persistent cff DNA on day 1-2 postpartum, compared with none of the women who delivered without labor. No woman had DNA that persisted up to 2 weeks postpartum. The presence of labor increases the rate of detectable DNA in women within 3 h of birth and on day 1-2 postpartum. Postpartum clearance was completed by 2 weeks in all women tested regardless of mode of delivery.
Publisher: Cold Spring Harbor Laboratory
Date: 21-01-2022
DOI: 10.1101/2022.01.18.21268443
Abstract: Congenital cytomegalovirus (cCMV) is the most common perinatal infection and a significant cause of sensorineural hearing loss, cerebral palsy and neurodevelopmental disability. There is a paucity of human gene expression studies examining the pathophysiology of CMV infection. The aim of this study was to perform a whole transcriptomic assessment of amniotic fluid from pregnancies with live fetuses to identify differentially-expressed genes and enriched Gene Ontology categories associated with cCMV infection. Amniotic fluid supernatant was prospectively collected from pregnant women undergoing amniocentesis for suspected cCMV due to first trimester maternal primary infection or ultrasound features suggestive of fetal infection. Women who had received therapy to prevent fetal infection were excluded. cCMV was diagnosed via viral PCR of amniotic fluid CMV-infected fetuses were paired with noninfected controls, matched for gestational age and fetal sex. Paired-end RNA sequencing was performed on amniotic fluid cell-free RNA with the Novaseq6000 at a depth of 30 million reads/s le. Following quality control and filtering, reads were mapped to the human genome and counts summarised across genes. Differentially expressed genes were identified using two approaches: voomWithQualityWeights in conjunction with limma and RUVSeq with edgeR . Genes with a false discovery rate (FDR) 0.05 were considered statistically significant. Differential exon usage was analysed using DEXSeq . Functional analysis was performed using Gene Set Enrichment Analysis and Ingenuity Pathway Analysis. Manual curation of differentially regulated genes was also performed. Amniotic fluid s les were collected from 50 women 16 (32%) had cCMV confirmed by PCR. After excluding 3 s les without matched controls, 13 CMV-infected s les collected at 18-23 weeks and 13 CMV-negative gestation matched controls were submitted for RNA sequencing and analysis (total n=26). Ten of the 13 pregnancies with CMV-infected fetuses had amniocentesis due to serological evidence of maternal primary infection with normal fetal ultrasound, and three had amniocentesis due to ultrasound abnormality suggestive of CMV infection. Four CMV-infected pregnancies ended in termination (n=3) or fetal death (n=1), and 9 resulted in live births. Pregnancy outcomes were available on 11 of the 13 CMV-negative controls all resulted in live births of clinically-well infants. Differential gene expression analysis revealed 309 up-regulated and 32 down-regulated genes in the CMV-infected group compared with the CMV-negative group. Gene set enrichment analysis showed significant enrichment of multiple Gene Ontology categories involving the innate immune response to viral infection and interferon signalling. Of the 32 significantly down-regulated genes, 8 were known to be involved in neurodevelopment and preferentially expressed by the brain. Six specific cellular restriction factors involved in host defence to CMV infection were upregulated in the CMV-infected group. Ingenuity Pathway Analysis predicted activation of pathways involved in ‘progressive neurological disease’, and ‘inflammatory neurological disease’. In this next generation sequencing study, we reveal new insights into the pathophysiology of cCMV infection. These data on the upregulation of the intraamniotic innate immune response to CMV infection and the dysregulation of neurodevelopmental genes may inform future approaches to developing prognostic markers and assessing fetal responses to in utero therapy.
Publisher: Wiley
Date: 06-2019
DOI: 10.1002/UOG.20141
Publisher: Cold Spring Harbor Laboratory
Date: 05-10-2021
DOI: 10.1101/2021.10.04.21264500
Abstract: The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many settings due to the combined impacts of maternal COVID-19 disease, disruptions to maternity care, and overloaded health systems. In 2020, Melbourne endured a unique natural experiment where strict lockdown conditions were accompanied by very low COVID-19 case numbers and the maintenance of health service capacity. The aim of this study was to compare stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy. Retrospective multi-centre cohort study of perinatal outcomes before and during COVID-19 lockdown Birth outcomes from all 12 public maternity hospitals in metropolitan Melbourne Singleton births without congenital anomalies from 24 weeks’ gestation. The lockdown-exposed cohort were those women for whom weeks 20- 40 of gestation would have occurred during the lockdown period of 23 March 2020 to 14 March 2021. The control cohort comprised all pregnancies in the corresponding periods one and two years prior to the exposed cohort. Odds of stillbirth, preterm birth (PTB), birth weight 3 rd centile, and iatrogenic PTB for fetal compromise, adjusting for multiple covariates. There were 24,017 births in the exposed and 50,017 births in the control group. There was a significantly higher risk of preterm, but not term, stillbirth in the exposed group compared with the control group (0.26% vs 0.18%, aOR 1.49, 95%CI 1.08 to 2.05, P = 0.015). There was also a significant reduction in preterm birth 37 weeks (5.93% vs 6.23%, aOR 0.93, 95%CI 0.87 to 0.99, P=0.03), largely mediated by a reduction in iatrogenic PTB for live births (3.01% vs 3.27%, aOR 0.89, 95%CI 0.81 to 0.98, P = 0.015), including iatrogenic PTB for suspected fetal compromise (1.25% vs 1.51%, aOR 0.79, 95%CI 0.69 to 0.91, P= 0.001). There was no significant difference in the spontaneous PTB rate between the exposed and control groups (2.69% vs 2.82%, aOR 0.94, 95%CI 0.86 to 0.1.03, P=0.25). Lockdown restrictions in a high-income setting, in the absence of high rates of COVID-19 disease, were associated with a significant increase in preterm stillbirths, and a significant reduction in iatrogenic PTB for suspected fetal compromise. This study was registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976).
Publisher: Wiley
Date: 30-09-2020
DOI: 10.1002/PD.5819
Abstract: Parvovirus B19 (B19V) infection is well known for its mild, self‐limiting clinical presentations in children, such as erythema infectiosum. Approximately 40% of women of childbearing age are susceptible to B19V infection. While maternal B19V infection usually has a good prognosis , B19V can cause severe fetal anaemia and pregnancy loss due to its ability to suppress erythroid progenitor cells. Non‐invasive ultrasound monitoring for fetal anaemia is usually performed if maternal seroconversion occurs in the first 20 weeks of gestation, with amniocentesis for fetal infection reserved for those who first present with fetal anaemia or hydrops of unknown cause. Intrauterine transfusion is the standard treatment for severe fetal anaemia and is associated with a significant improvement in survival. However, survivors of hydrops fetalis may have a higher rate of long‐term neurodevelopmental complications compared with non‐hydropic survivors. This review aims to synthesise published data on the diagnosis, surveillance and outcomes of congenital parvovirus infection to assist clinicians in diagnosing and managing this important condition.
Publisher: Wiley
Date: 20-04-2020
DOI: 10.1002/PD.5673
Publisher: Wiley
Date: 13-03-2017
DOI: 10.1111/AJO.12590
Abstract: In recent years, the superior accuracy of maternal plasma cell-free DNA-based prenatal screening has resulted in >50% national decline in amniocenteses and chorionic villus s ling (CVS), creating new implications for specialist training. To compare the annual figures on amniocenteses and CVS in a tertiary hospital with national population-based trends between 2012 and 2015. Retrospective study examining the amniocentesis and CVS procedures performed in a tertiary hospital between 2012 and 2015. Numbers of procedures, indications for testing, type of test and diagnostic results were analysed. Trends in the annual numbers of procedures were compared to national population-based data from Medicare Benefits Schedule database. The annual numbers of diagnostic procedures in our tertiary centre fell from 267 to 215 over the study period, representing a 19.5% decline. This was significantly smaller than the corresponding national decline of 53.7% for the same period (P < 0.0001). In 2015, ultrasound abnormality (including nuchal translucency ≥ 3.5 mm) surpassed high-risk screening results as the most common indication for invasive testing. Thirty percent of procedures performed for an ultrasound abnormality occurred prior to 18 weeks gestation. Our tertiary centre experienced a relatively smaller decline in prenatal diagnostic procedures compared with national figures, largely due to an increase in testing for ultrasound abnormalities. Our results demonstrate the increasing contribution of first trimester ultrasound in the detection of fetal abnormalities in the cell-free DNA era and the continued viability of specialist training in invasive procedures.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2015
Publisher: Elsevier BV
Date: 11-2021
Publisher: BMJ
Date: 11-2021
DOI: 10.1136/BMJOPEN-2021-055902
Abstract: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to maternity care with documented impacts on perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne has endured one of the longest and most stringent lockdowns in globally. This paper presents the protocol for a multicentre study to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic. Multicentre observational study analysing monthly deidentified maternal and newborn outcomes from births 20 weeks at all 12 public maternity services in Melbourne. Data will be merged centrally to analyse outcomes and create run charts according to established methods for detecting non-random ‘signals’ in healthcare. Perinatal outcomes will include weekly rates of total births, stillbirths, preterm births, neonatal intensive care admissions, low Apgar scores and fetal growth restriction. Maternal outcomes will include weekly rates of: induced labour, caesarean section, births before arrival to hospital, postpartum haemorrhage, length of stay, general anaesthesia for caesarean birth, influenza and COVID-19 vaccination status, and gestation at first antenatal visit. A prepandemic median for all outcomes will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≥6 consecutive weeks, all above or below the prepandemic median. Additional statistical analyses such as regression, time series and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests. Ethics approval for the collaborative maternity and newborn dashboard project has been obtained from the Austin Health (HREC/64722/Austin-2020) and Mercy Health (ref. 2020-031). ACTRN12620000878976 Pre-results.
Publisher: Wiley
Date: 04-2018
DOI: 10.1002/UOG.19027
Publisher: Informa UK Limited
Date: 11-07-2017
DOI: 10.1080/14767058.2017.1344968
Abstract: To assess the knowledge, practice and attitudes of maternity clinicians regarding congenital cytomegalovirus (CMV). It is the most common congenital infection, and well-recognized cause of neurodevelopmental disability and hearing loss. New consensus recommendations state all pregnant women and health-care providers should be educated about congenital CMV infection and preventive measures. An email questionnaire was distributed in October 2015 to specialists, diplomates (general practitioners), and trainees of the Royal Australian New Zealand College of Obstetricians and Gynaecologists (RANZCOG), and Victorian and New South Wales midwives. 774 responded: (37.3% specialists, 17.3% diplomates, 16.8% trainees, 28.6% midwives). Clinicians had variable knowledge of fetal sequelae, transmission routes and prevention. Overall, 30.2% felt confident about discussing CMV in pregnancy: less than 10% of midwives (7.4%) and less than half of specialists (47.1%, p < .0001). Only 8.8% of respondents routinely discussed CMV prevention with pregnant women. The majority (69.3%) responded that professional societies should make practice recommendations, and 88% thought more patient information was needed, preferably leaflets. Australasian maternity clinicians lack confidence and knowledge about congenital CMV. Few (<10%) routinely provide advice on prevention. There is urgent need for clinical guidance and patient information to reduce the burden of disease.
Publisher: Wiley
Date: 07-2013
DOI: 10.1111/AJO.12117
Abstract: The term 'Non invasive prenatal testing' is used to describe the rapidly emerging molecular technologies related to cell free DNA assessment that are being applied to prenatal screening for Down syndrome and other chromosomal abnormalities. This technology is now available to Australian women through a number of off-shore laboratories. We review the basis of this method of testing, the literature describing the effectiveness of NIPT in screening for trisomy 21 and the potential methods by which this tool could be incorporated into current screening strategies.
Publisher: Wiley
Date: 25-12-2013
DOI: 10.1002/UOG.12360
Publisher: Wiley
Date: 04-2018
DOI: 10.1002/UOG.18979
Abstract: To investigate by means of a population-based analysis of a cohort of women who underwent combined first-trimester screening (CFTS), changes in uptake of invasive prenatal diagnosis according to risk of trisomy 21 (T21) on CFTS, and prevalence and methods for ascertainment of atypical chromosome abnormalities. This was a retrospective cohort study using state-wide prenatal datasets from Victoria, Australia. A three-step approach was taken to analyze the data: (1) linkage of records between serum screening and diagnostic results (2) comparison of rates of diagnostic testing according to CFTS T21 risk result category in a 2014-2015 cohort with those of a historical 2002-2004 cohort (3) detailed analysis of atypical abnormalities in the 2014-2015 group according to CFTS T21 risk result, in idual serum analyte level and other indications for invasive diagnostic testing. In 2014-2015, there were 100 418 CFTS results issued for 146 776 births (68.4%). The overall prevalence of atypical chromosome abnormalities in the entire CFTS cohort was 0.10% and was highest in those with CFTS T21 risk > 1 in 10 (4.6%), or serum analyte levels < 0.2 multiples of the median (MoM) (6.9% for pregnancy-associated plasma protein-A (PAPP-A) and 5.2% for beta-human chorionic gonadotropin (β-hCG)). Almost half (49.2%) of women with PAPP-A 1 in 100, serum PAPP-A or β-hCG < 0.2 MoM, or ultrasound-detected abnormality. This has implications for contingent models of screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Wiley
Date: 10-11-2020
DOI: 10.1111/IJLH.13389
Publisher: Elsevier BV
Date: 02-2013
Publisher: Wiley
Date: 12-2020
DOI: 10.1002/PD.5843
Publisher: Wiley
Date: 2016
DOI: 10.1002/UOG.15806
Publisher: Elsevier BV
Date: 07-2015
Publisher: Wiley
Date: 11-2020
DOI: 10.1002/PD.5688
Publisher: Springer Science and Business Media LLC
Date: 07-07-2016
Publisher: Oxford University Press (OUP)
Date: 03-2020
Abstract: What is the frequency of major chromosome abnormalities in a population-based diagnostic data set of genomic tests performed on miscarriage, fetal and infant s les in a state with & 000 annual births? The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826), with a significant decrease in the detection of major chromosome abnormalities with later developmental stage, from 50.9% to 21.3% to 15.6% of tests in the miscarriage, prenatal and postnatal cohorts, respectively. Over the past decade, technological advances have revolutionized genomic testing at every stage of reproduction. Chromosomal microarrays (CMAs) are now the gold standard of chromosome assessment in prenatal diagnosis and pediatrics. A population-based cohort study including all chromosome analysis was performed in the Australian state of Victoria during a 24-month period from January 2015 to December 2016. All s les obtained via invasive prenatal diagnosis and postnatal s les from pregnancy tissue and infants ≤12 months of age were included. A research collaboration of screening and diagnostic units in the Australian state of Victoria was formed (the Perinatal Record Linkage collaboration), capturing all instances of prenatal and postnatal chromosome testing performed in the state. Victoria has over 73 000 births per annum and a median maternal age of 31.5 years. We analyzed our population-based diagnostic data set for (i) chromosome assessment of miscarriage, prenatal diagnosis and postnatal s les (ii) testing indications and diagnostic yields for each of these cohorts (iii) and the combined prenatal/infant prevalence of 22q11.2 deletion syndrome (DS) as a proportion of all births ≥20 weeks gestation. During the 24-month study period, a total of 8826 chromosomal analyses were performed on prenatal and postnatal specimens in Victoria. The vast majority (91.2%) of all chromosome analyses were performed with CMA. The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826). There was a significant decreasing trend in the percentage of chromosome abnormalities with later developmental stage from 50.9% to 21.3% to 15.6% in the miscarriage, prenatal and postnatal cohorts, respectively (χ2 trend = 790.0, P & 0.0001). The total frequency of abnormalities in the live infant subgroup was 13.4% (244/1816). The frequencies of pathogenic copy number variants (CNVs) detected via CMA for the miscarriage, prenatal and postnatal cohorts were 1.9% (50/2573), 2.2% (82/3661) and 4.9% (127/2592), respectively. There was a significant increasing trend in the frequency of pathogenic CNVs with later developmental stage (χ2 trend = 39.72, P & 0.0001). For the subgroup of live infants, the pathogenic CNV frequency on CMA analysis was 6.0% (109/1816). There were 38 diagnoses of 22q11.2 DS, including 1 miscarriage, 15 prenatal and 22 postnatal cases. After excluding the miscarriage case and accounting for duplicate testing, the estimated prevalence of 22q11 DS was 1 in 4558 Victorian births. Clinical information was missing on 11.6% of postnatal s les, and gestational age was rarely provided on the miscarriage specimens. We were unable to obtain rates of termination of pregnancy and stillbirth in our cohort due to incomplete data provided by clinical referrers. We therefore cannot make conclusions on pregnancy or infant outcome following diagnostic testing. Childhood and adult diagnoses of 22q11 DS were not collected. Our study marks a complete transition in genomic testing from the G-banded karyotype era, with CMA now established as the first line investigation for pregnancy losses, fetal diagnosis and newborn/infant assessment in a high-income setting. Integration of prenatal and postnatal diagnostic data sets provides important opportunities for estimating the prevalence of clinically important congenital syndromes, such as 22q11 DS. L.H. is funded by a National Health and Medical Research Council Early Career Fellowship (1105603) A.L. was funded by a Mercy Perinatal Research Fellowship J.H. was funded by a National Health and Medical Research Council Senior Research Fellowship (10121252). The funding bodies had no role in the conduct of the research or the manuscript. Discretionary funding from the Murdoch Children’s Research Institute has supported the prenatal diagnosis data collection and reporting over the years. Dr Ricardo Palma-Dias reports a commercial relationship with Roche Diagnostics, personal fees from Philips Ultrasound, outside the submitted work. Debbie Nisbet reports a commercial relationship with Roche Diagnostics, outside the submitted work. NA
Publisher: Wiley
Date: 09-07-2016
DOI: 10.1002/UOG.15803
Publisher: Wiley
Date: 03-11-2023
DOI: 10.1002/PD.6251
Abstract: What is already known about this topic? Through the introduction of the nuchal translucency scan at 11 + 0 to 13 + 6 weeks gestation for aneuploidy screening in the 1990s, the role of the first trimester scan has evolved to include an assessment of fetal anatomy. Advances in ultrasound technology and expertise now mean that many fetal anomalies that were previously detected on the routine second trimester anatomy scan are now detected in the first trimester. What does this study add? This report summarizes the oral debate that was presented at the 22nd International Conference on Prenatal Diagnosis and Therapy in Montreal, Canada, on 21 June 2022. Our maternal–fetal medicine experts argue for and against the proposition that a detailed review of fetal anatomy should be included in all scans performed at 11 + 0 to 13 + 6 weeks gestation.
Publisher: Cold Spring Harbor Laboratory
Date: 18-05-2023
DOI: 10.1101/2023.05.16.23289144
Abstract: Melbourne, Australia, recorded one of the longest and most stringent pandemic lockdowns in 2020, which was associated with an increase in preterm stillbirths among singleton pregnancies. Twin pregnancies may be particularly susceptible to the impacts of pandemic disruptions to maternity care due to their higher background risk of adverse perinatal outcomes. To compare the rates of adverse perinatal outcomes in twin pregnancies exposed and unexposed to lockdown restrictions in Melbourne. Multicenter retrospective cohort study of all twin pregnancies birthing in public maternity hospitals in Melbourne. We compared perinatal outcomes between a pre- pandemic group (‘unexposed’) and two lockdown-exposed groups: exposure 1 from 22 March 2020 to 21 March 2021 and exposure 2 from 22 March 2021 to 27 March 2022. We analyzed routinely-collected maternity data on all twin births ≥ 20 weeks where outcomes were available for both infants. The primary outcomes were rates of preterm birth weeks and all-cause stillbirth. Multivariable log-binomial regression models were used to compare perinatal outcomes between the pre-pandemic group and women in whom weeks 20 +0 to 40 +0 of their pregnancy occurred entirely during each lockdown-exposure period. Perinatal outcomes were calculated per infant maternal outcomes were calculated per pregnancy. We included 2267 women birthing twins. Total preterm births weeks were significantly lower in the exposure 1 group compared with the pre-pandemic group (63.1% vs 68.3% respectively adjusted risk ratio, aRR 0.92 95% CI 0.87-0.98, p=0.01). This was mainly driven by fewer spontaneous preterm births (18.9% vs 20.3% aRR 0.95 95%CI 0.90- 0.99, p=0.04) and a trend to fewer iatrogenic preterm births (44.1% vs 48.1% aRR 0.97 95%CI 0.92-1.03, p=0.39). There were also significantly lower rates of preterm birth weeks in the exposure 1 group compared with the pre-pandemic group (19.9% vs 23.0%, aRR 0.93 95%CI 0.89-0.98 p=0.01). Total iatrogenic births for fetal compromise were significantly lower (13.4% vs 20.4% aRR 0.94 95%CI 0.89–0.98, p=0.01). There were fewer special care nursery admissions (38.5% vs 43.4% aRR 0.91 95%CI 0.87-0.95, p .001). There was no associated difference in all-cause stillbirths (1.5% vs 1.6% aRR 1.00 95%CI 0.99-1.01, p=0.82), birthweight rd centile (5.7% vs 6.0% aRR 1.00, 95%CI 0.98-1.02 p=0.74) or neonatal intensive care unit admissions in the exposure 1 group compared to the pre-pandemic group. In contrast, when comparing the pre-pandemic group with exposure 2 group, there was no significant difference in the rates of preterm birth or weeks. However, during exposure 2 the rate of preterm birth weeks was significantly higher (7.2% vs 4.8% aRR 1.03 95%CI 1.01-1.05, p=0.04) and infants were more likely to be admitted to a neonatal intensive care unit (25.0% vs 19.6% aRR 1.06 95%CI 1.03-1.10, p .0001) compared with the pre-pandemic period. Melbourne’s first lockdown-exposure period was associated with fewer twin preterm births and weeks without significant differences in stillbirths or adverse newborn outcomes. These lower rates were not sustained in the second exposure period. Pandemic conditions may provide important lessons for future antenatal care of twin pregnancies, including prevention of preterm birth and optimal timing of birth.
Publisher: Wiley
Date: 05-10-2021
DOI: 10.1111/AJO.13438
Abstract: COVID‐19 has resulted in unprecedented changes to maternity care across Australia. This study aims to analyse trends in maternity consultations and the uptake of telehealth in Victoria and New South Wales (NSW) since the first restrictions to reduce COVID‐19 transmission were implemented. From March 2020 to April 2021, a higher proportion of antenatal care consultations was delivered via telehealth in Victoria compared to NSW (13.8% vs 7.4%, P 0.0001). Uptake of telehealth and a shift from in‐person care has been a major contributor to maintaining pregnancy care during pandemic restrictions. However, further research is required to understand women’s perspectives and health outcomes.
Publisher: Elsevier BV
Date: 2014
Publisher: Wiley
Date: 21-08-2018
Abstract: To evaluate the feasibility of self-reported ethnicity using the gestation-related optimal growth (GROW) classification in a contemporary multicultural antenatal population. Cross-sectional study. Tertiary obstetric hospital in Melbourne, Australia. Pregnant women attending the antenatal clinic. We surveyed pregnant women during April-June 2016 regarding their understanding of the term 'ethnicity', and how they would classify the ethnicity of themselves, their partner, and family members according to the Australian GROW classification. Two hundred and thirty-five women completed the survey. When describing 'ethnicity', most women (103, 44%) chose multiple descriptors, most frequently country of birth (54%) and region of ancestry (47%). Interpretation of 'ethnicity' varied significantly between ethnic groups: those choosing 'country of birth' were more likely to identify as Indian (odds ratio, OR 3.5, P = 0.03), whereas those choosing 'physical appearance' were more likely to identify as Chinese (OR 3.0, P = 0.047). Thirty participants (13%) were unable to describe their ethnicity from the available GROW options. Sixty-one (26%) respondents' ethnicity was inconsistent with that of their parents' heritage. A further 35% had a partner of different ethnicity. The agreement between country of birth and self-reported ethnicity was only fair (kappa 0.73, 95% confidence interval, 95% CI 0.64-0.82). This study confirms the complexity of defining ethnicity in contemporary multicultural settings. Self-reported ethnicity is often inaccurate, concepts of ethnicity vary by ethnic group, and country of birth is a poor descriptive surrogate. Adjustment for maternal ethnicity should be undertaken with caution in the customised assessment of fetal growth. Is self-reported maternal ethnicity reliable? We think not.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1038/GIM.2017.55
Abstract: PurposeTo assess the population-wide impact of noninvasive prenatal screening (NIPS) on combined first-trimester screening (CFTS), early ultrasound (11-13 weeks), and invasive prenatal diagnosis in a state with over 73,000 births per year.MethodsAnalysis of population-based data from 2000 to 2015 including (i) invasive prenatal tests, (ii) CFTS uptake, and (iii) total births. Utilization of early ultrasound was analyzed before and after NIPS (2010-2015).ResultsInvasive testing decreased significantly by 39.6% from 2012 to 2015 despite steady births. More than half of all confirmed cases of trisomy 21 were ascertained by NIPS in 2015, despite NIPS comprising only 11.7% of total indications for invasive testing. CFTS uptake declined significantly from 77.5% in 2013 to 68.1% in 2015, but 11- to 13-week ultrasounds did not. In 2015, ultrasound abnormality replaced CFTS as the most common indication for invasive testing and chromosomal microarray was performed for 85.3% of all prenatal karyotypes.ConclusionPrenatal testing is now unequivocally in the genomic era. NIPS is now the screening test that precedes the majority of confirmed diagnoses of trisomy 21. The contributions of NIPS, early ultrasound, and chromosome microarray have led to unprecedented detection rates of major chromosome abnormalities, now found in 20% of all invasive tests.
Publisher: Wiley
Date: 08-2020
DOI: 10.1002/UOG.21899
Abstract: To perform in idual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. In idual record linkage was performed using LinkageWiz During the study period, there were 79 140 births and 66 166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n = 61 877) of women who underwent screening, and of these, 73.2% (n = 45 275) had CFTS alone, 20.2% (n = 12 486) had cfDNA alone 5.3% (n = 3268) had STSS alone, 1.3% (n = 813) had both CFTS and cfDNA, and < 0.1% (n = 35) had both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21 (T21), 18 (T18) and 13 (T13) of 89.57% (95% CI, 82.64-93.93%) for a screen-positive rate (SPR) of 2.94%. There were 12 false-negative results in the CFTS pathway, comprising 10 cases of T21, one of T18 and one of T13. cfDNA had a combined sensitivity for T21, T18 and T13 of 100% (95% CI, 95.00-100%) for a SPR of 1.21%. When high-risk cfDNA results for any chromosome (including the sex chromosomes) and failed cfDNA tests were treated as screen positives, the SPR for cfDNA increased to 2.42%. The risk of any major chromosomal abnormality (including atypical abnormalities) detected on prenatal or postnatal diagnostic testing after a low-risk screening result was 1 in 1188 for CFTS (n = 37) and 1 in 762 for cfDNA (n = 16) (P = 0.13). The range of chromosomal abnormalities detected after a low-risk cfDNA result included pathogenic copy-number variants (n = 6), triploidy (n = 3), rare autosomal trisomies (n = 3) and monosomy X (n = 2). Our state-wide record-linkage analysis delineated the utilization and clinical performance of the multitude of prenatal screening pathways available to pregnant women. The sensitivity of cfDNA for T21, T18 and T13 was clearly superior to that of CFTS. While there was no statistically significant difference in the residual risk of any major chromosomal abnormality after a low-risk CFTS or cfDNA result, there were fewer live infants diagnosed with a major chromosomal abnormality in the cfDNA cohort. These data provide valuable population-based evidence to inform practice recommendations and health policies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
Publisher: Informa UK Limited
Date: 24-10-2019
DOI: 10.1080/14767058.2017.1391777
Abstract: The fetal left modified Myocardial Performance Index (Mod-myocardial performance index (MPI)) is a measure of systolic versus diastolic time intervals obtained from a single cardiac cycle with ultrasound. It is a measure of global ventricular function and has been investigated for potential utility in fetal conditions associated with cardiac dysfunction. The objective of this study is to compare values from a precisely replicated fetal left Mod-MPI technique to published reference ranges. Three hundred and sixty-five nulliparae prospectively underwent fetal left Mod-MPI measurement at 27 Compared with one selected reference, at 29 Concordance and interobserver variability between our cohort and similar populations were both improved at 35
Publisher: Springer Science and Business Media LLC
Date: 31-08-2018
Publisher: Wiley
Date: 03-08-2022
DOI: 10.1111/JPC.15673
Abstract: Children with a congenital upper limb difference (CoULD) are a erse group who often require multidisciplinary care and long-term support for functional and social impacts. The Australian Hand Difference Register (AHDR) provides a national database of children born with a CoULD and aims to facilitate research and improve health care for affected children. Using data from the first 3 years of its operation, we analysed the demographic and clinical features of participating families, including type of CoULDs and the frequency of pre-natal and syndromic diagnoses. Families were recruited from tertiary plastic surgery, orthopaedic and genetics clinics, as well as by self-referral. Hand differences were classified by the consulting physician according to the Oberg-Manske-Tonkin classification system. Primary carers were invited to complete an online questionnaire covering demographic information, pregnancy and newborn outcomes and diagnostic details. Between August 2017 and September 2020, 822 families consented and 320 questionnaires were reviewed. CoULDs were detected pre-natally in 66 (20.6%) and post-natally in 248 children (77.5%) data for 6 (1.9%) children were missing. The most common CoULDs were radial polydactyly, symbrachydactyly with ectodermal elements and radial longitudinal deficiency, hypoplastic thumb. Twenty-seven children (8.4%) had an associated syndrome, 7 diagnosed pre-natally and 19 post-natally the most common were VACTERL association, Poland anomaly, Holt-Oram and ectrodactyly-ectodermal dysplasia-clefting syndromes. The AHDR is a valuable resource for understanding the relative frequencies of CoULDs. Participation will assist future research into the diagnostic journeys of children with CoULDs, including risk factors, diagnosis and psychosocial impacts.
Publisher: Springer Netherlands
Date: 23-08-2015
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.SINY.2017.11.005
Abstract: Fetal structural anomalies are found in up to 3% of all pregnancies and ultrasound-based screening has been an integral part of routine prenatal care for decades. The prenatal detection of fetal anomalies allows for optimal perinatal management, providing expectant parents with opportunities for additional imaging, genetic testing, and the provision of information regarding prognosis and management options. Approximately one-half of all major structural anomalies can now be detected in the first trimester, including acrania/anencephaly, abdominal wall defects, holoprosencephaly and cystic hygromata. Due to the ongoing development of some organ systems however, some anomalies will not be evident until later in the pregnancy. To this extent, the second trimester anatomy is recommended by professional societies as the standard investigation for the detection of fetal structural anomalies. The reported detection rates of structural anomalies vary according to the organ system being examined, and are also dependent upon factors such as the equipment settings and sonographer experience. Technological advances over the past two decades continue to support the role of ultrasound as the primary imaging modality in pregnancy, and the safety of ultrasound for the developing fetus is well established. With increasing capabilities and experience, detailed examination of the central nervous system and cardiovascular system is possible, with dedicated examinations such as the fetal neurosonogram and the fetal echocardiogram now widely performed in tertiary centers. Magnetic resonance imaging (MRI) is well recognized for its role in the assessment of fetal brain anomalies other potential indications for fetal MRI include lung volume measurement (in cases of congenital diaphragmatic hernia), and pre-surgical planning prior to fetal spina bifida repair. When a major structural abnormality is detected prenatally, genetic testing with chromosomal microarray is recommended over routine karyotype due to its higher genomic resolution.
Publisher: Wiley
Date: 06-11-2019
DOI: 10.1002/PD.5577
Abstract: To explore the association between timing of diagnosis of common autosomal trisomies, maternal age, and socio-economic status (SES). Retrospective study of cytogenetic diagnoses of trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) in Victoria, Australia, in 2015 to 2016, stratified by timing (prenatal less than 17 weeks gestation, prenatal including or greater than or 17 weeks gestation, and postnatal before 12 months of age), maternal age, and SES region. Utilisation of prenatal testing following a live-born T21 infant was ascertained via record linkage. Among 160 230 total births were 571 diagnoses of T21 and 246 of T18/T13. The overall and live birth prevalences of T21 were 3.56 and 0.47 per 1000 births, respectively. Compared with women from disadvantaged SES regions, women from high SES regions were more likely to have a prenatal diagnosis of a trisomy before 17 weeks than after (P < .01) and less likely to have a live-born T21 infant than a prenatal diagnosis (P < .01). There was a significant trend to higher live birth rates of T21 with lower SES (P = .004). The majority (68.5%) of women who gave birth to a live infant with T21 did not utilise prenatal testing. There is a significant relationship between lower SES, later prenatal diagnosis of trisomy, and higher live birth rate of T21 in Victoria.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2012
Publisher: Wiley
Date: 09-2019
DOI: 10.1002/UOG.20150
Abstract: Fetal growth restriction (FGR) is a major risk factor for stillbirth and most commonly arises from uteroplacental insufficiency. Despite clinical examination and third-trimester fetal biometry, cases of FGR often remain undetected antenatally. Placental insufficiency is known to be associated with altered blood flow resistance in maternal, placental and fetal vessels. The aim of this study was to evaluate the performance of in idual and combined Doppler blood flow resistance measurements in the prediction of term small-for-gestational age and FGR. This was a prospective study of 347 nulliparous women with a singleton pregnancy at 36 weeks' gestation in which fetal growth and Doppler measurements were obtained. Pulsatility indices (PI) of the uterine arteries (UtA), umbilical artery (UA) and fetal vessels were analyzed, in idually and in combination, for prediction of birth weight < 10 The Doppler combination most strongly associated with placental insufficiency was a newly generated parameter, which we have named the cerebral-placental-uterine ratio (CPUR). CPUR is the cerebroplacental ratio (CPR) (middle cerebral artery PI/UA-PI) ided by mean UtA-PI. CPUR MoM detected FGR better than did mean UtA-PI MoM or CPR MoM alone. At ∼ 90% specificity, low CPUR MoM had sensitivities of 50% for birth weight < 10 In this cohort, a novel Doppler variable combination, the CPUR (CPR/UtA-PI), had the strongest association with indicators of placental insufficiency. CPUR detected more cases of FGR than did any other Doppler parameter measured. If these results are replicated independently, this new parameter may lead to better identification of fetuses at increased risk of stillbirth that may benefit from obstetric intervention. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Wiley
Date: 16-01-2023
DOI: 10.1002/PD.6305
Abstract: To determine the perinatal outcomes of fetuses diagnosed with a pathogenic copy number variant (CNV) or variant of uncertain significance (VUS) and to characterize these variants in terms of testing indication, genomic location, size, and inheritance. Retrospective study of singleton pregnancies with a pathogenic CNV or VUS from a single laboratory during 2012–2018. Probabilistic record linkage between the prenatal diagnosis dataset and perinatal outcome data for births from 20 weeks gestation was performed. If no birth record was found, this implied a pregnancy loss weeks. We included 6945 prenatal microarray results a pathogenic CNV was detected in 230 (3.3%, 95% CI: 2.9%–3.8%) and a VUS in 483 (7.0%, 95% CI: 6.4%–7.6%). Of pregnancies with a pathogenic CNV, 20.0% (95% CI: 15.3%–25.6%) had a live birth, 3.0% (95% CI: 1.5%–6.2%) had a perinatal death (stillbirth or neonatal death), and 77% (95% CI: 71.1%–81.9%) had no birth record. Of those with a VUS, 64.4% (95% CI: 60.0%–68.5%) had a live birth, 1.8% (95% CI: 1.0%–3.5%) had a perinatal death, and no birth record was found for 33.7% (95% CI: 29.7%–38.1%). Most pathogenic CNVs (61.1%) were Mb in size. The most common microdeletion syndromes were DiGeorge, Wolf‐Hirschhorn, and Cri‐du‐chat syndromes. This study provides an overview of perinatal outcomes and frequency of recurrent CNVs observed in the prenatal microarray era.
Publisher: Wiley
Date: 02-11-2021
DOI: 10.1111/AJO.13268
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 05-2023
Publisher: Wiley
Date: 06-08-2021
DOI: 10.1002/PD.6024
Abstract: Three decades ago, the observation that first trimester fetuses with excess fluid accumulation at the back of the neck were more likely to be aneuploid, gave rise to a new era of prenatal screening. The nuchal translucency (NT) measurement in combination with serum biomarkers and maternal age, resulted in the first trimester combined screening (FTCS) program. The introduction of noninvasive prenatal testing (NIPT) over the past decade has introduced the option for parents to receive highly sensitive and specific screening information for common trisomy from as early as 10 weeks gestation, altering the traditional pathway FTCS pathway. The retention of the 11–13‐week NT ultrasound remains important in the detection of structural anomalies however, the optimal management of pregnancies with a low‐risk NIPT result and an isolated increased NT measurement in an era of advanced genomic testing options is a new dilemma for clinicians. For parents, the prolonged period between the initial diagnosis in first trimester, and prognostic information at each successive stage of investigations up to 22–24 weeks, can be emotionally challenging. This article addresses the common questions from parents and clinicians as they navigate the uncertainty of having a fetus diagnosed with an increased NT after a low‐risk NIPT result and presents suggested approaches to management.
Publisher: SAGE Publications
Date: 22-06-2016
Abstract: The rapid global uptake of noninvasive prenatal testing for Down syndrome based on maternal plasma cell-free DNA has provided new data on the interrelationship between cell-free DNA and maternal health. Specific maternal conditions that can affect the performance of noninvasive prenatal testing include obesity, active autoimmune disease and low molecular weight heparin treatment. There is also a growing appreciation of the implications of discordant noninvasive prenatal testing results for maternal health, including unexpected diagnoses of maternal chromosomal conditions, or rarely, occult cancer. The interrelatedness of noninvasive prenatal testing and maternal health mean that the longstanding principles underpinning prenatal screening – voluntary testing, informed decision making, availability of specialist genetic counselling and well-defined clinical pathways – are more important than ever before.
Publisher: Public Library of Science (PLoS)
Date: 08-09-2020
Start Date: 04-2021
End Date: 12-2024
Amount: $475,000.00
Funder: Australian Research Council
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