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Objectives: To perform individual 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.Methods: 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. Individual record linkage was performed using LinkageWizTM .Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective: 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.Methods: This was a retrospective analysis of all ultrasound-indicated prenatal diagnostic testing (amniocentesis and chorionic villus sampling) 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 χ2 tests for trend or difference in proportions, as appropriate.Results: 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 < 16 weeks was significantly higher than that of tests performed after 20 weeks (31.5% vs 9.0%).Conclusions: Ultrasound-indicated invasive testing is contributing to prenatal diagnosis in new ways in the genomic era. A pathogenic CNV is now the most likely diagnosis after ultrasound-indicated testing, rather than trisomy 21 or other whole-chromosome aneuploidy. Despite steady improvements in first-trimester screening for aneuploidy, the diagnostic yield of ultrasound-indicated tests > 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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility of self-reported ethnicity using the gestation-related optimal growth (GROW) classification in a contemporary multicultural antenatal population.Design: Cross-sectional study.Setting: Tertiary obstetric hospital in Melbourne, Australia.Population: Pregnant women attending the antenatal clinic.Methods: 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.Results: 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).Conclusion: 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.Tweetable Abstract: Is self-reported maternal ethnicity reliable? We think not. [ABSTRACT FROM AUTHOR]

Objective: To analyse population-based trends over the entire history of prenatal testing for aneuploidy.Design: Retrospective analysis of state-wide data sets.Setting: Australian state of Victoria with ~70 000 annual births.Population: All pregnant women undergoing invasive prenatal testing at <25 weeks' gestation from 1976 to 2013.Methods: Analysis of three state-wide data sets: (1) Prenatal diagnosis data set of 119 404 amniocenteses and chorionic villus samplings from 1976 to 2013; (2) central serum screening laboratory data set from 1996 to 2013; (3) government birth statistics from 1976 to 2013.Main Outcome Measures: 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.Results: 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.Conclusions: 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.Tweetable Abstract: Invasive prenatal testing has reached historic lows due to dramatic improvements in Down syndrome screening. [ABSTRACT FROM AUTHOR]

Background: To analyze population-based trends in the prenatal diagnosis of sex chromosome aneuploidy (SCA) since the availability of non-invasive prenatal testing (NIPT)., Methods: Retrospective state-wide data for all prenatal diagnoses performed <25 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., Results: 46,518 amniocentesis and chorionic villus sampling 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)., Conclusion: 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., (© 2022 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

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., (© 2021 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objectives: To explore the association between timing of diagnosis of common autosomal trisomies, maternal age, and socio-economic status (SES)., Design: 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., Results: 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., Conclusion: There is a significant relationship between lower SES, later prenatal diagnosis of trisomy, and higher live birth rate of T21 in Victoria., (© 2019 John Wiley & Sons, Ltd.)

Objective: 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., Method: 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., Results: 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%)., Conclusion: 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., (© 2018 John Wiley & Sons, Ltd.)

Objective: To examine the statewide utilisation of prenatal diagnosis (PNDx) and preimplantation genetic diagnosis (PGT-M) for single gene disorders., Methods: 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 2 test., Results: 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., Conclusions: 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., (© 2018 John Wiley & Sons, Ltd.)

Background: 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., Aim: To analyse screening test indications for, and diagnostic yield of, invasive prenatal diagnostic testing (PNDx) according to socioeconomic status., Methods: 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., Results: 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)., Conclusion: 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., (© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To evaluate the feasibility of self-reported ethnicity using the gestation-related optimal growth (GROW) classification in a contemporary multicultural antenatal population., Design: Cross-sectional study., Setting: Tertiary obstetric hospital in Melbourne, Australia., Population: Pregnant women attending the antenatal clinic., Methods: 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., Results: 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)., Conclusion: 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., Tweetable Abstract: Is self-reported maternal ethnicity reliable? We think not., (© 2017 Royal College of Obstetricians and Gynaecologists.)