Association between timing of diagnosis of trisomy 21, 18, and 13 and maternal socio-economic status in Victoria, Australia: A population-based cohort study from 2015 to 2016.

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.

Prospective longitudinal assessment of the fetal left modified Myocardial Performance Index.

INTRODUCTION: 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. OBJECTIVES: The objective of this study is to compare values from a precisely replicated fetal left Mod-MPI technique to published reference ranges. METHODS: Three hundred and sixty-five nulliparae prospectively underwent fetal left Mod-MPI measurement at 27+0-29+0 and 35+0-37+0 weeks' gestation. Measurements from pregnancies complicated by gestational diabetes mellitus, preeclampsia, or a small-for-gestational-age (<10th centile) infant were excluded. Mod-MPI values were compared with three published references created using similar measurement techniques. RESULTS: Compared with one selected reference, at 29+0 and 35+0-37+0 weeks' gestation, 90-100% of our values fell within the 5th-95th percentile range as expected. Thus, this reference range was validated for our population in late pregnancy. However, the expected level of concordance was not seen at 27+0-28+6 weeks'. The other two references to which we compared our Mod-MPI values demonstrated poor concordance, especially at 27+0-29+0 weeks'. Pearson interobserver correlation was also improved at 35+0-37+0 weeks' at 0.434, compared with 0.083 at 27+0-29+0 weeks' gestation. CONCLUSIONS: Concordance and interobserver variability between our cohort and similar populations were both improved at 35+0-37+0 weeks' compared with 27+0-29+0 weeks' gestation. Overall, variable Mod-MPI reproducibility across gestations limits clinical application, especially earlier in pregnancy. Manual Mod-MPI measurement should be considered most reliable in late pregnancy until automated MPI measurement is possible.

What is the real "price" of more prenatal screening and fewer diagnostic procedures? Costs and trade-offs in the genomic era.

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.

Prenatal diagnosis and socioeconomic status in the non-invasive prenatal testing era: A population-based study.

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.

National decline in invasive prenatal diagnostic procedures in association with uptake of combined first trimester and cell-free DNA aneuploidy screening.

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 sampling (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.

Early clinical experience of cell-free DNA-based aneuploidy screening: A survey of obstetric sonologists in Australia and New Zealand.

BACKGROUND: 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. AIM: 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. METHOD: Email invitations with an embedded link to an anonymous online survey were sent to all 140 members of the AAOGU in December 2013. RESULTS: 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. CONCLUSIONS: 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.