Nodal positivity in patients with clinically and radiologically node-negative breast cancer treated with neoadjuvant chemotherapy: multicentre collaborative study.

BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. RESULTS: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2- tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. CONCLUSION: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes.

Willingness to pay for expanded non-invasive prenatal screening - An online discrete choice experiment from the perspective of women living in Western Australia.

INTRODUCTION: Ongoing advances in genetic technology may soon provide prenatal screening for multiple genetic conditions. AIMS: The aims were to investigate what prenatal screening test characteristics women prioritise and their willingness to pay for these tests. METHODS: We designed an online survey incorporating a series of discrete choice scenarios. Dimensions and levels were selected based on existing prenatal tests and a hypothetical prenatal test that could non-invasively detect multiple genetic disorders in pregnancy. Participants were recruited from social media platforms. Data were analysed using conditional logistic regression and latent class analysis (LCA). RESULTS: A total of 219 women completed the survey. Women with higher incomes and those with a tertiary education were willing to pay more than other groups. The maximum willingness to pay was AUD1870 (95% confidence interval: 1630, 2112) for a hypothetical non-invasive test to detect multiple genetic conditions in early pregnancy. An LCA demonstrated considerable heterogeneity in preferences, differing in both overall preference for testing and test characteristics considered most attractive. Among the participants, decision factors cited by 14.5% of participants were the risk of pregnancy loss, making them less likely to undergo testing; for 32.1% participants, accuracy was a major factor, and they were very likely to have testing; for 12.9%, test availability early in pregnancy was a decision factor. CONCLUSIONS: If a non-invasive test that could detect the greatest number of genetic disorders in pregnancy was available, the priorities were test accuracy, risk of pregnancy loss and a test available early in pregnancy.

Plasma collection and supply in Europe: Proceedings of an International Plasma and Fractionation Association and European Blood Alliance symposium.

At the symposium organized by the International Plasma and Fractionation Association and European Blood Alliance, experts presented their views and experiences showing that the public sector and its blood establishments may strengthen the collection and increase the supply of plasma using the right strategies in plasma donor recruitment, retention and protection, scaling-up collection by increasing the number of donors within improved/new infrastructure, supportive funding, policies and legislation as well as harmonization of clinical guidelines and the collaboration of all stakeholders. Such approaches should contribute to increased plasma collection in Europe to meet patients' needs for plasma-derived medicinal products, notably immunoglobulins and avoid shortages. Overall, presentations and discussions confirmed that European non-profit transfusion institutions are committed to increasing the collection of plasma for fractionation from unpaid donors through dedicated programmes as well as novel strategies and research.

Western Australian women's expectations for expanded NIPT-An online survey regarding NIPT for single gene, recessive and chromosomal conditions.

Prenatal screening has evolved rapidly following the introduction of non-invasive prenatal testing (NIPT), with screening now available for an increasing number of conditions. We explored the attitudes and expectations of women within the context of using NIPT to detect multiple different single gene and chromosome conditions during pregnancy. An online survey was used to assess these issues with a sample of 219 women from Western Australia. In our study, the majority of women (96%) support of the concept of expanded NIPT for single gene and chromosome conditions provided the test involves no risk to the pregnancy and can provide the parents with relevant medical information about the fetus at any stage of pregnancy. 80% believed that expanded NIPT for single gene and chromosome conditions should be available at any stage during pregnancy and 68% of women indicated that test cost would be a factor in determining their participation in testing. Under half (43%) of the women favored an option to terminate a pregnancy at any stage if the fetus had a medical condition that would interfere with day to day functioning. The majority (78%) of women believed that testing for multiple genetic conditions would provide reassurance and lead to the delivery of a healthy child.

Women's responses to prenatal genetic diagnosis and attitudes to termination of pregnancy after non-invasive prenatal testing: An online survey of Western Australian women.

BACKGROUND: Non-invasive prenatal testing (NIPT) using cell-free DNA (cfDNA) has expanded from detecting chromosome aneuploidy to testing for a variety of genetic conditions, including some select single gene disorders. As next generation sequencing/whole exome sequencing technology develops, it may be possible to expand NIPT of cfDNA to identify hundreds of single gene and chromosomal disorders in a fetus, thereby increasing the complexity of pretest counselling and parental decision-making. AIM: The aim of this study was to assess the views of women on the phenotypes of genetic conditions potentially detectable with expanded NIPT that they would consider severe enough to warrant pregnancy termination. MATERIALS AND METHODS: Using multiple clinical scenarios, we asked women via an online survey about the early detection of several well-described genetic phenotypes in pregnancy that in theory could be detected by expanded NIPT. RESULTS: Two hundred and nineteen women participated in this study. There was high support for early diagnosis and the option for termination of pregnancy in conditions perceived as severe (52-71%). Women expressed a preference for testing to be provided by general practitioners and assigned a high value to genetic counselling support (75-90%). In the case of a continuing pregnancy, women recognised the essential role of ongoing psychosocial counselling for family members and childhood early intervention programs. CONCLUSION: Women expressed clear preferences for termination of pregnancy for severe conditions and as early in gestation as feasible. Information and support from genetic counsellors are a highly valued resource in decision-making following a prenatal diagnosis of a fetal genetic abnormality.

Familial and non-familial risk factors associated with colorectal cancer survival in young and middle-aged patients.

BACKGROUND: Survival following colorectal cancer (CRC) survival may be influenced by a number of factors including family history, individual medical history, and comorbidities. The impact of these factors may vary based on the patient's age. METHODS: The study cohort consisted of individuals born in Western Australia between 1945 and 1996, who had been diagnosed with CRC prior to 2015 (n = 3220). Hospital, cancer, and mortality data were extracted for each patient from state health records and were used to identify potential risk factors associated with CRC survival. Family linkage data, in combination with cancer registry data, were used to identify first-degree family members with a history of CRC. The association between survival following CRC diagnosis and identified risk factors was examined using Cox proportional hazard models. RESULTS: Age and sex were not significantly associated with survival in young patients. However, in middle-aged patients increasing age (HR 1.03, 95% CI 1.01-1.05, p = 0.003) and being male (HR 0.72, 95% CI 0.60-0.87, p < 0.001) were associated with reduced survival. Being diagnosed with polyps and having a colonoscopy prior to CRC diagnosis were associated with improved survival in both young and middle-aged patients, while a history of non-CRC and liver disease was associated with reduced survival. In middle-aged patients, having diabetes-related hospital admissions (HR 1.53, 95% CI 1.15-2.03, p = 0.004) was associated with reduced survival. CONCLUSIONS: In both young and middle-aged patients with CRC, factors associated with early screening and detection were associated with increased CRC survival while a history of liver disease and non-CRC was associated with decreased CRC survival.

Costs and outcomes of Lynch syndrome screening in the Australian colorectal cancer population.

BACKGROUND AND AIM: Individuals with Lynch syndrome (LS) are at increased risk of LS-related cancers including colorectal cancer (CRC). CRC tumor screening for mismatch repair (MMR) deficiency is recommended in Australia to identify LS, although its cost-effectiveness has not been assessed. We aim to determine the cost-effectiveness of screening individuals with CRC for LS at different age-at-diagnosis thresholds. METHODS: We developed a decision analysis model to estimate yield and costs of LS screening. Age-specific probabilities of LS diagnosis were based on Australian data. Two CRC tumor screening pathways were assessed (MMR immunohistochemistry followed by MLH1 methylation (MLH1-Pathway) or BRAF V600E testing (BRAF-Pathway) if MLH1 expression was lost) for four age-at-diagnosis thresholds-screening < 50, screening < 60, screening < 70, and universal screening. RESULTS: Per 1000 CRC cases, screening < 50 identified 5.2 LS cases and cost $A7041 per case detected in the MLH1-Pathway. Screening < 60 increased detection by 1.5 cases for an incremental cost of $A25 177 per additional case detected. Screening < 70 detected 1.6 additional cases at an incremental cost of $A40 278 per additional case detected. Compared with screening < 70, universal screening detected no additional LS cases but cost $A158 724 extra. The BRAF-Pathway identified the same number of LS cases for higher costs. CONCLUSIONS: The MLH1-Pathway is more cost-effective than BRAF-Pathway for all age-at-diagnosis thresholds. MMR immunohistochemistry tumor screening in individuals diagnosed with CRC aged < 70 years resulted in higher LS case detection at a reasonable cost. Further research into the yield of LS screening in CRC patients ≥ 70 years is needed to determine if universal screening is justified.

Women's Understanding and Attitudes towards Down Syndrome and Other Genetic Conditions in the Context of Prenatal Screening.

In order to explore the impact of potential new technologies in the area of prenatal screening, we conducted a baseline study using qualitative interviews to explore women's attitudes and knowledge regarding current and future prenatal screening technology and methods. Three cohorts were interviewed, including healthy women without children, healthy women with healthy children, and healthy women with children who have de novo genetic disorders. This study aimed to assess the baseline understanding and attitudes of women in Western Australia. Women from each cohort demonstrated adequate knowledge of the differences between screening and diagnostic tests, but were mostly unaware of the conditions for which screening is currently available except Down syndrome. Women who had children with de novo genetic conditions were generally aware of more genetic conditions than women with or without healthy children. Most women recognised the genetic basis for the conditions mentioned. Two thirds of women understood that Down syndrome is a chromosomal condition; just one third recognised that the phenotype is variable. Most women expressed a positive attitude towards Down syndrome. Social acceptance of children with Down syndrome was commonly mentioned as a concern. While the majority of women with children supported screening for Down syndrome, they emphasised that it must be an autonomous choice. General knowledge of genetic conditions illustrated that women are exposed to diverse conditions from lived experience as well as the media.

Risk of persistent and recurrent cervical neoplasia following incidentally detected adenocarcinoma in situ.

BACKGROUND: Adenocarcinoma in situ of the uterine cervix is a precursor to cervical adenocarcinoma and may coexist with both adenocarcinoma and high-grade squamous dysplasia (cervical intraepithelial neoplasia 2 and 3). Up to 60% of adenocarcinoma in situ lesions are detected incidentally following excisional biopsies performed for the treatment of cervical intraepithelial neoplasia 2/3. To date there are no data regarding risk factors for persisting or progressive cervical neoplasia in these patients. OBJECTIVE: We sought to investigate patient outcomes following incidentally detected cervical adenocarcinoma in situ after loop electrosurgical excision procedure or cold knife cone biopsy performed for the treatment of high-grade cervical intraepithelial neoplasia. STUDY DESIGN: We conducted a retrospective, population-based cohort study of Western Australian patients with an incidental diagnosis of adenocarcinoma in situ from 2001 through 2012. Primary outcomes were persistent or recurrent cervical intraepithelial neoplasia 2/3 and or adenocarcinoma in situ, and invasive adenocarcinoma during follow-up (<12 months) and surveillance (≥12 months) periods. RESULTS: The cohort comprised 298 patients, with 228 (76.5%) treated initially by loop electrosurgical excision procedure and 70 (23.5%) treated by cold knife cone biopsy. The mean age was 31.2 (range 18-68) years and the median length of follow-up was 2.4 (range 0.3-12.2) years. Overall, 11 (3.7%) patients had cervical intraepithelial neoplasia 2/3, 23 (7.7%) had adenocarcinoma in situ, and 3 (1.0%) had adenocarcinoma diagnosed during the follow-up and surveillance periods. Age >30 years, pure adenocarcinoma in situ lesions, and larger lesions (>8 mm) were associated with a greater risk of disease persistence or recurrence. CONCLUSION: Following the incidental detection of adenocarcinoma in situ, age >30 years, pure adenocarcinoma in situ lesions, and lesions >8 mm were significantly associated with disease persistence/recurrence. In younger women, incidentally detected adenocarcinoma in situ that coexists with cervical intraepithelial neoplasia 2/3 and is <8 mm extent with clear margins may not require reexcision.

Do Inflammatory Indices Play a Role in Distinguishing between Uncomplicated and Complicated Diverticulitis?

BACKGROUND: The usefulness of inflammatory indices in assessment of the severity of acute diverticulitis remains unestablished. The aim of this study was to determine whether inflammatory indices and hematological ratios could be utilised to differentiate between uncomplicated and complicated diverticulitis. METHODS: Hematological and inflammatory indices were recorded for each admission with CT confirmed acute diverticulitis (101 complicated, 127 uncomplicated). Cases were divided into training (n = 57) and test sets (n = 171). A classification and regression tree (CART) analysis was employed in the training set to identify optimal inflammatory marker cut-off points associated with complicated diverticulitis. Samples (test set) were then categorized as (A) greater than and (B) less than CART identified cut-off points. The predictive properties of inflammatory marker cut-off points in distinguishing severity of diverticulitis were assessed using a univariate logistic regression analysis, summary receiver operating characteristic curves and confusion matrix generation. RESULTS: C-reactive protein >109 mg/ml (OR 3.07, 95% CI 1.43-6.61, p = 0.004, area under the curve; AUC = 0.64) and white cell lymphocyte ratio (WLR) >17.72 (OR 4.23, 95% CI 1.95-9.17, p < 0.001, AUC = 0.64) were the most accurate parameters in distinguishing complicated and uncomplicated disease. WCC >21 × 109/l (p = 0.02, AUC = 0.60) and lymphocyte count >0.55 × 109/l (p = 0.009, AUC = 0.60) were less accurate. CONCLUSION: Widely used inflammatory indices are useful in the depiction of complicated diverticulitis. The indices cut-off points highlighted in this study should be considered at the time of diagnosis in combination with radiological features of complicated diverticulitis.

Diagnostic performance and costs of contingent screening models for trisomy 21 incorporating non-invasive prenatal testing.

BACKGROUND: Contingent screening for trisomy 21 using non-invasive prenatal testing has the potential to reduce invasive diagnostic testing and increase the detection of trisomy 21. AIM: To describe the diagnostic and economic performance of prenatal screening models for trisomy 21 that use non-invasive prenatal testing as a contingent screen across a range of combined first trimester screening risk cut-offs from a public health system perspective. METHODS: Using a hypothetical cohort of 300 000 pregnancies, we modelled the outcomes of 25 contingent non-invasive prenatal testing screening models and compared these to conventional screening, offering women with a high-risk (1 > 300) combined first trimester screening result an invasive test. The 25 models used a range of risk cut-offs. High-risk women were offered invasive testing. Intermediate-risk women were offered non-invasive prenatal testing. We report the cost of each model, detection rate, costs per diagnosis, invasive tests per diagnosis and the number of fetal losses per diagnosis. RESULTS: The cost per prenatal diagnosis of trisomy 21 using the conventional model was $51 876 compared to the contingent models which varied from $49 309-66 686. The number of diagnoses and cost per diagnosis increased as the intermediate-risk threshold was lowered. Results were sensitive to trisomy 21 incidence, uptake of testing and cost of non-invasive prenatal testing. CONCLUSION: Contingent non-invasive prenatal testing models using more sensitive combined first trimester screening risk cut-offs than conventional screening improved the detection rate of trisomy 21, reduced procedure-related fetal loss and could potentially be provided at a lower cost per diagnosis than conventional screening.

The log TSH-free T4 relationship in a community-based cohort is nonlinear and is influenced by age, smoking and thyroid peroxidase antibody status.

BACKGROUND: The TSH-T4 relationship was thought to be inverse log-linear, but recent cross-sectional studies of selected populations report a complex, nonlinear relationship. The TSH-T4 relationship has not been evaluated in an unselected, community-based cohort, and there are limited data regarding clinical factors which affect it. OBJECTIVE: To analyse the TSH-free T4 relationship in a community-based cohort. DESIGN, PARTICIPANTS AND METHODS: In a cross-sectional, retrospective study, we analysed serum TSH and free T4 concentrations from 4427 participants (55% female) in the 1994 Busselton Health Study who were not taking thyroxine. Simple linear, segmented-linear and nonlinear regression models of log10 TSH on free T4 were compared for goodness of fit. RESULTS: All 5 log TSH-free T4 models tested (separate lines, segmented conterminal line, quartic, error function, double-sigmoid curve) fitted significantly better than a simple linear model (each P < 0·01 by Vuong test). Ranking by Akaike information criterion indicated that the segmented conterminal line and double-sigmoid models provided best fit, followed by the error function, quartic and separate lines models. From multiple regression analysis, age tertile, current smoking and TPOAb status each significantly influenced the TSH-free T4 relationship, whereas BMI category and diabetes did not. A sex difference in the TSH-free T4 relationship was apparent only in the lower part of the free T4 reference range. CONCLUSION: In a community-based setting, the relationship between log TSH and free T4 is complex, nonlinear and influenced by age, smoking and TPOAb status.

Spontaneous regression of CIN2 in women aged 18-24 years: a retrospective study of a state-wide population in Western Australia.

INTRODUCTION: CIN2 has a high rate of spontaneous regression in young women and may be managed conservatively in appropriately selected patients. This study aimed to investigate health outcomes in women aged 18-24 years with biopsy-confirmed CIN2. MATERIAL AND METHODS: A retrospective cohort study of Western Australian women aged 18-24 years diagnosed with CIN2 on cervical biopsy from 1 January 2001 to 31 December 2010. Women who had not received treatment at ≥4 months following CIN2 diagnosis were classified as managed 'conservatively'. Subsequent cervical cytology and/or biopsy test results were used to report lesion regression (absence of dysplasia or an epithelial lesion of lower grade than CIN2) and disease persistence (CIN2, CIN3 or ACIS). RESULTS: Follow-up data were available for 2417 women of whom 924 (38.2%) were 'conservatively' managed. In all, 152 (16.4%) conservatively managed women had a lesion more severe than CIN2 detected within 24 months of initial diagnosis, of which 144 were CIN3 and eight were ACIS. There was no statistically significant association between rates of regression and patient age, Socio-economic Indexes for Areas or Accessibility/Remoteness Index of Australia indices. The 2-year regression rate for CIN2 was estimated to be 59.5% (95%CI 0.5-0.6) in this cohort of women. CONCLUSION: In conservatively managed young women with CIN2 there was a high rate of spontaneous disease regression. Thus, excisional or ablative treatments may be avoided in selected patients who receive appropriate counseling and who are able to comply with more intensive and prolonged follow-up requirements.

First trimester screening cut-offs for noninvasive prenatal testing as a contingent screen: Balancing detection and screen-positive rates for trisomy 21.

OBJECTIVE: To provide data on how screen-positive and detection rates of first trimester prenatal screening for fetal Down syndrome vary with changes in the risk cut-off and maternal age to inform contingency criteria for publicly funded noninvasive prenatal testing. MATERIALS AND METHODS: First trimester screening and diagnostic data were collected for all women attending for first trimester fetal aneuploidy screening in Western Australia between 2005 and 2009. Prenatal screening and diagnostic data were linked to pregnancy outcomes, including data from the Midwives' Notification System and the Western Australian Registry of Developmental Anomalies. The prevalence of Down syndrome and performance of screening by risk cut-off and/or for women >35 years were analysed. RESULTS: The current screening risk cut-off of 1:300 has screen-positive and detection rates of 3.5% and 82%. The screen-positive rate increases by 0.7-0.8% for each 100 point change in risk, up to 19.2% at 1:2500 (96% detection rate). Including all women >35 years as screen positive would increase the screen-positive rate and detection rates to 30.2% and 97.2%. CONCLUSION: Variation in screening risk cut-off and the use of maternal age to assess eligibility for noninvasive testing could significantly impact the demand for, and cost of, the test. A contingent first trimester screening approach for risk assessment is superior to the use of a combination of screening and maternal age alone. These data will inform decisions regarding the criteria used to determine eligibility for publicly funded noninvasive prenatal testing.

Folate status in Aboriginal people before and after mandatory fortification of flour for bread-making in Australia.

BACKGROUND: Mandatory fortification of wheat flour for bread-making was introduced in Australia in September 2009, to assist in the prevention of neural tube defects (NTD). NTD are twice as common in Aboriginal compared with non-Aboriginal infants, and folate levels are lower in the Aboriginal population. AIMS: This study was undertaken to compare folate status and NTD in the Aboriginal population before and after fortification. METHODS: Postfortification, 95 Aboriginal men and nonpregnant women aged 16-44 years in metropolitan and regional Western Australia (WA) completed a rapid dietary assessment tool and had blood taken to measure red cell folate. Measures were compared with prefortification values obtained in an earlier study using the same methods. Data on NTD in Aboriginal infants were obtained from the WA Register of Developmental Anomalies. RESULTS: No participant was folate deficient. The mean red cell folate increased after fortification to 443 ng/mL for males and 567 ng/mL for females. The mean difference between red cell folate after fortification compared with before was 129 ng/mL for males (95% CI 81-177); t = 5.4; P < 0.0001) and 186 ng/mL for females (95% CI 139-233); t = 7.9; P < 0.0001). Most participants ate fortified shop-bought bread at least weekly, resulting in an estimated additional folate intake per day of 178 (males) and 145 (females) dietary folate equivalents. NTD prevalence fell by 68% following fortification (prevalence ratio 0.32 (CI 0.15-0.69)). CONCLUSIONS: The population health intervention of mandatory fortification of wheat flour for bread-making has had the desired effect of increasing folate status and reducing NTD in the Australian Aboriginal population.

Screening for Down syndrome in the second trimester of pregnancy.

Antenatal screening for fetal anomalies has provided women and their partners with information to make reproductive choices based on the risk of serious chromosomal or structural defects since the 1990s. Alternative tests include first-trimester screening (combined ultrasound and maternal serum markers), second-trimester maternal serum markers and noninvasive cell-free DNA testing. The recent recommendations by the Royal Australian and New Zealand College of Obstetrics and Gynaecology and the Human Genetics Society of Australasia against second-trimester triple testing are based on unsound performance criteria, raise several contestable issues around access and equity and challenge the principles of governments providing affordable options.

Impact of prenatal screening and diagnostic testing on trends in Down syndrome births and terminations in Western Australia 1980 to 2013.

OBJECTIVE: To assess how prenatal screening and diagnostic testing have impacted the diagnosis, termination and birth prevalence of Down syndrome in Western Australia (1980-2013). METHOD: We analysed trends in termination rates and birth prevalence of Down syndrome using aggregated data (1980-2013). We modelled the expected live-birth rate and prevalence of Down syndrome and compared different eras of screening and diagnosis with respect to the impact on live-birth rate and prevalence of Down syndrome. RESULTS: Between 1980 and 2013, the rate of Down syndrome pregnancies increased, corresponding to a greater proportion of babies born to older women. Following the introduction of screening in 1994, the rate of live-born infants with Down syndrome reduced significantly (p = 0.001). The rate of terminations of pregnancy for Down syndrome remained stable over this period. In the absence of termination, the Down syndrome live-birth rate would have risen from 1.1 per 1000 to 2.17 per 1000 between 1980 and 2013. CONCLUSION: Prenatal testing in Western Australia has reduced the birth prevalence of Down syndrome despite an increased rate of Down syndrome pregnancies. Most women for whom a prenatal diagnosis of fetal Down syndrome is made, chose to terminate the pregnancy (93%), and this proportion has not changed over the study period.

The potential impact of NIPT as a second-tier screen on the outcomes of high-risk pregnancies with rare chromosomal abnormalities.

AIM: To describe the potential impact of using noninvasive prenatal testing (NIPT) as a second-tier test, on the diagnosis and outcomes of pregnancies identified as high risk through first trimester screening (FTS) in a cohort of real pregnancies. MATERIALS AND METHODS: Western Australian FTS and diagnostic data (2007-2009) were linked to pregnancy outcomes. Karyotype results from invasive prenatal testing in high-risk women were analysed. The outcomes of abnormal results that would not be detected by NIPT, assuming a panel of trisomy 21/18/13 and sex chromosome aneuploidies, and the likelihood of diagnosis in a screening model using NIPT as a second-tier test are described. RESULTS: Abnormal karyotype results were reported in 224 of 1488 (15%) women with high-risk pregnancies having invasive diagnostic testing. NIPT potentially would have identified 85%. The 33 abnormalities unidentifiable by NIPT were triploidies (n = 7, 21%), balanced (n = 8, 24%) and unbalanced rearrangements (n = 10, 30%) and level III mosaicisms (n = 8, 24%). For conditions not identifiable by NIPT, fetal sonographic appearance was likely to have led to invasive testing for 10 of 17 (59%) pathogenic abnormalities. If a policy was adopted recommending invasive testing for FTS risk >1:50 and/or ultrasound detected abnormality, the residual risk of an unidentified pathogenic chromosomal abnormality in those without a diagnosis would have been 0.33% (95% CI 0.01-0.65%). CONCLUSIONS: A screening model with NIPT as a second-tier for high-risk pregnancies would be unlikely to have changed the outcome for the majority of pregnancies. Optimising the diagnosis of rare pathogenic abnormalities requires clear indicators for invasive testing over NIPT.