Trends in invasive prenatal diagnostic testing at a single institution.

OBJECTIVE: As diagnostic methodologies evolve, we sought to determine whether invasive testing rates would decline, whether there would be a shift in indications for invasive testing, and whether the diagnostic yield would increase. METHODS: We conducted a retrospective, observational study from 2006 through 2015. We quantified the number of invasive procedures per year and examined what percentage of these procedures yielded abnormal results. We also examined the indications for testing and determined the trend of these indications during the study period. RESULTS: The number of amniocenteses showed a steady decline (P < .05). The number of CVS procedures has increased and was recently equivalent to amniocentesis. The percentage of abnormal results steadily increased from 11.4% to 27.0% (P < .001). The abnormal aneuploidy screening indication remained constant over time. Advanced maternal age (AMA) as the sole indication substantially declined from 42.3% to 15.52% (P < .001). Testing for a known single gene disorder steadily increased from 3.0% to 9.20% (P = .018). CONCLUSION: Our study showed a significant decline in the number of amniocenteses, a steady increase in the percentage of abnormal results from invasive testing, and a decline in AMA as the sole indication for invasive testing.

Declining invasive prenatal diagnostic procedures: A comparison of tertiary hospital and national data from 2012 to 2015.

BACKGROUND: 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 sampling (CVS), creating new implications for specialist training. OBJECTIVE: To compare the annual figures on amniocenteses and CVS in a tertiary hospital with national population-based trends between 2012 and 2015. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Procedure-Related Fetal Loss following Chorionic Villus Sampling after First-Trimester Aneuploidy Screening.

OBJECTIVE: The aim was to determine the institutional procedure-related fetal loss rate after chorionic villus sampling (CVS) and the factors which may identify pregnancies at increased risk of having a procedure-related loss. MATERIALS AND METHODS: Pregnancy outcomes were retrieved of all women having a singleton pregnancy and undergoing a CVS procedure between 2004 and 2013 at a university hospital in Hong Kong. The incidence of procedure-related fetal loss due to unintended miscarriages adjusted for the background loss incidence of miscarriages was determined. Multivariate regression was performed to examine the factors contributing to an unintended fetal loss and miscarriage. RESULTS: CVS was performed on 1,906 fetuses. The procedure-related fetal loss rate was 0.17% (95% CI -0.2 to 0.7). After multivariate analysis, a decreased plasma protein-A (PAPP-A) multiple of the median (OR 0.27; 95% CI 0.08-0.98, p = 0.046) was significantly associated with miscarriage in women who did not undergo a CVS. Patient-specific prediction of spontaneous abortion in women who did not undergo CVS was not statistically significant (AUC 0.56; 95% CI 0.49-0.6, p = 0.14). CONCLUSIONS: The CVS-related fetal loss rate adjusted for background loss was 0.17%. Pregnancies with reduced PAPP-A carry an increased risk of miscarriage irrespective of whether they had undergone an invasive procedure.

Changing indications for invasive testing in an era of improved screening.

Prenatal diagnostic testing is available for a growing number of disorders. The goal of prenatal diagnosis was initially focused on the identification of Down syndrome in women aged 35 years and older, but invasive prenatal genetic techniques can now detect a far broader array of conditions. The risks of invasive procedures have also decreased over time. Advances in genomic medicine allow testing for smaller but significant chromosomal abnormalities known as copy number variants, in addition to major aneuploidies and structural rearrangements. Molecular DNA techniques can detect many single-gene conditions. In the future, it is likely that whole-exome and whole-genome sequencing will be applied to prenatal genetic testing to allow identification of yet more genetic disorders. With advances in technology, the indications for testing have likewise evolved far beyond recommendations based solely on maternal age to include a more patient-centered view of the goals of prenatal testing.

Genetics: update on prenatal screening and diagnosis.

There have been tremendous advances in the ability to screen for the "odds" of having a genetic disorder (both mendelian and chromosomal). With microarray analyses on fetal tissue now showing a minimum risk for any pregnancy being at least 1 in 150 and ultimately greater than 1%, it is thought that all patients, regardless of age, should be offered chorionic villus sampling/amniocentesis and microarray analysis. As sequencing techniques replace other laboratory methods, the only question will be whether these tests are performed on villi, amniotic fluid cells, or maternal blood.

Uptake of Noninvasive Prenatal Testing in Chinese Women following Positive Down Syndrome Screening.

OBJECTIVES: To investigate how the introduction of noninvasive prenatal testing (NIPT) influenced women's testing choices following a positive Down syndrome screening. METHODS: A retrospective study was conducted to compare differences in the uptake rates of invasive prenatal diagnosis (IPD) or no testing in one public hospital 1 year before (pre-NIPT) and 1 and 2 years after the introduction of NIPT in private in August 2011 using descriptive analysis and a χ² test. Conventional screening was funded publicly, but NIPT was not. Multivariable binary logistic regression was used to determine factors affecting choices. RESULTS: In pre-NIPT and in years 1 and 2 after the introduction of NIPT, 306, 362 and 401 women who screened positive were seen, respectively. In year 1 and year 2, 12.6 and 26.7% of them underwent NIPT while IPD was decreased by 16.3 and 25.6%, respectively (p < 0.001). Both chorionic villus sampling and amniocentesis decreased in year 1, but only the former in year 2. However, the rate of declining further testing was similar before and after NIPT (p = 0.213). In multivariable analysis, first trimester screening, nulliparity and working women were significant predictors of accepting NIPT, while only nulliparity was a predictor of declining IPD (OR = 0.61). CONCLUSIONS: Introduction of NIPT resulted in a significant decrease in IPD for 2 consecutive years..

Trends in the utilization of invasive prenatal diagnosis in The Netherlands during 2000-2009.

OBJECTIVE: To analyze trends in the number and type of invasive procedure, reasons for referral, maternal age and chromosomal abnormalities over a 10-year period and correlate the trends to changes in the national prenatal screening policy. METHODS: Data from 10 706 invasive prenatal procedures yielding a full karyotype, performed between 2000 and 2009 were extracted from the cytogenetic database in the central region of The Netherlands. Trends were analyzed. RESULTS: Over a 10-year period, the number of invasive procedures halved and the percentage of chromosomal abnormalities detected, increased from 5.5 to 9.4%. After 2007, however, 5.7% of karyotypes in women over 36 years were found to be abnormal, versus 18.1% in women below 36 years. In 2009, 71.5% of women over 36 are still referred for invasive prenatal diagnosis on the indication advanced maternal age. CONCLUSIONS: Changes in prenatal screening policy significantly increased referral after screening and improved the efficacy of invasive prenatal diagnosis. We show the continuing effect of the different policies applied in the past to women below and above the age of 36. To further improve efficacy of invasive prenatal diagnosis, first trimester combination screening should be actively offered to women of all ages.

Trends in prenatal screening and diagnostic testing among women referred for advanced maternal age.

OBJECTIVE: We evaluated the trends in uptake of amniocentesis and chorionic villi sampling (CVS) for prenatal diagnosis compared with uptake of first and second trimester prenatal serum screening for Down syndrome among patients referred for genetic counseling for advanced maternal age (AMA). METHODS: Patients referred for AMA genetic counseling from 2001 through 2008 were informed of both prenatal serum screening and invasive diagnostic testing options. Testing offered and testing decisions were entered in a computer database and uptake rates calculated for each year with trends compared using logistic regression analysis. RESULTS: From 2001 through 2007, we observed a decline in amniocentesis and CVS uptake (p = 0.0001). This trend reversed in 2008 for both invasive procedures (p = 0.0001). Uptake of prenatal serum screening increased over the study period with uptake of first trimester screening increasing 1.7 fold in 2008. CONCLUSION: Improved prenatal screening tests and increased availability of screening for AMA patients has led to a steady decline in uptake of invasive testing from 2001 through 2007. This trend reversed from 2007 through 2008. Possible reasons for this reversal are discussed.

Down syndrome screening in the United States in 2001 and 2007: a survey of maternal-fetal medicine specialists.

OBJECTIVE: The purpose of this study was to determine changes in screening and performance of invasive diagnostic procedures for Down syndrome between 2001 and 2007. STUDY DESIGN: The Society for Maternal-Fetal Medicine members completed a survey in 2007 regarding screening tests and diagnostic procedures for Down syndrome. With the use of descriptive statistics, the chi(2) test, and the Student t test, responses from 2007 were compared with responses from a similar 2001 survey. RESULTS: Performance of first-trimester screening more than doubled from 2001-2007 (43.1% in 2001, 97.3% in 2007; P < .0001). Between 2001 and 2007, the use of the quad screen increased 10-fold (8.5% in 2001, 85.6% in 2007; P < .0001). There was an estimated 20% decrease in invasive diagnostic procedures that were performed in risk-positive women (53.7% in 2001, 34.2% in 2007; P < .0001). In 2007, the average fetal loss rates that were quoted by maternal-fetal medicine specialists after chorionic villous sampling was 1:160 and after an amniocentesis was 1:493. CONCLUSION: Down syndrome screening evolved from 2001-2007, with an increasing emphasis on first-trimester screening. With more efficacious screening, the number of invasive procedures has declined.

Invasive prenatal diagnostic practice in Denmark 1996 to 2006.

The Danish National Board of Health recommended in 2004 routine ultrasound scanning in week 12 with nuchal translucency measurement, combined with the double test to all pregnant women. Those who were found to have a risk of trisomy 21 higher than 1:300 were offered amniocentesis or chorionic villus sampling (CVS). The total number of pregnancies in Denmark with an invasive prenatal procedure decreased from 6,929 in 1996 to 3,103 in 2006, the percentage of CVS increased from 45 to 69%, and the percentage of women below 35 years among those undergoing invasive procedures increased from 38 to 52%. The mean gestational age at which the procedures were done increased--for CVS from week 11 to 13, and for amniocentesis from week 16 to 17. We thus achieved to more than double the offer of prenatal screening and at the same time reduce the number of invasive procedures by 55%.

[Invasive prenatal diagnosis in the Netherlands, 1991-2000: number of procedures, indications and abnormal results detected]. / Invasieve prenatale diagnostiek in Nederland, 1991-2000: aantallen ingrepen, indicaties, en gevonden afwijkingen.

OBJECTIVE: To provide an overview of invasive prenatal diagnosis in the Netherlands during the period 1991-2000 and to analyse potential trends. DESIGN: Retrospective. METHOD: The annual results from all 13 Dutch centres for invasive prenatal diagnosis over the period 1991-2000 were combined and described, with particular emphasis on indications, number and type of invasive procedures, and number and type of abnormal results. RESULTS: The percentage of pregnancies in which invasive prenatal diagnostics were carried out increased from 5% in 1991 to 6% in 1996 and remained at the same level until 2000. 'Maternal age' was the main reason for prenatal testing (69.2-73.3% of procedures). However, the number of pregnant women aged 36 or over increased by 69.9%. An abnormal result was found in an average of 4.7% of procedures, rising from 3.6% in 1991 to 5.4% in 2000. In 70.8% of cases with abnormal results, the pregnancy was terminated. Important trends were the relative decrease of cordocentesis (-82%) and chorionic villi biopsy (-18%) in favour of amniocentesis (+48%), and a strong decrease in the number of amniocentesis procedures on indication of increased risk of neural tube defect. CONCLUSION: The total number of invasive prenatal diagnostic procedures remained stable. However, there was an important decrease in the percentage of pregnant women aged 36 or over who underwent invasive prenatal diagnosis without previous prenatal screening.

Trends in cytogenetic prenatal diagnosis in the UK: results from UKNEQAS external audit, 1987-1998.

The aim of this audit was to evaluate trends in mean reporting time, culture success rate and abnormality rate for conventional cytogenetic prenatal diagnoses for amniotic fluid samples (AFS) and chorionic villus samples (CVS) in the UK. Anonymized data in the form of retrospective external audits were obtained from UKNEQAS in Clinical Cytogenetics annual reports, for AFS (1987-1997/98) and CVS (1988-1997/98). UK laboratories providing a prenatal service by referral criteria applicable at local level participated in the scheme. Over the period the number of AFS processed per annum increased from 28 639 to 36 817 (29 per cent) and for CVS from 2294 to 7918 (245 per cent). CVS made up 17.6 per cent of the total sample numbers in 1997/98 compared with 7.4 per cent in 1988. Reporting times and culture success rates have improved, notably overall reporting time means have fallen from 20.2 to 13.8 days for AFS and 21.3 to 14.5 days for CVS. Data submitted by individual laboratories suggest that further reductions in mean reporting times for both sample types are feasible. Such a potential improvement, if achieved by all laboratories, may question the value of a supplementary FISH or PCR-based 'rapid' aneuploidy screening test prior to karyotyping.

Chorionic villus sampling: transabdominal versus transcervical approach in more than 4000 cases.

OBJECTIVE: To address the evolving trends in the choice of transabdominal or transcervical chorionic villus sampling (CVS) at a teaching hospital and to evaluate the influence of gestational age on the approach chosen. METHODS: We analyzed our CVS data base, which contained information from 1986-1991. The proportions of transabdominal and transcervical CVS were tabulated for each year. In addition, the distribution of the CVS approaches over the various gestational ages was examined. RESULTS: During the study period, 4290 CVS procedures were performed. The rate of the transabdominal technique was stable at about 15% per year except for the first 2 years, when essentially all procedures were transcervical. Use of transabdominal CVS increased with advancing gestational age, from 3.6% at less than 10 weeks' gestation to 97.6% at greater than 14 weeks (chi 2 = 120, P less than .001; r = 0.791). CONCLUSIONS: The choice between the transabdominal and transcervical approach to CVS largely reflects the route emphasized during the physician's training. When choice is based strictly on technical limitations due to placental position, the overall transabdominal CVS rate is approximately 15%. A shift from transcervical to transabdominal CVS occurs with increasing gestational age as the placenta gains bulk and moves away from the cervix. After 14 weeks' gestation, most procedures are performed transabdominally.