A survey of current clinical practice of chorionic villus sampling.

OBJECTIVE: The number of invasive procedures (chorionic villus sampling (CVS) or amniocentesis) for fetal testing is decreasing because of the availability of non-invasive prenatal test (NIPT) leading to a centralisation of prenatal diagnostic services to accredited fetal medicine centres. A new survey was conducted 10 years after the previous one to update the current clinical practice among clinicians who regularly perform CVS. METHOD: Consultants from 32 centres in the United Kingdom were invited to take part in an online survey evaluating: The total number of CVS procedures carried out in the unit in a typical week, the preferred route (transabdominal [TA] vs transcervical [TC]), technique (use of local anaesthetic [LA] and needle technique). RESULTS: Response rate was 96.9%; TA was the preferred route (96.8%) in all centres except one. Single-needle technique is used exclusively in half the centres (51.6%). LA is used by most operators (90.3%) before the procedure. Three centres did not routinely use LA for CVS. CONCLUSIONS: Operators across the United Kingdom almost exclusively use the TA route for CVS with single-needle technique in 51.6% of cases. The use of LA prior to CVS is a very common practice in the United Kingdom.

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.

Cytogenetic highlights and transitions.

Medical cytogenetics, genetic diagnostics, and medical genetics had their origins in the late 1950's, as evaluation of human chromosomes became possible, and it was recognized that chromosomal abnormalities could cause a variety of clinical phenotypes. Dr. Laird Jackson began his medical and scientific career just as this field was emerging and he was an early adopter and driver of several key trends in the development of these fields, notably in the area of prenatal diagnostics. Laird's greatest impact was in his work to demonstrate the clinical utility of amniocentesis, chorionic villous sampling, and chromosomal microarray analysis for prenatal diagnosis. © 2016 Wiley Periodicals, Inc.

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..

The impact of utilization of early aneuploidy screening on amniocenteses available for training in obstetrics and fetal medicine.

OBJECTIVE: First-trimester aneuploidy screening has high detection rates and low false-positive rates. Their use as well as the implementation of non-invasive prenatal testing may affect specialty training in prenatal diagnosis procedures. STUDY DESIGN: Descriptive study of first-trimester aneuploidy screening and amniocentesis in an obstetric training program. Screening methods were tracked from their introduction in 2004 through 2011. The volume of amniocentesis procedures from 2000 to 2011 was evaluated. RESULTS: First-trimester screening tests increased from 283 to 1225 between 2005 and 2011, whereas genetic amniocenteses declined from 460 to 168 during the same period. The percent of older women who chose a first-trimester screen test rose from 12.7% to 44.2% CONCLUSION: First-trimester screening options reduce genetic amniocenteses available for training. Fetal medicine and general obstetrics training programs need to evaluate their clinical experience and determine whether simulation training methods are needed for education.

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%.

Fear of pregnancy loss and fetal karyotyping: a place for third-trimester amniocentesis?

OBJECTIVE: To assess the complications of third-trimester amniocentesis for fetal karyotyping in women unwilling to accept the fetal loss risks of second-trimester amniocentesis. METHODS: Retrospective study of singleton pregnancies that underwent a third-trimester amniocentesis for karyotyping. 150 complete charts between 1998 and 2005 were reviewed. RESULTS: The indications were: isolated abnormal second-trimester biochemical markers (n = 57), isolated maternal age >38 years (n = 46), integrated risk (maternal age, first-trimester nuchal translucency, second-trimester maternal serum markers) >1/250 (n = 22), history of chromosomal abnormality (n = 17) or maternal choice (n = 8). The median maternal age and gestational age at sampling were: 40 years (23-48), 32.4 weeks (29.7-37.1). Median interval between amniocentesis, definitive result of amniocentesis, and delivery were 14 days (7-42), and 49 days (10-67) respectively. There were no abnormal karyotypes and no termination of pregnancy. Six women out of 150 (4%) had spontaneous labor before 36 weeks (2% after 36 weeks). CONCLUSION: The risk of spontaneous labor before 37 weeks after late amniocentesis is 4% (2% before 36 weeks). This technique provides a late but safe reassurance to women who are unwilling to accept the risks of earlier fetal karyotyping. This is of interest to countries such as France where legislation permits late termination of pregnancy.

Screening advances and diagnostic choice: the problem of residual risk.

OBJECTIVE: Over the past decade some authorities have suggested that advanced screening methodologies obviate the need for more invasive, diagnostic procedures. Data on Down syndrome (DS) births for Colorado from 1989 to 2005 were used to examine the implications of a decreasing use of amniocentesis. METHODS: Publicly available, State of Colorado Department of Public Health data on DS birth rates for women were compared to amniocentesis use at Colorado's largest prenatal diagnostic center. Longitudinal changes on DS birth rates by maternal age (>35 and <35), and utilization of amniocentesis. RESULTS: In Colorado, from 1989 to 2005, the rate for DS births for women 35+ rose considerably, while <35, rates remained stable (Cochran-Armitage test, p < 0.001). An autocorrelation-corrected test yielded a significant negative relationship between amniocentesis use (in 1,000 s) and AMA DS rates (b = -11.30; p < 0.006; DW = 1.55). Confounding explanations involving sampling problems, socio-demographic factors, political conservatism and prevention orientation do not appear to account for these results. CONCLUSIONS: Replacement of definitive diagnosis with screening tests must be implemented with caution, particularly when using technologies with wide individual operator-dependent variability. Screening paradigms when performed with accuracy can markedly improve assessment of risks, but caution must be used in presenting negative screening results to women who still have a relatively high residual risk after a negative screen, and more generally in the displacement of technologies that provide definitive answers.

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.

Multiple assessment techniques evaluate antepartum fetal risks.

As technology has advanced, the field of antepartum fetal evaluation has grown. As reviewed here, a variety of options are available for use in the complicated pregnancy, including application of fetal heart rate monitoring techniques, noninvasive assessment of amniotic fluid volume, sonographic evaluation of fetal behavior, and Doppler assessment of fetal blood flow. It remains unclear which test is the best for any particular situation. The NST is the simplest test to perform but has a higher false-positive rate than the biophysical profile or the CST. These two tests also appear to demonstrate superior sensitivity, at the expense of increased testing time and cost. The application of vibroacoustic stimulation improves the specificity of the NST, while the addition of a sonographic assessment of amniotic fluid volume increases sensitivity and creates an acceptable alternative as a primary test. The limited biophysical profile, with the NST component initially omitted, provides some savings in time and cost without apparent loss of sensitivity or specificity when compared with the full profile. Ultimately, while one particular technique of fetal assessment may never prove to be the best, certain techniques may have advantages over others in particular clinical situations. Umbilical artery Doppler velocimetry appears to be a useful adjunct to other forms of testing, especially in the pregnancy at risk for intrauterine growth restriction and pre-eclampsia. Recent data have shown the biophysical profile predicts the onset of amnionitis in the setting of preterm premature rupture of membranes (PROM). The sonographic assessment of amniotic fluid volume is particularly important in the serial evaluation of the pregnancy complicated by fetal growth restriction. As new technology leads to innovative forms of testing, it is expected that these new tests of fetal status will similarly add to, rather than replace, the existing items in our armamentarium.