Aneuploidy Screening Test Research Articles

Committee Opinion No. 640

Noninvasive prenatal screening that uses cell-free DNA from the plasma of pregnant women offers tremendous potential as a screening method for fetal aneuploidy. A number of laboratories have validated different techniques for the use of cell-free DNA as a screening test for fetal aneuploidy. All tests have a high sensitivity and specificity for trisomy 18 and trisomy 21, regardless of which molecular technique is used. Women whose results are not reported, indeterminate, or uninterpretable (a “no call” test result) from cell-free DNA screening should receive further genetic counseling and be offered comprehensive ultrasound evaluation and diagnostic testing because of an increased risk of aneuploidy. Patients should be counseled that cell-free DNA screening does not replace the precision obtained with diagnostic tests, such as chorionic villus sampling or amniocentesis and, therefore, is limited in its ability to identify all chromosome abnormalities. Cell-free DNA screening does not assess risk of fetal anomalies such as neural tube defects or ventral wall defects. Patients who are undergoing cell-free DNA screening should be offered maternal serum alpha-fetoprotein screening or ultrasound evaluation for risk assessment. The cell-free DNA screening test should not be considered in isolation from other clinical findings and test results. Management decisions, including termination of the pregnancy, should not be based on the results of the cell-free DNA screening alone. Patients should be counseled that a negative cell-free DNA test result does not ensure an unaffected pregnancy. Given the performance of conventional screening methods, the limitations of cell-free DNA screening performance, and the limited data on cost-effectiveness in the low-risk obstetric population, conventional screening methods remain the most appropriate choice for first-line screening for most women in the general obstetric population.

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.

Noninvasive Prenatal Screening for Genetic Diseases Using Massively Parallel Sequencing of Maternal Plasma DNA.

The identification of cell-free fetal DNA (cffDNA) in maternal plasma in 1997 heralded the most significant change in obstetric care for decades, with the advent of safer screening and diagnosis based on analysis of maternal blood. Here, we describe how the technological advances offered by next-generation sequencing have allowed for the development of a highly sensitive screening test for aneuploidies as well as definitive prenatal molecular diagnosis for some monogenic disorders.

Does diurnal variation affect the first trimester fetal aneuploidy screening test biochemical parameters of fetuses with normal nuchal translucency?

Objective: The purpose of this study was to investigate the effect of diurnal variation on biochemical results of first trimester aneuploidy screening test.Methods: A total of 2725 singleton pregnant female, who had normal fetal nuchal translucency (NT) thickness, were included in the study during this period. Individuals were divided into two groups according to the sampling time (morning group: 09:00–11:00 am and afternoon group: 02:00–04:00 pm). Hormonal parameters (free-beta human chorionic gonadotropin [free β-hCG] and pregnancy-associated plasma protein-A [PAPP-A] multiples of median [MoM] levels) of first trimester (11+0–13+6 weeks) combined aneuploidy screening test were compared between morning and afternoon groups.Results: PAPP-A MoM levels were significantly lower in the afternoon group when compared to the morning group (p = 0.001), whereas free β-hCG MoM levels were similar in the both groups (p = 0.392). Rate of high risk for Down syndrome (Combine risk >1/300) and amniocentesis ratio were found higher in the afternoon group than morning group, but there were no difference between groups for the number of fetuses with Down syndrome.Conclusion: Receiving the venous blood sample for first trimester aneuploidy screening test in the afternoon causes low PAPP-A MoM levels.

Non‐invasive prenatal testing: the new era in reproductive medicine

[Extract] Important advances in screening for genetic abnormalities have major ethical implications. In Australia, it is routine practice to offer pregnant women screening for fetal chromosomal and structural abnormalities, and, if serious anomalies are diagnosed, the option of terminating the pregnancy. Screening for chromosomal abnormalities commenced in the 1970s and was initially restricted to women whose pregnancies were considered to be of increased risk because of an obstetric history of aneuploidy or advanced maternal age. Over the past five decades, prenatal chromosome screening has been expanded to encompass the entire obstetric population. However, the commonly used aneuploidy screening tests are dogged by high false-positive rates, typically 4%–5%.1 Confirmation of an increased screening risk for aneuploidy involves diagnostic tests such as amniocentesis or chorionic villus sampling, each associated with low but definite risks of pregnancy loss.

Committee Opinion No. 640

Noninvasive prenatal screening that uses cell-free DNA from the plasma of pregnant women offers tremendous potential as a screening method for fetal aneuploidy. A number of laboratories have validated different techniques for the use of cell-free DNA as a screening test for fetal aneuploidy. All tests have a high sensitivity and specificity for trisomy 18 and trisomy 21, regardless of which molecular technique is used. Women whose results are not reported, indeterminate, or uninterpretable (a "no call" test result) from cell-free DNA screening should receive further genetic counseling and be offered comprehensive ultrasound evaluation and diagnostic testing because of an increased risk of aneuploidy. Patients should be counseled that cell-free DNA screening does not replace the precision obtained with diagnostic tests, such as chorionic villus sampling or amniocentesis and, therefore, is limited in its ability to identify all chromosome abnormalities. Cell-free DNA screening does not assess risk of fetal anomalies such as neural tube defects or ventral wall defects. Patients who are undergoing cell-free DNA screening should be offered maternal serum alpha-fetoprotein screening or ultrasound evaluation for risk assessment. The cell-free DNA screening test should not be considered in isolation from other clinical findings and test results. Management decisions, including termination of the pregnancy, should not be based on the results of the cell-free DNA screening alone. Patients should be counseled that a negative cell-free DNA test result does not ensure an unaffected pregnancy. Given the performance of conventional screening methods, the limitations of cell-free DNA screening performance, and the limited data on cost-effectiveness in the low-risk obstetric population, conventional screening methods remain the most appropriate choice for first-line screening for most women in the general obstetric population.

An alternative perspective on prenatal invasive techniques: Comparison of pre-procedural anxiety and depression scores for patients undergoing chorion villus sampling and amniocentesis

Objective:To compare the pre-procedural anxiety and depression levels of patients undergoing chorion villus sampling (CVS) and amniocentesis (AC).Methods:Patients referred to our department for fetal karyotype analysis with a positive first or second trimester screening test for aneuploidy between January 2013 to June 2015 were included. CVS and AC procedures were performed in patients with gestation periods of between 11-14 and 16-20 weeks, respectively. Anxiety was evaluated using the Spielberger State-Trait Anxiety Inventory (STAI), and depression was assessed using the Beck Depression Inventory II (BDI-II).Results:A total of 1,400 patients were included. Compared to first trimester controls, patients undergoing CVS had significantly higher STAI-state and BDI-II results. Likewise, patients undergoing AC had higher STAI-state and BDI-II scores than controls in the second trimester. In terms of STAI-trait results, no difference was found between the groups. Our results also showed that, compared to AC group, patients undergoing CVS had similar STAI-state, STAI-trait and but higher BDI-II scores.Conclusion:We conclude that evaluating the stress and depression levels of these patients should be one of the routine procedures in pregnancy follow-up.

The effect of inherited thrombophilia on second trimester combined aneuploidy screening test markers.

To determine whether inherited thrombophilia affects components of second trimester combined aneuploidy screening test. A case-control study was performed between 1 December 2010 and 1 February 2012, at a tertiary referral hospital. Singleton pregnancies with inherited thrombophilia that underwent second trimester (16-19(+6) week) combined aneuploidy screening test were included in the study. Maternal serum alfa fetoprotein, unconjugated estriol, human chorionic gonadotropin levels and multiple of median (MoM) levels were compared between the study group and controls. Within the study period, 18,943 women with singleton pregnancies had a combined second trimester aneuploidy screening test at our institution. Among these, 26 women met the criteria of thrombophilia. A control group that comprised 275 women with similar gestational age was generated, using a 1:1 ratio. Unconjugated estriol MoM levels were significantly lower in women with inherited thrombophilia (p=0.02). But there was no statistically significant difference for unconjugated estriol levels, human chorionic gonadotropin, alfa fetoprotein and their MoM levels. Our study suggest that in patients with hereditary thrombophilia a new correction factor should be used, when calculating unconjugated estriol MoM value, which is one of the markers of second trimester aneuploidy screening test.

The effects of isolated single umbilical artery on first and second trimester aneuploidy screening test parameters

Objective: Reliability of first and second trimester screening tests largely depends on accurate estimation of maternal serum marker values. Reduced reliability could lead redundant invasive tests or misdiagnosis. Adjustments of serum marker values for confounding factors like insulin-dependent diabetes, maternal weight or maternal rhesus status are essential. We aimed to investigate whether isolated single umbilical artery alters first and second trimester test parameters or not.Methods: Routine detailed obstetric ultrasonographies performed were retrospectively screened for this study. Among spontaneously conceived singleton pregnancies, women who were found to have single umbilical artery without any additional structural anomalies or aneuploidies were selected.First and second trimester screening test results were accessible for 98 and 102 of the cases with isolated single umbilical artery, respectively.Results: Among first trimester screening test parameters, PAPP-A (pregnancy-associated plasma protein A) MoMs were found significantly higher in isolated single umbilical artery group. AFP MoMs were found significantly elevated in isolated single umbilical artery group in second trimester quadruple tests.Conclusion: Existence of single umbilical artery could alter the estimation of MoM values of maternal serum markers. Reliability of prenatal screening tests could be improved by adjusting these parameters in accordance with isolated single umbilical artery.

Role of the second‐trimester ‘genetic sonogram’ for Down syndrome screen in the era of first‐trimester screening and noninvasive prenatal testing

Ultrasonography for the screening of Down syndrome was first introduced about 25 years ago. Different combinations of markers detectable at second-trimester ultrasonography have been proposed under the banner of 'genetic sonogram'. In recent years, several developments in first-trimester screening and the recent introduction of noninvasive prenatal testing for aneuploidy screening have had important implications for the prevalence of these conditions in the second-trimester and the screening performance of a genetic sonogram. Several second-trimester sonographic markers for Down syndrome have been reported; meta-analysis has shown that the most powerful predictors are mild ventriculomegaly, increased nuchal fold, hyperechoic bowel, and absent or hypoplastic nasal bone. Whereas use of individual markers should be discouraged and scoring systems of multiple markers are now obsolete, use of combined likelihood ratio and logistic regression analysis formulae provides better accuracy. However, there is significant heterogeneity in results among studies. Despite such limitations, the genetic sonogram will continue to have a place in prenatal screening, particularly in twin and higher-order multiple pregnancies, in countries with limited access to the most recent genetic screening tests, in cases with borderline results at maternal serum screening tests, and as noninvasive supplementary test for high-risk women reluctant to undergo invasive diagnostic testing.

Noninvasive prenatal testing.

Noninvasive prenatal testing (NIPT) refers to recently developed genetic tests of the maternal serum that allow higher detection rates of trisomy 21 and other chromosomal aneuploidies in high-risk pregnancies. Noninvasive prenatal test analyzes cell-free DNA (cfDNA) in the maternal serum. Approximately 3% to 15% of cfDNA in the maternal blood is of fetal origin. Analysis of cfDNA can help identify fetuses affected with trisomy 21 and several other fetal aneuploidies. Testing can be performed after 9 to 10 weeks' gestation and has a higher sensitivity and specificity for trisomy 21 than other aneuploidy screening test. Noninvasive prenatal test has been studied and validated in singleton pregnancies at risk for trisomy 21 secondary to advanced maternal age, an abnormal serum screen, personal or family history of aneuploidy, or abnormal ultrasound findings, if these are suggestive of trisomy 13, 18, or 21. The utilization of NIPT for genetic screening has increased rapidly since introduction of the first clinical test in October 2011. Currently, there are limitations to NIPT including the possibility of test failure (2.6%-5.4%) and the focus on only the common trisomies. Noninvasive prenatal test is a screening test, and both false-positive (0.2%-1%) and false-negative results can occur. As the technology for NIPT is further evaluated, this test is likely to be increasingly used for prenatal screening. This review provides the obstetric clinician with an update of the current issues concerning NIPT.

BACs-on-Beads technology: a reliable test for rapid detection of aneuploidies and microdeletions in prenatal diagnosis.

The risk of fetal aneuploidies is usually estimated based on high resolution ultrasound combined with biochemical determination of criterion in maternal blood, with invasive procedures offered to the population at risk. The purpose of this study was to investigate the effectiveness of a new rapid aneuploidy screening test on amniotic fluid (AF) or chorionic villus (CV) samples based on BACs-on-Beads (BoBs) technology and to compare the results with classical karyotyping by Giemsa banding (G-banding) of cultured cells in metaphase as the gold standard technique. The prenatal-BoBs kit was used to study aneuploidies involving chromosomes 13, 18, 21, X, and Y as well as nine microdeletion syndromes in 321 AF and 43 CV samples. G-banding of metaphase cultured cells was performed concomitantly for all prenatal samples. A microarray-based comparative genomic hybridization (aCGH) was also carried out in a subset of samples. Prenatal-BoBs results were widely confirmed by classical karyotyping. Only six karyotype findings were not identified by Prenatal-BoBs, all of them due to the known limitations of the technique. In summary, the BACs-on-Beads technology was an accurate, robust, and efficient method for the rapid diagnosis of common aneuploidies and microdeletion syndromes in prenatal samples.

Detection of Fetal Aneuploidy Using Cell-Free DNA

Cell-free fetal DNA (cffDNA) is a highly accurate screening test for major aneuploidies. Despite high detection rates and low false-positive rates compared to current screening methods, cffDNA testing is approved for use in only the high-risk population and is expensive for low-risk women because of a lack of insurance coverage. As the technology improves and research demonstrates the efficacy of cffDNA testing in the general population, insurance coverage of this test likely will be extended to all women. At that time, cffDNA testing in most cases will replace current screening methods. Furthermore, cffDNA testing may become a routine diagnostic test, effectively rendering most invasive diagnostic procedures obsolete.

Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies

Can independent predictors of pregnancy-associated plasma protein-A (PAPP-A) levels be identified in a group of women who conceived following IVF/ICSI? The significantly decreased PAPP-A level in IVF and ICSI pregnancies compared with non-IVF/ICSI pregnancies was correlated strongly with the serum estradiol (E2) level at ovulation triggering. The first trimester prenatal combined screening test for fetal aneuploidies in pregnancies conceived following assisted reproduction techniques (ART) is complicated by an alteration of the maternal biomarkers free β-hCG and PAPP-A, causing a higher false-positive rate compared with pregnancies which are conceived naturally. The use of controlled ovarian stimulation prior to IVF/ICSI is suggested to be the principle reason for these alterations of biomarkers in ART pregnancies. Between January 2010 and December 2011, 1474 women who conceived naturally and 374 women who conceived following IVF (n = 89), ICSI (n = 204) or intrauterine insemination (IUI, n = 81) were included in this retrospective study. Only singleton pregnancies were eligible for this study. For all women, serum analysis was performed in the same clinical laboratory. Measurement of nuchal translucency (NT) thickness was performed by four physicians belonging to the same infertility centre. First-trimester combined screening test of aneuploidy parameters (maternal age, PAPP-A and free β-hCG, NT thickness) were compared between non-ART and ART (IVF, ICSI and IUI) singleton pregnancies. Next, a minimal threshold E2 level at ovulation triggering was suggested for IVF/ICSI pregnancies above which the PAPP-A levels were significantly decreased compared with non-ART pregnancies. Finally, a multivariate analysis was performed to reveal independent predictors of PAPP-A level in IVF/ICSI pregnancies. We showed a decrease of the multiple of the median (MoM) PAPP-A level in IVF and ICSI singleton pregnancies compared with non-ART singleton pregnancies (P < 0.001), with MoM values of 0.74 (0.16-3.16) and 0.81 (0.12-4.61) versus 0.98 (0.14-5.76), respectively. Analysis of variance of the overall model was highly significant (Fisher test 3.76, P = 0.01), indicating that the model explains a significant portion of the variation in the data. No difference in PAPP-A level was found between non-ART and IUI pregnancies. The free β-hCG level and NT thickness did not differ between ART and non-ART pregnancies. PAPP-A levels in IVF and ICSI pregnancies were strongly correlated with the E2 level at ovulation triggering. We showed by multivariate analysis that an E2 cut-off level of 1300 pg/ml at the time of ovulation could predict a significantly lower PAPP-A level at first trimester combined screening (β -0.239 ± 0.088, P < 0.005). The measures of biochemical markers can differ between laboratories and with the used equipment; therefore, extrapolation of the E2 cut-off level to other infertility centres should be undertaken with caution. One should be careful when using correction factors for ART patients undergoing the first trimester combined screening test. The proposed E2 cut-off level may help to identify a subgroup of women within the population of ART patients for whom use of a correction factor is justified. None.

The impact of inherited thrombophilia on first trimester combined aneuploidy screening test parameters

Objective: To determine whether inherited thrombophilia affects components of first trimester combined aneuploidy screening test.Method: A case–control study was performed between January 1st and December 31st 2011, at a tertiary referral hospital. Singleton pregnancies with inherited thrombophilia that underwent first trimester (11–13+6 week) combined aneuploidy screening test were included in the study. Pregnancy associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotropin (fbHCG) and fetal nuchal translucency (NT) were compared between the study group and controls.Results: Within the study period, 15 881 women with singleton pregnancies had a combined first trimester aneuploidy screening test at our institution. Among these, 207 women met the inclusion criteria. A control group that comprised 625 women with similar gestational age was generated, using a 1:3 ratio. PAPP-A levels were significantly higher, whereas fbHCG levels and fetal NT measurements were lower in women with inherited thrombophilia (p < 0.001).Conclusion: Our study suggested that PAPP-A, free b-HCG and NT MoM levels display alterations in women with inherited thrombophilia. Future trials are needed to assess the need for readjustment of risk in these patients.

Contribution of “modified genetic sonography” to the combined test as a screening method for chromosomal abnormalities

Objectives: We propose to assess the contribution of “modified genetic sonography” (MGS) to the combined test (CT) as a method of stepwise sequential screening (1st step: CT, 2nd step: MGS) for chromosome abnormalities in the general population of pregnant women. Methods: Prospective study. During a 4 year study period (July 2005–June 2009) 16,548 pregnancies underwent a CT combined with MGS (major malformation and nuchal fold) as a screening method for chromosome abnormalities. We assessed sensitivity and false positive rate (FPR) (95% CI). Results: We offered a chromosome abnormalities screening test to 96.6% of pregnancies (15,995 cases). 14,160 cases are analyzed (1st step: CT, 2nd step: MGS) including 49 chromosome abnormalities and 35 Down’s syndrome (DS). The sensitivity of CT for DS was 77.1% [95% CI, 63.2–91] (27/35) and 77.5% for all chromosome abnormalities [95% CI, 65.8–89.2] (38/49) with a FPR of 4.4% [95% CI, 4.1–4.7]. If MGS was combined with CT, the sensitivity for DS was 91.4% [95% CI, 82.1–99] (32/35) and 93.8% for all chromosome abnormalities [95% CI, 87–99] (46/49) for a FPR of 5.1% [95% CI, 4.7–5.5]. Conclusions: The addition of an MGS to combined first-trimester screening test for aneuploidy improved sensitivity by 14.3% while only increasing the FPR by 0.7%.

Statistical Analysis and Interpretation of Prenatal Diagnostic Imaging Studies, Part 1

Screening and diagnostic testing play fundamental roles in all fields of clinical medicine, with obstetric imaging and prenatal diagnosis being no exceptions. With advances in maternal serum screening and ultrasound technology, much research effort in the field of pre-natal diagnosis has actually been dedicated to the development and refinement of screening tests for fetal aneuploidy and other congenital disorders. This article aims to review the differences between screening and diagnostic tests, describe the accepted criteria for an efficient screening test, and provide an overview of the calculation and interpretation of test performance characteristics in relation to prenatal imaging studies.

Prenatal Screening for and Diagnosis of Aneuploidy in Twin Pregnancies

ObjectiveTo provide a Canadian consensus document with recommendations on prenatal screening for and diagnosis of fetal aneuploidy (e.g., Down syndrome and trisomy 18) in twin pregnancies. OptionsThe process of prenatal screening and diagnosis in twin pregnancies is complex. This document reviews the options available to pregnant women and the challenges specific to screening and diagnosis in a twin pregnancy OutcomesClinicians will be better informed about the accuracy of different screening options in twin pregnancies and about techniques of invasive prenatal diagnosis in twins. EvidencePubMed and Cochrane Database were searched for relevant English and French language articles published between 1985 and 2010, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis, twin gestation). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. Searches were updated on a regular basis and incorporated in the guideline to August 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline. ValuesThe quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Benefits, harms, and costsThere is a need for specific guidelines for prenatal screening and diagnosis in twins These guidelines should assist health care providers in the approach to this aspect of prenatal care of women with twin pregnancies. Summary StatementsFetal nuchal translucency combined with maternal age is an acceptable first trimester screening test for aneuploidies in twin pregnancies. (II-2)First trimester serum screening combined with nuchal translucency may be considered in twin pregnancies It provides some improvement over the performance of screening by nuchal translucency and maternal age by decreasing the false-positive rate. (II-3)Integrated screening with nuchal translucency plus first and second trimester serum screening is an option in twin pregnancies. Further prospective studies are required in this area, since it has not been validated in prospective studies in twins (III)Non-directive counselling is essential when invasive testing is offered (III)When chorionic villus sampling is performed in non-monochorionic multiple pregnancies, a combination of transabdominal and transcervical approaches or a transabdominal only approach appears to provide the best results to minimize the likelihood of sampling errors. (II-2) RecommendationsAll pregnant women in Canada, regardless of age, should be offered, through an informed counselling process, the option of a prenatal screening test for the most common clinically significant fetal aneuploidies. In addition, they should be offered a second trimester ultrasound for dating, assessment of fetal anatomy, and detection of multiples. (I-A)Counselling must be non-directive and must respect a woman's right to accept or decline any or all of the testing or options offered at any point in the process. (III-A)When non-invasive prenatal screening for aneuploidy is available, maternal age alone should not be an indication for invasive prenatal diagnosis in a twin pregnancy. (II-2A) If non-invasive prenatal screening is not available, invasive prenatal diagnosis in twins should be offered to women aged 35 and over. (II-2B)Chorionicity has a major impact on the prenatal screening process and should be determined by ultrasound in the first trimester of all twin pregnancies (II-2A)

Rapid screening for chromosomal aneuploidies using array-MLPA

BackgroundChromosome abnormalities, especially trisomy of chromosome 21, 13, or 18 as well as sex chromosome aneuploidy, are a well-established cause of pregnancy loss. Cultured cell karyotype analysis and FISH have been considered reliable detectors of fetal abnormality. However, results are usually not available for 3-4 days or more. Multiplex ligation-dependent probe amplification (MLPA) has emerged as an alternative rapid technique for detection of chromosome aneuploidies. However, conventional MLPA does not allow for relative quantification of more than 50 different target sequences in one reaction and does not detect mosaic trisomy. A multiplexed MLPA with more sensitive detection would be useful for fetal genetic screening.MethodsWe developed a method of array-based MLPA to rapidly screen for common aneuploidies. We designed 116 universal tag-probes covering chromosomes 13, 18, 21, X, and Y, and 8 control autosomal genes. We performed MLPA and hybridized the products on a 4-well flow-through microarray system. We determined chromosome copy numbers by analyzing the relative signals of the chromosome-specific probes.ResultsIn a blind study of 161 peripheral blood and 12 amniotic fluid samples previously karyotyped, 169 of 173 (97.7%) including all the amniotic fluid samples were correctly identified by array-MLPA. Furthermore, we detected two chromosome X monosomy mosaic cases in which the mosaism rates estimated by array-MLPA were basically consistent with the results from karyotyping. Additionally, we identified five Y chromosome abnormalities in which G-banding could not distinguish their origins for four of the five cases.ConclusionsOur study demonstrates the successful application and strong potential of array-MLPA in clinical diagnosis and prenatal testing for rapid and sensitive chromosomal aneuploidy screening. Furthermore, we have developed a simple and rapid procedure for screening copy numbers on chromosomes 13, 18, 21, X, and Y using array-MLPA.

Risk and uncertainty: Shifting decision making for aneuploidy screening to the first trimester of pregnancy

PurposeThe clinical introduction of first trimester aneuploidy screening uniquely challenges the informed consent process for both patients and providers. This study investigated key aspects of the decision-making process for this new form of prenatal genetic screening. MethodsQualitative data were collected by nine focus groups that comprised women of different reproductive histories (N = 46 participants). Discussions explored themes regarding patient decision making for first trimester aneuploidy screening. Sessions were audio recorded, transcribed, coded, and analyzed to identify themes. ResultsMultiple levels of uncertainty characterize the decision-making process for first trimester aneuploidy screening. Baseline levels of uncertainty existed for participants in the context of an early pregnancy and the debate about the benefit of fetal genetic testing in general. Additional sources of uncertainty during the decision-making process were generated from weighing the advantages and disadvantages of initiating screening in the first trimester as opposed to waiting until the second. Questions of the quality and quantity of information and the perceived benefit of earlier access to fetal information were leading themes. Barriers to access prenatal care in early pregnancy presented participants with additional concerns about the ability to make informed decisions about prenatal genetic testing. ConclusionsThe option of the first trimester aneuploidy screening test in early pregnancy generates decision-making uncertainty that can interfere with the informed consent process. Mechanisms must be developed to facilitate informed decision making for this new form of prenatal genetic screening.