Noninvasive Prenatal Screening Research Articles

Performance of non-invasive prenatal screening for sex chromosome aneuploidies and parental decision-making.

Performance of non-invasive prenatal screening for sex chromosome aneuploidies and parental decision-making.

Detection of maternal X chromosome abnormalities using single nucleotide polymorphism–based noninvasive prenatal testing

Maternal X chromosome abnormalities may cause discordant results between noninvasive prenatal screening tests and diagnostic evaluation of the fetus/newborn, leading to unnecessary invasive testing. Women with X chromosome abnormalities are at increased risk for reproductive, pregnancy, or other health complications, which may be reduced or ameliorated by early diagnosis, monitoring, and intervention. This study aimed to validate a single nucleotide polymorphism-based noninvasive prenatal test to identify X chromosome abnormalities of maternal origin. All tests unable to evaluate fetal risk for aneuploidy because of uninformative algorithm results were eligible for inclusion. Two groups of cases were prospectively identified: Group A (n=106) where a maternal X chromosome abnormality was suspected and Group B (control group, n=107) where a fetal chromosome abnormality involving chromosome 13, 18, 21, or X was suspected but did not meet criteria for reporting. Maternal DNA was isolated from the plasma-depleted cellular pellet and sent to a reference laboratory for blinded analysis using chromosomal microarray. A chromosome abnormality involving chromosomes 13, 18, 21, or X was reported by the reference laboratory if ≥5 Mb in size and present in ≥20% of the DNA. A maternal X chromosome abnormality was suspected in 1/1305 tests (149/194,385; 0.08%). In Group A, a maternal X chromosome abnormality was confirmed in 100/106 cases (94.3% positive predictive value, 1-sided 97.5% confidence interval, 88.1%-100.0%). Turner syndrome was the most commonly suspected maternal abnormality (58/106, 54.7%), with confirmation of mosaic or nonmosaic 45,X by microarray in 38/58 (65.5%) cases. Noninvasive prenatal screening tests suspected the presence of maternal 47,XXX with or without mosaicism in 40/106 (37.7%) cases, confirmed by microarray in 38/40 (95.0%). In Group B (n=107), no maternal microarray abnormalities were reported, providing a negative predictive value of 100% (1-sided 97.5% confidence interval, 96.6%-100.0%). When noninvasive prenatal testing suspected a maternal X chromosome abnormality, maternal microarray confirmed an X chromosome abnormality with 94.3% positive predictive value. Of the maternal X chromosome abnormalities detected by array, >50% were 45,X. When fetal chromosome abnormalities involving chromosomes 13, 18, 21, or X were suspected, no maternal chromosome abnormalities were reported, yielding a negative predictive value of 100%. Women with maternal X abnormalities suspected with noninvasive prenatal testing may be at increased risk for reproductive and health complications; early evaluation and treatment may prevent long-term consequences or disability.

ART strategies in Klinefelter syndrome.

Patients with Klinefelter syndrome (KS) who receive assisted reproductive technology (ART) treatment often experience poor pregnancy rates due to decreased fertilization, cleavage, and implantation rates and even an increased miscarriage rate. Mounting evidence from recent studies has shown that various technological advances and approaches could facilitate the success of ART treatment for KS patients. In this review, we summarize the methods for guiding KS patients during ART and for developing optimal strategies for preserving fertility, improving pregnancy rate and live birth rate, and avoiding the birth of KS infants. We searched PubMed and Google Scholar publications related to KS patients on topics of controlled ovarian stimulation protocols, sperm extraction, fertility preservation, gamete artificial activation, round spermatid injection (ROSI), and non-invasive prenatal screening (PGD) methods. This review outlines the different ovulation-inducing treatments for female partners according to the individual sperm status in the KS patient. We further summarize the methods of retrieving sperm, storing, and freezing rare sperm. We reviewed different methods of gamete artificial activation and discussed the feasibility of ROSI for sterile KS patients who absolutely lack sperm. The activation of eggs in the process of intracytoplasmic sperm injection and non-invasive PGD are urgently needed to prevent the birth of KS infants. The integrated strategies will pave the way for the establishment of ART treatment approaches and improve the clinical outcome for KS patients.

A Retrospective Analysis Of Different Contingent Screening Models For Fetal Down Syndrome In Southwestern China

To discuss combinations of traditional screening and noninvasive prenatal screening (NIPS) and to compare which traditional screening is the most suitable first-line screening approach to NIPS, pregnant women were recruited in this retrospective observational study. Pregnant women underwent one of four traditional screening tests. The 9 contingent models were combined by high risk cut-offs of 1:50, 1:100, 1:270 and intermediate risk cut-offs of 1:1000, 1:1500, 1:2000. We analyzed cost and performance of various screening models with contingent screening of different risk cut-offs. Compared with other screening tests, combined first-trimester screening (CFTS) had the lowest proportion of high risk (≥1:270) with the highest detection rate (DR) (78.79%) and the lowest proportion of intermediate risk (1:271~1:1000). When intermediate risk was 1:51 ~1:1500, CFTS as first-line screening had the lowest cost with DR of 93.94%. Other screening tests as the first-line screening with intermediate risk of 1:51~1:1000 had the lowest cost, there DR were 90.91%, 84.62%, 91.67%, respectively. Our study demonstrated if only one traditional screening was allowed to screen pregnant women, CFTS was recommended as the first choice. According to local health and economic conditions, adopting appropriate traditional screening with suitable cut-offs as first-line screening will contributed to a cost-effective screening model.

Confirmatory testing illustrates additional risks for structural sex chromosome abnormalities in fetuses with a non-invasive prenatal screen positive for monosomy X.

More and more women rely on non-invasive prenatal screening (NIPS) to detect fetal sex and risk for aneuploidy. The testing applies massively parallel sequencing or single nucleotide polymorphism (SNP) microarray to circulating cell-free DNA to determine relative copy number. In addition to trisomies 13, 18, and 21, some labs offer screening for sex chromosome abnormalities as part of their test. In this study, an index neonate screened positive for monosomy X and had discordant postnatal chromosomes indicating an X;autosome translocation. This patient prompted a retrospective chart review for similar cases at a large NIPS testing center. The review found 28 patients with an abnormal NIPS for monosomy X who were eventually diagnosed with additional discrepant structural sex chromosome abnormalities including translocations, isochromosomes, deletions, rings, markers, and uniparental disomy. The majority of these were mosaic with monosomy X, but in seven cases, there was no evidence of mosaicism on confirmatory testing. The identification of multiple sex chromosome aneuploidies in these cases supports the need for additional genetic counseling prior to NIPS testing and following abnormal NIPS results that are positive for monosomy X. This finding broadens our knowledge about the variable outcomes of positive monosomy X NIPS results and emphasizes the importance of confirmatory testing and clinical follow up for these patients.

Minipuberty in Klinefelter syndrome: Current status and future directions.

Klinefelter syndrome is highly underdiagnosed and diagnosis is often delayed. With the introduction of non-invasive prenatal screening, the diagnostic pattern will require an updated description of the clinical and biochemical presentation of infants with Klinefelter syndrome. In the first months of life, the hypothalamic-pituitary-gonadal (HPG)-axis is transiently activated in healthy males during the so-called minipuberty. This period represents a "window of opportunity" for evaluation of the HPG-axis before puberty and without stimulation tests. Infants with Klinefelter syndrome present with a hormonal surge during the minipuberty. However, only a limited number of studies exist, and the results are contradictory. Further studies are needed to clarify whether infants with Klinefelter syndrome present with impaired testosterone production during the minipuberty. The aim of this review is to describe the clinical and biochemical characteristics of the neonate and infant with Klinefelter syndrome with special focus on the minipuberty and to update the clinical recommendations for Klinefelter syndrome during infancy.

Is Noninvasive Prenatal Screening Appropriate for Pregnant Women Age 35 or Older In Cases if Isolated Fetal Nasal Bone Abnormalities in The Chinese Han Population?

BackgroundEthnic background may affect the prevalence of nasal bone absence and the length of the nasal bone. This study aimed to elucidate the significance of absent or hypoplastic fetal nasal bone in the Chinese Han population and to formulate an optimal management plan for patients age 35 or older in cases of isolated abnormal fetal nasal bone.Material/MethodsWe prospectively assigned pregnant women whose fetuses had nasal bone absence or hypoplasia to separate groups according to their choice for noninvasive prenatal screening (NIPS) between January 1, 2013, and December 31, 2018. Demographic data, ultrasound findings, results of conventional maternal serum screening and NIPS, fetal karyotype, pregnancy outcomes, and expenses associated with prenatal testing were recorded. The incidence and odds ratio of nasal bone abnormality and the sensitivity and specificity of different prenatal genetic screening tests were calculated.ResultsA total of 1946 cases with fetal nasal bone absence or hypoplasia were included. Cases of isolated nasal bone abnormality (1736 cases) were divided into the NIPS group (Gr 1, n=429) and the non-NIPS group (Gr 2, n=1307). Sixty-four cases involved chromosomal abnormality. The sensitivity, specificity, and positive and negative predictive values of NIPS in Gr 1 were 100%, 100%, 100%, and 100%, respectively. The odds ratio of fetal chromosomal abnormalities for isolated fetal nasal bone abnormalities when maternal age was ≥35 was 4.615 (95% CI: 1.592–13.381). The cost-effectiveness ratio of contingent screening (NIPS first) was significantly lower than amniocentesis directly.ConclusionsThe nasal bone provides an important marker for chromosome abnormalities in some populations, but to a lesser extent in the Chinese Han population. NIPS is an excellent first option for follow-up among pregnant women age ≥35 in cases of absent or hypoplastic fetal nasal bone in the first trimester ultrasound scan.

Prenatal testing in pregnancies conceived by in vitro fertilization with pre-implantation genetic testing.

Women with pregnancies resulting from in vitro fertilization (IVF) with normal pre-implantation genetic testing for aneuploidy (PGT-A) are advised to undergo prenatal screening and testing during pregnancy. It is not well known how many follow these recommendations. Our objective was to study prenatal testing decisions made by women with pregnancies conceived through IVF with PGT-A. We performed a retrospective review of women who received genetic counseling during pregnancies conceived through IVF with normal PGT-A. We excluded those who received genetic counseling preconceptionally prior to IVF. Statistical analysis included descriptive statistics and after testing for normality by the Kolmogorov-Smirnov test, independent t test, Mann-Whitney U test, or Chi-square/Fisher's exact test. Data from 83 women were included. Of these, 53 (63.9%) had at least one of the following prenatal tests: first trimester combined screening (16.9%), non-invasive prenatal screening (NIPS) (45.8%), second trimester serum screening (6%), and invasive diagnostic testing (6%). 10.8% had more than one of the above tests and 36.1% declined all tests. Almost two-thirds of women who were pregnant after IVF with normal PGT-A had prenatal aneuploidy screening or testing. Future prospective studies with larger cohorts are needed to further ascertain decision making in this population.

SAT-068 Bewilderment! Sex Chromosome Non-Invasive Prenatal Screening (NIPS) Results Differ from Phenotype and Postnatal Karyotype

BackgroundNIPS uses cell-free DNA in maternal serum to identify fetal aneuploidies including sex chromosome aneuploidies (SCA).1 Despite reports of high sensitivity and specificity, NIPS results, phenotype, and postnatal karyotype may be inconsistent. This situation generates parental anxiety and physician apprehension especially when the apparent genital phenotype differs from the NIPS result. We report four cases involving genotype-phenotype discordance in infants with disorders of sex development (DSD).Case 1:Female infant with complex congenital heart disease had inconclusive NIPS results. Postnatal karyotype was 46,XY karyotype (positive for SRY gene). Ultrasound [US] confirmed female internal genitalia. Postnatal karyotype on uncultured peripheral blood cells with FISH showed mosaicism [46,XY (85%)/45,X (15%)]. Case 2: Female infant conceived via IVF had 46,XY karyotype on NIPS. Prenatal and postnatal US showed female internal genitalia. Postnatal results showed 46,XX karyotype and Urine FISH analysis reported XX in all examined cells. Maternal karyotype is 46,XX; maternal FISH results are pending. Case 3: NIPS reported 45,X. Prenatal US showed male external genitalia. Postnatal exam showed male phenotype with right gonad in inguinal region. Cord blood karyotype and FISH analyses showed mosaicism [45,X (56%)/46,XY (44%)] with 4 different Y chromosome rearrangements. Urine FISH showed mosaicism [45,X (95%)/46,XY (5%)]. Testosterone and AMH concentrations were normal. Case 4: NIPS reported 46,XY karyotype. Prenatal US showed normal female genitalia. Postnatal physical exam revealed low set ears; additional studies revealed horseshoe kidney and atrial septal defect. Cord blood showed mosaicism [45,X (90%)/46,XY (10%)].ConclusionDiscrepancies between NIPS and postnatal karyotype occur more commonly with SCA than for autosomal aneuploidies.2 Such inconsistencies generate anxiety regarding sex of fetus, suggest a DSD diagnosis, and warrant additional prenatal and postnatal investigations. Testing to prevent missed detection of sex chromosome mosaicism is necessary. Early diagnosis of DSDs benefits the infant and the family. In some instances, NIPS expose undiagnosed maternal factors.3 Most importantly, communication involving parents and both prenatal and postnatal health care providers is essential to promote timely holistic health care for the infant and family.

(Invited) Fluorogenic Error Correction Code Sequencing: Chemistry, Microfluidics, and Instrumentation

Next-generation sequencing has become a routine tool for biology and medicine. However, eliminating errors in next-generation DNA sequencing has proved challenging. I am going to talk about our newly developed error-correction code (ECC) sequencing, a method to greatly improve sequencing accuracy by combining fluorogenic sequencing-by-synthesis (SBS) with an information theory–based error-correction algorithm. ECC embeds redundancy in sequencing reads by creating three orthogonal degenerate sequences, generated by alternate dual-base reactions. This is similar to encoding and decoding strategies that have proved effective in detecting and correcting errors in information communication and storage. We showed that, when combined with a fluorogenic SBS chemistry with raw accuracy of 98.1%, ECC sequencing provides single-end, error-free sequences up to 200 bp. I also will discuss the recent development we have made on the high-throughput instrumentation of this ECC sequencing approach. We have integrated millions of femtoliter reaction wells into a novel microfluidic platform and have built a prototype upon it to perform high-throughput sequencing experiments such as RNA-seq, non-invasive prenatal screen, and small copy number variation identification.

Noninvasive prenatal diagnosis by genome-wide haplotyping of cell-free plasma DNA

PurposeWhereas noninvasive prenatal screening for aneuploidies is widely implemented, there is an increasing need for universal approaches for noninvasive prenatal screening for monogenic diseases. Here, we present a cost-effective, generic cell-free fetal DNA (cffDNA) haplotyping approach to scan the fetal genome for the presence of inherited monogenic diseases. MethodsFamilies participating in the preimplantation genetic testing for monogenic disorders (PGT-M) program were recruited for this study. Two hundred fifty thousand single-nucleotide polymorphisms (SNPs) captured from maternal plasma DNA along with genomic DNA from family members were massively parallel sequenced. Parental genotypes were phased via an available genotype from a close relative, and the fetal genome-wide haplotype and copy number were determined using cffDNA haplotyping analysis based on estimation and segmentation of fetal allele presence in the maternal plasma. ResultsIn all families tested, mutational profiles from cffDNA haplotyping are consistent with embryo biopsy profiles. Genome-wide fetal haplotypes are on average 97% concordant with the newborn haplotypes and embryo haplotypes. ConclusionWe demonstrate that genome-wide targeted capture and sequencing of polymorphic SNPs from maternal plasma cell-free DNA (cfDNA) allows haplotyping and copy-number profiling of the fetal genome during pregnancy. The method enables the accurate reconstruction of the fetal haplotypes and can be easily implemented in clinical practice.

Maternal plasma genome-wide cell-free DNA can detect fetal aneuploidy in early and recurrent pregnancy loss and can be used to direct further workup.

STUDY QUESTION Can maternal plasma cell-free DNA (cfDNA) detect chromosomal anomalies in early pregnancy loss (EPL) and recurrent pregnancy loss (RPL)?SUMMARY ANSWERGenome-wide cfDNA testing can serve as an alternative to cytogenetic analysis in products of conception (POCs) in RPLs and can guide further management.WHAT IS KNOWN ALREADYRandom chromosomal anomalies are the single most common cause for EPL and RPL. Cytogenetic analysis in POCs may be used to direct management in RPL because the detection of random chromosomal anomalies can eliminate further unwarranted testing.STUDY DESIGN, SIZE, DURATIONThis was a prospective diagnostic test study from March 2018 to January 2019 of 109 patients experiencing pregnancy loss before 14 weeks gestation at a tertiary-care academic medical center.PARTICIPANTS/MATERIALS, SETTING, METHODSBlood samples were drawn for genome-wide cfDNA testing prior to chorionic villous sampling for cytogenetic analysis of POCs with both short-term cultures (STCs) and long-term cultures (LTCs). Final analysis included 86 patients with non-mosaic cytogenetic results in POCs and available cfDNA results. Aneuploidy detection rates by cfDNA testing and POC cytogenetic analysis were compared. The first 50 samples served as the Training Set to establish pregnancy loss-specific log-likelihood ratio (LLR) thresholds using receiver-operator characteristic (ROC)-like analyses. These were then used for the entire cohort.MAIN RESULTS AND THE ROLE OF CHANCESeventy-eight samples (71.5%) had results available from both STC and LTC; 12 samples (11%) had a result from STC only, and 7 samples (6.4%) had a result from LTC only. A chromosomal anomaly was detected in 55/86 (64%). The rates of chromosomal anomalies were 61, 72, 73 and 44% in patients undergoing their first, second, third and ≥4th pregnancy losses, respectively. The median cfDNA fetal fraction was 5%. With standard LLR thresholds used for noninvasive prenatal screening, the sensitivity of cfDNA in detecting aneuploidy was 55% (30/55) and with a specificity of 100% (31/31). Using pregnancy loss-specific LLR thresholds, the sensitivity of cfDNA in detecting aneuploidy was 82% (45/55), with a specificity of 90% (28/31). The positive and negative likelihood ratios were 8.46 and 0.20, respectively. Fetal sex was correctly assigned in all cases.LIMITATIONS, REASONS FOR CAUTIONCases with a false-positive result by cfDNA analysis would not receive the indicated RPL workup. Specificity could be improved by using a fetal fraction (FF) cutoff of 4%, but this would result in exclusion of more than a quarter of cases.WIDER IMPLICATIONS OF THE FINDINGScfDNA-based testing can serve as an alternative to POC cytogenetic analysis and can guide further RPL management: if cfDNA demonstrates aneuploidy, no further action is taken and if no abnormality is detected, the recommended RPL workup is performed.STUDY FUNDING/COMPETING INTEREST(S)Cell-free DNA testing was funded by Illumina, Inc., San Diego, CA. Y.Y. is a member of Illumina’s Clinical Expert Panel and has received travel grants. A.B. has received travel grants from Illumina. All authors have no competing interest to declare.

Non-Invasive Prenatal Screening: Navigating the Relevant Legal Norms.

The implementation of non-invasive prenatalscreening (NIPS) in Canada will be affected by legal norms. The law can shapephysician behaviour, helpto crystallize standards of care, influence utilizationpatterns, and reflect and reinforce patient expectations. In Canada, failure to inform a patient about NIPS,or misinterpretation of NIPS results, could result in a successful "wrongful birth" claim if the patientsubsequently gives birth to a child with a condition that had been detectable. Given that research shows that physicians'decisions are influenced by concerns aboutliability, malpractice law seems likely to encourage increased recommendation and use ofNIPS. Physicians' fiduciaryand negligence-based disclosure standards require they consider both objectivefactors as well as a specific patient's subjectiveand reasonable beliefs,fears, desires, and expectations. Thus, physicians likely must address dominant publicdiscourses and controversies relevant toNIPS. Given the existence of spin, hype, and misinformation about NIPS, there is an increasing need for a robust consent process and, when appropriate, geneticcounselling. In sum, the law will defineand bound the acceptable behaviour of physicians recommending or administeringNIPS, and nudge the technology'simplementation forward. Physicians and policymakers should beaware of the potential impact of these legal norms on both utilization and public expectations.

Multiple Aneuploidy Pattern Detected by Non-invasive Prenatal Screening in Successive Pregnancies [25K

INTRODUCTION: We present a case where non-invasive prenatal screening (NIPS) detected a similar pattern of multiple aneuploidies in sequential pregnancies. METHODS: Case Presentation (with patient consent): A 25 year-old G3P2 patient had NIPS, by massively parallel sequencing (MPS), in her second and third pregnancies. Her first NIPS result was positive for trisomies 18 and 21. Further bioinformatics review revealed possible partial trisomy 13 and complete trisomies 14 and 20, in addition to the previously reported trisomies. NIPS by MPS repeated at another lab was non-reportable. Amniocentesis revealed normal karyotype, microarray, FISH for the chromosomes of interest, and chromosome 14 uniparental disomy testing. Maternal karyotype, microarray, and chromosomal breakage studies were normal. Patient had a negative oncology evaluation. Patient had an insignificant medical and medication history. Patient delivered a healthy girl. Placenta was small with a normal karyotype. Her current pregnancy shows a similar NIPS pattern. Patient declined amniocentesis and further aneuploidy screening. Second trimester ultrasound detected fetal hyperechoic bowel. Repeat maternal chromosomal breakage studies were normal. CONCLUSION: NIPS analyzes cell-free DNA in maternal blood originating from maternal and cytotrophoblast cells. The similar NIPS pattern in both pregnancies indicates a likely maternal etiology. When multiple aneuploidies are observed by NIPS, possible etiologies include maternal benign tumor or malignancy and fetal, placental or maternal chromosome abnormalities. However, subsequent fetal and maternal evaluations were normal. This case highlights that NIPS may yield unexpected results that are not representative of the fetal or maternal karyotypes and an extensive multi-specialty work-up may be recommended in these scenarios.

Most noninvasive prenatal screens failing due to inadequate fetal cell free DNA are negative for trisomy when repeated.

We aimed to test for an association between the amount of circulating fetal cell-free DNA and trisomy, and whether NIPS failure due to low fetal fraction indicates trisomy risk. Maternal BMI, maternal age, fetal sex, gestational age, fetal cfDNA fraction, and NIPS results was collected on 2374 pregnancies. Additional clinical information was available for 1180 research consented patients. We investigated associations between fetal fraction and available variables and determined the success rate of repeat NIPS testing. Fetal trisomy was marginally associated with decreased fetal fraction (P = .067). However, the proportions of trisomy events were not significantly increased in women who had failed NIPS due to low fetal fraction (<4%) (OR = 1.37 [0.3-7.4]; P = .714). 66% of repeated NIPS after a second blood draw were successful. Failure to meet the clinical cutoff of 4% fetal fraction established for NIPS accuracy did not suggest increased risk for trisomy in our cohort. Because repeat testing was successful in the majority of cases and most failures were explained by high BMI and low gestational age, a redraw may be an appropriate next step before invasive screening due to concerns for trisomic pregnancies.

Pre-analytical issues in liquid biopsy – where do we stand?

Abstract It is well documented that in the chain from sample to the result in a clinical laboratory, the pre-analytical phase is the weakest and most vulnerable link. This also holds for the use and analysis of extracellular nucleic acids. In this short review, we will summarize and critically evaluate the most important steps of the pre-analytical phase, i.e. the choice of the best control population for the patients to be analyzed, the actual blood draw, the choice of tubes for blood drawing, the impact of delayed processing of blood samples, the best method for getting rid of cells and debris, the choice of matrix, i.e. plasma vs. serum vs. other body fluids, and the impact of long-term storage of cell-free liquids on the outcome. Even if the analysis of cell-free nucleic acids has already become a routine application in the area of non-invasive prenatal screening (NIPS) and in the care of cancer patients (search for resistance mutations in the EGFR gene), there are still many unresolved issues of the pre-analytical phase which need to be urgently tackled.

Assessment of a change of protocol of prenatal screening by inclusion of non-invasive prenatal diagnosis.

Non-invasive prenatal screening (NIPS) is a test for the detection of major fetal chromosomal abnormalities in maternal blood during pregnancy. The purpose of this study was to assess the performance of NIPS implemented within the framework of the Screening Program for Congenital Abnormalities of the Andalusian Health System. A retrospective observational study was undertaken to determine the number of NIPS tests performed since its introduction. The number of invasive diagnostic tests done after the implementation of NIPS in the patients included in the program between March 2016 and August 2017 was also quantified. A total of 6,258 combined first- and second trimester screening tests were performed, covering 95% of the population. In total, 250 subjects were identified as high risk, of whom 200 underwent NIPS after loss to follow-up. NIPS showed a sensitivity of 100% (95% CI: 76.84-100%) and a specificity of 99.46% (95% CI: 97.04-99.99%). This test has proven to have a very high sensitivity and specificity. The results obtained demonstrate that the incorporation of NIPS in clinical practice minimizes the rate of miscarriages and reduces the frequency of invasive procedures by 70%.

Positive Rate of Noninvasive Prenatal Screening for Pregnancies with Fetal Congenital Heart Disease and Its Impact on Pregnancy Outcome

Abstract Objective: To evaluate the clinical utility of noninvasive prenatal screening (NIPS) for fetuses with congenital heart disease (CHD) and impact of NIPS results on pregnancy outcome. Methods: This was a retrospective study of pregnant women with fetuses diagnosed with CHDs by sonographic examination, who willing to underwent NIPS as a side-test for fetal aneuploidies. From August 2016 to October 2017, in the sonographic examination center of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. NIPS was offered to 117 women who carried fetuses with CHD diagnosed by fetal ultrasound (mean gestational age = 24 weeks). The pregnancy outcomes were followed-up. Results: NIPS positive rate in our pregnancies with CHD fetuses’ cohort is 11.1% (13/117), and the positive predictive value for aneuploidies is 85.7% (6/7). In the NIPS positive group (n = 13), all pregnancies terminated, 76.9% (10/13) of those decisions were made on ultrasound finding alone. In the NIPS negative group (n = 104), 2 lost follow-up, 79 pregnancies terminated, among which 77.2% (61/79) of the decision was made by ultrasound results alone. Twenty-three pregnancies continued and 78.3% of those fetuses carried single type CHD. In terminated pregnancies that did not considered NIPS results (71/115), 73.2% (52/71) of those carried fetuses with two or more types of CHDs. Conclusion: NIPS can detect common aneuploidy associated with CHD with high positive predictive value and screening yield. The NIPS result played certain meaningful roles in determining pregnancy outcomes, particularly for fetus with simplex CHD; yet the parents’ decision of pregnancy was mainly made based on ultrasound findings.

Benefits and limitations of noninvasive prenatal aneuploidy screening.

The introduction of noninvasive prenatal screening (NIPS) using cell-free DNA (cfDNA) is the newest option for aneuploidy screening during pregnancy. Compared with other aneuploidy screening options, NIPS offers a higher detection rate for trisomy 21 with a low false-positive rate. However, pretest and post-test patient counseling is essential and should include a discussion of the benefits and limitations, the screening rather than diagnostic nature of the test, and the association of a test failure with an increased risk of aneuploidy. Refer patients for genetic counseling when appropriate, particularly if test failure occurs due to a low fetal fraction or if maternal mosaicism or malignancy is suspected.

Chromosomal Microarray vs. NIPS: Analysis of 5541 Low-Risk Pregnancies

(Abstracted from Genet Med 2019;21:2462–2467) Prenatal genetic testing is conducted today using a variety of methods: noninvasive prenatal screening (NIPS) and invasive prenatal testing with karyotyping and/or chromosomal microarray analysis (CMA). While NIPS can detect some genetic aberrations without an invasive procedure, karyotyping and CMA require amniocentesis or chorionic villi sampling.