Non-invasive Prenatal Testing Research Articles

The Impact of Chromosomal Mosaicisms on Prenatal Diagnosis and Genetic Counseling-A Narrative Review.

Genetic disorders represent a high-impact diagnosis for both patients and their families. Prenatal screening methods and, when recommended, genetic testing allow parents to make informed decisions about the course a pregnancy is going to take. Although offering certainty about the potential evolution and prognosis of the pregnancy, and then the newborn, is usually not possible, genetic counseling can offer valuable insights into genetic disorders. Chromosomal mosaicisms are genetic anomalies that affect only some cell lines in either the fetus or the placenta or both. They can affect autosomal or heterosomal chromosomes, and they can be either numerical or structural. The prognosis seems to be more severe if the genetic alterations are accompanied by malformations visible in ultrasounds. Several genetic techniques can be used to diagnose certain mosaicisms, depending on their nature. A novel approach in prenatal care is non-invasive prenatal screening (NIPS), also known as non-invasive prenatal testing (NIPT), which, although it does not always have diagnostic value, can provide valuable information about potential genetic anomalies, especially numerical, with high sensitivity (Se).

The role of patient-reported experiences in disclosing genetic prenatal testing: Findings from a large-scale survey on pregnant women

IntroductionPregnant women can choose from different prenatal genetic tests throughout their maternity journey. We aim to investigate the clinical, societal, and economic determinants influencing the selection of different options (non-invasive, invasive, or both). MethodsA systematic survey focusing on maternity pathways was launched by the Region of Tuscany, Italy, to collect data on pregnant women’s experience, outcomes and satisfaction levels. Drawing from this survey, we retrospectively analyzed data on women who filled out the second-trimester questionnaire between March 2019 and February 2023 (n = 27,337), providing complete data on relevant variables. Logistic regression models were applied to identify the factors contributing to a higher likelihood of opting for non-invasive prenatal testing (NIPT) and invasive testing. ResultsAmong the participants, 42.7 % chose only NIPT, 3.8 % opted for invasive tests exclusively, 1.3 % underwent both tests, and 52.2 % did not pursue any genetic testing. NIPT was more often chosen by older, Italian, highly educated, nulliparous women, who perceived better health, were employed (versus unemployed), had higher economic status, planned pregnancy, received hospital-based care (versus counseling center), under gynecologist supervision (versus midwife), not opted for combined testing and received pregnancy vaccinations. Conversely, invasive testing was more prevalent among older women but less common among those who were nulliparous, had Italian nationality, and had a perceived better health status. This group also tended to experience unplanned and high-risk pregnancy, did not take folate during pregnancy, received public hospital-based assistance, less frequently chose combined tests or NIPT, and had frequent delays in examinations. ConclusionsVarious factors beyond clinical considerations influence the selection of a prenatal test. Therefore, NIPT pathways should include balanced, high-quality information about benefits and limitations, ensuring laboratory specialists' active and integrated involvement in decision-making.

Accuracy of fetal fraction measurements in a single-nucleotide polymorphism-based noninvasive prenatal test.

Noninvasive prenatal testing (NIPT) for fetal aneuploidy relies on the analysis of fetoplacental cell-free DNA (cfDNA) found in maternal plasma. A minimum cfDNA fetal fraction (FF) is required for reliable test performance, but some methods may have suboptimal accuracy for FF measurement. This study investigated the accuracy of a single-nucleotide polymorphism- (SNP-) based NIPT method to assess FF. FF measurements using SNP-based NIPT in consecutive samples from singleton male pregnancies were compared with FF measured using a "gold standard" Y-chromosome method. In a cohort of 106,846 samples, the SNP-based FF method showed a standard deviation (SD) of 0.42%. Compared to the Y chromosome FF method, a correlation coefficient, r, of 0.995, and bias of 0.17% were observed. The SD was not substantially different across specific FF ranges or for samples with high-risk NIPT results. The SNP-based NIPT method estimates FF with good accuracy, with a SD three to eight times better than other NIPT methods (0.42% vs. 1.3%-3.4%). FF is an important quality control parameter and should be routinely reported as part of NIPT.

Potential efficacy of digital polymerase chain reaction for non-invasive prenatal screening of autosomal aneuploidies: a systematic review and meta-analysis

BackgroundDigital Polymerase Chain Reaction (dPCR) presents a promising approach for quantifying DNA and analyzing copy number variants, particularly in non-invasive prenatal testing. This method offers a streamlined and time-efficient procedure in contrast to the widely used next-generation sequencing for non-invasive prenatal testing. Studies have reported encouraging results for dPCR in detecting fetal autosomal aneuploidies. Consequently, this systematic review aimed to evaluate the effectiveness of dPCR in screening for trisomy 21, 18, and 13.MethodsA systematic search was conducted in PubMed, Web of Sciences, and Embase for relevant articles published up to December 30, 2023. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was utilized for the quality assessment of the included articles. Furthermore, a bivariate random-effect regression model was used to conduct a meta-analysis on the utility of dPCR for trisomy 21 screening.ResultsA total of 9 articles were included in this review, with all of them assessing the utility of dPCR in trisomy 21 screening, and 2 and 1 studies conducting additional analysis on the screening abilities of dPCR for trisomy 18 and 13, respectively. A bivariate random-effects model calculated pooled sensitivity and specificity with a 95% confidence interval (CI). Meta-analysis of 6 studies comparing trisomy-21 screening with karyotyping demonstrated dPCR's pooled sensitivity of 98% [95% CI: 94 -100] and specificity of 99% [95% CI: 99 -100]. While conducting a meta-analysis for trisomy 13 and 18 proved impractical, reported values for sensitivity and specificity were favorable.ConclusionsThese findings suggest that dPCR holds promise as an effective tool for non-invasive prenatal testing, presenting a less time-consuming and intricate alternative to next-generation sequencing. However, further research is necessary to evaluate dPCR's applicability in clinical settings and to delineate its specific advantages over next-generation sequencing. This study contributes valuable insights into the potential of dPCR for enhancing prenatal screening methodologies.Trial registrationThe protocol of this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on 7/3/2024, with a registration code of CRD42024517523.

Chromosomal abnormalities detected by chromosomal microarray analysis and pregnancy outcomes of 4211 fetuses with high-risk prenatal indications

With the gradual liberalization of the three-child policy and the development of assisted reproductive technology in China, the number of women with high-risk pregnancies is gradually increasing. In this study, 4211 fetuses who underwent chromosomal microarray analysis (CMA) with high-risk prenatal indications were analysed. The results showed that the overall prenatal detection rate of CMA was 11.4% (480/4211), with detection rates of 5.82% (245/4211) for abnormal chromosome numbers and 5.58% (235/4211) for copy number variants. Additionally, the detection rates of clinically significant copy number variants were 3.78% (159/4211) and 1.8% (76/4211) for variants of uncertain significance. The detection rates of fetal chromosomal abnormalities were 6.42% (30/467) for pregnant women with advanced maternal age (AMA), 6.01% (50/832) for high-risk maternal serum screening (MSS) results, 39.09% (224/573) with abnormal non-invasive prenatal testing (NIPT) results, 9.21% (127/1379) with abnormal ultrasound results, and 5.1% (49/960) for other indications. Follow-up results were available for 4211 patients, including 3677 (3677/4211, 87.32%) whose infants were normal after birth, 462 (462/4211, 10.97%) who terminated their pregnancy, 51 (51/4211, 1.21%) whose infants were abnormal after birth, and 21 (21/4211, 0.50%) who refused follow-up. The results of this study demonstrate significant variation in the diagnostic rate of chromosomal microarray analysis across different indications, providing valuable guidance for clinicians to assess the applicability of CMA technology in prenatal diagnosis.

Performance of Massive Parallel Sequencing-Based Cell-Free DNA Testing in Compromised Pregnancies.

Background/Objectives: Non-Invasive prenatal test (NIPT) is used as a universal or contingent test after prior risk assessment. Screening is mainly performed for common trisomies (T21, T13, T18), although other chromosomal anomalies may be detected. Our objective was to study the performance of GWNIPT in the detection of chromosomal abnormalities in pregnancies in which an invasive prenatal study was performed and in early pregnancy losses, in comparison with the reference test. Method: VeriSeqTM NIPT Solution v2, a genome-wide NIPT (GWNIPT), was performed prior to invasive testing in fetal diagnostic study cases (FDS, n = 155) and in early pregnancy losses (EPL, n = 68). Results: In the FDS group, the diagnostic test (QFPCR, array and karyotype) detected anomalies in 32 pregnancies (21%), in twenty of them (61%) also detected by GWNIPT. Eleven of the twelve cases undetected by GWNIPT were balanced translocations (n = 4) or deletions/duplications <7 Mb (n = 7). In the EPL group, GWNIPT detected anomalies in 46% of cases (31/68) but comparison with reference test (QFPCR and karyotype) in products of conception (POC) was only possible in 18 cases. Concordant results between POC and GWNIPT test were obtained in 16 of the 18 cases. In EPL, with GWNIPT testing, common trisomies accounted for 25.8% of cases (8/31), rare trisomies 54.8% (17/31) and microdeletions/duplications 16.1% (5/31). Conclusions: The GWNIPT test may be useful in clinical practice in prenatal and in EPL's genetic diagnosis when the appropriate sample is not available.

Early Non-Invasive Prenatal Testing at 6-9 Weeks of Gestation.

Non-invasive prenatal testing (NIPT) is usually performed beyond 10 weeks of gestation, because earlier in pregnancy, the fetal fraction is low, resulting in failure to obtain reliable results. This study aimed to evaluate the clinical performance of NIPT earlier in pregnancy using a method for cell-free DNA (cfDNA) analysis that eliminates the need for polymerase chain reaction (PCR), DNA sequencing, or microarrays (Vanadis® system, PerkinElmer, Waltham, MA, USA). Cell-free DNA was extracted from the maternal plasma of 30 singleton pregnancies at 6-9 weeks of gestation (group 1) and at 11-14 weeks of gestation of the same patients (group 2). The mean crown-rump length (CRL) and gestational age in group A was 16.12 mm and that in group B was 61.45 mm. In group A, results were obtained in all, but one, cases (97%). From the remaining pregnancies, one miscarried at 8 weeks and, therefore, the follow-up NIPT at 12 weeks could not be performed. The fetal sex was diagnosed correctly in the 28 cases that had a successful early test, and the results were in accordance with the examination at 12 weeks. There were no cases of aneuploidies and disomy was diagnosed correctly in all. The "Vanadis" prenatal NIPT assay can successfully be used early during the first trimester at 6-9 weeks of gestation (early NIPT) to identify the fetal sex. Further studies are needed to explore the diagnostic potential for aneuploidies.

P-567 Is mosaic embryo transfer a valid alternative for patients lacking euploid embryos? a multicentric study from Argentina

Abstract Study question How does low-level mosaicism embryo transfer affect reproductive outcomes, including pregnancy rates and live birth success, compared to transfers involving euploid embryos? Summary answer Most mosaic embryo transfers do not affect reproductive outcomes, as live birth rates appear to be similar to those observed with euploid embryos. What is known already Preimplantation genetic testing (PGT) is used to identify embryonic genetic abnormalities and, ideally, select euploid embryos for intrauterine transfer, to improve clinical IVF outcomes. Chromosomal mosaicism is defined as the presence of two or more different chromosomal cell lines within an embryo. Numerous sources describe the proportion of mosaic embryos ranging from 4 to 22%. Several publications report that mosaic embryo transfer can lead to successful pregnancies and healthy deliveries, albeit at a lower frequency and with higher rates of pregnancy loss compared to euploid embryos. However, the impact of mosaicism on IVF outcomes remains a matter of controversy. Study design, size, duration Observational and retrospective multi-center study analyzed 6241 embryos from 1218 patients, across 4 IVF centers, who underwent PGT between 2016 and 2023 in a single genetics laboratory. Embryos were categorized as euploid, aneuploid, or mosaic. Patients in group A (n = 894) were transferred an euploid embryo, while in group B (n = 55), a low-grade mosaic embryo, defined as those having less than 40% (2016-2021) or 50% (2021-2023) aneuploid cells, was transferred. Participants/materials, setting, methods The embryos were biopsied and vitrified for later transfer. Blastocyst biopsy DNA was amplified using the SurePlex kit, processed with the VeriSeq kit (Vitrolife), and sequenced on a MiSeq platform. The results were analyzed using BlueFuse-Multi software. Mosaic embryo transfers were conducted only in the absence of a euploid embryo, following genetic counseling. beta-hCG levels &amp;gt;25 IU were considered positive, and clinical pregnancy was confirmed through ultrasound visualization of the gestational sac with heartbeat. Main results and the role of chance Among the analyzed embryos, the proportion of euploid was 46.2% (n = 2883), while mosaic embryos accounted for 19.3% (n = 1207), with 69.5% classified as low-grade and 30.5% as high-grade. Aneuploid embryos comprised 31.3% (n = 1954), and results could not be obtained for 3.2% (n = 197). Fifty-five low-grade mosaic embryos were transferred, including 19 with complete chromosomal mosaicism, 34 with segmental mosaicism, and 2 cases with 2 chromosomes involved in the mosaicism. The positive beta-hCG rate post-transfer was 50.3% for Group A, compared to 49.1% for Group B. Clinical pregnancy rates were 36.9% and 36.4%, respectively. Regarding live births, in Group A 328 (36.7%) children were born, and in Group B, 16 (29.1%), with 2 ongoing pregnancies. Conversely, pregnancy losses in Group B (9.1%) were higher compared to the euploid group (2.9%). Regarding pregnancy losses, in 3 cases no fetal heartbeats were identified, there was one miscarriage &amp;lt;20 weeks, and one twin gestation was lost after a normal non-invasive prenatal testing. In all cases the newborns were apparently healthy after mosaic embryo transfer, with an average gestational week at birth of 39 (37-41), and an average weight of 3197 (2900-4390) grams. Cesarean section was performed for 15/16 births, and one was born by vaginal delivery. Limitations, reasons for caution The study is limited by its retrospective nature and the small number of samples and mosaics transferred. Prenatal and postnatal tests were not conducted. Furthermore, the health of newborns was evaluated only in the initial months of life. Wider implications of the findings Mosaic embryo transfer is a valid alternative for couples lacking euploid embryos. This multicenter study adds evidence that mosaic embryo transfer does not have a clinically relevant impact on pregnancy and live birth rates, similar to what has been reported by other authors. Trial registration number ‘not applicable’

P-387 The use of cell-free DNA analysis to identify fetal aneuploidies in early pregnancy loss

Abstract Study question Can cell-free (cf) DNA-based analysis of a maternal blood sample be used to identify presence of fetal aneuploidies in early pregnancy loss (EPL) cases? Summary answer CfDNA analysis was able to detect fetal aneuploidies in EPL cases with 73.5% sensitivity and 100% specificity. What is known already Miscarriages occur in about 10%–20% of pregnancies, and the majority occur in the first trimester. About 50% of EPL cases result from the presence of fetal aneuploidy. Knowing the etiology of a miscarriage can be helpful for future reproductive planning along with providing a psychological benefit for patients. Although products of conception (POC) samples can be collected and assessed for presence of fetal aneuploidies, this is not always possible. Recent studies have shown that a noninvasive approach using cfDNA analysis of a blood sample can identify fetal aneuploidies in patients that experience EPL. Study design, size, duration In this prospective study, samples were collected from 78 patients across the United States from June 2021–December 2022. Blood specimens were collected for cfDNA analysis and maternal cell contamination analysis, and POC samples were collected following surgical evacuation for microarray analysis. Performance of the cfDNA assay was determined by comparing results from the cfDNA analysis against the gold standard of microarray results. Participants/materials, setting, methods Patients were recruited from six reproductive endocrinology/infertility practices. Eligible participants were between 5–20 weeks of gestation with miscarriage of a singleton pregnancy diagnosed by ultrasound and presence of pregnancy tissue in utero. Limited clinical information was collected, including demographics and expected clinical gestational age (GA) at sample collection. Blood samples underwent cfDNA analysis using an adapted version of a noninvasive prenatal test, which included establishment and use of pregnancy loss-specific log likelihood ratio thresholds. Main results and the role of chance Seventy-eight patients were recruited, of which two were excluded due to blood sample collection issues. Eleven of the 76 patients that underwent cfDNA analysis were excluded from performance calculations for several reasons including maternal cell contamination of POC samples and detection of triploidy by microarray. The final 65 samples included 49 affected and 16 unaffected samples based on POC microarray results; this included 42 with one fetal aneuploidy, six with two fetal aneuploidies, and one with three fetal aneuploidies. Average fetal fraction of these 65 samples was 4.9% (range: 0.6%–13.9%) and average expected clinical GA at time of sample collection was 8.7 weeks (range: 5.9–12.1 weeks). Performance of the cfDNA assay was determined by comparing cfDNA analysis results with POC microarray results using either a full concordance approach (correct classification of all affected chromosomes in an affected sample) or a partial concordance approach (correct classification of at least one affected chromosome in an affected sample). Based on the full concordance approach, sensitivity of the cfDNA assay was 69.4% and specificity was 100%. For the partial concordance approach, sensitivity of the cfDNA assay increased to 73.5% whilst specificity remained at 100%. The cfDNA assay failure rate was 0%. Limitations, reasons for caution Study limitations include a small study cohort, the inability of the cfDNA assay to detect triploidy or partial deletions/duplications &amp;lt;7 Mb and possibly mosaicism, and that this cfDNA analysis approach can only be used for EPL cases that are identified before complete expulsion of the products of conception. Wider implications of the findings This study provides further evidence of the ability of cfDNA analysis to detect fetal aneuploidies in EPL cases. A clinically available cost-effective noninvasive approach to determine the etiology of a miscarriage could help inform medical management of patients for future reproductive planning and could provide psychological benefits to patients. Trial registration number NCT04935138

Racial and ethnic disparities in non-invasive prenatal testing adherence: a retrospective cohort study.

Fetal aneuploidies, including trisomies 21, 13, and 18, represent a significant issue in prenatal care. The advent of non-invasive prenatal testing (NIPT) through the detection of cell-free DNA (cf-DNA) in maternal blood has modified screening for chromosomal abnormalities. This study evaluates NIPT adherence among pregnant of different ethnicities, addressing potential disparities in prenatal care. This was a retrospective, single-center study conducted at a tertiary care university hospital in Italy between March 31, 2021, and September 30, 2022. Participants were categorized by ethnicity (Asian/Pacific islander, Black, Latina, White, Middle Eastern). Maternal demographic characteristics and prenatal test data were recorded. Comparative analyses were executed utilizing a One-Way Analysis of Variance (ANOVA) Test, augmented by Tukey's honestly significant difference test for post-hoc evaluation. Statistical significance was denoted by a P value (P)<0.05. A multivariate analysis through a multinomial regression model was conducted for the results to detect potential bias. Six hundred seventeen pregnancies were included: 418 White, 105 Asian/Pacific islander, 46 Black, 40 Latina, and 8 Middle Eastern. Maternal age showed no significant variation. Black ethnicity had higher prepregnancy Body Mass Index (BMI; mean: 27.5 kg/m2±SD: 5.92, P=0.02), while Asian and White pregnancies had higher nulliparity rates (63.8% and 70.8%). Black ethnicity had no NIPT uptake (0.00%). Asian/Pacific islander and Latina pregnant had lower NIPT utilization (9.5% and 7.5%, P<0.001). White ethnicity had a higher NIPT rate (27.5%). In the NIPT group, 8.9% of White and 12.5% of Middle Eastern pregnancies chose cf-DNA without a prior first-trimester ultrasound test. Considering the first-trimester screening, 30.4% of Black pregnancies had nuchal translucency, while 17.4% combined it with beta-human chorionic gonadotrophin (β-hCG) and associated plasma protein-A (PAPP-A; P<0.001). White pregnancies had high adherence: 74.6% had nuchal translucency and 53.8% had a first-trimester combined test. Overall, 69.6% of Black pregnancies skipped both tests versus 16.5% in the White group (P<0.001). Significant disparities in prenatal care and NIPT adherence were observed among pregnant women of diverse ethnic backgrounds. Lower cf-DNA adhesion and limited adherence to first-trimester screening were observed among any ethnicities. These findings highlight the critical need for targeted interventions and policies to reduce barriers and facilitate access to prenatal care for all women.

Comprehensive Overview of Non-Invasive Prenatal Testing (NIPT) and its Ethical Considerations

This article provides an overview of Non-Invasive Prenatal Testing (NIPT), also known as noninvasive prenatal screening. It is a technique for estimating the likelihood that the fetus will have specific genetic defects at birth for pregnant women. The content is specifically tailored for pregnant women and ncompasses a detailed exploration of topics such as Genomics-based noninvasive prenatal tests, sample details for noninvasive prenatal testing, factors influencing test results, the interpretation of test results, limitations associated with the test, and the content included in the Declaration of Consent Form for Noninvasive Prenatal Testing.

Management and Delivery of a Patient with Maternal Myelomeningocele: A Case Report

Objective: To report and discuss the pregnancy course and delivery of a patient with maternal myelomeningocele at term Background: Spina bifida is a congenital malformation which results from incomplete closure of the neural tube. Open neural tube defects (NTD) comprise 80% of all NTDs. The most common open NTD is myelomeningocele (MMC), a form of spina bifida characterized by herniation of both the meninges and spinal cord. The incidence rate of MMC is approximately 1/1,000 live births worldwide, and is inversely related to socioeconomic status. There is a paucity of data on pregnant women with spina bifida, however a study by Shepard et al. investigated deliveries among 10,000 women with spina bifida and 42 million women without. This study revealed that women with spina bifida were significantly more likely to be delivered via cesarean section, even when vaginal delivery was possible. Also, pregnancy rates in spina bifida patients have risen over time. Case Description: A 29-year-old gravida 1 female at 12 weeks gestation presented to the Maternal Fetal Medicine (MFM) clinic due to maternal MMC. Past medical history was significant for MMC, Chiari malformation type II, neurogenic bowel, and neurogenic bladder. Past surgical history was significant for MMC repair, ventriculoperitoneal shunt, spine-to-abdomen shunt, cervical spine fusion, spinal cord untethering, and club foot correction. Patient ambulated using a walker. Noninvasive prenatal testing was low-risk. The alpha-fetoprotein was unremarkable at 22 ng/ml. Ultrasound revealed unilateral fetal pyelectasis. Fetal echocardiogram showed normal anatomy and function. The patient was admitted for 4 days at 33 weeks for a unilateral vulvar infection and hematoma that developed from repeated self-catheterization. The patient was admitted out of precaution due to past history of labial Fournier’s gangrene. Wound cultures grew prevotella bivia. Infectious disease recommended outpatient oral antibiotics at discharge. Anesthesiology recommended maternal MRI prior to delivery planning. MRI showed lumbar lordosis and severe canal compromise in the lumbosacral region. The low-lying conus terminated at L3-L4. Cauda equina nerve roots extended to the sacral region. Morphology of the sacrum and coccyx was abnormal, consistent with MMC. Imaging determined epidural and spinal anesthesia carried a high likelihood of analgesic failure from scar tissue due to prior surgeries. The patient ultimately agreed to general anesthesia. A primary low-transverse cesarean section was performed at 39 weeks 0 days. The baby was delivered without delayed cord clamping and had 1- and 5-minute APGAR scores of 6 and 9. Dense adhesions were present throughout the abdomen, which prevented uterine exteriorization during hysterotomy repair. The remainder of the surgery was uncomplicated and indwelling foley was kept in place postpartum. At 6-week postpartum visit, patient was fully healed and had resumed self-catheterization. Discussion: Pregnant women with spina bifida require complex multi-disciplinary co-management. This patient received care from MFM, neurology, urology, anesthesiology, infectious disease, and neurosurgery. Currently, there are no universally established guidelines on the management of pregnant women with spina bifida, but general principles of management exist. In the pre-conception period, it is recommended that patients at high-risk for fetal spina bifida, including type 1 diabetics, take 4mg of folate daily. High-risk patients should take folate for at least 3 months prior to conception and up until 12 weeks’ gestation. Since 9-12% of this population is affected by epilepsy, optimizing seizure medications is prudent. Lamotrigine or Carbamazepine monotherapy is preferred, as they pose the least risk of congenital malformations. In the antepartum period, providers should anticipate treating common comorbidities. Bladder dysfunction includes either hyper-reflexive or areflexive bladders. Intermittent self-catheterization is a viable option for those with incomplete bladder emptying. Pregnant patients with ventriculoperitoneal shunts are susceptible to displacement from the gravid uterus. Since limited mobility is prevalent in this population, risk assessments for venous thromboembolism should be completed, and prophylactic anticoagulation may be considered. Vaginal delivery is possible in some patients. However, epidural or spinal anesthesia can increase the risk of spinal cord injury in those with tethered cords or prior surgery. Patients with limited mobility may require cesarean section due to inability to position for labor. In conclusion, MMC is rarely encountered in obstetrical contexts but is becoming increasingly more commonplace. MMC requires co-management by multiple specialties to surveil and optimize common comorbidities. In this case, the patient’s pregnancy course was mainly complicated by her pre-existing neurogenic bladder and resulting vulvar wound secondary to self-catheterization. For MMC patients who are interested in pregnancy, preparations should be started in the pre-conception period, with close monitoring throughout the antepartum period to follow. Currently, there are generally accepted guidelines for managing MMC patients in pregnancy, but there is a lack of global standardization. The development of standardized treatment guidelines may be possible as more of these cases are discussed and appear in the literature.

Management and Delivery of a Patient with Maternal Myelomeningocele: A Case Report

Objective: To report and discuss the pregnancy course and delivery of a patient with maternal myelomeningocele at term Background: Spina bifida is a congenital malformation which results from incomplete closure of the neural tube. Open neural tube defects (NTD) comprise 80% of all NTDs. The most common open NTD is myelomeningocele (MMC), a form of spina bifida characterized by herniation of both the meninges and spinal cord. The incidence rate of MMC is approximately 1/1,000 live births worldwide, and is inversely related to socioeconomic status. There is a paucity of data on pregnant women with spina bifida, however a study by Shepard et al. investigated deliveries among 10,000 women with spina bifida and 42 million women without. This study revealed that women with spina bifida were significantly more likely to be delivered via cesarean section, even when vaginal delivery was possible. Also, pregnancy rates in spina bifida patients have risen over time. Case Description: A 29-year-old gravida 1 female at 12 weeks gestation presented to the Maternal Fetal Medicine (MFM) clinic due to maternal MMC. Past medical history was significant for MMC, Chiari malformation type II, neurogenic bowel, and neurogenic bladder. Past surgical history was significant for MMC repair, ventriculoperitoneal shunt, spine-to-abdomen shunt, cervical spine fusion, spinal cord untethering, and club foot correction. Patient ambulated using a walker. Noninvasive prenatal testing was low-risk. The alpha-fetoprotein was unremarkable at 22 ng/ml. Ultrasound revealed unilateral fetal pyelectasis. Fetal echocardiogram showed normal anatomy and function. The patient was admitted for 4 days at 33 weeks for a unilateral vulvar infection and hematoma that developed from repeated self-catheterization. The patient was admitted out of precaution due to past history of labial Fournier’s gangrene. Wound cultures grew prevotella bivia. Infectious disease recommended outpatient oral antibiotics at discharge. Anesthesiology recommended maternal MRI prior to delivery planning. MRI showed lumbar lordosis and severe canal compromise in the lumbosacral region. The low-lying conus terminated at L3-L4. Cauda equina nerve roots extended to the sacral region. Morphology of the sacrum and coccyx was abnormal, consistent with MMC. Imaging determined epidural and spinal anesthesia carried a high likelihood of analgesic failure from scar tissue due to prior surgeries. The patient ultimately agreed to general anesthesia. A primary low-transverse cesarean section was performed at 39 weeks 0 days. The baby was delivered without delayed cord clamping and had 1- and 5-minute APGAR scores of 6 and 9. Dense adhesions were present throughout the abdomen, which prevented uterine exteriorization during hysterotomy repair. The remainder of the surgery was uncomplicated and indwelling foley was kept in place postpartum. At 6-week postpartum visit, patient was fully healed and had resumed self-catheterization. Discussion: Pregnant women with spina bifida require complex multi-disciplinary co-management. This patient received care from MFM, neurology, urology, anesthesiology, infectious disease, and neurosurgery. Currently, there are no universally established guidelines on the management of pregnant women with spina bifida, but general principles of management exist. In the pre-conception period, it is recommended that patients at high-risk for fetal spina bifida, including type 1 diabetics, take 4mg of folate daily. High-risk patients should take folate for at least 3 months prior to conception and up until 12 weeks’ gestation. Since 9-12% of this population is affected by epilepsy, optimizing seizure medications is prudent. Lamotrigine or Carbamazepine monotherapy is preferred, as they pose the least risk of congenital malformations. In the antepartum period, providers should anticipate treating common comorbidities. Bladder dysfunction includes either hyper-reflexive or areflexive bladders. Intermittent self-catheterization is a viable option for those with incomplete bladder emptying. Pregnant patients with ventriculoperitoneal shunts are susceptible to displacement from the gravid uterus. Since limited mobility is prevalent in this population, risk assessments for venous thromboembolism should be completed, and prophylactic anticoagulation may be considered. Vaginal delivery is possible in some patients. However, epidural or spinal anesthesia can increase the risk of spinal cord injury in those with tethered cords or prior surgery. Patients with limited mobility may require cesarean section due to inability to position for labor. In conclusion, MMC is rarely encountered in obstetrical contexts but is becoming increasingly more commonplace. MMC requires co-management by multiple specialties to surveil and optimize common comorbidities. In this case, the patient’s pregnancy course was mainly complicated by her pre-existing neurogenic bladder and resulting vulvar wound secondary to self-catheterization. For MMC patients who are interested in pregnancy, preparations should be started in the pre-conception period, with close monitoring throughout the antepartum period to follow. Currently, there are generally accepted guidelines for managing MMC patients in pregnancy, but there is a lack of global standardization. The development of standardized treatment guidelines may be possible as more of these cases are discussed and appear in the literature

Correlation between types of ventricular septal defect and chromosomal abnormalities in low-risk non-invasive prenatal testing.

The aim of this study was to examine whether there is a correlation between different types of ventricular septal defects (VSD) and chromosomal abnormalities in the low-risk setting of non-invasive prenatal testing (NIPT) and to evaluate the prognosis of fetuses with varying types of VSD. Cases of pregnant women who underwent amniocentesis due to fetal VSD were collected by Tianjin Central Hospital of Obstetrics and Gynecology from May 2017 to May 2022. Exclusions were made for those without NIPT, with high-risk NIPT results, genetic disorders, and those lost to follow-up. Data collected included ultrasound classification of VSD, prenatal NIPT results, copy-number variations (CNVs) results, and neonatal outcomes. The prevalence of pathogenic CNVs was investigated in 74 cases of VSDs. Of these cases, 45 were isolated VSDs (9 muscular and 36 non-muscular) and 29 were non-isolated VSDs (10 with intracardiac and 19 with extra-cardiac structural anomalies). The results revealed that the incidence of pathogenic CNVs was lower in isolated VSDs compared to non-isolated VSDs in a low-risk NIPT condition (χ2 = 9.344, P = 0.002). There was no significant difference in the prevalence of pathogenic CNVs between VSDs with intracardiac and extra-cardiac structural anomalies (P = 0.541). Moreover, VSDs associated with intracardiac structural anomalies had the highest rate of surgical intervention. When NIPT is low-risk and VSD is isolated, the likelihood of fetal chromosomal defects is not increased. However, if there are intra- or extra-cardiac structural abnormalities present alongside VSD, the possibility of pathogenic CNV is considerably greater, necessitating invasive prenatal diagnosis. Isolated muscular VSDs usually do not require surgery, which can be used as a basis for prenatal counseling regarding fetal VSD.

Investigational Management for a Positive NIPT Result - Case Report

Non-invasive prenatal testing (NIPT), since its introduction in 2011, has revolutionized prenatal screening, becoming widely used globally and replacing traditional screening methods in developed countries. The accuracy of NIPT in detecting aneuploidies is etremely high and there has been a recent trend towards improving NIPT for detecting microdeletion and microduplication syndromes, monogenic diseases, fetal se determination, and RH genotyping. Significant progress has been made in molecular analysis techniques of fetal DNA, including methods such as massively parallel sequencing, RNA-based testing, digital PCR, and single nucleotide polymorphism analysis. We present the case of a 32-year-old patient who, at 12 weeks of gestation, had a non-invasive prenatal test result showing a maternal 22q11.2 deletion. Following genetic consultation, further investigations were conducted to stratify the fetal risk of inheriting the microdeletion syndrome. As a result, microarray CGH cytoarray from amniotic fluid was performed, and no 22q11.2 deletion was detected. In this case, complete elucidation of the origin of the deletion found in NIPT could not be achieved, as it would require arrayCGH testing for the mother, a test that was not performed due to financial reasons. Given the high rate of genetic syndromes with potential impact on fetal development and familial psychological impact, we wish to emphasize the necessity of financial support from the state to introduce non-invasive prenatal testing into the list of reimbursed analyses covered by health insurance. This would enable superior testing and, implicitly, genetic prevention of all pregnancies, facilitating appropriate risk stratification of pregnancies in our country.

Performance analysis of non-invasive prenatal testing for trisomy 13, 18, and 21: A large-scale retrospective study (2018–2021)

BackgroundNon-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. MethodsPregnant women (n = 282,911) participating in a free NIPT (April 2018–December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. ResultsAfter NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. ConclusionNIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

Understanding the Normativity of Health Technology Assessment: Ontological, Moral, and Epistemological Commitments.

The inherent normativity of HTA can be conceptualized as a result of normative commitments, a concept that we further specify to encompass moral, epistemological and ontological commitments at play in the practice of HTA. Based on examples from literature, and an analysis of the example of assessing Non-Invasive Prenatal Testing (NIPT), we will show that inevitable normative decisions in conducting an assessment commits the HTA practitioner to moral (regarding what makes a health technology desirable), ontological (regarding which effects of health technology are conceivable), and epistemological (regarding how to obtain reliable information about health technology) norms. This highlights and supports the need for integrating normative analysis and stakeholder participation, providing guidance to HTA practitioners when making normative choices. This will foster a shared understanding between those who conduct, use, or are impacted by assessments regarding what are conceivable and desirable outcomes of using health technology, and how to collect reliable information to assess whether these outcomes are (going to be) realized. It also provides more insight into the implications of different normative choices.

Insights Into Down Syndrome Screening and Diagnostic Test Preferences Among Pregnant Women: Findings from a Cross-Sectional Study in Vietnam

Background: Screening for Down syndrome (DS) conducted in the first trimester provides essential information for expectant parents and healthcare providers to make informed decisions about further diagnostic testing and potential interventions. Objectives: This study aimed to explore the preferences and influential factors for subsequent screening and diagnostic tests among Vietnamese women at risk for DS, including non-invasive prenatal testing (NIPT) and amniocentesis. Methods: A cross-sectional study was conducted from January 2022 to January 2023 with 125 pregnant women selected through convenience sampling at a public hospital in Vietnam. Data were collected from standardized medical records and analysis forms for each participant who underwent first-trimester Double test screening at the healthcare center. Participants were stratified by DS risk thresholds ranging from 1/51 to 1/1000. Chi-square and Fisher's exact tests were used to compare the acceptance rate of screening tests between groups. Logistic regression was utilized to explore factors related to participants' preferences. Results: The majority (71.2%) of participants were under 35 years old. The prevalence of consenting to further tests was 69.7% in the high-risk group (95% CI: [54.02%, 85.38%]) and 67.4% in the moderate-risk group (95% CI: [57.81%, 76.97%]), with all participants in the moderate-risk group selecting NIPT. In the high-risk group, 65.22% preferred NIPT and 34.78% chose amniocentesis. The key reasons for declining further testing included a preference for ultrasound monitoring (70%), financial constraints (7.5%), and religious beliefs (10%). Chi-square analysis indicated a statistically significant variation in diagnostic test selection by age group, with younger women more likely to choose NIPT (P &lt; 0.0001). Conclusions: There is a marked preference for NIPT over invasive methods, especially among younger moderately risk women. These results emphasize the need for individualized counseling and education, as well as increased support for noninvasive testing options through healthcare policy and insurance coverage.

Advancements of non-invasive prenatal testing: the role of obstetricians

Advancements of non-invasive prenatal testing: the role of obstetricians

The performance evaluation of NIPT for fetal chromosome microdeletion/microduplication detection: a retrospective analysis of 68,588 Chinese cases.

Chromosomal abnormalities are the main cause of birth defects in newborns. Since the inception of noninvasive prenatal testing (NIPT) technology, it has primarily been applied to the detection of common trisomy (T21, T18, T13). However, the application of NIPT in microdeletion and microduplication detection is still controversial. This study retrospectively analyzed the data of 68,588 cases that underwent NIPT at Ganzhou Maternal and Child Health Hospital in China. These data were used to evaluate the performance of NIPT in fetal chromosome microdeletion/microduplication detection and to investigate the key factors affecting the NIPT performance. A total of 281 cases (0.41%) had positive NIPT results with copy number variants (CNVs), of which 161 were validated by karyotyping and chromosome microarray analysis (CMA). Among the 161 cases, 92 were confirmed as true positives through karyotyping or CMA, including 61 microdeletion cases and 31 microduplication cases, resulting in a positive predictive value (PPV) of 57.14%. Improvements in library construction methods increased the fraction of cell-free fetal DNA (cffDNA) from 13.76% to 18.44%, leading to a significant improvement in the detection rate (0.47% vs. 0.15%) and PPV (59.86% vs. 28.57%) of NIPT for CNVs. This study proved the robust performance of NIPT for fetal chromosome microdeletion/microduplication detection. In addition, the cffDNA fraction is a key factor influencing NIPT, with increased cffDNA fraction improving the performance of NIPT.