Prenatal Test Results Research Articles

The distribution of regions of homozygosity (ROH) among consanguineous populations-implications for a routine genetic counseling service.

Regions of homozygosity (ROH) increase the risk of recessive disorders, and guidelines recommend reporting of excessive ROH in prenatal testing. However, ROH are common in populations that practice endogamy or consanguinity, and cutoffs for reporting ROH in such populations may not be evidence-based. We reviewed prenatal testing results (based on cytogenetic microarrays) from 2191 pregnancies in the Jewish and non-Jewish populations of Northern Israel and estimated the prevalence of ROH according to self-reported ethnicity and parental relationships. The proportion of the genome in ROH, ROH rate, was higher in non-Jews [Mean (SD) = 2.91% (3.92%); max = 25.54%; N = 689] than in Jews [Mean (SD) = 0.81% (0.49%); max = 3.93%; N = 1502]. In the non-Jewish populations, consanguineous marriages had the highest ROH rates [Mean (SD) = 7.14% (4.55%), N = 217], followed by endogamous [Mean (SD) = 1.13% (1.09%), N = 283] and non-endogamous [Mean (SD) = 0.69%(0. 56%), N = 189] marriages. ROH rates were greater than 5%, the ACMG-recommended cutoff, in 149/689 (21.63%) of the non-Jewish samples. Within the Jewish populations, the rates were similar between Ashkenazi, North African, and Middle Eastern Jews, but were higher for six consanguineous unions [Mean (SD) = 2.38% (1.23%)] and when spouses belonged to the same sub-population. Given the high ROH rates we observed in some subjects, we suggest that assessing the risk for recessive conditions in consanguineous/endogamous populations should be done before the first pregnancy, through genetic counseling and sequencing. Such an approach will: (1) identify couples who are at risk and counsel them on reproductive options; and (2) avoid the stress that couples who are not at risk may experience due to a prenatal ROH report.

Is intermediate risk really intermediate? Comparison of karyotype and non-invasive prenatal testing results of pregnancies at intermediate risk of trisomy 21 on maternal serum screening.

The purpose of this study was to assess the additional contribution of karyotyping compared with genome-wide non-invasive prenatal testing (NIPT) for pregnancies at intermediate risk for trisomy 21 (T21), calculated using the maternal serum screening without major structural anomalies detected through sonography. Karyotype results of all pregnancies undergoing invasive prenatal diagnostic testing between January 2013 and March 2022 were obtained from a large hospital-based laboratory. Pregnancies with no major structural anomalies on ultrasound (including soft markers) and an intermediate risk for T21 on maternal serum screening were included in this study. The additional contribution of karyotyping for abnormal karyotype results was calculated after excluding results that could theoretically be identified with genome-wide NIPT. Among the 511 pregnancies analyzed, 13 (2.54%) were found to have abnormal karyotype results, 9 (1.76%) of which could theoretically have been detected with genome-wide NIPT. Within the cohort, 6/263 (2.28%) of women aged 35 years and older, and 3/248 (1.20%) of women younger than 35 years had results that could have been detected with genome-wide NIPT. After excluding results detectable using genome-wide NIPT, the additional contribution of karyotyping was found as 4/502 (0.79%) for the entire cohort, 2/257 (0.77%) for women aged 35 years and older, 2/245 (0.81%) for women younger than 35 years. Of the 511 examined pregnancies at intermediate risk for T21 by maternal serum screening, genome-wide NIPT would have failed to detect 4 of 13 abnormal karyotype results. The findings hold importance in guiding couples' informed decision-making processes regarding their choice of genetic screening and diagnostic testing in case of intermediate risk for T21.

Hierarchical Classification of Factors Associated With Noninvasive Prenatal Testing Failures and Its Impact on Pregnancy Outcomes

Abstract Objective To conduct a hierarchical classification analysis of the nonreportable results of noninvasive prenatal testing in an attempt to reduce failure rates and provide pregnant women with accurate information to alleviate their anxiety. Methods In this study, 30,039 singleton pregnancies who underwent noninvasive prenatal testing in a single center from May 2019 to April 2022 were collected, and 811 samples with initial noninvasive prenatal testing failure were retrospectively analyzed. Grouping was based on the reasons for initial test failure; tracking the noninvasive prenatal testing results and prenatal diagnosis results (if any) of the “z-scores in the gray area” group and analyzing the possible influencing factors of the “low fetal fraction” group in the pre-experimental and experimental period by using one-way analysis of variance, Mann-Whitney U test, and χ2 test; and tracking the pregnancy outcomes of the test failures samples to analyze the risk of perinatal complications and adverse pregnancy outcomes of the different types of test failures. Results None of the samples' initial inconclusive results because of z-scores in the gray area were found to have chromosomal aneuploidy. However, pregnancy complications (P = 0.018) and a high likelihood of adverse pregnancy outcomes (P = 0.048) may still occur. Maternal gestational age (P < 0.001), body mass index (P < 0.001), library concentration (P < 0.001), and fetal gender (P < 0.001) were considered to be the associated factors for the initial low fetal fraction results. This may be associated with pregnancy complications (P < 0.001) and a high likelihood of adverse pregnancy outcomes (P = 0.034). The body mass index (P = 0.015) and time between draws (P = 0.001) were associated with the second test’s success. The incidence of low fetal fraction samples was more frequent with blood collection tubes of the G type than with the K type (P < 0.001). Conclusion Initial inconclusive results because of z-scores in the gray area did not imply an increased risk of aneuploidy, but vigilance is needed for an increased risk of pregnancy complications and adverse pregnancy outcomes. Because of the low fetal fraction, the initial absence of results may be related to the assay method, as well as the effect of blood collection tubes and the need to be alert to the risk of pregnancy complications and adverse pregnancy outcomes.

O-154 Chromosomal, gestational, and neonatal outcomes of mosaic embryos: analysis of 3074 cases from the international registry of mosaic embryo

Abstract Study question Which are the clinical outcomes and post-natal results of mosaic embryos with low and high-level of mosaicism? Summary answer The level of mosaicism negatively influences implantation and ongoing pregnancy rate. 6/7 cases in which mosaicism persisted in the foetuses were from low-level mosaic. What is known already Chromosomal mosaic embryos are characterized by the presence of chromosomally different cell lines within the same embryo. While the transfer of these embryos is now offered as an option for women who undergo in vitro fertilization (IVF), several concerns remain. For instance, the limited data on pregnancy outcome and the possibility that intra-biopsy mosaicism in the TE is a poor predictor of the ploidy status of the ICM. Therefore, some argue that mosaicism should be not reported until a clear classification of such embryos in relation to their reproductive potential has been defined. Study design, size, duration We collected the clinical outcomes of 3074 mosaic embryos transferred in women who underwent IVF between May 2019-May 2023. All embryos were cultured to blastocyst stage; trophectoderm (TE) biopsy was performed on Day-5 of development or Day6/7 for slow-growing embryos. The clinical outcome obtained after the transfer of mosaic embryos with the different chromosomal constitutions was compared with each other. Prenatal and post-natal outcomes were collected for available cases. Participants/materials, setting, methods Preimplantation genetic testing (PGT) was performed using high-resolution next-generation sequencing (NGS) methodology. TE biopsies were classified as mosaic if they had 20%-80% abnormal cells. For statistical analysis, mosaic embryos were divided into groups based on mosaic levels and chromosomal constitution detected in TE: single mosaic aneuploidy (monosomy/trisomy; SM), double mosaic chromosomes (monosomy/trisomy or combination, DM), complex mosaic aneuploidy (>2 different aneuploidies; CM) and mosaic segmental aneuploidy (single and double deletion/insertion >5Mb, MS). Main results and the role of chance Embryos classified as ‘low-mosaic’ by NGS-based PGT-A have a higher likelihood of achieving implantation compared to ‘high-mosaic’ embryos (48% vs. 39.%; p < 0.05 ), as well as ongoing pregnancy/live birth (40% vs. 29%; p < 0.05). Chromosomal composition of mosaicism abnormalities dictates the success rate of mosaic embryo transfers, with low and high segmental mosaics being preferable over low- and high-mosaics involving whole chromosomes. For 621/670 pregnancies, parental tests and post-natal data were available. The majority (99.75%) of the babies were largely healthy by routine physical inspection by neonatologists (no gross abnormalities in babies from mosaic embryos, n = 495). A combination of NIPT, CVS, and Amniocentesis prenatal testing results were collected for 552 pregnancies of mosaic embryo transfers, with predominantly normal findings. The mosaicism detected at the embryonic stage by PGT-A was reflected in prenatal testing in only 7 out of 552 pregnancies (0.9%), in which the mosaicism identified with PGT-A at the blastocyst stage was reflected in gestation by prenatal chromosomal testing as true fetal mosaicism. Limitations, reasons for caution Additional clinical data must be obtained to evaluate the contribution of each different chromosome before this approach can be evaluated as an additional tool to choose mosaic embryos for transfer. Wider implications of the findings The international registry of mosaic embryo transfers continues to grow in sample size, in turn increasing the power of analysis. The findings of the mosaic embryo transfer registry can help educate the management and selection of embryos in the clinic. Trial registration number no

Noninvasive Prenatal Test Results Indicative of Maternal Malignancies: A Nationwide Genetic and Clinical Follow-Up Study

The author describes the results and implications of a study on noninvasive prenatal test results that indicate maternal malignancies.

Zygotic-splitting after in vitro fertilization and prenatal parenthood testing after suspected embryo mix-up – a case report

After in vitro fertilization with a single embryo, the parents learned about being pregnant with twins in the 10th week with various indications that an embryonic mix-up could have taken place. The affected couple thus expressed the urgent desire for a clarification of parenthood considering an abortion. However, the prenatal test results would not have been available until the 14/15th week of pregnancy. Legally, then, severe physical or mental distress of the pregnant woman must be claimed by physicians to justify an abortion after the twelfth week. However, a lack of genetic relatedness could lead to serious psychological distress for the parents, making a pregnancy termination possible even after the twelfth week, which is discussed in this case study alongside the interdisciplinary team’s ethical, legal, and medical considerations.For the invasive relationship testing, cultivated chorionic villi samples (CVS) from both unborn and saliva samples from the putative parents were genetically analyzed using classical short tandem repeats (STR) analysis. The perfect match of both CVS profiles suggested the occurrence of an unusual late twin shaft, for which, fortunately, parenthood could be confirmed. To our knowledge, this is the first report on a prenatal investigation of a suspected embryo mix-up after assisted reproductive technology (ART), in which parenthood should be fixed. We want to draw attention to this unthinkable scenario, which may increase in the future with ART-induced rising multiple pregnancies.

Increased Nuchal Translucency and Pregnancy Outcomes: A Tertiary Center Data

Aim: This study aimed to evaluate the pregnancy outcomes of patients who applied to our clinic between the 11th and 14th weeks of pregnancy and whose nuchal translucency (NT) measurement was ≥1.5 multiples of the median (MoM). Material and Methods: The study included 85 patients whose NT measurement was determined ≥1.5 MoM and pregnancy results were available. Demographic characteristics of the patients, prenatal invasive diagnostic test results, fetal anomaly screening, fetal echocardiography (ECHO) results, and neonatal and obstetric results were evaluated. Results: Abnormal karyotype was detected in 10.6% (n=9) of the patients. Trisomy 21 was the most common chromosomal anomaly. Fetal structural anomaly was detected in 29.4% (n=25) of the patients. A structural fetal anomaly was detected in 21% (n=13) of fetuses with normal karyotypes and 66.7% (n=6) of fetuses with abnormal karyotypes. Cardiac anomalies were found to be the most common anomalies with 9.7% (n=6) in patients with normal karyotype. NT and NT MoM values in patients with fetal structural (both p=0.001) or chromosomal anomalies (p=0.011, and p=0.019, respectively) were found significantly higher than those without. NT and NT MoM values in patients whose pregnancies resulted in fetal loss were found significantly higher than in patients who had a live birth (both p=0.001). Conclusion: Increasing NT or NT MoM values indicate an increase in the risk of chromosomal anomalies, structural anomalies, and poor pregnancy outcomes in the fetus. Fetal anomaly screening and fetal ECHO should be recommended in patients with increased NT, even if a normal karyotype is detected.

Parental questions about sex chromosome aneuploidies regarding sex, gender, and sexual orientation as reported by genetic counselors in a prenatal setting.

The introduction of cell-free DNA screening has resulted in increased prenatal identification of sex chromosome aneuploidies (SCAs). This study aimed to evaluate genetic counselor experiences disclosing SCAs positive prenatal screening or testing results and genetic counselor-reported parental questions regarding sex, gender, and sexual orientation. Forty-eight prenatal genetic counselors completed the survey. When asked to quantify their experiences, 97.9% of counselors reported disclosing a SCAs positive screen result within the previous year, and 81.3% disclosed a diagnostic result. Of those counselors, 53.8% reported always or often receiving parental questions about sex, 33% always or often about gender, and 25% always or often regarding sexual orientation. Counselors were asked to share examples of parental questions following a positive screen or diagnostic testing for SCAs. Parental questions were stratified by karyotype and content analysis revealed questions about the fetus' sex, anatomy, reproduction, being cisgender, gender expression, behavior, being transgender, and sexual orientation. The examples of parental questions provided by genetic counselors suggested some parents may have misconceptions about the intersection of SCAs with sex, gender, and sexual orientation following prenatal screening or diagnostic testing. The majority of counselors (83.3%) agreed to some extent that they desired further education on responding to parental questions about SCAs. Findings from this research suggest a need for genetic counseling strategies that accurately and respectfully discuss SCAs in the context of sex, gender, and sexual orientation with prenatal patients.

Comprehensive Recommendations for the Clinical Management of Pregnant Women With Noninvasive Prenatal Test Results Suspicious of a Maternal Malignancy.

In this article, we defined comprehensive recommendations for the clinical follow-up of pregnant women with a malignancy-suspicious NIPT result, on the basis of the vast experience with population-based NIPT screening programs in two European countries complemented with published large data sets. These recommendations provide a tool for classifying NIPT results as malignancy-suspicious, and guide health care professionals in structured clinical decision making for the diagnostic process of pregnant women who receive such a malignancy-suspicious NIPT result.

Navigating Uncertain Waters: First-Trimester Screening's Role in Identifying Neonatal Complications.

Background: Contemporary diagnostic methods aimed at assessing neonatal outcomes predominantly rely on the medical history of pregnant women. Ideally, universal biomarkers indicating an increased risk of delivering infants in poor clinical condition, with a heightened likelihood of requiring hospitalization in a Neonatal Intensive Care Unit (NICU), would be beneficial for appropriately stratifying pregnant women into a high-risk category. Our study evaluated whether biochemical and ultrasonographical markers universally used in first-trimester screenings for non-heritable chromosomal aberrations could serve this purpose. Methods: This study encompassed 1164 patients who underwent first-trimester screening, including patient history, ultrasound examinations, and biochemical tests for pregnancy-associated plasma protein-A (PAPP-A) and the free beta-HCG subunit (fbHCG), from January 2019 to December 2021. The research concentrated on the correlation between these prenatal test results and neonatal outcomes, particularly Apgar scores, umbilical blood pH levels, and the necessity for NICU admission. Results: In our cohort, neonates scoring lower than 8 on the Apgar scale at birth exhibited lower concentrations of PAPP-A in the first trimester, both in raw and normalized values (PAPP-A MoM 0.93 vs. 1.027, p = 0.032). We also observed a higher pulsatility index in the venous duct in the first trimester in full-term neonates born with <8 points on the Apgar scale. Additionally, newborns born with an umbilical blood pH < 7.2 had lower normalized first-trimester PAPP-A concentrations (0.69 vs. 1.01 MoM, p = 0.04). We also noted that neonates requiring NICU hospitalization post-delivery had lower first-trimester bHCG concentrations (0.93 MoM vs. 1.11 MoM, p = 0.03). However, none of the correlations in our study translated into a robust prognostic ability for predicting dichotomous outcomes. All areas under the curve achieved a value < 0.7. Conclusions: Low concentrations of PAPP-A and free bHCG subunit in the first trimester may be associated with poorer clinical and biochemical conditions in neonates post-delivery. However, the relationship is weak and has limited predictive capability. Further research evaluating these relationships is necessary for the appropriate stratification of pregnant women into high-risk categories for neonatological complications.

The Evaluation of Invasive Prenatal Diagnostic Tests in North Cyprus: A Retrospective Study.

Congenital diseases are still an important medical, social, and economic problem all over the world. In North Cyprus, in addition to other reasons, early prenatal diagnostic measures are undertaken to prevent births with thalassemia major, a locally widespread genetic disease. This study aims to evaluate the results of prenatal invasive diagnostic tests performed in a private obstetrics clinic in Northern Cyprus and show the diagnosis process of thalassemia and chromosomal anomalies. This study is a retrospective, descriptive study. Chorionic villus sampling (CVS) results and the amniocentesis tests performed between 1990 and 2022 are evaluated. Thalassemia and chromosome analysis of samples obtained by CVS and amniocentesis tests were performed. To diagnose alpha or beta thalassemia and sickle cell, 239 CVS was performed. And to diagnose chromosomal anomalies, 396 CVS and amniocentesis were performed. The mean age of the 480 pregnant women included in the study was 31.12 years (18-46) and 30% of them were older than 34 years. The most common indications for invasive prenatal diagnostic test (IPDT) were; mother/father thalassemia minor/major, advanced maternal age, high risk of ultrasonography erase findings, and the noninvasive screening test. The result of IPDT detected 7.3% chromosomal anomaly and 69.5% thalassemia and sickle cell anemia. Of the 239 CVS performed to diagnose alpha or beta thalasemia and sickle cell, 23.4% beta major, 42.3% beta minor, and 2.1% alpha minor were diagnosed. Of the 396 CVS and amniocentesis performed to diagnose chromosomal anormalies; 2.8% of Down syndrome and 4.54% of other chromosomal anomalies were diagnosed. IPDT is important in correctly diagnosing fetal anomalies at the prenatal stage to help families decide at the right time.

Prenatal diagnosis of criss-cross heart – case series and review of the literature

Objective This study aimed to improve the accuracy of prenatal diagnosis by analyzing fetal echocardiographic features of criss-cross heart (CCH), to provide an effective basis for the development of management strategies and improve the prognosis of patients. Methods A retrospective analysis was performed on CCH cases diagnosed prenatally at our center between July 2016 and June 2022. Clinical data and prenatal fetal echocardiographic images were reviewed. Literature on prenatal diagnosis of CCH was searched from January 2000 to December 2023 in the PubMed database. Results Fourteen (0.03%) CCH cases were diagnosed from a database of fetal echocardiograms of 41354 cases at our center. The prenatal genetic testing results were normal in 10 cases and 4 cases didn’t check. All cases underwent termination of pregnancy. All cases showed crossed ventricular inflow tracts and combined with other cardiac structural abnormalities. A total of eight articles containing 25 cases were found in the literature review and all cases were associated with other cardiac structural abnormalities. Conclusion Prenatal echocardiography is the primary tool for fetal diagnosis of CCH. Continuous scanning helps avoid missing data and misdiagnosis.

Contribution of uniparental disomy to fetal growth restriction: a whole-exome sequencing series in a prenatal setting

Fetal growth restriction (FGR), a leading cause of perinatal morbidity and mortality, is caused by fetal, maternal, and placental factors. Uniparental disomy (UPD) is a rare condition that leads to imprinting effects, low-level mosaic aneuploidies and homozygosity for pathogenic variants. In the present study, UPD events were detected in 5 women with FGR by trio exome sequencing (trio-WES) of a cohort of 150 FGR cases. Furthermore, noninvasive prenatal testing results of the 5 patients revealed a high risk of rare autosomal trisomy. Trio-WES showed no copy-number variations (CNVs) or nondisease-causing mutations associated with FGR. Among the 5 women with FGR, two showed gene imprinting, and two exhibited confined placental mosaicism (CPM) by copy number variant sequencing (CNV-seq). The present study showed that in FGR patients with UPD, the detection of imprinted genes and CPM could enhance the genetic diagnosis of FGR.

Limited additional value of karyotyping cultured amniotic fluid cell colonies in addition to microarray on uncultured cells for confirmation of abnormal non-invasive prenatal testing results.

Non-invasive prenatal testing (NIPT) allows the detection of placental chromosome aberrations. To verify whether the fetus also has the chromosome aberration, diagnostic follow-up testing is required. The aim of this retrospective study was to assess the added value of analyzing amniotic fluid (AF) cell cultures in addition to uncultured AF cells for the detection of fetal mosaicism. NIPT was performed as part of the Dutch TRIDENT study. Cytogenetic studies in uncultured AF were performed using single nucleotide polymorphism (SNP)-array. Cultured AF cell colonies (in situ method) were investigated with fluorescent in situ hybridization and/or karyotyping. Clinical outcome data were collected in cases with discordant results. Between April 2014 and December 2021, 368 amniocenteses were performed after a chromosomal aberration was detected with NIPT. Excluding 134 cases of common aneuploidies (confirmed by quantitative fluorescence polymerase chain reaction), 29 cases with investigation of uncultured cells only and 1 case without informed consent, 204 cases were eligible for this study. In 196 (96%) cases, the results in uncultured and cultured cells were concordant normal, abnormal or mosaic. Five cases (2%) showed mosaicism in cultured AF cells, whereas uncultured AF cells were normal. Two (1%) of these, one mosaic trisomy 13 and one mosaic trisomy 16, were considered true fetal mosaics. The added value of investigating AF cell cultures in addition to uncultured cells is limited to two of 204 (1%) cases in which true fetal mosaicsm would otherwise be missed. The clinical relevance of one (trisomy 13) remained unknown and the other case also showed ultrasound anomalies, which determined pregnancy management. This seems to justify limiting prenatal cytogenetic confirmatory testing to SNP arrays on uncultured AF cells, considerably shortening the reporting time.

KNOWLEDGE LEVELS, ATTITUDES, AND BEHAVIORS OF PREGNANTS ABOUT PRENATAL SCREENING TESTS: A SECTIONAL STUDY

Aim: To determine the knowledge levels, attitudes, and behaviors of pregnant women who come to the obstetrics clinic in a university hospital about prenatal screening tests.&#x0D; Method: It is a descriptive cross-sectional study. The population consists of approximately 900 pregnant women who are 28 weeks and beyond, who applied to …….. University Faculty of Medicine, Obstetrics and Gynecology outpatient clinic between October-December 2021. The research questionnaire was applied face to face to those who agreed to participate in the study. The data form consisting of 21 questions included questions about the descriptive characteristics and obstetric histories of pregnant women.&#x0D; Results: 254 people participated. The mean gestational week of the participants was 34.9±3.9 (min:28-max:41). The most common screening tests were detailed ultrasound (80.7%) and double screening tests. Those who received information from their obstetrician had a significantly higher rate of having the test. When the participants' knowledge scores about prenatal screening tests are evaluated, respectively; Detailed ultrasound knowledge score was 5.6±0.9, Double test 5.0±1.3, Oral Glucose Tolerance Test 4.8±1.1, and Triple test 4.7±1.2(min:2-max:7). When the reasons for not having prenatal screening tests were questioned, the most common answer for all screening tests was "I don't think the test is necessary". For the OGTT, the second most common reason for not having it done was because they heard from the media that the test was harmful. The fact that the pregnant women had a double and triple screening, went to regular controls and had a high double-triple test knowledge score had a significant effect. Amniocentesis was recommended for 3.5% of the pregnant women based on prenatal test results, but none of them had amniocentesis. In case of unfavorable prenatal test results, the majority of pregnant women were considering continuing the pregnancy.&#x0D; Conclusion: In this study, we found that the rate of testing increased with the increasing knowledge level of pregnant women and physician counseling. In this context, health professionals should provide women with the necessary education about screening and diagnostic tests to enable them to make informed decisions.

Improving patient understanding of prenatal screening tests: Using naturally sampled frequencies, pictures, and accounting for individual differences

ObjectiveHealth professionals must communicate prenatal screening test results effectively to patients, but these tests involve very low prevalence and high false positive risks; a situation known to be difficult for people to understand. MethodsThe present experiments evaluated the effectiveness of presenting prenatal screening test results for Trisomy 21, Trisomy 13, or DiGeorge Syndrome, using either naturally sampled frequencies or standard percentages. Participants were given a task of interpreting the posterior probability of an embryo having the condition. ResultsPeople were significantly better with naturally sampled frequencies. Numerical literacy and visuospatial ability significantly accounted for individual differences in performance within conditions. Participants nevertheless did not differ in ratings of how useful the different presentation formats were, suggesting a lack of awareness of how format influenced understanding. These results held regardless of whether the respondents were undergraduates (Experiment 1) or members of the general population recruited online (Experiment 2). ConclusionUsing naturally sampled frequencies improves patient understanding of prenatal screening tests results, with low cost of implementation. InnovationUsing realistic prenatal screening test results, these results show how to improve patient counseling via the use of naturally sampled frequencies.

Analysis of the results of non-invasive prenatal testing (NIPT) in 545 pregnant women in advanced maternal age.

This research aimed to explore the value of non-invasive prenatal testing (NIPT) as a prenatal screening method for common aneuploidy in pregnant women in advanced maternal age. A retrospective analysis was conducted on a cohort of 545 mothers with singleton pregnancy who were of advanced age and underwent NIPT testing voluntarily at the Second Affiliated Hospital of Guangxi Medical University between November 2020 and February 2023. In cases where NIPT testing suggested chromosomal abnormalities, amniocentesis was conducted, karyotype analysis or gene copy number variation (CNV) testing was performed, and the pregnancy outcome was tracked. Among 545 pregnant women in advanced maternal age, 11 cases had high risk of NIPT, and the detection rate was 2.02%. Among 11 pregnant women deemed to be at high risk for NIPT, 10 cases underwent amniotic fluid puncture, and one case refused amniocentesis despite a suggestive chromosomal abnormality in NIPT. The overall rate of amniocentesis was 1.83%. Among 11 pregnant women deemed to be at high risk for NIPT, the results suggested that 5 of them had trisomy 21, 1 had trisomy 18, 2 had sex chromosome abnormalities (specifically, 47, XYY), and 3 had other autosomal abnormalities. The positive predictive values of NIPT were 100.00% for the cases of trisomy 21 and trisomy 18, while the values were 0.00% for the cases of sex chromosome abnormalities and other autosomal abnormalities, respectively. After the follow-up, each of the 6 cases that were diagnosed with definite chromosomal abnormalities during prenatal screening opted to induce labor and terminate the pregnancy, including 5 cases that exhibited a high risk of trisomy 21 (47, XN,+21) and 1 case that showed a high risk of trisomy 18 (47, XN,+18). One instance of NIPT indicated a potential abnormality in the sex chromosomes, the individual declined to undergo amniocentesis. Another instance of NIPT suggested a sex chromosome abnormality, amniocentesis revealed a deletion of 0.72 Mb in the 4q22.1 region. They all had normal pregnancies and normal newborns. The remaining three cases had normal prenatal diagnoses (46, XN) and experienced normal pregnancies with healthy neonatal outcomes. NIPT has demonstrated its efficacy as a screening tool in the face of increasing maternal age. As a result, it can substantially decrease the requirement for invasive prenatal diagnosis. Nonetheless, there are instances of erroneous positive outcomes in NIPT testing, and therefore, interventional prenatal diagnosis remains necessary for individuals with high-risk screening outcomes to prevent false positives or unwarranted labor induction.

The value of detailed first-trimester ultrasound in the era of noninvasive prenatal testing

In 2020, the American College of Obstetricians and Gynecologists recommended noninvasive prenatal testing be offered to all patients. However, current societal guidelines in the United States do not universally recommend a detailed first-trimester ultrasound. This study aimed to determine the additional findings identified through first-trimester ultrasound that would have otherwise been missed if noninvasive prenatal testing was used alone as a first-trimester screening method. This was a retrospective cohort study involving 2158 pregnant patients and 2216 fetuses that were seen at a single medical center between January 1, 2020, and December 31, 2022. All those included underwent both noninvasive prenatal testing and detailed first-trimester ultrasound between 11.0 and 13.6 weeks of gestation. Noninvasive prenatal testing results were categorized as low risk or high risk, and first-trimester ultrasound results were categorized as normal or abnormal. Abnormal first-trimester ultrasounds were further classified as first-trimester screening markers (increased nuchal translucency, absent nasal bone, tricuspid regurgitation, and ductus venosus reverse a-wave) or structural defects (the cranium, neck, heart, thorax, abdominal wall, stomach, kidneys, bladder, spine, and extremities). Descriptive statistics were used to report our findings. Of 2216 fetuses, 65 (3.0%) had a high-risk noninvasive prenatal testing result, whereas 2151 (97.0%) had a low-risk noninvasive prenatal testing result. Of those with a low-risk noninvasive prenatal testing result, 2035 (94.6%) had a normal first-trimester ultrasound, whereas 116 (5.4%) had at least 1 abnormal finding on first-trimester ultrasound. The most common screening marker detected within the low-risk noninvasive prenatal testing group was absent nasal bone (52/2151 [2.4%]), followed by reversed a-wave of the ductus venosus (30/2151 [1.4%]). The most common structural defect in this group was cardiac abnormality (15/2151 [0.7%]). Overall, 181 fetuses were identified as having "abnormal screening" through either a high-risk noninvasive prenatal testing result (n=65) or through a low-risk noninvasive prenatal testing result but abnormal first-trimester ultrasound (n=116). In summary, the incorporation of first-trimester ultrasound screening identified 116 additional fetuses (5.4%) that required further follow-up and surveillance than noninvasive prenatal testing alone would have identified. Detailed first-trimester ultrasound identified more fetuses with a potential abnormality than noninvasive prenatal testing alone. Therefore, first-trimester ultrasound remains a valuable screening method that should be used in combination with noninvasive prenatal testing.

Prenatal genomic testing for ultrasound‐detected fetal structural anomalies

Key content In the presence of a fetal structural anomaly, fetal DNA can be obtained through invasive testing (e.g. amniocentesis and chorionic villus sampling) in order to undertake genomic testing to attempt to uncover a unifying genetic diagnosis. There are number of traditional and more novel genomic tests available, which can identify aneuploidy, chromosomal structural variation and/or sequence variants within genes. The cumulative diagnostic yield of such technologies is approximately 25%, 6% and up to 80% in some cohorts for QF‐PCR/G‐banding karyotype, chromosome microarray and exome sequencing, respectively. Learning objectives To understand the technical basis and clinical indications for QF‐PCR, G‐banding karyotype, chromosome microarray and exome sequencing. To appreciate the potential benefits and challenges associated with exome sequencing. To gain awareness of modern technologies that may be utilised to address recurrence risk, e.g. preimplantation genetic diagnosis and non‐invasive prenatal diagnosis. Ethical issues Not all technologies are currently available across all four nations of the UK, hence challenges are raised regarding healthcare equity. There can be uncertainty around the interpretation of prenatal genomic test results, which can have implications in counselling, particularly regarding termination of pregnancy. Incidental findings may be revealed, which can have implications for counselling and the future health of the fetus and the parents.

Genetic Analysis of a Case of Sotos Syndrome with Suspected Germinal Mosaicism in Mother.

This study is to identify the pathogenic mutation of a child with Sots syndrome and provide prenatal diagnosis for his pregnant mother. Chromosome microarray technology was used to detect whether there were minor deletions/duplication in patients' chromosomes. The gene mutation of patients was screened by next-generation sequencing technology, and it was verified by Sanger sequencing. Prenatal diagnosis of the fetus was conducted according to the selected pathogenic sites, and genetic counseling was conducted for her parents. Chromosome microarray results showed that there was no minor deletion in a chromosome 5q35 region, and the second-generation sequencing results showed that there was a c.4138delG heterozygous mutation in the patient's NSD1 gene, and the pathogenic of this mutation was not reported in related databases. Sanger sequencing found that there was a c.4138delG heterozygous mutation in the NSD1 gene of the patient and her parents' genotype at this locus was wild type. The prenatal gene test results indicated that there was heterozygous mutation of NSD1 gene c.4138delG in the fetus, so it was suggested to terminate the pregnancy. Gentling results indicated that the fetus and the patient inherited the same maternal chromosome 5. The heterozygous mutation of NSD1 gene c.4138delG is the pathogenic mutation of this Sots syndrome patient, and the mother may be germinal mosaicism.