Red blood cell (RBC) alloimmunization remains a relevant cause of hemolytic disease of the fetus and newborn (HDFN). Although RhD immunization has significantly decreased since the implementation of systematic prophylaxis, it is still the main cause of alloimmunization in pregnancy. Clinically significant non-RhD alloantibodies, particularly those of the Rh (c, C, E), Kell, Kidd, Duffy, and MNS systems, are associated with variable risk of fetal anemia and account for an increasing proportion of alloimmunized pregnancies requiring specialized prenatal care. Most diagnostic algorithms and management protocols are based on evidence derived from RhD alloimmunization. Although these frameworks are often extrapolated to other alloantibodies, important differences exist regarding antibody titration and critical thresholds, the diagnostic accuracy of non-invasive fetal antigen genotyping, and the risk and timing of fetal and neonatal interventions. These differences underscore the need for antibody-specific considerations in the prenatal diagnosis and management of non-RhD alloimmunization. Though advances in non-invasive diagnostic techniques have improved risk stratification and optimized prenatal management, individualized care pathways in alloimmunized pregnancies are needed. This review will focus on the current strategies for prenatal diagnosis and risk assessment in pregnancies complicated by non-RhD red cell alloimmunization.

Counterfactual thinking (CT), the tendency to consider how events might have been different, is a common cognitive process following negative life events. This longitudinal study examines the prevalence and time-course evolution of CT immediately after early pregnancy loss. A sample of 119 women who experienced early pregnancy loss completed an online psychological assessment measuring traumatic impact, trait rumination, and CT presence, frequency, and content. The survey was administered at one week, one month, and four months post-loss. CT was highly prevalent (72%) and decreased over time. 99% of CT had an upward focus, imagining a better outcome than reality. Moreover, 91.6% were also self-referential, perceived as dependent on one’s own behaviors and emotions, frequently involving a heightened sense of personal responsibility for the loss. Rumination and traumatic impact predicted counterfactual thinking frequency over time, identifying psychological risk patterns. Findings support the idea that CT may serve an adaptive function by helping to process the loss and support future goal setting, including subsequent pregnancy. However, in individuals with high traumatic impact and rumination, CT may contribute to prolonged distress. Integrating psychological care alongside physical healthcare is essential to promoting long-term well-being after early pregnancy loss.

We aimed to develop a machine learning model for first-trimester prediction of gestational diabetes mellitus (GDM) in twin pregnancies using a prospective international, multi-center cohort and identify useful predictive markers. Pregnant women with two live fetuses were enrolled at 11 + 0 to 13 + 6 weeks’ gestation and followed until delivery. GDM was diagnosed at 24–28 weeks’ gestation using the two-stage GCT and OGTT tests. Biochemical, biophysical, and blood assessments were conducted at three periods during pregnancy. Multiple machine learning models evaluated demographic, clinical, and laboratory parameters, including maternal factors (BMI, age, medical history), sonographic markers (crown rump length, estimated fetal weight, uterine artery pulsatility index), and blood and biochemical markers (placental growth factors, blood glucose, cell counts). LightGBM, XGBoost, and logistic regression models were compared using area under the curve (AUC) analysis. Among 596 women, 99 (16.6

Introduction: While machine learning models successfully predict preeclampsia in singleton pregnancies and aspirin prophylaxis prevents preterm preeclampsia, no parallel models exist for twin pregnancies. This study developed machine learning algorithms to predict preeclampsia in twins using maternal factors and biomarkers from all three trimesters. Methods: We prospectively enrolled 596 pregnant women with twin pregnancies at 11+0 to 13+6 weeks' gestation. Machine learning models assessed the efficacy of maternal factors and biomarkers for preeclampsia prediction across all trimesters. Screening performance was evaluated using area under the receiver operating characteristic (ROC) curves. Women with first-trimester risk >1/100 received aspirin treatment (150-160 mg/day) based on Fetal Medicine Foundation (FMF) twin-specific algorithms, while others received 80-100 mg/day or no treatment according to local guidelines. Results: Sixty-seven women (11.2%) developed preeclampsia, including 40 (6.7%) with preterm preeclampsia. Key first-trimester markers included maternal factors, mean arterial pressure, cell-free fetal DNA, placental growth factor, and blood group B. Second- and third-trimester predictors comprised placental growth factor, soluble fms-like tyrosine kinase-1, and mean arterial pressure. The optimal machine learning model incorporating all three trimesters achieved an area under the ROC curve of 0.97 with 91% detection rate at 10% false-positive rate. Conclusion: Despite aspirin treatment in 257 (43.1%) women, logistic regression showed no significant reduction in preeclampsia rates. These findings suggest that while multi-trimester biomarkers effectively predict preeclampsia in twins, the effect of aspirin prophylaxis in twin pregnancies has yet to be proven. An app to predict this score is available at: twin-pe.math.biu.ac.il or by contact with the corresponding author.

Objective To evaluate whether the causative variants found upon clinical exome sequencing in fetuses affected with selected structural anomalies would also be detected if PanelApp-R21 or Human Phenotype Ontology (HPO)-driven gene selection terms were applied instead.Methods During 9 years (2016-2024), the whole exome was sequenced in 206 pregnancies with selected fetal structural anomalies, with prospective interpretation of about 5000 morbid OMIM genes. Retrospectively, 79 causative and 19 incidental findings were reviewed and assessed for their detectability under two alternative strategies: PanelApp-R21 or HPO-driven gene lists.Results Among the 79 causative genes identified by interpreting morbid OMIM genes in 78 structurally abnormal fetuses, PanelApp-R21 was able to detect 76 (96%) genes, while HPO-driven terms identified only 56 (71%). For 19 incidental findings, the PanelApp-R21 pathway could identify eight (42%), while HPO terms captured only one (5.3%).Conclusions In prenatal ES, reliance on HPO-driven gene selection significantly lowers diagnostic yield compared with clinical ES, with nearly one-third of primary findings and most incidental findings missed. PanelApp represents a pragmatic alternative, preserving a high primary diagnostic yield while limiting incidental findings.

As genomic technologies continue to evolve, understanding the scope and limitations of available prenatal testing methods is essential for accurate diagnosis and counseling. Chromosomal microarray analysis (CMA) and exome sequencing (ES) have emerged as key complementary tools in this setting. This review aims to outline the technical principles underlying CMA and ES and to compare their diagnostic capabilities and limitations in the prenatal context. This narrative review includes a literature search, with additional relevant articles identified through manual screening of reference lists from key publications and review articles. Due to the narrative nature of this review, no formal inclusion or exclusion criteria or quantitative synthesis were applied. Special focus was placed on clinical indications, variant interpretation challenges—particularly uncertain and incidental findings—gene selection strategies, and implications for prenatal counseling. Indications for both tests have increased over time but differ substantially. CMA is becoming the standard prenatal genetic test, particularly in the evaluation of fetal structural anomalies, whereas ES remains restricted to selected fetal structural anomalies. Interpretation of molecular results remains a major challenge, especially for variants of uncertain significance and incidental findings with unclear or unexpected implications for pregnancy management. For ES, agnostic gene selection strategies showed superior diagnostic yield compared with phenotype-driven approaches, likely reflecting the limited characterization of prenatal phenotypes. Continuous refinement of clinical indications, bioinformatic pipelines, variant classification criteria, and gene curation strategies is critical to ensure that prenatal results are accurate and clinically meaningful. Together, ongoing improvements in technology, interpretation, and clinical integration have the potential to transform prenatal genomics into a more precise, informed, and ethically responsible field.

Objectives: This study aimed to assess the role of olfactory sulci (OS) in diagnosing CHARGE syndrome among fetuses with major congenital heart defects (CHDs). Methods: We prospectively evaluated OS development in fetuses diagnosed with CHDs from 2017 to 2021. Neurosonography (NSG) was performed using transabdominal and transvaginal approaches after 30 weeks of gestation. OS assessment was conducted in the trans-frontal coronal plane, classifying their appearance as fully developed, hypoplastic, or absent. Abnormal OS cases underwent MRI and trio-based clinical exome sequencing (CES). Results: The study included 147 fetuses with CHD. Abnormal OS were found in 4 fetuses (2.7%) which also exhibited other additional anomalies. OS were absent in cases 1-3 and hypoplastic in case 4.. MRI confirmed OS abnormalities in all cases, and trio-based CES identified a CHD7 gene mutation in cases 1, 2, and 4, supporting the diagnosis of CHARGE syndrome. Case 3 had normal trio-based CES results. No other CHARGE syndrome cases were diagnosed postnatally among the cases with normal OS. Conclusions: Systematic evaluation of OS in fetuses with major CHD might contribute to the diagnosis of CHARGE syndrome. Our findings support the inclusion of OS assessment in the prenatal evaluation of fetuses with major CHDs.

Introduction: The aim of this study was to assess the clinical utility of low-set ears (LSE) as a novel 2D-ultrasound marker for the prenatal detection of chromosomal anomalies. Methods: A multicenter cohort study including 1,331 singleton pregnancies between 11+2 and 34+6 weeks of gestation was conducted in the two participating centers to determine the performance of LSE as an aneuploidy marker. LSE was defined as a dichotomous marker using a newly defined axial plane of the fetal head in 2D ultrasound. Intra- and interobserver variability were assessed to ensure marker reliability. Efficacy in predicting chromosomal anomalies was assessed using LSE alone or in combination with aneuploidy screening. Results: A new axial plane of the fetal head, defined by both lenses and the cerebellum, was adopted for LSE detection. Intra-observer concordance Kappa index for LSE measurement was 1.0, and 0.82 for interobserver reliability. LSE could be assessed in 99% of the studied fetuses and was detected in 30 (2.3%) fetuses: in 19 (86%) of the 22 fetuses with chromosomal anomalies, in all cases (5/5, 100%) with other genetic anomalies, and in six (18%) of the 34 malformed fetuses without a genetic disorder. In one (3.3%) of the fetuses, LSE was not confirmed postnatally while the remaining 29 fetuses had an adverse outcome. When LSE was combined with aneuploidy screening, the detection rate of chromosomal anomalies remained the same and specificity increased from 89% to 100%. Conclusions: Our study supports using LSE as a potential 2D-ultrasound marker for chromosomal anomaly detection. Studies with a larger sample size and in high-risk populations are warranted to prove its clinical utility before this marker can be included in prenatal screening protocols.

OBJECTIVE:To conduct a systematic review and meta-analysis of published series examining the efficacy of genome-wide cell-free DNA (cfDNA) testing in identifying aneuploidy in pregnancies ending in miscarriage. METHODS:A systematic review was conducted encompassing observational studies evaluating aneuploidy detection by genome-wide cfDNA testing in pregnancy losses before 22 weeks of gestation. A hierarchical summary receiver operating curve was employed to assess pooled sensitivity, specificity, and area under the curve (AUC) of genome-wide cfDNA versus genetic diagnostic studies in the detection of aneuploidy. Pooled aneuploidy rate, rate of no-calls, and concordance between cfDNA and diagnostic studies were analyzed using a single proportion meta-analysis based on the inverse of the variance. RESULTS:Out of 25 eligible series, eight studies were included for analysis, comprising 552 miscarriages with informative results for both cfDNA and diagnostic testing. Pooled sensitivity, specificity, and AUC were 78% (95% CI: 71%-83%), 91% (95% CI: 86%-95%), and 92%, respectively. Pooled aneuploidy rate, the proportion of no-calls, and concordance were 61% (95% CI: 53%-69%), 4% (95% CI: 0%-12%), and 84% (95% CI: 81%-87%), respectively. In cases of positive cfDNA results, the risk of aneuploidy increased to 93%, whereas negative results yielded a 28% risk of aneuploidy. CONCLUSION:cfDNA testing demonstrates acceptable accuracy in predicting fetal aneuploidy when employed as a screening test in miscarriages. The main advantage of cfDNA testing is that it does not require the availability of products of conception or prior chorionic villi sampling.

OBJECTIVE:To develop a nomogram of fetal ear length (FEL) by gestational age in a healthy pregnant Southern European population and assess its potential as a prenatal ultrasound marker of chromosomal anomalies in this demographic. METHODS:This prospective, multicenter cohort study included low-risk pregnancies from 11 + 2 to 34 + 6 gestational age. A nomogram was constructed based on gestational age for healthy fetuses with normal perinatal outcomes. Intraobserver and interobserver reliability were evaluated. To assess the efficacy of FEL as a marker of chromosomal anomalies, a multivariate logistic regression analysis was performed; sensitivity and specificity were calculated. RESULTS:A total of 1923 FEL measurements were obtained from 1331 singleton pregnancies. Using data from healthy fetuses, a nomogram was constructed through linear regression analysis. Measurement feasibility was excellent, with intra- and interobserver correlation coefficients of 0.996 (95% confidence interval [CI]: 0.995-0.997) and 0.998 (95% CI: 0.978-0.999), respectively. FEL achieved a sensitivity of 81.8% and a specificity of 49.8% in detecting chromosomal anomalies. Multivariate logistic regression indicated that FEL ≤ 5th percentile significantly increased the likelihood of detecting chromosomal anomalies (odds ratio = 3.11); although the wide 95% CI (1.92-10.7) suggests a cautious interpretation of this finding. CONCLUSIONS:While FEL demonstrates potential as a prenatal marker of chromosomal anomalies, its clinical utility remains limited due to moderate sensitivity and specificity. Further studies are warranted to refine its diagnostic value in routine screening practices.

Objectives: Different retrospective growth charts for twin pregnancies debates whether twin growth is similar to singletons. Recently, the fetal medicine foundation (FMF) published a retrospective fetal growth chart that indicated similar growth charts for twins and singleton if only term delivery of both twins without major malformation are included. A national Denish growth chart confirmed these finding. We constructed prospective growth chart of estimated fetal weight (EFW) throughout pregnancy of monochorionic diamniotic (MCDA) and dichorionic (DC) twins using a multi-center, multi-national cohort. Study Design: Pregnancies with two live fetuses at 11-13 wks’ gestation were enrolled. Gestational age was determined from crown-rump length of the larger twin in the first trimester. EFW charts were made from fetal growth at 11-13, 20-22, 24-26, 28-30, 32-34, and 36-37 wks’ gestation using Hadlock-4 formula made of biparietal diameter, head and abdominal circumference, and femur length. Chorionicity specific charts were built for 376 DC and 158 MCDA live twins who were born at term, without malformations. Centers included were from Montreal, Canada, Bonn and Tubingen, Germany, Barcelona, Spain, Rome, Italy, and Zerifin, Israel. ANOVA was used to compare ethnic and centers charts and functional fit to were compared our charts to retrospective EFW charts of the FMF. Results: Growth was slower in MCDA compared with DC twins starting from 21st wks’ gestation and increased with advancing gestation. Our charts were similar but marginally slower than the FMF ones. Smaller EFW were in Barcelona and Rome compared to the larger in Bonn and Tubingen, and fetuses of white women were larger than those of other ethnicities Conclusions: We developed a prospective growth chart for pregnancies with two live DC and MCDA twins born at term without malformations that are consistent with those of the FMF, with small differences between countries and ethnicities.

INTRODUCTION:The study investigated whether the disclosure of the chromosomal anomaly causing early pregnancy loss (EPL) favors the grief process and reduces psychological distress. METHODS:Women experiencing EPL were invited to participate in the study at the time they were offered chorionic villi sampling (CVS) and karyotyping before uterine evacuation. They completed two online surveys: one a week after EPL and another a month later, after receiving cytogenetic results. The surveys measured anxiety (Hospital Anxiety and Depression Scale [HADS]), Beck Depression Inventory (BDI-II) cognitive depression factor items, post-traumatic stress disorder (Impact of the Event Scale-Revised [IES-R]), and rumination (Ruminative Responses Scale [RRS-10]). Participants were divided into groups based on the chromosomal anomaly found at CVS: A1 (autosomal trisomy), A2 (other anomalies), and B (no anomalies). RESULTS:A significant score decline was observed in the four studied psychological scales assessing anxiety, depression, post-traumatic stress, and rumination, between the first and second survey. The proportion of women with a clinical score also demonstrated a significant decline, except for anxiety. When these changes were assessed after karyotypic group stratification, the group with other chromosomal anomalies (A2) showed the highest drop. This group also demonstrated a significantly higher depression score decline at multivariate regression analysis of the median. CONCLUSION:EPL significantly impacts women's mental health, with 19%-51% experiencing manifestations. Disclosing chromosomal anomalies may aid in psychological recovery, particularly in reducing clinical scores for depression.

Anomalies of the corpus callosum (CC) are amongst the most common fetal Central Nervous System (CNS) anomalies detectable on ultrasound. Underlying genetic disease plays an important part in defining prognosis. Associations with aneuploidy and submicroscopic chromosomal deletions or duplications have been well demonstrated using chromosomal microarray analysis. Next-generation sequencing techniques such as exome sequencing, have revolutionized the ability to detect monogenic disease in these fetuses. In the context of important recent publications on exome sequencing in prenatal populations, an updated review of genetic testing options in CC anomalies is presented.

Background/Objectives: Cell-free DNA (cfDNA) is a non-invasive prenatal test used to screen for common trisomies (target cfDNA) that can be expanded to assess all autosomal chromosomes (genome-wide cfDNA). As cfDNA testing gains popularity, it is crucial to examine the factors influencing the decision-making process of pregnant individuals when choosing between these two approaches. Methods: In this prospective cohort study, 190 individuals undergoing cfDNA testing for aneuploidy screening, according to the current screening protocol, were allowed to make their own choice between target and genome-wide cfDNA testing. They were asked to complete a first survey at 11–13 weeks, designed to explore their characteristics, preferences, and satisfaction with the prenatal genetic counseling session, as well as a Decisional Conflict Scale. A postnatal survey was administered three months after delivery, including the Decisional Regret Scale and two open questions. Results: 84% of participants opted for genome-wide cfDNA. However, 17% found the decision challenging, and 14% felt that the results might increase anxiety. No significant differences in participant characteristics were found when comparing decisions between genome-wide and target cfDNA. However, significant differences were observed regarding ethnicity (p = <0.001), educational level (p = 0.029), previous cfDNA experience (p = 0.004), and having sufficient information when comparing termination options (p = 0.002). After delivery, only 4% would have changed their decision. Conclusions: Individuals, regardless of their characteristics, prefer genome-wide cfDNA; however, the complexity of the results necessitates enhanced genetic education for prenatal care clinicians.

ABSTRACT Small for gestational age (SGA) newborns are generally defined as those with a birth weight below the 10th percentile. Fetuses diagnosed with fetal growth restriction (FGR) are usually evaluated to determine if there is a pathological cause and thus a higher risk for adverse outcomes due to being small. Often when this diagnosis is made early in the third trimester, chromosomal microarray analysis is recommended to detect genetic disease. This study was designed to determine the frequency of monogenic disorders in term infants with severely low birth weight but normal Doppler results, as well as to estimate the frequency of neurodevelopmental impairment when a genetic etiology was ruled out. Inclusion criteria for this study were singleton pregnancy; term delivery; birth weight more than 2.5 SDs below the mean; normal Doppler studies of the umbilical artery, fetal middle cerebral artery, cerebroplacental ratio, and uterine artery; no maternal hypertensive disease; and no prenatal fetal structural or identified genetic anomalies or fetal infection. Exclusion criteria included incomplete data. Exome sequencing was completed using saliva sampling and blood sampling, and standard neurodevelopmental assessment techniques were used for children 2 to 3.5 and 6 to 8 years old. Children aged between 3.5 and 6 years were not included because of lack of standardized neurodevelopmental testing. A total of 63 families were contacted, and 7 (11%) reported that a genetic disorder had been diagnosed after birth. In addition, 18 individuals without a known genetic disorder who met all the criteria underwent exome sequencing and neurodevelopmental testing. Of the 7 who reported a postnatally diagnosed genetic syndrome, 5 were Mendelian monogenetic and 2 were epigenetic, including Cockayne syndrome; short stature, microcephaly, and endocrine dysfunction syndrome; Renpenning syndrome; Noonan syndrome; Russell-Silver syndrome; and Prader-Willi syndrome. Median birth weight among the children with genetic disorders was not different from children without. Exome sequencing was normal in the 18 children who were tested and who had not been previously diagnosed with a genetic syndrome. None of the children showed less than average neurodevelopment on overall assessment in the lower age group. In the higher age group, 2 children were classified as having low IQ, with one borderline and one extremely low, with low scores in all other domains as well. In addition, 6 individuals showed a low score in at least 1 of the 5 domains, with the largest deviations showing in the domains of verbal comprehension and working memory. Clinicians should be aware of the potential outcomes of FGR even when other complications are not present. Counseling about genetic analysis prenatally or within a short postnatal timeframe could save a lot of time and effort in evaluating children later. In addition, children should be carefully assessed in later childhood for neurodevelopmental differences that are treatable or that may require different resources. Future research should focus on further homogenizing the population to get more accurate results, as well as dealing with potential biases in this study.

Ultrasound in Obstetrics & GynecologyEarly View Opinion Pitfalls of systematic reviews and meta-analyses to assess the clinical utility of genomic investigations in prenatal diagnosis F. Mone, Corresponding Author F. Mone [email protected] orcid.org/0000-0002-0718-7547 Centre for Public Health, Queen's University, Belfast, UK Correspondence. (e-mail: [email protected])Search for more papers by this authorD. L. Rolnik, D. L. Rolnik orcid.org/0000-0002-2263-3592 Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, AustraliaSearch for more papers by this authorA. Sotiriadis, A. Sotiriadis orcid.org/0000-0003-0876-5596 Second Department of Obstetrics and Gynecology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorR. J. Martinez-Portilla, R. J. Martinez-Portilla Evidence-Based Healthcare Department, National Institute of Perinatology 'Isidro Espinosa de lo Reyes', Mexico City, MexicoSearch for more papers by this authorA. Borrell, A. Borrell orcid.org/0000-0002-4304-4797 Barcelona Centre for Maternal–Fetal and Neonatal Medicine (BCNatal), Hospital Clínic Barcelona, Universitat de Barcelona, Barcelona, SpainSearch for more papers by this author F. Mone, Corresponding Author F. Mone [email protected] orcid.org/0000-0002-0718-7547 Centre for Public Health, Queen's University, Belfast, UK Correspondence. (e-mail: [email protected])Search for more papers by this authorD. L. Rolnik, D. L. Rolnik orcid.org/0000-0002-2263-3592 Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, AustraliaSearch for more papers by this authorA. Sotiriadis, A. Sotiriadis orcid.org/0000-0003-0876-5596 Second Department of Obstetrics and Gynecology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorR. J. Martinez-Portilla, R. J. Martinez-Portilla Evidence-Based Healthcare Department, National Institute of Perinatology 'Isidro Espinosa de lo Reyes', Mexico City, MexicoSearch for more papers by this authorA. Borrell, A. Borrell orcid.org/0000-0002-4304-4797 Barcelona Centre for Maternal–Fetal and Neonatal Medicine (BCNatal), Hospital Clínic Barcelona, Universitat de Barcelona, Barcelona, SpainSearch for more papers by this author First published: 30 July 2024 https://doi.org/10.1002/uog.29093Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Martinez-Portilla RJ, Pauta M, Hawkins-Villarreal A, et al. 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Objectives: To evaluate the use of Exome Sequencing (ES) for the detection of genome-wide Copy Number Variants (CNVs) and the frequency of SNVs-InDels in selected genes related to developmental disorders in a cohort of consecutive pregnancies undergoing invasive diagnostic procedures for minor or simple ultrasound findings with no indication of ES. Methods: Women undergoing invasive diagnostic testing (chorionic villus sampling or amniocentesis) for QF-PCR and chromosomal microarray analysis (CMA) due to prenatal ultrasound findings without an indication for ES were selected over a five-month period (May–September 2021). ES was performed to compare the efficiency of genome-wide CNV detection against CMA analysis and to detect monogenic disorders. Virtual gene panels were selected to target genes related to ultrasound findings and bioinformatic analysis was performed, prioritizing variants based on the corresponding HPO terms. The broad Fetal Gene panel for developmental disorders developed by the PAGE group was also included in the analysis. Results: A total of 59 out of 61 women consented to participate in this study. There were 36 isolated major fetal anomalies, 11 aneuploidy markers, 6 minor fetal anomalies, 4 multiple anomalies, and 2 other ultrasound signs. Following QF-PCR analysis, two uncultured samples were excluded from this study, and six (10%) common chromosome aneuploidies were detected. In the remaining 51 cases, no pathogenic CNVs were detected at CMA, nor were any pathogenic variants observed in gene panels only targeting the ultrasound indications. Two (3.9%) monogenic diseases, apparently unrelated to the fetal phenotype, were detected: blepharo-cheilo-odontic syndrome (spina bifida) and Duchenne muscular dystrophy (pyelocaliceal dilation). Conclusions: In our series of pregnancies with ultrasound findings, common aneuploidies were the only chromosomal abnormalities present, which were detected in 10% of cases. ES CNV analysis was concordant with CMA results in all cases. No additional findings were provided by only targeting selected genes based on ultrasound findings. Broadening the analysis to a larger number of genes involved in fetal developmental disorders revealed monogenic diseases in 3.9% of cases, which, although apparently not directly related to the indications, were clinically relevant.