Prenatal Diagnosis最新文献

Objective: To evaluate the prevalence of chromosomal aberrations in fetuses with isolated PRUV in a nationwide cohort with 1st-trimester screening for aneuploidies.

Method: A retrospective study including all pregnancies in Denmark with a due date between 2010 and 2022. We retrieved all cases from patient files, where we searched for "PRUV" in the conclusion field. All retrieved cases were manually assessed to determine if PRUV was present, associated anomalies were present, and genetic tests were performed including results. Additional data on postnatal genetics were retrieved from the Danish Cytogenetic Central Registry.

Results: A total of 262 cases with PRUV were retrieved, of which 19 (7.3%) had associated malformations. Among the isolated cases, 119 (49.0%) had a prenatal invasive genetic test that consisted of CMA, and 5 cases had an NIPT (2.1%): All tests were normal or showed low risk for aneuploidies, respectively. None of the children born with PRUV had a postnatal genetic test performed.

Conclusion: We found no chromosomal aberrations in fetuses with isolated or non-isolated PRUVs. Isolated PRUV does not seem associated with a higher incidence of chromosomal aberrations, so parents can be reassured. However, since PRUV was associated with other malformations in 7% of cases, thorough scans are needed.

Prenatal cell-free DNA (cfDNA) screening has advanced significantly, extending beyond detecting aneuploidies to sub-chromosomal copy number variations. However, its application for screening dominant single-gene conditions, often caused by de novo variants, remains underutilized in the general obstetric population. This study reviews recent data and experience on prenatal cfDNA screening for dominant monogenic conditions using multiple-gene panels, highlighting its potential to enhance early detection and management of genetic disorders. Integrating comprehensive cfDNA screening into routine prenatal care could complement current imaging techniques and standard prenatal cfDNA screening, which may overlook pre-symptomatic fetuses with dominant monogenic conditions in early gestation. Despite promising initial results, further research is needed to confirm the clinical validity and utility of cfDNA screening for these conditions. Larger and more diverse studies are necessary to assess the broader applicability of this technology. In addition, key challenges such as access, genetic counseling, ethical considerations, and policy development need to be addressed. A comprehensive approach, including rigorous test design, informed consent, and robust counseling, is essential for the successful adoption of expanded cfDNA screening, ultimately improving clinical outcomes.

Objective: Prenatal detection of Trisomy 16 mosaicism (MosT16) in a Chorionic Villus Sample (CVS) results may cause significant anxiety for expectant parents due to the risk of fetal malformation and fetal growth restriction (FGR). The aim of this study was to investigate the experiences and decision-making of women receiving a MosT16 results during pregnancy.

Methods: In-depth, semi-structured interviews with eight Danish women who received a MosT16 CVS results. Interviews were analyzed using reflexive thematic analysis.

Results: Four women terminated pregnancy following the MosT16 CVS result, emphasizing the emotional burden of waiting for amniocentesis and concerns about fetal involvement and FGR risk. Four women opted to await amniocentesis following which one terminated pregnancy due to fetal involvement, while three continued their pregnancies (one normal result, two low-percentage fetal involvement results). During pregnancy, all three fetuses were small for gestational age, and the concerns about their growth were burdensome for expectant parents. Two women delivered prematurely, but all three described their babies as healthy.

Conclusion: The prenatal MosT16 CVS result represents a critical decision point, requiring consideration of both fetal involvement and FGR risk. Thus, genetic counseling should be combined with counseling from obstetrics/fetal medicine specialists.

Twin reversed arterial perfusion (TRAP) sequence is an uncommon disease affecting monochorionic twin pregnancies. The diagnosis can be made by ultrasound allowing to plan optimal antenatal management. An electronic search was conducted from inception to July 2024 to systematically evaluate and compare the outcomes of different intrauterine interventions in this condition. Eighty-two studies were included, and 859 women with a prenatal ultrasound diagnosis of TRAP sequence with a total of 1763 fetuses were studied. The mean maternal age was 24.2 years (range 19-40) and the mean gestational age at diagnosis was 19.6 weeks (range 10-32). A total of 792 pregnancies were reported in which a fetal intervention was performed over the past 35 years. The mean gestational age at fetal intervention was 22.1 weeks (range 11-32). The two most frequent fetal interventions were radiofrequency ablation, performed in 293 cases and laser umbilical cord coagulation in 140 cases. Overall, 684 out of 828 non-acardiac fetuses following fetal intervention survived (82.6%) compared with 49 out of 76 (64.5%) non-acardiac fetuses in pregnancies managed expectantly (p = 0.0001). A higher survival rate was seen in fetuses undergoing umbilical cord ligation (100%) although this procedure was performed in only 8 women. Survival rates were 88.9%, 79.9%, 78.9% and 77.9% for monopolar coagulation of the umbilical cord, laser coagulation of the umbilical cord, fetoscopic laser ablation of placental anastomoses and radiofrequency ablation, respectively. Our results show that the survival rate is higher in patients with TRAP who have a prenatal intervention compared with those who have prenatal expectant management. The survival rate varies depending on the modality used for the prenatal intervention. Future studies are necessary to investigate the impact of the gestational age at the time of the procedure on the survival rate depending on the prenatal therapeutic modality.

Objective: To present the imaging features of Caroli's disease (CD) on prenatal ultrasound and magnetic resonance imaging (MRI).

Methods: This was a retrospective case series of prenatally diagnosed CD between 2017 and 2024. Clinical data from these cases were collected and reviewed.

Results: Five fetuses with CD were included, three of which had a definite combination of ARPKD and suspected in the other 2. Prenatal ultrasonography revealed multiple intrahepatic bile duct dilatations in four fetuses, each of which displayed the "horn comb" sign in a cross-section of the liver. All five fetuses had abnormal kidney ultrasounds: three showed enlarged and hyperechogenic kidneys and two showed hyperechogenic kidneys. The MRI scans of all fetuses showed a "central dot" (C-DOT) sign in the liver. By MRI, three fetuses had enlarged kidneys, one slightly had hyperintensity kidneys, and one had no significant kidney abnormalities. Pregnancy termination was chosen in all cases.

Conclusions: CD may be identified by fetal ultrasound through the characteristic arrangement of intrahepatic dilated bile ducts ("horn comb" sign). Fetal MRI is advantageous for detecting the C-DOT sign, which confirms the diagnosis of CD. In our experience, these findings tend to become apparent in the late second to early third trimester of pregnancy.

Objective: The first objective is to develop a nuchal thickness reference chart. The second objective is to compare rule-based algorithms and machine learning models in predicting small-for-gestational-age infants.

Method: This retrospective study involved singleton pregnancies at University Malaya Medical Centre, Malaysia, developed a nuchal thickness chart and evaluated its predictive value for small-for-gestational-age using Malaysian and Singapore cohorts. Predictive performance using conjunctive (AND)/disjunctive (OR) rule-based algorithms was assessed. Seven machine learning models were trained on Malaysia data and evaluated on both Malaysia and Singapore cohorts.

Results: 5519 samples were collected from the University Malaya Medical Centre. Small-for-gestational-age infants exhibit significantly lower nuchal thickness (small-for-gestational-age: 4.57 [1.04] mm, appropriate-for-gestational-age: 4.86 [1.06] mm, p < 0.001). Implementing disjunctive rule (nuchal thickness < 10th centile or estimated fetal weight < 10th centile) significantly improved small-for-gestational-age prediction across all growth charts, with balanced accuracy gains of 5.83% in Malaysia (p < 0.05) and 7.75% in Singapore. The best model for predicting small-for-gestational-age was: logistic regression with five variables (abdominal circumference, femur length, nuchal thickness, maternal age, and ultrasound-confirmed gestational age), which achieved an area under the curve of 0.75 for Malaysia cohorts; support vector machine with all variables, achieved area under the curve of 0.81 for Singapore cohorts.

Conclusions: Small-for-gestational-age infants demonstrate significantly reduced second-trimester nuchal thickness. Employing the disjunctive rule enhanced small-for-gestational-age prediction. Logistic regression and support vector machines show superior performance among all models, highlighting the advantages of machine learning. Larger prospective studies are needed to assess clinical utility.

Previous studies suggest that NIPT's implementation differed widely across countries but offer limited insight into what shaped these differences. To address this gap, we conducted an in-depth analysis of how NIPT was incorporated into prenatal care in the US, the Netherlands, and Japan-countries with similar economic status-to identify actionable lessons. We conducted an integrative literature review on the process of introducing and implementing NIPT, stakeholders' roles, documented considerations in the decision to introduce NIPT, implementation choices, and NIPT uptake. We included 184 sources, including white and gray literature and non-English sources. We identified 17 considerations that were documented to have influenced the decision whether to introduce NIPT across five domains: clinical considerations, ethical considerations and societal values, financial considerations, demand and capacity and applicable oversight. Fewer factors seem to have been considered in the US as compared to Japan or the Netherlands. Countries subsequently made choices on how to implement NIPT-we identified 35 such choices. While most of the identified choices were eventually considered by all three countries, they made different decisions (e.g., on out-of-pocket costs). In 2022, the estimated proportion of pregnant persons who used NIPT was 58% in the Netherlands, 49% in the US, and 9% in Japan. While differences in cultural values, population characteristics, and healthcare systems explain some variation, we identified other more adaptable aspects of the decision-making process (e.g., oversight) that may be useful for countries introducing NIPT or similar technologies to consider.

Objective: The study aimed to evaluate the frequency of pathogenic copy number variants (CNVs) classified as incidental findings (IFs) in prenatal diagnosis and to develop consensus recommendations for standardizing their reporting across six centers within the Catalan public health system (XIGENICS network).

Method: A retrospective review of 4219 consecutive prenatal microarrays performed within the network from 2018 to 2023 was conducted, including all referral reasons. To develop consensus recommendations, several discussion meetings were held along with an extensive review of the existing literature.

Results: A total of 69 IFs were identified in 68 samples, revealing a detection rate of 1.6%. They included: 5 CNVs associated with neurodevelopmental disorders and/or congenital defects with complete penetrance, 41 CNVs for neurodevelopmental disorders and/or congenital defects with incomplete penetrance, 4 disorders that can potentially be prevented or treated, 5 non-childhood onset neurological disorders, 13 X-linked disorders (mainly STS and DMD deletions), and 1 deletion of the SHOX gene. Long-term follow-up revealed that newborns with high penetrance neurosusceptibility CNVs exhibited clinical manifestations more frequently than those with low penetrance CNVs. At the time of reporting, 52 IFs were disclosed, while 17 were not. According to the new consensus criteria, 43 IFs would now be reported, 17 would not, and 9 would depend on parental decision. CNVs consistent with the referral reason were identified in 4% of cases.

Conclusion: This study represents the largest series rigorously documenting all identified IFs in consecutive pregnancies evaluated by microarray, including both reported and unreported findings. IFs were found at a higher frequency than previously recognized, underscoring the need for specific clinical attention. Comprehensive consensus reporting recommendations were developed to ensure uniformity of criteria, and an ad hoc committee was established to manage complex cases.

Introduction: Fetoscopic laser surgery (FLS) is the gold standard treatment for monochorionic (MC) twin pregnancies complicated by twin-twin transfusion syndrome (TTTS). The aim of our study was to evaluate the rate and risk factors for cord entanglement in the presence of iatrogenic monoamnioticity (iMA), a consequence of inadvertent septostomy during FLS.

Methods: This is a retrospective analysis of two consecutive cohorts of FLS performed either using the selective technique from January 2004 to January 2012, or with the Solomon technique, from that date onwards. Maternal and fetal characteristics, technical details, and obstetrical and perinatal outcomes were recorded. Cord entanglement was identified based on the presence of a galloping sign observed during prenatal ultrasound in the presence of iMA. At our center, mono-amniotic twins are electively delivered at 32 completed weeks.

Results: The mean gestational age of the 558 FLS, 52.3% selective and 47.6% Solomon, was 19.8 weeks (15.1-26.4). Solomon laser coagulation was associated with a lower occurrence of TAPS or TTTS (5.3% vs. 13%, p = 0.001) after the FLS and a higher number of placental abruption (9% vs. 2% p < 0.001) and by more cord entanglement in the presence of iMA (9.4% vs. 2.4% respectively, p < 0.001). The presence of iMA was correlated with a higher occurrence of limb defects (6.2% vs. 1% in non-iMA twins, p 0.001).

Conclusions: Solomon FLS was associated with a higher risk of cord entanglement and placental abruptio. As a consequence, we delivered twins with iMA earlier.