Search Results (41)

Background: Trisomy 21 (T21) is strongly associated with congenital heart disease, particularly atrioventricular septal defect (AVSD), ventricular septal defect (VSD), atrial septal defect (ASD) and selected conotruncal and arch anomalies. First- and second-trimester ultrasound, Doppler and fetal cardiac MRI enable increasingly early and detailed characterization of these lesions, while advances in molecular cardiogenesis have linked specific phenotypes to dosage-sensitive genes on chromosome 21. Methods: This narrative review synthesizes contemporary evidence on structural and functional cardiovascular anomalies in T21 fetuses in the first and second trimester, integrating fetal echocardiography, Doppler assessment and fetal cardiac MRI with embryologic and molecular insights, and summarizing trimester-specific detectability and pathophysiologic links to candidate genes in the Down syndrome-critical region. Approximately one quarter to one third of T21 fetuses have major congenital heart disease on high-quality prenatal echocardiography, with AVSD representing about half of all lesions and VSD, tetralogy of Fallot (TOF), arch anomalies, venous return abnormalities and functional markers (increased nuchal translucency, tricuspid regurgitation, ductus venosus abnormalities) comprising the remainder. Results: First-trimester detection relies on functional markers and early four-chamber and outflow-tract views, whereas second-trimester studies refine anatomic definition and hemodynamics, with MRI reserved for complex cases. Overexpression of genes such as DSCAM, COL6A1/COL6A2, DYRK1A and RCAN1 perturbs endocardial cushion, conotruncal and vascular development. Conclusions: Early, protocol-driven cardiac imaging in T21 supports timely diagnosis, risk stratification and multidisciplinary counselling, and links fetal imaging phenotypes with chromosome 21 gene dosage to advance personalized management and future genotype–phenotype research. Full article

First-trimester sonographic examination remains a fundamental part of antenatal care, providing crucial information for the well-being of both the mother and fetus and leading to the best possible perinatal outcomes. This study aimed to review and compare the most recently published guidelines on first-trimester ultrasound. Therefore, a descriptive review of guidelines from the American Institute of Ultrasound in Medicine (AIUM), the Australasian Society of Ultrasound in Medicine (ASUM), the Association of the Scientific Medical Societies in Germany (AWMF), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the Society of Obstetrician and Gynecologists of Canada (SOGC) and the World Association of Perinatal Medicine (WAPM) regarding first-trimester scans was conducted. There is a consensus regarding the main parameters that should be evaluated, the qualifications of the examiner and specifications of the ultrasound machine, as well as the importance of informed consent. Additionally, the importance of careful visualization of fetal anatomy is discussed, with minor discrepancies regarding the appropriate protocol used. The use of combined first-trimester examination is encouraged by all the reviewed medical societies, although cell-free DNA testing is addressed only by a few, with similar indications. Controversy exists regarding the indications and appropriate gestational age at which the first-trimester scan should be performed, as well as the proper establishment of pregnancy dating. Notably, recommendations regarding fetal growth restriction (FGR) and diagnostic invasive procedures are made only by few medical societies, with the AWMF and SOGC addressing screening for FGR. Furthermore, invasive diagnostic testing is discussed by the AIUM, AWMF and SOGC, with differentiations among them regarding the indications for pursuing such procedures. First-trimester sonographic examination is essential for assessing fetal viability, establishing accurate pregnancy dating, evaluating fetal and maternal anatomy and calculating the risk of various fetal and maternal conditions. The implementation of evidence-based, unified protocols would advance both maternal and fetal outcomes. Full article

Objectives: This study aimed to examine the association between the dangling choroid plexus sign and fetal structural, chromosomal, and genetic abnormalities, as well as to define the normal range of lateral ventricular width and the ratio of choroid plexus width to lateral ventricular width at 14–17 weeks of gestation. Methods: This retrospective study analyzed ultrasound images from early fetal anatomy scans performed between January 2018 and July 2025 at two tertiary fetal medicine centres. In centre A, 6063 singleton pregnancies underwent routine scans at 11–13 and 14–17 weeks. In centre B, 776 fetuses with suspected abnormalities or increased nuchal translucency at 11–13 weeks were reassessed at 14–17 weeks. Additionally, 400 fetuses without obvious abnormalities at 14–17 weeks were used to determine normal ventricular measurements. Results: In normal fetuses, the mean lateral ventricular width was 6.90 mm (95% CI 6.81–6.99) and the mean choroid plexus-to-ventricle ratio was 0.85 (95% CI 0.84–0.86). A dangling choroid plexus was identified in 38 fetuses (0.16% in routine and 3.6% in high-risk populations). Out of 38 cases of dangling choroid plexus, 37 were associated with additional structural defects, chromosomal abnormalities, or single-gene disorders. Chromosomal abnormalities were found in 11/30 tested cases, most commonly trisomy 21. The most common defects observed on initial or subsequent scans were ventriculomegaly, cardiac defects, and abnormal posterior fossa. Conclusions: A dangling choroid plexus at 14–17 weeks is a sonographic marker associated with major fetal abnormalities and should prompt detailed anatomical assessment and consideration of genetic testing. Full article

Background/Objectives: Twin pregnancies carry substantially elevated perinatal risks, yet tools for first-trimester risk stratification remain limited. This retrospective cohort study evaluated the predictive value of crown–rump length (CRL) and nuchal translucency (NT) discordance for adverse perinatal outcomes in 184 twin pregnancies at Ankara Etlik City Hospital, Turkey (October 2022–January 2024). Methods: CRL discordance ≥ 10% and NT discordance ≥ 20% were assessed for a birth-weight-based proxy of fetal growth restriction (FGR), preeclampsia, and neonatal outcomes using multivariable logistic regression adjusted for chorionicity, body mass index (BMI), and conception mode. Results: CRL discordance ≥ 10% was independently associated with the birth-weight-based FGR proxy (adjusted odds ratio [OR] 7.79, 95% confidence interval [CI] 3.95–20.12, p < 0.001; area under the curve [AUC] 0.736). NT discordance ≥ 20% was also independently associated with the birth-weight-based FGR proxy (OR 3.74, 95% CI 1.91–8.39, p < 0.001; AUC 0.612). Both parameters were associated with lower Apgar scores. IVF conception was independently associated with preeclampsia in an exploratory analysis (OR 5.31, 95% CI 1.41–28.66, p = 0.016). Continuous modelling confirmed a dose–response relationship for CRL discordance (OR per 1% increase = 1.20, 95% CI 1.13–1.32). Conclusions: These findings suggest that first-trimester CRL discordance may provide useful early prognostic information for birth-weight-based adverse growth outcome in twin pregnancies, pending prospective validation in cohorts with Doppler-based FGR ascertainment. Full article

Background: Increased nuchal translucency (NT) is associated with an elevated risk of genetic abnormalities and structural malformations. The clinical utility of invasive testing and the optimal diagnostic approach in mildly increased NT (3.0–3.4 mm) is debated. This study aimed to evaluate genetic and ultrasound findings in this subgroup and to assess the diagnostic yield of advanced genetic testing. Methods: We retrospectively included a total of 107 fetuses with NT between 3.0 and 3.4 mm from a single fetal medicine unit. Complete outcome data were available for 97 pregnancies. Invasive prenatal testing with standard karyotype, chromosomal microarray analysis (CMA) and RASopathy panel testing were offered. All patients underwent detailed ultrasound examination to detect structural abnormalities at 16 and 20 weeks, regardless of whether invasive testing was performed. Results: Invasive prenatal testing, amniocentesis or chorionic villus sampling, (CVS), was performed in 77/97 cases (79.4%). Genetic abnormalities were detected in 28/97 (28.9%). Overall, five rare genetic anomalies were identified; none would have been detected by quantitative fluorescent polymerase chain reaction (QF-PCR) or non-invasive prenatal testing (NIPT). Two anomalies were detectable by standard karyotype, two exclusively by CMA and one exclusively by RASopathy panel. When considering all cases undergoing advanced genetic testing (CMA or RASopathy panel, n = 35) the overall diagnostic yield was 8.5% (3/35). When calculated across the entire cohort with complete follow-up, the additional diagnostic yield was 3.1% (3/97). Major structural malformations were identified in 17/97 cases (17.5%), of which 10 (58.8%) were associated with genetic abnormalities. Conclusions: Fetuses with NT measurements between 3.0 and 3.4 mm show a substantially increased risk of genetic abnormalities and structural malformations. These findings support a comprehensive prenatal evaluation, including invasive testing with advanced genetic analysis and detailed ultrasound assessment, to optimize diagnosis and counseling. Full article

Background: First-trimester prenatal screening is a fundamental component of modern obstetric care, offering early insights into fetal health and development. A key focus of this screening is the detection of chromosomal abnormalities, such as Trisomy 21 (Down syndrome), which can have significant implications for pregnancy management and parental counseling. Over the years, various non-invasive methods have been developed, with ultrasound-based assessments becoming a cornerstone of early evaluation. Among these, the measurement of Nuchal Translucency (NT) has emerged as a critical marker. This sonographic measurement, typically performed between 11- and 13-weeks 6+ days of gestation, quantifies the fluid-filled space at the back of the fetal neck. An increased NT measurement is a well-established indicator of a higher risk for aneuploidies and other congenital conditions, including heart defects. The Fetal Medicine Foundation has established standardized criteria for this measurement to ensure its reliability and widespread adoption in clinical practice. Methods: We utilized two datasets comprising 2425 ultrasound images from Shenzhen People’s Hospital China and the National Hospital of Obstetrics and Gynecology Vietnam. The methodology employs a two-stage Deep Learning framework: first, a DenseNet121 model assesses image quality to filter non-standard planes; second, a novel DenseNet-based segmentation delineates the NT region for automated measurement. Results: The quality assessment module achieved 94% accuracy in distinguishing standard from non-standard planes. For segmentation, the proposed model achieved a Dice coefficient of 0.897 and an overall accuracy of 98.9%, outperforming the standard U-Net architecture. Clinically, 55.47% of automated measurements deviated by less than 1 mm from expert annotations, and the system demonstrated > 90% sensitivity and specificity for identifying high-risk cases (NT ≥ 2.5 mm). Conclusions: The proposed framework successfully integrates quality assurance with automated measurement, offering a robust decision-support tool to reduce variability and improve screening accuracy in prenatal care. Full article

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, often fatal congenital disorder characterized by severe neonatal respiratory distress and associated with complex multisystem malformations. In approximately 90% of cases, the condition is linked to deletions or mutations affecting the FOXF1 gene or its upstream enhancer region on chromosome 16q24.1. This review analyzes reported prenatal cases with 16q24.1 deletion involving FOXF1, aiming to identify recurrent sonographic features and elucidate the underlying genomic and epigenetic mechanisms. We reviewed prenatal cases reported in the literature involving deletions of the 16q24.1 region, including the FOXF1 gene. Here, we expand the case series by reporting a fetus with increased nuchal translucency measuring 8 mm and a de novo 16q24.1 deletion. We identified nine prenatal cases with a 16q24.1 deletion, all involving the FOXF1 gene or its enhancer region. The main ultrasound findings included increased nuchal translucency and cystic hygroma during the first trimester, and cardiac, renal, and intestinal malformations from 20 weeks of gestation onward. Prenatal diagnosis of ACDMPV based solely on ultrasound findings is challenging. In most reported cases, the pregnancy was carried to term, with the diagnosis being confirmed by post-mortem histopathological examination. In the only case in which the pregnancy was terminated at 14 weeks’ gestation, histological examination of the fetal lungs, despite them being in the early stages of development, revealed misaligned pulmonary veins in close proximity to the pulmonary arteries and bronchioles. Evidence highlights the significance of non-coding regulatory regions in the regulation of FOXF1 expression. Differential methylation patterns, and possible contributions of parental imprinting, highlight the complexity of FOXF1 regulation. Early detection through array comparative genomic hybridization (array CGH) or next-generation sequencing to identify point mutations in the FOXF1 gene, combined with increased awareness of ultrasound markers suggestive of the condition, could improve the accuracy of prenatal diagnosis and genetic counseling. Further research into the epigenetic regulation of FOXF1 is crucial for refining recurrence risk estimates and improving genetic counseling practices. Full article

Background and Objective: Thrombophilia significantly increases the risk of complications like recurrent pregnancy loss, preeclampsia, IUGR, and stillbirth. Objective: This study aimed to evaluate the impact of inherited thrombophilic mutations on first-trimester screening outcomes, focusing on their relationship with maternal biomarkers and ultrasonographic parameters. Materials and Methods: A prospective observational study was conducted on 105 pregnant women during the first trimester (10–13 weeks of gestation). Genetic testing identified common thrombophilic mutations, including factor V Leiden, prothrombin G20210A, and MTHFR polymorphisms. First-trimester screening parameters, including PAPP-A, free β-hCG, and nuchal translucency (NT), were assessed. Maternal demographic and clinical characteristics, such as parity and smoking status, were recorded. Pearson correlation and risk estimates were calculated to explore associations between thrombophilic mutations, maternal factors, and screening results. Results: Lower parity (≤2) was significantly associated with a reduced risk of low PAPP-A levels (<1.0 MoM) (OR = 0.173; 95% CI: 0.044–0.676). Non-smokers showed a trend toward lower risk of low PAPP-A, although the association was not statistically significant. NT measurements <2.5 mm were consistent with normal fetal development, while maternal factors such as chronic hypertension and a history of small-for-gestational-age infants showed no significant correlations with screening markers. No significant association was observed between thrombophilic mutations and biomarker levels. Conclusions: Parity emerges as a significant factor influencing first-trimester screening outcomes, particularly PAPP-A levels, underscoring the need for tailored risk assessments in multiparous women. While smoking and thrombophilic mutations showed no definitive impact, their potential role in placental dysfunction warrants further investigation. These findings emphasize the importance of integrating maternal characteristics into screening protocols to enhance predictive accuracy and maternal–fetal outcomes. Full article

Background and Objectives: Smoking has adverse effects on both maternal and fetal health and its incidence varies among different countries. The aim of this study was to identify the prevalence of smoking during pregnancy and to identify factors associated with smoking. Materials and Methods: This was a retrospective study conducted at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, during an 11-year period (2013–2023). All women receiving antenatal care in our unit were eligible to participate when they attended the prenatal unit for the first trimester nuchal translucency scan (11⁺⁰–13⁺⁶ weeks). Results: Of the 12,074 pregnant women included in the study, 5005 (41.5%) reported themselves as smokers before pregnancy; the smoking cessation rate due to pregnancy was 70.2% (3516/5005) and the prevalence of smoking in pregnancy was 12.3% (1489/12,074). Multiparity was associated with less odds of smoking before pregnancy (OR: 0.79; 95% CI: 0.73–0.85), whereas advanced maternal age (OR: 1.17; 95% CI: 1.07–1.27) and obesity (OR: 1.44; 95% CI: 1.29–1.6) were associated with higher odds of smoking before pregnancy. Smoking prevalence in pregnancy was lower in women that conceived via assisted reproductive techniques (ARTs) (OR: 0.52; 95% CI: 0.38–0.70) and higher in cases of multiparity (OR: 1.12; 95% CI: 1.008–1.26) and maternal obesity (OR: 1.55; 95% CI: 1.20–2.00). Conception via ARTs was associated with higher odds of smoking cessation (OR: 1.9; 95% CI: 1.38–2.69), whereas multiparous (OR: 0.7; 95% CI: 0.62–0.8) and obese women (OR: 0.72; 95% CI: 0.61–0.85) were less likely to quit smoking. Conclusions: Pregnancy is a strong motivator for women to quit smoking, especially in primiparous women and those undergoing ARTs. Our findings highlight the need for more consistent smoking prevention and health promotion strategies in Greece as a very high proportion of women smoke before pregnancy and a substantial proportion continue in pregnancy. Full article

Objective. Our objective was to assess the proportion of false-positive CHD cases at the first-trimester evaluation of the fetal heart, performed by experienced operators. Methods. This multicenter retrospective study included of pregnant women with suspicion of CHDs during first-trimester screening for aneuploidies. In all cases, the fetal heart assessments were performed by obstetricians with extensive experience in first-trimester scanning, following an extended protocol proposed by SIEOG national guidelines, which included an axial view of the fetal abdomen and chest to assess visceral situs and evaluation of the four-chamber view (4CV) and three-vessel trachea view (3VTV) with color Doppler. In all suspected cases, fetal echocardiography was offered within 16 and/or at 19–22 weeks’ gestation. Results. From a population of 4300 fetuses, 46 CHDs were suspected. Twenty-four cases were excluded from this analysis because the parents opted for early termination of the pregnancies due to associated structural and/or genetic anomalies. For the remaining 22, echocardiography was performed by 16 weeks in 14 cases (64%) and after 16 weeks in 8 cases. In 19 cases (86.4%), a fetal cardiologist confirmed the presence of a CHD. In three cases (13%), the cardiac anatomy was found to be normal at the fetal echocardiography and postnatally. Conclusions. This study shows that the proportion of false-positive cases at the first-trimester ultrasound examination of the fetal heart, performed by experienced operators, may carry a higher risk of false-positive diagnosis than expected. Therefore, this issue must be discussed in instances where a CHD is suspected at the first-trimester screening. Full article

Noonan syndro me is a rare autosomal dominant congenital abnormality associated with a gene defect located on the short arm of chromosome 12. It is characterized by dysmorphic facies, webbed neck, short stature, lymphatic obstruction, cardiac anomalies, and intellectual disability. Prenatal diagnosis of Noonan syndrome is rare because there are no pathognomonic sonographic signs. Studies on the prenatal sonographic features of Noonan syndrome have been reported in very limited numbers. This case series of severe fetal Noonan syndrome, together with a literature review, was conducted to establish prenatal sonographic features highly suggestive of Noonan syndrome to facilitate early detection by clinicians. This study reveals that Noonan syndrome has a relatively specific pattern, which facilitates prenatal molecular genetic diagnosis. Increased nuchal translucency (NT) in the late first trimester and fluid collection in the early second trimester could be warning signs for follow-up, prompting further investigation to detect late-onset features and leading to molecular genetic confirmation. Most structural abnormalities appear in the second trimester, with progressive changes noted throughout gestation. This review better characterizes the sonographic features of fetal Noonan syndrome based on a larger sample size, illustrating a wider spectrum of prenatal phenotypes, including lymphatic drainage disorders, cardiac abnormalities, polyhydramnios, and absent ductus venosus. Full article

Background: This study assesses the effects of the ‘Radiant’ image enhancement technique on fetal nuchal translucency (NT) measurements during first-trimester sonographic exams. Methods: A retrospective analysis of 263 ultrasound images of first-trimester midsagittal sections was conducted. NT measurements were obtained using a semi-automatic tool. Statistical methods were applied to compare NT measurements with and without ‘Radiant’ enhancement. An in vitro setup with predefined line distances provided additional data. Results: Incremental increases in NT measurements were observed with varying levels of ‘Radiant’ application: an average increase of 0.19 mm with ‘Radiant min’, 0.24 mm with ‘Radiant mid’, and 0.30 mm with ‘Radiant max.’ The in vitro results supported these findings, showing consistent effects on line thickness and measurement accuracy, with the smallest mean deviation occurring at the ‘Radiant mid’ setting. Conclusions: ‘Radiant’ image enhancement leads to significant increases in NT measurements. To avoid systematic biases in clinical assessments, it is advisable to disable ‘Radiant’ during NT measurement procedures. Further studies are necessary to corroborate these findings and to consider updates to the NT reference tables based on this technology. Full article

Introduction: Trophoblast-derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. Human Leukocyte Antigen-G (HLA-G) belongs to the non-classical human major histocompatibility complex (MHC-I) molecule and has membrane-bound and soluble forms. HLA-G is primarily expressed by extravillous cytotrophoblasts located in the placenta between the maternal and fetal compartments and plays a pivotal role in providing immune tolerance. The aim of this study was to establish a relationship between concentrations of soluble HLA-G (sHLA-G) in maternal serum and amniotic fluid at 16–22 weeks of gestation and the sonographic measurements of fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices, were determined in 41 singleton pregnancies with no complications. The level of sHLA-G (U/mL) was tested with a sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results: The sHLA-G levels were unchanged both in amniotic fluid and serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β = 0.63, p < 0.01). Serum sHLA-G level was significantly correlated with abdominal measurements (β = 0.41, p < 0.05) and estimated fetal weight (β = 0.41, p < 0.05). Conversely, amniotic sHLA-G level and placental perfusion (VI: β = −0.34, p < 0.01 and VFI: β = −0.44, p < 0.01, respectively) were negatively correlated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = −0.102, p < 0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator of placental function, whereas the sHLA-G level in serum can be a prognostic factor for feto-placental insufficiency. Full article

The modality of endometrial preparation for the transfer of frozen-thawed embryos may influence maternal and fetal adaptation to pregnancy and could thus impact the results of the first trimester combined screening test. We conducted a retrospective cross-sectional study on singleton pregnancies achieved by embryo transfer of a single frozen-thawed blastocyst, comparing two different endometrial preparation protocols: natural cycle (n = 174) and hormone replacement therapy (HRT) (n = 122). The primary outcome was the risk of preeclampsia at the first trimester combined screening test. Secondary endpoints included variable reflecting fetal cardiac function (nuchal translucency and fetal heart rate), maternal adaptation (median arterial blood pressure—MAP and uterine arteries pulsatility index—UtA-PI), and placentation (pregnancy associated plasma protein A and placental growth factor). The risk of early preeclampsia was comparable in the two groups (38% vs. a 28%, p = 0.12). However, women in the natural cycle group showed lower fetal heart rate (159 [155–164] vs. 164 [158–168], p = 0.002) and higher UtA-PI (0.96 [0.74–1.18] vs. 0.72 [0.58–0.90], p < 0.001). The frequency of a screening test at high risk for aneuploidies was similar. The modality of transfer of frozen-thawed embryos is associated with changes in the variables reflecting maternal and fetal cardiovascular function. Full article

Fetal growth restriction (FGR) is a major cause of stillbirth and poor neurodevelopmental outcomes. The early prediction may be important to establish treatment options and improve neonatal outcomes. The aim of this study was to assess the association of parameters used in first-trimester screening, uterine artery Doppler pulsatility index and the development of FGR. In this retrospective cohort study, 1930 singleton pregnancies prenatally diagnosed with an estimated fetal weight under the third percentile were included. All women underwent first-trimester screening assessing maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin levels, fetal nuchal translucency and uterine artery Doppler pulsatility index (PI). We constructed a Receiver Operating Characteristics curve to calculate the sensitivity and specificity of early diagnosis of FGR. In pregnancies with FGR, PAPP-A was significantly lower, and uterine artery Doppler pulsatility index was significantly higher compared with the normal birth weight group (0.79 ± 0.38 vs. 1.15 ± 0.59, p < 0.001 and 1.82 ± 0.7 vs. 1.55 ± 0.47, p = 0.01). Multivariate logistic regression analyses demonstrated that PAPP-A levels and uterine artery Doppler pulsatility index were significantly associated with FGR (p = 0.009 and p = 0.01, respectively). To conclude, these two parameters can predict FGR < 3rd percentile. Full article