Search Results (114)

The rhesus macaque (Macaca mulatta) is a valuable model for pregnancy research due to its physiological similarity to humans and the ability to conduct studies in a controlled environment. Our previous work used non-invasive imaging methods to assess placental hemodynamics across gestation with correlative tissue analysis post-delivery. Here, we expand access to longitudinal timepoints from ongoing pregnancies by obtaining placental biopsies using ultrasound-guided needle aspiration. This approach aligns with New Approach Methods (NAMs) and supports animal welfare by reducing the number of animals required. We describe a chorionic villus sampling (CVS) simulation model which facilitates training to gain proficiency in technical skills prior to performing the procedure on animals. We report outcomes from three rhesus macaques that underwent CVS three times between gestational days 40 to 106 (term: 165 days). Although biopsy samples are smaller than whole placenta, tissue yields were sufficient for multiple uses. We demonstrate (1) appropriate histology from aspirated samples, (2) good RNA quality and yield, and (3) the ability to isolate trophoblast organoids, an advancement in NAMs that reduces the need for first-trimester surgical delivery. No spontaneous preterm delivery occurred following serial CVS procedures, supporting the use of this sampling method to maximize animal utilization in longitudinal pregnancy studies. Full article

Background: Congenital cytomegalovirus (cCMV) infection is a leading cause of neonatal morbidity. This retrospective study aimed to evaluate the efficacy of valacyclovir in reducing vertical transmission after primary maternal CMV infection and to assess the diagnostic performance of amniocentesis and prenatal imaging. Methods: Eighty-two pregnant women with confirmed primary CMV infection were included. Maternal CMV serology and viral DNA were assessed in blood and urine, with standardized prenatal care including serial ultrasound examinations and fetal MRI when indicated. Amniocentesis was offered to confirm fetal infection. Valacyclovir (8 g/day) was administered before 24 weeks’ gestation, and neonatal infection was diagnosed by CMV DNA detection in urine at birth. Statistical analyses were performed using SPSS version 27.0. Results: Most infections (62.2%) were diagnosed in the first trimester. Valacyclovir was administered in 97.6% of cases, and amniocentesis was performed in 81.7%, with CMV DNA detected in 19.4%. Among 74 live births, 23% of neonates were CMV-positive and 6.8% symptomatic. Seven infected neonates had negative amniocentesis (false-negative rate, 13.2%). Prenatal ultrasound and MRI failed to detect abnormalities in symptomatic cases. Conclusions: Valacyclovir may reduce, but does not eliminate, the risk of cCMV transmission. Negative amniocentesis does not fully exclude fetal infection, highlighting postnatal follow-up. Full article

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformations, often presenting with atypical clinical findings. Fetal damage is most severe following primary maternal infection during the first trimester of pregnancy, with the likelihood of transmission increasing with pregnancy advancement. CMV damage may continue to intensify during the early postnatal years. In this narrative review we summarized publications from the last 30 years addressing the epidemiology, diagnosis, prevention and treatment of CMV in pregnancy, with a special emphasis on embryonic and fetal damage. Substantial progress has been made in the diagnosis and treatment of CMV infection during pregnancy, warranting a reconsideration of current clinical approaches. Assessment of viral load enables prediction of fetal infection; its reduction by maternal treatment with valacyclovir may lower both the rate and severity of transmission. Confirmed fetal infection can be diagnosed by amniocentesis and viral DNA detection. Clinical manifestations in infants may be evident at birth (cCMV) or gradually emerge during the first years. The most common fetal damage is hearing loss alongside a variety of brain lesions resulting in significant neurological deficits, including intellectual impairment. Brain involvement is diagnosed by ultrasound or magnetic resonance imaging (MRI). Pharmacological treatment with ganciclovir or valganciclovir, if initiated early after birth, can slow the progression of hearing loss and may ameliorate other neurological and neurodevelopmental deficits. As of today, there is no approved CMV vaccine for prevention. The mRNA-1647’s vaccine, currently in phase 3 clinical trial, appears promising. These advances underscore the need for screening pregnant women in the first trimester and newborn infants of mothers suspected of having CMV infection. Neurodevelopmental follow up for several years, including hearing and visual assessment, is advised in all infants positive for CMV. Infants with clinical manifestations should be offered treatment as early as possible following diagnosis of cCMV. Full article

Introduction: The scope and accessibility of prenatal testing have significantly expanded in recent years, reaching a broader population of pregnant women. Advances in non-invasive diagnostic methods support informed decision-making and help reduce the need for invasive procedures. Objective: The objective was to evaluate pregnant women’s knowledge regarding prenatal testing and assess the quality of information provided by healthcare professionals, including the frequency of screening and invasive procedures. Materials and Methods: A total of 310 obstetric patients from maternity wards in two hospitals in northern Poland completed a survey addressing prenatal tests, sources of information, and the quality of guidance received from medical staff. Results: Nearly 75% of respondents demonstrated adequate knowledge of the purpose, indications, and scope of prenatal testing. Physicians were identified as the primary source of information. Approximately 50% correctly indicated the recommended number of ultrasound examinations during pregnancy. No correlation was observed between knowledge of prenatal testing and a history of delivering a child with health complications. The combined first-trimester test was performed in 48.6% of cases, NIPT in 11.6%, and invasive testing in 1.8% of the study group. Conclusions: Public awareness of prenatal testing in Poland remains insufficient. With the introduction of partially reimbursed tests in 2024, we recommend strengthening educational efforts through social campaigns and targeted training for healthcare professionals. Full article

Background/Objectives: Timely initiation of antenatal care (ANC) services is crucial for ensuring maternal and fetal well-being. Despite the importance of ANC, research regarding its initiation remains limited in the Jazan region of Saudi Arabia, an area with notable adverse birth outcomes. Therefore, this study aimed to assess pregnant women’s initiation of ANC and identify associated factors and significant barriers for timely initiation. Methods: A cross-sectional study was conducted among 369 Saudi pregnant women in their third trimester attending ANC clinics in the Jazan region in 2024. A structured questionnaire was used to collect data. Andersen’s behavioral model of healthcare utilization provided the framework for the study. Descriptive statistics, chi-square tests, and binary logistic regression were used to analyze the data. Results: The majority of women (78.9%) initiated ANC in the first trimester. Higher maternal education was positively associated with early ANC initiation (aOR = 2.369, 95% CI: 1.154–4.901), whereas higher paternal education was negatively associated with early ANC initiation (aOR = 0.350, 95% CI: 0.175–0.699). When modeled independently, the positive association of higher maternal education was attenuated but was not significant, while the negative association of higher husband’s education remained the same. Those living more than three km from health facilities (aOR = 0.510, 95% CI: 0.276–0.941) and seeking care for reasons other than routine follow-up were less likely to initiate ANC early. Most women received essential services, but only 37.1% had ultrasound tests. Conclusions: While ANC initiation in Jazan showed promising trends, factors like geographical accessibility remain a significant barrier. Targeted interventions should address these identified barriers, which fall within predisposing, enabling, need, and external environmental factors. Further investigations of pregnant women’s familial decision-making and low ultrasound test utilization in relation to ANC are recommended. Full article

Background/Objectives: The role of luteal phase support (LPS) in frozen–thawed embryo transfer (FET) cycles has garnered increasing interest, particularly regarding its influence on uterine perfusion and pregnancy outcomes. This study aimed to investigate the effect of different oral LPS regimens on first-trimester uterine artery Doppler indices and their association with early pregnancy outcomes in naturally conceived and FET pregnancies. Methods: This retrospective cohort study included 289 singleton pregnancies comprising spontaneous conceptions, FET cycles supported with oral micronised progesterone, and FET cycles supported with oral dydrogesterone. The uterine artery pulsatility index (PI) was measured via Doppler ultrasound during the first trimester. Group comparisons were performed using non-parametric tests. Multivariable regression analyses were used to assess independent predictors of PI and associations with gestational diabetes and low birth weight. Results: Uterine artery PI values differed significantly among the groups (p < 0.001). The lowest PI was observed in the dydrogesterone group, followed by the naturally conceived and micronised progesterone groups. A higher maternal body mass index (BMI) was independently associated with lower PI (p = 0.009), while maternal age showed no significant effect. No significant associations were found between PI or maternal characteristics and adverse outcomes such as gestational diabetes or low birth weight. Conclusions: Dydrogesterone was associated with more favorable uterine artery Doppler indices in early pregnancy, suggesting improved uteroplacental adaptation in FET cycles. These findings support further prospective research to determine the clinical impact of LPS regimens on placental development and perinatal health. Full article

Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection, affecting approximately 0.5–2% of newborns, and is the leading non-genetic cause of sensorineural hearing loss and neurological impairment. The most severe outcome occurs following primary maternal infection during the first trimester of pregnancy, and up to 40–50% of affected fetuses sustain permanent damage. Diagnosis relies on early prenatal screening through maternal serum testing, optimally performed in the first trimester, followed by confirmatory amniocentesis after 17 weeks’ gestation. Prenatal imaging with ultrasound and magnetic resonance imaging (MRI) plays a critical role in the identification of fetal brain abnormalities. Prevention strategies emphasize hygiene measures aimed at reducing maternal exposure to bodily fluids of young children, particularly prior to conception and during early pregnancy. Despite progress in vaccine development, currently available ones demonstrate modest efficacy. This review presents a comprehensive summary of congenital CMV infection, addressing its epidemiology, pathogenesis, diagnostic approaches, clinical presentation, and preventive measures, with a focus on recent advances in vaccine research. Full article

Background: A short cervix in the second trimester significantly increases preterm birth risk, yet no reliable first-trimester prediction method exists. Current guidelines lack consensus on which women should undergo transvaginal ultrasound (TVUS) screening for cost-effective prevention. Therefore, it is vital to establish a highly accurate and economical method for use in the early stages of pregnancy to predict short cervix in mid-pregnancy. Methods: A total of 1480 pregnant women with singleton pregnancies and at least one risk factor for spontaneous preterm birth (<37 weeks) were recruited from January 2020 to December 2020 at the Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Cervical length was assessed at 20–24 weeks of gestation, with a short cervix defined as <25 mm. Feature selection employed tree models, regularization, and recursive feature elimination (RFE). Seven machine learning models (logistic regression, linear discriminant analysis, k-nearest neighbors, support vector machine, decision tree, random forest, XGBoost) were trained to predict mid-trimester short cervix. The XGBoost model—an ensemble method leveraging sequential decision trees—was analyzed using Shapley Additive Explanation (SHAP) values to assess feature importance, revealing consistent associations between clinical predictors and outcomes that align with known clinical patterns. Results: Among 1480 participants, 376 (25.4%) developed mid-trimester short cervix. The XGBoost-based prediction model demonstrated high predictive performance in the training set (Recall = 0.838, F1 score = 0.848), test set (Recall = 0.850, F1 score = 0.910), and an independent dataset collected in January 2025 (Recall = 0.708, F1 score = 0.791), with SHAP analysis revealing pre-pregnancy BMI as the strongest predictor, followed by second-trimester pregnancy loss history, peripheral blood leukocyte count (WBC), and positive vaginal microbiological culture results (≥10⁵ CFU/mL, measured between 11⁺⁰ and 13⁺⁶ weeks). Conclusions: The XGBoost model accurately predicts mid-trimester short cervix using first-trimester clinical data, providing a 6-week window for targeted interventions before the 20–24-week gestational assessment. This early prediction could help guide timely preventive measures, potentially reducing the risk of spontaneous preterm birth (sPTB). Full article

Background/Objectives: Cystic hygroma is a congenital lymphatic malformation often identified during early pregnancy and frequently associated with chromosomal abnormalities and adverse outcomes. We aimed to appraise the genetic and clinical characteristics of fetuses diagnosed with cystic hygroma in the first/early second trimester, assess the resolution patterns in chromosomally normal cases, and provide insights into prognosis—based on data collected over a 30-year period. Methods: A retrospective cohort study was conducted on 405 consecutive fetuses diagnosed with nuchal cystic hygroma between 8.0 and 14.0 weeks of gestation from 1993 to 2023 at two tertiary care centers. Diagnoses were established using high-resolution transabdominal and transvaginal 3D/4D ultrasonography. All cases underwent prenatal cytogenetic analysis, including karyotyping. Fetuses with a normal karyotype were observed through serial ultrasounds through the remainder of the pregnancy to verify the eventual resolution of hygromas. Both descriptive and inferential statistical methods were used, with p < 0.05 as a cut-off (two-tailed). Results: Of the 405 fetuses, 210 (51.9%) had chromosomal abnormalities, most commonly trisomy 21, while 195 (48.1%) had a normal karyotype. A significantly higher frequency of trisomy 21 was observed compared to other identified chromosomal abnormalities (p < 0.001). In the chromosomally normal group, 85 (43.6%) showed spontaneous resolution of the hygroma within four weeks, and these pregnancies resulted in phenotypically normal live births. Septated hygromas were significantly more frequent in the abnormal karyotype group (71.4%). Conclusions: The finding and diagnosis of cystic hygroma in first trimester and early second-trimester pregnancy represent a strong predictor of chromosomal aneuploidy and warrant comprehensive prenatal genetic testing and close follow-up. However, in the absence of genetic abnormalities and additional malformations, spontaneous resolution is common, and neonatal outcomes are generally favorable. Health systems should provide equitable access to genetic testing and fetal imaging to support accurate diagnosis and informed decisions. Full article

Objective: To describe first-trimester maternal, biochemical, biophysical, and ultrasound characteristics in women with recurrent pregnancy loss (RPL) compared to women without RPL. Methods: This was a retrospective cohort study analyzing data from 4440 pregnant women, including 142 women with previous RPL. Maternal and pregnancy characteristics, first-trimester biochemical markers, biophysical assessments, early-onset preeclampsia (EOPE) risk, and perinatal outcomes were compared. Results: Women with RPL were older (37.8 vs. 34.0 years, p < 0.001) and had higher rates of antiphospholipid syndrome (4.9% vs. 0.9%, p < 0.001), other thrombophilias (5.6% vs. 0.8%, p < 0.001), and thyroid disorders (14% vs. 7.5%, p = 0.010) than women without RPL. First-trimester uterine artery pulsatility index (UtA-PI) values, pregnancy-associated plasma protein-A (PAPP-A) levels, mean arterial pressure, and final risk for EOPE were comparable between groups. However, the RPL group had higher rates of very high risk for PE (10.6 vs. 5.1, p = 0.011). Likewise, second-trimester UtA-PI was higher in this group (1.10 vs. 1.01, p = 0.045). Aspirin and low molecular weight heparin prophylaxis were more frequent in women with RPL (23.8% vs. 9.6%, p < 0.001; 14.7% vs. 0.1%, p < 0.001). Regarding perinatal outcomes, we found a higher incidence of second-trimester intrauterine demise in the RPL group (6.4% vs. 1.4%, p = 0.011), with no other differences observed in the remaining outcomes. Conclusions: Women with RPL exhibit distinct maternal characteristics and worse pregnancy outcomes, although first-trimester markers do not seem to significantly differ from findings in women without RPL. These findings underscore the importance of tailored screening and intervention protocols to improve perinatal outcomes in this high-risk population. Full article

Introduction: Gestational diabetes mellitus (GDM) is a form of hyperglycemia that develops during pregnancy and poses risks to both the mother and fetus. In other words, it is a glucose intolerance disorder first recognized during pregnancy, specifically in the second and third trimesters, with approximately 7–14% of pregnancies worldwide being affected. Methodology: A systematic literature search was conducted across three major well-established databases; PubMed, Scopus, and ScienceDirect. The search was conducted with the aim of identifying the most suitable studies for the evaluation of fetal cardiac function using Doppler ultrasound techniques in pregnancies affected by GDM. Results: Following a comprehensive full-text assessment, 186 papers were excluded, mainly due to discrepancies in the population, unsuitable study design, publishing type, or unavailability of full-text access. Ultimately, 12 studies met all the inclusion criteria and were incorporated into the scoping review. From the studies included it was found that the conventional pulsed-wave Doppler was the most frequently used modality, assessing parameters such as the E/A ratios, myocardial performance index (MPI), and the isovolumic relaxation time (IVRT). The advanced techniques of choice included tissue Doppler imaging (TDI), speckle-tracking echocardiography (STE), dual-gate Doppler, and automated MPI. Conclusions: Doppler ultrasound techniques, particularly the advanced modalities like TDI and STE, provide valuable insights into fetal cardiac function in GDM pregnancies. Their integration into routine prenatal surveillance may enhance the early detection of cardiac dysfunction and inform timely clinical interventions. Full article

Background and Objectives: Doppler abnormalities in the ductus venosus (DV) during the first trimester can serve as an early marker for the detection of congenital heart defects (CHDs), but the feasibility of systematically assessing the DV remains underexplored. This study aimed to evaluate the feasibility of performing DV assessments during routine first-trimester ultrasound screenings. Materials and Methods: A multicenter, prospective, and descriptive study was conducted, including singleton pregnancies undergoing routine ultrasound screening between 11 + 0 and 13 + 6 weeks of gestation. Sonographers were instructed to acquire DV Doppler images during the scan, and each image was blindly reviewed by an expert using predefined quality criteria. The images were categorized as “good”, “medium”, or “unsatisfactory”, and feasibility was defined as the proportion of “good” images. Factors associated with feasibility were analyzed, including sonographer satisfaction, the Herman score and the acquisition time. Results: Of the 87 patients included in this study, a suitable DV Doppler image was feasible in 58.6% of cases. The feasibility was significantly higher when the sonographer was satisfied with the image, when the Herman score exceeded seven (p = 0.01), and when the acquisition time was less than five minutes. A strong correlation was observed between the expert’s assessment and the sonographer’s satisfaction. However, the gestational age, maternal BMI, parity, and operator-perceived image quality were not significantly associated with feasibility. Conclusions: The Doppler assessment of the ductus venosus during first-trimester ultrasound screening is feasible and reproducible in routine clinical practice without significantly increasing the examination time. This suggests DV measurements to enhance the early nuchal translucency measurement to enhance the early detection of congenital heart defects during the first trimester. 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/Objectives: Fetal thigh circumference (ThC) may be a valuable parameter for assessing fetal growth. Thus, this study aimed to establish reference ranges for ThC across gestational ages (GA). Methods: This retrospective study included singleton pregnancies between 12 and 38 weeks of gestation. ThC measurements were obtained during routine ultrasound examinations. GA was confirmed through the last menstrual period and first-trimester crown–rump length measurements. Percentile ranges for ThC were calculated for each gestational week, and statistical analyses evaluated the relationship between ThC and GA. Results: 48,841 singleton pregnancies were included. A positive correlation was observed between ThC and GA, with ThC values increasing progressively from 12 to 38 weeks. The study established the 10th, 50th, and 90th percentile ranges for ThC, providing reference values for clinical assessments. Conclusions: This study provides reference ranges for fetal ThC across a wide GA range, highlighting its potential as a tool in prenatal care. ThC may offer an additional parameter for monitoring fetal growth, especially when standard measurements are challenging. Further research should investigate the integration of ThC with other fetal growth parameters to enhance its clinical utility. Additionally, these nomograms can be used to assess their usefulness in certain conditions, such as intrauterine growth restriction (IUGR), macrosomia, and congenital skeletal dysplasias. Full article

Background: Noonan syndrome (NS) is a relatively common RASopathy that can be associated with a variety of phenotypic and genotypic variations and potential long-term health consequences. Its most described prenatal ultrasound features in the first trimester are thickened nuchal translucency (NT) and dilated jugular sacs; while heart defects, polyhydramnios and facial dysmorphisms are its known manifestations in the second and third trimesters. Methods: We present two cases of NS with the prenatal ultrasound diagnosis of external hydrocephalus (EH) in the second trimester. Results: Case 1 had a normal first trimester scan and showed mild polyhydramnios, an echogenic intracardiac focus (EIF) in the left ventricle and pyelectasis in the second trimester in association with the EH. The whole exome sequencing (WES) confirmed a pathogenic variant in the SOS1 gene. Case 2 showed increased NT, agenesis of the ductus venosus (DV), single umbilical artery (SUA), an EIF in the right ventricle and an abnormal prefrontal space ratio (PSFR). By the 19th gestational week, EH appeared. The ambient and quadrigeminal cisterns were also slightly widened. The WES revealed a PTPN11 gene variant. Conclusions: The most reported sonographic features of NS are either non-specific or difficult to integrate into routine screening, requiring substantial experience. In our two cases, we detected EH in the second trimester, which is rarely described as a prenatal ultrasound diagnosis. To our current knowledge, this is the first case reported of EH in NS caused by an SOS1 gene variant and these are the first cases reported with the prenatal sonographic diagnosis of EH in NS. Full article