Search Results (301)

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/Objectives: Cantú syndrome is a rare autosomal dominant genetic disorder caused by gain-of-function variants in the ABCC9 or KCNJ8 genes. Although its phenotypic expression is variable and can go unnoticed postnatally, certain ultrasound findings may raise suspicion during pregnancy. This article presents a case of prenatal diagnosis through exome sequencing, which also enabled retrospective diagnosis in the mother and a previously undiagnosed child, highlighting the clinical and emotional value of diagnostic certainty in fetal medicine. Methods: We conducted a descriptive observational study based on a case identified at the Fetal Medicine Unit of the Regional University Hospital of Málaga. The patient underwent high-resolution ultrasound and trio-based exome sequencing (fetus and both parents). Results: Prenatal exome sequencing revealed a heterozygous pathogenic variant in ABCC9, consistent with Cantú syndrome, identified simultaneously in the fetus and the mother as part of a trio-based analysis, confirming maternal inheritance. The same variant was later detected in the patient’s older daughter, who had been under pediatric evaluation for a suggestive phenotype but had not received a genetic diagnosis until this study. The prenatal diagnosis allowed for obstetric and neonatal planning, genetic counselling, and a reinterpretation of the clinical and emotional meaning of previous pregnancies. Conclusions: Prenatal diagnosis of Cantú syndrome enables anticipation of perinatal complications, planned clinical interventions, and also provides emotional relief and a coherent narrative for families. In scenarios of variable phenotypic expressivity, fetal medicine may represent a gateway to family diagnosis, with significant clinical and psychosocial implications. Full article

Background/Objective: Prenatal cytogenetic testing is essential for pregnant women who are at high risk of having a child with a chromosomal abnormality. While conventional karyotyping detects large aneuploidies and structural rearrangements (>5–10 Mb), chromosomal microarray analysis (CMA) identifies smaller copy number variants (CNVs), increasing the diagnostic yield by approximately 5%. CMA is now recommended as the first-line test for evaluating fetal structural anomalies that are detected by ultrasound. Method: From March 2023 to September 2024, we analyzed 344 prenatal samples using conventional karyotyping and SNP-based CMA. Karyotyping was performed via flask culture, and CMA was conducted using the Infinium Global Screening Array Cyto (GSA-Cyto) on the Illumina iScan platform. We interpreted the CNVs using NxClinical v6.0 and curated databases including ClinVar, DECIPHER, OMIM, and ClinGen, among others. Our results aligned with the GRCh37/hg19 reference genome. Results: Chromosomal abnormalities were identified in 57/344 cases (16.5%). Of these, 39 cases were numerical chromosomal anomalies, and 18 cases were pathogenic or likely pathogenic CNVs. Notably, 11 CNVs (3.2%) were undetectable by conventional karyotyping, emphasizing the added value of CMA. Conclusions: CMA enhances the prenatal diagnostic accuracy by detecting submicroscopic CNVs that are not visible with conventional methods, supporting the routine use of this analysis in prenatal genetic evaluation. 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

Background and Objectives: Congenital abnormalities are a leading cause of neonatal morbidity and mortality and are frequently detectable through prenatal ultrasound. While widely implemented in high-income countries, such screening remains inconsistently applied in low- and middle-income regions. This study aimed to estimate the prevalence of congenital abnormalities identified via prenatal ultrasound in Lebanon and to explore associated maternal, obstetric, and psychosocial factors. Methods: A multicenter retrospective observational study, supplemented by follow-up interviews, was conducted in five Order of Malta medical centers. Pregnant women in their second trimester underwent an obstetric ultrasound, and data were collected through structured questionnaires and follow-up phone interviews. Variables included maternal demographics, obstetric history, anxiety levels (GAD-7 scores), and ultrasound findings. Results: A total of 426 pregnant women were enrolled (mean age: 28.8 ± 5.9 years). The overall prevalence of congenital abnormalities was 13.1%. Growth abnormalities were observed in 8.5% of fetuses and were significantly associated with obstetric complications and the presence of multiple abnormalities. Morphological malformations were found in 10.1% of cases and were more common among women of advanced maternal age, those with a history of anomalies, and those reporting elevated anxiety scores. Combined abnormalities, as well as growth and morphological malformations, were significantly associated with higher parity, prior anomalies, and current pregnancy complications. Conclusions: Prenatal ultrasound is essential for early detection of congenital abnormalities, facilitating timely intervention and improved neonatal outcomes. These findings emphasize the need to integrate systematic screening into prenatal care in Lebanon and for ongoing research to identify context-specific risk factors. Full article

Background: Congenital anomalies impact 52 million infants worldwide with an estimated 94% living in low- and middle-income countries (LMICs). Approximately 200,000 children are born with a neural tube defect (NTD) in LMICs annually. Zambia is an LMIC with a high burden of myelomeningocele (MMC; a severe form of NTD). This study sought to characterize the barriers influencing access to healthcare for children born with MMC in Zambia. Methods: Two cross-sectional surveys were administered to healthcare providers at referring public health facilities and mothers of infants born with MMC undergoing surgical closure. The survey among mothers was nested in a longitudinal study evaluating surgical closure in Lusaka, Zambia from 28 May 2024 to 21 January 2025. Results: Sixty-nine mother–MMC baby dyads and 123 providers from 21 facilities were enrolled in the study. The median age at presentation for MMC was 7.5 (range 0–244) days old. Most patients were referred from rural district hospitals (51%; n = 35) and travelled greater than 250 km to access care (80%; n = 55). Seventy-seven percent (n = 53) of mothers reported receiving at least one antenatal ultrasound, with 62% (n = 43) undergoing an ultrasound after 20 weeks estimated gestational age. Of these, only 3% (n = 2) received an MMC diagnosis prior to delivery. Referring patients with MMC for further care greater than six hours after birth was reported by 59% providers (n = 73). Hospitals further away from the tertiary center were more likely to report late referrals (p < 0.001). Conclusions: There is a delay in the diagnosis and referral of infants with MMC to specialized care in Zambia, which may be attributed to inadequate in utero diagnosis capabilities and distance from the tertiary facility. Improving the accuracy of prenatal diagnosis and strengthening referral pathways to facilitate access to care among infants with MMC in Zambia are important for improving incidence and outcomes. 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

Objective: To investigate the association between prenatal ultrasonographic markers of macrossomia and C-peptide, a neonatal hyperinsulinemia marker, in pregnancies complicated by gestational diabetes mellitus (GDM), with a focus on fetal adipose tissue thickness, liver length, and interventricular septal thickness. Methods: This prospective cohort study included 223 pregnant women followed from 28 to 36 weeks of gestation in two referral centers in Brazil. The GDM group and matched controls underwent serial ultrasound assessments of fetal biometry, including thigh, abdominal, and subscapular skinfolds, fetal liver length, and interventricular septum thickness. Neonatal hyperinsulinemia was assessed using umbilical cord C-peptide levels. Statistical analyses included t-tests, chi-square tests, correlation analyses, and multivariate logistic regression. Results: Fetuses of mothers with GDM exhibited significantly greater abdominal [t(221) = −3.999, p < 0.01] and subscapular [t(221) = −2.502, p = 0.02] skinfolds, liver length [t(221) = −3.785, p < 0.01], and interventricular septum [t(221) = −4.781, p < 0.01] thickness. However, umbilical cord C-peptide levels did not differ significantly between groups [t(189) = −1.724, p = 0.09]. Only weak correlations were found between fetal ultrasound markers and C-peptide levels. Among all parameters, subcutaneous tissue thickness showed the highest (ρ = 0.30), though still limited, predictive value. Conclusions: Fetuses of mothers with GDM demonstrated increased measures of liver length, subscapular adiposity, and interventricular septal thickness compared to controls. However, these prenatal biometric markers showed weak correlations with neonatal C-peptide levels. Full article

Hypoplastic or absent fetal nasal bone (NB) is a significant soft marker in the risk assessment for aneuploidies. This study aimed to evaluate prenatal findings and perinatal outcomes in fetuses with absent or hypoplastic NB managed at our center. This retrospective analysis was conducted at the Department of Obstetrics at the Medical University of Vienna and including all cases with an absent or hypoplastic fetal NB between 2004 and 2022. Clinical data were extracted and analyzed using descriptive statistics. A total of 149 cases were included. Of these, 51% had chromosomal abnormalities, with trisomy 21 present in 30.9%. Malformations were identified in 55% of cases, most commonly congenital heart defects (34.9%) and facial dysmorphism (28.9%). Eighteen fetuses (12.1%) had structural anomalies without genetic disorders. In 32.9% (n = 49), the NB anomaly was isolated. Our findings show that only half of the cases had chromosomal abnormalities, and over half of the pregnancies resulted in live births with generally favorable perinatal outcomes. However, the presence of additional ultrasound abnormalities significantly increased the risk of adverse outcomes. Therefore, detection of a fetal NB anomaly should prompt comprehensive ultrasound evaluation and genetic testing. Full article

Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. 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

Objectives: The objectives are to evaluate the influence of different maternal characteristics on ultrasound image quality and operator satisfaction, and to assess, preliminarily, a rating scale to stratify the difficulty level of ultrasound examination in early gestation. Methods: A multicentric observational study of ultrasound scans was carried out on singleton pregnant women undergoing routine gestational ultrasound at 11–14 weeks and 19–21 weeks of gestation at two Prenatal Care Centers in the Apulia region (Southern Italy). Inclusion criteria included the presence of one or more limiting features, i.e., obesity, retroverted uterus, myomas, previous abdominal surgery, and limited echo-absorption. Each woman was given an overall pre-echographic limiting score from 0 to 9. The outcome measure was the operator’s satisfaction with the examination, scored on a Likert scale. Nested linear regression models (raw, semi- and fully adjusted) were built for each of the two trimesters on the pre-ecographic limiting score (0–9 points) as dependent variables, with the operator’s satisfaction as the regressor. Results: The whole sample included 445 pregnant women. The two-center samples did not show statistically different baseline features. The operator’s satisfaction with the sonographic examination was significantly (and inversely) related to the pre-echographic limiting score, regardless of the mother’s age, the operator performing the ultrasound, the Hospital Center where the ultrasound examination was performed, and the duration of the sonographic examination. Conclusions: A number of maternal conditions need to be monitored for good ultrasound performance; using a specific rating scale to stratify the level of difficulty of the ultrasound examination at early gestation could represent a potentially useful tool, although it requires further validation. Full article

Objectives: To evaluate the association between late CVS (placental biopsy, later than 13 weeks of gestations) and complications between sampling and delivery in 8599 cases in the Department of Obstetrics and Gynecology of a private hospital Podobnik, Zagreb, Croatia. Methods: Late chorionic villus sampling under ultrasound guidance was carried out in prospective monocentric cohort study of 7859 (91.4%) cases in the second trimester and 700 (8.6%) cases in the third trimester of pregnancy. Out of 8599 late CVS cases, 1476 (17.2%) were performed because of suspicious ultrasonographic findings. Results: In 43 patients (0.50%), complications were found between sampling and delivery. There were only 12 (0.15%) spontaneous abortions four to six weeks after late CVS (before 28 weeks). We found 190 (2.3%) chromosomal abnormalities. In the group with suspicious ultrasonographic findings, comparing 1476 cases, we found significant oligohydramnios in 375 (25.4%), significant polyhydramnios in 197 (13.3%) and chromosomal abnormalities in 125 (8.5%) cases. Among the 190 patients with chromosomal abnormalities, ultrasonographic findings were detected in 98 (49.2%) after the 22th week of pregnancy. Conclusions: Late CVS is a safe method of invasive prenatal diagnosis with lower spontaneous abortions rate (0.15%). This method, applicable after 13 weeks of gestation, offers a more flexible approach to invasive prenatal diagnosis of chromosome abnormalities, in very specialized fetal-maternal centres for this method. Full article

Background: Physical exercise during pregnancy is strongly recommended due to its well-established benefits for both mother and child. However, its impact on the pelvic floor remains insufficiently studied. This study aimed to evaluate pelvic floor adaptations to a structured prenatal exercise program using transperineal ultrasound, and to assess associations with the duration of the second stage of labor and mode of delivery. Methods: This is a planned secondary analysis of a randomized controlled clinical trial (RCT) (NCT04563065) including women with singleton pregnancies at 12–14 weeks of gestation. Participants were randomized to either an exercise group, which followed a supervised physical exercise program three times per week, or a control group, which received standard antenatal care. Transperineal ultrasound was used at the second trimester of pregnancy and six months postpartum to measure urogenital hiatus dimensions at rest, during maximal pelvic floor contraction, and during the Valsalva maneuver, to calculate hiatal contractility and distensibility and to evaluate levator ani muscle insertion. Regression analyses were performed to assess the relationship between urogenital hiatus measurements and both duration of the second stage of labor and mode of delivery. Results: A total of 78 participants were included in the final analysis: 41 in the control group and 37 in the exercise group. The anteroposterior diameter of the urogenital hiatus at rest was significantly smaller in the exercise group compared to controls (4.60 mm [SD 0.62] vs. 4.91 mm [SD 0.76]; p = 0.049). No other statistically significant differences were observed in static measurements. However, contractility was significantly reduced in the exercise group for both the latero-lateral diameter (8.54% vs. 4.04%; p = 0.012) and hiatus area (20.15% vs. 12.55%; p = 0.020). Distensibility was similar between groups. There were no significant differences in the duration of the second stage of labor or mode of delivery. Six months after delivery, there was an absolute risk reduction of 32.5% of levator ani muscle avulsion in the exercise group compared to the control group (53.3% and 20.8%, respectively; p = 0.009). Conclusions: A supervised exercise program during pregnancy appears to modify pelvic floor morphology and function, reducing the incidence of levator ani muscle avulsion without affecting the type or duration of delivery. These findings support the safety and potential protective role of prenatal exercise in maintaining pelvic floor integrity. Full article

Background and Clinical Significance: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by pathogenic variants in TSC1 or TSC2. Cardiac rhabdomyoma is a common prenatal finding and can be associated with severe complications, including pericardial effusion. We administered prenatal sirolimus to mitigate pericardial effusion, which led to postnatal complications. Case Presentation: A 28-year-old pregnant woman with no significant family history underwent routine fetal ultrasound at 28.1 weeks of gestation, which identified a large right ventricular mass consistent with rhabdomyoma. Further fetal brain MRI revealed cortical-subcortical tubers and subependymal nodules, leading to a clinical diagnosis of TSC. At 30.4 weeks, oral sirolimus (3 mg/day) was started due to the significant pericardial effusion. The effusion remained after treatment, requiring pericardiocentesis at 33.6 weeks. The sirolimus dosage was raised to 6 mg/day at 35.6 weeks, reaching a plasma level of 3.76 ng/mL, but there was no discernible improvement because of the continued fluid accumulation. The mother did not experience any adverse side effects from the procedure. Genetic testing confirmed a pathogenic variant in TSC2 (c.1372C>T). After birth, the neonate received a single dose of sirolimus but subsequently developed necrotizing enterocolitis (NEC), highlighting the potential adverse effects and the need for cautious consideration of treatment options. Conclusions: This case illustrates the complexities of managing prenatal tuberous sclerosis complex (TSC). While sirolimus has been explored for fetal cardiac rhabdomyoma and associated complications, its effectiveness in resolving pericardial effusion remains uncertain. Additionally, the development of NEC postnatally raises concerns about the safety of mTOR inhibitors in this context. Further studies are necessary to assess the risks and benefits of this approach in fetal therapy. Full article