Prenatal Diagnosis最新文献

Objective: To evaluate the diagnostic yield of exome sequencing (ES) in isolated polyhydramnios.

Methods: This retrospective study included 40 cases of isolated polyhydramnios. All patients underwent screening for gestational diabetes mellitus (GDM) and chromosomal microarray analysis (CMA). ES was performed in CMA-negative cases, along with targeted testing for spinal muscular atrophy, myotonic dystrophy type 1, and Prader-Willi syndrome.

Results: Pathogenic or likely pathogenic variants were identified in 7 cases, yielding a 17.5% diagnostic rate. Diagnostic yield was 12% (2/17) in mild cases and 22% (5/23) in moderate-severe cases. Diagnoses included Bartter syndrome (KCNJ1, BSND, MAGED2), Noonan syndrome (RIT1), Osteopathia Striata with Cranial Sclerosis (AMER1), and AUTS2-related neurodevelopmental disorder. In addition, one case was diagnosed postnatally with myotonic dystrophy 1. Two ES-positive cases had concurrent GDM. Postnatal follow-up showed normal development in 85% of live-born infants, with a few cases of global or speech delay.

Conclusions: ES yields a substantial diagnostic benefit in isolated polyhydramnios, including mild cases and those with GDM. These findings support incorporating ES into the diagnostic approach for isolated polyhydramnios.

Objective: To present the prenatal sonographic features and genomic spectrum of pregnancies with fetal Rubinstein-Taybi syndrome (RSTS).

Methods: This was a retrospective study of 12 cases with RSTS with fetal features identified by prenatal ultrasound and confirmed by genetic testing. Chromosomal microarray analysis utilizing an Affymetrix CytoScan 750k SNP array was employed to detect pathogenic copy number variations (CNVs). Trio exome sequencing was used to detect monogenic conditions. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, molecular testing sequencing results, and pregnancy outcomes.

Results: All cases had unremarkable first-trimester ultrasound scans without reporting limb malformations. Seven cases presented with abnormal second-trimester ultrasounds: three instances of cardiac defects, two instances of limb abnormalities (one with short long bones and one with duplication of big toes), one case of intracranial malformation (dysgenesis of the corpus callosum), and one instance of restricted fetal growth. Five pregnancies exhibited abnormal sonographic signs in the third trimester: two cases of restricted fetal growth, one with clubfeet and polyhydramnios, one with hypospadias, and one with isolated polyhydramnios. CNVs involving CREBBP deletions were detected in two cases. Variants were identified in two genes: CREBBP in six instances and EP300 in four instances; all CNVs or variants were de novo.

Conclusion: Our results underscore the challenges faced in the prenatal detection of RSTS due to the lack of specific clinical presentations. Our study highlights that even nonspecific findings on prenatal ultrasound may justify exome sequencing, enabling timely potential genetic diagnoses and improving clinical management.

Objective: To evaluate the perinatal outcome of monochorionic pregnancies complicated by Twin Anemia-Polycythemia Sequence (TAPS) and identify prognostic factors associated with adverse outcomes.

Methods: A retrospective study (2012-2024) analyzed TAPS cases at a tertiary center. Demographic, obstetric, and neonatal outcomes were compared between conservative management and interventions (intrauterine transfusion, laser surgery, or selective feticide). TAPS characteristics were also analyzed in three subgroups: deliveries before/after 32 weeks, CNS findings on MRI, and dual versus single/no survival.

Result: Of 32 TAPS cases, 68.75% were spontaneous, and 31.25% followed TTTS laser treatment. Conservative management was used in 62.5%, while 21.9% received intrauterine transfusions, 9.4% underwent laser treatment, and 9.4% had selective feticide. Gestational age at diagnosis and delivery was earlier in the intervention group (25 vs. 27 weeks, p = 0.05; 30.6 vs. 32.6 weeks, p = 0.04). CNS abnormalities (25%) were linked to earlier diagnosis. Perinatal survival was 86%, with dual, single, and no survival rates of 78.1%, 15.6%, and 6.2%, respectively. Patients with single/no survival were characterized by an earlier gestational age at diagnosis of TAPS compared to those with dual survival (21 vs. 27 weeks, p < 0.01).

Conclusion: Earlier TAPS diagnosis is associated with poorer outcomes, including reduced survival and increased risk of brain injury.

Objective: This study aimed to assess outcomes of fetuses with prenatally detected omphalocele and the frequency of successful vaginal delivery in pregnancies with suspected non-lethal omphalocele and intended active neonatal management and its impact on neonatal outcome.

Method: Prenatally diagnosed omphalocele cases in Amsterdam UMC from January 2007 to January 2023 were selected. Ultrasound data including the omphalocele circumference/abdominal circumference (OC/AC) ratio were collected and perinatal data were obtained for liveborn cases.

Results: A total of 225 cases were included, with a live birth rate of 20.0% (45/225). Of the suspected non-lethal cases with active neonatal management, vaginal delivery was pursued in 78.9% (30/38), of which 76.7% (23/30) succeeded. The rate of giant omphaloceles did not differ significantly between vaginal and caesarean deliveries, nor did the rate of nulliparity, maximum OC/AC ratio, extracorporeal liver on prenatal ultrasound and successful primary closure. Intrapartum sac rupture occurred in 13.0% (3/23) of successful vaginal deliveries, which was not associated with the OC/AC ratio and in none of the cases with cesarean section. Birth dystocia of the abdomen occurred in none of the cases.

Conclusion: In cases of intended vaginal delivery, 76.7% of vaginal deliveries succeeded, even in cases with giant omphalocele, of which the majority did not experience perinatal complications. Therefore, vaginal delivery appears to be a feasible option in cases with prenatally diagnosed omphaloceles.

Objective: Animal models have demonstrated impaired pancreatic islet development in fetal growth restriction (FGR) cases, which can become apparent at or before birth and persist into adulthood, resulting in glucose intolerance. This study assessed the relationship between fetal pancreatic biometry and FGR.

Methods: A retrospective cohort study included fetuses diagnosed with FGR who underwent prenatal ultrasound at a tertiary center. Pancreatic circumference was measured and compared with established normative reference values. Associations between pancreatic size and estimated fetal weight (EFW), abdominal circumference (AC), Doppler findings, gestational age (GA), concurrent gestational diabetes mellitus (GDM), and the presence of anatomical or genetic abnormalities were analyzed.

Results: The study group comprised 69 cases. The mean GA at the ultrasound examination and pancreatic measurement was 31.5 ± 3.5 weeks. Pancreatic circumference was at or smaller than the 50th percentile of normative references in the majority of the cohort (75%), with 36.2% of cases falling below the 10th percentile and 27.5% below the 5th percentile. Pancreas size correlated moderately with EFW (r = 0.53) and AC (r = 0.54) but not with GA.

Conclusion: Fetuses with FGR exhibited reduced pancreatic size. These findings highlight the pancreas as a novel imaging marker and warrant further investigation into long-term metabolic programming.

Objective: To assess the efficacy of high intensity focused ultrasound (HIFU) to target and ablate the fetal intra-umbilical vessels and terminate fetal perfusion in a pregnant rabbit model.

Methods: Pregnant New Zealand white rabbits (gestational age: E25-27, n = 6 rabbits, n = 18 treated fetuses, n = 6 controls) underwent high-resolution MRI for fetal localization, orientation assessment, beam guidance, and treatment monitoring. Ultrafast ultrasound with power Doppler quantified cardiac output and placental perfusion pre- and post-treatment. HIFU (100-120Wac, 16-20s) induced thermal ablation; MR-thermometry monitored intraoperative temperature; histology confirmed ablation. Ultrafast ultrasound imaging and gross examination confirmed termination.

Results: Target fetal livers (n = 18) reached a maximum temperature of $72°C\pm 8°C$ . Ultrafast ultrasound imaging confirmed the termination of target fetuses, verifying the treatment success in 11 fetuses. Successfully treated fetuses showed a 95% ± 7.4% decrease in cardiac output compared with 11% ± 4.6% decrease in controls, p = 0.022. Placental perfusion dropped 83% ± 10.0% in successfully treated fetuses compared with 16% ± 5.5% in control fetuses, p = 0.002. Overall, 83% (15/18) of targeted fetuses were terminated, with adjacent controls surviving. Thermal necrosis was present in all targeted livers.

Conclusions: MR-guided HIFU can effectively ablate fetal rabbit umbilical vessels to cause selective termination, modeling a non-invasive treatment for twin reversed arterial perfusion sequence.

Objective: To describe experiences of expectant mothers in gaining information and knowledge about diagnoses and surgical management, following prenatal diagnosis of a surgically correctable congenital anomaly (SCCA).

Method: Using semi-structured interviews, we studied women with pregnancies associated with SCCA, including congenital diaphragmatic hernia (CDH), congenital pulmonary airway malformation (CPAM), gastroschisis (GS), omphalocele (OM), and myelomeningocele (MMC), from 2018-2023 that resulted in infant live birth and survival until discharge at a tertiary care center. Interviews were coded and analyzed using thematic analysis.

Results: Interviews with 22 participants were included. Diagnoses included CDH (n = 8), CPAM (n = 4), GS (n = 4), OM (n = 1), and MMC (n = 5). Four thematic categories emerged: (i) prenatal care prior to fetal care center evaluation, (ii) maternal knowledge, (iii) information-gathering, and (iv) social networks. Prenatally, most participants had limited knowledge about SCCA and comfort with completing healthcare-related tasks. Multi-disciplinary fetal care was vital to their understanding of SCCA diagnosis and surgical management plan.

Conclusion: Following prenatal diagnosis of SCCA, expectant mothers struggle with obtaining information that is at their literacy level and specific to their informational needs. Studies are needed to develop literacy-informed approaches to counseling after prenatal diagnosis of SCCA to meet parents' unique informational needs and prepare them for their infants' postnatal care.