Prenatal Diagnosis最新文献

Objective: To investigate the additional clinical value of nuchal translucency (NT) measurement at the first-trimester anomaly scan (FTAS) in a setting with first-tier non-invasive prenatal testing (NIPT).

Method: This nationwide prospective cohort study, part of the IMITAS study on FTAS implementation, included all pregnancies with increased NT (≥ 3.5 mm) at FTAS, subsequently referred for detailed diagnostic scans at eight Dutch tertiary centers (Nov 2021-Nov 2022). Women with abnormal dating scans, abnormal NIPT before FTAS, or high-risk for fetal anomalies were not eligible for FTAS and received diagnostic ultrasound directly. The primary outcome was prenatal diagnosis of structural or genetic anomalies based on pre- and postnatal findings.

Results: FTAS was performed in 129,704 pregnancies, of which 230 (0.18%) had an increased NT. Anomalies were detected in 33.9% of these cases. Genetic anomalies included 76.8% aneuploidies, 14.3% SNVs, 8.9% CNVs; 39.3% beyond NIPT's detection scope. Trisomy 21/18 was diagnosed in 29.3% referred for increased NT without prior NIPT; 73.5% of these opted for termination. Anomaly prevalence increased with greater NT thickness.

Conclusion: NT measurement adds value in a national screening program including FTAS and NIPT. Prenatal counseling should address trisomies and other genetic abnormalities as a potential result of an abnormal FTAS, particularly when NIPT is declined.

Objective: This study evaluates an understudied perspective: the experiences of prospective parents who decline prenatal genome sequencing (pGS) for continuing pregnancies with fetal structural anomalies.

Method: We recruited a total cohort of 300 parents of 150 pregnancies who declined pGS, including 33 individuals who underwent an invasive procedure. These parents were invited to participate in a semi-structured interview between 1 and 15 months post-partum. We used Thematic Analysis to code and analyze interviews.

Results: We interviewed 22 parents of 16 pregnancies. Reasons for declining testing included risks of invasive procedures (n = 19, 86%), lack of prenatally actionable findings (n = 17, 77%), unclear benefits of testing (n = 9, 41%), satisfaction with previous testing (n = 11, 50%), expected low diagnostic yield (n = 13, 59%), emotional and information overload (n = 11, 50%), intolerance of uncertainty (n = 13, 59%), and privacy concerns (n = 5, 23%). Most individuals indicated that, if available, they would elect non-invasive prenatal sequencing. Overall, participants were satisfied with their choice to decline pGS and had no regrets postnatally.

Conclusions: The reasons individuals declined pGS included medical and emotional risks of testing and an understanding of potential results and their utility. To address these concerns, pretest genetic counseling should include the probability of diagnostic results, impact of prenatal/perinatal management, consideration of uncertain results, privacy concerns, and benefits and limitations of postnatal testing. Non-invasive prenatal sequencing, currently under investigation in research settings, may be an alternative future option, but will not address all concerns. Given that our cohort was small and homogenous, lacked cost burden, excluded terminated pregnancies, and included no postnatal genetic diagnoses, further research is needed to confirm that these findings are generalizable.

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.