Fetal Diagnosis and Therapy最新文献

Introduction: The aim of this study was to assess the clinical utility of low-set ears (LSE) as a novel 2D-ultrasound marker for the prenatal detection of chromosomal anomalies.

Methods: A multicenter cohort study including 1,331 singleton pregnancies between 11+2 and 34+6 weeks of gestation was conducted in the two participating centers to determine the performance of LSE as an aneuploidy marker. LSE was defined as a dichotomous marker using a newly defined axial plane of the fetal head in 2D ultrasound. Intra- and interobserver variability were assessed to ensure marker reliability. Efficacy in predicting chromosomal anomalies was assessed using LSE alone or in combination with aneuploidy screening.

Results: A new axial plane of the fetal head, defined by both lenses and the cerebellum, was adopted for LSE detection. Intra-observer concordance Kappa index for LSE measurement was 1.0, and 0.82 for interobserver reliability. LSE could be assessed in 99% of the studied fetuses and was detected in 30 (2.3%) fetuses: in 19 (86%) of the 22 fetuses with chromosomal anomalies, in all cases (5/5, 100%) with other genetic anomalies, and in six (18%) of the 34 malformed fetuses without a genetic disorder. In one (3.3%) of the fetuses, LSE was not confirmed postnatally while the remaining 29 fetuses had an adverse outcome. When LSE was combined with aneuploidy screening, the detection rate of chromosomal anomalies remained the same and specificity increased from 89% to 100%.

Conclusions: Our study supports using LSE as a potential 2D-ultrasound marker for chromosomal anomaly detection. Studies with a larger sample size and in high-risk populations are warranted to prove its clinical utility before this marker can be included in prenatal screening protocols.

Introduction: The clinical phenotypes associated with 1q21.1 deletion or duplication syndromes vary considerably among individuals, and the underlying mechanisms remain poorly elucidated. Moreover, data on prenatal ultrasound findings in fetuses carrying these copy number variants are still limited. This study aimed to preliminarily evaluate the association between prenatal phenotypic features and 1q21.1 deletion/duplication syndromes.

Methods: A retrospective analysis was performed on 16 cases diagnosed with 1q21.1 deletions and 13 cases with 1q21.1 duplications, employing single nucleotide polymorphism arrays (SNP-arrays).

Results: The deletion fragment sizes of the 16 deletion cases ranged from 1.30 Mb to 2.18 Mb, with the overlapping region located at 146.5 Mb to 147.5 Mb, encompassing nine OMIM genes such as ACP6, BCL9, and CHD1L. The fragment sizes of the 13 duplication cases ranged from 0.87 Mb to 3.87 Mb, with the overlapping region located at 146.5 Mb to 147.0 Mb, encompassing a total of 4 OMIM genes, namely, BCL9, CHD1L, FMO5, and PRKAB2. Among the 16 fetuses with deletions, eight exhibited ultrasound-detected abnormalities. Specifically, three fetuses had urinary tract malformations, four were diagnosed with fetal growth retardation, three displayed lateral ventricle enlargement, and one had aortic stenosis. Of the 13 fetuses with duplication, six were found to have ultrasound abnormalities, including four fetuses with cardiovascular malformations, one fetus with fetal growth retardation, one fetus with widened posterior fossa, and one fetus with widened lateral ventricle. Among the 16 fetuses identified with deletions, nine pregnancies were electively terminated, while seven pregnancies were carried to term, resulting in normal births. During follow-up, one child was diagnosed with epilepsy, and another exhibited delays in language and motor development. In the cohort of 13 fetuses with duplications, four pregnancies were terminated, and nine proceeded to term, yielding normal births. However, follow-up assessments revealed that one child experienced hearing impairment and another demonstrated speech delays.

Conclusion: This study suggests that fetuses with prenatal 1q21.1 deletions may be associated with malformations of the urinary system, whereas those with 1q21.1 duplications are likely associated with cardiac malformations. For fetuses diagnosed with 1q21.1 deletions or duplications who present with a normal phenotype prenatally, it is essential to conduct close monitoring of their neurodevelopmental trajectory postnatally.

Introduction: Tubulinopathies are a heterogeneous group of rare disorders which are primarily characterized by brain malformations caused by pathogenic variants in the genes that encode tubulin. Although scarce, prenatal diagnosis has been recently reported through expert neurosonography and magnetic resonance imaging, most commonly at 28-34 weeks' gestation, followed by identification of pathogenic variant in TUBA1A, TUBB, TUBB2A, TUBB2B, TUBB3, or TUBG1 using gene sequencing.

Case presentation: We present detailed ultrasound findings of 21-week fetus with brain abnormalities including low normal head circumference, cerebellar hypoplasia, dysmorphic cavum vellum pellucidum, partial agenesis and dysgenesis of the corpus callosum, distortion with interdigitation of the interhemispheric fissure, ventricular asymmetry with dysmorphic, and/or dilated frontal horns, as well as asymmetry in the basal ganglia. Amniocentesis with trio genome sequencing detected a novel, de novo heterozygous c.799T>C variant in TUBA1A that has not been previously reported.

Conclusions: This case offers a detailed characterization of the subtle neurosonographic phenotype in this fetus with early manifestation of malformations of cortical development related to tubulinopathy and provides information regarding the novel variant in the TUBA1A gene. It further underscores the importance of neurosonography and genetic analysis in identifying tubulinopathies and informing clinical decision-making during pregnancy.

Introduction: Invasive prenatal diagnostic tests have higher detection rates than screening tests. Cell-free DNA (cfDNA) screening has higher detection than combined testing (CT). We estimated the cost per cytogenetic abnormality diagnosed for prenatal testing and screening methods (US data).

Methods: We compared seven strategies: universal diagnosis with microarray and karyotype; cfDNA screening with four methodologies: Digital Analysis of Selected Regions (DANSR), massively parallel shotgun sequencing (MPSS), single-nucleotide polymorphisms (SNPs), and rolling circle amplification (RCA); and CT. Five abnormality groupings were considered: common autosomal trisomies (21,18,13), sex chromosome aneusomies, triploidy, clinically significant sub-chromosome changes, and copy number variants. Prevalence, detection, false-positive rates, and unit costs (literature) were obtained. The detection rate was aggregated across groups as were costs, including diagnostic tests following positive screening results.

Results: All six high detection strategies had greater cost per abnormality diagnosed than CT (USD 26,100). The costliest was cfDNA using MPSS (USD 96,100), followed by universal karyotyping (USD 95,900), cfDNA using SNPs, DANSR (USD 94,800-USD 92,800), universal microarray (USD 56,600), and cfDNA with RCA (USD 32,200). The additional cost per extra abnormality diagnosed compared to CT ("marginal" cost) was the lowest for cfDNA with RCA (USD 45,000); others were considerably higher (USD 59,400-USD 160,700).

Conclusion: Preferred prenatal strategies vary among stakeholders. However, as monopolies (large systems and Accountable Care Organizations) now control the majority of American healthcare policy decisions, the lowest cost cfDNA screening will likely prevail in actual practice.

Introduction: Pulmonary valve stenosis (PS) is a common congenital heart defect with variable severity. Prenatal echocardiography has limited ability to predict neonatal valvuloplasty. We aimed to evaluate the prediction accuracy of fetal echocardiography, including 2D speckle-tracking echocardiography (2D-STE).

Methods: A prospective cohort study including 24 cases of isolated PS (7 critical, 17 mild-moderate) and 48 gestational age-matched healthy controls was conducted at BCNatal. Cases were matched with 48 healthy controls adjusted by gestational age at echocardiography. Comprehensive fetal echocardiography and 2D-STE were performed for diagnosis.

Results: Median gestational age at echocardiography was 32.5 weeks (27.4-35.4). Half of the PS fetuses underwent valvuloplasty within the first month of life. PS fetuses showed impaired right ventricular function (reduced tricuspid annular plane systolic excursion, more pulsatile ductus venosus), with preserved left ventricular function. Four independent predictors were identified: ductus venosus pulsatility index ≥79th centile, right ventricular global longitudinal strain ≥-15.9%, reversed flow in the ductus arteriosus, and significant tricuspid regurgitation. When combined into a simple 4-point score, values ≥2 predicted valvuloplasty with 91.7% sensitivity and 100% specificity (AUC: 0.931).

Conclusion: These findings suggest that a fetal echocardiographic score may accurately identify a fetus with PS needing early neonatal valvuloplasty, allowing improved perinatal management. Further validation studies are needed.

Introduction: International medical conferences face evolving challenges in optimizing scientific exchange and professional networking while minimizing their environmental footprint. Digital platforms offer solutions that can enhance engagement while reducing ecological impact. This study evaluated implementation outcomes of a custom digital platform at the 41st International Fetal Medicine & Surgery Society (IFMSS) meeting.

Methods: We conducted a prospective observational study of a custom mobile application platform deployed during IFMSS 2024 (September 22-28, 2024). The system incorporated authenticated user access, real-time session management, networking capabilities, and comprehensive analytics. Primary outcomes included user engagement metrics, scientific content interaction rates, professional networking efficacy, and platform stability.

Results: Platform adoption reached 91.9% (339/369 registrants), generating 178,873 discrete interactions. Scientific content engagement included 56,344 abstract/presentation views by 335 unique users. Networking features facilitated 182 new professional connections and 485 direct message exchanges. Search functionality received 4,310 targeted queries, while speaker profiles were examined 780 times.

Conclusion: Implementation of a digital conference platform demonstrated significant efficacy in supporting conference objectives with high engagement rates. These findings suggest digital platforms can effectively enhance traditional conference structures, facilitate attendee engagement and interaction, reduce paper waste, and provide a more sustainable option for scientific exchange in subspecialty meetings.

Introduction: The Affordable Care Act was intended principally to increase healthcare insurance coverage to uninsured Americans. Ostensibly, 40 million people obtained coverage. However, American maternal mortality has significantly worsened. The overall health curve in conservative leaning states is shifted downward in comparison to liberal ones including COVID mortality, maternal mortality, neonatal mortality, life expectancy, heart disease, pulmonary, and diabetic deaths, obesity, smoking, suicides, and alcohol related auto deaths. Here, we focus on insurance coverage issues related to those outcomes and market alterations produced by Affordable Care Act (ACA) legislation and regulatory actions that may or may not have had unintended consequences.

Methods: Using authoritative national public databases, we analyzed 18 health status metrics in the context of Managed Care Organizations market consolidation and Accountable Care Organizations penetration fueled by the Medicaid expansion. We ranked states from best statistics to worst incorporating 10 measures of health access including: hospital beds, patients without examination for over a year, and incidence of maternity care deserts.

Results: There is considerable variation in the USA for both healthcare status and access. Our data show these are highly correlated (r2 = 0.47, p < 0.01). States with the best outcomes have the best access. States with highest healthcare metrics and healthcare access were all traditional liberal "blue states" with greater infrastructure and insurance coverage.

Conclusions: Hospital and clinic realignments created under the ACA appear to have worsened the healthcare of women and children in the USA, particularly for patients of color. Healthcare status and access to services are highly correlated. States allocating more resources for healthcare have better outcomes. Monopoly exemptions under ACA are temporally and statistically correlated with worsening of maternal outcomes across all geographic regions where control and consolidation was permitted or encouraged. Maternity care deserts have significantly disadvantaged women of color and working-class families in rural and urban zones. Further exacerbating the problem is the reduction of physician independence both within and outside of hospital systems.