Fetal Diagnosis and Therapy最新文献

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.

Introduction: This study aimed to assess whether levels of interleukin 6 (IL-6) in amniotic fluid (AF) can predict perinatal complications following fetal laser surgery in monochorionic twins with twin-to-twin transfusion syndrome (TTTS).

Methods: We conducted a retrospective cohort study at the Fetal Medicine Center from 2013 to 2024, analyzing AF samples from 152 monochorionic twin pregnancies prior to surgery. Cutoff levels for IL-6 were set at 400 ng/L and 2,000 ng/L based on a 10% false-positive and -negative rate.

Results: Among the 152 women who underwent laser surgery, significant associations were found between AF IL-6 levels and pregnancy duration in TTTS cases (p = 0.005); in cases complicated by selective growth restriction, no significant association was found (p = 0.584). Overall, 112 TTTS pregnancies were categorized into 3 groups according to IL-6 levels. The overall prevalence of short surgery-delivery interval (<14 days) was 11.6% (13/112), 1.9% in the low-risk group, and 21.4% in the high-risk group (OR 13.9, p = 0.028). The risk of preterm birth (≤28 weeks) was also higher in the high-risk group (50% vs. 9.6%, OR 9.4, p = 0.002), and adverse neonatal outcomes were more prevalent (63.6% vs. 20%, OR 7.0, p = 0.007).

Conclusion: AF IL-6 levels are a reliable marker for predicting adverse perinatal outcomes after fetal laser surgery, showing a high negative predictive value.

Introduction: In fetuses with open spina bifida (fSB), reduced middle cerebral artery resistance index (MCA-RI) has been described. In theory, compression of specific neuronal pathways due to hindbrain herniation (HH) leads to an imbalance of the autonomic nervous system, favoring sympathetic pathways with increased peripheral vasoconstriction resulting in reduced MCA-RI (similar to the brain sparing effect). While untethering the neural placode, the unavoidable surgical manipulation may lead to a temporarily increased tension of the spinal cord and even aggravate HH and compression of neuronal pathways. We assume that along with untethering the spinal cord, the downward pull disappears with a consequent ascensus of the cord, and HH regression (i.e., the hindbrain moves cephalad and out of the foramen magnum) and MCA values normalize after fSB repair. To confirm this hypothesis, the aim of this study was to compare MCA-RI values obtained before, during, and after fetal surgery.

Methods: In this prospective study, 28 consecutive patients operated for fSB were included. Ultrasound examinations of the MCA Doppler were performed pre-, intra-, and postoperatively with special focus on measurements during surgery, particularly while untethering the placode. Postoperatively, the HH regression was assessed. Regression of HH is defined as any degree of hindbrain decompression, which is marked by an ascensus of the hindbrain into the posterior fossa and, consequently, by the presence of cerebrospinal fluid around the cerebellum seen on US. MCA measurements were then compared with the postoperative HH regression.

Results: MCA-RI before surgery was 0.82 ± 0.02. Intraoperative MCA-RI obtained during untethering was significantly lower than the presurgical values (0.75 ± 0.11, p = 0.03). After fSB repair, the MCA-RI was significantly higher than during surgery (0.83 ± 0.08, p = 0.04). Sonographic findings showed preoperative HH in 24/28 cases (86%), where 23/24 (96%) regressed after fSB repair.

Conclusion: This study provides evidence that there might be cerebral blood flow redistribution, potentially due to iatrogenic forces applied to the spinal cord during the fetal operation. Postoperative HH regression seems to be associated with normalization of cerebral hemodynamics.

Introduction: With over 450 described skeletal dysplasia syndromes, prenatal ultrasound findings suggestive of skeletal dysplasia often have a wide differential diagnosis, and most accurate diagnoses are often made through molecular genetic testing. Previous studies have analyzed diagnostic yield of certain prenatal genetic testing methodologies, but there are limited data comparing relative detection rates in cases of suspected skeletal dysplasia. Our study aimed to compare diagnostic yields of available prenatal genetic testing options in suspected skeletal dysplasia cases.

Methods: We conducted a multicenter retrospective chart review of 118 cases with ultrasound findings suggestive of skeletal dysplasia over 10 years. Fetal biometry and genetic testing were analyzed for diagnostic accuracy. Theoretical diagnostic yields for various testing methods were also evaluated.

Results: Among the 99 individuals who underwent genetic testing, 52 received a molecular diagnosis. Skeletal dysplasia panels and exome sequencing could detect 96% of the syndromes, while single-gene noninvasive prenatal testing could detect 51.9%. In 7.69% of molecularly confirmed cases, ultrasonographic suspicion was incorrect compared to molecular diagnoses.

Conclusion: Our findings highlight the crucial role of diagnostic molecular testing in accurately diagnosing suspected skeletal dysplasia, determining recurrence risk, and providing family guidance.