Fetal Diagnosis and Therapy最新文献

Introduction: A hospital-based Duchenne muscular dystrophy (DMD) newborn screening (NBS) pilot that screened over 18,000 neonates between 2021 and 2024 did not identify a newborn with DMD (incidence 1/5,000 males). We hypothesized that prenatal expanded carrier screening (ECS) that included DMD might be impacting DMD incidence within our population. We therefore explored the extent of ECS and DMD carrier screening in the mothers of our DMD NBS newborns.

Methods: A retrospective chart review was performed on mothers of newborns screened during the first week of each month from 1/2022 to 5/2024.

Results: Of 2,613 mothers, 93.9% underwent ECS and 49.7% included DMD. Fifty percent of screened mothers underwent preconception screening. Screening panels with 11-50 genes were most commonly performed. ECS panels with ≥11 genes were most likely to include DMD. The number of mothers who underwent DMD carrier screening increased from 46.6% to 56.3% from the start to finish of the pilot.

Conclusion: With increasing uptake of prenatal maternal genetic screening, in conjunction with continuing expansion of gene lists for rare disorders, it is suggested that rare disorder incidence may decrease over time, either by avoiding an affected pregnancy with the help of artificial reproductive technology or pregnancy termination when prenatal diagnosis is initiated by ECS.

Introduction: The aim of the study was to investigate genetic defects in fetuses diagnosed with isolated hypospadias.

Methods: This retrospective study analyzed 61 cases of isolated fetal hypospadias identified through second-trimester or third-trimester ultrasound examinations. All participants underwent invasive prenatal diagnostic procedures for copy number variant (CNV) detection via chromosomal microarray analysis (CMA). For those with normal CNV results, trio whole-exome sequencing (WES) was offered as an alternative. Clinical and laboratory data were systematically collected and reviewed, encompassing maternal demographics, prenatal sonographic findings, molecular testing outcomes, and pregnancy results.

Results: Three cases of sex chromosomal abnormalities were identified. In the remaining 58 cases, all had the male karyotype. CMA detected only one case of pathogenic CNVs (2q13 microdeletion). Among the cases with normal CMA, 35 underwent trio WES; two had disease-causing variants: one carried a de novo CREBBP variant, and one carried two SRD5A2 variants.

Conclusions: From our perspective, CMA and WES are valuable tools in antenatal care for isolated cases of hypospadias detected via ultrasound; this information should be communicated to patients through prenatal counseling.

Introduction: Various treatment options for the prenatal open spina bifida (OSB) repair have evolved over the past decades, including the laparotomy-assisted fetoscopic repair. However, little is known about the fetal vascular regulation during the laparotomy-assisted fetoscopic repair. Therefore, we aimed to describe cardiovascular effects during the intervention in our cohort.

Methods: A total of 26 fetuses underwent laparotomy-assisted fetoscopic repair at a single center between July 2021 and July 2024 and were prospectively included in this study. The intervention was performed using a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach. Fetal heart rate (FHR) and pulsed-wave Doppler flow measurement of the pulsatility index (PI) in the umbilical artery (UA) and middle cerebral artery (MCA) were recorded at 13 defined time points throughout the surgery. The occurrence of absent or reverse end-diastolic (ARED) UA flow was documented. The MCA waveform was assessed for signs of fetal vasoconstriction (M-sign).

Results: The mean gestational age at surgery was 25 weeks. A significant increase in the PI in the UA before laparotomy (PI: 1.22 ± 0.24) and after laparotomy (PI: 1.75 ± 0.37) was observed (p < 0.001). An ARED flow was recorded in 13.3% of cases after maternal general anesthesia, but not before and at the latest on the first day after surgery. MCA PI decreased nonsignificantly during the intervention. Before surgery, the M-sign was present in 6 fetuses; however, during surgery, it was seen only in 1 fetus. There were no significant changes in FHR during surgery except for a drop after gas insufflation (FHR: 129 ± 5; FHR: 125 ± 7.0, p < 0.001) compared to the FHR before surgery. During the postoperative course, the FHR increased significantly (day 0: 141 ± 10; day 4: 143 ± 9.8, p = 0.003).

Conclusion: Our study shows changes in the UA PI and the occurrence of ARED during laparotomy-assisted fetoscopic repair. FHR remained stable during surgery. Furthermore, the findings confirm the transient nature of these changes. The occurrence of Doppler and waveform abnormalities was related to maternal-fetal anesthesia and the procedure itself.

Introduction: Fetoscopy is a minimally invasive technique widely used for the treatment of twin-to-twin transfusion syndrome (TTTS), offering significant perinatal benefits. However, maternal complications of fetoscopy are underreported and incompletely characterized.

Case presentation: We present the case of a 19-year-old primigravida with a monochorionic diamniotic pregnancy, diagnosed with Quintero stage II TTTS at 18 weeks of gestation, managed with fetoscopy and laser ablation. The clinical course remained stable until 30+3 weeks, 12 weeks after the fetoscopic procedure, when fetal demise of the donor twin and preterm labor were documented, prompting cesarean delivery. During surgery, a 5-mm myometrial defect was identified in the anterior-left lateral uterine wall, with herniation of ovular membranes through the defect at the site of the previous trocar insertion. This long interval between fetoscopy and detection of the defect is notably unusual.

Conclusion: Herniation of ovular membranes through a myometrial defect is an uncommon and often asymptomatic complication following fetoscopy, which can be diagnosed incidentally during cesarean delivery, as in our case. The identification of this defect 12 weeks post-procedure highlights the importance of prolonged surveillance. Therefore, a thorough ultrasound assessment, including the fetus, amniotic fluid, and careful evaluation of the uterine wall for potential defects, should be considered a routine part of post-fetoscopy care.

Introduction: Prenatal ultrasound (US) and MRI guide the diagnosis and management of congenital diaphragmatic hernia (CDH). A challenge arises when one imaging modality suggests a moderate case and the other a severe case ("discordant severe CDH"). We aimed to analyze newborn outcomes for this group.

Methods: We reviewed all left-sided CDH cases at our fetal care center from 2012 to 2023. Discordant severe was defined as severe by either US (trace observed-to-expected lung-to-head ratio ≤25%) or MRI (percent predicted lung volume ≤15%) and moderate by the other. Concordant severe and concordant moderate groups were defined as both US and MRI predicting the same severity. Primary outcomes were rate of extracorporeal membrane oxygenation (ECMO) cannulation and survival to discharge.

Results: We identified 35 concordant moderate, 21 discordant severe, and 11 concordant severe CDH cases. Compared to the concordant moderate group, the discordant severe group had significantly higher ECMO cannulation rates and significantly lower survival to discharge. No significant differences were found between concordant severe and discordant severe groups.

Conclusion: Outcomes for discordant severe CDH are similar to concordant severe, suggesting teams should rely on the imaging modality that predicts the more severe categorization in the setting of discordant severe CDH.

Introduction: The aim of the study was to compare obstetrical, survival, and nephro-urological outcomes of fetuses diagnosed with lower urinary tract obstruction (LUTO) undergoing antenatal procedures by vesicoamniotic shunting (VAS) or fetal cystoscopy (FC).

Methods: This study was a literature search using MEDLINE, Scopus, Embase, and Cochrane reference lists. All studies reporting VAS and FC's effectiveness, complications, and technical issues in the prenatal treatment of LUTO were selected for a single-proportion meta-analysis. Two reviewers independently selected studies, extracted data, and assessed quality. We computed and declared effect sizes for estimating a single proportion using the Freeman-Turkey transformed proportion.

Results: Out of a total of 467 citations identified, 49 studies were included for a detailed evaluation of VAS and FC perinatal outcomes. Overall, VAS and FC were burdened by a similar incidence of intrauterine fetal demise (VAS: 0.51 [0.42-0.61] vs. FC: 0.47 [0.28-0.67]; p = 0.73), postnatal death (VAS: 0.87 [0.75-0.99] vs. FC: 0.86 [0.62-1.09]; p value: 0.87), and postnatal renal impairment (VAS: 1.22 [1.06-1.39] vs. FC: 0.96 [0.67-1.25]; p value: 0.12). Likewise, the two procedures were complicated by a similar rate of chorioamnionitis (VAS: 0.38 [0.28-0.47] vs. FC: 0.39 [0.12-0.66]; p value: 0.92), premature rupture of membranes/preterm premature rupture of membranes (VAS: 0.77 [0.60-0.94] vs. FC: 0.84 [0.60-1.07]; p value: 0.65), premature birth (VAS: 1.83 [1.55-2.10] vs. FC: 1.56 [0.92-2.21]: p value: 0.46), and fetal abdominal wall/intestinal problems (VAS: 0.43 [0.29-0.57] vs. FC: 0.50 [0.19-0.81]; p value: 0.69). Termination of pregnancy (TOP) was chosen significantly more often after FC than VAS (VAS: 0.65 [0.53-0.77] vs. FC: 1.18 [1.03-1.33]; p value: <0.001).

Conclusion: Our meta-analysis yields similar results in terms of obstetric, survival, and nephro-urological outcomes between VAS and FC. The higher incidence of TOP in FC over the VAS group may be associated with the fact that FC is also considered a diagnostic tool and can guide for TOP for those with more complex diseases.

Introduction: Twin-to-twin transfusion syndrome (TTTS) is associated with high perinatal morbidity and mortality. Krispin et al. [Ultrasound Obstet Gynecol. 2023;61(4):511-7] developed a prediction model to estimate the likelihood of dual twin survival after fetoscopic laser photocoagulation (FLPC). This study aimed to evaluate the predictive value of sonographic parameters at diagnosis of TTTS treated with FLPC for postnatal dual twin survival and to validate Krispin et al.'s calculator.

Methods: This is a retrospective cohort study of cases of TTTS treated by FLPC. The primary outcome was dual survival 30 days after delivery. The calculator used preoperative variables: donor's estimated fetal weight (EFW) <10th centile, intertwin growth discordance >25%, anterior placenta, pulsatility index (PI) in the umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA), with scores ranging 0-300.

Results: Among 157 patients, 84 (53.5%) had dual twin survival (Group A), compared to 73 (46.5%) with one or no survivors (Group B). No significant differences were seen in donor's EFW <10th centile (57.1% [A] vs. 57.5% [B], p = 0.96), intertwin growth discordance (26.2% [A] vs. 38.4% [B] p = 0.95), rates of PI >95th centile in the donor's UA and DV, and PI <5th centile in the MCA (p > 0.05). However, a significant difference was found for anterior placenta (38.1% [A] vs. 58.9% [B], p = 0.009). The observed dual survival was higher than predicted for scores ≥100.

Conclusion: We were not able to externally validate the calculator of dual survival after laser for TTTS, especially for elevated scores. Among the parameters analyzed, only anterior placenta was significantly associated with poorer outcomes.

Introduction: Amniotic membrane disruption during laparotomy-assisted fetoscopic myelomeningocele closure port insertion is a precursor to iatrogenic preterm prelabor rupture of membranes (iPPROM), the primary contributor to obstetric complications. We hypothesized that visualization of port insertion from the intrauterine perspective could offer insight into mechanisms affecting chorioamniotic integrity.

Methods: Fetoscopically video-recorded uterine port insertions during myelomeningocele closure were independently reviewed by six observers for suture placement, associated chorioamniotic separation of the membrane (referred to as tenting), and bleeding at port insertion. Findings were analyzed for interobserver agreement and related to iPPROM and gestational age at delivery.

Results: In 23 surgical videos, average interobserver agreement was 78% for membrane tenting, myometrial bleeding, visible debris on the port, and the number of suture placements as distinct mechanical factors. Tenting occurred at 30.4% of suture and 30.4% of trocar insertions. Port step occurred in 100.0% of insertions, and port debris occurred in 60.9% of insertions. Bleeding occurred in 8.7% of port, and 21.7% of suture insertions. Amniotic membrane plication used 2 stitches in 65.2% of cases. iPPROM occurred in 47.8% of cases. The average gestational age at the time of surgery was 24 weeks and 4 days and, at the time of delivery, was 35 weeks and 3 days.

Conclusions: Fetoscopic port insertions produce identifiable chorioamniotic disruption without any specific precursors to membrane rupture. The number, rather than the type of membrane punctures, may be more relevant for iPPROM risk.

Introduction: Congenital pulmonary airway malformations (CPAM), intra- and extralobar bronchopulmonary sequestrations (iBPS/eBPS), CPAM-BPS hybrid lesions (HL), congenital lobar emphysema (CLE), bronchial atresia (BA), and foregut duplication cysts (FDC), collectively referred to as congenital thoracic lesions (CTL), are mostly solitary. Patients with multiple CTL are rare, and reports on such cases are scarce. To address this dearth, we analyzed a large multifocal CTL patient cohort.

Methods: Retrospective chart review of patients born between September 1, 2013, and March 31, 2023, who underwent surgery for a CTL at our tertiary center. Patients with radiological and surgical diagnosis of multifocal CTL, defined as ≥2 CTL present in more than one lobe were included to record pre-, peri-, and postnatal patient characteristics.

Results: Among 701 CTL patients, 74 (10.5%) had multiple CTL. CTL multifocality was prenatally recognized correctly in 8 (12.9%) patients. Most multiple CTL were right-sided, unilateral multilobar lesions (n = 33, 44%). Bilateral CTL were found in 9 (12.1%) patients. CPAM-CPAM lesions were the most prevalent CTL types (n = 36, 49%). Genetic syndromes were confirmed in 3 (4%) and additional congenital anomalies in 9 (12.9%) patients, 5 of those had multiple congenital anomalies. Of 49 (65%) patients with multilobar CTL, 25 (51%) underwent bilobectomy and 24 (49%) lung-sparing surgery. Length of stay was similar. Mortality was 5.4%.

Conclusion: We report on the largest patient cohort with multiple CTL to date. Multiple CTL occurred in 1/10 patients with CTL, and only 12.9% were recognized prenatally. Lung-sparing surgery can be considered. Multiple additional congenital anomalies and genetic syndromes may be more common and genetic testing should be considered. Overall, outcomes in this patient population are favorable.

Introduction: Spina bifida guidelines recommend neurosurgical involvement in prenatal counseling to inform decision-making between prenatal and postnatal myelomeningocele (MMC) repair. This study examines whether families with MMC presenting to one fetal center had timely neurosurgical prenatal counseling (nPNC) encounters and assesses modifiable and non-modifiable treatment-determining factors.

Methods: History and timing of nPNC were quantified among infants undergoing postnatal and prenatal MMC repair, pregnant patients referred, and MMC studies in a fetal MRI database (2015-2023). Fetal repair exclusions, presentation timing, social determinants, and reported rationale for not selecting offered fetal therapy were assessed.

Results: Nearly all patients (34/35; 97%) engaged in nPNC, 82% prior to 24 weeks GA. Fourteen patients were excluded from fetal repair for lack of hindbrain herniation (43%), obstetric exclusions (21%), fetal exclusions (21%), suspected closed defect (7%), and delayed presentation (7%). These patients ultimately underwent postnatal repair (71%), and pregnancy termination (14%). The 20 fetal-repair-eligible patients selected fetal repair (50%), postnatal repair (45%), and pregnancy termination (5%). Reasons for declining fetal repair included risk (55%) and cost (22%).

Conclusions: Among MMC families presenting to a regional fetal therapy center, nPNC was widely extended, in a mostly timely fashion. Very few were deterred from fetal repair by potentially modifiable barriers.