Fetal Diagnosis and Therapy最新文献

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.

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.