Fetal Diagnosis and Therapy最新文献

Introduction: Technical advances are rapidly improving the ability to detect anatomical malformations and genetic abnormalities during pregnancy. We aimed to identify the sequence of events leading to medical abortion ≥34 weeks' gestation, to determine whether the procedure could have been carried out earlier.

Method: Retrospective study of medical abortions in singleton pregnancies carried out in our department over a 23-year period from 1998 to 2021.

Results: 36/4,055 (0.88%) abortions were carried out ≥34 weeks' gestation. The indications were anatomical in 20 (55%), chromosomal or genetic in 14 (39%) and CMV infection in two. Evaluation of the sequence of events suggests that an earlier diagnosis would have been unfeasible before the third trimester in 18 cases (50%) because the disorder was developmental and ultrasound findings would not have presented earlier. By contrast, certain other cases might have been diagnosed earlier if the patient had not delayed routine screening or if screening had been administered on schedule.

Conclusion: In this series, full adherence to local screening tests and protocols, and timely decision-making could have substantially reduced the late abortion rate by as much as half.

Introduction: Spina bifida (SB) is a severe neural tube defect affecting motor function, mobility, and quality of life. Prenatal repair has become the gold standard in selected cases, offering better outcomes than postnatal approaches. This study evaluated SB prenatal repair outcomes in a middle-income country, comparing our results with the Management of Myelomeningocele Study (MOMS) trial. It also reports the impact of routine use of uterine wound retractor on reducing uterine trauma and improving outcomes.

Methods: This retrospective observational study analyzed 90 fetuses undergoing open prenatal SB repair between 2012 and 2024 at a single center in Chile. Inclusion/exclusion criteria followed the MOMS trial, later adjusted to include higher maternal body mass index (BMI) (n = 11) and gestational age at surgery >26 weeks (n = 12) based on emerging evidence. Clinical outcomes were assessed at 12 and 30 months postnatally and compared with MOMS trial results.

Results: Our cohort had a higher maternal BMI, shorter cervical length, and more severe lesion level (L1-L4) than the MOMS trial. Maternal outcomes were favorable, with lower chorioamniotic separation (1% vs. 26%), oligohydramnios (4% vs. 21%), and preterm prelabor rupture of membranes (25% vs. 46%). Neonatal outcomes included more births ≥37 weeks (47% vs. 21%) but a greater proportion of low-birth-weight neonates <10th percentile (14% vs. 4%). At 12 months, ventriculo-peritoneal shunting was less frequent (33% vs. 40%) but not statistically significant. At 30 months, walking with orthesis was higher (48% vs. 29%), but independent walking was lower (13% vs. 42%).

Conclusions: This study confirms the feasibility and effectiveness of open prenatal SB repair in a middle-income setting, with outcomes comparable and in some instances even better than the MOMS trial. Our results suggest that the combined use of a smaller hysterotomy and an atraumatic, low-cost, and widely available uterine wound retractor could significantly improve maternal and obstetric results. This is the largest cohort evaluating this approach in a single referral center.

Introduction: Anhydramnios due to renal failure prior to 22 weeks of gestational age (WGA) is associated with lethal pulmonary hypoplasia but after 22 WGA outcomes are less clear. We evaluated whether these fetuses, with new anhydramnios after 22 WGA, incur significant risk of severe neonatal pulmonary morbidity.

Methods: This retrospective study of singleton pregnancies diagnosed with new-onset renal anhydramnios after 22 WGA following verifiable normal AFI on ultrasound before 22 WGA from 2021 to 2023. Cases with bilateral renal agenesis, premature rupture of membranes, and nonrenal malformations were excluded.

Results: During the study period 53,698 s trimester ultrasound examinations were performed, of which 82 patients had new anhydramnios after 22 weeks, and 6 met criteria for inclusion in the study. Renal anhydramnios in each was secondary to a lower urinary tract outlet obstruction. Two of these (2/6, 33%) underwent procedures that corrected anhydramnios and survived, the rest suffered lethal pulmonary hypoplasia.

Conclusion: Onset of, and persistent, renal anhydramnios after 22 WGA is associated with lethal pulmonary morbidity. Although clinical trials to date have focused on intervention for patients with renal anhydramnios prior to 22 WGA, investigation of treatments those with renal anhydramnios after 22 WGA is warranted to mitigate severe pulmonary hypoplasia.

Introduction: Double outlet left ventricle (DOLV) is a rare congenital heart anomaly, and cases of DOLV with an intact ventricular septum are uncommon. To date, only four such cases have been reported in the medical literature.

Case presentation: This report presents a case of prenatally diagnosed DOLV. A fetal echocardiogram at 21 weeks of gestation demonstrated both great arteries, aorta and pulmonary artery, arising from the left ventricle with severely dysplastic tricuspid valve and severe hypoplasia of the right ventricle. Subsequent echocardiograms demonstrated no ventricular septal defect. The patient required balloon atrial septostomy in the first week of life, underwent pulmonary artery banding at 5 weeks of life, and is currently status post-bidirectional Glenn, and is awaiting final Fontan palliation.

Conclusion: Prenatal diagnosis aided in predicting and guiding postnatal management.

Introduction: Data on near- and long-term clinical outcomes are critical for the care of all maternal-fetal patients presenting to a fetal center. This is especially important since physiologic and neurodevelopmental attributes do not manifest until later childhood when multilevel (e.g., individual, family, policy) factors have a direct influence on health outcomes. Electronic health records (EHRs) create opportunity for efficient data collection. However, documentation structures are not designed for acquisition of key attributes, and changes over time and between-clinician differences can affect resultant output. Therefore, EHR derived datasets have limited ability to accurately characterize the clinical presentation and care trajectory of patients with congenital anomalies. In addition, in most systems, the fetus lacks a digital identity and requires relinking fetal attributes documented in the maternal chart to those from the pediatric EHR. This conundrum amplifies in the setting of multiple gestation, returning maternal patients, and pregnancies with fetal demise. Moreover, current data capture systems result in incomplete abstraction of variables that may confound, mediate, or moderate critical associations. Our objective was to develop and implement a prospective data capture platform to transform EHR data into an analytic-grade database for multipurpose use.

Methods: A unified platform for longitudinal follow-up of maternal-child dyads cared for at our fetal center, named the Clinical Outcomes Data Archive (CODA), was constructed. CODA was designed using a data dictionary based on multidisciplinary and interprofessional expert input, a relational identity for each patient, fetus, and pregnancy, and a process by which EHR-sourced and chart-abstracted data are validated by a well-trained team. Descriptive analyses were performed for data acquired between July 2022 and July 2023, and a comparison of studies before and after implementation of CODA is presented.

Conclusion: 5,394,106 data points were validated for 7,662 patients across 12 conditions. 2% of data points were found to be unreliable or undocumented. 91% of data points were sourced from the EHR. Eighty-five percent of condition-specific variables required manual chart abstraction. The study conducted with CODA was able to contribute to 18 other studies. CODA successfully merges EHR-sourced and manually abstracted documentation for longitudinal study of the maternal-child dyad.

Introduction: The objective of this study was to assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester and to assess their ability to predict term preeclampsia (PE).

Methods: A cohort of low-risk pregnant women was scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ∼30 and ∼36 weeks. The performance of both parameters and their change over time in predicting term PE was evaluated.

Results: A total of 1,191 women were analyzed, of which 28 (2.4%) women developed term PE. At ∼30 weeks, a model including the sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio and the uterine Doppler explained 16.2% of the uncertainty of developing term PE, while at ∼36 weeks, the same variables explained 25.2% [p < 0.001]. The longitudinal changes of both predictors had an R2 of 26.8%, which was not different from that of the ∼36 weeks evaluation [p = 0.45]. The area under the curve (AUC) of the ∼36 weeks ratio was significantly higher than at ∼30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p = 0.043). The AUC of the longitudinal change of the ratio (0.85 [0.77-0.94]) did not differ from that of at ∼36 weeks (p = 0.82). At ∼36 weeks, for a 10% of false positives, the ratio had a detection rate of 71.4%.

Conclusion: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term PE. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between weeks.

Introduction: Arhinencephaly have been identified as a significant feature in CHARGE syndrome. This study aimed to evaluate the diagnostic role of olfactory sulci (OS) in identifying CHARGE syndrome among fetuses with major congenital heart defects (CHDs).

Methods: We prospectively evaluated OS development in fetuses diagnosed with CHDs from 2017 to 2021. Neurosonography was performed using transabdominal and transvaginal approaches after 30 weeks of gestation. OS assessment was conducted in the trans-frontal coronal plane, classifying their appearance as fully developed, hypoplastic, or absent. Abnormal OS cases underwent MRI and trio-based clinical exome sequencing (CES).

Results: The study included 147 fetuses with CHD. Abnormal OS were found in 4 fetuses (2.7%) which also exhibited other additional anomalies. OS were absent in cases 1-3 and hypoplastic in case 4. MRI confirmed OS abnormalities in all cases, and trio-based CES identified a CHD7 gene mutation in cases 1, 2, and 4, supporting the diagnosis of CHARGE syndrome. Case 3 had normal trio-based CES results. No other CHARGE syndrome cases were diagnosed postnatally among the cases with normal OS.

Conclusions: Systematic evaluation of OS in fetuses with major CHD might contribute to the diagnosis of CHARGE syndrome. Our findings support the inclusion of OS assessment in the prenatal evaluation of fetuses with major CHDs.

Introduction: This study evaluated the surgical details and outcomes of fetal myelomeningocele (MMC) repair using a minimally invasive fetoscopic approach with uterine exposure.

Methods: This retrospective case series study examines consecutive fetuses who underwent fetoscopic spina bifida repair performed by a single team. The pregnant women's demographic data, surgical technical aspects, complications, and neonatal surgical outcomes were analyzed.

Results: From 2019 to 2022, 32 fetuses underwent the fetoscopic repair of MMC at an average gestational age of 25.2 ± 0.9 weeks (range 23.2-26.6). Dura mater collagen substitutes were used for duraplasty in all cases, and in three, an additional myofascial flap was used. There were no significant maternal complications. Overall perinatal complication rate was 18% (6/32), including a perinatal mortality rate of 12.5% (4/32) and two cases of skin suture dehiscence. No cases of cerebrospinal fluid (CSF) leakage were observed. The mean gestational age at birth was 34.6 ± 3.6 weeks, and 31% of deliveries were vaginal. Among the 28 neonates followed for at least 12 months, and only 14% required CSF diversion.

Conclusion: Exteriorized uterus fetoscopic repair of MMC proved safe for the mother and effective in closing the neural tube defect. It also reduced the necessity for CSF diversion and preserved uterine function for future pregnancies. These findings endorse the potential of minimally invasive techniques in fetal MMC repair.

Background: This review of genomic perinatal opportunities and uses will provide counseling and personal genetic knowledge for improved patient care.

Summary: This focused systematic analysis and review has used PubMed keywords to identify genomic testing for ultrasound-identified fetal anomaly(ies) that require diagnostic testing after an informed consent process. Multiple fetal anomalies, using TRIO sequencing processes, have a better diagnostic yield, with certain cohorts >50%. For the single anatomic categories, skeletal system, central nervous system, and renal system, using WES fetal sequencing (most commonly) for a diagnostic result, have the larger incremental diagnostic yield over the chromosome micro-array.

Key messages: The phenotype-genotype (fetal-genomic result) consideration and use of the prenatal exome sequencing technology can be summarized using a SWOT analysis: strength (enhanced evaluation of fetal-neonatal genomic abnormalities not identified by standard chromosomal microarray and improved ethical care decisions); weakness (the understanding and complexity of genomic pathology and testing/the fiscal cost for professional time and the health system services); opportunity (an increased recognition of fetal genetic risk pathology [de novo or inherited carrier mutations] with improved understanding and knowledge translation of counseling for recurrence risk); threat (inability to provide a genetic diagnosis or interpret a variant of unknown significance or the discovery of incidental findings or unanticipated parental genomic diagnoses).

Introduction: Delivery room (DR) interventions for infants with congenital diaphragmatic hernia (CDH) are not well described. This study sought to describe timing and order of DR interventions and identify system factors impacting CDH DR resuscitations using a human factors framework.

Methods: This was a single-center observational study of video-recorded CDH DR resuscitations documenting timing and order of interventions. The team used the Systems Engineering Initiative for Patient Safety (SEIPS) model to identify system factors impacting DR resuscitations and time to invasive ventilation.

Results: We analyzed 31 video-recorded CDH resuscitations. We observed variability in timing and order of resuscitation tasks. The "Internal Environment" and "Tasks" components of the SEIPS model were prominent factors affecting resuscitation efficiency; significant room and bed spatial constraints exist, and nurses have a significant task burden. Additionally, endotracheal tube preparation was a prominent barrier to timely invasive ventilation.

Conclusion: Video review revealed variation in event timing and order during CDH resuscitations. Standardization of the room setup, equipment, and event order and reallocation of tasks facilitate more efficient intubation and ventilation, representing targets for CDH DR improvement initiatives. This work emphasizes the utility of rigorous human factors review to identify areas for improvement during DR resuscitation.