Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary hypoplasia due to isolated ...congenital diaphragmatic hernia on the left side, but data from randomized trials are lacking.
In this open-label trial conducted at centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with severe isolated congenital diaphragmatic hernia on the left side to FETO at 27 to 29 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcome was infant survival to discharge from the neonatal intensive care unit. We used a group-sequential design with five prespecified interim analyses for superiority, with a maximum sample size of 116 women.
The trial was stopped early for efficacy after the third interim analysis. In an intention-to-treat analysis that included 80 women, 40% of infants (16 of 40) in the FETO group survived to discharge, as compared with 15% (6 of 40) in the expectant care group (relative risk, 2.67; 95% confidence interval CI, 1.22 to 6.11; two-sided P = 0.009). Survival to 6 months of age was identical to the survival to discharge (relative risk, 2.67; 95% CI, 1.22 to 6.11). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (47% vs. 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs. 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. In an analysis that included 11 additional participants with data that were available after the trial was stopped, survival to discharge was 36% among infants in the FETO group and 14% among those in the expectant care group (relative risk, 2.65; 95% CI, 1.21 to 6.09).
In fetuses with isolated severe congenital diaphragmatic hernia on the left side, FETO performed at 27 to 29 weeks of gestation resulted in a significant benefit over expectant care with respect to survival to discharge, and this benefit was sustained to 6 months of age. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT01240057.).
Accurate medical image segmentation is essential for diagnosis, surgical planning and many other applications. Convolutional Neural Networks (CNNs) have become the state-of-the-art automatic ...segmentation methods. However, fully automatic results may still need to be refined to become accurate and robust enough for clinical use. We propose a deep learning-based interactive segmentation method to improve the results obtained by an automatic CNN and to reduce user interactions during refinement for higher accuracy. We use one CNN to obtain an initial automatic segmentation, on which user interactions are added to indicate mis-segmentations. Another CNN takes as input the user interactions with the initial segmentation and gives a refined result. We propose to combine user interactions with CNNs through geodesic distance transforms, and propose a resolution-preserving network that gives a better dense prediction. In addition, we integrate user interactions as hard constraints into a back-propagatable Conditional Random Field. We validated the proposed framework in the context of 2D placenta segmentation from fetal MRI and 3D brain tumor segmentation from FLAIR images. Experimental results show our method achieves a large improvement from automatic CNNs, and obtains comparable and even higher accuracy with fewer user interventions and less time compared with traditional interactive methods.
High-resolution volume reconstruction from multiple motion-corrupted stacks of 2D slices plays an increasing role for fetal brain Magnetic Resonance Imaging (MRI) studies. Currently existing ...reconstruction methods are time-consuming and often require user interactions to localize and extract the brain from several stacks of 2D slices. We propose a fully automatic framework for fetal brain reconstruction that consists of four stages: 1) fetal brain localization based on a coarse segmentation by a Convolutional Neural Network (CNN), 2) fine segmentation by another CNN trained with a multi-scale loss function, 3) novel, single-parameter outlier-robust super-resolution reconstruction, and 4) fast and automatic high-resolution visualization in standard anatomical space suitable for pathological brains. We validated our framework with images from fetuses with normal brains and with variable degrees of ventriculomegaly associated with open spina bifida, a congenital malformation affecting also the brain. Experiments show that each step of our proposed pipeline outperforms state-of-the-art methods in both segmentation and reconstruction comparisons including expert-reader quality assessments. The reconstruction results of our proposed method compare favorably with those obtained by manual, labor-intensive brain segmentation, which unlocks the potential use of automatic fetal brain reconstruction studies in clinical practice.
Monochorionic twin pregnancies are at increased risk of adverse outcome because of the vascular anastomoses that connect the 2 fetal circulation systems. The shared circulation is responsible for ...some unique complications in monochorionic twins, such as the twin-to-twin transfusion syndrome, the twin anemia polycythemia sequence, the twin reversed arterial perfusion sequence, and monoamniotic twinning. Another consequence of the shared circulation is that the well-being of one twin critically depends on that of the other. In this review, we will describe the technique of placental injection. Further, we will discuss the role of the vascular anastomoses in each of the complications described above and provide an update on their management.
Abstract
Objective
Prenatal tracheal occlusion (TO) promotes lung growth and is applied clinically in fetuses with congenital diaphragmatic hernia (CDH). Limited data are available regarding the ...effect of duration versus timepoint of TO. Our objective was to document the impact of TO on lung development in the near‐term period in rats with nitrofen‐induced CDH.
Method
Nitrofen was administered on embryonic day (ED)9 and fetal TO was performed on ED18.5, 19, or 20 (term = ED22). Sham‐operated and untouched littermates served as controls. Lungs were harvested in 0.5‐day steps and only fetuses with a left‐sided CDH were included in further analyses. Healthy fetuses provided a reference for normal near‐term lung development.
Results
Duration of TO in the nitrofen rat model for CDH predicts lung growth in terms of lung‐body‐weight ratio as well as an increased mRNA level of the proliferation marker Ki67. Longer TO also induced a more complex airway architecture. The timepoint of TO was not predictive of lung growth.
Conclusion
In the nitrofen rat model of CDH, a longer period of TO leads to enhanced lung growth and more refined airway architecture.
Key points
What is already known about this topic?
Prenatal tracheal occlusion is investigated as a treatment for pulmonary hypoplasia due to congenital diaphragmatic hernia in humans. Limited information exists on the optimal timepoint and duration of occlusion.
What does this study add?
In the nitrofen rat model, our study shows that pulmonary development after tracheal occlusion differs with timepoint and duration. It points to enhanced lung proliferation after a longer occlusion period irrespective of the timepoint.
One of the drawbacks of fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia is the need for a second invasive intervention to reestablish airway patency. The ..."Smart-TO" (Strasbourg University-BSMTI, France) is a new balloon for FETO, which spontaneously deflates when positioned near a strong magnetic field, e.g., generated by a magnetic resonance image (MRI) scanner. Translational experiments have demonstrated its efficacy and safety. We will now use the Smart-TO balloon for the first time in humans. Our main objective is to evaluate the effectiveness of prenatal deflation of the balloon by the magnetic field generated by an MRI scanner.
These studies were first in human (patients) trials conducted in the fetal medicine units of Antoine-Béclère Hospital, France, and UZ Leuven, Belgium. Conceived in parallel, protocols were amended by the local Ethics Committees, resulting in some minor differences. These trials were single-arm interventional feasibility studies. Twenty (France) and 25 (Belgium) participants will have FETO with the Smart-TO balloon. Balloon deflation will be scheduled at 34 weeks or earlier if clinically required. The primary endpoint is the successful deflation of the Smart-TO balloon after exposure to the magnetic field of an MRI. The secondary objective is to report on the safety of the balloon. The percentage of fetuses in whom the balloon is deflated after exposure will be calculated with its 95% confidence interval. Safety will be evaluated by reporting the nature, number, and percentage of serious unexpected or adverse reactions.
These first in human (patients) trials may provide the first evidence of the potential to reverse the occlusion by Smart-TO and free the airways non-invasively, as well a safety data.
Introduction and hypothesis
Pregnancy and childbirth are considered risk factors for pelvic floor dysfunction, including anorectal dysfunction. We aimed to assess the effect of obstetric events on ...anal incontinence and constipation after delivery.
Methods
We systematically reviewed the literature by searching MEDLINE, Embase and CENTRAL. We included studies in women after childbirth examining the association between obstetric events and anorectal dysfunction assessed through validated questionnaires. We selected eligible studies and clustered the data according to the type of dysfunction, obstetric event and interval from delivery. We assessed risk of bias using the Newcastle Ottawa Scale and we performed a random-effects meta-analysis and reported the results as odds ratios (ORs) with their 95% confidence intervals. Heterogeneity across studies was assessed using I
2
statistics.
Results
Anal sphincter injury (OR: 2.44 1.92–3.09) and operative delivery were risk factors for anal incontinence (forceps—OR :1.35 1.12–1.63; vacuum—OR: 1.17 1.04–1.31). Spontaneous vaginal delivery increased the risk of anal incontinence compared with caesarean section (OR: 1.27 1.07–1.50). Maternal obesity (OR:1.48 1.28–1.72) and advanced maternal age (OR: 1.56 1.30–1.88) were risk factors for anal incontinence. The evidence on incontinence is of low certainty owing to the observational nature of the studies. No evidence was retrieved regarding constipation after delivery because of a lack of standardised validated assessment tools.
Conclusions
Besides anal sphincter injury, forceps delivery, maternal obesity and advanced age were associated with higher odds of anal incontinence, whereas caesarean section is protective. We could not identify obstetric risk factors for postpartum constipation, as few prospective studies addressed this question and none used a standardised validated questionnaire.
Objective The purpose of this study was to document pregnancy and neonatal outcome of monochorionic diamniotic twin pregnancies. Study Design This observational study describes a prospective series ...included in the first trimester in 2 centers of the Eurotwin2twin project. Results Of the 202 included twin pairs, 172 (85%) resulted in 2 survivors, 15 (7.5%) in 1 survivor, and 15 (7.5%) in no survivors. The mortality was 45 of 404 (11%), and 36 of 45 (80%) were fetal losses of 24 weeks or less, 5 of 45 (11%) between 24 weeks and birth, and 4 of 45 (9%) were neonatal deaths. Twin-to-twin transfusion syndrome (TTTS) occurred in 18 of 202 (9%). The mortality of TTTS was 20 of 36 (55%), which accounted for 20 of 45 (44%) of all losses. Severe discordant growth without TTTS occurred in 29 of 202 (14%). Its mortality was 5 of 58 (9%), which accounted for 5 of 45 (11%) of all losses. Major discordant congenital anomalies occurred in 12 of 202 (6%). Of the 178 pairs that continued after 24 weeks, 10 (6%) had severe hemoglobin differences at birth. After 32 weeks, the prospective risk of intrauterine demise was 2 in 161 pregnancies (1.2%; 95% confidence interval, 0.3-4.6). Conclusion Of the monochorionic twins recruited in the first trimester, 85% resulted in the survival of both twins, and 92.5% resulted in the survival of at least 1 twin. Most losses were at 24 weeks or less, and TTTS was the most important cause of death. After 32 weeks, the risk of intrauterine demise appears to be small.
Summary Background Monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome are typically treated with fetoscopic laser coagulation. Postoperative complications can occur due ...to residual vascular anastomoses on the placenta. We aimed to assess the efficacy and safety of a novel surgery technique that uses laser coagulation of the entire vascular equator (Solomon technique). Methods We undertook an open-label, international, multicentre, randomised controlled trial at five European tertiary referral centres. Women with twin-to-twin transfusion syndrome were randomly assigned by online randomisation (1:1) with permuted blocks to the Solomon technique or standard laser coagulation. The primary outcome was a composite of incidence of twin anaemia polycythaemia sequence, recurrence of twin-to-twin transfusion syndrome, perinatal mortality, or severe neonatal morbidity. Analyses were by intention to treat, with results expressed as odds ratios (ORs) and 95% CIs. This trial is registered with the Dutch Trial Registry, number NTR1245. Findings Between March 11, 2008, and July 12, 2012, 274 women were randomly assigned to either the Solomon group (n=139) or the standard treatment group (n=135). The primary outcome occurred in 94 (34%) of 274 fetuses in the Solomon group versus 133 (49%) of 270 in the standard treatment group (OR 0·54; 95% CI 0·35–0·82). The Solomon technique was associated with a reduction in twin anaemia polycythaemia sequence (3% vs 16% for the standard treatment; OR 0·16, 95% CI 0·05–0·49) and recurrence of twin-to-twin transfusion syndrome (1% vs 7%; 0·21, 0·04–0·98). Perinatal mortality and severe neonatal morbidity did not differ significantly between the two groups. Outside of the common and well-known complications of twin-to-twin transfusion syndrome and its treatment, no serious adverse events occurred. Interpretation Fetoscopic laser coagulation of the entire vascular equator reduces postoperative fetal morbidity in severe twin-to-twin transfusion syndrome. We recommend that fetoscopic surgeons consider adopting this strategy for treatment of women with twin-to-twin transfusion syndrome. Funding Netherlands Organization for the Health Research and Development (ZonMw 92003545).
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