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Introduction: Ultrasonography in the first trimester of pregnancy offers an early screening tool to identify high risk pregnancies. Artificial intelligence (AI) algorithms have the potential to improve the accuracy of diagnosis and assist the clinician in early risk stratification., Objective: The objective of the study was to conduct a systematic review of the use of AI in imaging in the first trimester of pregnancy., Methods: We conducted a systematic literature review by searching in computerized databases PubMed, Embase, and Google Scholar from inception to January 2024. Full-text peer-reviewed journal publications written in English on the evaluation of AI in first-trimester pregnancy imaging were included. Review papers, conference abstracts, posters, animal studies, non-English and non-peer-reviewed articles were excluded. Risk of bias was assessed by using PROBAST., Results: Of the 1,595 non-duplicated records screened, 27 studies were included. Twelve studies focussed on segmentation, 8 on plane detection, 6 on image classification, and one on both segmentation and classification. Five studies included fetuses with a gestational age of less than 10 weeks. The size of the datasets was relatively small as 16 studies included less than 1,000 cases. The models were evaluated by different metrics. Duration to run the algorithm was reported in 12 publications and ranged between less than one second and 14 min. Only one study was externally validated., Conclusion: Even though the included algorithms reported a good performance in a research setting on testing datasets, further research and collaboration between AI experts and clinicians is needed before implementation in clinical practice., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objectives: The objective of this study is to determine additional variables, next to umbilical artery (UA) Doppler, to help differentiate between Type II and III selective fetal growth restriction (sFGR)., Methods: Retrospective analysis categorizing monochorionic diamniotic twin pregnancies with sFGR and abnormal UA Doppler as either Type II or III sFGR based on the diameter of the artery-to-artery (AA) anastomosis of ≤2 or >2 mm, respectively on placental examination after birth. This exploratory study compared maternal characteristics, pregnancy outcome, placental characteristics, and ultrasound features between the two groups., Results: We included 40 sFGR placentas, 13 were classified as Type II and 27 as Type III. Maternal age was higher in Type II. Small Type II twins had lower birth weights (BWs) for gestational age and BW discordance was higher in Type II. Type III placentas were more unevenly divided, but Type III pairs differed less in BW than expected relative to their placental discordance. Type III placentas more commonly had a vein-to-vein anastomosis and larger artery-to-vein anastomoses than Type II placentas, and proximate cord insertions were only observed in Type III. On the ultrasound scan at first diagnosis, small Type II twins were more growth-restricted. An AA anastomosis was detected in half of the Type III cases and in none of the Type II group. Signs of high-output cardiac strain were observed only in large Type III twins. In contrast, placental dichotomy was detected in nearly half of the Type II cases and only one Type III case., Conclusions: The presence of an AA anastomosis, signs of cardiac strain in the large twin, and proximate cord insertions suggested Type III sFGR, whereas placental dichotomy and a severe growth restriction were typically present in Type II. Prospective studies need to validate if these markers help prenatal differentiation between Type II and III sFGR., (© 2022 S. Karger AG, Basel.)

Background: Sildenafil is a phosphodiesterase-5 inhibitor considered for antenatal use for a variety of indications. We sought to assess sildenafil pharmacokinetics in the pregnant ewe and fetus and evaluate its physiological fetal effects., Methods: Twelve fetal lambs (127-133 days GA, term 145) were chronically catheterized in utero. Ewes received different doses of sildenafil, either via subcutaneous injection (1.6, 2.0 mg/kg/day) or intravenous (IV) infusion (3, 5, 7, 10, and 12 mg/kg/day). Maternal and fetal sildenafil concentrations and metabolic status (blood gas analysis) were measured at given intervals. The fetal heart rate, pulmonary blood flow, systemic and aortic pressure, and maternal uterine artery pressure were continuously monitored., Results: The transplacental sildenafil transfer was 2.9% (range: 1.4-7.8%), preventing attainment of fetal target concentrations without toxic maternal levels. IV sildenafil infusion induced an immediate, temporary, dose-dependent reduction of pulmonary vascular resistance (38-78%) and increased both pulmonary blood flow (32-132%) and heart rate (13-49%), with limited nonlinear dose-dependent effects on systemic and pulmonary pressures. Fetal and maternal blood gases and maternal uterine artery pressures were unaffected by sildenafil infusion., Conclusion: In sheep, transplacental transfer of sildenafil is extremely low. Though, minimal fetal sildenafil concentrations induce an acute transient pulmonary vasodilation, well-tolerated by the fetus and ewe., (© 2021 S. Karger AG, Basel.)

Background: Evidence to support a fortnightly scan protocol for monochorionic diamniotic (MCDA) pregnancies to detect twin-twin transfusion syndrome (TTTS) is scarce. Also, TTTS-related mortality in an unselected cohort is not well documented. Finally, common knowledge suggests that a more frequent follow-up may pick up the disease at a milder stage, but little is known on the ultrasound findings before the diagnosis., Objectives: We examine if a fortnightly ultrasound scan from 16 weeks onward detects TTTS in time. Also, we document the outcomes in a large unselected cohort of MCDA twins and examine the ultrasound findings within 14 days before diagnosis., Methods: Retrospective cohort of 675 MCDA twin pregnancies followed with a fortnightly scan protocol from 16 weeks onward. Timely detection of TTTS was defined as before fetal demise (stage V), ruptured membranes, or a dilated cervix. We compared the ultrasound findings before the diagnosis between stage I-II and stage III-IV., Results: A total of 82/675 (12%) pregnancies developed TTTS, of which 74/82 (90%) were detected in time. In 8/82 (10%), TTTS was diagnosed in stage V: 5 before 16 weeks and 2 after 26 weeks. Fetoscopic laser photocoagulation (FLP) of the placental anastomoses was performed in 48/82 (59%). The survival of TTTS in the entire cohort was 105/164 (64%). In contrast, survival after FLP was 77/96 (80%). In 16/19 (84%) of stage III-IV TTTS, abnormal Doppler findings preceded the diagnosis of TTTS., Conclusions: A scheme of fortnightly ultrasound scans from 16 weeks onward detects 9 out of ten TTTS pregnancies in time. Most stage V cases presented outside the typical time window of 16 and 26 weeks. Survival rates after FLP underestimate the mortality of TTTS. Most stage III-IV cases have abnormal Doppler findings before the diagnosis of TTTS., (© 2021 S. Karger AG, Basel.)

Introduction: Anesthesia during pregnancy can impair fetal neurodevelopment, but effects of surgery remain unknown. The aim is to investigate effects of abdominal surgery on fetal brain development. Hypothesis is that surgery impairs outcome., Methods: Pregnant rabbits were randomized at 28 days of gestation to 2 h of general anesthesia (sevoflurane group, n = 6) or to anesthesia plus laparoscopic appendectomy (surgery group, n = 13). On postnatal day 1, neurobehavior of pups was assessed and brains harvested. Primary outcome was neuron density in the frontal cortex, and secondary outcomes included neurobehavioral assessment and other histological parameters., Results: Fetal survival was lower in the surgery group: 54 versus 100% litters alive at birth (p = 0.0442). In alive litters, pup survival until harvesting was 50 versus 69% (p = 0.0352). No differences were observed for primary outcome (p = 0.5114) for surviving pups. Neuron densities were significantly lower in the surgery group in the caudate nucleus (p = 0.0180), but not different in other regions. No differences were observed for secondary outcomes. Conclusions did not change after adjustment for mortality., Conclusion: Abdominal surgery in pregnant rabbits at a gestational age corresponding to the end of human second trimester results in limited neurohistological changes but not in neurobehavioral impairments. High intrauterine mortality limits translation to clinical scenario, where fetal mortality is close to zero., (© 2021 S. Karger AG, Basel.)

Introduction: Preterm prelabor rupture of membranes (PPROM) is a common complication after fetal surgeries. The aim of this study was to assess risk factors for and outcomes after PPROM following cord occlusion (CO) in monochorionic diamniotic (MCDA) pregnancies., Methods: This was a retrospective cohort study of 188 consecutive MCDA pregnancies treated by bipolar or laser CO, either primarily because of discordant malformation (dMF) or severe selective fetal growth restriction (sFGR), or secondarily when complete bichorionization was not possible in case of twin-to-twin transfusion syndrome (TTTS) or sFGR. Intentional septostomy was performed when needed. The procedure-related PPROM was defined as rupture of membranes <32 weeks' gestation (PROM <32 weeks). Selected pre-, intra-, and early postoperative variables were analyzed by univariate and binomial logistic regression to determine they are correlated to PROM <32 weeks after CO., Results: Between 2006 and 2017, 188 cases underwent CO. Diagnosis was TTTS in 28.2% (n = 53), severe sFGR in 49.5% (n = 93), and dMF in 22.3% (n = 42). PROM <32 weeks occurred in 21.3% (n = 40), resulting in worse perinatal outcomes, as preterm birth <32 weeks occurred in 80.7% (vs. 8.3%, p = 0.000), procedure-to-delivery interval was 47.5 days (vs. 125, p = 0.000), gestational age (GA) at birth 30.0 weeks (vs. 37.7 weeks, p = 0.000), and survival 65.0% (vs. 91.1%, p = 0.000). In univariate analysis, indication, anterior placenta, cervical length, GA at surgery, operation time, amniodistention and drainage fluid volumes, chorioamniotic membrane separation, and septostomy were selected as relevant factors to be included in the regression model. In a multivariate analysis, TTTS was the only factor associated to PROM <32 weeks (OR 3.5 CI 95% 1.5-7.9)., Conclusions: PROM <32 weeks after CO increases the risk of preterm delivery. In this cohort, the membrane rupture was more likely when CO was done in the context of TTTS., (© 2021 S. Karger AG, Basel.)

The COVID-19 pandemic has stressed patients and healthcare givers alike and challenged our practice of antenatal care, including fetal diagnosis and therapy. This document aims to review relevant recent information to allow us to optimize prenatal care delivery. We discuss potential modifications to obstetric management and fetal procedures in SARS-CoV2-negative and SARS-CoV2-positive patients with fetal anomalies or disorders. Most fetal therapies are time sensitive and cannot be delayed. If personnel and resources are available, we should continue to offer procedures of proven benefit, acknowledging any fetal and maternal risks, including those to health care workers. There is, to date, minimal, unconfirmed evidence of spontaneous vertical transmission, though it may theoretically be increased with some procedures. Knowing a mother's preoperative SARS-CoV-2 status would enable us to avoid or defer certain procedures while she is contagious and to protect health care workers appropriately. Some fetal conditions may alternatively be managed neonatally. Counseling regarding fetal interventions which have a possibility of additional intra- or postoperative morbidity must be performed in the context of local resource availability. Procedures of unproven benefit should not be offered. We encourage participation in registries and trials that may help us to understand the impact of COVID-19 on pregnant women, their fetuses, and neonates., (© 2020 S. Karger AG, Basel.)

Background: Fetal growth may vary significantly in different congenital heart defects (CHDs)., Objectives: To investigate prenatal growth of CHD fetuses and its correlation with classifications based upon expected oxygen delivery to the fetal brain or structural findings., Methods: Seventy-nine euploid fetuses with isolated CHD were recruited prospectively and categorized by the expected oxygen supply to the brain (low, intermediate, and high) or by the expected arterial mixing considering two categories (cyanotic or non-cyanotic). Biometry and Doppler were recorded, and Z-scores (Zs) calculated. Growth changes at different time points were analyzed and compared with 150 controls., Results: A total of 664 exams were performed on 229 fetuses. Median head circumference (HC) Zs were lower in all CHD fetuses from the second trimester onwards and in cyanotic CHD fetuses from the first onwards, with associated smaller abdominal circumference (AC) in the third trimester (first-trimester biparietal diameter Zs cyanotic: -1.3 [-2.36; -0.98], non-cyanotic -0.72 [-1.25; -0.6], p = 0.044, second-trimester HC Zs cyanotic: -1.47 [-2.3; -0.84]; non-cyanotic -0.45 [-0.83; -0.02], p < 0.0001; AC Zs cyanotic 0.0 [-0.44; 0.86]; non-cyanotic 0.65 [0.31; 1], p = 0.0006). Birth-weight centiles were smaller in CHDs (particularly in cyanotic) with no differences between categories of brain oxygen delivery., Conclusions: Fetuses with cyanotic CHD have fetal growth restriction, impaired head growth, yet normal posterior fossa dimensions and fetal-placental Doppler., (© 2018 S. Karger AG, Basel.)

A 27-year-old woman, gravida 2, para 0, presented with an incomplete Pentalogy of Cantrell with an omphalocele, diaphragmatic hernia, and a pericardial defect at 32 weeks' gestation. A large pericardial effusion compressed the lungs and had led to a reduced lung growth with an observed-to-expected total lung volume of 28% as measured by MRI. The effusion disappeared completely after the insertion of a pericardio-amniotic shunt at 33 weeks. After birth, the newborn showed no signs of pulmonary hypoplasia and underwent a surgical correction of the defect. Protracted wound healing and a difficult withdrawal from opioids complicated the neonatal period. The child was discharged on postnatal day 105 in good condition. This case demonstrates that in case of Pentalogy of Cantrell with large pericardial effusion, the perinatal outcome might be improved by pericardio-amniotic shunting., (© 2017 S. Karger AG, Basel.)

More than 3 decades ago, a small group of physicians and other practitioners active in what they called "fetal treatment" authored an opinion piece outlining the current status and future challenges anticipated in the field. Many advances in maternal, neonatal, and perinatal care and diagnostic and therapeutic modalities have been made in the intervening years, yet a thoughtful reassessment of the basic tenets put forth in 1982 has not been published. The present effort will aim to provide a framework for contemporary redefinition of the field of fetal treatment, with a brief discussion of the necessary minimum expertise and systems base for the provision of different types of interventions for both the mother and fetus. Our goal will be to present an opinion that encourages the advancement of thoughtful practice, ensuring that current and future patients have realistic access to centers with a range of fetal therapies with appropriate expertise, experience, and subspecialty and institutional support while remaining focused on excellence in care, collaborative scientific discovery, and maternal autonomy and safety., (© 2017 S. Karger AG, Basel.)

Objective: To compare outcomes of fetoscopic spina bifida aperta repair (FSBAR) with the results of the open approach (OSBAR) as in the Management Of Myelomeningocele Study (MOMS)., Methods: This was a systematic comparison of reports on FSBAR with data from the MOMS (n = 78). Inclusion criteria were studies of spina bifida aperta patients who underwent FSBAR and were followed for ≥12 months. Primary outcome was perinatal mortality. Secondary outcomes included operative, maternal, fetal, neonatal and infant outcomes., Results: Out of 16 reports, we included 5 from 2 centers. Due to bias and heterogeneity, analysis was restricted to two overlapping case series (n = 51 and 71). In those, FSBAR was technically different from OSBAR, had comparable perinatal mortality (7.8 vs. 2.6%, p = 0.212) and shunt rate at 12 months (45 vs. 40%, p = 0.619), longer operation time (223 vs. 105 min, p < 0.001), higher preterm prelabor membrane rupture rate (84 vs. 46%, p < 0.001), earlier gestational age at birth (32.9 vs. 34.1 weeks, p = 0.03), higher postnatal reoperation rate (28 vs. 2.56%, p < 0.001) and absence of uterine thinning or dehiscence (0 vs. 36%, p < 0.001). Functional outcomes were not available., Conclusion: FSBAR utilizes a different neurosurgical technique, takes longer to complete, induces more prematurity, requires additional postnatal procedures, yet has a comparable shunt rate and is not associated with uterine thinning or dehiscence. Long-term functional data are awaited., (© 2016 S. Karger AG, Basel.)

Introduction: Continuous improvements in perinatal care have allowed the survival of increasingly more prematurely born infants. The establishment of respiration in an extremely immature yet still developing lung results in chronic lung injury with significant mortality and morbidity. We experimentally evaluated a novel medical strategy to prevent hyperoxia-induced lung injury by prenatal rosiglitazone., Materials and Methods: Pregnant rabbits were injected with saline or rosiglitazone (3 mg/kg) 48 and 24 h prior to preterm delivery at 28 days of gestation (term = 31 days). The pups were held in normoxia (21% O2) or hyperoxia (>95% O2), and assessment was done at three different time points (1 h, 24 h and 7 days)., Results: The administration of rosiglitazone resulted in a significant decrease in tissue damping (resistance) on day 7. Furthermore, significantly increased expression of vascular endothelial growth factor, fetal liver kinase 1 and surfactant protein B immediately after delivery was noted by immunohistochemistery. On day 7, there was a more mature lung parenchymal architecture in rosiglitazone-exposed pups., Discussion: In a preterm rabbit model, prenatal maternal administration of rosiglitazone attenuates neonatal hyperoxic lung injury and results in a more mature pulmonary parenchyma., (© 2015 S. Karger AG, Basel.)

Objective: To correlate prenatal indicators of pulmonary hypoplasia with neonatal lung function and pulmonary hypertension (PHT) in isolated congenital diaphragmatic hernia (iCDH)., Materials and Methods: Prospective single-center study on 40 fetuses with iCDH either expectantly managed (n = 13) or undergoing tracheal occlusion (n = 27). Prenatal predictors included observed/expected lung-head ratio (O/E LHR), observed/expected total fetal lung volume, fetal pulmonary reactivity to maternal O2 administration (Δpulsatility index, ΔPI) and liver-to-thorax ratio (LiTR) as measured in the second and third trimesters. Postnatal outcome measures included survival until discharge, best oxygenation index (OI) and alveolar-arterial oxygen gradient [D(A-a)O2] in the first 24 h of life and the occurrence of PHT in the first 28 days of life., Results: Median gestational age (GA) at evaluations was 27.2 and 34.3 weeks. GA at delivery was 36.0 weeks, and overall survival was 55%. In the second trimester, measurement of lung size, LiTR and pulmonary reactivity were significantly related to survival and the best OI and D(A-a)O2.The occurrence of PHT was better predicted by ΔPI and LiTR., Conclusions: O/E LHR, LiTR and vascular reactivity correlate with ventilatory parameters in the first 24 h of life. Occurrence of PHT at ≥28 days was best predicted by LiTR and ΔPI, but not by lung size., (© 2014 S. Karger AG, Basel.)

Introduction: Percutaneous fetoscopic endoluminal reversible tracheal occlusion (FETO) was developed to prevent the pulmonary complications of fetal congenital diaphragmatic herniation. There is an urgent need to establish the closest to human translational model of FETO in order to improve fetal outcomes and to determine new clinical approaches and applications., Material and Methods: Seven non-human primates underwent two subsequent surgeries: the first, the FETO in the experimental group (n = 3) or sham operation in the control animals (S-FETO, n = 4) at 132-142 days of gestation (dGA); the second, the reversal of occlusion or sham operation at 162 ± 5 dGA. Maternal stress axis, complete blood count, and biochemical parameters were evaluated and newborn tracheal radiography was performed., Results: The average pregnancy duration and neonatal weights in the FETO group did not differ from the animals in the S-FETO group. There was no bleeding or premature fetal membrane rupture during the procedures in any of the baboons. The maximal tracheal width was 7.02 ± 0.6 mm in the FETO versus 5.46 ± 0.6 mm in S-FETO group., Discussion: This is the very first report of a successful FETO model in non-human primates. Similarities to human tracheomegaly were for the first time documented in any model studied., (© 2014 S. Karger AG, Basel.)

Objective: To compare the outcomes of twin-to-twin transfusion syndrome (TTTS) cases treated with fetoscopic laser coagulation of vascular anastomoses before 25 + 6 weeks of gestation and between 26 and 28 weeks of gestation., Material and Methods: 28 consecutive cases of TTTS at Quintero stages II-IV treated with laser therapy between 26 + 0 and 28 + 6 weeks of gestation were compared with 324 cases treated between 15 + 0 and 25 + 6 weeks during a 3-year period in two centers. The following data were recorded and compared: duration of the fetoscopy, rate of complications (preterm labor before 28 weeks and before 32 weeks, chorioamnionitis, twin anemia-polycythemia syndrome and recurrent TTTS), gestational age at delivery and neonatal survival rate., Results: The study groups were similar as regards Quintero staging and the frequency of anterior placental location (50.0 vs. 47.8%, p = 0.85 in late and conventional laser, respectively). There were no significant differences in the duration of surgery (29 vs. 30, p = 0.27, respectively) and in the rates of any of the complications evaluated. Gestational age at delivery (33 vs. 33.3 weeks, p = 0.69) and neonatal survival of at least one fetus (92.3 vs. 88.6%, p = 0.24) were also similar., Conclusion: Fetoscopic laser coagulation for TTTS performed between 26 + 0 and 28 + 6 weeks of gestation was associated with similar outcomes as those observed in cases treated before 26 weeks., (Copyright © 2011 S. Karger AG, Basel.)

Objective: To assess the value of gestational age and cardiovascular Doppler indices in predicting perinatal mortality in a multicenter cohort of early-onset intrauterine growth-restricted (IUGR) fetuses., Methods: A multicenter prospective cohort study including 157 early-onset (<34 weeks) IUGR cases with abnormal umbilical artery (UA) Doppler was conducted. Cardiovascular assessment included the ductus venosus (DV), the aortic isthmus flow index (IFI), and the myocardial performance index (MPI). Isolated and combined values to predict the risk of perinatal death were evaluated by logistic regression and by decision tree analysis, where the gestational age at delivery, UA, and middle cerebral artery (MCA) were also included as covariates., Results: Perinatal mortality was 17% (27/157). All parameters were significantly associated with perinatal death, with individual odds ratios (OR) of 25.2 for gestational age below 28 weeks, 12.1 for absent/reversed DV atrial flow, 5.3 for MCA pulsatility index <5th centile, 4.6 for UA absent/reversed diastolic end-flow, 1.8 for IFI <5th centile, and 1.6 for MPI >95th centile. Decision tree analysis identified gestational age at birth as the best predictor of death (<26 weeks, 93% mortality; 26-28 weeks, 29% mortality, and >28 weeks, 3% mortality). Between 26 and 28 weeks, DV atrial flow allowed further stratification between high (60%) and low risk (18%) of mortality., Conclusions: Gestational age largely determines the risk of perinatal mortality in early-onset IUGR before 26 weeks and later than 28 weeks of gestation. The DV may improve clinical management by stratifying the probability of death between 26 and 28 weeks of gestation., (Copyright © 2012 S. Karger AG, Basel.)

Objective: Fetal cardiac output is conventionally measured using two-dimensional (2D) and Doppler ultrasound (Doppler). New methods based on 3D measurements of ventricular size in systole and diastole have been proposed. Our aim was to validate these tools against the conventional Doppler-based methods., Methods: Fetal combined cardiac output was prospectively measured at 16, 20, and 24 weeks of gestation in 15 uncomplicated pregnancies using Doppler and three different 3D algorithms [virtual organ computer-aided analysis (VOCAL), sonographic automatic volume calculation (SonoAVC), and inversion mode]. We determined the inter- and intraobserver variability of the 3D techniques and assessed the correlation between Doppler and 3D., Results: The 3D techniques showed adequate inter- and intraobserver reproducibility (intraclass correlation coefficient 0.69-0.98), with the best reproducibility for SonoAVC and inversion mode. Bland-Altman analysis revealed low bias and relatively good correlations when comparing the 3D methods among each other, albeit with wide 95% confidence intervals. Doppler measurement of fetal weight-adjusted combined cardiac output (349.0 ml·min⁻¹·kg⁻¹) yielded significantly higher results than 3D CO measurements (177.2, 160.7, and 174.0 ml·min⁻¹·kg⁻¹ for VOCAL, SonoAVC, and inversion mode, respectively; p < 0.0001) and correlated poorly with the 3D methods., Conclusions: Although 3D volume-based cardiac output measurements are reproducible, results obtained with different methods are not interchangeable. SonoAVC and inversion have the highest intra- and interobserver reproducibility. Results of cardiac output measurement by 3D and Doppler cannot be interchanged., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To assess the impact of lung perfusion by fractional moving blood volume (FMBV) for the prediction of survival in fetuses with congenital diaphragmatic hernia (CDH) treated with fetal endoscopic tracheal occlusion (FETO)., Study Design: Lung perfusion by FMBV (%) and the observed/expected lung-to-head ratio (o/e LHR) were evaluated 1 day before and 7-14 days after FETO in a cohort of 62 CDH fetuses, and their isolated and combined values to predict survival was assessed., Results: Preoperative lung perfusion did not show association with survival. However, after FETO, an increase in 30% of the preoperative lung FMBV and an increase in 50% of the LHR was significantly associated with the probability of survival. A model combining the changes in FMBV and o/e LHR after therapy allowed discrimination of cases with poor (10% survival), moderate (40-70% survival) and very good prognosis (100% survival)., Conclusion: Changes in lung tissue perfusion, evaluated by FMBV after FETO, improved the prediction of survival in fetuses with CDH., (Copyright © 2010 S. Karger AG, Basel.)

Pulmonary Doppler may play an important role in the prediction of survival and postnatal morbidity in fetuses with congenital diaphragmatic hernia treated with fetoscopic tracheal occlusion (FETO). Spectral Doppler indexes such as pulsatility index and peak early diastolic reversed flow could help to refine the selection of fetuses that might benefit from fetal therapy. When combined with lung-to-head ratio (LHR), these Doppler indices allow to discriminate cases with moderate-to-high survival rates from fetuses with extremely low chances to survive after FETO. In addition, they discriminate groups with a high or low risk of serious neonatal morbidity in surviving fetuses. After therapy, the combined evaluation of the relative increase of LHR with the increase in lung tissue perfusion by power Doppler seems to improve the prediction of fetal survival. In conclusion, while LHR remains the strongest predictive index, Doppler measurements allow to substantially improve the accuracy in the prediction of the chances of survival of fetuses with congenital diaphragmatic hernia treated with FETO., (Copyright © 2010 S. Karger AG, Basel.)

About 30% of monochorionic twin pregnancies are complicated by twin-to-twin transfusion syndrome (TTTS), isolated discordant growth, twin anemia-polycythemia sequence, congenital defects or intrauterine demise. About 15% will be eligible for invasive fetal therapy, either fetoscopic laser treatment for TTTS or fetoscopic or ultrasound-guided umbilical cord coagulation for a severe congenital defect in one twin or severe discordant growth with imminent demise of the growth-restricted twin. Ultrasound examination in the first and early second trimester can differentiate the monochorionic twins at high risk for adverse outcome from those likely to be uneventful, which may be useful for patient counselling and planning of care., (Copyright 2010 S. Karger AG, Basel.)

Objectives: If fetal ECG (fECG) devices could be miniaturized sufficiently, one could consider their implantation at the time of fetal surgery to allow permanent monitoring of the fetus and timely intervention in the viable period. We set up an experiment to evaluate the feasibility of in utero direct fECG monitoring and telemetric transmission using a small implantable device in a lamb model., Methods: A 2-lead miniature ECG sensor (volume 1.9 cm(3); weight 3.9 g) was subcutaneously implanted in 2 fetal lambs at 122 days gestation (range 119-125; term 145 days). The ECG sensor can continuously register and transmit fECG. The signal is captured by an external receiving antenna taped to the maternal abdominal wall. We developed dedicated software running on a commercial laptop for on-line analysis of the transmitted fECG signal. This was a noninterventional study, i.e. daily readings of the fECG signal were done without clinical consequences to the observations., Results: fECG could be successfully registered, transmitted by telemetry and analyzed from the moment of implantation till term birth in one case (24 days). In the second case, unexplained in utero fetal death occurred 12 days after implantation. In this subject, agonal fECG changes were recorded., Conclusion: An implanted miniature (<2 ml) ECG sensor can be used to retrieve, process and transmit continuously a qualitative fECG signal in third-trimester fetal lambs. The telemetric signal could be picked up by an external antenna located within a 20-cm range. In this experiment, this was achieved through taping the external receiver to the maternal abdomen. Any acquired signal could be transmitted to a commercially available laptop that could perform on-line analysis of the signal., ((c) 2008 S. Karger AG, Basel.)

Objective: As an aid to evaluate lung hypoplasia, we investigated the difference between T2 value in fetal lungs of lambs with surgically-induced left-sided diaphragmatic hernia (DH) and gestational age (GA)-matched control littermates (normal [NL])., Methods: Lungs were divided into two groups: DH (n = 4) and NL (n = 6). DH was induced at 65-75 days GA (term = 145 days). Fetal MRI was performed (mean GA: 120 days) with half-Fourier acquisition single-shot turbo spin-echo (TE: 60 ms) and rapid acquisition with relaxation enhancement (TE: 350 ms) in the same location (1.5-T Philips, Gyroscan, Best, The Netherlands). T2 of each lung was calculated for multiple regions of interest by taking natural logarithm of signal-to-noise ratio. Mean T2 was compared between DH and NL (unpaired analysis for entire group). Paired comparison between left/right lung was made within DH and NL., Results: Unpaired analysis showed significantly lower T2 of left respectively right lungs in DH (p = 0.02 [respectively] 0.05]) compared to NL (n = 6), as well as between the T2 of all DH versus NL (p = 0.001). In DH, calculated T2 appeared to be lower in left than in right lungs (difference ranged from -2 to +49%). In NL, left and right lungs showed comparable T2., Conclusion: Measurement of T2 signal intensity in DH lungs is feasible and show lower T2 in comparison to NL lungs. Left lungs from lambs with DH show lower T2 than right lungs.

We present a patient who developed complete chorioamniotic membrane separation (CMS) in two consecutive pregnancies. The first pregnancy ended with an intrauterine fetal death at 25 weeks of gestation. The entire separated amniotic sac had twisted around the umbilical cord. In the subsequent pregnancy, a complete CMS was diagnosed at 34 weeks of gestation. In both pregnancies, the patient underwent an early 2nd-trimester genetic amniocentesis. A review of the literature shows that extensive CMS is associated with miscarriage, in utero fetal death, umbilical cord complications, and preterm delivery. Most reported cases occurred after invasive intrauterine procedures., (Copyright 2004 S. Karger AG, Basel)

Objective: To develop a small animal model for fetoscopy., Methods: In 12 time-dated pregnant rabbits at 22 days' gestational age (term 32 days) one amniotic sac in each uterine horn (n = 24) was used for a fetoscopic procedure. After laparotomy, a 2- to 3-mm microsurgical myometrial incision was made to expose the chorionic and amniotic membrane. Under microscopic control, a 2-mm needle was inserted into the amniotic sac. Through this a 1.2-mm endoscope was passed to carry out fetoscopy during maximally 10 min, using 5-10 ml saline amnioinfusion. Mean outcome measurements were ability to visualize the placenta, umbilical cord and the different fetal elements during fetoscopy, as well as fetal survival and weight at second-look operation at 30 days. The untreated amniotic sacs served as negative controls., Results: In all cases, fetoscopy could be carried out successfully, and all fetuses survived till delivery without significant influence on fetal birth weight., Conclusion: The midgestational rabbit can be used to perform fetoscopy.

In this study, we have investigated the maternal effects of distending the uterine cavity with Hartmann's solution in 2nd trimester equivalent pregnant sheep. In 7 pregnant ewes, double endoscopic cannulation of the amniotic cavity was performed under general anesthesia, and 1 liter of Hartmann's solution at 38 degrees C, radiolabeled with 99mTc-red blood cells, was infused. Maternal central venous pressure, hematocrit, serum and amniotic fluid osmolarity, and amniotic fluid volume were measured at nine time points within a 2-hour period. Over this time interval, no significant fluid shift to the maternal compartment was observed. We detected no adsorption of radioactivity to the fetus or membranes, and no diffusion of radioactivity to maternal or fetal tissues was noticed. We conclude from these experiments that following double cannulation and intra-amniotic infusion of Hartmann's solution into the 2nd-trimester pregnant ovine uterus, no significant shift of fluid to the maternal compartment was observed over a 2-hour time period.

Endoscopic coagulation of placental and umbilical cord vessels has been suggested as a treatment for selected cases of twin-twin transfusion syndrome and of acardiac twin. The feasibility, safety and hemostatic effect of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser in an underwater environment were experimentally studied in an in vivo model, mimicking the in utero situation and fetoplacental vessels. In 10 male Wistar rats, immersed in normal saline at 38 degrees C, femoral vessels, carotid artery, abdominal aorta and vena cava were coagulated under endoscopic control. A 100-Watt Nd:YAG laser was used in continuous mode with a 600-micron fiber. Outcome measurements were vascular diameter, total energy (joules) used to obtain visual coagulation and subsequent vascular obliteration. Overall failure rate was 32% and perforation of the vessel occurred in 7.7% of cases.

The strong light sources used in fetoscopy and embryoscopy may cause eye injuries to the fetus. To circumvent this potential hazard, we have successfully used an infrared light source and infrared video camera to perform 'night vision' fetoscopy in a fetal lamb model.

Recently developed techniques of video-endoscopic surgery may offer new hope for the future of fetal surgery. To allow this approach, the amniotic cavity has to be temporarily enlarged, either by carbon dioxide (CO2) insufflation or by amnioinfusion. In 6 anesthetized ewes, CO2 insufflation of the amniotic cavity produced severe fetal hypercapnia (from 57.6 +/- 1.6 to 87.0 +/- 7.0 torr) and acidosis (from 7.22 +/- 0.03 to 7.11 +/- 0.08) despite normal maternal CO2 pressure and pH. CO2 pneumoamnios does not therefore appear to be an ideal working medium. Fetal endoscopic surgery through amnioinfusion of physiologic fluid may be a safer alternative.