Preterm membranes are mechanically more resistant than term membranes.

OBJECTIVE: To compare the biomechanical properties of fetal preterm membranes (20 + 0 weeks to 30 + 0 weeks) to those of the term (37 + 0 to 41 + 0 weeks). METHOD: Amnion and chorion were manually separated and samples were cut to the required geometry. Rectangular samples with (mode 1) and without (uniaxial) a notch, were tested for tearing energy, critical elongation, and tangent stiffness. Suture retention and inter-suture distance testing investigated the effect of suture placement. RESULTS: From the 15 preterm and 10 term placentas studied, no notable differences were observed in uniaxial testing. Mode 1 fracture testing showed a difference in tearing energy between the preterm and term chorion (0.025 ± 0.005 vs. 0.017 ± 0.005 J/m-1 ; p = 0.027) but not in the amnion (0.030 ± 0.017 vs. 0.029 ± 0.009 J/m-1 ; p = 0.895). Both preterm amnion and chorion showed a higher critical elongation compared with term (1.229 ± 0.057 vs. 1.166 ± 0.046; p = 0.019 and 1.307 ± 0.049 vs. 1.218 ± 0.058; p = 0.012). Preterm amnion had a higher suture retention strength than its term counterpart (0.189 ± 0.065 vs. 0.121 ± 0.031 N; p = 0.023). In inter-suture distance tests, no significant interaction was observed beyond 3 mm, but the preterm chorion showed less interaction at 1-2 mm distances. CONCLUSION: Preterm membranes have equivalent or superior tensile properties to term membranes. The chorion appears to contribute to the mechanical integrity of fetal membranes, particularly in preterm stages.

Fetal-onset Alexander disease with radiological-neuropathological correlation.

Alexander disease is a leukodystrophy caused by mutations in the GFAP gene, primarily affecting the astrocytes. This report describes the prenatal and post-mortem neuroimaging findings in a case of genetically confirmed, fetal-onset Alexander disease with pathological correlation after termination of pregnancy. The additional value of fetal brain magnetic resonance imaging in the third trimester as a complementary evaluation tool to neurosonography is shown for suspected cases of fetal-onset Alexander disease. Diffuse signal abnormalities of the periventricular white matter in association with thickening of the fornix and optic chiasm can point towards the diagnosis. Furthermore, the presence of atypical imaging findings such as microcephaly and cortical folding abnormalities in this case broadens our understanding of the phenotypic variability of Alexander disease.

Incidence and patterns of abnormal corpus callosum in fetuses with isolated spina bifida aperta.

OBJECTIVE: To determine the incidence and characterise corpus callosum (CC) abnormalities in fetuses with spina bifida aperta (SBA) between 18 and 26 weeks of gestation. METHODS: This was a retrospective study on fetuses with isolated SBA and who were assessed for fetal surgery. Digitally stored ultrasound images of the brain were reviewed for the presence/absence of the CC, and the length and diameter of its constituent parts (rostrum, genu, body and splenium). We used regression analysis to determine the relationship between CC abnormalities and gestational age, head circumference, ventricle size, lesion level and lesion type. RESULTS: Nearly three-quarters of fetuses with isolated SBA had an abnormal CC (71.7%, 76/106). Partial agenesis was most common in the splenium (18.9%, 20/106) and the rostrum (13.2%, 14/106). The most common abnormal pattern was of a short CC with normal diameter throughout. Of note, 20.8% (22/106) had a hypoplastic genu and 28.3% (30/106) had a thick body part. Larger lateral ventricle size was associated with partial agenesis of the CC (odds ratio [OR]: 0.14, p < 0.001) and inversely associated with a shorter CC (OR: 2.60, p < 0.01). CONCLUSION: An abnormal CC is common in fetuses with isolated SBA who are referred for fetal surgery.

SARS-CoV2 (COVID-19) infection: is fetal surgery in times of national disasters reasonable?

Even though the global COVID-19 pandemic may affect how medical care is delivered in general, most countries try to maintain steady access for women to routine pregnancy care, including fetal anomaly screening. This means that, also during this pandemic, fetal anomalies will be detected, and that discussions regarding invasive genetic testing and possibly fetal therapy will need to take place. For patients, concerns about Severe Acute Respiratory Syndrome-Corona Virus 2 will add to the anxiety caused by the diagnosis of a serious fetal anomaly. Yet, also for fetal medicine teams the situation gets more complex as they must weigh up the risks and benefits to the fetus as well as the mother, while managing a changing evidence base and logistic challenges in their healthcare system.

Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

BACKGROUND: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. OBJECTIVE: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. STUDY DESIGN: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. RESULTS: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. CONCLUSION: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.

Proton-pump inhibitor omeprazole attenuates hyperoxia induced lung injury.

BACKGROUND: The administration of supplemental oxygen to treat ventilatory insufficiency may lead to the formation of reactive oxygen species and subsequent tissue damage. Cytochrome P4501A1 (CYP1A1) can modulate hyperoxic lung injury by a currently unknown mechanism. Our objective was to evaluate the effect of administration of omeprazole on the induction of CYP1A1 and its influence on hyperoxic lung injury in an established preterm rabbit model. METHODS: Omeprazole was administered either (1) directly to the fetus, (2) to the mother or (3) after birth to the pups in different doses (2-10 or 20 mg/kg). Controls were injected with the same amount of saline. Pups were housed in normoxia (21 %) or hyperoxia (>95 %) for 5 days. Outcome parameters were induction of CYP1A1 measured by real-time polymerase chain reaction (RT-PCR) immediately after delivery, at day 3 and day 5 as well as lung function, morphometry and immunohistochemistry assessed at day 5 of life. Transcriptome analysis was used to define the targeted pathways. RESULTS: Daily neonatal injections demonstrated a dose-dependent increase in CYP1A1. Lung function tests showed a significant improvement in tissue damping, tissue elasticity, total lung capacity, static compliance and elastance. Morphometry revealed a more developed lung architecture with thinned septae in animals treated with the highest dose (20 mg/kg) of omeprazole. Surfactant protein B, vascular endothelial growth factor and its receptor were significantly increased on immunohistochemical stainings after omeprazole treatment. CONCLUSIONS: Neonatal administration of omeprazole induces CYP1A1 in a dose-dependent matter and combined pre- and postnatal administration attenuates hyperoxic lung injury in preterm rabbits, even with the lowest dose of omeprazole without clear CYP1A1 induction.

Transplacental Administration of Rosiglitazone Attenuates Hyperoxic Lung Injury in a Preterm Rabbit Model.

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.

Thrombin Generation by Fetoscopic Trauma to the Fetal Membranes: An in vivo and in vitro Study.

OBJECTIVE: We first aimed to investigate in vivo thrombin generation induced by fetoscopy, and second we used term membrane explants for measurement of thrombin generation, thrombin receptor location and induction of selected matrix metalloproteinases (MMPs) in tissue culture. MATERIALS AND METHODS: In vivo study (37 cases): samples of amniotic fluid were taken at the beginning and end of fetoscopy (mean gestational age 26.7 weeks) and analyzed by ELISA for thrombin-antithrombin complexes. In vitro study: fetal membranes were put in culture and punctured for measurement of thrombin generation by calibrated automated thrombography and ELISA. Induction of MMP-9 and MMP-2 was analyzed by zymography. PAR-1 was localized by immunohistochemistry. RESULTS: No significant increase in thrombin-antithrombin was measured in amniotic fluid obtained during fetoscopy. In vitro, thrombin generation induced by needle trauma of membrane cultures is correlated to the amount of plasma. Activity of MMP-9 but not MMP-2 was elevated in cultured membranes but could not be inhibited by a thrombin inhibitor. On histology, the thrombin receptor PAR-1 was located in the chorion and decidua, but not in the amnion. DISCUSSION: Despite the influence of thrombin on punctured fetal membranes in vitro, the role of thrombin in iatrogenic preterm premature rupture of membranes is questionable.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

The use of human amniotic fluid stem cells as an adjunct to promote pulmonary development in a rabbit model for congenital diaphragmatic hernia.

OBJECTIVE: This study aimed to evaluate the potential benefit of intra-tracheal injection of human amniotic fluid stem cells (hAFSC) on pulmonary development combined with TO in a rabbit model for CDH. METHODS: In time-mated pregnant does a left diaphragmatic defect was created at d23 (term = 31). At d28, previously operated fetuses were assigned to either TO and injection with 70 µL of phosphate buffered saline (PBS) or 1.0 × 10(6) c-Kit positive hAFSC expressing LacZ or were left untouched (CDH). Harvesting was done at d31 to obtain their lung-to-body weight ratio (LBWR), airway and vascular lung morphometry, X-gal staining and immunohistochemistry for Ki67 and surfactant protein-B (SP-B). RESULTS: CDH-induced pulmonary hypoplasia is countered by TO + PBS, this reverses LBWR, mean terminal bronchiole density (MTBD) and medial thickness to normal. The additional injection of hAFSC decreases MTBD and results in a non-significant decrease in muscularization of intra-acinary vessels. There were no inflammatory changes and LacZ positive hAFSC were dispersed throughout the lung parenchyma 4 days after injection. CONCLUSION: HAFSC exert an additional effect on TO leading to a decrease in MTBD, a measure of alveolar number surrounding the terminal bronchioles, without signs of toxicity. © 2015 John Wiley & Sons, Ltd.

Prenatal diagnosis and patient preferences in patients with neural tube defects around the advent of fetal surgery in Belgium and Holland.

INTRODUCTION: We review the characteristics and prenatal choices of patients recently evaluated for neural tube defects (NTD) at two tertiary units. The prenatal diagnosis of NTD allows parents to consider all prenatal options. In selected cases of spina bifida aperta this also includes fetal surgery, which we started offering after combined 'in-house' and 'exported' training. MATERIAL AND METHODS: This is a retrospective review of prospectively collected data on NTD diagnosed over the last 8 years and recent fetal surgery referrals. RESULTS: A total of 167 patients were referred for assessment at a median of 19 weeks. Cranial lesions were diagnosed significantly earlier than spinal lesions. Of the open spinal lesions, 77% were isolated. Of these, 22% were managed expectantly and 1 (1%) had fetal surgery. There was no correlation between parental decisions on prenatal management with disease-specific severity markers. We had 14 fetal surgery referrals, all but 1 from beyond our typical referral area; 6 of the assessed patients were operated on, 4 were expectantly managed and 4 requested termination of pregnancy (TOP). These pregnancy outcomes were in the expected range. DISCUSSION: Open spina bifida is mainly diagnosed in the second trimester and 76% of subjects request TOP, irrespective of the severity indicators. The number of local patients considering fetal surgery is low.

Functional assessment of hyperoxia-induced lung injury after preterm birth in the rabbit.

The objective of this study was to document early neonatal (7 days) pulmonary outcome in the rabbit model for preterm birth and hyperoxia-induced lung injury. Preterm pups were delivered at 28 days (term = 31 days; early saccular phase of lung development) by cesarean section, housed in an incubator, and gavage fed for 7 days. Pups were divided into the following groups: 1) normoxia (21% O2; normoxia group) and 2) and hyperoxia (>95% O2; hyperoxia group). Controls were pups born at term who were housed in normoxic conditions (control group). Outcome measures were survival, pulmonary function tests using the whole body plethysmograph and forced oscillation technique, and lung morphometry. There was a significant difference in survival of preterm pups whether they were exposed to normoxia (83.3%) or hyperoxia (55.9%). Hyperoxic exposure was associated with increased tissue damping and elasticity and decreased static compliance compared with normoxic controls (P < 0.01). Morphometry revealed an increased linear intercept and increased mean wall transection length, which translates to larger alveoli with septal thickening in hyperoxia compared with normoxia (P < 0.01). In conclusion, the current experimental hyperoxic conditions to which preterm pups are exposed induce the typical clinical features of bronchopulmonary dysplasia. This model will be used to study novel preventive or therapeutic interventions.

Speckle tracking echocardiography in fetuses diagnosed with congenital diaphragmatic hernia.

OBJECTIVE: The aim of this study is to evaluate cardiac function in fetuses with congenital diaphragmatic hernia (CDH) using speckle tracking. METHOD: Case-control study assessed cardiac contractility in consecutive fetuses with CDH. Controls were anatomically normal fetuses, adjusted for gestational age. Speckle tracking software calculated ventricular peak longitudinal velocity, displacement and strain. Pulmonary hypoplasia was assessed using observed/expected lung-to-head ratio (O/E LHR). RESULTS: Thirty-eight fetuses with CDH (29 left and nine right) were evaluated at a mean gestational age of 26.9 ± 2.5 weeks. In six fetuses, the acquired images were of insufficient quality (feasibility 83%). Velocity and displacement showed regional differences, as well as significant differences between the ventricular walls, similar to control fetuses. Strain measurements also demonstrated regional differences yet less uniformly arranged. In left CDH, we observed increased strain values in the left ventricle compared with controls (-18.7 ± 7.2 vs -15.1 ± 4.9). There was no correlation between strain values in the left ventricle and O/E LHR. In fetuses with right CDH, deformation analysis was not different from controls. CONCLUSIONS: In fetuses with CDH, no cardiac dysfunction could be detected despite the often concurrent hypoplasia of ipsilateral cardiac structures. In fetuses with left CDH, the decrease in ventricular size coincides with increased strain values in the free left ventricular wall.

A pictorial essay on fetal rabbit anatomy using micro-ultrasound and magnetic resonance imaging.

INTRODUCTION: With this pictorial essay, we aimed to provide gestational age specific reference ranges of relevant fetal structures using micro-ultrasound, as well as its correlation with postmortem MRI and whole body sections. MATERIAL AND METHODS: Time-mated pregnant rabbits (n = 24) were assessed once at various gestational ages in the second half of pregnancy (15, 17, 21 to 23, 25 to 28, and 30 to 31 days; term = 31 days). We obtained biometric data, together with Doppler flow patterns in the ductus venosus, umbilical artery and umbilical vein. After euthanasia, micro-ultrasound images were compared with images obtained by 9.4 Tesla MRI and whole body paraffin sections at 15, 23, 26, and 28 days. RESULTS: We constructed biometric normative curves, which showed a significant correlation with gestational age. The pulsatility index (PI) in the umbilical artery decreased with gestation (PI = 5.746-0.2969(GA) + 0.004931(GA)(2) ; R(2) = 0.30), whereas pulsatility index for veins (PIV) in the ductus venosus remained constant (median PIV = 0.82 (0.60-1.12)). In this report, we provide an anatomical atlas of fetal thoracic development using both micro-ultrasound and MRI. CONCLUSION: We describe anatomical fetal leporine development as can be visualized by micro-ultrasound and MR imaging. The reported reference ranges may be useful for researchers using the fetal rabbit model.

COVID-19 vaccination protects infected pregnant women from developing SARS-CoV-2 placentitis and decreases the risk for stillbirth.

INTRODUCTION: The impact of COVID-19 infection in pregnant women remained unclear for a long time. Previous research showed that SARS-CoV-2 virus is able to infect the placenta, potentially causing significant lesions leading to placental insufficiency. The impact of maternal vaccination status on the prevalence of SARS-CoV-2 placentitis remains unclear. We characterized placental lesions in SARS-CoV-2 infected pregnant women and studied the impact of vaccination on placental involvement. METHODS: We retrospectively studied 180 placentas sent to the Department of Pathology in UZ Leuven or AZ Turnhout between January 2020 and August 2022, from non-vaccinated and vaccinated mothers suffering a SARS-CoV-2 proven infection during pregnancy. All reports and hematoxylin-eosin stained sections were revised by two pathologists to determine the presence of histopathological lesions that have been described in SARS-CoV-2 infection. SARS-CoV-2 immunostainings were available for a subgroup of 109 placentas. We gathered clinical data: date of delivery, date of positive serologic test result, vaccination status, SARS-CoV-2 variant and outcome of the pregnancy. RESULTS: Of the 180 placentas, 37,2% showed histopathological lesions and in 12,8% an immunohistochemically proven SARS-CoV-2 placentitis was present. SARS-CoV-2 immunohistochemical positivity was only seen in non-vaccinated mothers. The risk of fetal demise was more than 5 times higher for non-vaccinated mothers and their placentas showed significantly more syncytiotrophoblast necrosis and chronic histiocytic intervillositis compared to vaccinated mothers (both p < 0,001). DISCUSSION: Maternal vaccination was associated with a reduced risk of SARS-CoV-2 placentitis and stillbirth. This study provides new evidence of the protective effect of vaccination on the placenta.

Amniopatch procedure after previable iatrogenic rupture of the membranes: a two-center review.

OBJECTIVE: This study aimed to analyze success rates and pregnancy outcomes of amniopatch procedures for previable iatrogenic preterm prelabour rupture of the membranes (PPROM) with associated oligohydramnios. METHODS: Retrospective analysis of amniopatch procedures performed at the University Hospitals Leuven, Belgium, and the Mount Sinai Hospital Toronto, Canada. Cases were analyzed overall and in two sub-groups: PPROM after a needle-based procedure (NP group, n = 13) or after fetoscopic intervention (FI group, n = 11). Complete technical success was defined as cessation of leakage and normalization of amniotic fluid volume, partial success as cessation of leakage, or re-establishment of volume. Further outcomes were pregnancy duration and outcome, fetal/neonatal morbidity and mortality, and maternal morbidity. RESULTS: Gestational age at amniopatch was comparable in both groups (NP: 20.1, FI: 21.0 weeks). Amniopatch was completely and partially successful in 29% (NP: 31%; FI: 27%) and 29% (NP: 15%; FI: 45%), respectively. Mean gestational age at delivery was 27.5 weeks (NP: 25.5; FI: 29.4 weeks). Overall neonatal survival was 17/31 (55%) (NP: 4/13 (31%), FI: 13/18 (72%); p = .02). Chorioamnionitis occurred in three cases, two associated with maternal sepsis. Severe neonatal morbidity occurred in two survivors. CONCLUSION: Amniopatch for iPPROM was successful in 58%, with an overall live birth rate of 68% and survival to discharge of 55%.

Sonographic evaluation of vascular pulmonary reactivity following oxygen administration in fetuses with normal lung development.

OBJECTIVE: This study aimed to establish nomograms for sonographic assessment of fetal pulmonary vascular reactivity following maternal hyperoxygenation. STUDY DESIGN: Sixty-two healthy fetuses were assessed at four weekly intervals from 26 weeks onwards. Pulmonary reactivity was evaluated using Doppler ultrasound in the main pulmonary artery and in the first branch of this main pulmonary artery. The difference in pulsatility index (∆PI) during maternal inhalation of a mixture of room air and oxygen (9 L/min) for at least 10 min was expressed as a percentage. Nomograms were constructed, and Kaplan-Meier curves were used to express the occurrence of a reactive test (∆PI ≥ 20%) with advancing gestation. RESULTS: In the first branch, linear regression analysis revealed a significant correlation of ∆PI (%) with gestational age (r(2) = 0.04, p = 0.0057). Large inter-individual and intra-individual variability was noted. The ∆PI (%) in the main pulmonary artery remained constant throughout gestation (6.62 ± 17.83%). CONCLUSION: Vascular reactivity in the pulmonary circulation increases in the first branch of the pulmonary artery. Large individual variability is limiting its use as a management tool.

Fetoscopic release of an amniotic band with risk of amputation: case report and review of the literature.

Amniotic bands can cause limb amputation as well as intrauterine fetal demise. Fetoscopic release of amniotic bands has been shown to rescue limb function. Herein, we describe an interesting case of an amniotic band wrapped around the right forearm as well as the umbilical cord, which was released by fetoscopy. Following the procedure, the blood flow in the forearm was restored and the edema gradually reduced. Full functionality of the arm was confirmed after birth, though the esthetic problem of the imprint of the band on the arm persisted. Furthermore, we review the available literature regarding fetoscopic interventions in amniotic band syndrome.

Comparison of Doppler-based and three-dimensional methods for fetal cardiac output measurement.

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.

Congenital cystic adenomatoid malformations of the lung: a retrospective study of diagnosis, treatment strategy and postoperative morbidity in surgically treated patients.

OBJECTIVES: The purpose of this study was to evaluate the diagnosis of, clinical signs of and strategy for congenital cystic adenomatoid malformations (CCAM). METHODS: In this retrospective study, patients who had thoracic surgery for CCAM lesions at the University Hospitals of Leuven from July 1993 to July 2016 were identified. Data on diagnosis, prenatal ultrasound findings, clinical signs, lesion site, CCAM type, associated anomalies, imaging, surgical approach and postoperative morbidity were reviewed. The Fisher exact and Mann-Whitney tests were used as appropriate. RESULTS: A total of 55 patients were identified with CCAM. In 65% (n = 36/55), CCAM was detected on prenatal ultrasound scans. Prenatal symptoms due to hydrops or mass effect were present in 22% (n = 8/36), 6 of whom eventually needed prenatal intervention (thoracoamniotic shunting or intrauterine puncture). Elective surgery was performed in 40% of patients (n = 22/55); others developed clinical signs that indicated the need for semi-urgent surgery, with clinical signs of pulmonary infection and respiratory distress being the most common. Most patients had a single lobectomy via a minithoracotomy. Postoperative complications and length of stay were significantly higher in patients with CCAM with preoperative clinical signs. CONCLUSIONS: Surgery in asymptomatic patients with CCAM can be performed safely with few postoperative complications and can be planned at a young age in patients with a high risk of developing clinical signs later in life.