Ruano, Rodrigo

ABSTRACTObjectiveCongenital lower urinary tract obstruction (LUTO) is a rare condition with high perinatal mortality and morbidity when associated with severe oligohydramnios or anhydramnios in the second trimester of pregnancy. Severe pulmonary hypoplasia and end‐stage renal disease are the underlying causes of poor neonatal outcome in these cases. However, little is known about the subset of fetal LUTO that is associated with a normal volume of amniotic fluid at midgestation. The objective of the current study was to describe the natural history, underlying causes, survival and postnatal renal function outcomes in pregnancies with fetal LUTO and normal amniotic fluid volume during the second trimester of pregnancy.MethodsThis was a retrospective study of all pregnancies with fetal LUTO and normal amniotic fluid volume in the second trimester that received prenatal and postnatal care at our quaternary care institution between 2013 and 2017. Data on demographic characteristics, fetal interventions, perinatal survival, need for neonatal respiratory support, postnatal renal function and need for dialysis at the age of 1 and 24 months were analyzed.ResultsOf the 18 fetuses that met the study criteria, 17 (94.4%) survived the perinatal period. Eleven (61.1%) pregnancies developed oligohydramnios in the third trimester, six of which were eligible for and underwent fetal intervention with vesicoamniotic shunt placement, which was performed successfully in all six cases. Two (11.1%) neonates required respiratory support owing to pulmonary hypoplasia. At the age of 2 years, 14 children had follow‐up information available, two (14.3%) of whom had normal renal function, eight (57.1%) had developed some degree of chronic kidney disease (Stage 1–4) and four (28.6%) had developed end‐stage renal disease (ESRD), including two who had already manifested ESRD in the neonatal period.ConclusionsMost fetuses diagnosed prenatally with LUTO that is associated with a normal volume of amniotic fluid at midgestation will have a favorable outcome in terms of perinatal survival and few will need long‐term respiratory support. However, these children are still at increased risk for chronic renal disease, ESRD and need for renal replacement therapy. Larger multicenter studies are needed to characterize the prenatal factors associated with postnatal renal function, and to investigate the role of fetal intervention in the group of fetuses that present with late‐onset oligohydramnios and evidence of preserved fetal renal function. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

AbstractObjectiveTo determine the antenatal sonographic lung area measurement method in left congenital diaphragmatic hernia (CDH) with the highest interrater agreement among North American Fetal Therapy Network (NAFTNet) centers within and outside the fetoscopic tracheal occlusion (FETO) consortium and in comparison with a European “expert” reviewer (ER).MethodsNineteen members from nine FETO consortium centers and 29 reviewers from 17 non‐FETO centers reviewed ultrasound clips of the chest from 13 fetuses with isolated left CDH and were asked to select a static plane for lung area measurement using anteroposterior (AP), longest, and trace methods. Interrater agreement in lung area measurements was determined using intraclass correlation coefficient (ICC). Bland‐Altman analysis was used to evaluate mean difference (bias) between NAFTNet reviewers and ER.ResultsAmong FETO centers, agreement was highest using trace (ICC 0.94; 95% CI, 0.83‐0.98), followed by longest (ICC 0.89; 95% CI, 0.75‐0.97) and lowest for A‐P (ICC 0.83; 95% CI, 0.67‐0.94). Similar trends were noted in non‐FETO centers. When compared with ER, bias was lowest for trace: 14 ± 38 mm2 and 19 ± 36 mm2 for FETO and non‐FETO centers, respectively.ConclusionThe trace method demonstrated the highest interrater agreement and lowest bias for lung area estimation in left CDH across NAFTNet.

ObjectivesThe aim of this study was to investigate the reproducibility of a standardized method to assess the ultrasound liver‐to‐thoracic area ratio in fetuses with congenital diaphragmatic hernia.MethodsWe selected 24 images of 9 fetuses diagnosed with left‐sided at our institution between January 2010 and December 2017. Eight operators (1 maternal‐fetal medicine specialist and 7 sonographers) reviewed the selected images and assessed the ultrasound liver‐to‐thoracic area ratio according to a standardized protocol. We evaluated the correlation between operators using the intraclass correlation coefficient and compared agreement between the sonographers and a physician with experience in measuring the ultrasound liver‐to‐thoracic area ratio using a Bland‐Altman analysis.ResultsGood intraoperator reproducibility was observed for the standardized ultrasound liver‐to‐thoracic area ratio (intraclass correlation coefficient, 0.78). Good agreement among sonographers and the physician was also observed for the standardized measurements (bias, 0.01; precision, 0.03; limits of agreement, –0.05 to + 0.07).ConclusionsWe demonstrated that good intraoperator and interoperator reproducibility of ultrasound liver‐to‐thoracic area ratio assessment is feasible after standardizing the method in our center.

AbstractMelatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis. Pathological pregnancies, such as preeclampsia, are associated with placental H/R, and decreased placental melatonin synthesis as well as lower melatonin levels in the placenta and maternal plasma. However, the effects of exogenous melatonin on inflammation and autophagy induced by pregnancy complications associated with H/R await investigation. This study aimed to determine as to whether melatonin protects human primary villous trophoblasts against H/R‐induced autophagy, inflammation, and apoptosis. Human primary villous cytotrophoblasts were isolated and immunopurified from normal term placentas. These cells were then exposed or not to 1 mmol/L melatonin for 72 hour in normoxia (8% O2), thereby inducing differentiation into syncytiotrophoblast that was then exposed to H/R (0.5% O2, for 4 hour) or normoxia. H/R decreased endogenous melatonin synthesis (by 68%) and interleukin (IL)‐10 levels (by 72%), coupled to increased tumor necrosis factor (TNF) (by 114%), IL‐6 (by 55%), and NFκB (by 399%), compared to normoxia. Melatonin treatment reversed the H/R effect, restoring IL‐10, TNF, and IL‐6 levels to those of the normoxia condition. Melatonin, as well as NFκB inhibition, enhanced autophagy activation, consequently increasing syncytiotrophoblast survival in H/R conditions. This study suggests that H/R, which is present in pregnancy complications, inhibits endogenous melatonin production, thereby contributing to reduced syncytiotrophoblast viability. Results indicate that exogenous melatonin treatment may afford protection against H/R‐induced damage, thereby enhancing placental cell survival, and contributing to improved fetal outcomes.

AbstractObjectivesFetal endoscopic tracheal occlusion (FETO) is offered to fetuses with congenital diaphragmatic hernia (CDH) and severe lung hypoplasia to promote lung growth and may secondarily affect left heart growth. The effects of FETO on left heart hypoplasia (LHH) are not described post‐CDH repair.MethodsA retrospective analysis was performed for fetuses with left‐sided CDH who underwent FETO and severity‐matched controls from 2007 to 2016 at our institution. Echocardiographic, ultrasound, and MRI data were reviewed. Left heart dimensions were assessed prenatally and postnatally. Primary clinical outcome evaluated was death.ResultsTwelve FETO patients and 18 controls were identified. Fetal LHH was noted in both groups and worsened after FETO. Postnatal mitral valve dimensions were larger in the FETO group pre‐CDH repair (P = .03). Post‐CDH repair, mitral valve and left ventricular dimensions were not significantly different between groups (P = .79 and P = .63 respectively) while FETO aortic valve dimensions were smaller (P = .04). Extracorporeal membrane oxygenation use was lower in the FETO group. No associations were found between left heart dimensions and outcomes.ConclusionAlthough increased lung growth was seen after FETO, fetal LHH persisted with relative normalization seen post‐repair. Persistent LHH post‐FETO could be secondary to a small contribution of pulmonary venous return to the fetal left heart and increased intrathoracic pressures post‐FETO.