Ruano, Rodrigo

INTRODUCTION: Umbilical vein varix (UVV) is a focal dilation of the fetal umbilical vein. Clinical significance is not clearly established but it has been associated with adverse outcomes. This study investigates the clinical outcomes of UVV diagnosed during pregnancy. METHODS: We performed a multicenter retrospective (USA, Chile, Italy and Brazil) study by reviewing 19 fetuses diagnosed with UVV between 2012 and 2017. We investigated gestational age at diagnosis and at delivery, UVV maximum diameter, fetal gender, associated anatomical anomalies, intrauterine growth restriction, fetal demise, type of delivery, birth weight, Apgar scores. RESULTS: UVV was diagnosed at 26.4+/- 4.4 weeks of gestation. Maximum diameter of the defect at diagnosis typically was 13.1+/- 5mm. The majority of fetuses were male (n=12, 63%). Growth restriction was diagnosed in 26% (n=5) of the fetuses. Seventeen (89%) infants survived. Fetal demise occurred in 2 (11%) patients; one was associated with structural anomalies, and the other fetus did not have any other associated anomaly. Vaginal delivery was performed in 10 (53%) patients; median weight at birth was 2870 g (270-4960 g). Median Apgar scores were 8 and 9 on 1st and 5th minutes consecutively (ranging from 0 to 10). Genetic and anatomical anomalies were present in 21% (n=4) of the fetuses and included: karyotype 47,XY+13, cleft lip and palate, cerebellar hypoplasia, aortic hypoplasia, cardiomegaly, Blake's pouch cyst, ambiguous genitalia, campomelic dysplasia with SOX9 mutation. CONCLUSION: UVV is a rare congenital condition that is usually associated with low frequency of other structural/genetic anomalies and with good prognosis. ACKNOWLEDGEMENTS: Waldo Sepulveda, Edward Araujo Junior, Mari Charisse Trinidad, and Heron Werner

ObjectivesThis study investigated the reproducibility of standardization of lung‐to‐head ratio measurements in congenital diaphragmatic hernia (CDH) at our center among sonographers after we standardized the method.MethodsWe reviewed ultrasound images of 12 fetuses with CDH at Mayo Clinic from 2010 to 2016. Nine operators (1 maternal‐fetal medicine specialist with experience in measuring the lung‐to‐head ratio and 8 sonographers), who were blinded to previous findings, reviewed 33 selected images from 12 fetuses with left CDH. The method for lung‐to‐head ratio measurement was standardized before starting the measurements. The lung‐to‐head ratio was assessed by different methods to obtain the lung areas: anteroposterior, longest, and area tracing. We evaluated the correlation between operators using the intraclass correlation coefficient (ICC). We also compared agreement between the sonographers and a physician with experience in measuring the lung‐to‐head ratio using a Bland‐Altman analysis.ResultsThe methods with the best interoperator reproducibility were the standardized anteroposterior lung‐to‐head ratio (ICC, 0.69) and the standardized lung‐to‐head ratio tracing (ICC, 0.65) compared to the longest lung‐to‐head ratio (ICC, 0.56). The standardized lung‐to‐head ratio tracing had the best agreement among sonographers and the physician (bias, 0.11; limits of agreement, −0.27 to +0.49) than the anteroposterior lung‐to‐head ratio (bias, 0.35; limits of agreement, −0.13 to + 0.83) and the longest lung‐to‐head ratio (bias, 0.27; limits of agreement, −0.35 to +0.89).ConclusionsWe demonstrated that the lung‐to‐head ratio tracing method has high interoperator reproducibility and the best agreement among the operators at our center. Further multicenter studies are necessary to confirm our results.

What's already known about this topic? LUTO is a rare but life‐threatening condition affecting the fetus and child in which prenatal therapy is currently being offered but remains controversial. A recent RCT comparing this treatment to post‐natal treatment in selected cases failed to come to robust conclusions due to under‐recruitment. So, the controversy persists. What does this study add? In this debate, 2 renown experts in the field develop their arguments pro and against shunting for all LUTO cases based on the current literature and a long‐standing clinical experience in the field of fetal therapy.

ProblemPregnancy requires balance between tolerance to the haploidentical fetus and the mother's ability to mount immune responses. There are parallels to this phenomenon that occur in metastatic cancer. We assessed soluble program death ligand‐1 soluble PD‐L1 (sPD‐L1) and galectin‐9 in the blood of pregnant women during gestation as these molecules are highly involved in immune suppression during cancer.Method of studyMaternal blood was collected from 30 primigravida women at monthly intervals during pregnancy, delivery and 6‐week post‐partum. Blood was analyzed for sPD‐L1 and galectin‐9 concentrations by ELISA. Term placentas were collected in formalin and IHC was completed for PD‐L1 and galectin‐9 expression.ResultsMaternal blood levels of sPD‐L1 (0.438 ng/mL) and galectin‐9 (1976 pg/mL) were elevated early in normal pregnancies compared to non‐pregnant controls (0.242 ng/mL and 773 pg/mL, respectively). sPD‐L1 increased throughout gestation, whereas galectin‐9 remained elevated until parturition; both proteins returned to control levels post‐partum. Women carrying male fetuses had significantly higher galectin‐9 levels, but not sPD‐L1, than those carrying females (2263 pg/mL vs 1874 pg/mL; P = .0005). Trophoblast cells of the term placenta coexpress galectin‐9 and PD‐L1.ConclusionImmune‐regulatory molecules galectin‐9 and sPD‐L1 increased during pregnancy and may play a role in immune tolerance that is critical for the fetus.

What is already known about this topic? Lower urinary tract obstruction is associated with high morbidity and mortality. Fetal cystoscopy may allow the correct identification of the etiology of the obstruction and may provide the adequate treatment. What does this study add? Three‐dimensional virtual navigation is a noninvasive approach that provides an immersive virtual reality in the assessment of fetal structures. Three‐dimensional virtual cystoscopy provides a noninvasive evaluation of fetal lower urinary tract obstruction that in the future may help in the selection of candidates for fetal cystoscopy.

AbstractObjectiveTo evaluate the association between ultrasonographic renal parameters and urine biochemistry in fetuses with lower urinary tract obstruction (LUTO).MethodsData were collected prospectively from 31 consecutive fetuses with LUTO that underwent vesicocentesis for fetal urinary biochemistry between April 2013 and September 2015. The following renal ultrasound markers were assessed immediately before the vesicocentesis: renal echogenicity, presence of cortical cysts, presence of findings suggestive of ‘renal dysplasia’ (hyperechogenic cystic kidneys with no cortical‐medullary differentiation) and severe oligohydramnios (amniotic fluid < 5th percentile). The association of these parameters to the fetal urinary concentration of sodium, chloride, calcium, osmolality and beta2‐microglobulin was investigated by logistic regression analysis.ResultsThere was no relationship between any of the ultrasonographic fetal renal characteristics and fetal urinary biochemistry.ConclusionsIn LUTO, the ultrasound appearance of the fetal kidneys and urinary biochemistry are not correlated. It may be better to take both ultrasound and biochemistry into account when evaluating fetuses with fetal LUTO. © 2016 John Wiley & Sons, Ltd.

ABSTRACTObjectiveTo evaluate the effect on perinatal and postnatal survival of vesicoamniotic shunt (VAS) as treatment for fetal lower urinary tract obstruction (LUTO).MethodsAn electronic search of Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews and Scopus using relevant search terms was conducted from inception to June 2015 to identify studies comparing outcomes of VAS vs conservative management for treatment of LUTO. Cohort studies and clinical trials were considered eligible. Single‐arm studies and studies that did not report survival were excluded. Sample size and language were not criteria for exclusion. Two reviewers extracted independently data in a standardized form, including study characteristics and results. Primary outcomes were perinatal and postnatal survival. Secondary outcome was postnatal renal function. Data on fetal survival were expressed as odds ratio (OR) and 95% CI.ResultsOf the 423 abstracts retrieved, nine studies were eligible for inclusion. These studies included 112 fetuses treated with VAS and 134 that were managed conservatively. There was heterogeneity in study design. Although the data demonstrated a difference in effect estimates between the study arms in terms of perinatal survival (OR, 2.54 (95% CI, 1.14–5.67)), there was no difference in 6–12‐month survival (OR, 1.77 (95% CI, 0.25–12.71)) or 2‐year survival (OR, 1.81 (95% CI, 0.09–38.03)). In addition, there was no difference in effect on postnatal renal function between fetuses that underwent intervention and those that did not (OR, 2.09 (95% CI, 0.74–5.94)).ConclusionsAvailable data seem to support an advantage for perinatal survival in fetuses treated with VAS compared with conservative management. However, 1–2‐year survival and outcome of renal function after VAS procedure remain uncertain. Further studies are necessary to evaluate the effectiveness of fetal intervention for LUTO based on different severity of the disease, due to the very low quality of the studies according to GRADE guidelines. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.