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Hui L.,Mother Infant Research Institute | Hui L.,University of Sydney | Wick H.C.,Tufts University | Moise K.J.,University of Houston | And 9 more authors.
Prenatal Diagnosis | Year: 2013

Objective: The objective of this study was to understand the biological pathways involved in twin-twin transfusion syndrome (TTTS) by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA. Methods: A prospective whole transcriptome microarray study analyzing cell-free RNA in AF from TTTS recipient twins and singleton controls was carried out. Significantly differentially regulated genes in TTTS cases (N=8) versus matched controls (N=8) were identified and pathways analyses performed. Significant gene expression differences between stage II TTTS recipients (N=5) and stage III TTTS recipients with abnormal Doppler measurements (N=5) were also analyzed. Results: Analysis of paired data from TTTS cases and controls revealed differential expression of 801 genes, which were significantly enriched for neurological disease and cardiovascular system pathways. We also identified cardiovascular genes and pathways associated with the presence of critically abnormal Doppler measurements in stage III TTTS recipients. Conclusions: This study provides the first transcriptome-wide data on the impact of TTTS on fetal development. Our results show that gene expression involving neurological and cardiovascular pathways are altered in recipient fetuses prior to surgical treatment. This has relevance for the origins of long-term complications seen in survivors and for the development of future fetal biomarkers. © 2013 John Wiley & Sons, Ltd.

Ruano R.,University of Sao Paulo | Ruano R.,Baylor College of Medicine | Ruano R.,Texas Childrens Fetal Center | Sananes N.,Hopitaux Universitaires Of Strasbourg | And 10 more authors.
Ultrasound in Obstetrics and Gynecology | Year: 2015

Objective: To evaluate the efficacy of fetal intervention using fetal cystoscopy or vesicoamniotic shunting in the treatment of severe lower urinary obstruction (LUTO). Methods: A cohort of 111 fetuses with severe LUTO attending two centers between January 1990 and August 2013 were included retrospectively. Fetuses were categorized into three groups based on the method of intervention: (1) fetal cystoscopy, (2) vesicoamniotic shunting or (3) no intervention. Multivariate analyses were performed to determine the probability of survival and normal renal function until 6 months of age by comparing fetal cystoscopy and vesicoamniotic shunting to no fetal intervention. Results: Of the 111 fetuses with severe LUTO that were included in the analysis, fetal cystoscopy was performed in 34, vesicoamniotic shunting was performed in 16 and there was no fetal intervention in 61. Gestational age at diagnosis, method of fetal intervention and cause of bladder obstruction were associated with prognosis. In multivariate analysis and after adjustment for potential confounders (considering all causes of LUTO) the overall probability of survival was significantly higher with fetal cystoscopy and vesicoamniotic shunting when compared to no intervention (adjusted relative risk (ARR), 1.86 (95% CI, 1.01-3.42; P = 0.048) and ARR, 1.73 (95% CI, 1.01-3.08; P = 0.04) respectively). A clear trend for normal renal function was present in the fetal cystoscopy group (ARR, 1.73 (95% CI, 0.97-3.08; P = 0.06)) but was not observed in the vesicoamniotic shunt group (ARR, 1.16 (95% CI, 0.86-1.55; P = 0.33)). In cases in which there was a postnatal diagnosis of posterior urethral valves, fetal cystoscopy was effective in improving both the 6-month survival rate and renal function (ARR, 4.10 (95% CI, 1.75-9.62; P < 0.01) and 2.66 (95% CI, 1.25-5.70; P = 0.01) respectively) while vesicoamniotic shunting was associated only with an improvement in the 6-month survival rate (ARR, 3.76 (95% CI, 1.42-9.97; P < 0.01)) with no effect on renal function (ARR, 1.03 (95% CI, 0.49-2.17, P = 0.93)). Conclusion: Fetal cystoscopy and vesicoamniotic shunting improve the 6-month survival rate in cases of severe LUTO. However, only fetal cystoscopy may prevent impairment of renal function in fetuses with posterior urethral valves. Our data support the idea of performing a subsequent randomized controlled trial to compare the effectiveness of fetal cystoscopy vs vesicoamniotic shunting for severe fetal LUTO. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Connell J.P.,Rice University | Augustini E.,Rice University | Moise K.J.,Baylor College of Medicine | Moise K.J.,Texas Childrens Fetal Center | And 3 more authors.
Journal of Cellular and Molecular Medicine | Year: 2013

Amniotic fluid-derived stem cells (AFSC) have been reported to differentiate into cardiomyocyte-like cells and form gap junctions when directly mixed and cultured with neonatal rat ventricular myocytes (NRVM). This study investigated whether or not culture of AFSC on the opposite side of a Transwell membrane from NRVM, allowing for contact and communication without confounding factors such as cell fusion, could direct cardiac differentiation and enhance gap junction formation. Results were compared to shared media (Transwell), conditioned media and monoculture media controls. After a 2-week culture period, AFSC did not express cardiac myosin heavy chain or troponin T in any co-culture group. Protein expression of cardiac calsequestrin 2 was up-regulated in direct transmembrane co-cultures and media control cultures compared to the other experimental groups, but all groups were up-regulated compared with undifferentiated AFSC cultures. Gap junction communication, assessed with a scrape-loading dye transfer assay, was significantly increased in direct transmembrane co-cultures compared to all other conditions. Gap junction communication corresponded with increased connexin 43 gene expression and decreased phosphorylation of connexin 43. Our results suggest that direct transmembrane co-culture does not induce cardiomyocyte differentiation of AFSC, though calsequestrin expression is increased. However, direct transmembrane co-culture does enhance connexin-43-mediated gap junction communication between AFSC. © 2013 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Cass D.L.,Baylor College of Medicine | Cass D.L.,Texas Childrens Fetal Center
Seminars in Fetal and Neonatal Medicine | Year: 2011

The field of neonatal surgery is now inextricably linked to the field of obstetrics. Neonatologists and surgical specialists experienced with the postnatal management and outcomes of infants with various disorders now look in utero along with obstetricians and fetal medicine specialists to characterize the development and well-being of fetuses with congenital anomalies with a goal to optimize fetal, perinatal and postnatal management. The purpose of this article is to examine how prenatal diagnosis and therapy has influenced neonatal surgery. An overview of prenatal diagnosis and the evolution of fetal therapy are provided. In addition, we review the impact of prenatal diagnosis and therapy on the management and outcomes of infants with specific anomalies, including congenital lung malformations, sacrococcygeal teratoma, myelomeningocele, giant fetal neck masses, diaphragmatic hernia and congenital heart defects. © 2011 Elsevier Ltd.

Molina S.,Texas Childrens Fetal Center | Papanna R.,Texas Childrens Fetal Center | Moise Jr. K.J.,Texas Childrens Fetal Center | Johnson A.,Texas Childrens Fetal Center
Ultrasound in Obstetrics and Gynecology | Year: 2010

Objective To determine practice patterns for evaluation and treatment of Stage I twin-to-twin transfusion syndrome (TTTS) among international physicians. Methods An e-mail cross-sectional survey of members from the IFMSS, NAFTNet and SMFM societies and participants at a Eurofoetus-sponsored TTTS meeting was undertaken between May 2008 and November 2008. Questionnaires consisted of physician demographics and their recommendations for managing Stage I TTTS. Alternative therapies to expectant management were assessed based on the following special circumstances of the patient: residence more than 200 miles from the center, severe symptoms, or a cervical length of ≤15 mm. Results Eighty-one surveys were returned, giving a response rate of 84%. Five surveys were excluded as a result of duplication or missing data. Of the remaining 76 surveys, 48 were from North America, 20 were from Europe and eight were from other continents. Expectant management was the predominant recommendation (78%), followed by amnioreduction (11%), laser ablation (11%) and septostomy (1%). Recommendations for amnioreduction were exclusively from North American centers. Laser centers recommended expectant management more frequently than non-laser facilities (89% vs. 59%; P < 0.01). When examples of special patient circumstances were presented, North American centers changed their recommendation from expectant management to amnioreduction more often than did European centers. However, a greater proportion of European centers recommended laser surgery for special patient circumstances. Conclusion Expectant management remains the predominant management of Stage I TTTS. In some patient circumstances, North American centers are more likely to recommend amnioreduction while European centers aremore likely to recommend laser therapy. A randomizedcontrolled trial will be necessary to evaluate the most effi-cacious management strategy for Stage I TTTS. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.

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