Outcome reporting across randomized trials and observational studies evaluating treatments for twin–twin transfusion syndrome: systematic review

Objective Twin–twin transfusion syndrome (TTTS) is associated with significant mortality and morbidity. Potential treatments for the condition require robust evaluation. The aim of this study was to evaluate outcome reporting across observational studies and randomized controlled trials assessing treatments for TTTS. Methods Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE were searched from inception to August 2016. Observational studies and randomized controlled trials reporting outcome following treatment for TTTS in monochorionic–diamniotic twin pregnancy and monochorionic–triamniotic or dichorionic–triamniotic triplet pregnancy were included. Outcome reporting was systematically extracted and categorized. Results Six randomized trials and 94 observational studies were included, reporting data from 20 071 maternal participants and 3199 children. Six different treatments were evaluated. Included studies reported 62 different outcomes, including six fetal, seven offspring mortality, 25 neonatal, six early childhood and 18 maternal/operative outcomes. Outcomes were reported inconsistently across trials. For example, when considering offspring mortality, 31 (31%) studies reported live birth, 31 (31%) reported intrauterine death, 49 (49%) reported neonatal mortality and 17 (17%) reported perinatal mortality. Four (4%) studies reported respiratory distress syndrome. Only 19 (19%) studies were designed for long‐term follow‐up and 11 (11%) of these reported cerebral palsy. Conclusions Studies evaluating treatments for TTTS have often neglected to report clinically important outcomes, especially neonatal morbidity outcomes, and most are not designed for long‐term follow‐up. The development of a core outcome set could help standardize outcome collection and reporting in TTTS studies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd

The Epidemiology, Genetics and Future Management of Syndactyly

Syndactyly is a condition well documented in current literature due to it being the most common congenital hand defect, with a large aesthetic and functional significance

Prenatal diagnosis and management of the fetus with an abdominal wall defect

Prenatal ultrasound has advanced our understanding of congenital abdominal wall defects. In addition to providing insights into the divergent embryological origins and natural history of abdominal wall defects, ultrasound has had an important impact on the management of these anomalies. For fetuses with gastroschisis, the changes in appearance of the bowel may suggest expeditious delivery. In cases of omphalocele, the presence of additional anomalies is significantly associated with the ultimate prognosis for these fetuses. Giant omphalocele may preclude vaginal delivery secondary to dystocia. Exstrophies of the cloaca and bladder are rare congenital abnormalities that often present complex management issues, including gender reassignment in cases of cloacal exstrophy, for those couples wishing to continue the pregnancy. We believe that the optimal management of a fetus diagnosed with an abdominal wall defect requires a coordinated effort among specialists from maternal fetal medicine, pediatric surgery, and pediatrics

Prenatal diagnosis and management of gastrointestinal anomalies

The increased use of prenatal sonography has led to earlier and more frequent diagnosis of a wide range of gastrointestinal anomalies. Many of these anomalies are associated with other severe cardiac, renal, and genetic abnormalities that may impact on decisions regarding timing and site of delivery. The majority of these patients should be referred to a center that provides perinatal, neonatal, and pediatric surgical expertise. After a complete prenatal evaluation, a decision regarding the site of delivery and the need for subspecialty referral can be made. Prenatal diagnosis of the conditions discussed in this article does not influence the mode of delivery, but subsequent management of the newborn is improved by delivery in a tertiary care center

Expression of human collagenase-3 (MMP-13) by fetal skin fibroblasts is induced by transforming growth factor beta via p38 mitogen-activated protein kinase.

Human collagenase-3 (MMP-13) is characterized by wide substrate specificity and limited tissue specific expression. We have previously noted that human collagenase-3 (MMP-13) is expressed by gingival fibroblasts in culture and during gingival wound repair characterized by minimal scarring. Here we show that human MMP-13 is expressed by dermal fibroblasts during early wound repair in fetal skin grafted on SCID mice. The expression of MMP-13 by fetal skin fibroblasts in monolayer culture was enhanced by transforming growth factor β 1 (TGF- β 1) and TGF- β 3, whereas MMP-13 expression was not detected in neonatal skin fibroblasts. Treatment of fetal skin fibroblasts with TGF- β 1 potently activated p38 mitogen-activated protein kinase (MAPK). Induction of MMP-13 expression by TGF- β 1 was blocked by p38 MAPK inhibitor SB203580, and by adenovirally delivered dominant negative form of p38 α . These observations demonstrate a remarkable difference in the regulation of collagenolytic capacity between fetal and neonatal skin fibroblasts, which suggests a role for MMP-13 in rapid turnover of collagenous matrix during repair of fetal cutaneous wounds, which heal without scar.</div

Placental gene transfer: transgene screening in mice for trophic effects on the placenta

Objective: We hypothesized that gene transfer of select growth factors to the placenta may enhance placental and fetal growth. Thus, we examined the effect of 8 growth factor transgenes on murine placenta. Study Design: Adenoviral-mediated site-specific intraplacental gene transfer of 8 different growth factor transgenes at embryonic day (e) 14 was performed. Transgenes included angiopoietin-1, angiopoietin-2 (Ang-2), basic fibroblast growth factor, hepatocyte growth factor, insulin-like growth factor-1 (IGF-1), placenta growth hormone, platelet-derived growth factor-B (PDGF-B), and vascular endothelial growth factor121. Fetuses and placentas were harvested at e17 and assessed for survival, gene transfer efficiency, placenta area, and fetal and placental weights. Results: Efficient gene transfer to the placenta was detected with minimal dissemination to the fetus. Overexpression of IGF-1, PDGF-B, and Ang-2 resulted in an increase in placenta cross-sectional area. Only Ang-2 gene transfer resulted in increased fetal weight, and only Ang-2 and basic fibroblast growth factor resulted in a change in placental weight. Conclusion: Site-specific placental gene transfer results in efficient gene transfer with minimal dissemination to the fetus. Adenoviral-mediated IGF-1, adenoviral-mediated PDGF-B, and adenoviral-mediated Ang-2 significantly increase placenta growth. © 2009 Mosby, Inc. All rights reserved