Foong Y. Lim

Prevalence and progression of recipient-twin cardiomyopathy in early-stage twin–twin transfusion syndrome

The management of twin–twin transfusion syndrome (TTTS) in its early stages (Quintero Stages I and II) is controversial. We describe the prevalence, severity, incidence and rate of progression of recipient‐twin cardiomyopathy in Stages I and II TTTS.

Late gestation fetal magnetic resonance imaging–derived total lung volume predicts postnatal survival and need for extracorporeal membrane oxygenation support in isolated congenital diaphragmatic hernia

PURPOSE Magnetic resonance imaging (MRI) has been used as an imaging modality to assess pulmonary hypoplasia in congenital diaphragmatic hernias (CDHs). The objective of this study was to determine if there is a correlation between late gestational fetal MRI-derived total lung volumes (TLVs) and CDH outcomes. METHODS From 2006 to 2009, 44 patients met criteria of an isolated CDH with a late gestational MRI evaluation. The prenatal TLV (in milliliters) was obtained between 32 and 34 weeks gestation. The measured study outcomes included survival, need for extracorporeal membrane oxygenation (ECMO), and length of stay. RESULTS There were 39 left and 5 right CDH patients. The average TLV was significantly lower for nonsurvivors (P = .01), and there was a significant association between lower TLV and the need for ECMO (P = .0001). When stratified by TLV, patients with a TLV of greater than 40 mL had a 90% survival vs 35% survival for a TLV of less than 20 mL. Furthermore, patients with a TLV greater than 40 mL had a lower rate of ECMO use (10%) than patients with a TLV of less than 20 mL (86%). Shorter length of stay was found to correlate with increasing TLV (P = .022). CONCLUSION Late gestation fetal MRI-derived TLV significantly correlates with postnatal survival and need for ECMO. Fetal MRI may be useful for the evaluation of patients who present late in gestation with a CDH.

Tissue-engineered provisional matrix as a novel approach to enhance diabetic wound healing.

Inherent pathologies associated with diabetic wound microenvironment including increased proteolysis, inflammatory dysregulation, and impaired neovascularization prevent timely resolution of chronic diabetic ulcers. It is hypothesized that augmentation of local wound microenvironment with a stable provisional matrix formed by proteolysis‐resistant angiogenic peptide nanofibers (NFs) will create permissive environment for attenuated inflammation, enhanced neovascularization, and improved diabetic wound healing. Using murine excisional wound healing models, full‐thickness dorsal skin wounds were treated with either NFs or control solutions (phosphate buffered saline; hyaluronic acid) and analyzed for morphology, inflammatory response, neovascularization, and biomechanical properties. NF treatment of diabetic wounds stimulated formation of a robust pro‐angiogenic in situ tissue‐engineered provisional matrix leading to a significant decrease in wound inflammatory cell infiltration and proinflammatory interleukin‐6 levels, a significant increase in endothelial and endothelial progenitor cell infiltration, vascular endothelial growth factor levels, and neovascularization (day 7), as well as improved wound morphology, accelerated wound closure, and significantly stronger repair tissue (day 28). These results suggest that appropriate design of provisional matrix may compensate for some of the complex disruptions in diabetic wound microenvironment and provide missing cues to cells and direct in situ responses toward improved healing, which is promising for future development of new therapies for diabetic ulcers.

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 factor(121). 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.

Favorable outcomes in high-risk congenital pulmonary airway malformations treated with multiple courses of maternal betamethasone

BACKGROUND/PURPOSE Congenital pulmonary airway malformations (CPAMs) are rare congenital lung lesions often diagnosed by prenatal ultrasound. High-risk cases can result in hydrops and prenatal or postnatal demise. Antenatal betamethasone has resulted in improved survival but it is unclear how to manage patients who do not respond to a single course. METHODS We present a bi-institutional retrospective review of patients treated with multiple courses of prenatal steroids for high-risk CPAMs between 2007 and 2013. RESULTS Nine patients met inclusion criteria. All but one either had an increased CPAM volume ratio (CVR) or number of fluid-containing compartments involved after a single course of antenatal betamethasone, prompting additional courses. Four patients stabilized, three improved and two progressed after the second course. The two cases with disease progression underwent an in utero resection. There were one in utero fetal demise and two deaths within the delivery room. Both fetuses that underwent a fetal resection died. All but one mother who delivered a viable fetus had complications of pregnancy. CONCLUSIONS Multiple courses of antenatal betamethasone for high-risk fetal CPAMs often result in favorable short-term outcomes without the need for open fetal resection. Pregnancy complications are common and women within this cohort should be monitored closely.

Assessment of fetal cardiomyopathy in early‐stage twin–twin transfusion syndrome: comparison between commonly reported cardiovascular assessment scores

To assess the relationship between commonly reported fetal cardiomyopathy scoring systems in early‐stage twin–twin transfusion syndrome (TTTS).

TdTomato and EGFP identification in histological sections: insight and alternatives

Abstract Tandem dimer Tomato (tdTomato) provides a useful alternative to enhanced green fluorescent protein (eGFP) for performing simultaneous detection of fluorescent protein in histological sections together with fluorescence immunohistochemistry (IHC). eGFP has many properties that make it useful for cell labeling; however, during simultaneous fluorescence IHC, the usefulness of eGFP may be limited. This limitation results from a fixation step required to identify eGFP in histological tissue sections that can mask antibody epitopes and adversely affect staining intensity. An alternative fluorescent protein, tdTomato, may assist concurrent detection of fluorescent protein within tissue sections and fluorescence IHC, because detection of tdTomato does not require tissue fixation. Tissue sections were obtained from various organs of mice ubiquitously expressing eGFP or tdTomato that were either unfixed or fixed with 4% paraformaldehyde. These tissues later were combined with fluorescence IHC. Both eGFP and tdTomato displayed robust signals in fixed frozen sections. Only tdTomato fluorescence, however, was detected in unfixed frozen sections. Simultaneous detection of fluorescence IHC and fluorescent protein in histological sections was observed only in unfixed frozen tdTomato tissue. For this reason, tdTomato is a useful substitute for eGFP for cell labeling when simultaneous fluorescence IHC is required.

Use of an Amnioport to Maintain Amniotic Fluid Volume in Fetuses with Oligohydramnios Secondary to Lower Urinary Tract Obstruction or Fetal Renal Anomalies.

Objective: We describe a technique to maintain amniotic fluid in fetuses with severe oligo-/anhydramnios secondary to lower urinary tract obstruction or fetal renal disease when urine production is inadequate to maintain a normal amniotic fluid volume (AFV). Methods: An amnioport was inserted into the amniotic space. The catheter was secured to prevent dislodgment and tunneled to a subcutaneous reservoir. The reservoir was accessed as necessary, infusing normal saline to maintain AFV. Pregnancy continued until term or indicated delivery. Results: Since 2010, 15 patients in this category were considered for an amnioport. Six chose comfort care and one elected percutaneous amnioinfusions. Nine amnioport procedures were performed in eight patients. There were no fetal deaths. All eight had successful restoration and maintenance of amniotic fluid. Delivery ranged from 9 to 96 days after placement (mean 63.7 days). One died due to unrecognized laryngeal web and another one died of pulmonary hypoplasia after preterm premature rupture of membranes. None of the remaining six had pulmonary hypoplasia. Three remain alive. Discussion: Severe oligo-/anhydramnios in the second trimester secondary to fetal anomalies is almost uniformly lethal due to pulmonary hypoplasia without restoration of amniotic fluid. The amnioport procedure may allow pulmonary survival but commits families to postnatal care decisions regarding pulmonary and renal complications.

Management of fetal teratomas

Fetal teratomas are the most common tumors diagnosed prenatally. The majority of these tumors are benign and cured by complete resection of the mass during the neonatal period. Prenatal diagnosis has improved the perinatal management of these lesions and especially for the teratomas that might benefit from fetal intervention. A comprehensive prenatal evaluation including conventional ultrasounds, Doppler, echocardiography and fetal MRI, is essential for an effective counseling and perinatal management. Antenatal counseling helps the parents to better understand the natural history, fetal intervention, and perinatal management of these tumors, which differ dramatically depending on their size and location. Fetal surgical debulking improves survival in cases of sacrococcygeal teratoma with cardiac decompensation. Additionally, the use of an EXIT procedure reduces the morbidity and mortality if a complicated delivery in cases of cervical and mediastinal teratomas. Here, we offer an overview of all fetal teratomas and their recommended management, with emphasis on in utero treatment options.

Pre- and post-operative visualization of neonatal esophageal atresia/tracheoesophageal fistula via magnetic resonance imaging

Esophageal atresia (EA) is a relatively uncommon congenital anomaly, often observed in conjunction with tracheoesophageal fistula (TEF). Surgical repair in neonates typically takes place with little information about the pre-existing EA/TEF structure because there are currently no acceptable tools for evaluating EA/TEF anatomy prior to repair; chest x-ray radiograph does not identify malformation sub-type or gap length, while x-ray computed tomography (CT) demonstrate an unacceptably high exposure to ionizing radiation. There is a need for safe imaging methods to evaluate pre-operative EA/TEF anatomy, which would add value in surgical planning; this need may be met with high-resolution structural MRI. We report three cases of Type-C EA/TEF in neonates. Patients were imaged prior to surgical repair using high-resolution ultrashort echo time (UTE) magnetic resonance imaging (MRI) to visualize tracheoesophageal anatomy and allow for informed surgical planning and risk management. One of the three patients was imaged post-repair to evaluate surgical efficacy and evolution of the tracheoesophageal anatomy.