Effect of allograft patch closure on incidence of spinal inclusion cyst formation following open fetal myelomeningocele repair.

OBJECTIVE: The aim of this study was to evaluate the incidence of spinal inclusion cyst (sIC) formation after open fetal myelomeningocele (fMMC) repair and the effect of dural patch closure. METHODS: The authors conducted a retrospective review of patients who underwent open fMMC repair at their institution between March 2011 and June 2020. All patients met the criteria for intervention defined by the Management of Myelomeningocele Study (MOMS). The primary outcomes investigated were development of sIC and need for surgical intervention. Secondary outcomes included need for CSF diversion, extent of reversal of hindbrain herniation, and ambulatory status. RESULTS: Of 56 patients who underwent open fMMC repair, 52 had adequate spinal imaging for review. Twelve of these patients (23%) developed sIC (95% CI 0.11-0.35). Six patients experienced symptoms and required surgical detethering with sIC resection. Six additional patients had evidence of sIC on surveillance MRI but remained asymptomatic. The authors found a statistically significant relationship between the use of a dural allograft patch and sIC formation (p = 0.05). In terms of sIC development, there was no statistically significant difference between patients who underwent primary closure and those who received an allograft at the level of the fascia (p = 0.34) or skin (p = 0.26). The rate of hydrocephalus requiring CSF diversion was 52%. Interestingly, 98% of patients had improvement in extent of hindbrain herniation. Dural patch closure did not have any effect on the rate of progressive hydrocephalus (p = 0.33) or degree of reversal of hindbrain herniation (p > 0.99). CONCLUSIONS: This study suggested that children with prenatally repaired MMC are at higher risk for development of sIC and associated symptoms than those who undergo postnatal repair. The presentation of symptoms was also earlier in these patients than previously reported after postnatal repair. The use of a dural allograft patch appears to have a positive correlation with sIC formation. Future investigations evaluating the incidence of sIC after fetoscopic MMC repair, in which primary dural closure typically cannot be achieved and a dural patch is most often utilized, will be helpful in facilitating prenatal counseling for patients considering fetal intervention.

A Technical Look at Fetoscopic Laser Ablation for Fetal Laryngeal Surgical Recanalization in Congenital High Airway Obstruction Syndrome.

Background: Congenital high airway obstruction syndrome (CHAOS) is a rare condition characterized by complete obstruction of the upper fetal airways. Left untreated, it is uniformly fatal. Ex utero intrapartum treatment (EXIT) has been used to establish a surgical airway in affected fetuses during delivery. While this procedure benefits those fetuses that survive to delivery, high mortality in the prenatal period necessitates earlier innovative strategies. Herein, we report a novel technique for in utero intervention. Methods: A fetoscopic intervention was performed at 28 weeks on a 35-year-old G1P0 woman with fetal CHAOS from a laryngeal obstruction measuring 11 mm in length on prenatal imaging. Under ultrasound guidance, a 3.3-mm curved fetoscope was used to access the uterine cavity through a single subcentimeter maternal skin incision. The scope was driven through the fetal oral cavity and manipulated to attain a view of the vocal cords. A subglottic obstruction was observed. A 600-micron laser fiber was passed through the working channel of the scope and used to ablate the obstructed airway. Using the laser fiber and a guidewire, the ablated opening was traversed with the fetoscope to the level of the carina. Results: Postoperatively, the lungs became less hyperinflated. There was improvement in ascites and diaphragmatic eversion. At 31 1/7 weeks' gestation, the mother experienced preterm premature rupture of membranes with active labor and the fetus was delivered through EXIT to tracheostomy. The infant was managed on mechanical ventilation and is currently thriving at home with a tracheostomy at 2 years of age. Conclusion: Fetoscopy with laser ablation of the airway obstruction is an effective prenatal management strategy that offers the potential to alter the devastating natural course of CHAOS.

Evaluation of Lung Injury in Infants with Congenital Diaphragmatic Hernia.

BACKGROUND/PURPOSE: The presence of lung injury and the factors that contribute to it in infants with congenital diaphragmatic hernia (CDH) have not been objectively measured during their clinical course. In adults with acute respiratory distress syndrome, higher serum levels of surfactant protein D (SP-D) are linked to lung injury and worse outcomes. We hypothesized that serum SP-D levels would be elevated in CDH infants and that the levels would correlate to the amount of lung injury present. METHODS: In this retrospective cohort study, serum SP-D levels were analyzed in 37 CDH infants and 5 control infants using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Infants with more severe CDH had a statistically significant increase (p < 0.001) in serum SP-D over their first month of life. SP-D levels in CDH infants were similar to control infants while on extracorporeal membrane oxygenation (ECMO) but were 2.5-fold higher (p = 0.03) than controls following ECMO termination. SP-D levels increased 1.6-fold following surgical repair of the diaphragm and were significantly higher in the second week following surgery when compared to pre-operative levels (p < 0.03). CONCLUSIONS: These results demonstrate that CDH infants experience lung injury during the first week of life, around the time of surgery, and at the time of ECMO termination. Level II prognosis study.

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.

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.

Perinatal Management of Fetal Tumors.

Progress in the last three decades in prenatal genetic diagnosis and advancement in prenatal imaging and characterization of fetal anomalies have allowed better preparation in family counseling and afforded the opportunity to consider prenatal treatment for congenital defects that would have fatal outcomes, among them the fetal tumors. Advances in fetal therapy and surgical approaches including minimally invasive procedures, have permitted not just the survival of rare tumor cases but improved long-term outcomes. In this review, we described some of the most common fetal tumors and their recommended management with emphasis on in utero treatment options.

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.

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.

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.