Hepcidin, an Iron Regulatory Hormone of Innate Immunity, is Differentially Expressed in Premature Fetuses with Early-Onset Neonatal Sepsis.

OBJECTIVE: Hepcidin, a mediator of innate immunity, binds the iron exporter ferroportin, leading to functional hypoferremia through intracellular iron sequestration. We explored hepcidin-ferroportin interactions in neonates clinically diagnosed with early-onset neonatal sepsis (EONS). STUDY DESIGN: Hepcidin and interleukin (IL)-6 were quantified by enzyme-linked immunosorbent assay (ELISA) in 92 paired cord blood-maternal blood samples in the following groups: "Yes" EONS (n = 41, gestational age [GA] 29 ± 1 weeks) and "No" EONS (n = 51, GA 26 ± 1 weeks). Placental hepcidin and ferroportin expression were evaluated by immunohistochemistry and real-time-polymerase chain reaction (RT-PCR). Liver hepcidin and ferroportin expression patterns were ascertained in autopsy specimens of neonates (n = 8) who died secondary to culture-proven sepsis. RESULTS: Cord blood hepcidin was significantly elevated (GA corrected, p = 0.018) and was positively correlated with IL-6 (r = 0.379, p = 0.001) in EONS. Hepcidin localized at syncytiotrophoblast and fetal vascular endothelium. Placental ferroportin, but not hepcidin mRNA correlated with cord blood hepcidin levels (r = 0.46, p = 0.039) and funisitis severity (r = 0.50, p = 0.018). Newborns who died from sepsis (n = 4) had higher hepatic hepcidin and iron sequestration, but lower ferroportin staining than those who died of nonsepsis causes (n = 4). CONCLUSION: Premature fetuses with EONS have elevated circulating hepcidin, likely related to lower placenta and liver ferroportin expression. Fetal hepcidin-ferroportin interaction appears to play a role in EONS pathophysiology independent of maternal response to intrauterine inflammation.

Fetoscopic Multilayer, Dural Patch Closure Technique for Intrauterine Myelomeningocele Repair: 2-Dimensional Operative Video.

Myelomeningocele (MMC) is the most common open neural tube defect associated with long-term survival. In 2011, The Management of Myelomeningocele Study (MOMS) trial demonstrated that fetal repair for MMC reduced the rate of shunted hydrocephalus and improved developmental, motor, and ambulation outcomes at 30 mo compared to postnatal intervention.1 Recent studies have demonstrated the safety and feasibility of fetoscopic MMC repair as well as reduction in preterm birth, lower risk of uterine dehiscence, and the option of vaginal delivery with this approach compared to open fetal repair.2-4 The patient is a 25-yr-old female, G4 P2, who presented at 20 wk's gestation with ultrasound findings concerning for MMC and Chiari II malformation. These findings were further corroborated with fetal magnetic resonance imaging. After extensive prenatal counseling in a multidisciplinary fashion and discussion regarding risks and benefits of prenatal closure of the MMC, the patient chose to undergo prenatal repair and surgical consent was obtained. At 25 wk's gestation, the patient underwent a fetoscopic multilayer closure with dural patch repair using a standardized, 3-port, carbon dioxide insufflation technique for the intrauterine treatment of MMC without any postoperative complications. The duration of the entire procedure was 275 min. At 36 wk's and 1 d's gestational age, the patient had a spontaneous vaginal delivery, resulting in a healthy male newborn. The surgical site was well healed without complications, and follow-up radiographic imaging was reassuring. This edited, 2-dimensional operative video highlights the key steps of the fetoscopic closure with follow-up postnatal clinical and radiographic outcomes.

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.