Neonatal pneumothorax in congenital diaphragmatic hernia: Be wary of high ventilatory pressures.

Background: Patients with congenital diaphragmatic hernia (CDH) require invasive respiratory support and higher ventilator pressures may be associated with barotrauma. We sought to evaluate the risk factors associated with pneumothorax in CDH neonates prior to repair. Methods: We retrospectively reviewed newborns born with CDH between 2014 and 2019 who developed a pneumothorax, and we matched these cases to patients with CDH without pneumothorax. Results: Twenty-six patients were included (n=13 per group). The pneumothorax group required extracorporeal life support (ECLS) more frequently (85% vs 54%, p=0.04), particularly among type A/B defects (31% vs 7%, p=0.01). The pneumothorax group had higher positive end-expiratory pressure (PEEP) within 1 hour of birth (p=0.02), at pneumothorax diagnosis (p=0.003), and at ECLS (p=0.02). The pneumothorax group had a higher mean airway pressure (Paw) at birth (p=0.01), within 1 hour of birth (p=0.01), and at pneumothorax diagnosis (p=0.04). Using multiple logistic regression with cluster robust SEs, higher Paw (OR 2.2, 95% CI 1.08 to 3.72, p=0.03) and PEEP (OR 1.8, 95% CI 1.15 to 3.14, p=0.007) were associated with an increased risk of developing pneumothorax. There was no difference in survival (p=0.09). Conclusions: Development of a pneumothorax in CDH neonates is independently associated with higher Paw and higher PEEP. A pneumothorax increases the likelihood of treated with ECLS, even with smaller defect.

The in-utero diagnosis of choledochal cyst: can postnatal imaging predict benefit from early surgical intervention?

BACKGROUND: Infants prenatally suspected of having a choledochal cyst (CDC) typically undergo ultrasound imaging shortly after birth. This study sought to evaluate features on the initial postnatal ultrasound (IPU) that could identify newborns at risk for early complications. METHODS: Following IRB approval, patients from four US fetal centers with prenatal suspicion for CDC and postnatal imaging from 2000 to 2017 were reviewed. Imaging and clinical courses were assessed. RESULTS: Forty-two patients had prenatal ultrasounds suspicious for CDC. Nineteen (45.2%) were excluded due to diagnostic revision (n = 9), cyst resolution (n = 5), lack of IPU measurements (n = 3), or lack of follow-up (n = 2). The 23 remaining patients were included in the study. Of these, five (21.7%) developed symptoms at a median age of 16.5 days (IQR 16-19 days), and 18 (78.3%) remained asymptomatic throughout the first year after birth. Five patients (21.7%) had cysts ≥ 4.5 cm on IPU (Symptomatic: n = 3; Asymptomatic: n = 2). Eighteen patients (78.3%) had cysts < 4.5 cm on IPU (Symptomatic: n = 2; Asymptomatic: n = 16). An IPU cyst size ≥ 4.5 cm was associated with neonatal symptom manifestation (p = 0.048), with 88.9% specificity (95% CI 65.3-98.6%) and 60% sensitivity (95% CI 14.7-94.7%). CONCLUSIONS: In newborns with prenatally diagnosed CDC, a cyst size ≥ 4.5 cm on IPU is associated with symptom development during the first month after birth and therefore early cyst excision is recommended.

Risk factors for perioperative hypothermia and infectious outcomes in gastroschisis patients.

INTRODUCTION: Prior data suggest that infants with gastroschisis are at high risk for hypothermia and infectious complications (ICs). This study evaluated the associations between perioperative hypothermia (PH) and ICs in gastroschisis using a multi-institutional cohort. METHODS: Retrospective review of infants with gastroschisis who underwent abdominal closure from 2013-2017 was performed at 7 children's hospitals. Any-IC and surgical site infection (SSI) were stratified against the presence or absence of PH, and perioperative characteristics associated with PH and SSI were determined using multivariable logistic regression. RESULTS: Of 256 gastroschisis neonates, 42% developed PH, with 18% classified as mild hypothermia (35.5-35.9 °C), 10.5% as moderate (35.0-35.4 °C), and 13% severe (<35 °C). There were 82 (32%) ICs with 50 (19.5%) being SSIs. No associations between PH and any-IC (p = 0.7) or SSI (p = 0.98) were found. Pulmonary comorbidities (odds ratio (OR)=3.76, 95%CI:1.42-10, p = 0.008) and primary closure (OR=0.21, 95%CI:0.12-0.39, p<0.001) were associated with PH, while silo placement (OR=2.62, 95%CI:1.1-6.3, p = 0.03) and prosthetic patch (OR=3.42, 95%CI:1.4-8.3, p = 0.007) were associated with SSI on multivariable logistic regression. CONCLUSIONS: Primary abdominal closure and pulmonary comorbidities are associated with PH in gastroschisis, however PH was not associated with increased risk of ICs. Independent risk factors for SSI include silo placement and prosthetic patch closure.

Fetoscopic insufflation modeled in the extrauterine environment for neonatal development (EXTEND): Fetoscopic insufflation is safe for the fetus.

BACKGROUND: Minimally invasive fetal surgery, or fetoscopy, is an alternative to open fetal surgery to repair common birth defects like myelomeningocele. Although this hysterotomy-sparing approach reduces maternal morbidity, the effects of in utero insufflation on the fetus are poorly understood. Our purpose was to determine the optimal fetal insufflation conditions. METHODS: Fetal sheep at gestational age 104 to 107 days were studied under insufflation conditions in utero and ex utero. The ex utero fetuses were cannulated via their umbilical vessels into a support device, the EXTra-uterine Environment for Neonatal Development (EXTEND). EXTEND fetuses were exposed to four different insufflation conditions for four hours: untreated carbon dioxide (CO2) (n=5), warm humidified (whCO2) (n=4), whCO2 with the umbilical cord exposed (n=3), and whCO2 without amniotic fluid (skin and cord exposed) (n=3). RESULTS: In utero insufflation led to significant increases in fetal CO2 and reductions in fetal pH. Ex utero insufflation with whCO2 did not lead to changes in fetal blood gas measurements or cerebral perfusion parameters. Insufflation with whCO2 with an exposed umbilical cord led to reduced umbilical blood flow. CONCLUSIONS: Insufflation with warm humidified CO2 with an amniotic fluid covered umbilical cord is well tolerated by the fetus without significant changes in hemodynamics or cerebral perfusion parameters. TYPE OF STUDY: Basic science LEVEL OF EVIDENCE: N/A.

A Rabbit Model for Optimization of Amniotic Fluid Components in the EXTrauterine Environment for Newborn Development (EXTEND) System.

In this model article, we present a protocol for continuous amniotic fluid exchange in rabbits using a novel system to test the effects of growth factor-deficient, artificial amniotic fluid on bowel development. BACKGROUND: Ideally, the EXTrauterine Environment for Neonatal Development (EXTEND) will provide physiologic support to the extreme premature infant. An important component of that environment is the amniotic fluid. Thus, we developed an animal model to study the growth factors found within amniotic fluid and inform design of a synthetic fluid to optimize fetal development. METHODS: We designed a model of amniotic fluid exchange within the pregnant rabbit, continuously removing the natural fluid from around 2 fetuses per doe and replacing it with a physiologic electrolyte solution during the final 100 h of gestation. Two fetuses from the contralateral uterine horn were used as sham-operated controls. Thirty-eight fetuses were analyzed, 19 in each group. We analyzed the fetal growth and bowel development. RESULTS: Ultrasound after 100 h of exchange showed equivalent fluid volumes, p = 0.63. Cultures were negative for bacterial colonization. Final fluid protein concentrations were 11.6% that of control fluid (mean 1,451 ± 224.2 vs. 12,491 ± 849.2 µg/mL). There was no significant difference in fetal growth, with experimental weights 91.4% of control weights, p = 0.07. Fetal bowel weights (90.1%, p = 0.16) and lengths (94.2%, p = 0.49) were also not significantly less compared to controls. There was no significant difference in villous height or crypt depth measurements between the groups, and absorptive capacity of the bowel was not different between groups, p = 0.44. CONCLUSION: This animal model allows for manipulation of the components of amniotic fluid. Marked reduction of natural amniotic fluid proteins during gestation does not appear to significantly impair fetal growth or bowel development. Further work with this model will assess the importance of amniotic fluid components for normal development to inform design of a synthetic fluid for use during EXTEND.

Predicting lethal pulmonary hypoplasia in congenital diaphragmatic hernia (CDH): Institutional experience combined with CDH registry outcomes.

BACKGROUND: The Severe Pulmonary Hypoplasia and Evaluation for Resuscitative Efforts (SPHERE) protocol was developed to attempt to identify CDH patients with likely lethal pulmonary hypoplasia. We present our experience with this protocol and utilize the CDH Registry to critically assess the protocol. METHODS: SPHERE patients identified based on prenatal imaging (10/2009-1/2018) were offered ECMO if meeting postnatal physiologic criteria, while others received comfort measures. Within the CDH Registry, patients with suspected severe CDH were identified and separated into "passed" (lowest pCO2 ≤100) versus "failed" (lowest pCO2 >100) groups. RESULTS: Of 23 SPHERE patients, 57% (13/23) passed criteria for ECMO and survival was 46% (6/13) in that cohort. Of 4912 patients in the CDH Registry, 265 met criteria. There was no difference in survival rates between those that "passed" (122/227; 54%) versus "failed" (18/38; 47%). However, the latter had longer ECMO runs and more required ventilator/ECMO support at 30 days. Amongst survivors, the "failed" group had longer hospital stays and more frequently required tube feeds at discharge. CONCLUSIONS: The SPHERE protocol did not predict mortality in the CDH Registry. However, our data suggest resource utilization is significant when unable to reach pCO2 ≤100 despite resuscitation. Morbidity remains high in this group. LEVEL OF EVIDENCE: Level III ANNOTATION OF CHANGES: Institutional Review Board Approval at University of Michigan (HUM00031524 and HUM00044010) TYPE OF STUDY: Retrospective Review.

The EXTrauterine Environment for Neonatal Development Supports Normal Intestinal Maturation and Development.

BACKGROUND AND AIMS: The Extra-Uterine Environment for Neonatal Development (EXTEND) aims to avoid the complications of prematurity, such as NEC. Our goal was to determine if bowel development occurs normally in EXTEND-supported lambs, with specific emphasis on markers of immaturity associated with NEC. METHODS: We compared terminal ileum from 17 pre-term lambs supported on EXTEND for 2- 4 weeks to bowel from age-matched fetal lambs that developed in utero. We evaluated morphology, markers of epithelial integrity and maturation, enteric nervous system structure, and bowel motility. RESULTS: EXTEND-supported lamb ileum had normal villus height, crypt depth, density of mucin-containing goblet cells, and enteric neuron density. Expression patterns for I-FABP, activated caspase-3 and EGFR were normal in bowel epithelium. Transmural resistance assessed in Ussing chambers was normal. Bowel motility was also normal as assessed by ex vivo organ bath and video imaging. However, Peyer's patch organization did not occur normally in EXTEND ileum, resulting in fewer circulating B cells in experimental animals. CONCLUSION: EXTEND supports normal ileal epithelial and enteric nervous system maturation in pre-term lambs. The classic morphologic changes and cellular expression profiles associated with NEC are not seen. However, immune development within the EXTEND supported lamb bowel does not progress normally.

The Effects of Nitric Oxide in Oxygenator Sweep Gas During Extracorporeal Circulation in a Neonatal Ovine Model.

Extracorporeal membrane oxygenation is a life-saving intervention, but bleeding complications are frequent. Given that the combination of platelet loss and dysfunction is a major contributor to this acquired bleeding diathesis, efforts to combat these phenomena are of great clinical importance. In this study, we investigated the effects of nitric oxide (NO) added to the sweep gas of an extracorporeal circuit in a neonatal ovine model. Eight lambs (age 9.6 ± 1.9 days) were cannulated via the neck vessels and maintained on a pumpless arteriovenous extracorporeal membrane oxygenation circuit with blood flow restricted to 100 ml/min for 72 hours. All animals were heparinized, and a subset (n = 4) also received NO in the sweep gas at a concentration of 200 ppm. We observed no adverse effects from NO administration, and methemoglobin levels remained unchanged. Platelet counts significantly declined in all animals over the course of the study; however, mean counts were higher in the NO-treated group, and this difference was statistically significant at 24 hours (62 ± 3% vs. 32 ± 7% of baseline, P < 0.01). Likewise, mean plasma levels of beta-thromboglobulin, a marker of platelet activation, were lower in the NO-treated group, and this difference was also significant at the 24 hour time point (9.5 ± 2.2 vs. 19.7 ± 6.5 pg/mL/10 platelets, P < 0.05). We conclude that 200 ppm NO can be safely blended into the oxygenator sweep gas of a low-flow extracorporeal circuit and that it may transiently attenuate platelet consumption and activation.

Discordant prenatal ultrasound and fetal MRI in CDH: wherein lies the truth?

PURPOSE: Prenatal risk assessment of congenital diaphragmatic hernia (CDH) relies on prenatal ultrasound (U/S) and fetal magnetic resonance imaging (MRI). When the modalities differ in prognosis, it is unclear which is more reliable. METHODS: Retrospective chart review identified cases of prenatally diagnosed CDH from 4/2010-6/2018 meeting inclusion criteria. Demographic, radiologic, and postnatal outcomes data were collected. Ultrasound- versus MRI-based prognosis (mild, moderate, and severe) was compared with clinical outcomes. Kappa measures compared congruency in disease severity scaling between imaging modalities, while logistic regression and receiver operating characteristics curves compared the ability of each modality to predict outcomes. RESULTS: Forty-two patients met criteria. Both U/S- and MRI-based prognosis categories differentiated for survival. MRI categories differentiated for ECMO use, surgical repair, and defect type. O/e TFLV better discriminated for survivors and defect type than o/e LHR. Seventeen (40.5%) had discordant prenatal prognostic categories. In 13/17 (76.5%), o/e TFLV predicted higher severity when compared to o/e LHR, but sample size was insufficient to compare accuracy in cases of discordance. CONCLUSIONS: Clinical outcomes suggest fetal MRI may more accurately predict severe pulmonary hypoplasia compared to prenatal ultrasound. Our analysis suggests fetal MRI is a valuable adjunct in the prenatal evaluation of CDH. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective Review.

Calculating Observed-to-Expected Total Fetal Lung Volume in CDH Fetuses in Twin Gestation: Is There a Better Way?

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a potentially lethal birth defect, and identifying prenatal predictors of outcome is important. Observed-to-expected total fetal lung volume (o/e TFLV) has been shown to be a predictor of severity and useful in risk stratification but is variable due to different TFLV formulas. OBJECTIVES: To calculate o/e TFLV for CDH patients part of a twin gestation using the unaffected sibling as an internal control and comparing these values to those calculated using published formulas for TFLV. METHODS: Seven twin gestations with one fetus affected by CDH were identified between 2006 and 2017. The lung volume for each twin was calculated using magnetic resonance imaging (MRI), and o/e TFLV was calculated using the unaffected twin's TFLV. This percentage was then compared to the o/e TFLV calculated using published formulas. RESULTS: Lung volumes in the unaffected twins were within normal ranges at the lower end of the spectrum. No single TFLV formula was found to correlate perfectly. Intraclass correlation coefficient estimate was most consistent for o/e TFLV calculated with the Meyers formula and supported by Bland-Altman plots. CONCLUSIONS: O/e TFLV measured in CDH/non-CDH twin gestations using the unaffected sibling demonstrated agreement with o/e TFLV calculated using the Meyers formula. We urge the fetal community to standardize the method, use, and interpretation of fetal MRI in the prenatal evaluation of CDH.

Prenatal hypoxemia alters microglial morphology in fetal sheep.

OBJECTIVE: Neuroimmune cells, particularly microglia and astrocytes, play a critical role in neurodevelopment. Neurocognitive delays are common in children with congenital heart disease, but their etiology is poorly understood. Our objective was to determine whether prenatal hypoxemia, at levels common in congenital heart disease, induced neuroimmune activation to better understand the origins of neurobehavioral disorders in congenital heart disease. METHODS: Eight fetal sheep at gestational age 109 ± 3 days (term ∼145 days) were cannulated onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid environment for 22 ± 2 days under normoxic (n = 4) or hypoxic (n = 4) conditions. Control fetuses (n = 7) were harvested at gestational age 133 ± 4 days. At necropsy, brains were stained with ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein antibodies to quantify microglia and astrocytes, respectively, in gray and white matter in frontotemporal and cerebellar sections. Microglia were classified into 4 morphologic types based on cell shape. Data were analyzed with 1-way analysis of variance or Fisher exact test, as appropriate. RESULTS: Oxygen delivery was significantly reduced in hypoxic fetuses (15.6 ± 1.8 mL/kg/min vs 24.3 ± 2.3 mL/kg/min; P < .01). Rates of apoptosis were similar in hypoxic, normoxic, and intrauterine control animals in all examined areas. There were also no differences between groups in area occupied by glial fibrillary acidic protein-labeled astrocytes or ionized calcium-binding adaptor molecule 1-labeled microglia in all examined areas. However, round microglia were significantly increased in hypoxic animals compared with normoxic animals (33% vs 6%; P < .01) and control animals (33% vs 11%; P < .01). CONCLUSIONS: Prenatal hypoxemia altered microglial morphology without significant gliosis. Additional studies characterizing these mechanisms may provide insight into the origins of neurobehavioral disabilities in children with congenital heart disease.

Donor cell engineering with GSK3 inhibitor-loaded nanoparticles enhances engraftment after in utero transplantation.

Host cell competition is a major barrier to engraftment after in utero hematopoietic cell transplantation (IUHCT). Here we describe a cell-engineering strategy using glycogen synthase kinase-3 (GSK3) inhibitor-loaded nanoparticles conjugated to the surface of donor hematopoietic cells to enhance their proliferation kinetics and ability to compete against their fetal host equivalents. With this approach, we achieved remarkable levels of stable, long-term hematopoietic engraftment for up to 24 weeks post-IUHCT. We also show that the salutary effects of the nanoparticle-released GSK3 inhibitor are specific to donor progenitor/stem cells and achieved by a pseudoautocrine mechanism. These results establish that IUHCT of hematopoietic cells decorated with GSK3 inhibitor-loaded nanoparticles can produce therapeutic levels of long-term engraftment and could therefore allow single-step prenatal treatment of congenital hematological disorders.

Prenatal Dilated Rectum: Do We Need to Worry?

BACKGROUND: Advances in prenatal imaging is increasing detection of abnormally dilated bowel. There is no literature to date defining the criteria for a dilated rectum or its association with postnatal pathology. The aim of this study is to investigate the clinical significance of a prenatally identified dilated rectum. METHODS: A retrospective review was performed of all cases of "dilated bowel" on prenatal ultrasound between January 2000 and December 2017 at a single institution. We excluded ventral wall defects from review and sought to include only cases of a prominent or dilated rectum. Collected data included prenatal bowel measurements, postnatal diagnoses, need for surgical intervention, and outcomes. Descriptive statistics were applied. RESULTS: One hundred and ninety-three cases of prenatal "dilated bowel" were identified in which 12 (6.2%) had specifically visualized a prominent or dilated rectum. Nine of these (75.0%) had no rectal or intestinal abnormality on postnatal evaluation and were discharged feeding and defecating normally. The remaining three cases exhibited clinical pathology necessitating additional management: (1) meconium plug, (2) jejunal atresia with cecal perforation, and (3) rectal perforation with retroperitoneal abscess. All three had rectal biopsies with identification of ganglionated submucosa. CONCLUSIONS: Although a prenatal dilated rectum is a normal variant in the vast majority of cases, it may be associated with a gastrointestinal abnormality requiring surgical intervention. Interestingly, there were no cases of Hirschsprung's disease or anorectal malformations in this cohort. These results, in conjunction with continued efforts to identify and define rectal dilation, are useful for prenatal counseling and postnatal evaluation.

In Utero Transplantation of Expanded Autologous Amniotic Fluid Stem Cells Results in Long-Term Hematopoietic Engraftment.

In utero transplantation (IUT) of hematopoietic stem cells (HSCs) has been proposed as a strategy for the prenatal treatment of congenital hematological diseases. However, levels of long-term hematopoietic engraftment achieved in experimental IUT to date are subtherapeutic, likely due to host fetal HSCs outcompeting their bone marrow (BM)-derived donor equivalents for space in the hematopoietic compartment. In the present study, we demonstrate that amniotic fluid stem cells (AFSCs; c-Kit+/Lin-) have hematopoietic characteristics and, thanks to their fetal origin, favorable proliferation kinetics in vitro and in vivo, which are maintained when the cells are expanded. IUT of autologous/congenic freshly isolated or cultured AFSCs resulted in stable multilineage hematopoietic engraftment, far higher to that achieved with BM-HSCs. Intravascular IUT of allogenic AFSCs was not successful as recently reported after intraperitoneal IUT. Herein, we demonstrated that this likely due to a failure of timely homing of donor cells to the host fetal thymus resulted in lack of tolerance induction and rejection. This study reveals that intravascular IUT leads to a remarkable hematopoietic engraftment of AFSCs in the setting of autologous/congenic IUT, and confirms the requirement for induction of central tolerance for allogenic IUT to be successful. Autologous, gene-engineered, and in vitro expanded AFSCs could be used as a stem cell/gene therapy platform for the in utero treatment of inherited disorders of hematopoiesis. Stem Cells 2019;37:1176-1188.

Premature Lambs Exhibit Normal Mitochondrial Respiration after Long-Term Extrauterine Support.

BACKGROUND: In an effort to mitigate the major morbidities and mortality associated with extreme prematurity, we have developed an EXTrauterine Environment for Neonatal Development (EXTEND) designed to provide physiologic support of extremely premature infants. OBJECTIVES: We have previously shown that long-term, physiologic support of premature fetal lambs is possible with EXTEND, but in this study, we sought to demonstrate bioenergetic equipoise at the tissue level. METHODS: Four premature fetal lambs were delivered by hysterotomy at gestational ages (GA) of 105-107 days (term ∼145 days), cannulated via the umbilical vessels, and transitioned to support on EXTEND for 3-4 weeks. Five control fetuses were age-matched to the GA of experimental fetuses at the time of study end (128-134 days GA) and immediately sacrificed after hysterotomy. Mitochondria were isolated from the heart, liver, kidney, and skeletal muscle of fetuses at the time of sacrifice, and oxygen consumption rates (OCRs) were measured. RESULTS: There were no differences in basal mitochondrial OCR between EXTEND and control fetuses for heart, kidney, or skeletal muscle. For liver, the basal OCR was higher in EXTEND fetuses compared to controls. There were no differences in physiologic maximal OCR or reserve capacity for any tissue analyzed. CONCLUSIONS: Fetal lambs supported by EXTEND demonstrate physiologic mitochondrial function as evidenced by adequate basal and physiologic maximal cellular respiration as well as preserved reserve capacity.

Current operative management of congenital lobar emphysema in children: A report from the Midwest Pediatric Surgery Consortium.

PURPOSE: The purpose of this study was to evaluate the clinical presentation and operative outcomes of patients with congenital lobar emphysema (CLE) within a large multicenter research consortium. METHODS: After central reliance IRB-approval, a retrospective cohort study was performed on all operatively managed lung malformations at eleven participating children's hospitals (2009-2015). RESULTS: Fifty-three (10.5%) children with pathology-confirmed CLE were identified among 506 lung malformations. A lung mass was detected prenatally in 13 (24.5%) compared to 331 (73.1%) in non-CLE cases (p < 0.0001). Thirty-two (60.4%) CLE patients presented with respiratory symptoms at birth compared to 102 (22.7%) in non-CLE (p < 0.0001). The most common locations for CLE were the left upper (n = 24, 45.3%), right middle (n = 16, 30.2%), and right upper (n = 10, 18.9%) lobes. Eighteen (34.0%) had resection as neonates, 30 (56.6%) had surgery at 1-12 months of age, and five (9.4%) had resections after 12 months. Six (11.3%) underwent thoracoscopic excision. Median hospital length of stay was 5.0 days (interquartile range, 4.0-13.0). CONCLUSIONS: Among lung malformations, CLE is associated with several unique features, including a low prenatal detection rate, a predilection for the upper/middle lobes, and infrequent utilization of thoracoscopy. Although respiratory distress at birth is common, CLE often presents clinically in a delayed and more insidious fashion. LEVEL OF EVIDENCE: Level III.

Thoracoscopic thymectomy for juvenile myasthenia gravis.

PURPOSE: A randomized controlled trial of thymectomy in myasthenia gravis demonstrated improved clinical outcomes in adults, but data surrounding juvenile cases, especially those treated with minimally invasive approaches, are limited. Here, we review our experience with thoracoscopic thymectomy for juvenile myasthenia gravis (JMG) in the largest cohort to date. METHODS: All cases of thymectomy for JMG in a single tertiary referral center between 2007 and 2018 were reviewed (N = 50). Patients underwent left thoracoscopic approach with extended dissection and without use of monopolar energy. Demographics, diagnostic criteria, and clinical classification, as well as surgical data were collected. Clinical status and medications were reviewed in follow-up. RESULTS: The mean age at surgery was 10.5 ± 0.8 years. Ocular disease and generalized disease each comprised half of the cohort. No patients suffered complications or increased risk of morbidity or mortality with thymectomy. At any interval of follow-up through 3.5 years, 49.8% of patients were improved compared to their pre-operative presentation, and there was a significant trend towards decreased steroid use. CONCLUSION: Thoracoscopic thymectomy is a safe treatment for juvenile myasthenia gravis in pediatric patients over a wide range of ages, body masses, and symptoms. Our experience adds evidence that pediatric patients likely benefit from thymectomy with improved clinical status and reduced medications.

Amniotic Fluid Concentrations of Glial Fibrillary Acidic Protein Do Not Correlate with Prenatal Metrics in Fetuses with Myelomeningocele.

INTRODUCTION: We investigated the correlation of amniotic fluid (AF) concentrations of glial fibrillary acidic protein (GFAP) with prenatal features of myelomeningocele (MMC) and neurodevelopmental outcome after fetal MMC (fMMC) surgery. MATERIALS AND METHODS: AF was collected during fMMC surgery between December 2012 and November 2015. AF-GFAP concentration was determined by ELISA. Retrospective chart review identified the characteristics of the defect. Data regarding delivery and 1-year neurodevelopmental outcome was collected from The Children's Hospital of Philadelphia fMMC Registry. RESULTS: Eighty-two AF samples were collected from fMMC surgeries. Perinatal data were obtained from 77 subjects, and 1-year follow-up data from 65 subjects. GFAP concentrations were significantly elevated in MMC compared to myeloschisis (24.1 ± 2.9 and 10.3 ± 1.5 ng/mL; p < 0.0001). A larger percentage of subjects with myeloschisis defects delivered before their scheduled due date (myeloschisis 88.5%; MMC 55.0%; p = 0.003) and delivered at an earlier mean gestational age (34.6 ± 0.4 weeks, n = 26) compared to those with MMC defects (35.2 ± 0.4 weeks, n = 51) (p = 0.04). DISCUSSION: AF-GFAP levels differentiate between MMC and myeloschisis, and raise interesting questions regarding the clinical significance between the 2 types of defects.