Epidemiology of Hirschsprung disease in California from 1995 to 2013.

PURPOSE: This study seeks to update current epidemiology of Hirschsprung disease (HD) in California. METHODS: Using data from the California Office of Statewide Health Planning and Development Linked Birth (1995-2012) and Patient Discharge Databases (1995-2013), patients from either dataset with an ICD-9 diagnosis code of HD (751.3) or procedure code of Soave (48.41), Duhamel (48.65), or Swenson/other pull-through (48.49) were included. Patients > age 18 during their first admission were excluded. RESULTS: Of 9.3 million births, 2,464 patients were identified. Incidence was 2.2 cases/10,000 live births, with rates peaking at 2.9/10,000 births in 2002. Incidence was highest among African American (4.1/10,000) and Asian/Pacific Islander (2.5/10,000) births. Most were male (n = 1652, 67.1%). Sixty patients (2.4%) had Down syndrome. The median gestational age at birth was 38 weeks 6 days (interquartile range [IQR] 37 weeks 1 day-40 weeks 1 day). Mortality during the first year of life was 1.7%. Median age at death was 14.5 days (IQR 0-113 days). CONCLUSION: This is one of the largest population-based studies of HD. In California, the incidence of HD is stable, risk is highest among African American children, and the mortality rate is < 2%.

Fetal Surgery for Myelomeningocele: A Systematic Review and Meta-Analysis of Outcomes in Fetoscopic versus Open Repair.

BACKGROUND/OBJECTIVES: The Management of Myelomeningocele (MMC) Study (MOMS) showed that prenatal repair of MMC resulted in improved neurological outcomes but was associated with high rates of obstetrical complications. This study compares outcomes of open and fetoscopic MMC repair. DATA SOURCES: PubMed and Embase studies reporting outcomes of fetal MMC repair published since the completion of the MOMS. RESULTS: We analyzed 11 studies and found no difference in mortality or the rate of shunt placement for hydrocephalus. Percutaneous fetoscopic repair was associated with higher rates of premature rupture of membranes (91 vs. 36%, p < 0.01) and preterm birth (96 vs. 81%, p = 0.04) compared to open repair, whereas fetoscopic repair via maternal laparotomy reduced preterm birth. The rate of dehiscence and leakage from the MMC repair site was higher after both types of fetoscopic surgery (30 vs. 7%, p < 0.01), while the rate of uterine dehiscence was higher after open repair (11 vs. 0%, p < 0.01). DISCUSSION: Fetoscopic repair is a promising alternative to open fetal MMC repair with a lower risk of uterine dehiscence; however, fetoscopic techniques should be optimized to overcome the high rate of dehiscence and leakage at the MMC repair site. A fetoscopic approach via maternal laparotomy reduces the risk of preterm birth.

New directions in fetal surgery for myelomeningocele.

The treatment of children with myelomeningocele (MMC) has improved over time, from supportive management to early postnatal closure to prenatal repair of the defect. The Management of Myelomeningocele Study (MOMS) showed that prenatal repair of MMC resulted in improved neurological outcomes compared to postnatal closure. Follow-up studies showed that prenatal repair was, as with any other fetal intervention, associated with higher rates of obstetrical complications. There was no significant difference in urological outcomes. Long-term follow-up of ambulatory status, executive functioning, and urological outcomes is needed to determine the durable effects of fetal MMC repair on mobility, functional independence, and the prevalence of renal insufficiency in patients with MMC who survive to adulthood. The future of fetal MMC repair consists of developing strategies to reduce maternal morbidity and improve infant outcomes. Fetoscopic MMC repair has been suggested as an alternative to open repair that may reduce obstetrical complications and the need for cesarean delivery in subsequent pregnancies. Translational research using mesenchymal stromal cells to augment fetal repair of ovine MMC has shown improvement in motor function.

The hidden mortality of pediatric firearm violence.

INTRODUCTION: Firearms and motor vehicle collisions (MVC) are leading causes of mortality in children. We hypothesized that firearm injuries would have a higher mortality than MVCs in children and a higher level of resource utilization METHODS: Trauma patients <18 years old at a Level 1 pediatric trauma center sustaining gunshot wounds (GSW) or MVCs 2009-2019 were included. The primary outcome was mortality. The secondary outcome was immediate surgery. The California Department of Public Health's Overall Injury Surveillance tool was queried for patients <18 with GSW or MVC 2006-2015 to compare statewide case fatality rates (CFRs), and analyze proportions of GSWs by intent: assault, self-inflicted, and unintentional. RESULTS: Of 13,840 pediatric trauma patients at our institution, 295 GSWs (2.1%) and 4467 MVCs (32.3%) were included. Mortality was higher for GSWs (7.5% vs. 0.8%, p<0.0001). GSW patients were more likely to require immediate surgery (34.4% vs. 11.2%, p<0.0001). On multivariable analysis, GSW patients were 7.8-times more likely to die than MVC patients (OR 7.83, 95% CI 3.68-16.66, p<0.0001), adjusted for age, sex, and injury severity. Statewide, there were 10,790 pediatric GSWs with 1586 deaths (CFR 14.7%) vs. 710 deaths in 261,363 children in MVCs (CFR 0.3%, p<0.0001). The GSW CFR rose (13.4% to 16.5%, p = 0.05) while the MVC CFR decreased (0.5% to 0.2%, p<0.0001) in 2015 vs. 2006. CONCLUSION: Firearm violence in pediatric patients is significantly more lethal than MVCs and is resource intensive. The case fatality rate for pediatric firearm violence is rising. Resources must be directed at preventing pediatric firearm injuries. LEVEL OF EVIDENCE: Prognosis study, Level II.

Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model.

INTRODUCTION: Translational models of myelomeningocele (MMC) are needed to test novel in utero interventions. An ideal animal model for MMC has locomotor function at birth and is low cost enough to allow for high throughput. The rat MMC model is limited by immature locomotor function at birth. The ovine MMC model is a costly surgical model. Guinea pigs are uniquely suited for an MMC model being a small animal model with locomotor function at birth. We aimed to develop a retinoic acid (RA) model of MMC in the guinea pig and to evaluate if pregnant guinea pigs could tolerate uterine manipulation. METHODS: Time-mated Dunkin Hartley guinea pig dams were dosed with 60 mg/kg of RA between gestation age (GA) 12 and 15 days in the development of an RA model. Fetuses were grossly evaluated for MMC lesions at Cesarean section after GA 31 days. Evaluation of the ability of pregnant guinea pig dams to tolerate uterine surgical intervention was performed by hysterotomy of a separated group of time-mated guinea pigs at GA 45, 50, and 55. RESULTS: Forty-two pregnant guinea pigs were dosed with RA, with a total of 189 fetuses. The fetal demise rate was 38% (n = 71). A total of 118 fetuses were viable, 83% (n = 98) were normal fetuses, 8% (n = 10) had a neural tube defect, and 8% (n = 10) had a hematoma or other anomalies. No fetuses developed an MMC defect. None of the fetuses that underwent hysterotomy survived to term. CONCLUSION: RA dosed at 60 mg/kg in guinea pigs between GA 12 and 15 did not result in MMC. Dunkin Hartley guinea pigs did not tolerate a hysterotomy near term in our surgical model. Further work is needed to determine if MMC can be induced in guinea pigs with alternate RA dosing.

Total gastrectomy with delayed Hunt-Lawrence pouch reconstruction for neonatal gastric perforation presenting with hematemesis.

The differential for neonatal hematoma sis ranges from benign etiologies to life-threatening emergencies. Neonatal gastric perforation is a rare cause of neonatal hematoma sis but is a deadly condition, requiring prompt diagnosis and treatment. The etiology is usually related to conditions predisposing to over distension of the stomach, such as positive pressure ventilation or distal obstruction, but in some cases cannot be determined. Patients generally present with abdominal distension and respiratory distress. We present a case of a 1-day old term baby girl who developed sudden onset hematoma sis and clinical deterioration, who was found to have a large proximal gastric perforation requiring emergent total gastrectomy with delayed reconstruction.

In utero treatment of myelomeningocele with placental mesenchymal stromal cells - Selection of an optimal cell line in preparation for clinical trials.

BACKGROUND: We determined whether in vitro potency assays inform which placental mesenchymal stromal cell (PMSC) lines produce high rates of ambulation following in utero treatment of myelomeningocele in an ovine model. METHODS: PMSC lines were created following explant culture of three early-gestation human placentas. In vitro neuroprotection was assessed with a neuronal apoptosis model. In vivo, myelomeningocele defects were created in 28 fetuses and repaired with PMSCs at 3 × 105 cells/cm2 of scaffold from Line A (n = 6), Line B (n = 7) and Line C (n = 5) and compared to no PMSCs (n = 10). Ambulation was scored as ≥13 on the Sheep Locomotor Rating Scale. RESULTS: In vitro, Line A and B had higher neuroprotective capability than no PMSCs (1.7 and 1.8 respectively vs 1, p = 0.02, ANOVA). In vivo, Line A and B had higher large neuron densities than no PMSCs (25.2 and 27.9 respectively vs 4.8, p = 0.03, ANOVA). Line C did not have higher neuroprotection or larger neuron density than no PMSCs. In vivo, Line A and B had ambulation rates of 83% and 71%, respectively, compared to 60% with Line C and 20% with no PMSCs. CONCLUSION: The in vitro neuroprotection assay will facilitate selection of optimal PMSC lines for clinical use. LEVEL OF EVIDENCE: n/a. TYPE OF STUDY: Basic science.

Lessons from the Barn to the Operating Suite: A Comprehensive Review of Animal Models for Fetal Surgery.

The International Fetal Medicine and Surgery Society was created in 1982 and proposed guidelines for fetal interventions that required demonstrations of the safety and feasibility of intended interventions in animal models prior to application in humans. Because of their short gestation and low cost, small animal models are useful in early investigation of fetal strategies. However, owing to the anatomic and physiologic differences between small animals and humans, repeated studies in large animal models are usually needed to facilitate translation to humans. Ovine (sheep) models have been used the most extensively to study the pathophysiology of congenital abnormalities and to develop techniques for fetal interventions. However, nonhuman primates have uterine and placental structures that most closely resemble those of humans. Thus, the nonhuman primate is the ideal model to develop surgical and anesthetic techniques that minimize obstetrical complications.