A role for abdominal ultrasound in discriminating suspected necrotizing enterocolitis in congenital heart disease patients.

PURPOSE: We evaluated the diagnostic utility of abdominal ultrasound (AUS), an adjunct to abdominal X-ray (AXR), for necrotizing enterocolitis (NEC) in congenital heart disease (CHD) patients. METHODS: 86 patients with suspected NEC from 2009 to 2018 were classified as with CHD (n = 18) if they required cardiac intervention versus without CHD (n = 68). Clinical and radiological data were collected, including AXR and AUS concordance. Wilcoxon rank-sum test and Fisher's exact test were performed. RESULTS: CHD patients had higher birth weights (p < 0.001) and gestational ages (p < 0.001) than non-CHD patients. CHD patients presented more frequently with hypotension (p = 0.041) and less frequently with bilious emesis (p < 0.001). Overall, CHD patients were less likely to have AUS findings of pneumatosis (33.3 vs. 72.1%; p = 0.005) and decreased mural flow (0 vs. 20.6%; p = 0.035) compared to non-CHD patients. On concordance analysis, CHD patients had 3.9-fold more discordant studies with pneumatosis on AXR but not on AUS (33.3 vs. 8.8%; p = 0.016) compared to non-CHD patients. Urgent surgery was required in 5.6% of CHD patients versus 16.2% of non-CHD patients. CONCLUSION: CHD patients with suspected NEC represent a distinct clinical population. AUS has particular utility in assessing findings of bowel viability in the CHD NEC population, reflecting reduced rates of surgical NEC.

Abdominal ultrasound findings contribute to a multivariable predictive risk score for surgical necrotizing enterocolitis: A pilot study.

BACKGROUND: Abdominal ultrasound (AUS) is a promising adjunct to abdominal x-ray (AXR) for evaluating necrotizing enterocolitis (NEC). We developed a multivariable risk score incorporating AUS to predict surgical NEC. METHODS: 83 patients were evaluated by AXR and AUS for suspected NEC. A subset had surgical NEC. Multivariate logistic regression determined predictors of surgical NEC, which were incorporated into a risk score. RESULTS: 14/83 patients (16.9%) had surgical NEC. 10/83 (12.0%) patients required acute intervention, while 4/83 (4.8%) patients only required delayed surgery. Four predictors of surgical NEC were identified: abdominal wall erythema (OR: 8.2, p = 0.048), portal venous gas on AXR (OR: 29.8, p = 0.014), and echogenic free fluid (OR: 17.2, p = 0.027) and bowel wall thickening (OR: 12.5, p = 0.030) on AUS. A multivariable risk score incorporating these predictors had excellent area-under-the-curve of 0.937 (95% CI: 0.879-0.994). CONCLUSIONS: AUS, as an adjunct to physical exam and AXR, has utility for predicting surgical NEC.

Transamniotic Stem Cell Therapy for Experimental Congenital Diaphragmatic Hernia: Structural, Transcriptional, and Cell Kinetics Analyses in the Nitrofen Model.

PURPOSE: We examined select pulmonary effects and donor cell kinetics after transamniotic stem cell therapy (TRASCET) in a model of congenital diaphragmatic hernia (CDH). METHODS: Pregnant dams (n = 58) received nitrofen on gestational day 9.5 (E9) to induce fetal CDH. Fetuses (n = 681) were divided into 4 groups: untreated (n = 99) and 3 groups receiving volume-matched intra-amniotic injections on E17 of either saline (n = 142), luciferase-labeled amniotic fluid-derived mesenchymal stem cells (afMSCs; n = 299), or acellular recombinant luciferase (n = 141). Pulmonary morphometry, quantitative gene expression of pulmonary vascular tone mediators, or screening for labeled afMSCs were performed at term (E22). Statistical comparisons were by Mann-Whitney U-test, nested ANOVA, and Wald test. RESULTS: TRASCET led to significant downregulation of endothelial nitric oxide synthase and endothelin receptor-A expressions compared to both untreated and saline groups (both p < 0.001). TRASCET also led to a significant decrease in arteriole wall thickness compared to the untreated group (p < 0.001) but not the saline group (p = 0.180). Donor afMSCs were identified in the bone marrow and umbilical cord (p = 0.035 and 0.015, respectively, vs. plain luciferase controls). CONCLUSIONS: The effects of TRASCET in experimental CDH appear to be centered on the pulmonary vasculature and to derive from circulating donor cells.

Initial Mechanistic Screening of Transamniotic Stem Cell Therapy in the Rodent Model of Spina Bifida: Host Bone Marrow and Paracrine Activity.

PURPOSE: Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can induce spina bifida coverage with neoskin. We initiated a mechanistic analysis of this host response. METHODS: Pregnant dams (n = 28) exposed to retinoic acid to induce fetal spina bifida were divided into an untreated group and 2 groups receiving intra-amniotic injections on gestational day 17 (E17; term = E21-22) of either amniotic fluid-derived MSCs (afMSCs; n = 105) or saline (n = 107). Gene expressions of multiple paracrine and cell clonality markers were quantified at term by RT-qPCR at the defect and fetal bone marrow. Defects were examined histologically for neoskin coverage. Comparisons were by Mann-Whitney U tests and logistic regression. RESULTS: Defect coverage was associated with significant downregulation of both epidermal growth factor (Egf; p = 0.031) and fibroblast growth factor-2 (Fgf-2; p = 0.042) expressions at the defect and with significant downregulation of transforming growth factor-beta-1 (Tgfb-1; p = 0.021) and CD45 (p = 0.028) expressions at the fetal bone marrow. CONCLUSIONS: Coverage of experimental spina bifida is associated with local and bone marrow negative feedback of select paracrine factors, as well as increased relative mesenchymal stem cell activity in the bone marrow. Further analyses informed by these findings may lead to strategies of nonsurgical induction of prenatal coverage of spina bifida.

Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia.

Esophageal atresia (EA) is a congenital anomaly occurring in 2.3 per 10,000 live births. Due to advances in prenatal imaging, EA is more readily diagnosed, but data on the associated genetic diagnoses, other anomalies, and postnatal outcome for fetuses diagnosed prenatally with EA are scarce. We collected data from two academic medical centers (n = 61). Our data included fetuses with suspected EA on prenatal imaging that was confirmed postnatally and had at least one genetic test. In our cohort of 61 cases, 29 (49%) were born prematurely and 19% of those born alive died in the first 9 years of life. The most commonly associated birth defects were cardiac anomalies (67%) and spine anomalies (50%). A diagnosis was made in 61% of the cases; the most common diagnoses were vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, radial or renal dysplasia, and limb anomalies association (43%, although 12% met only 2 of the criteria), trisomy 21 (5%), and CHARGE syndrome (5%). Our findings suggest that most fetuses with prenatally diagnosed EA have one or more additional major anomaly that warrants a more comprehensive clinical genetics evaluation. Fetuses diagnosed prenatally appear to represent a cohort with a worse outcome.

Hematogenous Donor Cell Routing Pathway After Transamniotic Stem Cell Therapy.

Donor mesenchymal stem cells (MSCs) have been documented in fetal and maternal circulations after plain intra-amniotic injection, with diverse therapeutic effects. We sought to determine the pathway of this unique cell kinetic route. Rat fetuses (n = 226) were divided into two groups based on the content of intra-amniotic injections performed on gestational day 17 (E17): either a concentrated suspension of luciferase-labeled syngeneic amniotic fluid-derived MSCs (afMSCs; n = 111), or acellular luciferase (n = 115). Samples from placenta, chorion, amnion, amniotic fluid, stomach fluid, peripheral blood, and umbilical cord were procured at five daily time points thereafter until term (E18-22) for luminometry. In addition, 53 sets of fresh gestational membranes (chorion/amnion combined) from nonmanipulated term fetuses were secured to transwell inserts for in vitro analysis of MSC migration using luciferase-labeled afMSCs. Statistical analyses included the Mann-Whitney U-test, Wald test, nonlinear regression modeling, and Fisher's exact test. In vivo, luciferase activity was observed in the amnion, chorion, and placenta of fetuses receiving cells, but not in those receiving acellular luciferase (P < 0.001). There was a consistent nonlinear age-dependent relationship of luciferase activity between the amnion, chorion, and placenta following a parabolic bimodal pattern characterized by significantly higher early preterm (E18) and late-term (E22) activities (P < 0.001), with no differences between E21 and E22 (P = 0.12). In vitro, the presence of cells was documented by luminometry in 21/53 (39.6%) of the assays, in suspension and/or attached to the plastic substrate, and within all screened gestational membrane sets, irrespective of stimuli with collagen coating or fetal bovine serum. We conclude that, after intra-amniotic injection, donor MSCs undergo controlled cell routing, as opposed to passive clearance. Transgestational membrane transport appears to constitute the path for donor cells to reach the placenta, a known gateway to the fetal circulation, significantly expanding the potential applications of transamniotic stem cell therapy.

Postnatal fate of donor mesenchymal stem cells after transamniotic stem cell therapy in a healthy model.

PURPOSE: We sought to examine donor mesenchymal stem cell (MSC) fate after birth following transamniotic stem cell therapy (TRASCET) in a healthy model. METHODS: Lewis rat fetuses (n = 91) were divided into two groups based on the content of volume-matched intraamniotic injections performed on gestational day 17 (term = 21-22 days): either a suspension of amniotic fluid-derived MSCs (afMSCs) labeled with luciferase (n = 38) or acellular luciferase only (n = 53). Infused afMSCs consisted of syngeneic Lewis rat cells phenotyped by flow cytometry. Samples from 14 anatomical sites (heart, lung, brain, liver, spleen, pancreas, bowel, kidney, thyroid, skin, skeletal muscle, thymus, peripheral blood and bone marrow) from survivors were screened for luciferase activity 16 days after birth. Statistical analysis was by logistic regression and the Wald test (p < 0.05). RESULTS: Overall survival was 32% (29/91). When controlled by the acellular luciferase injections, donor afMSCs were not identified at any anatomical site in any neonate as measured by relative light units (all p > 0.05). Donor afMSC viability was confirmed in term placentas. CONCLUSIONS: Donor mesenchymal stem cells are not detectable in the neonate after intraamniotic injection in a normal syngeneic rodent model. This finding suggests that clinical trials of transamniotic stem cell therapy may be amenable to regulatory approval. LEVEL OF EVIDENCE: N/A (animal and laboratory study).

Donor mesenchymal stem cell kinetics after transamniotic stem cell therapy (TRASCET) in a rodent model of gastroschisis.

PURPOSE: We sought to comprehensively scrutinize donor mesenchymal stem cell kinetics following transamniotic stem cell therapy (TRASCET) in experimental gastroschisis. METHODS: A gastroschisis was surgically created in 102 rat fetuses at gestation day 18 (term = 22 days), immediately followed by volume-matched amniotic injections of either amniotic fluid mesenchymal stem cells (afMSCs) labeled with a luciferase reporter gene (n = 58), or luciferase protein alone (n = 44). Samples from multiple anatomical sites from survivors were screened for luciferase activity via microplate luminometry at term. Statistical analysis included Mann-Whitney U-test, Wald test, and kappa coefficient (p < 0.05). RESULTS: Overall survival was 42% (43/102), with no significant difference between the two groups (p = 0.82). When controlled by acellular luciferase, donor afMSCs were identified selectively in the placenta (p < 0.001) and bowel (p = 0.005), independently of the dams (respectively, p < 0.001 and p = 0.041). Bowel homing was documented exclusively in areas exposed to the amniotic cavity. There was no mutual correlation between placental and bowel homing (kappa = -0.02; p = 0.91). CONCLUSIONS: Amniotic mesenchymal stem cells home to specific sites after TRASCET in the setting of gastroschisis. Placental homing and intestinal homing are central yet seemingly independent constituents of cell trafficking, suggesting that both direct amniotic seeding and hematogenous routing take place. LEVEL OF EVIDENCE: N/A (animal and laboratory study).

Congenital diaphragmatic hernia as a potential target for transamniotic stem cell therapy.

PURPOSE: We sought to determine whether TRASCET could impact congenital diaphragmatic hernia (CDH). METHODS: Twelve pregnant dams received Nitrofen on gestational day 9.5 (E9; term = 22 days) to induce fetal CDH. Fetuses were divided into three groups: untreated (n = 31) and two groups receiving volume-matched intraamniotic injections of either saline (n = 37) or a suspension of 2 × 106 cells/mL of amniotic fluid-derived mesenchymal stem cells (afMSCs; n = 65) on E17. Animals were euthanized at term. Expression of fibroblast growth factor-10 (FGF-10), vascular endothelial growth factor-A (VEGF-A), and surfactant protein-C (SPC) was quantified by qRT-PCR. Statistical analysis was by the Mann-Whitney U test with Bonferroni adjusted criterion (p ≤ 0.01). RESULTS: Among survivors with CDH (n = 27/133), the TRASCET group showed significant downregulation of FGF-10 and VEGF-A gene expressions compared to the untreated (p < 0.001 for both) and saline groups (p = 0.005 and p = 0.004, respectively). SPC expression was higher in the TRASCET group compared to the untreated group (p = 0.01), but not the saline group (p = 0.043). Lung laterality had minimal impact on these comparisons. CONCLUSIONS: Transamniotic stem cell therapy affects select processes of lung development in experimental congenital diaphragmatic hernia. Further scrutiny into this novel therapy as a potential component of the prenatal management of this disease is warranted. LEVEL OF EVIDENCE: N/A (animal and laboratory study).

A comparison between placental and amniotic mesenchymal stem cells in transamniotic stem cell therapy for experimental gastroschisis.

PURPOSE: We compared placental and amniotic fluid-derived mesenchymal stem cells (pMSCs and afMSCs, respectively) in transamniotic stem cell therapy for experimental gastroschisis. METHODS: Gastroschisis was surgically created in 126 rat fetuses at gestational day 18 (term = 22 days), immediately followed by volume-matched intraamniotic injections of suspensions of afMSCs (n = 32), pMSCs (n = 33), or normal saline (NS) (n = 33). Untreated fetuses served as controls (n = 28). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thickness on the herniated bowel at term. Statistical analysis included ANOVA, the Wald test, and Levene's test (p < 0.05). RESULTS: Among survivors, there were statistically significant decreases in segmental and total bowel wall thicknesses in both the afMSC and pMSC groups vs. the untreated (p < 0.001 to 0.003) and saline (p < 0.001 to 0.011) groups. There were significant differences between the afMSC and pMSC groups favoring the former in both therapeutic impact and its variability (p < 0.001 to 0.031). Labeled cells were comparably identified within the intestinal wall in the afMSC and pMSC groups. CONCLUSIONS: Both placental and amniotic mesenchymal stem cells can mitigate bowel damage in experimental gastroschisis as agents of transamniotic stem cell therapy. However, amniotic cells lead to improved and more consistent outcomes. LEVEL OF EVIDENCE: N/A (animal and laboratory study).

A comparison of clinically relevant sources of mesenchymal stem cell-derived exosomes: Bone marrow and amniotic fluid.

BACKGROUND/PURPOSE: Exosomes may constitute a more practical alternative to live cells in select stem cell-based therapies. We sought to compare exosomes from two mesenchymal stem cell (MSC) sources relevant to perinatal and pediatric diseases. METHODS: Exosomes were isolated by reagent-enhanced centrifugation from cell culture media of banked human bone marrow (bm) and amniotic fluid (af) MSCs after serum starvation. Characterization was by flow exometry for tetraspanin markers CD9, CD63, and CD81, transmission electron microscopy for size and morphology, and tunable resistive pulse sensing for size distribution and concentration. Statistical comparisons of count data were made by Poisson regression modeling and Student's T-test. RESULTS: Exosomes of appropriate size and morphology were isolated with comparable expressions of CD9 (96% vs. 94%), CD63 (88% vs. 66%), and CD81 (71% vs. 63%) for bmMSC and afMSC, respectively. Total exosome yield (particles/mL) adjusted for number of cells was higher from afMSCs than bmMSCs by an estimated 25% (P < 0.001). CONCLUSIONS: While bone marrow and amniotic fluid mesenchymal stem cells are comparable sources of exosomes in size distribution, morphology, and expression of typical surface markers, yield may be higher from amniotic fluid cells. The amniotic fluid appears to be a preferable source of exosomes for clinical applications. LEVEL OF EVIDENCE: N/A (bench laboratory study).

Transamniotic stem cell therapy (TRASCET) in a rabbit model of spina bifida.

PURPOSE: Transamniotic stem cell therapy (TRASCET) with select mesenchymal stem cells (MSCs) has been shown to induce partial or complete skin coverage of spina bifida in rodents. Clinical translation of this emerging therapy hinges on its efficacy in larger animal models. We sought to study TRASCET in a model requiring intra-amniotic injections 60 times larger than those performed in the rat. METHODS: Rabbit fetuses (n = 65) with surgically created spina bifida were divided into three groups. One group (untreated) had no further manipulations. Two groups received volume-matched intra-amniotic injections of either saline or a concentrated suspension of amniotic fluid MSCs (afMSCs) at the time of operation. Infused afMSCs consisted of banked heterologous rabbit afMSCs with mesenchymal identity confirmed by flow cytometry, labeled with green fluorescent protein. Defect coverage at term was blindly categorized only if the presence of a distinctive neoskin was confirmed histologically. Statistical comparisons were by logistic regression and the likelihood ratio test. RESULTS: Among survivors with spina bifida (n = 19), there were statistically significant higher rates of defect coverage (all partial) in the afMSC group when compared with the saline and untreated groups (0-50%; p = 0.022-0.036), with no difference between the saline and untreated groups (p = 1.00). Donor afMSCs were identified locally, though sparsely and not in the neoskin. CONCLUSIONS: Concentrated intra-amniotic injection of amniotic mesenchymal stem cells can induce partial coverage of experimental spina bifida in a leporine model. Transamniotic stem cell therapy may become a feasible strategy in the prenatal management of spina bifida. LEVEL OF EVIDENCE: N/A (animal and laboratory study).

The Distended Fetal Hypopharynx: A Sensitive and Novel Sign for the Prenatal Diagnosis of Esophageal Atresia.

BACKGROUND/PURPOSE: Although advances have been made in the prenatal diagnosis of esophageal atresia (EA), most neonates are not identified until after birth. The distended hypopharynx (DHP) has been suggested as a novel prenatal sign for EA. We assess its diagnostic accuracy and predictive value on ultrasound (US) and magnetic resonance imaging (MRI), both alone and in combination with the esophageal pouch (EP) and secondary signs of EA (polyhydramnios and a small or absent fetal stomach). METHODS: We retrospectively reviewed fetal US and MRI reports and medical records of 88 pregnant women evaluated for possible EA from 2000 to 2016. Seventy-five had postnatal follow-up that confirmed or disproved the diagnosis of EA and were included in our analysis. RESULTS: Seventy-five women had 107 study visits (range 1-4). DHP and/or EP were seen on US and/or MRI in 36% of patients, and 78% of those patients had EA. DHP was 24% more sensitive for EA than EP, while EP was 30% more specific. After 28weeks of gestation, DHP had a predictive accuracy for EA of 0.929 (P=0.001). CONCLUSIONS: DHP is a sensitive additional prenatal sign of EA. More accurate diagnosis of EA allows for improved counseling regarding delivery, postnatal evaluation, and surgical correction. TYPE OF STUDY: Diagnostic. LEVEL OF EVIDENCE: Level II.

Fetal bone marrow homing of donor mesenchymal stem cells after transamniotic stem cell therapy (TRASCET).

PURPOSE: Donor cell engraftment patterns following transamniotic stem cell therapy (TRASCET) with amniotic fluid mesenchymal stem cells (afMSCs) are incompatible with solely direct amniotic seeding. We sought to determine whether fetal bone marrow is a component of such engraftment and to examine the chronology of afMSC placental trafficking. METHODS: Two groups of Sprague-Dawley rat fetuses received volume-matched intraamniotic injections on gestational day 17 (E17; term E22): either afMSCs labeled with a luciferase reporter gene or luciferase protein alone. Placental samples were procured at daily time points thereafter until term. Fetal bone marrow was obtained at term only owing to size constraints. Specimens were screened for luminescence via microplate luminometry. RESULTS: Donor afMSCs were identified in the bone marrow and placenta of fetuses receiving labeled afMSCs, but not in those receiving luciferase alone (P<0.001). Luminescence was significantly higher in placentas at E18 compared to E19 (P<0.001), E20 (P=0.007), and E21 (P=0.004), with no difference with E22/term (P=0.97). CONCLUSIONS: Donor mesenchymal stem cells home to the fetal bone marrow after intraamniotic injection. The chronology of placental trafficking is suggestive of controlled cell routing rather than plain cell clearance. Fetal bone marrow engraftment of donor cells significantly expands potential applications of transamniotic stem cell therapy.

Barriers to Adoption of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure: A Mixed-Methods Study.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are the most underutilized pharmacotherapy for heart failure. Minimal data are available on the barriers to MRA adoption from the perspective of prescribing clinicians. METHODS AND RESULTS: A mixed-methods study consisting of a survey (n=50), focus groups (n=39), interviews (n=6) with clinicians at a single US Department of Veterans Affairs medical center served to ascertain barriers to optimal use of MRAs. Participants were drawn from 6 groups: cardiology providers, cardiology fellows, hospitalists, clinical pharmacists, internal medicine residents, and primary care providers. Qualitative data were iteratively coded with qualitative data analysis software. The survey response rate was 17.3%. Overall, 51% of survey respondents were unfamiliar with eplerenone, and 6% were unfamiliar with spironolactone. In addition, 30% of respondents reported that they would order a laboratory test >2 weeks after a new MRA prescription, although that is beyond the guideline recommendation. Most providers correctly identified New York Heart Association class 3 and 4 patients as MRA eligible, but only 42% identified class 2 patients as MRA eligible. Through analysis of focus groups, we identified 8 barriers to MRA use in 3 categories: patient-based barriers (concerns about polypharmacy and comorbidities, adverse effects, perceived patient nonadherence), provider-based barriers (unclear roles and responsibilities, coordination and transitions of care, lack of experience or familiarity with MRAs), and system-based barriers (system overload and provider time constraints, lack of systematic follow-up procedures). CONCLUSIONS: Eight primary barriers to MRA adoption at the provider, patient, and health system levels were identified from the prescriber perspective. These barriers can inform the creation of multilevel interventions that will be required to close the gap in MRA adoption.

Simple formulas to determine optimal subclavian central venous catheter tip placement in infants and children.

BACKGROUND/PURPOSE: Optimal central venous catheter (CVC) tip location is necessary to decrease the incidence of complications related to their use. We sought to create a practical method to reliably predict the length of catheter to insert into the subclavian vein during CVC placement in children. METHODS: We performed a retrospective review of 727 chest radiographs of children who underwent either left or right subclavian CVC placement. We measured the distance from the subclavian entry site to the to the right atrium/superior vena cava (RA/SVC) junction, following the catheter's course. We analyzed the relationship between that length and patient characteristics, including: age, gender, height, weight and body surface area (BSA). RESULTS: Two derived formulas using the BSA best correlated with the optimal subclavian CVC length. For the left subclavian vein approach, the optimal catheter length was 6.5 BSA+7 cm, and for the right subclavian vein approach it was 5 BSA+6. The use of these formulas correlated in CVC tip placement in a clinically proper location in 92.9% of smaller children and in 95.7% of larger children. CONCLUSION: The optimal length of central venous catheter to insert into the subclavian vein may be determined through the use of a simple formula using the BSA.

Sensorineural hearing loss in congenital diaphragmatic hernia survivors is associated with postnatal management and not defect size.

BACKGROUND/PURPOSE: We determined the incidence of sensorineural hearing loss (SNHL; >20dB at any frequency) in a contemporary cohort of congenital diaphragmatic hernia (CDH) survivors at a single tertiary care center and identified potential risk factors for SNHL. METHODS: From 2000 through 2011, clinical and audiologic data were collected on 122 surgically-repaired Bochdalek CDH patients. CDH defect size, duration of ventilation, and cumulative aminoglycoside treatment were used for multivariate logistic regression. RESULTS: Incidence of SNHL was 7.4% (9/122). We identified one significant independent predictor of SNHL: cumulative length of aminoglycoside treatment (P<.001; OR 1.44, 95% CI: 1.13-1.83). CONCLUSIONS: Over the last decade, the incidence of SNHL in our CDH patients is low compared to previous reports in the literature (7.4%) and is not associated with CDH defect size or the need for extracorporeal membrane oxygenation. Prolonged duration of aminoglycoside treatment increases the risk of SNHL independent of defect size and duration of ventilation.

Prenatally-counseled congenital diaphragmatic hernia parents exhibit positive well-being before and after surgical repair.

BACKGROUND/PURPOSE: The purpose of this paper was to examine the effect of prenatal counseling in the Advanced Fetal Care Center (AFCC) on the well-being of parents of infants with congenital diaphragmatic hernia (CDH). METHODS: From 2008 through 2012, 26 mothers and fathers of surgically repaired CDH patients who received prenatal counseling at our institution, and 15 who received no prenatal counseling, each completed the Short-Form 36 version 1 (SF-36v1) at the appropriate time points: prenatal, two weeks, and six months post-surgery. RESULTS: Parents in both groups did not differ by demographic characteristics. Patients who received prenatal counseling had significantly longer ventilatory time and length of stay (LOS) in the ICU and in the hospital compared to those who did not receive prenatal counseling (all P<.01). Mothers and fathers had similar SF-36v1 mental and physical component summary (MCS, PCS) post-surgery scores when compared by counseling status. Prenatal MCS scores for mothers and fathers (47 vs. 41; P=.24) were similar to those at six months post-surgery (47 vs. 47; P=.90). CONCLUSIONS: When hospital LOS was controlled between groups stratified by AFCC counseling status, MCS scores were comparable prenatally and were sustained at six months post-surgery for both parents. These findings may reflect the support services parents received beginning in the prenatal period.

Ultrasonography-guided bilateral rectus sheath block vs local anesthetic infiltration after pediatric umbilical hernia repair: a prospective randomized clinical trial.

IMPORTANCE: Regional anesthetic techniques can be used to alleviate postoperative pain in children undergoing pediatric surgical procedures. Use of ultrasonographic guidance for bilateral rectus sheath block (BRSB) has been shown to improve immediate pain scores and reduce use of postoperative analgesia in the postanesthesia care unit (PACU). OBJECTIVE: To compare efficacy of ultrasonography-guided BRSB and local anesthetic infiltration (LAI) in providing postoperative analgesia after pediatric umbilical hernia repair. DESIGN: Prospective, observer-blinded, randomized clinical trial. SETTING: Tertiary-referral urban children's hospital. PARTICIPANTS: Eligible children 3 to 12 years of age undergoing elective umbilical hernia repair from November 16, 2009, through May 31, 2011. INTERVENTIONS: Ropivacaine hydrochloride administered at the conclusion of surgery as LAI by the surgeon (n = 25) or as ultrasonography-guided BRSB by the anesthesiologist (n = 27). MAIN OUTCOMES AND MEASURES: Scores on the FACES Pain Rating Scale measured at 10-minute intervals and all use of analgesic medications in the PACU. RESULTS: Median FACES scores in the PACU were lower in the BRSB group compared with the LAI group at 10 minutes (0 vs 1; P = .04), 30 minutes (0 vs 1; P = .01), and 40 minutes or later (0 vs 1; P = .03). Fewer doses of opioid and nonopioid medications were given to the BRSB group compared with the LAI group (5 vs 11 doses for opioids; 5 vs 10 for nonopioids). CONCLUSIONS AND RELEVANCE: In the PACU, ultrasonography-guided BRSB after umbilical hernia repair in children is associated with lower median FACES scores and decreased use of opioid and nonopioid medications compared with LAI. Future studies could examine the use of longer-acting anesthetic agents with ultrasonography-guided BRSB. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01015053.