Mesenchymal stromal cell extracellular vesicles improve lung development in mechanically ventilated preterm lambs.

Novel therapies are needed for bronchopulmonary dysplasia (BPD) because no effective treatment exists. Mesenchymal stromal cell extracellular vesicles (MSC-sEVs) have therapeutic efficacy in a mouse pup neonatal hyperoxia BPD model. We tested the hypothesis that MSC-sEVs will improve lung functional and structural development in mechanically ventilated preterm lambs. Preterm lambs (∼129 days; equivalent to human lung development at ∼28 wk gestation) were exposed to antenatal steroids, surfactant, caffeine, and supported by mechanical ventilation for 6-7 days. Lambs were randomized to blinded treatment with either MSC-sEVs (human bone marrow MSC-derived; 2 × 1011 particles iv; n = 8; 4 F/4 M) or vehicle control (saline iv; 4 F/4 M) at 6 and 78 h post delivery. Physiological targets were pulse oximetry O2 saturation 90-94% ([Formula: see text] 60-90 mmHg), [Formula: see text] 45-60 mmHg (pH 7.25-7.35), and tidal volume 5-7 mL/kg. MSC-sEVs-treated preterm lambs tolerated enteral feedings compared with vehicle control preterm lambs. Differences in weight patterns were statistically significant. Respiratory severity score, oxygenation index, A-a gradient, distal airspace wall thickness, and smooth muscle thickness around terminal bronchioles and pulmonary arterioles were significantly lower for the MSC-sEVs group. S/F ratio, radial alveolar count, secondary septal volume density, alveolar capillary surface density, and protein abundance of VEGF-R2 were significantly higher for the MSC-sEVs group. MSC-sEVs improved respiratory system physiology and alveolar formation in mechanically ventilated preterm lambs. MSC-sEVs may be an effective and safe therapy for appropriate functional and structural development of the lung in preterm infants who require mechanical ventilation and are at risk of developing BPD.NEW & NOTEWORTHY This study focused on potential treatment of preterm infants at risk of developing bronchopulmonary dysplasia (BPD), for which no effective treatment exists. We tested treatment of mechanically ventilated preterm lambs with human mesenchymal stromal cell extracellular vesicles (MSC-sEVs). The results show improved respiratory gas exchange and parenchymal growth of capillaries and epithelium that are necessary for alveolar formation. Our study provides new mechanistic insight into potential efficacy of MSC-sEVs for preterm infants at risk of developing BPD.

Pilot dose-ranging of rhIGF-1/rhIGFBP-3 in a preterm lamb model of evolving bronchopulmonary dysplasia.

BACKGROUND: Low levels of insulin-like growth factor-1 (IGF-1) protein in preterm human infants are associated with bronchopulmonary dysplasia (BPD). We used our preterm lamb model of BPD to determine (1) dosage of recombinant human (rh) IGF-1 bound to binding protein-3 (IGFBP-3) to reach infant physiologic plasma levels; and (2) whether repletion of plasma IGF-1 improves pulmonary and cardiovascular outcomes. METHODS: Group 1: normal, unventilated lambs from 128 days gestation through postnatal age 5 months defined normal plasma levels of IGF-1. Group 2: continuous infusion of rhIGF-1/rhIGFBP-3 (0.5, 1.5, or 4.5 mg/kg/day; n = 2) for 3 days in mechanically ventilated (MV) preterm lambs determined that 1.5 mg/kg/day dosage attained physiologic plasma IGF-1 concentration of ~125 ng/mL, which was infused in four more MV preterm lambs. RESULTS: Group 1: plasma IGF-1 protein increased from ~75 ng/mL at 128 days gestation to ~220 ng/L at 5 months. Group 2: pilot study of the optimal dosage (1.5 mg/kg/day rhIGF-1/rhIGFBP-3) in six MV preterm lambs significantly improved some pulmonary and cardiovascular outcomes (p < 0.1) compared to six MV preterm controls. RhIGF-1/rhIGFBP-3 was not toxic to the liver, kidneys, or lungs. CONCLUSIONS: Three days of continuous iv infusion of rhIGF-1/rhIGFBP-3 at 1.5 mg/kg/day improved some pulmonary and cardiovascular outcomes without toxicity. IMPACT: Preterm birth is associated with rapid decreases in serum or plasma IGF-1 protein level. This decline adversely impacts the growth and development of the lung and cardiovascular system. For this pilot study, continuous infusion of optimal dosage of rhIGF-1/rhIGFBP-3 (1.5 mg/kg/day) to maintain physiologic plasma IGF-1 level of ~125 ng/mL during mechanical ventilation for 3 days statistically improved some structural and biochemical outcomes related to the alveolar formation that would favor improved gas exchange compared to vehicle-control. We conclude that 3 days of continuous iv infusion of rhIGF-1/rhIGFBP-3 improved some physiological, morphological, and biochemical outcomes, without toxicity, in mechanically ventilated preterm lambs.

Transforming Growth Factor-induced Protein Promotes NF-κB-mediated Angiogenesis during Postnatal Lung Development.

Pulmonary angiogenesis is a key driver of alveolarization. Our prior studies showed that NF-κB promotes pulmonary angiogenesis during early alveolarization. However, the mechanisms regulating temporal-specific NF-κB activation in the pulmonary vasculature are unknown. To identify mechanisms that activate proangiogenic NF-κB signaling in the developing pulmonary vasculature, proteomic analysis of the lung secretome was performed using two-dimensional difference gel electrophoresis. NF-κB activation and angiogenic function was assessed in primary pulmonary endothelial cells (PECs) and TGFBI (transforming growth factor-ß-induced protein)-regulated genes identified using RNA sequencing. Alveolarization and pulmonary angiogenesis was assessed in wild-type and Tgfbi null mice exposed to normoxia or hyperoxia. Lung TGFBI expression was determined in premature lambs supported by invasive and noninvasive respiratory support. Secreted factors from the early alveolar, but not the late alveolar or adult lung, promoted proliferation and migration in quiescent, adult PECs. Proteomic analysis identified TGFBI as one protein highly expressed by the early alveolar lung that promoted PEC migration by activating NF-κB via αvß3 integrins. RNA sequencing identified Csf3 as a TGFBI-regulated gene that enhances nitric oxide production in PECs. Loss of TGFBI in mice exaggerated the impaired pulmonary angiogenesis induced by chronic hyperoxia, and TGFBI expression was disrupted in premature lambs with impaired alveolarization. Our studies identify TGFBI as a developmentally regulated protein that promotes NF-κB-mediated angiogenesis during early alveolarization by enhancing nitric oxide production. We speculate that dysregulation of TGFBI expression may contribute to diseases marked by impaired alveolar and vascular growth.

Early extubation to noninvasive respiratory support of former preterm lambs improves long-term respiratory outcomes.

Invasive mechanical ventilation (IMV) and exposure to oxygen-rich gas during early postnatal life are contributing factors for long-term pulmonary morbidities faced by survivors of preterm birth and bronchopulmonary dysplasia. The duration of IMV that leads to long-term pulmonary morbidities is unknown. We compared two durations of IMV (3 h vs. 6 days) during the first 6-7 days of postnatal life in preterm lambs to test the hypothesis that minimizing the duration of IMV will improve long-term respiratory system mechanics and structural outcomes later in life. Moderately preterm (∼85% gestation) lambs were supported by IMV for either 3 h or 6 days before weaning from all respiratory support to become former preterm lambs. Respiratory system mechanics and airway reactivity were assessed monthly from 1 to 6 mo of chronological postnatal age by the forced oscillation technique. Quantitative morphological measurements were made for smooth muscle accumulation around terminal bronchioles and indices of alveolar formation. Minimizing IMV to 3 h led to significantly better (P < 0.05) baseline respiratory system mechanics and less reactivity to methacholine in the first 3 mo of chronological age (2 mo corrected age), significantly less (P < 0.05) accumulation of smooth muscle around peripheral resistance airways (terminal bronchioles), and significantly better (P < 0.05) alveolarization at the end of 5 mo corrected age compared with continuous IMV for 6 days. We conclude that limiting the duration of IMV following preterm birth of fetal lambs leads to better respiratory system mechanics and structural outcomes later in life.

Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age.

Preterm birth and mechanical ventilation (MV) frequently lead to bronchopulmonary dysplasia, the histopathological hallmark of which is alveolar simplification. How developmental immaturity and ongoing injury, repair, and remodeling impact completion of alveolar formation later in life is not known, in part because of lack of suitable animal models. We report a new model, using former-preterm lambs, to test the hypothesis that they will have persistent alveolar simplification later in life. Moderately preterm lambs (~85% gestation) were supported by MV for ~6 days before being transitioned from all respiratory support to become former-preterm lambs. Results are compared with term control lambs that were not ventilated, and between males (M) and females (F). Alveolar simplification was quantified morphometrically and stereologically at 2 mo (4 M, 4 F) or 5 mo (4 M, 6 F) corrected postnatal age (cPNA) compared with unventilated, age-matched term control lambs (4 M, 4 F per control group). These postnatal ages in sheep are equivalent to human postnatal ages of 1-2 yr and ~6 yr, respectively. Multivariable linear regression results showed that former-preterm lambs at 2 or 5 mo cPNA had significantly thicker distal airspace walls ( P < 0.001 and P < 0.009, respectively), lower volume density of secondary septa ( P < 0.007 and P < 0.001, respectively), and lower radial alveolar count ( P < 0.003 and P < 0.020, respectively) compared with term control lambs. Sex-specific differences were not detected. We conclude that moderate preterm birth and MV for ~6 days impedes completion of alveolarization in former-preterm lambs. This new model provides the opportunity to identify underlying pathogenic mechanisms that may reveal treatment approaches.

Preterm birth and ventilation decrease surface density of glomerular capillaries in lambs, regardless of postnatal respiratory support mode.

BACKGROUND: Prematurity is often complicated by respiratory support, including invasive mechanical ventilation (IMV) and noninvasive support (NIS). Compared with IMV, NIS reduces injury to the lung and brain. Prematurity may also disrupt glomerular architecture. Whether NIS differentially affects glomerular architecture is incompletely understood. We hypothesized that IMV would lead to greater disruption of glomerular architecture than NIS. METHODS: This is a secondary analysis of kidneys from moderately preterm lambs delivered at ~131 d gestation (term ~150 d) that had antenatal steroid exposure and surfactant treatment before resuscitation by IMV. At ~3 h of age, half of the lambs were switched to NIS. Support was for 3 d or 21 d. Structural indices of glomerular architecture were quantified. RESULTS: The number of glomerular generations was unaffected by moderate preterm birth and respiratory support, either IMV or NIS. At 3 d and 21 d of IMV or NIS, glomerular capillary surface density was not different. Glomerular capillary surface density was significantly lower in the inner and outer cortex compared with unventilated gestation age-matched or postnatal age-matched reference lambs. CONCLUSION: Moderate preterm birth and invasive or noninvasive respiratory support decreases glomerular capillarization in the lamb kidney. This adverse effect on glomerular development may contribute to increased risk for adult-onset hypertension and renal dysfunction.

Alveolar formation is dysregulated by restricted nutrition but not excess sedation in preterm lambs managed by noninvasive support.

BACKGROUND: Preterm birth and respiratory support with invasive mechanical ventilation frequently leads to bronchopulmonary dysplasia (BPD). A hallmark feature of BPD is alveolar simplification. For our preterm lamb model of BPD, invasive mechanical ventilation is associated with postnatal feeding intolerance (reduced nutrition) and sedation. In contrast, preterm lambs managed by noninvasive support (NIS) have normal alveolar formation, appropriate postnatal nutrition, and require little sedation. We used the latter, positive-outcome group to discriminate the contribution of reduced nutrition vs. sedation on alveolar simplification. We hypothesized that, restricted nutrition, but not sedation with pentobarbital, contributes to impaired indices of alveolar formation in preterm lambs managed by NIS. METHODS: Preterm lambs managed by NIS for 21d were randomized into three groups: NIS control, NIS plus restricted nutrition, and NIS plus excess sedation with pentobarbital. We quantified morphological and biochemical indices of alveolar formation, as well as mesenchymal cell apoptosis and proliferation. RESULTS: Restricted nutrition impaired morphological and biochemical indices of alveolar formation, and reduced mesenchymal cell apoptosis and proliferation. Excess sedation with pentobarbital did not alter these indices, although mesenchymal cell apoptosis was less. CONCLUSION: Our results demonstrate that restricted nutrition, but not excess sedation, contributes to impaired alveolar formation during the evolution of BPD in chronically ventilated preterm lambs.

High-frequency nasal ventilation for 21 d maintains gas exchange with lower respiratory pressures and promotes alveolarization in preterm lambs.

BACKGROUND: Short-term high-frequency nasal ventilation (HFNV) of preterm neonates provides acceptable gas exchange compared to endotracheal intubation and intermittent mandatory ventilation (IMV). Whether long-term HFNV will provide acceptable gas exchange is unknown. We hypothesized that HFNV for up to 21 d would lead to acceptable gas exchange at lower inspired oxygen (O2) levels and airway pressures compared to intubation and IMV. METHODS: Preterm lambs were exposed to antenatal steroids and treated with perinatal surfactant and postnatal caffeine. Lambs were intubated and resuscitated by IMV. At ~3 h of age, half of the lambs were switched to noninvasive HFNV. Support was for 3 or 21 d. By design, Pao2 and Paco2 were not different between groups. RESULTS: At 3 d (n = 5) and 21 d (n = 4) of HFNV, fractional inspired O2 (FiO2), peak inspiratory pressure (PIP), mean airway, intratracheal, and positive end-expiratory pressures, oxygenation index, and alveolar-arterial gradient were significantly lower than matched periods of intubation and IMV. Pao2/FiO2 ratio was significantly higher at 3 and 21 d of HFNV compared to matched intubation and IMV. HFNV led to better alveolarization at 3 and 21 d. CONCLUSION: Long-term HFNV provides acceptable gas exchange at lower inspired O2 levels and respiratory pressures compared to intubation and IMV.

A family-based paradigm to identify candidate chromosomal regions for isolated congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that causes high newborn mortality. Isolated or non-syndromic CDH is considered a multifactorial disease, with strong evidence implicating genetic factors. As low heritability has been reported in isolated CDH, family-based genetic methods have yet to identify the genetic factors associated with the defect. Using the Utah Population Database, we identified distantly related patients from several extended families with a high incidence of isolated CDH. Using high-density genotyping, seven patients were analyzed by homozygosity exclusion rare allele mapping (HERAM) and phased haplotype sharing (HapShare), two methods we developed to map shared chromosome regions. Our patient cohort shared three regions not previously associated with CDH, that is, 2q11.2-q12.1, 4p13 and 7q11.2, and two regions previously involved in CDH, that is, 8p23.1 and 15q26.2. The latter regions contain GATA4 and NR2F2, two genes implicated in diaphragm formation in mice. Interestingly, three patients shared the 8p23.1 locus and one of them also harbored the 15q26.2 segment. No coding variants were identified in GATA4 or NR2F2, but a rare shared variant was found in intron 1 of GATA4. This work shows the role of heritability in isolated CDH. Our family-based strategy uncovers new chromosomal regions possibly associated with disease, and suggests that non-coding variants of GATA4 and NR2F2 may contribute to the development of isolated CDH. This approach could speed up the discovery of the genes and regulatory elements causing multifactorial diseases, such as isolated CDH.

Novel Use of a Bronchial Blocker in a Challenging Case of Congenital Diaphragmatic Hernia-A Case Report.

The diagnosis of congenital diaphragmatic hernia (CDH) is associated with significant morbidity and mortality. Survival of neonates with CDH has improved recently, although the clinical course is complicated by sequelae of hypoplastic pulmonary parenchyma and vasculature, pulmonary hypertension, ventilation/perfusion (V/Q) mismatch, reduced pulmonary function and poor somatic growth. In this case report, we describe an infant with an antenatal diagnosis of CDH with a poor prognosis who underwent initial surgery followed by a tracheostomy but had a worsening clinical course due to a large area of ventilated but poorly perfused lung based on a V/Q nuclear scintigraphy scan. The emphysematous left lung was causing mediastinal shift and compression of the right lung, further compromising gas exchange. The infant had clinical improvement following bronchial blockade of the under-perfused left lung. This paved the way for further management with resection of the under-perfused lung lobe and continued clinical improvement. We present the novel use of selective bronchial blockade in a challenging case of CDH to determine if surgical lung resection may benefit the infant. We also review the physiology of gas exchange during the use of a bronchial occluder and the relevant literature.

Inhaled nitric oxide in preterm infants undergoing mechanical ventilation.

BACKGROUND: Bronchopulmonary dysplasia in premature infants is associated with prolonged hospitalization, as well as abnormal pulmonary and neurodevelopmental outcome. In animal models, inhaled nitric oxide improves both gas exchange and lung structural development, but the use of this therapy in infants at risk for bronchopulmonary dysplasia is controversial. METHODS: We conducted a randomized, stratified, double-blind, placebo-controlled trial of inhaled nitric oxide at 21 centers involving infants with a birth weight of 1250 g or less who required ventilatory support between 7 and 21 days of age. Treated infants received decreasing concentrations of nitric oxide, beginning at 20 ppm, for a minimum of 24 days. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. RESULTS: Among 294 infants receiving nitric oxide and 288 receiving placebo birth weight (766 g and 759 g, respectively), gestational age (26 weeks in both groups), and other characteristics were similar. The rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was 43.9 percent in the group receiving nitric oxide and 36.8 percent in the placebo group (P=0.042). The infants who received inhaled nitric oxide were discharged sooner (P=0.04) and received supplemental oxygen therapy for a shorter time (P=0.006). There were no short-term safety concerns. CONCLUSIONS: Inhaled nitric oxide therapy improves the pulmonary outcome for premature infants who are at risk for bronchopulmonary dysplasia when it is started between 7 and 21 days of age and has no apparent short-term adverse effects. (ClinicalTrials.gov number, NCT00000548 [ClinicalTrials.gov] .).

Very high users of platelet transfusions in the neonatal intensive care unit.

BACKGROUND: In neonatal intensive care unit (NICU) practice, a small percentage of the patients receive a large proportion of the platelet (PLT) transfusions administered. This study sought to better define this very-high-user group. To accomplish this, records of all NICU patients in a multihospital health care system who, during a recent 5(1/2)-year period, received 20 or more PLT transfusions were examined. STUDY DESIGN AND METHODS: Electronic medical record repositories of Intermountain Healthcare neonates with dates of birth from January 1, 2002, through June 30, 2007, who received 20 or more PLT transfusions were identified. The causes of the thrombocytopenia were sought, whether each transfusion given was a treatment for bleeding versus prophylaxis was determined, whether each transfusion was compliant with our transfusion guidelines was judged, and the outcomes were tabulated. RESULTS: During this period, 45 patients received 20 or more PLT transfusions (median, 29; range, 20-79). Medical conditions could be categorized into six diagnoses: 1) extracorporeal membrane oxygenation (ECMO) for congenital diaphragmatic hernia (CDH; n = 13), 2) fungal sepsis (n = 8), 3) ECMO for reasons other than CDH (n = 8), 4) necrotizing enterocolitis (n = 7), 5) bacterial sepsis (n = 7), and 6) congenital hyporegenerative thrombocytopenia (n = 2). Nineteen percent of the transfusions were ordered for oozing, bruising, or bleeding and 81 percent for prophylaxis. Thirty-six percent of transfusions were given in violation of our transfusion guidelines. Forty-nine percent of the high users died, but no deaths were due to hemorrhage. All survivors developed chronic lung disease, and all survivors weighing less than 1250 g at birth developed retinopathy of prematurity. CONCLUSIONS: Almost all patients that received 20 or more PLT transfusions had an acquired, consumptive thrombocytopenia. All could have received fewer transfusions had the guidelines already in place been observed. Eighty-one percent fewer PLT transfusions would have been administered had the paradigm been transfusing only if oozing, bruising, or bleeding was present.

Nasal ventilation alters mesenchymal cell turnover and improves alveolarization in preterm lambs.

RATIONALE: Bronchopulmonary dysplasia (BPD) is a frequent cause of morbidity in preterm infants that is characterized by prolonged need for ventilatory support in an intensive care environment. BPD is characterized histopathologically by persistently thick, cellular distal airspace walls. In normally developing lungs, by comparison, remodeling of the immature parenchymal architecture is characterized by thinning of the future alveolar walls, a process predicated on cell loss through apoptosis. OBJECTIVES: We hypothesized that minimizing lung injury, using high-frequency nasal ventilation to provide positive distending pressure with minimal assisted tidal volume displacement, would increase apoptosis and decrease proliferation among mesenchymal cells in the distal airspace walls compared with a conventional mode of support (intermittent mandatory ventilation). METHODS: Accordingly, we compared two groups of preterm lambs: one group managed by high-frequency nasal ventilation and a second group managed by intermittent mandatory ventilation. Each group was maintained for 3 days. MEASUREMENTS AND MAIN RESULTS: Oxygenation and ventilation targets were sustained with lower airway pressures and less supplemental oxygen in the high-frequency nasal ventilation group, in which alveolarization progressed. Thinning of the distal airspace walls was accompanied by more apoptosis, and less proliferation, among mesenchymal cells of the high-frequency nasal ventilation group, based on morphometric, protein abundance, and mRNA expression indices of apoptosis and proliferation. CONCLUSIONS: Our study shows that high-frequency nasal ventilation preserves the balance between mesenchymal cell apoptosis and proliferation in the distal airspace walls, such that alveolarization progresses.

Effect of Heliox on Respiratory Outcomes during Rigid Bronchoscopy in Term Lambs.

Objective To (1) compare physiologic changes during rigid bronchoscopy during spontaneous and mechanical ventilation and (2) evaluate the efficacy of a helium-oxygen (heliox) gas mixture as compared with room air during rigid bronchoscopy. Study Design Crossover animal study evaluating physiologic parameters during rigid bronchoscopy. Outcomes were compared with predicted computational fluid analysis. Setting Simulated ventilation via computational fluid dynamics analysis and term lambs undergoing rigid bronchoscopy. Methods Respiratory and physiologic outcomes were analyzed in a lamb model simulating bronchoscopy during foreign body aspiration to compare heliox with room air. The main outcome measures were blood oxygen saturation, heart rate, blood pressure, partial pressure of oxygen, and partial pressure of carbon dioxide. Computational fluid dynamics analysis was performed with SOLIDWORKS within a rigid pediatric bronchoscope during simulated ventilation comparing heliox with room air. Results For room air, lambs desaturated within 3 minutes during mechanical ventilation versus normal oxygen saturation during spontaneous ventilation ( P = .01). No improvement in respiratory outcomes was seen between heliox and room air during mechanical ventilation. Computational fluid dynamics analysis demonstrates increased turbulence within size 3.5 bronchoscopes when comparing heliox and room air. Meaningful comparisons could not be made due to the intolerance of the lambs to heliox in vivo. Conclusion During mechanical ventilation on room air, lambs desaturate more quickly during rigid bronchoscopy on settings that should be adequate. Heliox does not improve ventilation during rigid bronchoscopy.

Noninvasive Respiratory Support During Transportation.

To minimize ventilator-associated lung injury in neonates, use of noninvasive (NIV) respiratory support has markedly increased over the past decade, especially in neonates younger than 28-weeks gestational age and 1250 g. Previously, neonates with respiratory failure who required anything greater than an oxyhood or low-flow nasal cannula were intubated for transport. This increased use has required transport teams to develop or incorporate a new set of support tools to minimize lung injury. This article reviews the various modes of NIV used during neonatal transport, important patient selection criteria, appropriate assessment, and the associated risks and benefits.

Safety and immunogenicity of palivizumab (Synagis) administered for two seasons.

To evaluate the safety and immunogenicity of palivizumab, 55 children who received palivizumab in the IMpact-RSV trial received 5 monthly doses of 15 mg/kg palivizumab (Synagis) during the subsequent year. The single child with an antipalivizumab titer of >1/40 had no associated serious adverse events and had expected serum palivizumab trough concentrations. Second year palivizumab prophylaxis was safe and well-tolerated.

Utility of neuroradiographic imaging in predicting outcomes after neonatal extracorporeal membrane oxygenation.

BACKGROUND: The need for routine neuroimaging after extracorporeal membrane oxygenation (ECMO) and the optimal radiographic study remains unclear. We sought to evaluate the correlation between findings on head ultrasound (HUS) and magnetic resonance imaging (MRI) and determine the association of these findings to neurodevelopmental outcome. METHODS: A retrospective review was performed (2003-2010) to identify neonates who had a MRI after ECMO. Each MRI was reviewed by a single pediatric neuroradiologist. Neurodevelopmental data was collected from the high-risk neonatal follow-up clinic. RESULTS: Fifty neonates had a MRI (venoarterial 37, venovenous 13) after ECMO. HUS was abnormal in 24%, whereas MRI was abnormal in 62%. All infants with an abnormal HUS had an abnormal MRI, but an additional 50% of patients with a normal HUS had an abnormal MRI. Venoarterial ECMO was significantly associated with an abnormal MRI. Follow-up data was available for 26 neonates. The only predictor of abnormal neurodevelopment was the need for supplemental tube feeds at discharge. CONCLUSIONS: MRI identified significantly more abnormalities compared to routine HUS after neonatal ECMO. However, neither MRI nor HUS findings correlated with early neurodevelopmental outcome. Feeding ability at discharge was the overall best predictor of neurologic impairment in survivors.

Coarctation repair in neonates and young infants: is small size or low weight still a risk factor?

OBJECTIVE: Previous reports of neonatal coarctation repair demonstrate a high rate of recurrent arch obstruction in small neonates. This study assesses the effect of patient size on reintervention and survival in neonates and infants undergoing repair of simple aortic coarctation. METHODS: From 1996 to 2006, 167 neonates and infants younger than 90 days with simple coarctation underwent repair. Median patient age was 16 days (range, 1-85 days). Median patient weight was 3.4 kg (range, 0.8-6.0 kg), with 29 patients weighing less than 2.5 kg. All 167 patients included in the study underwent repair through a left thoracotomy. RESULTS: There was 1 early death (1/167, 0.6%). Median follow-up of 4.8 years (range, 0-11.8 years) demonstrated 2 late deaths unrelated to recurrent coarctation. Eighteen patients underwent intervention for recurrent arch obstruction a median of 0.48 years postoperatively (range, 0.14-9.8 years). All were treated with balloon angioplasty and have required no additional intervention. Actuarial freedom from reintervention was 90% at 1 year and 89% at 5 years for infants weighing more than 2.5 kg and 89% at 1 year and 86% at 5 years (P = .31) for infants weighing less than 2.5 kg. There was no difference between survival or reintervention for neonates 30 days of age or younger compared with infants 31 to 90 days of age. Use of polypropylene sutures and female sex did correlate with increased reintervention. CONCLUSIONS: Low weight does not affect survival or reintervention rates after coarctation repair in neonates and infants less than 3 months of age. Balloon angioplasty is an effective treatment for recurrent obstruction after coarctation repair in infancy. In the current era, timing of the operation should be based on clinical status.

Use of the Duotron transporter high frequency ventilator during neonatal transport.

In the past, transport of neonates with severe respiratory failure was hampered by the lack of an appropriate transport ventilator capable of providing high frequency ventilation (HFV). This article reports on the experiences of the Intermountain Health Care Life Flight Program in selecting a high frequency ventilator and preparing the transport team members for its use. Once the use of the Duotron ventilator was initiated, pre- and posttransport data were collected for the first 134 neonates requiring HFV on transport. Analysis of the data determined that 96 percent of the infants were successftslly transported using the Duotron ventilator. Inspired oxygen requirements staved the same or improved in the majority of intubated patients for whom comparison data xvere available. Ventilation and acid-base balance improved. Although HFV has been a common therapy in neonatal care for some time, its adoption for use during transport required modification and considerable education for transport team members.