James S. Barry

Neonatal intubation performance: room for improvement in tertiary neonatal intensive care units.

OBJECTIVE To describe neonatal tracheal intubation (TI) performance across five neonatal intensive care units. METHODS This prospective descriptive study was conducted at five level III neonatal intensive care units (NICU) between July 2010 and July 2011. TI performance data were collected using a standardized data collection instrument (provider, procedure, and patient characteristics) and analyzed using descriptive and inferential statistics. The primary outcome of interest was procedural success rate defined as a tube placed in the airway between the vocal cords that could be used to provide ventilation. RESULTS Forty-four percent of 455 TI attempts (203 patients) were successful. Attending physicians and 3rd year neonatal fellows had the highest success rates; 72.2% and 70%, respectively. Pediatric residents had the lowest success rate (20.3%). The median duration of attempts was 30s for residents, 25s for fellows, and 20s for neonatal attending physicians. The most common reasons cited for failure were inability to visualize the vocal cords (25%), patient decompensation (desaturation/bradycardia, 41%) and esophageal TI (19%). The duration of all TI attempts ranged from 5s to 180s and there was no difference between successful and failed attempts. Impending respiratory failure (46.5%) was the most common indication for TI. Patient factors (weight, gestational age, or number of previous TI attempts) were not associated with TI success. CONCLUSIONS Overall TI procedure success rates were poor. Providers with advanced training were more likely to be successful. Patient factors were not associated with TI success.

An animal model of placental insufficiency-induced intrauterine growth restriction.

Intrauterine growth restriction (IUGR), often associated with functional placental insufficiency, results in increased perinatal mortality and morbidity. For obvious reasons, many questions regarding the progression of IUGR pregnancies cannot be addressed experimentally in humans, predicating the use of animal models. Although no animal model fully recapitulates human pregnancy, the pregnant sheep has been used extensively to investigate maternal-fetal interactions. In sheep, surgical placement of catheters in both the maternal and fetal vasculature allows repeated sampling from nonanesthetized pregnancies. Considerable insight has been gained on placental oxygen and nutrient transfer and utilization from use of pregnant sheep, often confirmed in the human once appropriate technologies became available. This review will focus on one sheep model, used to examine the impact of placental insufficiency-induced IUGR on oxygen and nutrient transport and utilization.

Glucose replacement to euglycemia causes hypoxia, acidosis, and decreased insulin secretion in fetal sheep with intrauterine growth restriction

Nutritional interventions for intrauterine growth restriction (IUGR) have raised concerns for fetal toxicity, the mechanisms of which are unknown. Most of these attempts did not aim to normalize fetal metabolic conditions. Therefore, we used a model of IUGR to determine whether normalization of fetal hypoglycemia for 2 wks would be tolerated and increase insulin concentrations and pancreatic β-cell mass. IUGR fetuses received either a direct saline infusion (Sal, the control group) or a 30% dextrose infusion (Glu) to normalize glucose concentrations. Neither insulin concentrations (0.11 ± 0.01 Glu vs. 0.10 ± 0.01 ng/mL Sal) nor β-cell mass (65.2 ± 10.3 Glu vs. 74.7 ± 18.4 mg Sal) changed. Glucose stimulated insulin secretion (GSIS) was lower in the Glu group. Glu fetuses became progressively more hypoxic: O2 content 1.4 ± 0.5 Glu vs. 2.7 ± 0.4 mM Sal, p < 0.05. Partial pressure of carbon dioxide (Paco2) (53.6 ± 0.8 Glu vs. 51.6 ± 0.8 Sal, p < 0.05) and lactate (7.74 ± 3.82 Glu vs. 2.47 ± 0.55 mM Sal, p < 0.0001) were greater and pH lower (7.275 ± 0.071 Glu vs. 7.354 ± 0.003 Sal, p < 0.01) in the Glu group. We conclude that correction of fetal hypoglycemia is not well tolerated and fails to increase insulin concentrations or β-cell mass in IUGR fetuses.

Insulin is Required for Amino Acid Stimulation of Dual Pathways for Translational Control in Skeletal Muscle in the Late Gestation Ovine Fetus

During late gestation, amino acids and insulin promote skeletal muscle protein synthesis. However, the independent effects of amino acids and insulin on the regulation of mRNA translation initiation in the fetus are relatively unknown. The purpose of this study was to determine whether acute amino acid infusion in the late-gestation ovine fetus, with and without a simultaneous increase in fetal insulin concentration, activates translation initiation pathway(s) in skeletal muscle. Fetuses received saline (C), mixed amino acid infusion plus somatostatin infusion to suppress amino acid-stimulated fetal insulin secretion (AA+S), mixed amino acid infusion with concomitant physiological increase in fetal insulin (AA), or high-dose insulin infusion with euglycemia and euaminoacidemia (HI). After a 2-h infusion period, fetal skeletal muscle was harvested under in vivo steady-state conditions and frozen for quantification of proteins both upstream and downstream of mammalian target of rapamycin (mTOR). In the AA group, we found a threefold increase in ribosomal protein S6 kinase (p70(S6k)) and Erk1/2 phosphorylation; however, blocking the physiological rise in insulin with somatostatin in the AA+S group prevented this increase. In the HI group, Akt, Erk1/2, p70(S6k), and ribosomal protein S6 were highly phosphorylated and 4E-binding protein 1 (4E-BP1) associated with eukaryotic initiation factor (eIF)4E decreased by 30%. These data show that insulin is a significant regulator of intermediates involved in translation initiation in ovine fetal skeletal muscle. Furthermore, the effect of amino acids is dependent on a concomitant increase in fetal insulin concentrations, because amino acid infusion upregulates p70(S6k) and Erk only when amino acid-stimulated increase in insulin occurs.

Escherichia hermannii Infection of a Cephalohematoma: Case Report, Review of the Literature, and Description of a Novel Invasive Pathogen

We describe a neonate with bacterial infection of a cephalohematoma by Escherichia hermannii and with meningitis. We review the literature on infected cephalohematomas and E. hermannii and document the first case of invasive disease due to this pathogen.

Developmental Changes in Ovine Myocardial Glucose Transporters and Insulin Signaling Following Hyperthermia-Induced Intrauterine Fetal Growth Restriction

Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction (IUGR) were the focus of our study. Our objective was to test the hypothesis that the fetal ovine myocardium adapts during an IUGR gestation by increasing glucose transporter protein expression, plasma membrane-bound glucose transporter protein concentrations, and insulin signal transduction protein concentrations. Growth measurements and whole heart tissue were obtained at 55 days gestational age (dGA), 90 dGA, and 135 dGA (term = 145 dGA) in fetuses from control (C) and hyperthermic (HT) pregnant sheep. Additionally, in 135 dGA animals, arterial blood was obtained and Doppler ultrasound was used to determine umbilical artery systolic (S) and diastolic (D) flow velocity waveform profiles to calculate pulsatility (S – D/mean) and resistance (S – D/S) indices. Myocardial Glut-1, Glut-4, insulin signal transduction proteins involved in Glut-4 translocation, and glycogen content were measured. Compared to age-matched controls, HT 90-dGA fetal body weights and HT 135-dGA fetal weights and gross heart weights were lower. Heart weights as a percent of body weights were similar between C and HT sheep at 135 dGA. HT 135-dGA animals had (i) lower fetal arterial plasma glucose and insulin concentrations, (ii) lower arterial blood oxygen content and higher plasma lactate concentrations, (iii) higher myocardial Glut-4 plasma membrane (PM) protein and insulin receptor β protein (IRβ) concentrations, (iv) higher myocardial glycogen content, and (v) higher umbilical artery Doppler pulsatility and resistance indices. The HT ovine fetal myocardium adapts to reduced circulating glucose and insulin concentrations by increasing plasma membrane Glut-4 and IRβ protein concentrations. The increased myocardial Glut-4 PM and IRβ protein concentrations likely contribute to or increase the intracellular delivery of glucose and, together with the increased lactate concentrations, enhance glycogen synthesis, which allows for maintained myocardial growth commensurate with fetal body growth.

Prolonged maternal amino acid infusion in late-gestation pregnant sheep increases fetal amino acid oxidation

Protein supplementation during human pregnancy does not improve fetal growth and may increase small-for-gestational-age birth rates and mortality. To define possible mechanisms, sheep with twin pregnancies were infused with amino acids (AA group, n = 7) or saline (C group, n = 4) for 4 days during late gestation. In the AA group, fetal plasma leucine, isoleucine, valine, and lysine concentrations were increased (P < 0.05), and threonine was decreased (P < 0.05). In the AA group, fetal arterial pH (7.365 +/- 0.007 day 0 vs. 7.336 +/- 0.012 day 4, P < 0.005), hemoglobin-oxygen saturation (46.2 +/- 2.6 vs. 37.8 +/- 3.6%, P < 0.005), and total oxygen content (3.17 +/- 0.17 vs. 2.49 +/- 0.20 mmol/l, P < 0.0001) were decreased on day 4 compared with day 0. Fetal leucine disposal did not change (9.22 +/- 0.73 vs. 8.09 +/- 0.63 micromol x min(-1) x kg(-1), AA vs. C), but the rate of leucine oxidation increased 43% in the AA group (2.63 +/- 0.16 vs. 1.84 +/- 0.24 micromol x min(-1) x kg(-1), P < 0.05). Fetal oxygen utilization tended to be increased in the AA group (327 +/- 23 vs. 250 +/- 29 micromol x min(-1) x kg(-1), P = 0.06). Rates of leucine incorporation into fetal protein (5.19 +/- 0.97 vs. 5.47 +/- 0.89 micromol x min(-1) x kg(-1), AA vs. C), release from protein breakdown (4.20 +/- 0.95 vs. 4.62 +/- 0.74 micromol x min(-1) x kg(-1)), and protein accretion (1.00 +/- 0.30 vs. 0.85 +/- 0.25 micromol x min(-1) x kg(-1)) did not change. Consistent with these data, there was no change in the fetal skeletal muscle ubiquitin ligases MaFBx1 or MuRF1 or in the protein synthesis regulators 4E-BP1, eEF2, eIF2alpha, and p70(S6K). Decreased concentrations of certain essential amino acids, increased amino acid oxidation, fetal acidosis, and fetal hypoxia are possible mechanisms to explain fetal toxicity during maternal amino acid supplementation.

Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction

Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128–132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ∼38% (P < 0.01), but insulin-stimulated LV myocardial blood flow in IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r2 = 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P < 0.01), but to a greater extent in the IUGR fetuses compared to controls. During basal and hyperinsulinemic–euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy supply in the IUGR condition via increased glucose uptake and metabolic response to insulin, which support myocardial function and growth.

High surgical burden for infants with severe chronic lung disease (sCLD)

BACKGROUND/PURPOSE Infants with severe chronic lung disease (sCLD) may require surgical procedures to manage their medical problems; however, the scope of these interventions is undefined. The purpose of this study was to characterize the frequency, type, and timing of operative interventions performed in hospitalized infants with sCLD. METHODS The Childrens Hospital Neonatal Database was used to identify infants with sCLD from 24 childrens hospitals NICUs hospitalized over a recent 16-month period. RESULTS 556 infants were diagnosed with sCLD; less than 3% of infants had operations prior to referral and 30% were referred for surgical evaluation. In contrast, 71% of all sCLD infants received ≥1 surgical procedure during the CHND NICU hospitalization, with a mean of 3 operations performed per infant. Gastrostomy insertion (24%), fundoplication (11%), herniorrhaphy (13%), and tracheostomy placement (12%) were the most commonly performed operations. The timing of gastrostomy (PMA 48±10 wk) and tracheostomy (PMA 47±7 wk) insertions varied, and for infants who received both devices, only 33% were inserted concurrently (13/40 infants). CONCLUSIONS A striking majority of infants with sCLD received multiple surgical procedures during hospitalizations at participating NICUs. Further work regarding the timing, coordination, perioperative complications, and clinical outcomes for these infants is warranted.

Effect of small for gestational age on hemodynamic parameters in the neonatal period

Objective: The time course over which hypertension develops in children with a history of growth restriction has not been fully elucidated. The purpose of this study was to determine whether commonly obtained hemodynamic parameters were different between small for gestational age (SGA) and appropriate for gestational age (AGA) neonates. Methods: This was a retrospective case–control study matching 24 SGA neonates in a 1:2 fashion with 48 AGA neonates delivered during the same gestational week. Hemodynamic parameters were evaluated during the first week of life and the week prior to discharge. Results: There were no differences in blood pressure (BP) parameters during the first week of life. Compared to AGA controls, SGA neonates had a significantly lower heart rate (HR) at birth (148.2 ± 19.2 vs. 159.2 ± 17.1, p < 0.001), and a greater need for vasopressor support (OR 5.66; 95% CI 2.28, 14.04). The SGA neonates had a lower systolic BP during the week prior to discharge (68.3 ± 1.2 vs. 73.5 ± 1.2 mmHg, p < 0.001). Conclusions: SGA newborns had a lower HR at birth and greater need for vasopressor support during the first week of life despite similar BP parameters. SGA newborns had a lower systolic BP prior to discharge. Further studies are needed to understand the progression to adult hypertension.