Faculty Bibliography

BACKGROUND: Transport of premature infants incurs transfer-related morbidity, including intraventricular hemorrhage, a contributing factor to cerebral palsy. The force transmitted to the neonate during transport as a consequence of motion may be implicated in the increased morbidity in this population. Morbidity may occur via direct concussive force to a vulnerable germinal matrix, induction of an inflammatory reaction, or via transient desaturation via extubation. This transmitted force, measured as accelerations per unit time (impulse), is not well characterized. Any modification of a neonatal transporter which increases the time for a neonate in motion to come to rest may decrease the impulse experienced by the infant. OBJECTIVE: The objective of the study was to quantify the magnitude of impulse experienced by neonates during inter- and intra-hospital transport using a novel biophysical model and determine whether a specialized air-foam mattress can reduce the transmitted impulse on the neonate. METHODS: Five roundtrip trials were conducted for a transported neonate using a standard medical ambulance and transport isolette outfitted with an air-foam mattress. During the trials, measurements were made per second in the X (front-to-back), Y (side-to-side), and Z (up-and-down) planes using a computerized accelerometer attached to a neonatal resuscitation mannequin. Results were integrated over the trial time in each dimension to yield a measure of impulse (acceleration-per-unit-time). Total impulse for the trial was calculated. A second design included five trials from the delivery room to the NICU utilizing four different transport configurations with a standard neonatal isolette outfitted with a gel pillow, air-foam mattress, and air-foam mattress with gel pillow. RESULTS: Mean impulse for the transport model was statistically greater than at rest. In the X and Z dimensions, the mean impulse was significantly lower using the air-foam mattress. The impulse of the Z dimension with the air-foam mattress did not differ from that experienced by the experimental model at rest. For the intra-hospital trial, all experimental set-ups produced significantly less cumulative impulse than the standard isolette, though in each specific dimension, no significant differences were noted. For cumulative impulse, no significant differences between any of the three experimental designs were observed. A trend toward decreased transport time was seen with the addition of the air-foam mattress and gel pillow. CONCLUSIONS: The mechanical trauma induced by transport can be measured and quantified using this system. Neonates transported with the air-foam mattress experienced less impulse in the front-to-back and up-and-down dimensions. For transports between the delivery room and NICU, neonates transported using the air-foam mattress and gel pillow experienced significantly less total impulse

Pertussis infections in the United States are increasing as a consequence of waning immunity and increased surveillance. Those most at-risk of mortality include infants less than 6 months of age and premature infants. The 2006 immunization schedule emphasizes an adolescent pertussis booster at 12 years of age. However, of concern is the current generation of parents and grandparents who will still be un-immunized and therefore, available vectors of pertussis to vulnerable neonates. Given the proximity of parents to medical care in the Neonatal Intensive Care Unit (NICU), and the potential for severe disease in their children, NICU personnel should consider administration of acellular pertussis vaccine to parents of hospitalized infants

The purpose of this study was to determine an association between packed red blood cell (PRBC) transfusions for anemia and necrotizing enterocolitis (NEC) in a subset of stable, growing, premature neonates. As part of a survey of current clinical practices over a 17-month period from June 1999 to October 2000, a chart review was performed to determine the relationship between elective PRBC transfusions and the occurrence of NEC. Demographic data were tabulated and compared between the NEC patients with a prior history of immediate blood transfusion (within 48 hours of onset of symptoms) and those NEC patients without a prior history of immediate blood transfusion. A total of 908 (inborn) neonatal admissions had received 751 PRBC transfusions during the study period; of these, 17 patients (1.8%) had developed radiographic, clinical, or surgical signs of NEC. Six cases of NEC (35%; six of 17 patients) were associated with PRBC transfusions (0.8%; six of 751 transfusions). The transfusion-associated NEC group developed presenting signs within 22 +/- 5 hours (median, 19; range, 12 to 38) of a PRBC transfusion at a mean age of 32 +/- 7 days. In contrast, the non-transfusion-associated NEC group (n = 11) had onset of NEC at a mean age of 12 +/- 7 days ( P < 0.05) after 185 +/- 91 hours (median, 180; range, 96 to 312; P < 0.02] of a transfusion. Prior to the onset of NEC, all of the neonates in the transfusion-associated NEC group were stable, growing, not ventilated, receiving full enteral feedings, and had no other active medical problems except anemia (hematocrit, 24 +/- 3%). In contrast, the nontransfusion NEC group was more often ventilated, was receiving < 50% of fluids by mouth, had lower Apgar scores, and was transfused for an average hematocrit of 37 +/- 7% ( P < 0.05). There was no significant difference in the type, storage, volume, or preservative used between the blood products in the two groups. We identified an unanticipated relationship between late-onset NEC in stable, growing, premature neonates who were transfused electively for anemia of prematurity

Introduction: Endotracheal tubes are shortened to various lengths to prevent tube obstruction (kinking). The degree of this remaining length in the ET tube contributes increased resistance and dead space in the mechanical ventilatory circuit. Knowing ET tube resistance, at laminar flow, is inversely related to the fourth power of the radius (Poiseuille's Law) of the tube and proportional to length, additional work of breathing is created at different tube lengths. Neonates are at high risk for lobar atelectasis and congenital lung abnormalities, which reduce the lung available for gas exchange and if not acutely compensated for, can cause significant barotrauma to the remaining, intact lung. Yet, the relation of these variables and their clinical impact has not yet been mathematically defined. Hypothesis: For neonates with small ET tube diameters, there is a linear mathematical relationship between ET tube length and the positive inspiratory pressure (PIP) required to sustain tidal volume. These relationships can be derived graphically and are described by the equation for a line: y = mx + b. (where m equals the slope of a linear plot of positive inspiratory pressure versus ET length and b is set to the positive end expiratory pressure). There also exists a linear relationship between the lobar volume lost which can be described by the same equation on a graph of tidal volume vs. percentage of isolated atelectasis. Methods: Four endotracheal tubes ranging from 2.5mm to 4.0mm in diameter were shortened at one centimeter intervals and the pressure required by a mechanical ventilator in a pressure regulated, volume control mode (with a positive end expiratory pressure of 5ml H<inf>2</inf>O and without pressure support) to generate a tidal volume of 10ml was monitored in a synthetic, pre-formed plastic respiratory test lung with normal lung compliance (Cd<inf>2</inf>O/Cd of 0.94). Successive measurements at each tube length were sampled in each of three combined trials, the average of which used for calculations. Lobar parenchymal lung losses were simulated by external compression of the compliant lung model using a 3.0 mm tube at 8cm using ventilatory settings of PIP 15, PEEP 5. Tidal volume measurements were made using the calibrated Pneumotac of a VIP GOLD ventilator (ViaSys, California, USA). Results: For endotracheal tubes of 2.5mm, a graphical linear relationship between tube length and pressure was observed using the least squares method as described by the equation: PIP = 0.67 ETL + PEEP (Positive Inspiratory Pressure equals 0.67 multiplied by Endotracheal Tube Length plus Positive End Expiratory Pressure) For ET tubes of 3.0 mm the equation described was: PIP = 0.5 ETL = PEEP (Positive Inspiratory Pressure equals 0.5 multiplied by Endotracheal Tube Length plus Positive End Expiratory Pressure) For patients with lobar lung loss due to congenital malformation or atelectasis: Tidal Volume Lost = 0.04 (Percentage of lobar loss) + Tidal Volume Measured at PEEP (3.5 cm3 in this model). Conclusions: For neonatal infants with ET tubes of small diameters but with acceptable lung compliance, small increases in pressure may be needed to overcome intrinsic resistance of the ET tube and deliver adequate tidal volume. Further studies are needed to observe if these changes are clinically significant or are maintained in a poorly compliant lung model

Multiple intracellular and extracellular regulatory factors affect transcription of the tyrosine hydroxylase (TH) gene encoding the rate-limiting enzyme in the biosynthesis of the neurotransmitters dopamine, norepinephrine and epinephrine. Short chain fatty acids like butyrate are known to alter TH gene expression, but the mechanism of action is unknown. In this report, transient transfection assays identified the proximal TH promoter to contain sufficient genetic information to confer butyrate responsiveness to a reporter gene. Deletion studies and gel shift analyses revealed that the promoter region spanning the cAMP response element is an absolute requirement for transcriptional activation by butyrate. The branched short chain fatty acid valproate is used for seizure control in humans. Significantly, it has a similar aliphatic structure to butyrate, and it was found to have similar effects on TH in PC12 cells. Site-directed mutagenesis indicated that the effects of both fatty acids were mediated through the canonical CRE. Butyrate treatment also resulted in CREB phosphorylation without changing CREB protein levels. The increased phosphorylation of CREB correlated with accumulation of TH mRNA. The adenylate cyclase inhibitor dideoxyadenosine blocked both CREB phosphorylation and accumulation of TH mRNA. The data are consistent with the conclusion that butyrate induces post-translational modifications of pre-existing CREB molecules in a cAMP/PKA-dependent manner to alter TH transcription. These results support the role of butyrate as a novel exogenous regulatory factor in TH gene expression. Our data delineate a molecular mechanism through which diet-derived environmental signals (e.g. butyrate) can modulate catecholaminergic systems by affecting TH gene transcription