Pradeep Mally

Packed red blood cell transfusion increases regional cerebral and splanchnic tissue oxygen saturation in anemic symptomatic preterm infants.

Preterm infants often receive multiple packed red blood cell (PRBC) transfusions that are intended to improve tissue oxygen levels. Near-infrared spectroscopy (NIRS) monitors regional cerebral tissue oxygen saturation (CrSO(2)) and splanchnic tissue oxygen saturation (SrSO(2)). Before such technology can be employed in neonatal transfusion management, it must first be established that transfusions result in an increase in tissue oxygen saturation. This prospective, observational study used NIRS to determine if PRBC transfusions increase the CrSO(2) and SrSO(2) of symptomatic anemic premature neonates. CrSO(2) and SrSO(2) values were compared for 20-minute duration immediately before, during, immediately after, and 12 hours after transfusion. As a secondary objective, CrSO(2) and SrSO(2) values were correlated with hemoglobin (Hgb) levels. One-way analysis of variance and Pearson correlation statistical tests were used for analysis. A statistically significant increase in CrSO(2) and SrSO(2) values were observed after transfusion in the 30 subjects included (CrSO(2): 62.8 +/- 1.6, 65.6 +/- 1.7, 68.0 +/- 1.3, 67.6 +/- 1.4, P < 0.001 and SrSO(2): 41.3 +/- 2.2, 46.7 +/- 3.0, 52.1 +/- 2.8, 48.2 +/- 2.5, P < 0.001). No correlation was found between CrSO(2) or SrSO(2) and Hgb values. NIRS identified increases in CrSO(2) and SrSO(2) in preterm neonates after PRBC transfusions and has the potential to become incorporated into neonatal transfusion management paradigms.

Clinical issues in the management of late preterm infants.

Prematurity is defined as birth before 37 weeks of gestation and is the major determinant of morbidity and mortality in newborns. The gestational ages known as near term or late preterm represent about 75% of preterm births and are the fastest growing subgroups of premature infants. These infants range in gestational age from 34 0/7 to 36 6/7 weeks and are at greater risk of morbidity, such as respiratory complications, temperature instability, hypoglycemia, kernicterus, feeding problems, neonatal intensive care unit admissions, and adverse neurological sequelae when compared with term infants. Long-term neurological and school-age outcomes of late preterm infants are concerns of major public health importance because even a minor increase in the rate of neurological disability and scholastic failure in this group can have a huge impact on the health care and educational systems. There is an urgent need to educate health care providers and parents about the vulnerability of late preterm infants, who are in need of diligent monitoring and care during the initial hospital stay and a comprehensive follow-up plan for post neonatal and long-term evaluations. Clinicians involved in the day-to-day care of late preterm infants, as well as those developing guidelines and recommendations, would benefit from having a clear understanding of the potential differences in risks faced by these infants, compared with their more mature counterparts.

Splanchnic‐cerebral oxygenation ratio as a marker of preterm infant blood transfusion needs

BACKGROUND: Premature neonates often receive red blood cell (RBC) transfusions to improve tissue perfusion and oxygen delivery. Clinical and laboratory indicators used to guide transfusion therapy are inadequate to determine physiologic need with high predictability and transfusions frequently do not result in clinical improvement. The splanchnic‐cerebral oxygenation ratio (SCOR) provides insight into overall tissue oxygen sufficiency and can be determined using near‐infrared spectroscopy (NIRS). Our aim was to assess the usefulness of SCOR as a marker for transfusion need in preterm infants.

Stereospecific Regulation of Tyrosine Hydroxylase and Proenkephalin Genes by Short-Chain Fatty Acids in Rat PC12 Cells

Circulating short-chain fatty acids (SCFAs) are primarily derived from bacterial fermentation of carbohydrates in the colon where they function as physiologic modulators of epithelial cell maturation. Butyrate has been shown to induce tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis, and enkephalin neuropeptide gene transcription, suggesting a role in perinatal sympathoadrenal stress-adaptation. We sought to determine whether there were SCFA structural requirements for this effect. Nine biologically relevant SCFAs and butyrate derivatives were tested in an in vitro model (PC12, rat pheochromocytoma cells) for their ability to regulate neurotransmitter-related gene expression. Our results revealed that among all the studied SCFAs, only propionate and butyrate increased tyrosine hydroxylase and proenkephalin mRNA levels. The functional activity was selective to the carbon atom chain length and associated with the presence of an ethyl moiety in the carbon atom backbone chain. Modifications or absence of this domain affected the gene induction response, suggesting a receptor-mediated mechanism(s). Moreover, propionate, butyrate, and the drug 4-phenyl-butyrate were each shown to regulate transmitter genes via at least three independent mechanisms: histone hyperacetylation, cAMP signaling, or peroxisome proliferator-activated receptor gamma–mediated pathways. Thus, the biologic impact of SCFAs on catecholaminergic and opioid systems depend on the activation of SCFA-specific, dose-specific, and gene-specific molecular mechanisms. We speculate that 1) circulating levels of SCFAs may influence sympathoadrenal transmitter biosynthesis and hence whole animal stress-adaptive responsiveness after birth, and 2) the adverse effects of antibiotics on delayed acquisition of postnatal gut flora may affect this apparent evolutionary advantage of gut colonization.

Incidence and Etiology of Late Preterm Admissions to the Neonatal Intensive Care Unit and Its Associated Respiratory Morbidities When Compared to Term Infants

OBJECTIVE To determine etiology of neonatal intensive care unit (NICU) admission and acute morbidities in late preterm (LPT) neonates. METHODS Neonates admitted at New York University Langone Medical Centers NICU were grouped as follows: period 1: all LPT neonates with gestational age between 34(0)/(7) and 36(6)/(7) weeks and born between January 2006 and June 2007; period 2: all term neonates born between January 2007 and June 2008. Neonatal and maternal data were collected from both the groups and compared. RESULTS Thirty-three percent of LPT births were admitted to the NICU, compared with 7% of term births (p < 0.05). LPT neonates had an increased incidence of low birth weight, hypoglycemia, hypothermia, and hyperbilirubinemia as an admission diagnosis (p < 0.001). The overall incidence of respiratory distress syndrome (RDS) was 9%, 4%, 3%, 0.7%, 0.2% and 0% in 34-week, 35-week, 36-week, 37-week, 38- to 39-week, and 40-week gestational age neonates (p < 0. 001).There was an increased incidence of RDS and persistent pulmonary hypertension, along with an increased need for surfactant replacement therapy, continuous positive airway pressure, and ventilator support in the LPT group when compared with the term neonates (p < 0.001). CONCLUSIONS LPT neonates are at increased risk for hypothermia, hypoglycemia, hyperbilirubinemia, and respiratory morbidity requiring increased respiratory support when compared with term neonates.

Evacuation of a Neonatal Intensive Care Unit in a Disaster: Lessons From Hurricane Sandy

NICU patients are among those potentially most vulnerable to the effects of natural or man-made disaster on a medical center. The published data on evacuations of NICU patients in the setting of disaster are sparse. In October of 2012, New York University Langone Medical Center was evacuated during Hurricane Sandy in the setting of a power outage secondary to a coastal surge. In this setting, 21 neonates were safely evacuated from the medical center’s NICU to receiving hospitals within New York City in a span of 4.5 hours. Using data recorded during the evacuation and from staff debriefings, we describe the challenges faced and lessons learned during both the power outage and vertical evacuation. From our experience, we identify several elements that are important to the functioning of an NICU in a disaster or to an evacuation that may be incorporated into future NICU-focused disaster planning. These include a clear command structure, backups (personnel, communication, medical information, and equipment), establishing situational awareness, regional coordination, and flexibility as well as special attention to families and to the availability of neonatal transport resources.

Cerebral, renal, and splanchnic tissue oxygen saturation values in healthy term newborns.

OBJECTIVE To determine cerebral regional tissue oxygen saturation (CrSO2), renal regional tissue oxygen saturation (RrSO2), and splanchnic regional tissue oxygen saturation (SrSO2) values in healthy term infants. STUDY DESIGN Near-infrared spectroscopy was used to simultaneously measure CrSO2, RrSO2, and SrSO2 continuously for a 1-hour period on the first and second days of life. RESULTS  A total of 41 subjects were monitored out of which complete data were available for 38 subjects. Mean CrSO2 was 78.2  ± 7.9% on first day; 78.3 ± 6.1% on second day (p = 0.95). Mean RrSO2 was 92.1 ± 5.3% on first day; 88.9 ± 5.9% on second day (p < 0.01). Mean SrSO2 was 69.9 ± 12.1% on first day and 75.3 ± 12.4% on second day (p = 0.02). CONCLUSION There appears to be consistency in rSO2 values in healthy newborns. CrSO2 was similar on both days. Differences observed in RrSO2 and SrSO2 between days may represent a shift in somatic blood flow distribution taking place during the first day of life.

Quantification of impulse experienced by neonates during inter- and intra-hospital transport measured by biophysical accelerometery.

Abstract 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.

Variability in splanchnic tissue oxygenation during preterm red blood cell transfusion given for symptomatic anaemia may reveal a potential mechanism of transfusion-related acute gut injury.

BACKGROUND There is increasing evidence indicating an association between red blood cell (RBC) transfusions and necrotising enterocolitis (NEC) in preterm infants, especially late-onset NEC. This phenomenon is referred to as transfusion-related acute gut injury (TRAGI). One theory as to a pathophysiological mechanism is that transfusion may result in an ischemia-reperfusion injury to intestinal tissue. We tested the hypothesis that there is significantly greater variability during transfusion in splanchnic tissue oxygen saturation (SrSO2) than in cerebral tissue oxygen saturation (CrSO2). MATERIALS AND METHODS This was a prospective, observational study using near-infrared spectroscopy to monitor SrSO2 and CrSO2 in preterm neonates undergoing RBC transfusion for symptomatic anaemia. Mean, standard deviation, highest and lowest SrSO2 and CrSO2 values during each transfusion were determined. The greatest difference in SrSO2 and CrSO2 during each transfusion was calculated, along with the coefficient of variation. RESULTS We studied 37 subjects. Throughout all transfusions, the mean SrSO2 was 45.6% ±13.8 and the mean CrSO2 was 65.4% ±6.9 (p<0.001). The variability of SrSO2 was significantly greater than that of CrSO2. Averaging data from all subjects, the greatest difference in SrSO2 was 43.8% ±13.4 compared with 23.3% ±7.6 for CrSO2 (p<0.001). The mean coefficient of variation in all transfusions was 20.5% for SrSO2 and 6.0% for CrSO2 (p<0.001). Increasing post-conceptional age did not affect SrSO2 variability (R(2) =0.022; p=0.379), whereas CrSO2 variability during transfusion decreased with increasing post-conceptional age (R(2)=0.209; p=0.004). DISCUSSION In preterm infants, there is a large degree of tissue oxygenation variability in splanchnic tissue during RBC transfusion and this does not change with increasing maturity. We speculate that these findings, combined with lower average tissue oxygenation, may demonstrate susceptibility of the preterm gut to TRAGI.

Usefulness of Urinary Immune Biomarkers in the Evaluation of Neonatal Sepsis A Pilot Project

Objective. Our hypothesis is that specific proinflammatory and anti-inflammatory urinary cytokines are useful in the diagnostic evaluation of risk for sepsis in term neonates. We conducted a pilot, prospective hospital-based longitudinal observational study to test the urine of term neonates with a 13 biomarker panel of cytokines. Methods. Infants were divided into 2 groups: The control group (n = 15) consisted of infants admitted to newborn nursery, and the test group (n = 15) consisted of infants admitted to the neonatal intensive care unit for presumed sepsis. Bagged urine samples were collected from 30 term neonates for testing our hypothesis. Results. Urinary interleukin (IL)-8 (P = .004*), inducible protein (IP)-10 (P = .007*), and monocyte chemoattractant protein (MCP)-1 (P = .02) were significantly increased in the test group compared with the control group. Conclusions. Urinary IL-8, IP-10, and MCP-1 are proinflammatory cytokines that are increased in the neonate during an infectious inflammatory process. These may be useful predictors as an adjunct to the current protocols to recognize neonatal sepsis.