We previously reported that global insulin receptor substrate-2 (IRS2)-deficient mice demonstrated enhanced pulmonary vascular remodeling in response to allergen exposure or to hypoxia. To evaluate the specific contribution of IRS2 in myeloid cells to this process, we analyzed responses in mice with conditional IRS2-deficiencies in myeloid cells by crossing Irs2fl/fl mice to LysM-Cretg/wt mice and examined responses to allergens and hypoxia. There were no significant differences in the allergic inflammatory response induced by either ovalbumin adsorbed to aluminum hydroxide or by house dust mite (HDM) between Irs2fl/flLysM-Crewt/wt (Cre-/-) and Irs2fl/flLysM-Cretg/wt (Cre+/-) littermates. However, there was a significant difference between Cre-/- and Cre+/- mice in the HDM-induced remodeling of small pulmonary blood vessels. Such remodeling can lead to changes in cardiopulmonary function including increases in right ventricular systolic pressure (RVSP) and pulmonary hypertension (PH). While we did observe an increase in RVSP in response to hypoxia or allergen, there was no significant difference in RSVP between Cre-/- and Cre+/- mice. However, there was a significant difference in right heart remodeling as indicated by changes in right ventricular internal diameter and Fulton Index. These results indicate that IRS2 expression in myeloid cells limits pulmonary and cardiac remodeling responses that are induced by allergic inflammation or hypoxia.

ABSTRACT Objective To identify risk factors for tracheostomy among infants born < 33 week gestational age. Methods We conducted a retrospective matched case‐control study of infants < 33 week gestation who underwent tracheostomy between 2000 and 2018 at a single level IV NICU. For each case, we identified two controls matched for gestational age ± 1 week and birthweight ± 100 g who were admitted during the same year. Records were reviewed for IMV duration, number of intubations/extubations, postnatal steroid exposure, BPD severity and other clinical factors. Odds ratios and 95% CI were calculated by a conditional logistic regression. Results The mean (SD) gestation of the cohort (30 tracheostomy cases; 60 controls) was 26.2 (2.2) week. Tracheostomies were performed at 158 d (127–183) of age and 48 week (44.6–55) post‐menstrual age (PMA) following 92 d (64–134) IMV; median (IQR). Tracheostomy was indicated for severe BPD [N = 19(68%)], acquired airway obstruction [ N = 4(14%)], or severe BPD with airway obstruction [ N = 5(18%)]. Additional risk factors included male sex, outborn birth, intrauterine growth retardation, pulmonary hypertension, and sepsis. IMV duration and length of stay were longer, postnatal steroid exposure was more common and PMA at discharge was later for tracheostomy cases than controls. The number of intubations, extubations (planned and unplanned) and extubations adjusted for IMV duration were significantly higher in cases than controls. In the final logistic model, the number of unplanned extubations and steroid courses were independently associated with tracheostomy. Conclusion Strategies to minimize tracheostomy risk should target modifiable risk factors such as reducing unplanned extubations and limiting postnatal steroids in high‐risk infants.

This study aimed to determine hearing screen outcomes and identify clinical and environmental risk factors for hearing screen failure in very preterm infants at a level IV single-family room (SFR) neonatal intensive care unit (NICU).We conducted a retrospective study of infants <33 weeks gestational age admitted to a level IV SFR NICU who survived to discharge and had automated auditory brainstem response results available. Demographics, antenatal and postnatal factors, and respiratory support modes and their duration were collected from the electronic medical record.Of 425 eligible infants with documented hearing screen results, 353 (83%) passed and 72 (17%) failed the hearing screen (unilateral, N = 44 [61%]; bilateral, N = 28 [39%]). Compared to infants who passed the hearing screen, infants with hearing screen failure were lower gestational age and birth weight, male sex, were screened at later postnatal and postmenstrual ages (PMAs), had lower 1- and 5-minute Apgar scores, longer duration of furosemide therapy, early hypotension, intraventricular hemorrhage (IVH) ≥Grade 3, and bronchopulmonary dysplasia (BPD) at 36 weeks PMA. Infants with hearing screen failure experienced longer exposures to invasive and noninvasive respiratory support. Heated, humidified, high flow nasal cannula >2 liters per minute exposure was significantly longer in infants with bilateral hearing screen failure (18.4 ± 18.4 d) compared to duration in infants who passed (7.4 ± 12.8 d) and those with unilateral failure (9 ± 13 d), (mean ± standard deviation [SD], p < 0.001). In the final logistic model, IVH ≥Grade 3 (odds ratio [OR] = 3.22, 95% confidence interval [CI]: 1.15-8.98, p = 0.026) and BPD (OR = 2.27, 95% CI: 1.25-4.11, p = 0.007) were the factors with the greatest risk for hearing screen failure.We speculate that the association of BPD with hearing screen failure may be mediated, in part, by chronic noise exposure, including from respiratory support devices. Attention to hearing protection in at-risk infants during respiratory support may mitigate the risk of hearing loss. · NICU noise often exceeds recommended sound levels.. · Seventeen percent of infants with <33 weeks GA in SFR NICU failed hearing screenings.. · BPD and IVH are risk factors for hearing screen failure.. · Respiratory devices contribute to increased NICU noise.. · hearing protection should be considered during respiratory support..

OBJECTIVES:Early exposure to mother's own milk (MOM) promotes intestinal barrier maturation in preterm infants. We hypothesized (1) donor human milk (DHM) supplementation reduces intestinal permeability (IP) similar to exclusive MOM and (2) early HM exposure and low IP at 7-10 days postnatal age (PNA) are associated with improved growth outcomes. METHODS:IP was measured by the standard sugar absorption test (SAT) in infants <33 weeks gestation between 7-10 days PNA. Nutritional and anthropometric data were recorded. Postnatal growth failure (PNGF) was defined as a decrease in weight z-score >1 from birth to discharge to home. RESULTS:Of 158 preterm infants, the mean (SD) gestational age was 29.9(2.3) weeks and birthweight 1388(424) g. Diet prior to SAT was exclusive MOM [N = 55(35%)], DHM ± MOM [N = 52(33%)], or preterm formula±MOM [N = 51(32%)]. The mean Lactulose(La)/Rhamnose(Rh) ratio was lower in the exclusive MOM [0.06(0.07)] and DBM ± MOM [0.05(0.07)] groups compared to the preterm formula±MOM group [0.11(0.11)], p < 0.01). Cumulative intake >150 ml/kg MOM ± DHM, but not preterm formula within 7-10 days PNA was associated with early intestinal barrier maturation. Low IP was not associated with lower risk of PNGF at discharge. CONCLUSIONS:Low IP is associated with cumulative intake of MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days PNA. CLINICAL TRIAL REGISTRATION:Clinicaltrials.gov NCT01756040 ; web link to study on registry: https://clinicaltrials.gov/study/NCT01756040 . IMPACT:Key message Early intestinal barrier maturation is associated with cumulative intake of exclusive MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days after birth, but is not associated with lower risk of PNGF at time of discharge. What it adds to existing literature? This observational study is the first study to demonstrate that supplemental DHM promotes intestinal barrier maturation similar to MOM alone. What is the impact? The findings underscore the importance of early introduction of human milk feeds as MOM or MOM supplemented with DHM in sufficient volume to promote early intestinal barrier maturation.

Previous work has shown that Secretory-IgA (SIgA) binding to the intestinal microbiota is variable and may regulate host inflammatory bowel responses. Nevertheless, the impact of the SIgA functional binding to the microbiota remains largely unknown in preterm infants whose immature epithelial barriers make them particularly susceptible to inflammation. Here, we investigated SIgA binding to intestinal microbiota isolated from stools of preterm infants <33 weeks gestation with various levels of intestinal permeability. We found that SIgA binding to intestinal microbiota attenuates inflammatory reactions in preterm infants. We also observed a significant correlation between SIgA affinity to the microbiota and the infant's intestinal barrier maturation. Still, SIgA affinity was not associated with developing host defenses, such as the production of mucus and inflammatory calprotectin protein, but it depended on the microbiota shifts as the intestinal barrier matures. In conclusion, we reported an association between the SIgA functional binding to the microbiota and the maturity of the preterm infant's intestinal barrier, indicating that the pattern of SIgA coating is altered as the intestinal barrier matures.

Objective To develop predictive models of Ureaplasma spp lower airway tract infection in preterm infants. Methods A dataset was assembled from five cohorts of infants born <33 weeks gestational age (GA) enrolled over 17 years (1999–2016) with culture and/or PCR-confirmed tracheal aspirate Ureaplasma status in the first week of life (n=415). Seventeen demographic, obstetric and neonatal factors were analysed including admission white blood cell (WBC) counts. Best subset regression was used to develop three risk scores for lower airway Ureaplasma infection: (1) including admission laboratory values, (2) excluding admission laboratory values and (3) using only data known prenatally. Results GA and rupture of membranes >72 hours were significant predictors in all 3 models. When all variables including admission laboratory values were included in the regression, WBC count was also predictive in the resulting model. When laboratory values were excluded, delivery route was found to be an additional predictive factor. The area under the curve for the receiver operating characteristic indicated high predictive ability of each model to identify infants with lower airway Ureaplasma infection (range 0.73–0.77). Conclusion We developed predictive models based on clinical and limited laboratory information available in the perinatal period that can distinguish between low risk (<10%) and high risk (>40%) of lower airway Ureaplasma infection. These may be useful in the design of phase III trials of therapeutic interventions to prevent Ureaplasma -mediated lung disease in preterm infants and in clinical management of at-risk infants.

Intestinal barrier immaturity, or “leaky gut”, is the proximate cause of susceptibility to necrotizing enterocolitis in preterm neonates. Exacerbated intestinal immune responses, gut microbiota dysbiosis, and heightened barrier injury are considered primary triggers of aberrant intestinal maturation in early life. Inordinate host immunity contributes to this process, but the precise elements remain largely uncharacterized, leaving a significant knowledge gap in the biological underpinnings of gut maturation. In this study, we investigated the fecal cytokine profile and gut microbiota in a cohort of 40 early preterm infants <33-weeks-gestation to identify immune markers of intestinal barrier maturation. Three distinct microbiota types were demonstrated to be differentially associated with intestinal permeability (IP), maternal breast milk feeding, and immunological profiles. The Staphylococcus epidermidis- and Enterobacteriaceae-predominant microbiota types were associated with an elevated IP, reduced breast milk feeding, and less defined fecal cytokine profile. On the other hand, a lower IP was associated with increased levels of fecal IL-1α/β and a microbiota type that included a wide array of anaerobes with expanded fermentative capacity. Our study demonstrated the critical role of both immunological and microbiological factors in the early development of intestinal barrier that collectively shape the intestinal microenvironment influencing gut homeostasis and postnatal intestinal maturation in early preterm newborns.

ABSTRACT“Leaky gut”, or high intestinal barrier permeability, is common in preterm newborns. The role of microbiota in this process remains largely uncharacterized. We employed both short- and long-read sequencing of the 16S rRNA gene and metagenomes to characterize the intestinal microbiome of a longitudinal cohort of 113 preterm infants born between 240/7-326/7 weeks of gestation. Enabled by enhanced taxonomic resolution, we found significantly increased abundance of Bifidobacterium breve and a diet rich in mother’s breastmilk to be associated with intestinal barrier maturation during the first week of life. We combined these factors using genome- resolved metagenomics and identified a highly specialized genetic capability of the Bifidobacterium strains to assimilate human milk oligosaccharides and host-derived glycoproteins. Our study proposed mechanistic roles of breastmilk feeding and intestinal microbial colonization in postnatal intestinal barrier maturation; these observations are critical towards advancing therapeutics to prevent and treat hyperpermeable gut- associated conditions, including necrotizing enterocolitis.IMPORTANCEDespite improvements in neonatal intensive care, necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality. “Leaky gut”, or intestinal barrier immaturity with elevated intestinal permeability, is the proximate cause of susceptibility to NEC. Early detection and intervention to prevent leaky gut in “at-risk” preterm neonates is critical to lower the risk for potentially life-threatening complications like NEC. However, the complex interactions between the developing gut microbial community, nutrition, and intestinal barrier function, remain largely uncharacterized. In this study, we revealed the critical role of sufficient breastmilk feeding volume and specialized carbohydrate metabolism capability of Bifidobacterium in coordinated postnatal improvement of intestinal barrier. Determining the clinical and microbial biomarkers that drive the intestinal developmental disparity will inform early detection and novel therapeutic strategies to promote appropriate intestinal barrier maturation, prevent NEC and other adverse health conditions in preterm infants.

The present paper describes a rapid, specific and sensitive method for quantitating ribonucleoside triphosphates (ATP and UTP) in cell extracts. The principle of the method is based on the synthesis of a ribonucleotide polymer in the presence of UTP, ATP and poly(dA-dT) as template. A method for calculation is also described, making the determination of UTP and ATP pool sizes in the cells possible under the same experimental conditions. The calculation takes into account the isotope dilution effect caused by the intracellular ATP. Our experiments show that the neutralized perchloric acid soluble fraction of human tonsillar lymphocytes contains no inhibitors for the RNA polymerase test. According to our results, this cell extract contains 80 pmol of UTP and 340 pmol of ATP per mug RNA.

Asthma is a common and ubiquitous chronic respiratory disease that is associated with airway inflammation and hyperreactivity resulting in airway obstruction. It is now accepted that asthma is controlled by a combination of host genetics and environment in a rather complex fashion; however, the link between sensing of the environment and development and exacerbation of allergic lung inflammation is unclear. Human populations expressing cosegregating D299G and T399I polymorphisms in the TLR4 gene are associated with a decreased risk for asthma in adults along with hyporesponsiveness to inhaled LPS, the TLR4 ligand. However, these data do not account for other human genetic or environmental factors. Using a novel mouse strain that expresses homologous human TLR4 polymorphisms (TLR4-single nucleotide polymorphism [SNP]), we directly tested the effect of these TLR4 polymorphisms on in vivo responses to allergens using two models of induction. We report that intact TLR4 is required for allergic inflammation when using the OVA and LPS model of induction, as cellular and pathological benchmarks were diminished in both TLR4-SNP and TLR4-deficent mice. However, in the more clinically relevant model using house dust mite extract for induction, responses were enhanced in the TLR4-SNP mice, as evidenced by greater levels of eosinophilic inflammation, Th2 cytokine production, and house dust mite-specific IgG1 production compared with wild-type mice; however, mucus production and airway hyperreactivity were not affected. These results suggest that the TLR4 polymorphic variants (genes) interact differently with the allergic stimulation (environment).

BACKGROUND:To assess the potential impact of azithromycin treatment in the first week following birth on 2-year outcomes in preterm infants with and without Ureaplasma respiratory colonization who participated in a double-blind, placebo-controlled randomized controlled trial. METHODS:Respiratory morbidity was assessed at NICU discharge and at 6, 12, and 22-26 months corrected age using pulmonary questionnaires. Comprehensive neurodevelopmental assessments were completed between 22 and 26 months corrected age. The primary and secondary composite outcomes were death or severe respiratory morbidity and death or moderate-severe neurodevelopmental impairment, respectively, at 22-26 months corrected age. RESULTS:One hundred and twenty-one randomized participants (azithromycin, N = 60; placebo, N = 61) were included in the intent-to-treat analysis. There were no significant differences in death or serious respiratory morbidity (34.8 vs 30.4%, p = 0.67) or death or moderate-severe neurodevelopmental impairment (47 vs 33%, p = 0.11) between the azithromycin and placebo groups. Among all trial participants, tracheal aspirate Ureaplasma-positive infants experienced a higher frequency of death or serious respiratory morbidity at 22-26 months corrected age (58%) than tracheal aspirate Ureaplasma-negative infants (34%) or non-intubated infants (21%) (p = 0.028). CONCLUSIONS:We did not observe strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes in preterm infants treated with azithromycin in the first week of life compared to placebo. IMPACT:No strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes was identified at 22-26 months corrected age in infants treated with azithromycin in the first week of life compared to placebo. The RCT is the first study of 2-year pulmonary and neurodevelopmental outcomes of azithromycin treatment in ELGANs. Provides evidence that ELGANs with lower respiratory tract Ureaplasma have the most frequent serious respiratory morbidity in the first 2 years of life, suggesting that a Phase III trial of azithromycin to prevent BPD targeting this population is warranted.

Introduction: Neonatal intensive care unit (NICU) provider point-of-care ultrasound (POCUS) procedural competency for umbilical line placement confirmation has not been defined, and the necessary training to achieve competency has not been previously studied. This study's objective was to test the hypothesis that a simulation-enhanced curriculum will improve NICU providers' POCUS competency to confirm umbilical line placement. Methods: Neonatal intensive care unit providers without prior ultrasound experience were randomized to a curriculum with or without simulation-based training. Competency for catheter detection, tip localization, and scan interpretation on patients was determined using learning curve-cumulative summation, a specific statistical tool designed to indicate when a predefined level of performance is reached. Differences in success rates were analyzed by chi(2) test. Results: Two thirds (22/33) of participants completed 10 scans. Three (simulation) and 1 (control) attained catheter detection competency (P = 0.28). The simulation group was more successful for catheter detection (81% vs. 69%, P = 0.04) and scan interpretation (61% vs. 48%, P = 0.04). Success did not differ by umbilical vessel location, provider role, or duration of NICU experience. Conclusions: A simulation-enhanced POCUS curriculum improved catheter detection rate and scan interpretation, but there was no difference in procedural competency between groups on ultrasound scans performed on patients with umbilical catheters. We speculate that more than 10 scans may be needed for NICU providers to obtain POCUS competency.

PURPOSE This study was conducted to test the hypothesis of autonomic imbalance in overtrained athletes during sleep and after awakening with analyses of heart rate variability (HRV) and nocturnal urine stress hormones. METHODS We examined 12 athletes diagnosed to be severely overtrained (OA, 6 men and 6 women, mean age (+/-SD) 25 +/- 7 yr) and 12 control athletes (CA, 6 men and 6 women, mean age 24 +/- 5 yr). Overtraining diagnosis was further supported by higher perceived stress in OA than in CA (24.8 +/- 10.8 vs 15.3 +/- 5.5, P < 0.05). HRV was analyzed with time and frequency domain methods from RR intervals (RRI) recorded during sleep and after awakening. Nocturnal urine stress hormones were analyzed by liquid chromatography. RESULTS No differences were found in HRV or stress hormones during night sleep. After awakening, the standard deviation of RRI (84 +/- 31 vs 116 +/- 41 ms, P < 0.05) and low-frequency power of RRI (2153 +/- 2232 vs 4286 +/- 2904 ms, P < 0.05) were lower in OA than in CA. From sleep to after awakening, the coefficient of variation of RRI decreased more in OA than in CA (from 11.8 +/- 3.3 to 7.7 +/- 2.5%, P < 0.001 vs from 11.9 +/- 1.8 to 10.0 +/- 2.5%, P < 0.01, respectively, interaction P < 0.05). CONCLUSION The present findings suggest that in OA, cardiac autonomic modulation is at the level of control athletes during sleep, but the parasympathetic cardiac modulation is slightly diminished after awakening. Further investigations should concentrate on autonomic responses to different challenges, such as awakening in the present study.

ObjectiveTo test whether azithromycin eradicates Ureaplasma from the respiratory tract in preterm infants.DesignProspective, phase IIb randomised, double-blind, placebo-controlled trial.SettingSeven level III–IV US, academic, neonatal intensive care units (NICUs).PatientsInfants 240–286 weeks’ gestation (stratified 240–266; 270–286 weeks) randomly assigned within 4 days following birth from July 2013 to August 2016.InterventionsIntravenous azithromycin 20 mg/kg or an equal volume of D5W (placebo) every 24 hours for 3 days.Main outcome measuresThe primary efficacy outcome was Ureaplasma-free survival. Secondary outcomes were all-cause mortality, Ureaplasma clearance, physiological bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age, comorbidities of prematurity and duration of respiratory support.ResultsOne hundred and twenty-one randomised participants (azithromycin: n=60; placebo: n=61) were included in the intent-to-treat analysis (mean gestational age 26.2±1.4 weeks). Forty-four of 121 participants (36%) were Ureaplasma positive (azithromycin: n=19; placebo: n=25). Ureaplasma-free survival was 55/60 (92% (95% CI 82% to 97%)) for azithromycin compared with 37/61 (61% (95% CI 48% to 73%)) for placebo. Mortality was similar comparing the two treatment groups (5/60 (8%) vs 6/61 (10%)). Azithromycin effectively eradicated Ureaplasma in all azithromycin-assigned colonised infants, but 21/25 (84%) Ureaplasma-colonised participants receiving placebo were culture positive at one or more follow-up timepoints. Most of the neonatal mortality and morbidity was concentrated in 21 infants with lower respiratory tract Ureaplasma colonisation. In a subgroup analysis, physiological BPD-free survival was 5/10 (50%) (95% CI 19% to 81%) among azithromycin-assigned infants with lower respiratory tract Ureaplasma colonisation versus 2/11 (18%) (95% CI 2% to 52%) in placebo-treated infants.ConclusionA 3-day azithromycin regimen effectively eradicated respiratory tract Ureaplasma colonisation in this study.Trial registration numberNCT01778634.

OBJECTIVE:Evaluate the association between carbon dioxide (pCO2), cerebral blood flow (CBF), and cerebral autoregulation (CA) in preterm infants. STUDY DESIGN:Cerebral saturations (rScO2, surrogate for CBF using NIRS) and mean arterial blood pressure (MAP) monitored for 96 h in infants <29 weeks gestation. Relationship between rScO2, the rScO2-MAP correlation (CA analysis) and pCO2 category assessed by mixed effects modeling. RESULTS:Median pCO2 differed by postnatal day (p < 0.0001)-pCO2 increased between day 1 and 2, and low variability seen on day 4. A 5% increase in rScO2 was noted when pCO2 was >55 mmHg on each postnatal day (p < 0.001). No association observed between the overall rScO2-MAP correlation and pCO2. On day 1 only, the correlation coefficient decreased from 0.26 to -0.09 as pCO2 category increased (p = 0.02). CONCLUSIONS:CBF increased above a pCO2 threshold of 55 mmHg, but overall, no association between pCO2 and CA was noted.

Supplemental digital content is available in the text. Introduction Neonatal intensive care unit (NICU) provider point-of-care ultrasound (POCUS) procedural competency for umbilical line placement confirmation has not been defined, and the necessary training to achieve competency has not been previously studied. This study's objective was to test the hypothesis that a simulation-enhanced curriculum will improve NICU providers' POCUS competency to confirm umbilical line placement. Methods Neonatal intensive care unit providers without prior ultrasound experience were randomized to a curriculum with or without simulation-based training. Competency for catheter detection, tip localization, and scan interpretation on patients was determined using learning curve-cumulative summation, a specific statistical tool designed to indicate when a predefined level of performance is reached. Differences in success rates were analyzed by χ2 test. Results Two thirds (22/33) of participants completed 10 scans. Three (simulation) and 1 (control) attained catheter detection competency (P = 0.28). The simulation group was more successful for catheter detection (81% vs. 69%, P = 0.04) and scan interpretation (61% vs. 48%, P = 0.04). Success did not differ by umbilical vessel location, provider role, or duration of NICU experience. Conclusions A simulation-enhanced POCUS curriculum improved catheter detection rate and scan interpretation, but there was no difference in procedural competency between groups on ultrasound scans performed on patients with umbilical catheters. We speculate that more than 10 scans may be needed for NICU providers to obtain POCUS competency.

Microbiome analysis based on 16S ribosomal ribonucleic acid gene sequencing has identified unique microbiota in microenvironments previously considered sterile, such as the placenta and lung, and suggests that the lung microbiome may be established before birth. The microbiome established early in life may affect the development of chronic lung disease such as asthma later in life. Recent studies of preterm infants suggest that the airway microbiome in infants in whom bronchopulmonary dysplasia (BPD) develops differs in composition and is less diverse compared with term and preterm infants without BPD. The role of the genital mycoplasmas Ureaplasma parvum and Ureaplasma urealyticum alone and as part of a polymicrobial infection in preterm birth, neonatal lung injury, and host immune responses is reviewed.

Background: Oxygen therapy in the premature neonatal population is associated with negative outcomes and neonatal intensive care units (NICU) use continuous pulse oximetry to limit its use in these vulnerable subjects. The NICU at a large university hospital has a 4-pronged Target Oxygen Protocol 1) Set correct SpO2 alarm limits 2) Use Nellcor OxiMax N-600x pulse oximeter (Covidien, Mansfield, Massachusetts) to display histogram of percent time in each SpO2 quintile per 24h period 3) Display correct postmenstrual age oxygen target saturation card 4) Set oxygen blender FIO2

OBJECTIVE:To determine the relationships of red blood cell (RBC) transfusion and enteral feeding to changes in intestinal permeability (IP) measured by the relative intestinal uptake of lactulose (La) and rhamnose (Rh) in preterm infants <33 wk gestation. DESIGN/METHODS:Infants 240-326wk gestation received La/Rh solution enterally on study days 1, 8 and 15.Urinary La/Rh ratio was measured by HPLC. Hematocrit preceding transfusion, total RBC transfusion volume, volume/kg, and feeding status during each study interval (birth-d1; d1-d8, and d8-d15) were determined. RESULTS:Of the seventeen (40.5%) subjects who received≥1 transfusion during the study period, 12 (70.6%) infants were <28 wk gestation and 5 (29.4%) infants were≥28 wk gestation, p < 0.0001. Lower pre-transfusion hematocrit was observed in intervals preceding high IP (La/Rh > 0.05) than in intervals preceding low IP (La/Rh≤0.05) measurements (33 vs 35.8, p = 0.1051). RBC transfusions occurred more frequently in intervals preceding high IP than in intervals preceding low IP (26.8%; vs 8.3%, p = 0.0275) with 5-fold higher total RBC volume and volume/kg in intervals preceding any time point with high IP. RBC transfusion during an interval was associated with a three-fold increased risk of high IP (aOR 2.7; 95% C.I 0.564-12.814; p = 0.2143). Exclusive breast milk exposure and post-menstrual age reduced the risk for high IP following RBC transfusion. CONCLUSIONS:Both RBC transfusion number and volume was associated with subsequent high IP measurements in preterm infants <33 weeks gestation and potentially may contribute to impairment of the preterm intestinal barrier.