Kurt Schibler - Academia.edu (original) (raw)

Papers by Kurt Schibler

Research paper thumbnail of Fucosyltransferase 2 Non-Secretor and Low Secretor Status Predicts Severe Outcomes in Premature Infants

The Journal of Pediatrics, 2011

To investigate secretor gene fucosyltransferase 2 (FUT2) polymorphism and secretor phenotype in r... more To investigate secretor gene fucosyltransferase 2 (FUT2) polymorphism and secretor phenotype in relation to outcomes of prematurity. Study infants were ≤32 weeks gestational age. Secretor genotype was determined from salivary DNA. Secretor phenotype was measured with H antigen, the carbohydrate produced by secretor gene enzymes, in saliva samples collected on day 9 ± 5. The optimal predictive cutoff point in salivary H values was identified with Classification and Regression Tree analysis. Study outcomes were death, necrotizing enterocolitis (NEC, Bell's stage II/III), and confirmed sepsis. There were 410 study infants, 26 deaths, 30 cases of NEC, and 96 cases of sepsis. Analyzed by genotype, 13% of 95 infants who were non-secretors, 5% of 203 infants who were heterozygotes, and 2% of 96 infants who were secretor dominant died (P = .01). Analyzed by phenotype, 15% of 135 infants with low secretor phenotype died, compared with 2% of 248 infants with high secretor phenotype (predictive value = 76%, P < .001). Low secretor phenotype was associated (P < .05) with NEC, and non-secretor genotype was associated (P = .05) with gram negative sepsis. Secretor status remained significant after controlling for multiple clinical factors. Secretor genotype and phenotype may provide strong predictive biomarkers of adverse outcomes in premature infants.

Research paper thumbnail of Association of Increased Seizures During Rewarming With Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up

Research paper thumbnail of Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth

The Journal of Pediatrics

Research paper thumbnail of Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic–Ischemic Encephalopathy in the Late Hypothermia Trial

The Journal of Pediatrics

Research paper thumbnail of Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants

New England Journal of Medicine

BACKGROUND Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may r... more BACKGROUND Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. METHODS We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. RESULTS A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher-and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. CONCLUSIONS In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.

Research paper thumbnail of Behavior Profiles at 2 Years for Children Born Extremely Preterm with Bronchopulmonary Dysplasia

The Journal of Pediatrics

Research paper thumbnail of Heart Rate Characteristic Index Monitoring for Early Detection of Infections in Very Low Birth Weight Infants

American Journal of Pediatrics

The aim of this study is 1) to determine the sensitivity and specificity of continuous heart rate... more The aim of this study is 1) to determine the sensitivity and specificity of continuous heart rate characteristics (HRC) monitoring in detection of infections and 2) to evaluate whether HRC monitoring detects infections prior to onset of clinical symptoms in very low birth weight (VLBW) infants. A retrospective cohort study was conducted analyzing HRC scores and episodes of infection for VLBW infants in the Neonatal Intensive Care Unit (NICU) at Cincinnati Children's Hospital Medical Center from January 2015 through May 2016. HRC scores were acquired using the HRC monitor system and entered into the electronic medical record by bedside staff. Culture-positive and culture-negative clinical infections were recorded. Positive HRC scores were defined as an increase 1 point above the baseline or the first rise above 2. HRC scores within 24 hours and also within the 5-day period before the start of antibiotics for infections were analyzed for sensitivity, specificity, positive predictive value and negative predictive value for detection of neonatal infection. The HRC score increase 1 point above the baseline or the first rise above 2 in the 24 hours before the start of antibiotics for infectious events had a sensitivity of 68.0%, a specificity of 10.8%. Positive predictive value (PPV) and negative predictive value (NPV) were 34.0% and 33.3%, respectively. The PPV and NPV were modestly higher for elevated HRC scores during the 5-day period before infections, 41.1% and 66.7%, respectively. In our single-center retrospective study, elevated HRC scores had limited ability to detect infection. More than half of the positive monitor events were not related to infection. The potential clinical impact of the monitor to detect infection before the onset of clinical symptoms was limited and the risk for unnecessary evaluation and treatment was high.

Research paper thumbnail of Possible mechanisms accounting for the growth factor independence of hematopoietic progenitors from umbilical cord blood

Blood

Hematopoietic progenitors obtained from the bone marrow of healthy adults fail to undergo clonoge... more Hematopoietic progenitors obtained from the bone marrow of healthy adults fail to undergo clonogenic maturation in vitro if a source of hematopoietic growth factors is not included in the culture dishes. In contrast, a fraction of similarly purified progenitors obtained from umbilical cord blood undergo clonogenic maturation even in the absence of added growth factors. We postulated that production of hematopoietic growth factors within the culture dishes containing the progenitors of umbilical cord blood origin might be responsible. We postulated further, that this production might be by non-progenitor cells co- plated along with the progenitors, or alternatively by CD34+ cells themselves, or by cells clonally derived from CD34+ cells. To test these possibilities we first assessed the effect of including in the cultures neutralizing antibody directed against various growth factors. Inclusion of anti-granulocyte macrophage colony-stimulating factor (GM- CSF) and anti-interleukin-3 (...

Research paper thumbnail of Morbidity and cost burden of prenatal myelomeningocele repair

The Journal of Maternal-Fetal & Neonatal Medicine

Research paper thumbnail of Achieved oxygen saturations and retinopathy of prematurity in extreme preterms

Archives of Disease in Childhood - Fetal and Neonatal Edition

ObjectiveTo identify achieved oxygen saturations (SpO2) associated with increased risk of severe ... more ObjectiveTo identify achieved oxygen saturations (SpO2) associated with increased risk of severe retinopathy of prematurity (ROP).DesignThis is a secondary analysis of the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT)randomised controlled trial. SpO2 was recorded up to 36 weeks’ postmenstrual age. Saturations through 9 postnatal weeks were explored graphically, and logistic regression models were created to predict severe ROP.Setting20 centres of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.Patients984 surviving infants of 24–27 weeks’ gestational age born in 2005–2009.InterventionsSUPPORT targeted SpO2 to a lower (85%–89%) or higher (91%–95%) range through 36 weeks’ postmenstrual age or off respiratory support.Main outcome measuresSevere ROP defined as threshold ROP, ophthalmological surgery or bevacizumab treatment.ResultsThere were statistically significant interactions between duration of o...

Research paper thumbnail of Association between Policy Changes for Oxygen Saturation Alarm Settings and Neonatal Morbidity and Mortality in Infants Born Very Preterm

The Journal of Pediatrics

Research paper thumbnail of Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial

JAMA, Oct 23, 2018

Previous studies of myo-inositol in preterm infants with respiratory distress found reduced sever... more Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age. Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then e...

Research paper thumbnail of Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial

The Journal of pediatrics, Jan 15, 2018

To assess whether length of hospital stay is decreased among moderately preterm infants weaned fr... more To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the...

Research paper thumbnail of A quality improvement initiative to reduce necrotizing enterocolitis across hospital systems

Journal of perinatology : official journal of the California Perinatal Association, 2018

Necrotizing enterocolitis (NEC) is a devastating intestinal disease in premature infants. Local r... more Necrotizing enterocolitis (NEC) is a devastating intestinal disease in premature infants. Local rates of NEC were unacceptably high. We hypothesized that utilizing quality improvement methodology to standardize care and apply evidence-based practices would reduce our rate of NEC. A multidisciplinary team used the model for improvement to prioritize interventions. Three neonatal intensive care units (NICUs) developed a standardized feeding protocol for very low birth weight (VLBW) infants, and employed strategies to increase the use of human milk, maximize intestinal perfusion, and promote a healthy microbiome. The primary outcome measure, NEC in VLBW infants, decreased from 0.17 cases/100 VLBW patient days to 0.029, an 83% reduction, while the compliance with a standardized feeding protocol improved. Through reliable implementation of evidence-based practices, this project reduced the regional rate of NEC by 83%. A key outcome and primary driver of success was standardization across...

Research paper thumbnail of Multi-center Study of Enteral Feeding Practices in Hospitalized Late Preterm Infants in China

Biomedical and environmental sciences : BES, 2018

To investigate the current enteral feeding practices in hospitalized late preterm infants in the ... more To investigate the current enteral feeding practices in hospitalized late preterm infants in the Beijing area of China. A multi-center, cross-sectional study was conducted. Infants born after 34 weeks and before 37 weeks of gestation were enrolled from 25 hospitals in the Beijing area of China from October 2015 to October 2017. Data on enteral feeding practices were collected and analyzed. A total of 1,463 late preterm infants were enrolled, with a mean gestational age (GA) of 35.6 (34.9, 36.1) weeks. The percentage of exclusive breastfeeding was 4.5% at the initiation of enteral feeding but increased to 14.4% at discharge. When human milk was not available, most infants (46.1%) were fed with preterm infant formula. The rate of exclusive human milk feeding in infants born at 34 weeks gestation was higher than at discharge (21.1% of infants born at 34 weeks' GA versus 12.1% of infants born at 35 weeks' GA versus 12.3% of infants born at 36 weeks' GA, P < 0.001). Only 2...

Research paper thumbnail of Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome eight

Pediatric research, Jan 14, 2018

Twin studies suggest that genetic factors may account for up to 50% increased risk for necrotizin... more Twin studies suggest that genetic factors may account for up to 50% increased risk for necrotizing enterocolitis (NEC), but genome-wide association studies (GWAS) for NEC are lacking. Genotyping was done on Illumina BeadChip, followed by analysis using PLINK with logistic regression under an additive model. Among 751 extremely low birth weight (<1000 g, >401 g) neonates, 30 had surgical NEC. 261 single nucleotide polymorphisms (SNPs) showed association with NEC at P<0.05, of which 35 were significant at P<10. Minor allele(s) in a a cluster of SNPs spanning a 43 Kb region of chromosome 8 (8q23.3) conferred an odds ratio of 4.72 (95% CI 2.51-8.88) for elevated risk of NEC. Two smaller clusters on chromosome 14 and chromosome 11 exhibited P values 10-10. The chromosome 8 cluster is in an intergenic region between CUB And Sushi Multiple Domains 3 (-1.43 Mb) and Trichorhinophalangeal Syndrome I (+542 kb). RNA sequencing in this region identified a potential novel open reading...

Research paper thumbnail of Outcome of Preterm Infants with Transient Cystic Periventricular Leukomalacia on Serial Cranial Imaging Up to Term Equivalent Age

The Journal of pediatrics, Jan 2, 2018

To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disap... more To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disappeared" on serial screening cranial imaging studies. Infants ≤26 weeks of gestation born between 2002 and 2012 who had cranial imaging studies at least twice, the most abnormal study at <28 days of age and another closest to 36 weeks, were reviewed. The outcome of late death (after 36 weeks postmenstrual age) or neurodevelopmental impairment (NDI) in surviving infants at 18-26 months corrected age was compared between the infants with no cystic periventricular leukomalacia on both studies and cystic periventricular leukomalacia that disappeared (cystic periventricular leukomalacia at <28 days but not at 36 weeks), persisted (cystic periventricular leukomalacia on both studies), or appeared late (cystic periventricular leukomalacia only at 36 weeks). Predictors of NDI were evaluated by logistic regression. Of 7063 eligible infants, 433 (6.1%) had cystic periventricular leukomal...

Research paper thumbnail of Delivery Room Resuscitation and Short-Term Outcomes in Moderately Preterm Infants

The Journal of pediatrics, Jan 3, 2018

To describe the frequency and extent of delivery room resuscitation and evaluate the association ... more To describe the frequency and extent of delivery room resuscitation and evaluate the association of delivery room resuscitation with neonatal outcomes in moderately preterm (MPT) infants. This was an observational cohort study of MPT infants delivered at 290/7 to 336/7 weeks' gestational age (GA) enrolled in the Neonatal Research Network MPT registry. Infants were categorized into 5 groups based on the highest level of delivery room intervention: routine care, oxygen and/or continuous positive airway pressure, bag and mask ventilation, endotracheal intubation, and cardiopulmonary resuscitation including chest compressions and/or epinephrine use. The association of antepartum and intrapartum risk factors and discharge outcomes with the intensity of resuscitation was evaluated. Of 7014 included infants, 1684 (24.0%) received routine care and no additional resuscitation, 2279 (32.5%) received oxygen or continuous positive airway pressure, 1831 (26.1%) received bag and mask ventilat...

Research paper thumbnail of Association of Chorioamnionitis with Aberrant Neonatal Gut Colonization and Adverse Clinical Outcomes

PloS one

Chorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal... more Chorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal colonization have been associated with an increased risk of sepsis and death in preterm infants, but whether chorioamnionitis causes abnormal pioneering gastrointestinal colonization in infants is not known. We determined the relationship between chorioamnionitis, altered infant fecal microbiome indicating abnormal gastrointestinal colonization, and adverse outcomes. Preterm infants ≤ 28 weeks at birth were enrolled from 3 level III NICUs in Cincinnati, Ohio and Birmingham, Alabama. Sequencing for 16S microbial gene was performed on stool samples in the first 3 weeks of life. Chorioamnionitis was diagnosed by placental histology. Late onset sepsis and death outcomes were analyzed in relation to fecal microbiota and chorioamnionitis with or without funisitis (inflammation of the umbilical cord). Of the 106 enrolled infants, 48 infants had no chorioamnionitis, 32 infants had chorioamnioni...

Research paper thumbnail of Association between Use of Prophylactic Indomethacin and the Risk for Bronchopulmonary Dysplasia in Extremely Preterm Infants

The Journal of pediatrics, Jul 28, 2017

To assess the association between prophylactic indomethacin and bronchopulmonary dysplasia (BPD) ... more To assess the association between prophylactic indomethacin and bronchopulmonary dysplasia (BPD) in a recent, large cohort of extremely preterm infants. Retrospective cohort study using prospectively collected data for infants with gestational ages < 29 weeks or birth weights of 401-1000 g born between 2008 and 2012 at participating hospitals of the National Institute of Child Health and Human Development Neonatal Research Network. Infants treated with indomethacin in the first 24 hours of life were compared with those who were not. Study outcomes were BPD, defined as use of supplemental oxygen at 36 weeks postmenstrual age among survivors to that time point, death, and the composite of death or BPD. Prespecified subgroup analyses were performed. Prophylactic indomethacin use varied by hospital. Treatment of a patent ductus arteriosus after the first day of life was less common among 2587 infants who received prophylactic indomethacin compared with 5244 who did not (21.0% vs 36.1...

Research paper thumbnail of Fucosyltransferase 2 Non-Secretor and Low Secretor Status Predicts Severe Outcomes in Premature Infants

The Journal of Pediatrics, 2011

To investigate secretor gene fucosyltransferase 2 (FUT2) polymorphism and secretor phenotype in r... more To investigate secretor gene fucosyltransferase 2 (FUT2) polymorphism and secretor phenotype in relation to outcomes of prematurity. Study infants were ≤32 weeks gestational age. Secretor genotype was determined from salivary DNA. Secretor phenotype was measured with H antigen, the carbohydrate produced by secretor gene enzymes, in saliva samples collected on day 9 ± 5. The optimal predictive cutoff point in salivary H values was identified with Classification and Regression Tree analysis. Study outcomes were death, necrotizing enterocolitis (NEC, Bell&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s stage II/III), and confirmed sepsis. There were 410 study infants, 26 deaths, 30 cases of NEC, and 96 cases of sepsis. Analyzed by genotype, 13% of 95 infants who were non-secretors, 5% of 203 infants who were heterozygotes, and 2% of 96 infants who were secretor dominant died (P = .01). Analyzed by phenotype, 15% of 135 infants with low secretor phenotype died, compared with 2% of 248 infants with high secretor phenotype (predictive value = 76%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Low secretor phenotype was associated (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) with NEC, and non-secretor genotype was associated (P = .05) with gram negative sepsis. Secretor status remained significant after controlling for multiple clinical factors. Secretor genotype and phenotype may provide strong predictive biomarkers of adverse outcomes in premature infants.

Research paper thumbnail of Association of Increased Seizures During Rewarming With Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up

Research paper thumbnail of Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth

The Journal of Pediatrics

Research paper thumbnail of Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic–Ischemic Encephalopathy in the Late Hypothermia Trial

The Journal of Pediatrics

Research paper thumbnail of Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants

New England Journal of Medicine

BACKGROUND Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may r... more BACKGROUND Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. METHODS We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. RESULTS A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher-and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. CONCLUSIONS In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.

Research paper thumbnail of Behavior Profiles at 2 Years for Children Born Extremely Preterm with Bronchopulmonary Dysplasia

The Journal of Pediatrics

Research paper thumbnail of Heart Rate Characteristic Index Monitoring for Early Detection of Infections in Very Low Birth Weight Infants

American Journal of Pediatrics

The aim of this study is 1) to determine the sensitivity and specificity of continuous heart rate... more The aim of this study is 1) to determine the sensitivity and specificity of continuous heart rate characteristics (HRC) monitoring in detection of infections and 2) to evaluate whether HRC monitoring detects infections prior to onset of clinical symptoms in very low birth weight (VLBW) infants. A retrospective cohort study was conducted analyzing HRC scores and episodes of infection for VLBW infants in the Neonatal Intensive Care Unit (NICU) at Cincinnati Children's Hospital Medical Center from January 2015 through May 2016. HRC scores were acquired using the HRC monitor system and entered into the electronic medical record by bedside staff. Culture-positive and culture-negative clinical infections were recorded. Positive HRC scores were defined as an increase 1 point above the baseline or the first rise above 2. HRC scores within 24 hours and also within the 5-day period before the start of antibiotics for infections were analyzed for sensitivity, specificity, positive predictive value and negative predictive value for detection of neonatal infection. The HRC score increase 1 point above the baseline or the first rise above 2 in the 24 hours before the start of antibiotics for infectious events had a sensitivity of 68.0%, a specificity of 10.8%. Positive predictive value (PPV) and negative predictive value (NPV) were 34.0% and 33.3%, respectively. The PPV and NPV were modestly higher for elevated HRC scores during the 5-day period before infections, 41.1% and 66.7%, respectively. In our single-center retrospective study, elevated HRC scores had limited ability to detect infection. More than half of the positive monitor events were not related to infection. The potential clinical impact of the monitor to detect infection before the onset of clinical symptoms was limited and the risk for unnecessary evaluation and treatment was high.

Research paper thumbnail of Possible mechanisms accounting for the growth factor independence of hematopoietic progenitors from umbilical cord blood

Blood

Hematopoietic progenitors obtained from the bone marrow of healthy adults fail to undergo clonoge... more Hematopoietic progenitors obtained from the bone marrow of healthy adults fail to undergo clonogenic maturation in vitro if a source of hematopoietic growth factors is not included in the culture dishes. In contrast, a fraction of similarly purified progenitors obtained from umbilical cord blood undergo clonogenic maturation even in the absence of added growth factors. We postulated that production of hematopoietic growth factors within the culture dishes containing the progenitors of umbilical cord blood origin might be responsible. We postulated further, that this production might be by non-progenitor cells co- plated along with the progenitors, or alternatively by CD34+ cells themselves, or by cells clonally derived from CD34+ cells. To test these possibilities we first assessed the effect of including in the cultures neutralizing antibody directed against various growth factors. Inclusion of anti-granulocyte macrophage colony-stimulating factor (GM- CSF) and anti-interleukin-3 (...

Research paper thumbnail of Morbidity and cost burden of prenatal myelomeningocele repair

The Journal of Maternal-Fetal & Neonatal Medicine

Research paper thumbnail of Achieved oxygen saturations and retinopathy of prematurity in extreme preterms

Archives of Disease in Childhood - Fetal and Neonatal Edition

ObjectiveTo identify achieved oxygen saturations (SpO2) associated with increased risk of severe ... more ObjectiveTo identify achieved oxygen saturations (SpO2) associated with increased risk of severe retinopathy of prematurity (ROP).DesignThis is a secondary analysis of the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT)randomised controlled trial. SpO2 was recorded up to 36 weeks’ postmenstrual age. Saturations through 9 postnatal weeks were explored graphically, and logistic regression models were created to predict severe ROP.Setting20 centres of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.Patients984 surviving infants of 24–27 weeks’ gestational age born in 2005–2009.InterventionsSUPPORT targeted SpO2 to a lower (85%–89%) or higher (91%–95%) range through 36 weeks’ postmenstrual age or off respiratory support.Main outcome measuresSevere ROP defined as threshold ROP, ophthalmological surgery or bevacizumab treatment.ResultsThere were statistically significant interactions between duration of o...

Research paper thumbnail of Association between Policy Changes for Oxygen Saturation Alarm Settings and Neonatal Morbidity and Mortality in Infants Born Very Preterm

The Journal of Pediatrics

Research paper thumbnail of Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial

JAMA, Oct 23, 2018

Previous studies of myo-inositol in preterm infants with respiratory distress found reduced sever... more Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age. Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then e...

Research paper thumbnail of Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial

The Journal of pediatrics, Jan 15, 2018

To assess whether length of hospital stay is decreased among moderately preterm infants weaned fr... more To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the...

Research paper thumbnail of A quality improvement initiative to reduce necrotizing enterocolitis across hospital systems

Journal of perinatology : official journal of the California Perinatal Association, 2018

Necrotizing enterocolitis (NEC) is a devastating intestinal disease in premature infants. Local r... more Necrotizing enterocolitis (NEC) is a devastating intestinal disease in premature infants. Local rates of NEC were unacceptably high. We hypothesized that utilizing quality improvement methodology to standardize care and apply evidence-based practices would reduce our rate of NEC. A multidisciplinary team used the model for improvement to prioritize interventions. Three neonatal intensive care units (NICUs) developed a standardized feeding protocol for very low birth weight (VLBW) infants, and employed strategies to increase the use of human milk, maximize intestinal perfusion, and promote a healthy microbiome. The primary outcome measure, NEC in VLBW infants, decreased from 0.17 cases/100 VLBW patient days to 0.029, an 83% reduction, while the compliance with a standardized feeding protocol improved. Through reliable implementation of evidence-based practices, this project reduced the regional rate of NEC by 83%. A key outcome and primary driver of success was standardization across...

Research paper thumbnail of Multi-center Study of Enteral Feeding Practices in Hospitalized Late Preterm Infants in China

Biomedical and environmental sciences : BES, 2018

To investigate the current enteral feeding practices in hospitalized late preterm infants in the ... more To investigate the current enteral feeding practices in hospitalized late preterm infants in the Beijing area of China. A multi-center, cross-sectional study was conducted. Infants born after 34 weeks and before 37 weeks of gestation were enrolled from 25 hospitals in the Beijing area of China from October 2015 to October 2017. Data on enteral feeding practices were collected and analyzed. A total of 1,463 late preterm infants were enrolled, with a mean gestational age (GA) of 35.6 (34.9, 36.1) weeks. The percentage of exclusive breastfeeding was 4.5% at the initiation of enteral feeding but increased to 14.4% at discharge. When human milk was not available, most infants (46.1%) were fed with preterm infant formula. The rate of exclusive human milk feeding in infants born at 34 weeks gestation was higher than at discharge (21.1% of infants born at 34 weeks' GA versus 12.1% of infants born at 35 weeks' GA versus 12.3% of infants born at 36 weeks' GA, P < 0.001). Only 2...

Research paper thumbnail of Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome eight

Pediatric research, Jan 14, 2018

Twin studies suggest that genetic factors may account for up to 50% increased risk for necrotizin... more Twin studies suggest that genetic factors may account for up to 50% increased risk for necrotizing enterocolitis (NEC), but genome-wide association studies (GWAS) for NEC are lacking. Genotyping was done on Illumina BeadChip, followed by analysis using PLINK with logistic regression under an additive model. Among 751 extremely low birth weight (<1000 g, >401 g) neonates, 30 had surgical NEC. 261 single nucleotide polymorphisms (SNPs) showed association with NEC at P<0.05, of which 35 were significant at P<10. Minor allele(s) in a a cluster of SNPs spanning a 43 Kb region of chromosome 8 (8q23.3) conferred an odds ratio of 4.72 (95% CI 2.51-8.88) for elevated risk of NEC. Two smaller clusters on chromosome 14 and chromosome 11 exhibited P values 10-10. The chromosome 8 cluster is in an intergenic region between CUB And Sushi Multiple Domains 3 (-1.43 Mb) and Trichorhinophalangeal Syndrome I (+542 kb). RNA sequencing in this region identified a potential novel open reading...

Research paper thumbnail of Outcome of Preterm Infants with Transient Cystic Periventricular Leukomalacia on Serial Cranial Imaging Up to Term Equivalent Age

The Journal of pediatrics, Jan 2, 2018

To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disap... more To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disappeared" on serial screening cranial imaging studies. Infants ≤26 weeks of gestation born between 2002 and 2012 who had cranial imaging studies at least twice, the most abnormal study at <28 days of age and another closest to 36 weeks, were reviewed. The outcome of late death (after 36 weeks postmenstrual age) or neurodevelopmental impairment (NDI) in surviving infants at 18-26 months corrected age was compared between the infants with no cystic periventricular leukomalacia on both studies and cystic periventricular leukomalacia that disappeared (cystic periventricular leukomalacia at <28 days but not at 36 weeks), persisted (cystic periventricular leukomalacia on both studies), or appeared late (cystic periventricular leukomalacia only at 36 weeks). Predictors of NDI were evaluated by logistic regression. Of 7063 eligible infants, 433 (6.1%) had cystic periventricular leukomal...

Research paper thumbnail of Delivery Room Resuscitation and Short-Term Outcomes in Moderately Preterm Infants

The Journal of pediatrics, Jan 3, 2018

To describe the frequency and extent of delivery room resuscitation and evaluate the association ... more To describe the frequency and extent of delivery room resuscitation and evaluate the association of delivery room resuscitation with neonatal outcomes in moderately preterm (MPT) infants. This was an observational cohort study of MPT infants delivered at 290/7 to 336/7 weeks' gestational age (GA) enrolled in the Neonatal Research Network MPT registry. Infants were categorized into 5 groups based on the highest level of delivery room intervention: routine care, oxygen and/or continuous positive airway pressure, bag and mask ventilation, endotracheal intubation, and cardiopulmonary resuscitation including chest compressions and/or epinephrine use. The association of antepartum and intrapartum risk factors and discharge outcomes with the intensity of resuscitation was evaluated. Of 7014 included infants, 1684 (24.0%) received routine care and no additional resuscitation, 2279 (32.5%) received oxygen or continuous positive airway pressure, 1831 (26.1%) received bag and mask ventilat...

Research paper thumbnail of Association of Chorioamnionitis with Aberrant Neonatal Gut Colonization and Adverse Clinical Outcomes

PloS one

Chorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal... more Chorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal colonization have been associated with an increased risk of sepsis and death in preterm infants, but whether chorioamnionitis causes abnormal pioneering gastrointestinal colonization in infants is not known. We determined the relationship between chorioamnionitis, altered infant fecal microbiome indicating abnormal gastrointestinal colonization, and adverse outcomes. Preterm infants ≤ 28 weeks at birth were enrolled from 3 level III NICUs in Cincinnati, Ohio and Birmingham, Alabama. Sequencing for 16S microbial gene was performed on stool samples in the first 3 weeks of life. Chorioamnionitis was diagnosed by placental histology. Late onset sepsis and death outcomes were analyzed in relation to fecal microbiota and chorioamnionitis with or without funisitis (inflammation of the umbilical cord). Of the 106 enrolled infants, 48 infants had no chorioamnionitis, 32 infants had chorioamnioni...

Research paper thumbnail of Association between Use of Prophylactic Indomethacin and the Risk for Bronchopulmonary Dysplasia in Extremely Preterm Infants

The Journal of pediatrics, Jul 28, 2017

To assess the association between prophylactic indomethacin and bronchopulmonary dysplasia (BPD) ... more To assess the association between prophylactic indomethacin and bronchopulmonary dysplasia (BPD) in a recent, large cohort of extremely preterm infants. Retrospective cohort study using prospectively collected data for infants with gestational ages < 29 weeks or birth weights of 401-1000 g born between 2008 and 2012 at participating hospitals of the National Institute of Child Health and Human Development Neonatal Research Network. Infants treated with indomethacin in the first 24 hours of life were compared with those who were not. Study outcomes were BPD, defined as use of supplemental oxygen at 36 weeks postmenstrual age among survivors to that time point, death, and the composite of death or BPD. Prespecified subgroup analyses were performed. Prophylactic indomethacin use varied by hospital. Treatment of a patent ductus arteriosus after the first day of life was less common among 2587 infants who received prophylactic indomethacin compared with 5244 who did not (21.0% vs 36.1...