Spectral features of non-nutritive suck dynamics in extremely preterm infants.

Background: Non-nutritive suck (NNS) is used to promote ororhythmic patterning and assess oral feeding readiness in preterm infants in the neonatal intensive care unit (NICU). While time domain measures of NNS are available in real time at cribside, our understanding of suck pattern generation in the frequency domain is limited. The aim of this study is to model the development of NNS in the frequency domain using Fourier and machine learning (ML) techniques in extremely preterm infants (EPIs). Methods: A total of 117 EPIs were randomized to a pulsed or sham orocutaneous intervention during tube feedings 3 times/day for 4 weeks, beginning at 30 weeks post-menstrual age (PMA). Infants were assessed 3 times/week for NNS dynamics until they attained 100% oral feeding or NICU discharge. Digitized NNS signals were processed in the frequency domain using two transforms, including the Welch power spectral density (PSD) method, and the Yule-Walker PSD method. Data analysis proceeded in two stages. Stage 1: ML longitudinal cluster analysis was conducted to identify groups (classes) of infants, each showing a unique pattern of change in Welch and Yule-Walker calculations during the interventions. Stage 2: linear mixed modeling (LMM) was performed for the Welch and Yule-Walker dependent variables to examine the effects of gestationally-aged (GA), PMA, sex (male, female), patient type [respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD)], treatment (NTrainer, Sham), intervention phase [1, 2, 3], cluster class, and phase-by-class interaction. Results: ML of Welch PSD method and Yule-Walker PSD method measures revealed three membership classes of NNS growth patterns. The dependent measures peak_Hz, PSD amplitude, and area under the curve (AUC) are highly dependent on PMA, but show little relation to respiratory status (RDS, BPD) or somatosensory intervention. Thus, neural regulation of NNS in the frequency domain is significantly different for each identified cluster (classes A, B, C) during this developmental period. Conclusions: Efforts to increase our knowledge of the evolution of the suck central pattern generator (sCPG) in preterm infants, including NNS rhythmogenesis will help us better understand the observed phenotypes of NNS production in both the frequency and time domains. Knowledge of those features of the NNS which are relatively invariant vs. other features which are modifiable by experience will likewise inform more effective treatment strategies in this fragile population.

Examination of cord blood at birth in women with SARS-CoV-2 exposure and/or vaccination during pregnancy and relationship to fetal complete blood count, cortisol, ferritin, vitamin D, and CRP.

Background: SARS-CoV-2 is known to manifest a robust innate immune response. However, little is known about inflammatory influences from maternal SARS-CoV-2 infection or maternal mRNA vaccination upon the fetus. In addition, it is unknown if Vitamin D deficiency influences fetal homeostasis or if an anti-inflammatory mechanism to the development of possible innate cytokines or acute phase reactants by the maternal/fetal dyad, in the form of cortisol elevations, occur. In addition, effects on Complete Blood Count (CBC) are not known. Objective: To evaluate the neonatal acute phase reactants and anti-inflammatory responses after maternal SARS-CoV-2 disease or mRNA vaccination. Methods: Samples and medical records reviews from mother/baby dyads (n = 97) were collected consecutively, and were categorized into 4 groups; no SARS-CoV-2 or vaccination exposure (Control), Vaccinated mothers, maternal SARS-CoV-2 disease positive/IgG titer positive fetal blood, and maternal SARS-CoV-2 positive/IgG titer negative fetal blood. SARS-CoV-2 IgG/IgM/IgA titers, CBC, CRP, ferritin, cortisol, and Vitamin D were obtained to examine the possible development of an innate immune response and possible anti-inflammatory response. Student's t-test, Wilcoxon rank-sum, and Chi-squared with Bonferroni corrections were used to compare groups. Multiple imputations were performed for missing data. Results: Cortisol was higher in babies of both mothers who were vaccinated (p = 0.001) and SARS-CoV-2 positive/IgG positive (p = 0.009) as compared to the control group suggesting an attempt to maintain homeostasis in these groups. Measurements of ferritin, CRP, and vitamin D did not reach statistical significance. CBC showed no variation, except for the mean platelet volume (MPV), which was elevated in babies whose mothers were vaccinated (p = 0.003) and SARS-CoV-2 positive/IgG positive (p = 0.007) as compared to the control group. Conclusion: Acute phase reactant elevations were not noted in our neonates. Vitamin D levels were unchanged from homeostatic levels. Cord blood at birth, showed Cortisol and MPV higher in vaccinated and SARS-CoV-2 IgG positive mother/baby dyads as compared to the Control group, indicating that possible anti-inflammatory response was generated. The implication of possible inflammatory events and subsequent cortisol and/or MPV elevation effects upon the fetus after SARS-CoV-2 disease or vaccination is unknown and merits further investigation.

Ondansetron to reduce neonatal opioid withdrawal severity a randomized clinical trial.

OBJECTIVE: To determine if treatment with a 5-HT3 antagonist (ondansetron) reduces need for opioid therapy in infants at risk for neonatal opioid withdrawal syndrome (NOWS). STUDY DESIGN: A multicenter, randomized, placebo controlled, double blind clinical trial of ninety (90) infants. The intervention arms were intravenous ondansetron or placebo during labor followed by a daily dose of ondansetron or placebo in infants for five days. RESULTS: Twenty-two (49%) ondansetron-treated and 26 (63%) placebo-treated infants required pharmacologic treatment (p > 0.05). The Finnegan score was lower in the ondansetron-treated group (4.6 vs. 5.6, p = 0.02). A non-significant trend was noted for the duration of hospitalization. There was no difference in need for phenobarbital or clonidine therapy, or total dose of morphine in the first 15 days of NOWS treatment. CONCLUSIONS: Ondansetron treatment reduced the severity of NOWS symptoms; and there was an indication that it could reduce the length of stay. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT01965704.

Neutralizing antibody activity against SARS-CoV-2 variants in gestational age-matched mother-infant dyads after infection or vaccination.

Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there are limited data comparing vaccine- and infection-induced neutralizing Abs (nAbs) against COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines (from December 2020 through August 2021) were matched with 30 naturally infected women (from March 2020 through January 2021) by gestational age of exposure. Neutralization activity against the 5 SARS-CoV-2 spike sequences was measured by a SARS-CoV-2-pseudotyped spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared with WT spike protein, these nAbs were less effective against the Delta and Mu spike variants. Vaccination during the third trimester induced higher cord-nAb levels at delivery than did infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared with infection during the first trimester. The transfer ratio (cord nAb level divided by maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicits effective nAbs with differing neutralization kinetics that are influenced by gestational time of exposure.

Are preterm birth and very low birth weight rates altered in the early COVID (2020) SARS-CoV-2 era?

Objective: We evaluated the prevalence of preterm birth (PTB) and very low birth weight (VLBW) during Jan-Dec 2,020 (early COVID era) at 5 hospitals (2 in West Virginia, 3 in California) compared to Jan 2017-Dec 2019 (pre-COVID) inclusive of 2 regional perinatal centers (1 in Huntington, WV and 1 in San Jose, CA) and 3 community hospitals (1 each in Cabell, Los Angeles and Santa Clara counties). Design/methods: We examined PTB and VLBW rates of live births at 5 US hospitals from Jan 2017-Dec 2020. We compared PTB and VLBW rates in 2020 to 2017-2019 using Poisson regression and rate ratio with a 95% confidence interval. We stratified live births by gestational age (GA) (<37, 33-36, and <33 weeks) and birth weight (≤1,500 g, >1,001 g to ≤1,500 g, ≤1,000 g). We examined PTB rates at 4 of the hospitals during Jan-Dec 2020 and compared them to the prior period of Jan 2017-Dec 2019 using Statistical Process Control (SPC) for quarterly data. Results: We examined PTB and VLBW rates in 34,599 consecutive live births born Jan 2017-Dec 2019 to rates of 9,691 consecutive live births in 2020. There was no significant change in PTB (<37 weeks GA) rate, 10.6% in 2017-2019 vs. 11.0% in 2020 (p = 0.222). Additionally, there was no significant change when comparing VLBW rates in 2017-2019 to 2020, 1.4% in 2017-2019 vs. 1.5% in 2020 (p = 0.832). Conclusion: We found no significant change in the rates of PTB or VLBW when combining the live birth data of 5 US hospitals in 3 different counties.

Effect of Delayed Cord Clamping on Umbilical Blood Gas Values in Term Newborns: A Systematic Review.

OBJECTIVE: To compare the effect of delayed cord clamping on cord blood gas values in vaginally delivered, healthy, term singletons. DATA SOURCE: We used MEDLINE, CINAHL, CENTRAL, EMBASE, and ClinicalTrials.gov databases. METHODS OF STUDY SELECTION: Eligible studies included randomized controlled trials (RCTs) comparing cord blood gas values obtained from early compared with delayed cord clamping groups and observational studies using serial cord blood gas from the same umbilical cord. We described the difference in means of cord blood gas parameters and comparative descriptive statistics when a difference in means was not available. We used a domain-based risk bias tool to extract methodologic details and assess potential risk of bias. TABULATION, INTEGRATION, AND RESULTS: This review included two RCTs and three observational studies. These studies included a total of 234 newborns with early cord clamping and 218 newborns with delayed cord clamping. The observational studies showed that 45-90 seconds delayed cord clamping was associated with mean decreases in umbilical arterial pH (0.02-0.03), HCO3 (0.3-0.8 mmol/L) and increases in base deficit (0.3-1.3 mmol/L) compared with early cord clamping. One observational study showed that delayed cord clamping was associated with decreases in umbilical venous pH (0.01) and HCO3 (0.2 mmol/L) and increase in venous base deficit (0.1-0.3 mmol/L) compared with early cord clamping. These changes were not observed in the two RCTs. CONCLUSION: Delayed cord clamping up to 120 seconds has either no effect or only a small effect on cord blood acid-base balance; overall, the magnitude of these changes is not clinically significant in vaginally delivered, healthy, term singletons. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019135779.

Haematocrit in <35 weeks preterm infants who received at least 60 seconds of delayed cord clamping: a retrospective observational study.

OBJECTIVE: To describe haematocrit at birth in preterm infants who received ≥60 s of delayed cord clamping (DCC). DESIGN: Retrospective observational study. SETTING: A California public hospital with an American Academy of Pediatrics level 4 neonatal intensive care unit, with 3500-4000 deliveries annually. PARTICIPANTS: 467 preterm infants born at <35 weeks' gestational age (GA) between January 2013 and December 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: Haematocrit reference ranges for 0-4 hours after birth and paired haematocrit differences between 0-4 and 4-24 hours. METHODS: Haematocrits were obtained when clinically indicated and collected from arterial, venous and capillary sources. Haematocrits obtained after packed red blood cell transfusions were excluded. We summarised the first available haematocrit between 0 and 4 hours by GA strata. We used mixed-effects linear regression to describe the associations between haematocrit and predictor variables including GA, male sex and hours after an infant's birth. We also compared paired haematocrits at 0-4 and 4-24 hours after birth. RESULTS: The median GA of the 467 included infants was 33.3 weeks, birth weight was 1910 g and DCC duration was 60 s. The mean (95% CI) first haematocrit at 0-4 hours was 46.6 (45.0% to 48.1%), 51.2 (49.6% to 52.8%), 50.6 (49.1% to 52.1%), 54.3 (52.8% to 55.8%) and 55.6 (54.6% to 56.6%) for infants 23-29, 30-31, 32, 33 and 34 weeks' GA strata, respectively. The subanalysis of 174 infants with paired haematocrits at 0-4 and 4-24 hours showed that for each additional hour after birth, the mean (95% CI) haematocrit increased by 0.2 (0.1% to 0.3%), 0.2 (0.1% to 0.4%) and 0.1 (0.0% to 0.2%) for infants in 23-29, 30-31 and 32 weeks' GA strata, respectively. The subanalysis showed no change between the paired haematocrits in the 33 and 34 weeks' GA strata. CONCLUSIONS: Our study describes haematocrit in preterm infants who received ≥60 s DCC as standard of care. Haematocrit during the first 0-4 hours in our study is higher than the previously described reference ranges prior to DCC becoming routine clinical practice. The paired second haematocrit at 4-24 hours is higher than haematocrit at 0-4 hours.

Neonatal outcomes in preterm multiples receiving delayed cord clamping.

OBJECTIVE: To compare neonatal outcomes in singletons versus multiples, first-born versus second-born multiples and monochorionic versus dichorionic/trichorionic multiples <33 weeks' gestational age (GA) who received delayed cord clamping (DCC). DESIGN: Retrospective, observational study of 529 preterm infants receiving ≥30 s DCC. Generalised estimating equations and mixed effects models were used to compare outcomes in singletons versus multiples and monochorionic versus dichorionic/trichorionic multiples. Wilcoxon signed-rank and McNemar tests were used to compare first-born versus second-born multiples. SETTING: Level III neonatal intensive care unit, California, USA. PATIENTS: 433 singletons and 96 multiples <33 weeks' GA, born January 2008-December 2017, who received DCC. RESULTS: 86% of multiples and 83% of singletons received DCC. Multiples had higher GA (31.0 weeks vs 30.6 weeks), more caesarean sections (91% vs 54%), fewer males (48% vs 62%) and higher 12-24 hour haematocrits (54.3 vs 50.5) than singletons. Haematocrit difference remained significant after adjusting for birth weight, delivery type and sex. Compared with first-born multiples, second-born multiples were smaller (1550 g vs 1438 g) and had lower survival without major morbidity (91% vs 77%). Survival without major morbidity was not significant after adjusting for birth weight. Compared with dichorionic/trichorionic multiples, monochorionic multiples had slightly lower admission temperatures (37.0°C vs 36.8°C), although this difference was not clinically significant. There were no other differences in delivery room, respiratory, haematological or neonatal outcomes between singletons and multiples or between multiples' subgroups. CONCLUSIONS: Neonatal outcomes in preterm infants receiving DCC were comparable between singletons and multiples, first and second order multiples and monochorionic and dichorionic/trichorionic multiples.

Patterned frequency-modulated oral stimulation in preterm infants: A multicenter randomized controlled trial.

OBJECTIVE: To evaluate the effect of patterned, frequency-modulated oro-somatosensory stimulation on time to full oral feeds in preterm infants born 26-30 weeks gestation. STUDY DESIGN: This is a multicenter randomized controlled trial. The experimental group (n = 109) received patterned, frequency-modulated oral stimulation via the NTrainer system through a pulsatile pacifier and the control group (n = 101) received a non-pulsatile pacifier. Intent-to-treat analysis (n = 210) was performed to compare the experimental and control groups and the outcomes were analyzed using generalized estimating equations. Time-to-event analyses for time to reach full oral feeds and length of hospital stay were conducted using Cox proportional hazards models. RESULTS: The experimental group had reduction in time to full oral feeds compared to the control group (-4.1 days, HR 1.37 (1.03, 1.82) p = 0.03). In the 29-30 weeks subgroup, infants in the experimental group had a significant reduction in time to discharge (-10 days, HR 1.87 (1.23, 2.84) p < 0.01). This difference was not observed in the 26-28 weeks subgroup. There was no difference in growth, mortality or morbidities between the two groups. CONCLUSIONS: Patterned, frequency-modulated oro-somatosensory stimulation improves feeding development in premature infants and reduces their length of hospitalization. TRIAL REGISTRATION: ClinicalTrials.gov NCT01158391.

Eliminating Risk of Intubation in Very Preterm Infants with Noninvasive Cardiorespiratory Support in the Delivery Room and Neonatal Intensive Care Unit.

INTRODUCTION: Avoiding intubation and promoting noninvasive modes of ventilator support including continuous positive airway pressure (CPAP) in preterm infants minimizes lung injury and optimizes neonatal outcomes. Discharge home on oxygen is an expensive morbidity in very preterm infants (VPI) with lung disease. In 2007 a standardized bundle was introduced for VPI admitted to the neonatal care unit (NICU) which included delayed cord clamping (DCC) at birth and noninvasive ventilation as first-line cardiorespiratory support in the delivery room (DR), followed by bubble CPAP upon NICU admission. OBJECTIVE: Our goal was to evaluate the risk of (1) intubation and (2) discharge home on oxygen after adopting this standardized DR bundle in VPI born at a regional perinatal center and treated in the NICU over a ten-year period (2008-2017). MATERIALS AND METHODS: We compared maternal and neonatal demographics, respiratory care processes and outcomes, as well as neonatal mortality and morbidity in VPI (< 33 weeks gestation) and extremely low birth weight (ELBW, < 1000 g) subgroup for three consecutive epochs: 2008-2010, 2011-2013, and 2014-2017. RESULTS: Of 640 consecutive inborn VPI, 55% were < 1500 g at birth and 23% were ELBW. Constant through all three epochs, DCC occurred in 83% of VPI at birth. There was progressive increase in maternal magnesium during the three epochs and decrease in maternal antibiotics during the last epoch. Over the three epochs, VPI had less risk of DR intubation (23% versus 15% versus 5%), NICU intubation (39% versus 31% versus 18%), and invasive ventilation (37% versus 30% versus 17%), as did ELBW infants. Decrease in postnatal steroid use, antibiotic exposure, and increase in early colostrum exposure occurred over the three epochs both in VPI and in ELBW infants. There was a sustained decrease in surfactant use in the second and third epochs. There was no significant change in mortality or any morbidity in VPI; however, there was a significant decrease in pneumothorax (17% versus 0%) and increase in survival without major morbidity (15% versus 41%) in ELBW infants between 2008-2010 and 2014-2017. Benchmarked risk-adjusted rate for oxygen at discharge in a subgroup of inborn VPI (401-1500 g or 22-31 weeks of gestation) is 2.5% (2013-2017) in our NICU compared with > 8% in all California NICUs and > 10% in all California regional NICUs (2014-2016). CONCLUSION: Noninvasive strategies in DR and NICU minimize risk of intubation in VPI without adversely affecting other neonatal or respiratory outcomes. Risk-adjusted rates for discharge home on oxygen remained significantly lower for inborn VPI compared with rates at regional NICUs in California. Reducing intubation risk in ELBW infants may confer an advantage for survival without major morbidity. Prenatal magnesium may reduce intubation risk in ELBW infants.

Prevention of Prematurity: Advances and Opportunities.

Preterm birth (PTB) rate varies widely and has significant racial and ethnic disparities. Although causal mechanisms are ill understood, socioenvironment, phenotype, and genotype provide insight into pathways for preventing PTB. Data suggest varied response to current medical interventions is explicable Approved by underlying pharmacogenomics. Currently, prevention focuses on minimizing iatrogenic PTB and risk reduction especially in those with prior PTB using proven medical and public health strategies. In the future, preventive approaches will be based on better understanding of sociodemography, nutrition, lifestyles, and underlying individual genetic and epigenetic variation. Statistical approaches and "big-data" models are critical in future study.

Perfusion index in healthy newborns during critical congenital heart disease screening at 24 hours: retrospective observational study from the USA.

OBJECTIVE: To describe the distribution of perfusion index (PI) in asymptomatic newborns at 24 hours of life when screening for critical congenital heart disease (CCHD) using an automated data selection method. DESIGN: This is a retrospective observational study. SETTING: Newborn nursery in a California public hospital with ~3500 deliveries annually. METHODS: We developed an automated programme to select the PI values from CCHD screens. Included were term and late preterm infants who were screened for CCHD from November 2013 to January 2014 and from May 2015 to July 2015. PI measurements were downloaded every 2 s from the pulse oximeter and median PI were calculated for each oxygen saturation screen in our cohort. RESULTS: We included data from 2768 oxygen saturation screens. Each screen had a median of 29 data points (IQR 17 to 49). The median PI in our study cohort was 1.8 (95% CI 1.8 to 1.9) with IQR 1.2 to 2.7. The median preductal PI was significantly higher than the median postductal (1.9 vs 1.8, p=0.03) although this difference may not be clinically significant. CONCLUSION: Using an automated data selection method, the median PI in asymptomatic newborns at 24 hours of life is 1.8 with a narrow IQR of 1.2 to 2.7. This automated data selection method may improve accuracy and precision compared with manual data collection method. Further studies are needed to establish external validity of this automated data selection method and its clinical application for CCHD screening.

Somatosensory Modulation of Salivary Gene Expression and Oral Feeding in Preterm Infants: Randomized Controlled Trial.

BACKGROUND: Despite numerous medical advances in the care of at-risk preterm neonates, oral feeding still represents one of the first and most advanced neurological challenges facing this delicate population. Objective, quantitative, and noninvasive assessment tools, as well as neurotherapeutic strategies, are greatly needed in order to improve feeding and developmental outcomes. Pulsed pneumatic orocutaneous stimulation has been shown to improve nonnutritive sucking (NNS) skills in preterm infants who exhibit delayed or disordered nipple feeding behaviors. Separately, the study of the salivary transcriptome in neonates has helped identify biomarkers directly linked to successful neonatal oral feeding behavior. The combination of noninvasive treatment strategies and transcriptomic analysis represents an integrative approach to oral feeding in which rapid technological advances and personalized transcriptomics can safely and noninvasively be brought to the bedside to inform medical care decisions and improve care and outcomes. OBJECTIVE: The study aimed to conduct a multicenter randomized control trial (RCT) to combine molecular and behavioral methods in an experimental conceptualization approach to map the effects of PULSED somatosensory stimulation on salivary gene expression in the context of the acquisition of oral feeding habits in high-risk human neonates. The aims of this study represent the first attempt to combine noninvasive treatment strategies and transcriptomic assessments of high-risk extremely preterm infants (EPI) to (1) improve oral feeding behavior and skills, (2) further our understanding of the gene ontology of biologically diverse pathways related to oral feeding, (3) use gene expression data to personalize neonatal care and individualize treatment strategies and timing interventions, and (4) improve long-term developmental outcomes. METHODS: A total of 180 extremely preterm infants from three neonatal intensive care units (NICUs) will be randomized to receive either PULSED or SHAM (non-pulsing) orocutaneous intervention simultaneous with tube feedings 3 times per day for 4 weeks, beginning at 30 weeks postconceptional age. Infants will also be assessed 3 times per week for NNS performance, and multiple saliva samples will be obtained each week for transcriptomic analysis, until infants have achieved full oral feeding status. At 18 months corrected age (CA), infants will undergo neurodevelopmental follow-up testing, the results of which will be correlated with feeding outcomes in the neo-and post-natal period and with gene expression data and intervention status. RESULTS: The ongoing National Institutes of Health funded randomized controlled trial R01HD086088 is actively recruiting participants. The expected completion date of the study is 2021. CONCLUSIONS: Differential salivary gene expression profiles in response to orosensory entrainment intervention are expected to lead to the development of individualized interventions for the diagnosis and management of oral feeding in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT02696343; https://clinicaltrials.gov/ct2/show/NCT02696343 (Archived by WebCite at http://www.webcitation.org/6r5NbJ9Ym).

Homecare and Healthcare Utilization Errors Post-Neonatal Intensive Care Unit Discharge.

BACKGROUND: High-risk infants transitioning from the neonatal intensive care unit (NICU) to home represent a vulnerable population, given their complex care requirements. Little is known about errors during this period. PURPOSE: Identify and describe homecare and healthcare utilization errors in high-risk infants following NICU discharge. METHODS: This was a prospective observational cohort study of homecare (feeding, medication, and equipment) and healthcare utilization (appointment) errors in infants discharged from a regional NICU between 2011 and 2015. Chi-square test and Wilcoxon rank-sum test were used to compare infant and maternal demographics between infants with and without errors. RESULTS: A total of 363 errors were identified in 241 infants during 635 home visits. The median number of visits was 2. No significance was found between infant and maternal demographics in those with or without errors. IMPLICATIONS OF PRACTICE: High-risk infants have complex care needs and can benefit from regular follow-up services. Home visits provide an opportunity to identify, intervene, and resolve homecare and healthcare utilization errors. IMPLICATIONS OF RESEARCH: Further research is needed to evaluate the prevalence and cause of homecare errors in high-risk infants and how healthcare resources and infant health outcomes are affected by those errors. Preventive measures and mitigating interventions that best address homecare errors require further development and subsequent description.

Effect of Catheter Dwell Time on Risk of Central Line-Associated Bloodstream Infection in Infants.

BACKGROUND AND OBJECTIVE: Central venous catheters in the NICU are associated with significant morbidity and mortality because of the risk of central line-associated bloodstream infections (CLABSIs). The purpose of this study was to determine the effect of catheter dwell time on risk of CLABSI. METHODS: Retrospective cohort study of 13,327 infants with 15,567 catheters (93% peripherally inserted central catheters [PICCs], 7% tunneled catheters) and 256,088 catheter days cared for in 141 NICUs. CLABSI was defined using National Health Surveillance Network criteria. We defined dwell time as the number of days from line insertion until either line removal or day of CLABSI. We generated survival curves for each week of dwell time and estimated hazard ratios for CLABSI at each week by using a Cox proportional hazards frailty model. We controlled for postmenstrual age and year, included facility as a random effect, and generated separate models by line type. RESULTS: Median postmenstrual age was 29 weeks (interquartile range 26-33). The overall incidence of CLABSI was 0.93 per 1000 catheter days. Increased dwell time was not associated with increased risk of CLABSI for PICCs. For tunneled catheters, infection incidence was significantly higher in weeks 7 and 9 compared with week 1. CONCLUSIONS: Clinicians should not routinely replace uninfected PICCs for fear of infection but should consider removing tunneled catheters before week 7 if no longer needed. Additional studies are needed to determine what daily maintenance practices may be associated with decreased risk of infection, especially for tunneled catheters.

Duration of Cord Clamping and Neonatal Outcomes in Very Preterm Infants.

BACKGROUND: Delayed cord clamping (DCC, ≥30 s) increases blood volume in newborns and is associated with fewer blood transfusions and short-term neonatal complications. The optimal timing of cord clamping for very preterm infants should maximize placental transfusion without interfering with stabilization and resuscitation. AIM: We compared the effect of different durations of DCC, 30-45 s vs. 60-75 s, on delivery room (DR) and neonatal outcomes in preterm infants <32 weeks gestational age (GA). METHODS: This is a single-center prospective observational study. Data were collected prospectively from eligible infants from two groups: 30-45 s DCC group (January 2008 to February 2011, n = 187) and 60-75 s DCC group (March 2011 to April 2014, n = 166). RESULTS: The 60-75 s DCC group compared to the 30-45 s DCC group had higher hematocrits at <2 hours (49.2% vs. 47.4%, p = 0.02). In infants <28 weeks GA, the 12-36 hours hematocrit was higher in the 60-75 s DCC group compared to the 30-45 s DCC group (47.9% vs. 42.1%, p = 0.002). The 60-75 s DCC group had reductions in DR intubation (11% vs. 22%, p = 0.004), hypothermia on admission (1% vs. 5%, p = 0.01), surfactant therapy (13% vs. 28%, p = 0.001), intubation in the first 24 hours (20% vs. 34%, p = 0.004), any intubation (27% vs. 40%, p = 0.007), and any red blood cell transfusion (20% vs. 33%, p = 0.008) during the hospitalization compared to the 30-45 s DCC group. These reductions remained significant after adjusting for GA, gender and >48 hours of antenatal steroid exposure. There was no difference between the two groups in neonatal death, intraventricular hemorrhage, chronic lung disease, late onset sepsis, necrotizing enterocolitis and severe retinopathy of prematurity. CONCLUSION: In this study cohort increasing DCC duration from 30-45 s to 60-75 s is associated with decreased hypothermia on admission, neonatal respiratory interventions and red blood cell transfusions without increase in neonatal mortality and morbidities.

Modulation of EEG spectral edge frequency during patterned pneumatic oral stimulation in preterm infants.

BACKGROUND: Stimulation of the nervous system plays a central role in brain development and neurodevelopmental outcomes. Thalamocortical and corticocortical development is diminished in premature infants and correlated to electroencephalography (EEG) progression. The purpose of this study was to determine the effects of orocutaneous stimulation on the modulation of spectral edge frequency fc = 90% (SEF-90), which is derived from EEG recordings in preterm infants. METHODS: A total of 22 preterm infants were randomized to experimental and control conditions. Pulsed orocutaneous stimulation was presented during gavage feedings begun at ~32 wk postmenstrual age. The SEF-90 was derived from two-channel EEG recordings. RESULTS: Compared with the control condition, the pulsed orocutaneous stimulation produced a significant reorganization of SEF-90 in the left (P = 0.005) and right (P < 0.0001) hemispheres. Notably, the left and right hemispheres showed a reversal in the polarity of frequency shift, demonstrating hemispheric asymmetry in the frequency domain. Pulsed orocutaneous stimulation also produced a significant pattern of short-term cortical adaptation and a long-term neural adaptation manifested as a 0.5 Hz elevation in SEF-90 after repeated stimulation sessions. CONCLUSION: This is the first study to demonstrate the modulating effects of a servo-controlled oral somatosensory input on the spectral features of EEG activity in preterm infants.

Elimination of admission hypothermia in preterm very low-birth-weight infants by standardization of delivery room management.

CONTEXT: Temperature instability is a serious but potentially preventable morbidity in preterm infants. Admission temperatures below 36°C are associated with increased mortality and late onset sepsis. OBJECTIVE: The goal of our quality-improvement effort was to increase preterm infants' admission temperatures to above 36°C by preventing heat loss in the immediate postnatal period. DESIGN: This quality-improvement initiative used the rapid-cycle Plan-Do-Study-Act approach. Preterm infants born at less than 33 weeks' gestation with very low birth weight less than 1500 g who were born at a Regional Level III Neonatal Intensive Care Unit (NICU) in San Jose, CA, were enrolled. Our intervention involved standardizing the management of thermoregulation from predelivery through admission to the NICU. Data on admission temperature were collected prospectively. MAIN OUTCOME MEASURES: The primary outcome measure was hypothermia, defined as temperature below 36°C on admission to the NICU. RESULTS: The hypothermia rate was reduced from 44% in early 2006 to 0% by 2009. There was a slight increase to 6% in 2010. Subsequently, with further real-time feedback, we were able to sustain 0% hypothermia through 2011. Our hypothermia rate remained substantially lower than state and national hypothermia benchmarks that have shown moderate improvement over the same period. CONCLUSION: We reduced hypothermia in very low-birth-weight infants using a standardized protocol, multidisciplinary team approach, and continuous feedback. Sustaining improvement is a challenge that requires real-time progress evaluation of outcomes and ongoing staff education.