Major cardiorespiratory events do not increase after immunizations, eye exams, and other stressors in most very low birth weight infants.

BACKGROUND: Increased cardiorespiratory events with bradycardia and oxygen desaturation have been reported in very low birthweight (VLBW) infants following stressors such as immunizations. These events are difficult to quantify and may be mild. Our group developed an automated algorithm to analyze bedside monitor data from NICU patients for events with bradycardia and prolonged oxygen desaturation (BDs) and used this to compare BDs 24 hours before and after potentially stressful interventions. METHODS: We included VLBW infants from 2012-2017 with data available around at least one of four interventions: two-month immunizations, retinopathy of prematurity (ROP) examinations, ROP therapy, and inguinal hernia surgery. We used a validated algorithm to analyze electrocardiogram heart rate and pulse oximeter saturation data (HR, SpO2) to quantify BD events of HR < 100 beats/minute for≥4 seconds with oxygen desaturation < 80%SpO2 for≥10 seconds. BDs were analyzed 24 hours before and after interventions using Wilcoxon rank-sum tests. RESULTS: In 354 of 493 (72%) interventions, BD frequency stayed the same or decreased in the 24 hours after the event. An increase of at least five BD's occurred in 17/146 (12%) after immunizations, 85/290 (29%) after ROP examinations, 4/33 (12%) after ROP therapy, and 3/25 (12%) after hernia surgery. Infants with an increase in BDs after interventions had similar demographics compared to those without. More infants with an increase in BDs following immunizations were on CPAP or caffeine than those without. CONCLUSIONS: Most VLBW infants in our cohort had no increase in significant cardiorespiratory events in the 24 hours following potentially stressful interventions.

Correction: Recovery from bradycardia and desaturation events at 32 weeks corrected age and NICU length of stay: an indicator of physiologic resilience?

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Recovery from bradycardia and desaturation events at 32 weeks corrected age and NICU length of stay: an indicator of physiologic resilience?

BACKGROUND: Preterm very low birth weight (VLBW) infants experience physiologic maturation and transitions off therapies from 32 to 35 weeks postmenstrual age (PMA), which may impact episodic bradycardia and oxygen desaturation. We sought to characterize bradycardias and desaturations from 32 to 35 weeks PMA and test whether events at 32 weeks PMA are associated with NICU length of stay. METHODS: For 265 VLBW infants from 32 to 35 weeks PMA, we quantified the number and duration of bradycardias (HR <100 for ≥4 s) and desaturations (SpO2 <80% for ≥10 s) and compared events around discontinuation of CPAP, caffeine, and supplemental oxygen. We modeled associations between clinical variables, bradycardias and desaturations at 32 weeks PMA, and discharge PMA. RESULTS: Desaturations decreased from 60 to 41 per day at 32 and 35 weeks, respectively (p < 0.01). Duration of desaturations and number and duration of bradycardias decreased to a smaller extent (p < 0.05), and there was a non-significant trend toward increased desaturations after stopping CPAP and caffeine. Controlling for clinical variables, longer duration of bradycardias and desaturations at 32 weeks PMA was associated with later discharge PMA. CONCLUSION: Delayed recovery from bradycardias and desaturations at 32 weeks PMA, perhaps reflecting less physiologic resilience, is associated with prolonged NICU stay for VLBW infants.

Neonatal Intensive Care Unit Length of Stay Reduction by Heart Rate Characteristics Monitoring.

OBJECTIVE: To examine the effect of heart rate characteristics (HRC) monitoring on length of stay among very low birth weight (VLBW; <1500 g birth weight) neonates in the HeRO randomized controlled trial (RCT). STUDY DESIGN: We performed a retrospective analysis of length of stay metrics among 3 subpopulations (all patients, all survivors, and survivors with positive blood or urine cultures) enrolled in a multicenter, RCT of HRC monitoring. RESULTS: Among all patients in the RCT, infants randomized to receive HRC monitoring were more likely than controls to be discharged alive and prior to day 120 (83.6% vs 80.1%, P = .014). The postmenstrual age at discharge for survivors with positive blood or urine cultures was 3.2 days lower among infants randomized to receive HRC monitoring when compared with controls (P = .026). Although there were trends in other metrics toward reduced length of stay in HRC-monitored patients, none reached statistical significance. CONCLUSIONS: HRC monitoring is associated with reduced mortality in VLBW patients and a reduction in length of stay among infected surviving VLBW infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00307333.

Evidence of Early Pulmonary Hypertension Is Associated with Increased Mortality in Very Low Birth Weight Infants.

Objective The objective of this study was to describe the inhospital outcomes of a high-risk cohort of very low birth weight infants with evidence of pulmonary hypertension (PHT) within the first 2 weeks after delivery. Design A retrospective cohort study of consecutively admitted neonates with birth weight < 1,500 g admitted to a Level IV neonatal intensive care unit who were evaluated by echocardiogram between 72 hours and 14 days. Results A total of 343 eligible infants were included in the cohort with a median gestational age of 25.5 weeks and birth weight of 790 g. Evidence of early PHT was associated with birth weight Z-score (odds ratio [OR]: 0.65, confidence interval [CI]: 0.48-0.87) and maternal African American race (OR: 1.9, CI: 1.03-3.69). Early PHT was associated with decreased in-hospital survival compared with those with no evidence of PHT (OR: 2.0, CI: 1.02-3.90), and was associated with an increased rate of moderate-to-severe bronchopulmonary dysplasia at 36 weeks postmenstrual age (OR: 2.92, CI: 1.24-6.89). Conclusion The presence of early PHT on echocardiogram between 72 hours and 14 days of age was associated with decreased in-hospital survival and worse pulmonary outcomes. This population represents a group of infants who warrant further investigation to improve outcomes.

Clinical associations with immature breathing in preterm infants: part 2-periodic breathing.

BACKGROUND: Periodic breathing (PB) is a normal immature breathing pattern in neonates that, if extreme, may be associated with pathologic conditions. METHODS: We used our automated PB detection system to analyze all bedside monitor chest impedance data on all infants <35 wk' gestation in the University of Virginia Neonatal Intensive Care Unit from 2009-2014 (n = 1,211). Percent time spent in PB was calculated hourly (>50 infant-years' data). Extreme PB was identified as a 12-h period with PB >6 SDs above the mean for gestational age (GA) and postmenstrual age and >10% time in PB. RESULTS: PB increased with GA, with the highest amount in infants 30-33 wk' GA at about 2 wk' chronologic age. Extreme PB was identified in 76 infants and in 45% was temporally associated with clinical events including infection or necrotizing enterocolitis (NEC), immunizations, or caffeine discontinuation. In 8 out of 28 cases of septicemia and 10 out of 21 cases of NEC, there was a >2-fold increase in %PB over baseline on the day prior to diagnosis. CONCLUSION: Infants <35 wk GA spend, on average, <6% of the time in PB. An acute increase in PB may reflect illness or physiological stressors or may occur without any apparent clinical event.

Cost Analysis of Fluconazole Prophylaxis for Prevention of Neonatal Invasive Candidiasis.

BACKGROUND: Fluconazole prophylaxis (FP) in premature infants is well studied and has been shown to decrease invasive candidiasis (ICs). IC in neonates has significant financial costs; determining the cost-benefit of FP may provide additional justification for targeting high-risk neonates. We aimed to determine the IC rate in premature infants at which FP is cost-beneficial. METHODS: A decision tree cost-analysis model using cost of FP related to costs associated with IC was used. We searched PubMed for all papers that used intravenous FP and reported rates of IC in very low birth weight neonates. Average IC rates in those who received FP (2.0%; range, 0-6.1%) and in those who did not receive FP (9.2%; range, 0-20.5%) were used. Incremental hospital costs because of IC and for FP were retrieved from the literature. Sensitivity analysis was performed to determine the incremental cost of FP across the range of published IC rates. RESULTS: The average cost per patient attributed to IC in patients receiving FP was $785 versus $2617 in those not receiving FP. Sensitivity analysis demonstrates the rate of IC would need to be <2.8% for FP to lose its cost-benefit. In Monte Carlo simulation, targeting infants <1000 g would lead to $50,304,333 in cost savings per year in the United States. CONCLUSIONS: FP provides a cost-advantage across most IC rates seen in the youngest premature infants. Using a rate of 2.8% for their individual high-risk neonatal intensive care unit patients, providers can determine if FP is cost-beneficial in determining for whom to provide IC prophylaxis.

Testing the Feasibility of Skype and FaceTime Updates With Parents in the Neonatal Intensive Care Unit.

BACKGROUND: Effective provider-parent relationships are essential during critical illness when treatment decisions are complex, the environment is crowded and unfamiliar, and outcomes are uncertain. OBJECTIVES: To evaluate the feasibility of daily Skype or FaceTime updates with parents of patients in the neonatal intensive care unit (NICU) and to assess the intervention's potential for improving parent-provider relationships. METHODS: A pre/post mixed-methods approach was used. NICU parent participants received daily Skype or FaceTime updates for 5 days and completed demographic and feasibility surveys. Parents also completed Penticuff's Parents' Understanding survey before and after the intervention. Nurses and physicians completed feasibility surveys after each update. RESULTS: Twenty-six parents were enrolled and 15 completed the study. More than 90% of providers and parents perceived the intervention to be reliable and easy to use, and about 80% of parents and providers rated video and audio quality as either excellent or good. Frozen screens and missed updates due to scheduling problems were challenges. Two of the 4 subscores on the Parents' Understanding survey improved significantly. Qualitative data favor the intervention as meaningful for parents. CONCLUSIONS: Real-time videoconferencing via Skype or FaceTime is feasible for providing updates for parents when they cannot be present in the NICU and can be used to include parents in bedside rounds. Videoconferencing updates may improve relationships between parents and the health care team.

Quantification of periodic breathing in premature infants.

Periodic breathing (PB), regular cycles of short apneic pauses and breaths, is common in newborn infants. To characterize normal and potentially pathologic PB, we used our automated apnea detection system and developed a novel method for quantifying PB. We identified a preterm infant who died of sudden infant death syndrome (SIDS) and who, on review of her breathing pattern while in the neonatal intensive care unit (NICU), had exaggerated PB.We analyzed the chest impedance signal for short apneic pauses and developed a wavelet transform method to identify repetitive 10-40 second cycles of apnea/breathing. Clinical validation was performed to distinguish PB from apnea clusters and determine the wavelet coefficient cutoff having optimum diagnostic utility. We applied this method to analyze the chest impedance signals throughout the entire NICU stays of all 70 infants born at 32 weeks' gestation admitted over a two-and-a-half year period. This group includes an infant who died of SIDS and her twin.For infants of 32 weeks' gestation, the fraction of time spent in PB peaks 7-14 d after birth at 6.5%. During that time the infant that died of SIDS spent 40% of each day in PB and her twin spent 15% of each day in PB.This wavelet transform method allows quantification of normal and potentially pathologic PB in NICU patients.

Transition from fetus to newborn.

The fetus to newborn transition is a complex physiologic process that requires close monitoring. Approximately 10% of all newborns require some support in facilitating a successful transition after delivery. Clinicians should be aware of the physiologic processes and pay close regard to the newborn's cardiopulmonary transition at birth to provide appropriate treatment and therapies as required. Trained Personnel in the Neonatal Resuscitation program should be available at the delivery for all newborns to ensure that immediate and appropriate care is provided to achieve the best possible outcomes for those babies not smoothly transitioning to extrauterine life.

Cognitive workload changes for nurses transitioning from a legacy system with paper documentation to a commercial electronic health record.

OBJECTIVE: Healthcare institutions worldwide are moving to electronic health records (EHRs). These transitions are particularly numerous in the US where healthcare systems are purchasing and implementing commercial EHRs to fulfill federal requirements. Despite the central role of EHRs to workflow, the cognitive impact of these transitions on the workforce has not been widely studied. This study assesses the changes in cognitive workload among pediatric nurses during data entry and retrieval tasks during transition from a hybrid electronic and paper information system to a commercial EHR. MATERIALS AND METHODS: Baseline demographics and computer attitude and skills scores were obtained from 74 pediatric nurses in two wards. They also completed an established and validated instrument, the NASA-TLX, that is designed to measure cognitive workload; this instrument was used to evaluate cognitive workload of data entry and retrieval. The NASA-TLX was administered at baseline (pre-implementation), 1, 5 and 10 shifts and 4 months post-implementation of the new EHR. RESULTS: Most nurse participants experienced significant increases of cognitive workload at 1 and 5 shifts after "go-live". These increases abated at differing rates predicted by participants' computer attitudes scores (p = 0.01). CONCLUSIONS: There is substantially increased cognitive workload for nurses during the early phases (1-5 shifts) of EHR transitions. Health systems should anticipate variability across workers adapting to "meaningful use" EHRs. "One-size-fits-all" training strategies may not be suitable and longer periods of technical support may be necessary for some workers.

NASCAR pit-stop model improves delivery room and admission efficiency and outcomes for infants <27 weeks' gestation.

AIM: To evaluate a new process based on teamwork in a manner similar to the race car pit stop on organization and efficiency during the "Golden Hours" for extremely preterm infants. METHODS: A team designed an improved process focused on checklists, preparation, assigning roles, and best practices, for the care of infants <27 weeks' gestation in the delivery room (DR) through admission to the neonatal intensive care unit (NICU). Clinical outcomes 2 years before and after implementation were analyzed. A survey was administered to NICU staff prior to and 14 months after implementation. The survey assessed organization and efficiency in the DR and during the admission process of the target population. RESULTS: There were 62 inborn infants prior to and 90 infants after implementation with overall survival of 90.3% and 86.6%, respectively (p = 0.61). Infants were more stable on admission with a mean arterial blood pressure equal to or greater than their gestational age in the post intervention group compared to the pre-cohort (76% vs 57%, p = 0.02) and discharged home at a lower mean postmenstrual age (39.0 ± 2.2 vs 40.1 ± 3.5 weeks, p = 0.04) The survey demonstrated improvement in assessment of roles being clearly defined in the DR and in the organization and the efficiency both in the DR and during the NICU admission (p < 0.05). CONCLUSIONS: A systematic approach to the care of the <27 weeks' gestation neonate increased staff perception of improved organization and efficiency in the DR through admission processes and improved outcomes.

Very long apnea events in preterm infants.

Apnea is nearly universal among very low birth weight (VLBW) infants, and the associated bradycardia and desaturation may have detrimental consequences. We describe here very long (>60 s) central apnea events (VLAs) with bradycardia and desaturation, discovered using a computerized detection system applied to our database of over 100 infant years of electronic signals. Eighty-six VLAs occurred in 29 out of 335 VLBW infants. Eighteen of the 29 infants had a clinical event or condition possibly related to the VLA. Most VLAs occurred while infants were on nasal continuous positive airway pressure, supplemental oxygen, and caffeine. Apnea alarms on the bedside monitor activated in 66% of events, on average 28 s after cessation of breathing. Bradycardia alarms activated late, on average 64 s after cessation of breathing. Before VLAs oxygen saturation was unusually high, and during VLAs oxygen saturation and heart rate fell unusually slowly. We give measures of the relative severity of VLAs and theoretical calculations that describe the rate of decrease of oxygen saturation. A clinical conclusion is that very long apnea (VLA) events with bradycardia and desaturation are not rare. Apnea alarms failed to activate for about one-third of VLAs. It appears that neonatal intensive care unit (NICU) personnel respond quickly to bradycardia alarms but not consistently to apnea alarms. We speculate that more reliable apnea detection systems would improve patient safety in the NICU. A physiological conclusion is that the slow decrease of oxygen saturation is consistent with a physiological model based on assumed high values of initial oxygen saturation.

Nonsterile glove use in addition to hand hygiene to prevent late-onset infection in preterm infants: randomized clinical trial.

IMPORTANCE: Late-onset infections commonly occur in extremely preterm infants and are associated with high rates of mortality and neurodevelopmental impairment. Hand hygiene alone does not always achieve the desired clean hands, as microorganisms are still present more than 50% of the time. We hypothesize that glove use after hand hygiene may further decrease these infections. OBJECTIVE: To determine if nonsterile glove use after hand hygiene before all patient and intravenous catheter contact, compared with hand hygiene alone, prevents late-onset infections in preterm infants. DESIGN, SETTINGS, AND PARTICIPANTS: A prospective, single-center, clinical, randomized trial was conducted in infants admitted to the neonatal intensive care unit who weighed less than 1000 g and/or had a gestational age of less than 29 weeks and were less than 8 days old. There were 175 eligible infants, of which 120 were enrolled during a 30-month period from December 8, 2008, to June 20, 2011. INTERVENTIONS: Infants were randomly assigned to receive care with nonsterile gloves after hand hygiene (group A) or care after hand hygiene alone (group B) before all patient and intravenous line (central and peripheral) contact. Study intervention was continued while patients had central or peripheral venous access. MAIN OUTCOMES AND MEASURES: One or more episodes of late-onset (>72 hours of age) infection in the bloodstream, urinary tract, or cerebrospinal fluid or necrotizing enterocolitis. RESULTS: The 2 groups were similar in baseline demographic characteristics. Late-onset invasive infection or necrotizing enterocolitis occurred in 32% of infants (19 of 60) in group A compared with 45% of infants (27 of 60) in group B (difference, -12%; 95% CI, -28% to 6%; P = .13). In group A compared with group B, there were 53% fewer gram-positive bloodstream infections (15% [9 of 60] vs 32% [19 of 60]; difference, -17%; 95% CI, -31% to -1%; P = .03) and 64% fewer central line-associated bloodstream infections (3.4 vs 9.4 per 1000 central line days; ratio, 0.36; 95% CI, 0.16 to 0.81; P = .01). CONCLUSIONS AND RELEVANCE: Glove use after hand hygiene prior to patient and line contact is associated with fewer gram-positive bloodstream infections and possible central line-associated bloodstream infections in preterm infants. This readily implementable infection control measure may result in decreased infections in high-risk preterm infants. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01729000.

The apolipoprotein gene and recovery from brain injury among extremely preterm infants.

BACKGROUND: Extremely preterm infants have an increased risk of brain injury and, consequently, are more likely to exhibit signs of motor, cognitive or behavioral impairment. Various factors, including genetic, may influence how the brain responds to an injury, ranging from no to complete recovery. The apolipoprotein E (APOE) gene codes for a protein in the brain involved in maintenance and repair of neurons. OBJECTIVE: To determine whether any of the three APOE alleles are related to improved outcome. METHODS: A total of 87 preterm infants with birth weights less than 1,000 g and no obvious preexisting brain abnormalities were genotyped for the APOE gene; 71 of these were assessed with the Bayley III Scales at a corrected age of 12-15 months. Brain MRI was obtained on a subgroup of 52 infants at term equivalent. RESULTS: No significant relationship was found between the three APOE alleles and developmental outcomes or brain MRI findings. CONCLUSION: APOE does not appear to be related in a direct way to the developmental sequelae of white or gray matter injury in extremely preterm infants.

Early births and congenital birth defects: a complex interaction.

Congenital birth defects and early/premature birth are common complex conditions affecting populations throughout the world, the interaction of which accounts for a significant proportion of neonatal morbidity and mortality. The relationship between these two conditions is not well understood. Several congenital birth defects can directly lead to early delivery. In addition, certain fetal conditions may necessitate early or premature delivery, several of which are also associated with maternal conditions necessitating early birth. Further understanding of both the incidences and causes of congenital birth defects and of early and premature birth will facilitate establishment of strategies to improve neonatal mortality and morbidity.

Factors associated with neonatal intensive care follow-up appointment compliance.

BACKGROUND AND METHODS: Our goal was to identify factors that affect neonatal intensive care unit (NICU) follow-up appointment compliance. Compliant and noncompliant infants discharged from the NICU over 1 year and scheduled for follow-up (133) were compared retrospectively; a prospective telephone survey of noncompliant families was also undertaken. RESULTS: Maternal drug use (odds ratio [OR] = 0.049, 95% confidence interval [CI] = 0.005-0.506), multiple gestation pregnancy (OR = 0.163, 95% CI = 0.050-0.533), male sex (OR = 0.308, 95% CI = 0.112-0.850), and greater distance from the hospital (OR = 0.987, 95% CI = 0.976-0.999) were independently associated with lower appointment compliance. A greater number of days on oxygen was associated with greater odds of compliance (OR = 1.057, 95% CI = 0.976-0.999). Shorter NICU stays (P = .047) and less chronic lung disease (P = .026) were significantly associated with noncompliance by bivariate analysis only. Distance from the hospital and travel expense were the most often self-cited reasons for appointment noncompliance. CONCLUSION: Understanding factors associated with NICU follow-up noncompliance is a starting point for providing targeted intervention.

Frequency of elevations in markers of cardiomyocyte damage in otherwise healthy newborns.

Myocardial damage in infancy is a risk factor for eventual cardiac disease. Given that myocardial stress is greatest during the perinatal period and that the neonatal period is when most pediatric heart failure occurs, the aim of this study was to determine whether even otherwise healthy neonates might have subclinical myocardial damage and, if so, what characteristics might identify them. Umbilical cord and neonatal serum samples from 32 normal neonates were assayed for biomarkers of myocardial injury. No neonate had clinical evidence of cardiac or other abnormalities. Serum cardiac troponin T was elevated in 19 of 25 cords (76%) and in 16 of 17 neonates (94%); levels indicating myocardial infarction (> or =0.2 ng/ml) were found in 2 patients (1 umbilical cord and 1 neonatal sample). Creatine kinase-MB was elevated in 6 of 16 cords (38%) and in 8 of 15 neonates (53%). Cardiac troponin I was elevated in 11% and 17% of samples, myoglobin in 4% and 17%, and high-sensitivity C-reactive protein in 9% and 40%. Measures of myocardial injury were associated with longer hospitalization (r = 0.50, p = 0.04), non-Caucasian race (p = 0.012), lower birth weights (p = 0.014), positive maternal cervical cultures (r = 0.41, p = 0.046), and elevated high-sensitivity C-reactive protein (r = 0.66, p = 0.005). In conclusion, clinically occult myocardial injury appears to occur in some healthy newborns, although whether it is pathologic or not remains to be determined.

Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes.

OBJECTIVE: The objective of the study was to determine whether indomethacin used as a tocolytic agent is associated with adverse neonatal outcomes. STUDY DESIGN: We used published guidelines of the Metaanalysis of Observational Studies in Epidemiology Group (MOOSE) to perform the metaanalysis. The search strategy used included computerized bibliographic searches of MEDLINE (1966-2005), PubMed (1966-2005), abstracts published in Obstetrics and Gynecology (1991-2005), abstracts published in Pediatric Research (1991-2005), and references of published manuscripts. Study inclusion criteria were publication in English, more than 30 deliveries less than 37 weeks' gestation, and meeting diagnostic criteria for individual neonatal outcomes. Exclusion criteria included case reports, case series, and multiple publications from the same author. Metaanalysis was performed using random effects model if there were more than 2 observational studies for a specific outcome. Eggers test was performed to exclude publication bias. Sensitivity analysis was performed to evaluate the effect of antenatal steroid exposure, gestation, and recent antenatal indomethacin exposure (duration of 48 hours or more between the last dose and delivery). RESULTS: Fifteen retrospective cohort studies and 6 case-controlled studies met inclusion criteria. Antenatal indomethacin was associated with an increased risk of periventricular leukomalacia (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.3-3.1). Recent exposure to antenatal indomethacin was associated with necrotizing enterocolitis (OR, 2.2; 95% CI; 1.1-4.2). Antenatal indomethacin was not associated with intraventricular hemorrhage, patent ductus arteriosus, respiratory distress syndrome, bronchopulmonary dysplasia, and mortality. CONCLUSION: Antenatal indomethacin may be associated with an increased risk of periventricular leukomalacia and necrotizing enterocolitis in premature infants and therefore should be used judiciously for tocolysis.