Intratracheal Instillation of Budesonide-Surfactant for Prevention of Bronchopulmonary Dysplasia in Extremely Premature Infants.

OBJECTIVE: This study aimed to determine the effect of intratracheal instillation of a budesonide-surfactant combination on the incidence of bronchopulmonary dysplasia (BPD) or death compared with surfactant alone in extremely preterm infants. STUDY DESIGN: In this retrospective, single-center study, we included extremely preterm infants (<28 weeks' gestation) who received surfactant for respiratory distress in the first 3 days of life. We compared infants who received budesonide-surfactant combination (intervention group: infants born between February 2016 and October 2021) with surfactant alone (control group: infants born from January 2010 through January 2016). The primary outcome was a composite of BPD grade 2 or 3 (as defined by Jensen et al, 2019) or death before 36 weeks' postmenstrual age (PMA). RESULTS: We included 966 extremely preterm infants (528 in the control group and 438 in the intervention group). While the incidence of death/BPD grade 2 or 3 at 36 weeks of PMA was not different between the two groups (66% in the intervention group vs. 63% in the control group; adjusted relative risk [aRR], 0.99; 95% confidence interval [CI], 0.90-1.07; p-value = 0.69), budesonide was associated with a reduction in the primary outcome only in a subgroup of infants with birth weight ≥ 750 grams (36.8 vs. 43.5%, respectively; aRR 0.75; 95% CI, 0.57-0.98). Primary and secondary outcomes did not differ between the two groups within the subgroup of infants weighing <750 grams. CONCLUSION: In extremely preterm infants, the budesonide-surfactant combination therapy reduced the rates of BPD or death in infants weighing ≥750 grams; however, this beneficial effect was not seen in infants weighing <750 grams. Further investigation of this treatment may be indicated before it is considered a standard approach to management. KEY POINTS: · Intratracheal budesonide-surfactant therapy reduces BPD in preterm infants weighing ≥750 grams.. · Intratracheal budesonide-surfactant therapy does not affect BPD in preterm infants weighing <750 grams.. · Intratracheal budesonide-surfactant therapy does not affect the mortality rate in preterm infants..

Back vs. chest ECG electrode placement in neonatal resuscitation: A pilot randomized controlled trial.

BACKGROUND: The recent Neonatal Resuscitation Program advises the early utilization of an electrocardiogram (ECG) for non-vigorous newborns in the delivery room. However, placing ECG electrodes on the chest may delay obtaining a reliable heart rate (HR) and could interfere with chest compressions. Our previous study showed that preset ECG electrodes, attached to the back of the newborn, are quicker than a pulse oximeter (POX) for detecting HR. AIM: To compare time to detect a reliable HR using back-placed ECG electrodes versus standard front placement. METHODS: Infants were randomly assigned to back (n = 85) or chest (n = 89) electrode placement. Time measurement began upon placing infants on a Panda warmer ResusView. Failure was defined as no HR detected within 5 minutes. Intention-to-treat analysis compared HR signal acquisition time between groups. RESULTS: Both groups showed similar proportions of detectable HR within the first minute. Median (IQR) time to obtain HR was 26 (13,38) seconds for the chest group and 21 (12,54) seconds for the back group (p = 0.91). A large number of vigorous infants were included. In the chest group, these vigorous infants had shorter HR acquisition times than non-vigorous infants (Mean ± SD of 34 ± 48 seconds vs. 50 ± 44 seconds respectively; p = 0.049). Failure rates and time to acquire a HR for infants who were non-vigorous and required advanced resuscitation were similar between the back and chest groups (p = 0.51). CONCLUSION: Preset back ECG electrodes have shown encouraging results in neonates requiring advanced resuscitation. Further studies are needed to enhance guidance during neonatal resuscitation.

Optimizing the hospital discharge process to facilitate family-centered care for well newborns.

BACKGROUND: The perceptions of discharge readiness differ among caregivers and providers. An efficient planning process ensures timely attainment of discharge readiness. Our aim was to increase the percentage of discharge orders placed by 10 a.m. from 0.5% to 10% within 6 months thereby improving discharge readiness. METHODS: We conducted a quality improvement initiative in the newborn nursery between March 2021 and June 2022 (n = 2307). We implemented a physician-led early discharge huddle and standardized the newborn screen (NBS) and circumcision process. RESULTS: By 10 a.m., our primary outcome measure, discharge orders, improved from 0.5 to 19%. Our process measures also increased. NBS specimens collected improved from 56 % to 98 % and circumcision rates increased from 66 to 88%. Balancing measure of postpartum hospital days remained stable. CONCLUSIONS: Optimizing family-centered discharge processes by addressing key drivers is essential and can be achieved without an increase in postpartum hospital days.

The Impact of Phenobarbital on the Ability of Electroencephalogram to Predict Adverse Outcome in Asphyxiated Neonates during Therapeutic Hypothermia.

OBJECTIVE: Classification of electroencephalogram (EEG) background has been established to predict outcome in neonates with hypoxic ischemic encephalopathy (HIE). However, the impact of phenobarbital therapy on the predictability of EEG background has not been studied. Our objective is to determine if EEG background after treatment with phenobarbital during therapeutic hypothermia (TH) remains a good predictor for brain injury in neonates with HIE. STUDY DESIGN: This is a single-center, retrospective study of consecutive neonates with HIE who underwent TH and EEG monitoring from October 2017 to March 2021. Per institutional protocol, all infants received a dose of prophylactic phenobarbital and bumetanide therapy at the onset of TH for sedative and neuroprotective measures. The initial 3 hours of EEG background activity was classified based on national guidelines. Infants were separated into two groups based on EEG background scores: group 1 (normal-mild, n = 30) and group 2 (moderate-severe, n = 36). Brain magnetic resonance imaging (MRI) results were scored based on the National Institute of Child Health and Human Development (NICHD) criteria. Adverse outcomes were defined as death before MRI or NICHD brain injury score > 1A. RESULTS: Infants in group 2 had lower Apgar scores at 5 minutes of age, severe acidemia, moderate to severe encephalopathy score, and earlier initiation of EEG monitoring than infants in group 1. Moderate to severe EEG background score was associated with presence of brain injury on MRI or death (p = 0.003), and this association remained significant even after adjustment for independent risk factors (odds ratio = 56.24 [95% confidence interval = 1.841-1718], p = 0.021). CONCLUSION: Phenobarbital therapy does not affect the ability of EEG to predict adverse outcome in infants with perinatal asphyxia during TH. KEY POINTS: · EEG has a clinical utility for predicting outcome in neonates with hypoxia-ischemia.. · Phenobarbital therapy is commonly used in neonates, and may impact EEG background findings.. · In spite phenobarbital therapy, moderate to severe EEG background abnormalities in infants with perinatal asphyxia during TH remain an excellent predictor for poor outcome..

Bevacizumab for Retinopathy of Prematurity: 2-Year Neurodevelopmental Follow-up.

OBJECTIVE: This study aimed to determine whether infants who were treated with intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP) were at higher risk of death or neurodevelopmental impairment (NDI) when compared with infants who were not treated with IVB (Laser only). STUDY DESIGN: This retrospective study included 146 infants born from 2009 through 2016 with a birth weight (BW) <1,000 g, gestational age <27 weeks, and required ROP therapy. Death and NDI rates were assessed at 18 to 24 months' corrected age. RESULTS: Rates of death or severe NDI were 62 and 53% in the IVB (n = 61) and Laser only (n = 85) groups, respectively. This difference was not statistically different despite sample selection bias in treating growth-restricted infants with IVB, BW (median [IQR]) was 481 (420-583) versus 547 (473-640) g in IVB and Laser only groups, respectively, p = 0.003. The adjusted odds ratio and 95% confidence interval of death or severe NDI was 0.86 (0.33-2.20). CONCLUSION: Bevacizumab therapy for ROP did not affect survival and neurodevelopment of extremely preterm infants. KEY POINTS: · Intravitreal bevacizumab therapy for retinopathy of prematurity may be safe in periviable preterm infants.. · Intravitreal bevacizumab therapy does not increase mortality rate in periviable preterm infants.. · Intravitreal bevacizumab therapy does not increase adverse neurodevelopmental outcome in periviable infants..

Implementation of a Modified Neonatal Early-onset Sepsis Calculator in Well-baby Nursery: a Quality Improvement Study.

BACKGROUND: The use of sepsis risk scores (SRSs), calculated based on the neonatal early-onset sepsis (EOS) calculator, has been shown to limit the unwarranted sepsis evaluations and to reduce the empirical use of antibiotics in neonates.s. PURPOSE: To reduce both the sepsis evaluation rate (SER) and antibiotic initiation rate (AIR) by 25% from baseline by incorporating conservative SRS cutoff values into the routine sepsis risk assessment of well-appearing neonates born at 34 weeks and older gestation. METHODS: During a pre quality improvement (QI) period (June 2016-August 2016), a QI team calculated SRS on all newborn infants to determine safe SRS cutoff values. During the QI-study period (September 2016-November 2017), we implemented an EOS evaluation algorithm based on 2 SRS cutoff values, 0.05 (later increased to 0.1) for sepsis evaluation and 0.3 for the initiation of antibiotic therapy. Monthly SER and AIR were summarized and analyzed by using standard statistical tests and statistical process control charts. During the surveillance phase (January 2019-June 2019), we evaluated whether previously attained improvements in SER and AIR were sustained. RESULTS: During the pre-QI period, the mean (±SD) of monthly SER and monthly AIR were 23.8% (±5.7%) and 6.2% (±0.4%), respectively. During the QI-study period, the mean (±SD) of monthly SER and monthly AIR decreased to 15% (±4.7%), P = 0.01, and 3.2% (±1.5%), P = 0.005, respectively. During the surveillance period, both outcome measures were comparable with the QI-study period. CONCLUSION: The implementation of a modified EOS calculator-based EOS algorithm using a conservative approach was successful in reducing antibiotic exposure and the need for blood work in well-appearing neonates.

Correction to: A single-dose indomethacin prophylaxis for reducing perinatal brain injury in extremely low birth weight infants: a non-inferiority analysis.

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

A single-dose indomethacin prophylaxis for reducing perinatal brain injury in extremely low birth weight infants: a non-inferiority analysis.

OBJECTIVE: To evaluate whether rates of perinatal brain injury among extremely low birth weight infants are comparable between two treatments: single-dose indomethacin prophylaxis (SGL-IP) (0.2 mg/kg, given once) vs. standard-dose indomethacin prophylaxis (STD-IP) (0.1 mg/kg/day, 3 days). METHODS: In this retrospective study, the primary outcome was perinatal brain injury (neuro-imaging evidence of intraventricular hemorrhage or periventricular leukomalacia) or death before discharge. A non-inferior efficacy of an SGL-IP regimen compared with a STD-IP regimen was determined by calculating the adjusted difference in the risk of the primary outcome using a multivariable logistic regression model. A 10-percentage point non-inferiority margin was favored. RESULTS: Prevalence rates of primary outcome were 41.7% in the SGL-IP group (n = 403) and 42.5% in the STD-IP group (n = 509) (adjusted risk difference: -1.2, 95% CI: -7.6 to +5.2, p = 0.71). CONCLUSION: Use of a single prophylactic indomethacin dose was as effective as a standard regimen in preventing perinatal brain injury.

Comparison of the Pharmacoeconomics of Calfactant and Poractant Alfa in Surfactant Replacement erapy.

OBJECTIVE: To compare the pharmacy costs of calfactant (Infasurf, ONY, Inc.) and poractant alfa (Curosurf, Chiesi USA, Inc., Cary, NC). METHODS: The University of South Alabama Children's and Women's Hospital switched from calfactant to poractant alfa in 2013 and back to calfactant in 2015. Retrospectively, we used deidentified data from pharmacy records that provided type of surfactant administered, gestational age, birth weight, and number of doses on each patient. We examined differences in the number of doses by gestational ages and the differences in costs by birth weight cohorts because cost per dose is based on weight. RESULTS: There were 762 patients who received calfactant and 432 patients who received poractant alfa. The average number of doses required per patient was 1.6 administrations for calfactant-treated patients and 1.7 administrations for poractant alfa-treated patients, p = 0.03. A higher percentage of calfactant patients needed only 1 dose (53%) than poractant alfa patients (47%). The distribution of the number of doses for calfactant-treated patients was significantly lower than for the poractant alfa-patients, p < 0.001. Gestational age had no consistent effect on the number of doses required for either calfactant or poractant alfa. Per patient cost was higher for poractant alfa than for calfactant in all birth weight cohorts. Average per patient cost was $1160.62 for poractant alfa, 38% higher than the average per patient cost for calfactant ($838.34). Using poractant alfa for 22 months is estimated to have cost $202,732.75 more than it would have cost if the hospital had continued using calfactant. CONCLUSION: Our experience showed a strong pharmacoeconomic advantage for the use of calfactant compared to the use of poractant alfa because of similar average dosing and lower per patient drug costs.

Presetting ECG electrodes for earlier heart rate detection in the delivery room.

AIM: To determine whether heart rate (HR) could be detected earlier than by pulse oximeter (POX), using a novel method of application of electrocardiogram (ECG) electrodes during neonatal resuscitation in the delivery room. METHODS: ECG electrodes were set before delivery to be applied to the back of infants' thorax. Time to detect HR was recorded as soon as a numerical HR along with a recognizable and persistent QRS complex was observed on ECG monitor (HRECG) and a plethysmographic waveform was seen on POX monitor (HRPOX). RESULTS: Out of 334 infants, 49 were <31 weeks of gestational age. Overall, the median (interquartile range, IQR) time to detect HRECG was significantly shorter [29 (5, 60) seconds] than time by POX [60 (45,120) seconds], (p < 0.001). Similarly, in <31-week infants, the median (IQR) time to detect HRECG was 10 (2, 40) seconds compared to 60 (30,120) seconds by POX, (p < 0.001). Failure to have HR detected by 1 minute occurred in 30%, 54% and 20% of infants by ECG, POX and either of the devices, respectively. CONCLUSION: In the delivery room, electrodes applied by the study method are more effective than pulse oximetry in providing the neonatal team with timely HR information that is necessary for proper resuscitative actions.

Reducing antibiotic utilization rate in preterm infants: a quality improvement initiative.

BACKGROUND: Judicious use of antibiotic therapy in preterm infants is necessary as prolonged and unwarranted use of antibiotics have been associated with adverse short-term and long-term outcomes. LOCAL PROBLEM: Our baseline data review revealed overuse and unnecessary prolonged antibiotic exposure among preterm infants despite a low suspicion for sepsis. METHODS AND INTERVENTIONS: The baseline overall AUR was calculated retrospectively from our pharmacy database for a period of 4 months prior to the quality improvement (QI) initiative (pre-QI phase). The principal QI intervention included the development and implementation of guidance algorithms for evaluation and management of suspected sepsis incorporating key QI measures, such as an emphasis on early discontinuation of antibiotics by 36 h if blood culture remained negative and the introduction of multiplex polymerase chain reaction assay for early identification of causative organisms. This QI initiative was implemented through multiple Plan-Do-Study-Act cycles, starting in February 2016 (QI phase), with an objective to achieve a 10% reduction in the baseline overall AUR by December 2016, in preterm infants with gestational ages between 250/7 and 336/7 weeks. Data for the QI phase of the study were collected prospectively. RESULT: The overall AUR (outcome measure) decreased from 154.8 to 138.4 days of treatment per 1000 hospital days (10.6% decrease, p < 0.05) over the 11-month period. However, the overall rate of adherence to guidance algorithm (process measure) remained below the target goal of 90%. CONCLUSION: This multiphase QI initiative was able to reduce the overall AUR at our NICU. The beneficial impact of this decrease in AUR in preterm infants remains to be determined.

Nonsurgical Management of Persistent and Hemodynamically Significant Patent Ductus Arteriosus among Extremely Low Birth Weight Infants: A Propensity Score Matched Analysis.

OBJECTIVE: The objective of this study was to evaluate the impact of a nonsurgical approach (with the incorporation of late postnatal hydrocortisone treatment to facilitate extubation) in comparison to the surgical approach for the management of persistent hemodynamically significant patent ductus arteriosus (hsPDA) among chronically ventilator-dependent extremely low birth weight (ELBW) infants. METHODS: In this retrospective study, ELBW infants with a diagnosis of hsPDA (diagnosed based on the echocardiographic criteria and chronic ventilator dependence) that were persistent beyond 14 days of postnatal age despite adequate medical treatment were included. RESULTS: Out of 127 infants (surgical approach group, n = 67 and nonsurgical approach group, n = 60), 72 infants were matched based on the propensity scores. In the matched cohort, in comparison to infants managed with the surgical approach (control group, n = 36), infants in the nonsurgical approach group (treatment group, n = 36) had a lower rate of surgical ligation (14 vs. 100%, p = < 0.001), but there were no differences in both primary outcome (death or bronchopulmonary dysplasia) and secondary outcome measures. CONCLUSION: For chronically ventilator-dependent ELBW infants with persistent hsPDA, a nonsurgical management approach is associated with a reduced rate of surgical ligation of PDA, but not associated with increased risk of adverse major short-term neonatal outcomes.

Infantile Hepatic Hemangioendothelioma: An Uncommon Cause of Persistent Pulmonary Hypertension in a Newborn Infant.

Multifocal and diffuse infantile hepatic hemangioendotheliomas commonly present with signs of high-output congestive heart failure. In addition, prolonged persistent pulmonary overcirculation eventually leads to the development of pulmonary hypertension at a later age. We report a 2-day old, full-term infant with multifocal, large infantile hepatic hemangioendothelioma, who presented with an early onset of pulmonary hypertension, managed successfully with supportive care and systemic therapy directed toward the involution of infantile hepatic hemangioendothelioma.

Acidemia versus hypercapnia and risk for severe intraventricular hemorrhage.

In extremely low birth weight (ELBW) infants, levels of hypercapnia (Paco 2) > 60 mm Hg are considered a risk factor for severe intraventricular hemorrhage (IVH). Since cerebral vasoreactivity depends on arterial pH (apH) rather than Paco 2, we hypothesize that the role of mild-to-moderate hypercapnia (45-60 mm Hg) in the occurrence of severe IVH is modulated by the metabolic component of acid-base status. ELBW infants (n = 580, born < 28 wk gestation, and BW < 1,000 g) were separated into "high-base deficit (BD)" (n = 291) and "low-BD" (n = 289) groups if infants' median BD were > 4 mEq/L or ≤4 mEq/L, respectively. Rates of severe IVH were higher in "high-BD" (16%) than "low-BD" (9%) group. Although adjusted risk for severe IVH increased with higher Paco 2 and higher BD, apH was the sole predictor of severe IVH. In ELBW infants, higher degree of acidemia, rather than hypercapnia per se, during the first 48 hours of life, is associated with higher occurrences of severe IVH.

The limit of viability: a single regional unit's experience.

OBJECTIVE: To establish the limit between beneficial and futile management in the extremely preterm infant, born at the limit of viability, at 22 to 26 weeks of gestational age (GA). DESIGN: Retrospective study (11-year study period). SETTING: A tertiary regional neonatal unit. PARTICIPANTS: Inborn infants (n = 841) with a birth weight of 1000 g or less and GA 2207 through 2667 weeks. INTERVENTION: We compared mortality and neurodevelopmental outcome between 2 periods, epoch 1 (January 1998 to June 2003) and epoch 2 (July 2003 to December 2008). For neurodevelopmental data, epoch 2 extended only to December 2006. MAIN OUTCOME MEASURES: We reviewed survival rates and adverse neurodevelopmental outcome rates at 18 to 24 months' corrected age. RESULTS: In the past decade, survival rates continued to increase while neurodevelopmental impairment rates in the extremely preterm infant decreased. From epoch 1 to epoch 2, the increase in survival rate occurred in infants born at 22 weeks' estimated GA, from 20% to 40%, while the decrease in neurodevelopmental impairment (54% to 28%) and severe neurodevelopmental impairment (35% to 8%) occurred in infants born at 23 to 24 weeks' estimated GA. CONCLUSIONS: Novel and aggressive neonatal therapies continue to affect neonatal outcome, mainly in infants born at the limit of viability. Our data suggest that each center offer prospective parents an assessment of the limits of viability based on their updated outcome results.