A Flipped Classroom Pilot in Neonatal Mechanical Ventilation.

Background: Pediatric residents frequently manage critically ill neonates but have limited systematic training in mechanical ventilation (MV). Competing demands, varying learner levels, and topic complexity contribute to inconsistent education. A blended learning approach may be ideally suited to achieve meaningful learning but has not been described for this topic and learner. Objective: To design, implement, and evaluate a flipped classroom for pediatric residents in neonatal MV. Methods: We used Kern's six-step framework for curricular development to create a flipped classroom curriculum in neonatal MV. Individual prework included interaction with six prerecorded animated whiteboard videos, while in-person learning occurred in small groups at the bedside of a ventilated infant. A mixed-methods evaluation included surveys, quantitative knowledge test scores (before, immediately after, and six months after course completion), and qualitative analysis of participant focus groups. Results: Twenty-six learners participated in the curriculum. Mean knowledge test scores rose and were sustained after course completion (51% baseline, 82% immediate posttest, 90% retention; P < 0.001). Learners identified various design elements, technology affordances, and instructor factors as meaningful, and they identified unexpected impacts of the curriculum beyond knowledge acquisition, including effects on professional identities, interdisciplinary communication skills, and contribution to the culture of safety. Conclusion: This curriculum aligned with resident roles, was meaningful to learners, and led to long-term increases in knowledge scores and access to quality education; flipped classroom design using meaningful learning theory and leveraging animated whiteboard technology may be a useful strategy for other highly complex topics in graduate medical education.

Impact of an Online Program of Bubble Continuous Positive Airway Pressure Education in a Resource-Constrained Setting.

Background: Respiratory distress is a leading cause of preterm infant mortality in sub-Saharan Africa. Bubble continuous positive airway pressure (CPAP) is emerging as a potentially safe, cost-effective way of delivering noninvasive respiratory support in low-income and middle-income countries. However, without healthcare providers who are knowledgeable and skilled in the use of this technology, suboptimal neonatal care and related health disparities are likely to persist. Objective: We hypothesized that an Internet-based, blended curriculum on bubble CPAP for bedside providers in low-resource mother-baby units (MBUs) could be developed and implemented and lead to improvements in clinical knowledge, reasoning, and learner confidence in bubble CPAP. Methods: Clinical educators from Israel, Ghana, and the United States used the analysis, design, development, implementation, and evaluation (ADDIE) design framework to create an online curriculum for two MBUs in Kumasi, in the Ashanti Region of Ghana. Participants completed pre and post curriculum knowledge tests and completed surveys on their perspectives. Results: Fifty-four interdisciplinary health professionals from the MBUs participated in the curriculum. Median knowledge test scores improved from 64% (interquartile range [IQR] = 50-72%) to 81% (IQR = 71-89%) after participation in the curriculum (P < 0.001). Learners reported high levels of confidence with bubble CPAP after participating in the curriculum and evaluated the curricular components highly. Conclusion: An online curriculum was successfully implemented and led to changes in healthcare worker knowledge in bubble CPAP. This may be an effective way to deliver education to healthcare professionals in resource-constrained countries and warrants further study.

Poor Neonatal Adaptation After Antidepressant Exposure During the Third Trimester in a Geographically Defined Cohort.

Objective: To examine the associations between antidepressant exposure during the third trimester of pregnancy, including individual drugs, drug doses, and antidepressant combinations, and the risk of poor neonatal adaptation (PNA). Patients and Methods: The Rochester Epidemiology Project medical records-linkage system was used to study infants exposed to selective serotonin reuptake inhibitors (SSRIs; n=1014), bupropion, (n=118), serotonin-norepinephrine reuptake inhibitors (n=80), antidepressant combinations (n=20), or other antidepressants (n=22) during the third trimester (April 11, 2000-December 31, 2013). Poor neonatal adaptation was defined based on a review of medical records. Poisson regression was used to examine the risk of PNA with serotonergic antidepressant and drug combinations compared with that with bupropion monotherapy as well as with high- vs standard-dose antidepressants. When possible, analyses were performed using propensity score (PS) weighting. Results: Forty-four infants were confirmed cases of PNA. Serotonin-norepinephrine reuptake inhibitor monotherapy, antidepressant combinations, and paroxetine monotherapy were associated with a significantly higher risk of PNA than bupropion monotherapy in unweighted analyses. High-dose SSRI exposure was associated with a significantly increased risk of PNA in unadjusted (relative risk, 2.61; 95% confidence interval, 1.35-5.04) and PS-weighted models (relative risk, 2.29; 95% confidence interval, 1.17-4.48) compared with standard-dose SSRI exposure. The risk of PNA was significantly higher with high-dose paroxetine and sertraline than with standard doses in the PS-weighted analyses. The other risk factors for PNA included maternal anxiety disorders. Conclusion: Although the frequency of PNA in this cohort was low (3%-4%), the risk of PNA was increased in infants exposed to serotonergic antidepressants, particularly with SSRIs at higher doses, during the third trimester of pregnancy compared with that in infants exposed to standard doses. Potential risk factors for PNA also included third-trimester use of paroxetine (especially at higher doses) and maternal anxiety.

Necrotizing Enterocolitis in Very Low Birth Weight Neonates: A Natural History Study.

OBJECTIVE: We characterize the most recent natural history of necrotizing enterocolitis (NEC), as this is an essential first step in guiding the prevention and treatment of this disease in the present day. STUDY DESIGN: We performed a retrospective cohort study of neonates who were born at 23 to 29 weeks' gestation and birth weight <1,500 g who received care from the Pediatrix Medical Group between 2004 and 2019. We assessed the incidence of medical and surgical NEC and the patterns of initial antibiotic treatment to develop a contemporary cohort for further analysis. Among patients discharged between 2015 and 2019, we characterized the stage-specific risk factors for patients diagnosed with medical or surgical NEC, as well as patterns of disease onset, progression, biomarkers, and outcomes. We used the same approach to characterize patients diagnosed with suspected NEC. RESULTS: Among 34,032 patients in the contemporary cohort, 1,150 (3.4%) were diagnosed with medical NEC and 543 (1.6%) were diagnosed with surgical NEC. The temporal pattern of disease onset was different for medical and surgical NEC, with gestational age- and birth weight-specific risk disparities emerging earlier in surgical NEC. Thirty-day mortality was much greater among surgical NEC patients (medical NEC 16.4% vs. surgical NEC 43.0%), as were rates of various in-hospital and long-term outcomes. Suspected NEC was diagnosed in 1,256 (3.7%) patients, among whom risk factors and disease onset, progression, and outcomes closely resembled those of medical NEC. CONCLUSION: Analyzing data from a contemporary cohort enabled us to characterize the current, stage-specific natural history of NEC, including novel insights into suspected NEC. Future studies could leverage this cohort to characterize how specific patient characteristics, care processes, or biomarkers may influence or predict disease outcomes. KEY POINTS: · The incidence of NEC has reached a stable baseline in recent years.. · Risk factors for NEC vary in a stage-specific manner.. · The stage-specific onset and progression of NEC differ by gestational age and birth weight..

Automated Microfluidic System with Active Mixing Enables Rapid Analysis of Biomarkers in 5 µL of Whole Blood.

We developed a microfluidic device for the rapid analysis of biomarkers in small volumes of whole blood. This device includes an onboard plasma separation module connected to a downstream bioanalysis module in which plasma mixes with reagents and the results of a colorimetric assay are recorded. Actuation of onboard microvalves within a bioanalysis module creates active mixing conditions that allowed us to achieve solution homogeneity within 5 min. To demonstrate utility, we carried out glucose detection in our device. With 5 µL of whole blood as an input, our microfluidic device enabled a time-to-answer of 10 min with a limit of detection of 0.21 ± 0.04 mM for glucose. This device has immediate applications for rapid and sensitive monitoring of hypoglycemia at the point of care (POC). Furthermore, our automated microfluidic device represents a platform technology that may be used to detect other biomarkers in whole blood.

Training fellows in neonatal tele-resuscitation using a simulation-based mastery learning model.

BACKGROUND: Neonatal tele-resuscitation uses real-time, audio-video telemedicine to connect neonatologists with community hospital care teams during advanced neonatal resuscitations. While telemedicine continues to expand, best practices for training fellows in tele-resuscitation are not known. OBJECTIVE: We aimed to develop a neonatal tele-resuscitation curriculum using a simulation-based mastery learning model that provides neonatal-perinatal medicine (NPM) fellows with the knowledge, skills, and behaviors needed to lead tele-resuscitations. METHODS: Using technology-enhanced simulation education and a mastery learning model, we developed a longitudinal pilot tele-resuscitation curriculum. From 07/2018 to 03/2021, NPM fellows participated in the curriculum, which included individualized telemedicine learning, observing and leading simulated tele-resuscitations, and finally, performing clinical (non-simulated) tele-resuscitations. A performance assessment tool was developed to assess competency through eight questions mapped to the Accreditation Council for Graduate Medical Education (ACGME) core competencies, with responses on a 1 to 5 scale (1 = critical deficiencies; 5 = competence of an expert). RESULTS: Four NPM fellows participated in the curriculum, progressing through the curriculum at an individualized pace. Median scores on the three learning modules were 96-100%. Fellows participated in variable number of simulated tele-resuscitations based on when mastery was achieved (2-3 supervised simulations per fellow, 1-4 unsupervised simulations per fellow). In total, eighteen simulated tele-resuscitations (eight unsupervised, 10 supervised) and one clinical tele-resuscitation were conducted. Twenty-five performance assessments were completed. Assessment scores across the ACGME competencies were consistently high, with mean scores ranging from 4.2-4.6, with 4 equating to 'ready for unsupervised practice' and 5 equating to 'competence of an expert'. CONCLUSIONS: As telemedicine use continues to expand, curricula that improve learners' comfort with and proficiency in tele-resuscitation are essential. A simulation-based mastery learning model may be one approach that affords learners gradual exposure to and mastery of complex tele-resuscitation skills and behaviors.

Association of outborn versus inborn birth status on the in-hospital outcomes of neonates treated with therapeutic hypothermia: A propensity score-weighted cohort study.

OBJECTIVE: To compare the risk of in-hospital mortality and morbidity between outborn and inborn neonates treated with whole body hypothermia. METHODS: The association of outborn birth status with in-hospital mortality and morbidity, prior to NICU discharge or transfer, was assessed in a large historical cohort of neonates who had therapeutic hypothermia initiated on the day of birth. The cohort was restricted to neonates born at ≥35 weeks gestational age from 2007 to 2018. Since the sample was non-random, inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalance in baseline maternal and neonatal characteristics between outborn and inborn neonates. Cox proportional hazards regression was used to assess the association between outborn status and in-hospital mortality. RESULTS: There were 4447 neonates included in the study (2463 outborn). Outborn status was not significantly associated with an increased risk of in-hospital mortality in the unadjusted cohort (HR = 1.17, 95% CI 0.97-1.42, p = 0.10) or IPW cohort (HR = 1.09, 95% CI 0.95-1.26, p = 0.22). However, in the IPW cohort, outborn neonates were significantly more likely to have seizures (28% vs 24%, p = 0.006), anticonvulsant exposure (46% vs 41%, p = 0.002), and gastrostomy tube placement (5.8% vs 3.8%, p = 0.009) during their newborn hospitalization. CONCLUSION: Outborn status was not significantly associated with increased in-hospital mortality among neonates treated with whole body hypothermia. However, outborn neonates were more likely to have seizures, receive anticonvulsant treatment, and undergo gastrostomy tube placement. Further study is needed to better understand the etiologies of these outcome disparities and potential implications for long-term neurodevelopmental outcomes.

Survival of Ventilated Extremely Premature Neonates With Severe Intraventricular Hemorrhage.

BACKGROUND: Severe intraventricular hemorrhage (IVH) is a leading mortality risk factor among extremely premature neonates. Because other life-threatening conditions also occur in this population, it is unclear whether severe IVH is independently associated with death. The existence and potential implications of regional variation in severe IVH-associated mortality are unknown. METHODS: We performed a retrospective cohort study of mechanically ventilated neonates born at 22 to 29 weeks' gestation who received care in 242 American NICUs between 2000 and 2014. After building groups composed of propensity score-matched and center-matched pairs, we used the Cox proportional hazards analysis to test our hypothesis that severe IVH would be associated with greater all-cause in-hospital mortality, defined as death before transfer or discharge. We also performed propensity score-matched subgroup analyses, comparing severe IVH-associated mortality among 4 geographic regions of the United States. RESULTS: In our analysis cohort, we identified 4679 patients with severe IVH. Among 2848 matched pairs, those with severe IVH were more likely to die compared with those without severe IVH (hazard ratio 2.79; 95% confidence interval 2.49-3.11). Among 1527 matched pairs still hospitalized at 30 days, severe IVH was associated with greater risk of death (hazard ratio 2.03; 95% confidence interval 1.47-2.80). Mortality associated with severe IVH varied substantially between geographic regions. CONCLUSIONS: The early diagnosis of severe IVH is independently associated with all-cause in-hospital mortality in extremely premature neonates. Regional variation in severe IVH-associated mortality suggests that shared decision-making between parents and neonatologists is strongly influenced by ultrasound-based IVH assessment and classification.

Prolonged Tracheal Intubation and the Association Between Patent Ductus Arteriosus and Bronchopulmonary Dysplasia: A Secondary Analysis of the PDA-TOLERATE trial.

In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required <10 days of intubation. However, in infants requiring intubation for ≥10 days, prolonged PDA exposure (≥11 days) was associated with an increased risk of moderate/severe BPD.

Proposed Plasma Ammonia Reference Intervals in a Reference Group of Hospitalized Term and Preterm Neonates.

BACKGROUND: Plasma ammonia is commonly measured in the diagnostic evaluation of hospitalized newborns, but reference values are not well defined. METHODS: We prospectively enrolled newborns admitted to the level III/IV neonatal intensive care unit and level II intermediate special care nursery from January 2017 to January 2018. Infants with inborn errors of metabolism or liver disease were excluded. Plasma ammonia concentrations were measured once within the first week of life and evaluated by sex, gestational age, timing of the draw, blood collection method, and type of nutrition. Reference intervals were calculated. RESULTS: 127 neonates were included; one third (34%) were term infants born at ≥37 weeks gestation, and two thirds (66%) were born preterm at <37 weeks gestation. Median plasma ammonia concentrations were 32 µmol/L (range <10 to 86 µmol/L). Median ammonia concentrations were higher among preterm compared to term infants (35 vs. 28 µmol/L, p = 0.0119), and term female compared to term male infants (34 vs. 26 µmol/L, p = 0.0228). There was no difference in median ammonia concentrations between female and male preterm infants, based on gestational age within the preterm group, timing of the blood draw, presence of hyperbilirubinemia, blood collection method, or type of nutritional intake. CONCLUSIONS: Plasma ammonia concentrations among newborns are higher than the expected adult concentrations and may vary by gestational age and sex. Blood collection method, type of nutrition, hyperbilirubinemia, and timing of the draw do not impact concentrations. We propose a reference limit of ≤82 µmol/L for newborns less than one week of age.

In Utero Restoration of Hindbrain Herniation in Fetal Myelomeningocele as Part of Prenatal Regenerative Therapy Program at Mayo Clinic.

OBJECTIVE: To assess our initial experience with prenatal restoration of hindbrain herniation following in utero repair of myelomeningocele (MMC). PATIENTS AND METHODS: Three consecutive patients with prenatally diagnosed MMC (between January 1, 2018 and September 30, 2018) were managed with open in utero surgery. As per institutional review board approval and following a protocol designed at the Mayo Clinic Maternal & Fetal Center, fetal intervention was offered between 19 0/7 and 25 6/7 weeks of gestation. Prenatal improvement of hindbrain herniation was the declared restorative end point. Obstetrical and perinatal outcomes were also assessed. RESULTS: Diagnosis of MMC was confirmed upon referral between 20 and 21 weeks' gestation by using fetal ultrasound and magnetic resonance imaging. In all cases reported here, the spinal defect was lumbosacral with evidence of hindbrain herniation. Open in utero MMC repair was performed between 24 and 25 weeks' gestation with no notable perioperative complications. Postprocedure fetal magnetic resonance imaging performed 6 weeks after in utero repair documented improvement of hindbrain herniation. Deliveries were at 37 weeks by cesarean section without complications. Most recent postnatal follow-ups were unremarkable at both 11 months (baby 1) and 3 months of age (baby 2), with mild ventriculomegaly. Antenatal and postnatal follow-up of baby 3 at 1 month of age was also unremarkable. CONCLUSION: Our study highlights the prenatal restoration of hindbrain herniation following in utero MMC repair in all cases presented here as an example of a prenatal regenerative therapy program in our institution.

Universal Electrocardiographic Screening for Long QT Syndrome in Hospitalized Neonates.

OBJECTIVE: Long QT syndrome (LQTS) is a known cause of unexpected death, leading some to recommend routine neonatal electrocardiographic (ECG) screening. We used continuous electronic heart rate corrected QT interval (QTc) monitoring to screen for interval prolongation in a cohort of hospitalized neonates to identify those at a risk of having LQTS. We hypothesized that this screening method would yield an acceptable positive predictive value (PPV). STUDY DESIGN: A cohort of 589 infants hospitalized in a level II neonatal intensive care unit were screened through continuous electronic QTc monitoring linked to an investigator-designed, computerized data sniffer. Screening was conducted from days-of-life 3 through 7 or until hospital discharge. The data sniffer alerted investigators for a 24-hour average QTc of ≥475 ms. Positively screened patients were further evaluated with 12-lead ECG. RESULTS: Positive screens were obtained in 5.6% of patients, all of whom had negative follow-up ECG testing (PPV = 0%). Furthermore, one-quarter of positively screened neonates underwent echocardiography based on ECG findings, none of which identified clinically relevant pathology. CONCLUSION: Electronic monitoring of QTc in hospitalized neonates during the first week of life was not an efficient way to identify those at a risk of having LQTS. Conversely, screening triggered unnecessary testing.

Outcomes of outborn extremely preterm neonates admitted to a NICU with respiratory distress.

OBJECTIVE: To compare the risk of mortality and morbidity between outborn and propensity score-matched inborn extremely preterm neonates. SETTING: Multiple neonatal intensive care units (NICU) across the USA. PATIENTS: Singleton neonates born at 22-29 weeks' gestation with no major anomalies who were admitted to a NICU and discharged between 2000 and 2014. Outborn neonates were restricted to those who transferred into a NICU on the day of birth. METHODS: The association between inborn-outborn status and the time-to-event outcomes of in-hospital mortality and necrotising enterocolitis (NEC) were assessed using Cox proportional hazards regression. Logistic regression was used to assess the remaining secondary outcomes: retinopathy of prematurity requiring treatment (tROP), chronic lung disease (CLD), periventricular leucomalacia (PVL) and severe intraventricular haemorrhage (IVH). Since outborn status was not random, we used 1:1 propensity score matching to reduce the imbalance in illness severity. RESULTS: There were 59 942 neonates (7991 outborn) included in the study. Outborn neonates had poorer survival than inborns and higher rates of NEC, severe IVH, tROP and PVL. Inborn-outborn disparities in mortality were reduced over the study period. When analysing the matched cohort (6524 matched pairs), outborns were less likely to die in-hospital compared with inborns (HR 0.84, 95% CI 0.77 to 0.91). However, outborns experienced higher rates of NEC (HR 1.14, 95% CI 1.04 to 1.25), severe IVH (OR 1.52, 95% CI 1.38 to 1.68), tROP (OR 1.45, 95% CI 1.25 to 1.69) and CLD (OR 1.12, 95% CI 1.01 to 1.24). CONCLUSION: Additional research is needed to understand the contributors to increased morbidity for outborn extremely preterm neonates and identify interventions that mitigate this risk.

Lack of Equipoise in the PDA-TOLERATE Trial: A Comparison of Eligible Infants Enrolled in the Trial and Those Treated Outside the Trial.

The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants <280/7 weeks of gestation; however 137 potentially eligible infants were not recruited and received treatment of their PDA outside the PDA-TOLERATE trial due to "lack-of-physician-equipoise" (LPE). Despite being less mature and needing more respiratory support, infants with LPE had lower rates of mortality than enrolled infants. Infants with LPE treated before day 6 had lower rates of late respiratory morbidity than infants with LPE treated ≥day 6. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.

Comparative effectiveness of drugs used to constrict the patent ductus arteriosus: a secondary analysis of the PDA-TOLERATE trial (NCT01958320).

OBJECTIVE: To evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks. METHODS: We performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants). RESULTS: Indomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen = 2.03 (1.05-3.91), and acetaminophen = 1.33 (0.55-3.24). The initial rate of acetaminophen-induced constriction was 27%. Infants with persistent moderate-to-large PDA after acetaminophen were treated with indomethacin. The final rate of constriction after acetaminophen ± indomethacin was 60% (similar to the rate in infants receiving indomethacin-alone (62%)). CONCLUSION: Indomethacin was more effective than acetaminophen in producing ductus constriction.

Birth Size and Gestational Age Specific Outcomes of Inhaled Nitric Oxide Therapy in Preterm Neonates with Clinically Diagnosed Pulmonary Hypertension.

OBJECTIVE: Among neonates of 22 to 29 weeks' gestational age (GA) who required mechanical ventilation for the treatment of respiratory distress syndrome (RDS) and clinically diagnosed pulmonary hypertension (PH), we tested our hypothesis that the association between early treatment with inhaled nitric oxide (iNO) and survival would vary according to birth size and GA. STUDY DESIGN: Because iNO was not randomly prescribed to patients in this cohort, we used propensity score matching to pair a neonate who received iNO at a chronological age of ≤7 days with an unexposed neonate with similar baseline characteristics. The primary outcome was inhospital mortality, which we evaluated based on size for GA and GA strata using the Cox proportional hazards regression model. RESULTS: Among 1,531 neonates who met study criteria, we created a propensity score matched cohort of 615 pairs of neonates (iNO-exposed and unexposed). The risk of inhospital mortality for iNO-exposed neonates was observed only in the minority (<10%) who were large for GA, though this finding did not persist when matching for illness severity. CONCLUSION: Early treatment with iNO is not associated with survival in most extremely premature neonates with RDS and clinically diagnosed PH when stratified for birth size or GA.

PDA-TOLERATE Trial: An Exploratory Randomized Controlled Trial of Treatment of Moderate-to-Large Patent Ductus Arteriosus at 1 Week of Age.

OBJECTIVE: To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given. STUDY DESIGN: A total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial. RESULTS: At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%). CONCLUSIONS: In preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.

Outcomes of early inhaled nitric oxide use in premature African American neonates.

OBJECTIVE: Meta-analysis of individual-patient clinical trial data suggests that inhaled nitric oxide (iNO) improves respiratory outcomes in premature African American neonates. We hypothesized that early iNO therapy would be associated with lower mortality and less chronic lung disease (CLD) in extremely premature African American neonates. STUDY DESIGN: We conducted a retrospective cohort study of propensity score- and race-matched neonates 22-29 weeks gestation who were mechanically ventilated for treatment of respiratory distress and associated pulmonary hypertension (RDS + PPHN). We evaluated the association of iNO within 7 days of life with in-hospital mortality and CLD, using Cox proportional hazards regression and logistic regression, respectively. RESULT: Among 178 matched pairs of African American patients, iNO was not associated with lower mortality (HR = 0.94, 95% CI 0.69-1.30) or less CLD (OR = 0.94, 95% CI 0.47-1.87). CONCLUSIONS: Early, off-label iNO use is not associated with improved outcomes in premature African American neonates with RDS + PPHN.