Low Rate of Spontaneous Closure in Premature Infants Discharged with a Patent Ductus Arteriosus: A Multicenter Prospective Study.

OBJECTIVES: To assess the rate of spontaneous closure and the incidence of adverse events in infants discharged home with a patent ductus arteriosus. STUDY DESIGN: In a prospective multicenter study, we enrolled 201 premature infants (gestational age of 23-32 weeks at birth) discharged home with a persistently patent ductus arteriosus (PDA) and followed their PDA status at 6-month intervals through 18 months of age. The primary study outcome was the rate and timing of spontaneous ductal closure. Secondary outcomes included rate of assisted closure and the incidence of serious adverse events. RESULTS: Spontaneous ductal closure occurred in 95 infants (47%) at 12 months and 117 infants (58%) by 18 months. Seventeen infants (8.4%) received assisted closure with surgical ligation or device assisted occlusion. Three infants died (1.5%). Although infants with spontaneous closure had a higher mean birth weight and gestational age compared with infants with a persistent PDA or assisted closure, we did not identify other factors predictive of spontaneous closure. CONCLUSIONS: Spontaneous closure of the PDA occurred in slightly less than one-half of premature infants discharged with a patent ductus by 1 year, lower than prior published reports. The high rate of assisted closure and/or adverse events in this population warrants close surveillance following discharge. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02750228.

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.

Effect of Inhaled Nitric Oxide on Survival Without Bronchopulmonary Dysplasia in Preterm Infants: A Randomized Clinical Trial.

Importance: Bronchopulmonary dysplasia (BPD) occurs in approximately 40% of infants born at younger than 30 weeks' gestation and is associated with adverse pulmonary and neurodevelopmental outcomes. Objective: To test whether administration of inhaled nitric oxide to preterm infants requiring positive pressure respiratory support on postnatal days 5 to 14 improves the rate of survival without BPD. Design, Setting, and Participants: This intent-to-treat study was a randomized clinical trial performed at 33 US and Canadian neonatal intensive care units. Participants included 451 neonates younger than 30 weeks' gestation with birth weight less than 1250 g receiving mechanical ventilation or positive pressure respiratory support on postnatal days 5 to 14. Enrollment spanned from December 23, 2009, to April 23, 2012, and neurodevelopmental outcome studies were completed by April 4, 2014. Interventions: Placebo (nitrogen) or inhaled nitric oxide initiated at 20 ppm was decreased to 10 ppm between 72 and 96 hours after starting treatment and then to 5 ppm on day 10 or 11. Infants remained on the 5-ppm dose until completion of therapy (24 days). Main Outcomes and Measures: The primary outcome was the rate of survival without BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes included BPD severity, postnatal corticosteroid use, respiratory support, survival, and neurodevelopmental outcomes at 18 to 24 months' PMA. Results: In total, 222 infants (52.3% male [n = 116]) received placebo, and 229 infants (50.2% male [n = 115]) received inhaled nitric oxide. Their mean (SD) gestation was 25.6 (1.5) vs 25.6 (1.4) weeks, and their mean (SD) birth weight was 750 (164) vs 724 (160) g. Survival without BPD at 36 weeks' PMA was similar between the placebo and inhaled nitric oxide groups (31.5% [n = 70] vs 34.9% [n = 80]) (odds ratio, 1.17; 95% CI, 0.79-1.73). Rates for severe BPD (26.6% [55 of 207] vs 20.5% [43 of 210]) and postnatal corticosteroid use for BPD (41.0% [91 of 222] vs 41.5% [95 of 229]) and the mean (SD) days of positive pressure respiratory support (55 [40] vs 54 [42]), oxygen therapy (88 [41] vs 91 [59]), and hospitalization (105 [37] vs 108 [54]) were equivalent between the 2 groups. No differences in the incidence of common morbidities were observed. Respiratory outcomes on discharge to home, at 1 year, and at age 18 to 24 months' PMA and neurodevelopmental assessments at 18 to 24 months' PMA did not differ between groups. Conclusions and Relevance: Inhaled nitric oxide, initiated at 20 ppm on postnatal days 5 to 14 to high-risk preterm infants and continued for 24 days, appears to be safe but did not improve survival without BPD at 36 weeks' PMA or respiratory and neurodevelopmental outcomes at 18 to 24 months' PMA. Trial Registration: clinicaltrials.gov Identifier: NCT00931632.

Changes in the Diagnosis and Management of Patent Ductus Arteriosus from 2006 to 2015 in United States Neonatal Intensive Care Units.

OBJECTIVE: To identify changes in the diagnosis, pharmacotherapy, and surgical ligation of patent ductus arteriosus (PDAs) in infants born premature and report on temporal changes in mortality and morbidity from a large volume of neonatal intensive care units (NICUs) in the US. STUDY DESIGN: We queried the Pediatrix Clinical Data Warehouse for all inborn infants without major anomalies born between 23 and 30 weeks' gestation from 2006 to 2015 for a diagnosis of PDA, use of indomethacin or ibuprofen, history of ductal ligation, mortality, and major morbidities. RESULTS: There were 829 091 infants entered in the Clinical Data Warehouse; 61 520 infants from 280 NICUs met our inclusion criteria. The diagnosis of PDA declined from 51% to 38% (P < .001), use of indomethacin or ibuprofen decreased from 32% to 18%, and PDA ligation decreased from 8.4% to 2.9% (both P < .001). During the study period, mortality decreased with no increase in any measured morbidity. Of the 163 sites with data for both periods, 128 (79%) showed a decrease in the diagnosis of PDA, and 132 (81%) showed a decrease in the use indomethacin and/or ibuprofen when 2011-2015 was compared with 2006-2010. Of 103 sites with at least 1 PDA ligation, 85 (83%) showed a decrease in PDA ligation in a similar comparison. CONCLUSIONS: In this large population of infants <30 weeks' gestation from 280 NICUs across the US, there were significant decreases in the diagnosis and treatment of the PDA. Although there was no evidence of increased morbidities, it remains uncertain how these changes may directly affect infant outcomes.

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.

Septicemia mortality reduction in neonates in a heart rate characteristics monitoring trial.

BACKGROUND: Abnormal heart rate characteristics (HRC) wax and wane in early stages of culture-positive, late-onset septicemia (LOS) in patients in the neonatal intensive care unit (NICU). Continuously monitoring an HRC index leads to a reduction in mortality among very low birth weight (VLBW) infants. We hypothesized that the reduction in mortality was due to a decrease in septicemia-associated mortality. METHODS: This is a secondary analysis of clinical and HRC data from 2,989 VLBW infants enrolled in a randomized clinical trial of HRC monitoring in nine NICUs from 2004 to 2010. RESULTS: LOS was diagnosed 974 times in 700 patients, and the incidence and distribution of organisms were similar in HRC display and nondisplay groups. Mortality within 30 d of LOS was lower in the HRC display as compared with the nondisplay group (11.8 vs. 19.6%; relative risk: 0.61; 95% confidence interval: 0.43, 0.87; P < 0.01), but mortality reduction was not statistically significant for patients without LOS. There were fewer large, abrupt increases in the HRC index in the days leading up to LOS diagnosis in infants whose HRC index was displayed. CONCLUSION: Continuous HRC monitoring is associated with a lower septicemia-associated mortality in VLBW infants, possibly due to diagnosis earlier in the course of illness.

Complex multifactorial nature of significant hyperbilirubinemia in neonates.

OBJECTIVE: To determine whether glucose-6-phosphate dehydrogenase (G6PD), uridine-diphosphoglucuronosyltransferase 1A1 (UGT1A1), and hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) gene variants occur at greater frequency in neonates with significant hyperbilirubinemia. METHODS: Infants with gestational ages of >or=37 weeks and ages of <7 days were studied. Case subjects had >or=1 bilirubin level above the 95th percentile (high-risk zone), whereas control subjects had bilirubin levels of <40th percentile (low-risk zone) at study entry. RESULTS: A total of 153 case subjects (median bilirubin level: 15.7 mg/dL) and 299 control subjects (median bilirubin level: 4.6 mg/dL) were evaluated. There were no statistical differences in the frequencies of G6PD, UGT1A1, and SCLO1B1 gene variants between case and control subjects (G6PD: 5.2% vs 3.3%; UGT1A1: 14.4% vs 9.4%; SLCO1B1: 73.2% vs 73.6%). However, coexpression of the G6PD African A- mutation with UGT1A1 and/or SLCO1B1 variants was seen more frequently for case subjects. Case subjects more often demonstrated >or=2 factors contributing to hyperbilirubinemia, including ABO blood group heterospecificity in which the mother had blood group O (47.7% vs 11.4%), positive direct Coombs test results (33.3% vs 4%), sibling treated with phototherapy (16.3% vs 5.4%), maternal circulating blood group antibodies (10.5 vs 0.7%), maternal diabetes mellitus (13.1% vs 6.4%), and maternal East Asian ethnicity (6.5% vs 1.3%). CONCLUSIONS: Clinical contributors to hyperbilirubinemia were identified more frequently for case subjects but individually G6PD, UGT1A1, and SLCO1B1 variants were not. Coexpression of the G6PD African A- mutation with UGT1A1 and SLCO1B1 variants was seen more often for case subjects.

Prevalence of gastroschisis and associated hospital time continue to rise in neonates who are admitted for intensive care.

PURPOSE: The purpose of this study was to evaluate recent trends in the prevalence of gastroschisis. METHODS: The study used a retrospective review of a deidentified neonatal intensive care patient data set. To control for ascertainment bias, the prevalence of omphalocele was calculated to provide an internal comparison to another anomaly requiring surgical intervention. RESULTS: During the study period (1997-2007), there were 473,366 discharges from the neonatal intensive care unit in the data set. There were 2057 (5.3/1000 discharges) neonates who had a gastroschisis and 853 (1.8/1000 discharges) who had an omphalocele. Between 1997 and 2004, the reported rate of gastroschisis increased from 2.9 to 6.1/1000 discharges, a relative increase of 210% (P < .001). Since 2004, the values have remained relatively stable at between 5.5 and 6.2/1000 discharges. Between 1997 and 2007, the hospital days for patients with gastroschisis/total hospital days increased from 0.6% to 1.3%, a relative increase of 220% (P < .001). In contrast, the reported rate of neonates with and the number of hospital days attributed to neonates with omphalocele has not changed significantly. CONCLUSION: The prevalence and the number of hospital days needed to care for neonates with gastroschisis have continued to increase since 2001.

Clinical process improvement: reduction of pneumothorax and mortality in high-risk preterm infants.

OBJECTIVE: To develop multidisciplinary clinical process improvement methods using evidence-based medicine to decrease the incidence of pneumothorax in a NICU. STUDY DESIGN: All inborn infants <28 weeks' gestation (n=79) served as the historical baseline group. A prospective protocol, using evidence-based medicine and a rapid-cycle, multidisciplinary clinical process improvement method, was designed to measure changes in the incidence of pneumothorax in subsequent infants of similar gestational ages. RESULTS: Sixty consecutive inborn infants <28 weeks' gestational age comprised the study group. In comparison to the historical control group, there was a significant reduction in the incidence of pneumothorax (from 26.6% to 10%, p=0.018) and in mortality (36.7% to 15%, p=0.007) without adversely affecting any other measured outcome variable. CONCLUSIONS: Introduction of multidisciplinary clinical process improvement methods can significantly decrease the incidence of adverse outcomes in neonatal intensive care units.