Trends in morbidities of late preterm infants in the neonatal intensive care unit.

OBJECTIVE: To characterize demographics and trends in length of stay (LOS), morbidities, and mortality in late preterm infants. STUDY DESIGN: Cohort study of infants born between 34 0/7 and 36 6/7 weeks gestation between 1999 and 2018 without major congenital anomalies at Pediatrix Medical Group neonatal intensive care units (NICUs). RESULTS: 307,967 infants from 410 NICUs met inclusion criteria. The median (25th-75th percentile) LOS was 11 (8-16) days in the entire period. Postmenstrual age (PMA) at discharge increased during the cohort for all gestational ages (p < 0.001). There was a decrease in invasive ventilation, receipt of phototherapy, and reflux medications observed (p < 0.001). CONCLUSION: In this large cohort, given 20 years of time for medical advancement, there was no significant improvement in the LOS of late preterm infants. All infants had an increased PMA at discharge, despite multiple practice changes that were observed.

Progressive Metabolic Dysfunction and Nutritional Variability Precedes Necrotizing Enterocolitis.

Necrotizing Enterocolitis (NEC) is associated with prematurity, enteral feedings, and enteral dysbiosis. Accordingly, we hypothesized that along with nutritional variability, metabolic dysfunction would be associated with NEC onset. Methods: We queried a multicenter longitudinal database that included 995 preterm infants (<32 weeks gestation) and included 73 cases of NEC. Dried blood spot samples were obtained on day of life 1, 7, 28, and 42. Metabolite data from each time point included 72 amino acid (AA) and acylcarnitine (AC) measures. Nutrition data were averaged at each of the same time points. Odds ratios and 95% confidence intervals were calculated using samples obtained prior to NEC diagnosis and adjusted for potential confounding variables. Nutritional and metabolic data were plotted longitudinally to determine relationship to NEC onset. Results: Day 1 analyte levels of alanine, phenylalanine, free carnitine, C16, arginine, C14:1/C16, and citrulline/phenylalanine were associated with the subsequent development of NEC. Over time, differences in individual analyte levels associated with NEC onset shifted from predominantly AAs at birth to predominantly ACs by day 42. Subjects who developed NEC received significantly lower weight-adjusted total calories (p < 0.001) overall, a trend that emerged by day of life 7 (p = 0.020), and persisted until day of life 28 (p < 0.001) and 42 (p < 0.001). Conclusion: Premature infants demonstrate metabolic differences at birth. Metabolite abnormalities progress in parallel to significant differences in nutritional delivery signifying metabolic dysfunction in premature newborns prior to NEC onset. These observations provide new insights to potential contributing pathophysiology of NEC and opportunity for clinical care-based prevention.

Paradoxical Antibiotic Effect of Ampicillin: Use of a Population Pharmacokinetic Model to Evaluate a Clinical Correlate of the Eagle Effect in Infants With Bacteremia.

BACKGROUND: High doses of ampicillin are often used to achieve therapeutic drug concentrations in infants. A paradoxical antibiotic effect, often called the Eagle effect, occurs when increasing concentrations of antibiotic above a threshold results in decreased efficacy. It is unknown if infants treated with ampicillin are at risk for this paradoxical effect. METHODS: We identified infants <28 days of age with Escherichia coli, Enterococcus or Streptococcus agalactiae (group B streptococcus) bloodstream infections from 1997 to 2012 and previously included in an ampicillin pharmacokinetic (PK) modeling study. We compared the odds of death for ampicillin dose, estimated time above the minimum inhibitory concentration (T > MIC) and PK parameters using separate logistic regression models. Adjusted logistic regression and Poisson models were used to calculate the odds of prolonged bacteremia ≥3 days and the duration of bacteremia, respectively, for dose, T > MIC and multiple PK parameters. RESULTS: Among 1272 infants meeting inclusion criteria, odds of death 7 or 30 days after the positive blood culture were not consistent with a paradoxical effect across any of the dosing regimens or PK parameters evaluated. The odds of prolonged bacteremia was lowest at the lowest dose category and the lowest daily dose category but not associated with the area-under-the-concentration time curve from 0 to 24 hours, or the maximum or minimum concentrations at steady state. T > MIC of ≥50% of the dosing interval was associated with decreased duration of bacteremia and odds of prolonged bacteremia. CONCLUSIONS: It is unlikely that a paradoxical antibiotic effect will have a clinical correlate when ampicillin is used for neonatal bacteremia. A T > MIC ≥50% decreased both duration of bacteremia and odds of prolonged bacteremia.

The Benefit of a Triage System to Expedite Acute Stroke Head Computed Tomography Interpretations.

BACKGROUND AND PURPOSE: We developed and tested a triage system to accelerate the interpretation of stroke head computed tomographies (CTs), with the goal of optimizing the time available for acute stroke therapy. MATERIALS AND METHODS: In our practice, acute stroke protocol head CTs have been given the highest reading priority. We implemented a technologically enabled prioritization infrastructure to consistently present these critical cases to our radiologists so they are evaluated before other examinations. In our 1-year retrospective multicenter study of 350,495 head CT examinations, we compared the reading time of stroke protocol head CTs to our next highest priority head CT. RESULTS: Our average acute stroke head CT reading turnaround time was 6.5 minutes. This represented a 17.3-minute improvement over the next highest priority head CT in our practice (confidence interval: 17.2-17.4 minutes, P < .001). CONCLUSIONS: A technologically enabled acute stroke protocol CT triage system consistently improves the reading times of critically time-dependent head CT examinations. As a result, this system has the potential to improve treatment times, treatment eligibility, and clinical outcomes.

The effect of the national shortage of vitamin A on death or chronic lung disease in extremely low-birth-weight infants.

IMPORTANCE: Prophylactic vitamin A supplementation has been shown to reduce the incidence of chronic lung disease or death in extremely low-birth-weight infants. Beginning in 2010, a national shortage reduced the supply of vitamin A available. OBJECTIVE: To estimate the association between vitamin A supplementation and death or chronic lung disease in the context of the recent drug shortage. Intercenter variability in vitamin A use was assessed secondarily. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 7925 infants with birth weights between 401 and 1000 g who were cared for in US neonatal intensive care units managed by the Pediatrix Medical Group. Infants were discharged between January 1, 2010, and June 30, 2012, and data were collected from the Pediatrix Clinical Data Warehouse. Infants who had major congenital anomalies, died during the first 3 days of life, or had missing data were excluded from the analysis. EXPOSURES: Vitamin A supplementation. MAIN OUTCOMES AND MEASURES: The primary outcome was either death before hospital discharge or chronic lung disease, defined as receiving any respiratory support at 36 weeks' corrected gestational age. RESULTS: Of the 6210 eligible infants, 3011 (48.5%) experienced the primary outcome. Those who received vitamin A were more immature and more likely to receive mechanical ventilation during the first 3 days of life. During the study period, vitamin A supplementation significantly decreased (27.2% to 2.1%); however, the primary outcome was similar (48.4% to 49.5%; P = .40). Vitamin A was unrelated to death or chronic lung disease in unadjusted or multivariable analyses (relative risk [RR], 0.97; 95% CI, 0.91-1.03; P = .32) when demographic and clinical information were considered. After classifying centers by vitamin A use, the center of birth was significantly associated with the outcome, with birth in low- and medium-use centers related to a reduced likelihood of death or chronic lung disease. CONCLUSIONS AND RELEVANCE: The occurrence of death or chronic lung disease appears unaffected by the recent shortage of vitamin A. However, the center of birth appears to be an important risk factor for these infants' outcomes.

Increasing supplemental thyroid hormone use among premature infants born at 23 to 32 weeks' gestation.

We assessed the pattern of levo-thyroxine (l-thyroxine) therapy in very premature newborns over a 10-year period. We analyzed the electronic database of a large private neonatal practice group (Pediatrix, Ft. Lauderdale, FL) for 23- to 32-week gestation neonates ( N = 96,813) managed during 1997 to 2006. L-thyroxine use was analyzed by birth year and by gestational age (GA). L-thyroxine use increased with decreasing GA (nadir 0.3% at 32 weeks, peak 8.4% at 24 weeks). L-thyroxine supplementation increased 2.6-fold over time among infants ≤26 weeks' GA (3.4% in 1997 to 1999 to 8.7% in 2004 to 2006), but did not change among infants born at ≥29 weeks' GA. The highest rate of l-thyroxine supplementation (12.8%) occurred among 24-week GA infants in 2006. Median age at start of l-thyroxine was 23 days (25 to 75%, 15 to 38 days). Only 2% of treated infants were started on day of life 1. Despite no clear evidence from randomized trials supporting thyroid supplementation, l-thyroxine treatment of very preterm infants has significantly increased over the past decade. As l-thyroxine treatment was not consistent with protocols from published randomized trials, new focused randomized controlled trials are needed.

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.

Effects of two different doses of amino acid supplementation on growth and blood amino acid levels in premature neonates admitted to the neonatal intensive care unit: a randomized, controlled trial.

OBJECTIVES: The goal was to measure the effects of 2 distinct strategies for parenteral nutrition on neonatal growth and blood amino acid profiles. METHODS: In a multicenter trial (n = 11 sites), we randomly allocated premature (23-29 weeks and 6 days of gestation) neonates to 1 of 2 approaches to intravenous amino acid administration. In one group, amino acid supplementation was started at 1.0 g/kg per day and advanced by 0.5 g/kg per day to a maximum of 2.5 g/kg per day (2.5 g/kg per day group). The other group received amino acids starting at 1.5 g/kg per day and advancing by 1.0 g/kg per day to a maximum of 3.5 g/kg per day (3.5 g/kg per day group). Filter paper blood spots were obtained from each infant on the day of random assignment and on days 7 and 28 of age, to monitor blood amino acid levels. RESULTS: We enrolled 122 neonates (64 in the 3.5 g/kg per day group and 58 in the 2.5 g/kg per day group). There were no differences in demographic or baseline characteristics between the 2 treatment groups. There was no significant difference in growth by day 28 after birth (median weight gain: 12.9 and 11.4 g/kg per day for the 3.5 and 2.5 g/kg per day groups, respectively), and the incidences of secondary morbidities were similar in the 2 groups. On day 7, blood levels of several amino acids and the serum urea nitrogen level were higher in the 3.5 g/kg per day group, compared with the 2.5 g/kg per day group; none of the amino acid levels were lower. CONCLUSIONS: Higher doses of amino acid supplementation did not improve neonatal growth and were associated with increased blood amino acid and urea nitrogen levels.