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OBJECTIVE Although levetiracetam is used for the prevention of early Post-traumatic seizures (EPTS) after traumatic brain injury (TBI), limited data exist describing the incidence of seizures in pediatric patients receiving levetiracetam prophylaxis. The objective of this research is to evaluate the prevalence of EPTS in children given prophylactic levetiracetam after severe TBI. METHODS This study was conducted at a Level 1 pediatric trauma center and included pediatric patients with severe TBI who received levetiracetam for EPTS prophylaxis. Demographics and clinical information were retrospectively collected and evaluated. The primary outcome was prevalence of clinical or electrographic seizures within 7 days of initial injury as noted in the EMR. RESULTS In 4 of 44 patients (9%), seizures developed despite levetiracetam prophylaxis. Concurrent use of other medications with antiepileptic properties was common (91%). There were no differences in demographic or baseline clinical characteristics between the group of patients experiencing seizures and those who did not. However, craniotomy was significantly more common in the seizure group (75% vs. 18%, p = 0.03). CONCLUSIONS Children receiving prophylaxis with levetiracetam after severe TBI had a lower incidence of seizures (9%) than had previously been reported in the literature (18%). Given the limited literature available supporting the use of levetiracetam for the prevention of EPTS in children experiencing severe TBI, further study is needed to support routine use. ABBREVIATIONS EEG, electroencephalogram; EMR, electronic medical record; EPTS, early post-traumatic seizures; FDA, US Food and Drug Administration; GCS, Glasgow Coma Scale; ICP, intracranial pressure; IV, intravenous; PICU, pediatric intensive care unit; TBI, traumatic brain injury. [ABSTRACT FROM AUTHOR]

Herpes simplex virus (HSV) acquired during delivery places the neonate at risk for mortality or long-term neurodevelopmental disability. Exposure generally occurs from recurrent genital herpes infection, although primary infections result in the highest risk of neonatal disease. Neonates generally present in the second or third week of life with lesions. Encephalitis with seizures indicates the presence of central nervous system involvement, and other end organs may also be impacted. Clinical suspicion for neonatal HSV infection warrants immediate initiation of appropriate antiviral therapy. In the last 50 years, antiviral therapy has progressed from agents with prohibitive toxicity or cumbersome administration to herpes virus–specific agents that dramatically improve clinical outcomes with manageable toxicity. Multicenter clinical trials have demonstrated the superiority of high-dose intravenous acyclovir for acute therapy, followed by long-term oral suppressive therapy. This work has dramatically reduced morbidity and mortality from neonatal HSV, representing the benchmark for future clinical trials in neonatal pharmacotherapy. [ABSTRACT FROM AUTHOR]

Lymphatic malformations in neonates often manifest as a chylothorax, and although rare, morbidity and mortality can be significant. First-line treatment with medium-chain triglyceride--enriched formulas, or enteric rest with total parenteral nutrition, are not always successful. We describe the case of a premature neonate with trisomy 21 who presented with bilateral pleural effusions and a pericardial effusion that worsened with the initiation of enteral nutrition. Clinical improvement was not seen until the initiation of treatment with oral propranolol at a maximum dosage of 0.5 mg/kg/day divided every 8 hours with extubation 8 days after propranolol initiation. Two case reports have described the use of propranolol in similar patients receiving 2 mg/kg/day; however, our experience is the first to report treatment success at a much lower dose. A review of the literature for alternative medication treatments uncovered numerous case reports and series documenting variable results with incongruent definitions of treatment success in a diverse patient population. The rarity of this disease state makes accrual of patients difficult and more robust treatment data unlikely. Therefore, selection of the optimal adjunctive treatment must be based on individual patient and disease state characteristics as well as safety and efficacy profile of the medication. [ABSTRACT FROM AUTHOR]

Pyridoxal 5′-phosphate (PLP), the principal circulating form of vitamin B 6 (B 6), is elevated in the plasma of individuals with hypophosphatasia (HPP). HPP is the inborn-error-of-metabolism caused by loss-of-function mutation(s) of ALPL , the gene that encodes the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP). PLP accumulates extracellularly in HPP because it is a natural substrate of this cell-surface phosphomonoester phosphohydrolase. Even individuals mildly affected by HPP manifest this biochemical hallmark, which is used for diagnosis. Herein, an exclusively breast-fed newborn boy with life-threatening perinatal HPP had uniquely normal instead of markedly elevated plasma PLP levels before beginning asfotase alfa (AA) TNSALP-replacement therapy. These abnormal PLP levels were explained by B 6 deficiency, confirmed by his low plasma level of 4-pyridoxic acid (PA), the B 6 degradation product. His mother, a presumed carrier of one of his two ALPL missense mutations, had serum ALP activity of 50 U/L (Nl 40–130) while her plasma PLP level was 9 μg/L (Nl 5–50) and PA was 3 μg/L (Nl 3−30). Her dietary history and breast milk pyridoxal (PL) level indicated she too was B 6 deficient. With B 6 supplementation using a breast milk fortifier, the patient's plasma PA level corrected, while his PLP level remained in the normal range but now in keeping with AA treatment. Our experience reveals that elevated levels of PLP in the circulation in HPP require some degree of B 6 sufficiency, and that anticipated increases in HPP can be negated by hypovitaminosis B 6. • Hypophosphatasia (HPP) denotes heritable alkaline phosphatase (ALP) deficiency. • In HPP, pyridoxal 5′-phosphate (PLP), an ALP substrate, is increased extracellularly. • Elevated plasma PLP helps diagnose HPP. • A vitamin B 6 deficient neonate with perinatal HPP had normal plasma levels of PLP. • Elevation of plasma PLP expected in HPP can be negated by hypovitaminosis B 6. [ABSTRACT FROM AUTHOR]

Background: Antibiotics are widely used in very low-birth-weight infants (VLBW, <1500 g), and excess exposure, particularly to broad-spectrum antibiotics, is associated with significant morbidity. An antibiotic spectrum index (ASI) quantifies antibiotic exposure by relative antimicrobial activity, adding information to exposure measured by days of therapy (DOT). We compared ASI and DOT across multiple centers to evaluate differences in antibiotic exposures., Methods: We extracted data from patients admitted to 3 level-4 NICUs for 2 years at 2 sites and for 1 year at a third site. We calculated the ASI per antibiotic days and DOT per patient days for all admitted VLBW infants <32 weeks gestational age. Clinical variables were compared as percentages or as days per 1,000 patient days. We used Kruskal-Wallis tests to compare continuous variables across the 3 sites., Results: Demographics were similar for the 734 VLBW infants included. The site with the highest DOT per patient days had the lowest ASI per antibiotic days and the site with the highest mortality and infection rates had the highest ASI per antibiotic days. Antibiotic utilization varied by center, particularly for choice of broad-spectrum coverage, although the organisms causing infection were similar., Conclusion: An antibiotic spectrum index identified differences in prescribing practice patterns among 3 NICUs unique from those identified by standard antibiotic use metrics. Site differences in infection rates and unit practices or guidelines for prescribing antibiotics were reflected in the ASI. This comparison uncovered opportunities to improve antibiotic stewardship and demonstrates the utility of this metric for comparing antibiotic exposures among NICU populations.

Objective: To evaluate the association between cumulative fentanyl dose during neonatal intensive care and 5-year neurodevelopmental and socioemotional outcomes in very preterm infants., Materials and Methods: Patient demographics and clinical factors during the perinatal and neonatal course were collected in 84 patients born between 23- and 30-weeks gestational age (GA). Cumulative fentanyl dose during neonatal intensive care was calculated. Developmental testing at age 5 years included the Wechsler Preschool and Primary Scale of Intelligence Full-Scale Intelligence Quotient, Third Edition, Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, Movement Assessment Battery for Children, Second Edition (MABC-2), and Shape School Assessment. Socioemotional outcomes were assessed via caregiver's responses on the Child Behavior Checklist/1.5-5 (CBCL/1.5-5.5) and Social Responsiveness Scale, Second Edition (SRS-2). Covariates were identified on bivariate analysis ( p < 0.1). Linear regression models related outcome measures to the log of cumulative fentanyl dose adjusted for covariates., Results: Higher cumulative fentanyl dose was associated with lower composite motor scores on bivariate analysis ( p < 0.01). Cumulative fentanyl dose did not correlate with composite intelligence quotient, language, or executive function. The Clinical Risk Index for Babies score, log of mechanical ventilation, inotrope, and anesthesia duration, and log of cumulative midazolam and hydrocortisone dose were also associated with MABC-2 scores ( p < 0.1). Cumulative fentanyl dose was not associated with composite MABC-2 scores on multiple linear regression. Higher cumulative fentanyl dose was associated with decreased socioemotional problems based on caregiver's response on CBCL/1.5-5.5 t-scores driven by fewer symptoms of depression. The McMaster Family Assessment Device general functioning scale score, maternal age, GA, log of total parenteral nutrition days, patent ductus arteriosus requiring treatment, and log of inotrope hours were also associated with CBCL/1.5-5.5 t-scores ( p < 0.1). Cumulative fentanyl dose ( p = 0.039) and family dysfunction score ( p = 0.002) remained significant after controlling for covariates on multiple linear regression., Conclusion: Cumulative fentanyl dose during neonatal intensive care did not correlate with 5-year motor, cognitive, or language outcomes after controlling for other variables. Fentanyl dose was associated with caregiver reported total socioemotional problems on the CBCL/1.5-5.5 on multivariate modeling. Additional long-term studies are needed to fully elucidate the safety of fentanyl in very preterm neonates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mills, Lean, Smyser, Inder, Rogers and McPherson.)

Objectives  Methylnaltrexone is U.S. Food and Drug Administration (FDA) approved as a subcutaneous injection for adults with opioid-induced constipation (OIC). Case series have described the use of methylnaltrexone for OIC in the pediatric oncology population. There are limited data describing its intravenous use in critically ill pediatric patients. Methods  We conducted a retrospective observational study at St. Louis Children's Hospital. Patients less than 18 years old who received at least one dose of intravenous methylnaltrexone while admitted to an intensive care unit between January 2016 and August 2019 were included. The primary outcome was documented laxation within 24 hours of methylnaltrexone administration. Results  Sixteen patients received a total of 34 doses of intravenous methylnaltrexone. Patients received a median of 1.69 (interquartile range [IQR], 0.9-4.86) morphine milligram equivalents per kilogram per 24 hours, over a median of 14 days (IQR, 11-30), before methylnaltrexone administration. The median dose of methylnaltrexone was 0.15 mg/kg (IQR, 0.15-0.16). Ten patients (63%) responded to the first dose of methylnaltrexone, and 14 patients (88%) responded to at least one dose. Overall, 26 doses (76%) led to patient response. Four patients (25%) experienced adverse events (emesis, abdominal pain) after methylnaltrexone administration. No signs or symptoms of opioid withdrawal were documented. Conclusions  Intravenous methylnaltrexone appears to be safe and effective in treating OIC in critically ill pediatric patients. No serious adverse events or signs of opioid withdrawal were observed after single and repeat dosing. Patients responded to methylnaltrexone with varying opioid dosing and durations prior to administration., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Optimizing pediatric antimicrobial stewardship is challenging. In this retrospective study, we evaluated 515 original e-mails to 482 members of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative electronic mailing list (idlistserv@kids.wustl.edu). The plurality of threads discussed clinical practice guidelines, and pharmacists were most likely to initiate and respond. Representation was geographically diverse within and outside the United States.

Bronchopulmonary dysplasia (BPD) is a severe pulmonary complication of prematurity and is associated with significant morbidity or death. Early use of systemic corticosteroids may alter the trajectory of the disease and improve outcomes. A BPD Outcomes estimator, developed by the NICHD using a large population dataset, can be used to calculate individual risk. Risk above a certain threshold may indicate that the benefits of corticosteroids outweigh the risks. Empiric analysis of this calculator by systematic entry of synthetic patient information reveals a marked racial disparity; black infants have lower risk of moderate/severe BPD due to a higher risk of death despite equivalent severity of illness. Interpretation and analysis of this finding can be found in "The challenge of risk stratification of preterm infants in the setting of competing and disparate healthcare outcomes" [1]. In this report, we provide the underlying data used in this analysis. Calculator output for 108 example patients, systematically varied by sex, birthweight, race, type of ventilator, and fraction of inspired oxygen (FiO 2 ), is reported., (© 2020 The Authors. Published by Elsevier Inc.)

Antimicrobial stewardship programs typically use days of therapy to assess antimicrobial use. However, this metric does not account for the antimicrobial spectrum of activity. We applied an antibiotic spectrum index to a population of very-low-birth-weight infants to assess its utility to evaluate the impact of antimicrobial stewardship interventions.

Competing Interests: Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Management of the patent ductus arteriosus (PDA) represents an ongoing challenge in the care of extremely premature neonates. Determining the optimal treatment strategy requires careful consideration of the potential risks and benefits of available therapies. Surgical ligation results in reliable ductal closure, but may result in numerous short-term complications and have a negative impact on long-term outcome. Intravenous indomethacin was the first pharmacologic agent widely utilized for PDA closure. Intravenous indomethacin effectively closes the ductus arteriosus and prevents pulmonary hemorrhage and severe intraventricular hemorrhage, but fails to mitigate short-term morbidities and improve long-term outcomes. Intravenous ibuprofen represents an alternative therapy with fewer renal adverse effects. However, intravenous ibuprofen does not prevent severe intraventricular hemorrhage and also has concerning adverse effects, including bilirubin displacement and the potential to increase the risk of chronic lung disease. Enteral ibuprofen has also been investigated, although gastrointestinal adverse effects limit widespread utilization. Acetaminophen (paracetamol) represents an enticing novel therapy due to wide availability, low cost, and an appealing safety profile. Ongoing investigation is required to determine the role of this agent in PDA treatment algorithms. Pending these results, clinicians must weigh the potential risks and benefits of each therapy for individual neonates considering all available evidence.