Nephrotoxic medications and associated acute kidney injury in hospitalized neonates.

OBJECTIVES: Hospitalized neonates are often treated with nephrotoxic medications, a known risk factor for acute kidney injury (AKI). Nephrotoxic medications and AKI, especially in periviable neonates, could be detrimental to nephrogenesis. Our objectives were to evaluate the prevalence of neonatal treatment with nephrotoxic medications and its relationship with AKI in in the first 28 days of life, and to delineate the associated demographics and diagnoses. STUDY DESIGN: Multicenter retrospective analysis using the national Pediatric Hospital Information System database, including 49 pediatric hospitals. Neonates admitted within the first two postnatal days were included. Treatment with 37 nephrotoxic medications across demographics and clinical variables, and relationship with AKI were evaluated. AKI was determined by using the International Classification of Diseases codes. RESULTS: Of 192,229 neonates, 74% were treated with at least one nephrotoxic medication. Incidence of AKI was significantly higher in the treated group (aRR 3.68 [95% CI: 2.85, 4.75]). The aRRs of treatment were increased in infants born < 32-week, and < 2000 g. Nephrotoxic medications were prescribed to 90-95% of neonates born ≤ 28-week gestational age. Most treatments (95-98%) occurred in the first 3 days. Intravascular aminoglycosides were the most frequent type; 28% of neonates were treated for ≥ 4 calendar days. Most common diagnoses were infections (25%) and patent ductus arteriosus (20%). CONCLUSIONS: Neonatal treatment with nephrotoxic medications is common, especially among the smallest, most immature preterm neonates and demonstrates a need for initiatives to reduce neonatal exposure to these agents, when feasible. Across all gestational age categories, the prevalence of AKI is higher in the neonates treated with nephrotoxic drugs. The long-term effects of treatment with nephrotoxic medications and subsequent AKI on nephrogenesis and nephron endowment will need to be evaluated.

Prophylactic Indomethacin in extremely preterm infants: association with death or BPD and observed early serum creatinine levels.

OBJECTIVES: To identify the relationship between prophylactic indomethacin (PI) administration and (1) mortality and bronchopulmonary dysplasia (BPD) at 36-week postmenstrual age (PMA) (primary outcome), and (2) to evaluate for PI-associated acute kidney injury. STUDY DESIGN: Retrospective cohort investigation of 22-28 weeks gestation infants (N = 1167) who were admitted to Nationwide Children's Hospital on postnatal days 0-1 between May 2009 and September 2017 and survived ≥24-h postnatal. The associations of PI treatment with mortality or BPD, and other secondary outcomes, were evaluated via multivariable robust-error-variance Poisson regression. RESULTS: The adjusted risks of death or BPD (1.02, 95% CI: 0.83, 1.25), BPD (0.97, 95% CI: 0.77, 1.21), and death 1.33 (95% CI: 0.84, 2.10) by 36-week PMA were unchanged following PI treatment after multivariable adjustment. No changes in mean creatinine levels were detected in exposed versus unexposed infants to suggest PI-induced AKI. CONCLUSION: Prophylactic indomethacin treatment was unrelated to mortality or BPD outcomes.

Neonatal Antiepileptic Medication Treatment Patterns: A Decade of Change.

OBJECTIVE: This study aims to describe the frequency and characteristics of anticonvulsant medication treatments initiated in the neonatal period. STUDY DESIGN: We analyzed a cohort of neonates with a seizure diagnosis who were discharged from institutions in the Pediatric Health Information System between 2007 and 2016. Adjusted risk ratios and 95% confidence intervals for characteristics associated with neonatal (≤ 28 days postnatal) anticonvulsant initiation were calculated via modified Poisson regression. RESULTS: A total of 6,245 infants from 47 institutions were included. There was a decrease in both phenobarbital initiation within the neonatal period (96.9 to 91.3%, p = 0.015) and continuation at discharge (90.6 to 68.6%, p <0.001). Levetiracetam (7.9 to 39.6%, p < 0.001) initiation within the neonatal period and continuation at discharge (9.4 to 49.8%, p < 0.001) increased. Neonates born at ≥ 37 weeks' gestation and those diagnosed with intraventricular hemorrhage, ischemic/thrombotic stroke, other hemorrhagic stroke, and hypoxic ischemic encephalopathy (HIE) had a higher probability of anticonvulsant administration. The most prevalent diagnosis was HIE (n = 2,223, 44.4%). CONCLUSION: Phenobarbital remains the most widely used neonatal seizure treatment. Levetiracetam is increasingly used as a second line therapy. Increasing levetiracetam use indicates a need for additional study to determine its effectiveness in reducing seizure burden and improving long-term outcomes.

Gabapentin Use for Hospitalized Neonates.

BACKGROUND: Despite some clinician advocacy for the use of gabapentin to treat neonatal irritability of presumed neurological origin, the extent of gabapentin administration to hospitalized neonates is unknown. We aimed to identify trends in gabapentin utilization among infants hospitalized in neonatal intensive care units (NICUs) across the United States and to evaluate the associations between clinical diagnoses and gabapentin treatment. METHODS: We analyzed neonates admitted to the NICU using the Pediatric Health Information System (2005 to 2016) to measure treatment timing, duration, and frequency. We used modified Poisson regression with a robust between-cluster variance estimator to calculate a probability (adjusted relative risk) for gabapentin administration. RESULTS: Of 278,403 neonates, 374 were administered gabapentin (0.13%). The median treatment duration was 16 days (25th to 75th percentile: 8; 40). Gabapentin use increased from 0% in 2005 to 0.39% in 2016. Treatment was prescribed to neonates at 31 of 48 studied hospitals; 73% of total treated infants localized to five neonatal intensive care units. Term (0.16%) and ≤28 weeks' gestation preterm infants (0.22%) were most likely to receive gabapentin. Varying by gestational age, a diagnosis of chromosomal abnormalities, severe bronchopulmonary dysplasia, hemorrhagic stroke, and neonatal abstinence syndrome were associated with higher treatment with gabapentin. The majority (88.8%) of treated infants did not have a seizure diagnosis. CONCLUSION: Gabapentin use in NICU in the United States increased in recent years and varies markedly between institutions. Term infants, ≤28 weeks' gestation preterm infants, and neonates with chronic genetic, neurological, and gastrointestinal diagnoses were more likely to receive gabapentin.