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Practice variation in anti-epileptic drug use for neonatal hypoxic-ischemic encephalopathy among regional NICUs.

ABSTRACT: BACKGROUND:While intercenter variation (ICV) in anti-epileptic drug (AED) use in neonates with seizures has been previously reported, variation in AED practices across regional NICUs has not been specifically and systematically evaluated. This is important as these centers typically have multidisciplinary neonatal neurocritical care teams and protocolized approaches to treating conditions such as hypoxic ischemic encephalopathy (HIE), a population at high risk for neonatal seizures. To identify opportunities for quality improvement (QI), we evaluated ICV in AED utilization for neonates with HIE treated with therapeutic hypothermia (TH) across regional NICUs in the US. METHODS:Children's Hospital Neonatal Database and Pediatric Health Information Systems data were linked for 1658 neonates ?36?weeks' gestation, >?1800?g birthweight, with HIE treated with TH, from 20 NICUs, between 2010 and 2016. ICV in AED use was evaluated using a mixed-effect regression model. Rates of AED exposure, duration, prescription at discharge and standardized AED costs per patient were calculated as different measures of utilization. RESULTS:Ninety-five percent (range: 83-100%) of patients with electrographic seizures, and 26% (0-81%) without electrographic seizures, received AEDs. Phenobarbital was most frequently used (97.6%), followed by levetiracetam (16.9%), phenytoin/fosphenytoin (15.6%) and others (2.4%; oxcarbazepine, topiramate and valproate). There was significant ICV in all measures of AED utilization. Median cost of AEDs per patient was $89.90 (IQR $24.52,$258.58). CONCLUSIONS:Amongst Children's Hospitals, there is marked ICV in AED utilization for neonatal HIE. Variation was particularly notable for HIE patients without electrographic seizures, indicating that this population may be an appropriate target for QI processes to harmonize neuromonitoring and AED practices across centers.

SUBMITTER: Dizon MLV

PROVIDER: S-EPMC6391819 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Practice variation in anti-epileptic drug use for neonatal hypoxic-ischemic encephalopathy among regional NICUs.

Dizon Maria L V MLV Rao Rakesh R Hamrick Shannon E SE Zaniletti Isabella I DiGeronimo Robert R Natarajan Girija G Kaiser Jeffrey R JR Flibotte John J Lee Kyong-Soon KS Smith Danielle D Yanowitz Toby T Mathur Amit M AM Massaro An N AN

BMC pediatrics 20190227 1

<h4>Background</h4>While intercenter variation (ICV) in anti-epileptic drug (AED) use in neonates with seizures has been previously reported, variation in AED practices across regional NICUs has not been specifically and systematically evaluated. This is important as these centers typically have multidisciplinary neonatal neurocritical care teams and protocolized approaches to treating conditions such as hypoxic ischemic encephalopathy (HIE), a population at high risk for neonatal seizures. To i ...[more]

PMID: 30813933

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Project description:BACKGROUND: The issue concerning neurologic outcome in patients with perinatal Hypoxic-Ischemic Encephalopathy (H.I.E) has inspired many studies which tried to identify adequate prognostic factors. Our work aims to find among neonatal parameters:- factors which help to predict the risk to develop both Cerebral Palsy (CP) and secondary Epilepsy at one year of age in subjects affected by perinatal Hypoxic-Ischemic Encephalopathy,- correlations between the neonatal parameters and the variable severity of above mentioned sequelae. METHODS: We have recruited 32 subjects, whose history and neuroimages suggested a perinatal H.I.E and we have retrospectively analysed clinical-instrumental parameters at birth and at one year of age. RESULTS: At one year cut-off, 9 patients developed both secondary epilepsy and CP (28%), whereas the other subjects showed only motor delay (31%), only secondary epilepsy (3%) or only CP (38%). Patients with both the severest sequelae were essentially term infants (only 2/9 were pre-term infants), with normal weight (only 3 LBW) and 7 of them with early pathologic EEG and neuroimages pointing out cortex injuries (typical of term infants). A statistic analysis showed the following correlations: birth weight and global prognosis (chi2 = 14,03; p = 0,04); neonatal clinical pattern and CP's severity (chi2 = 14,03; p = 0,0009); early EEG and CP's severity (chi2 = 4,32; p = 0,04); epileptic onset age and CP and Epilepsy's severity (F = 16,01; p = 0,005).Birth weight represented a predictive factor of early neurological outcome (<1,5 kg birth weight neonates are not at risk of both epilepsy and CP); neonatal clinical pattern and early EEG were correlated with variable severity of CP; an epileptic exordium in the first 6 months led up to a more severe epileptic and paretic outcome. CONCLUSION: From a clinical point of view it is of crucial importance to have some parameters which enable to discriminate patients at risk of more severe sequelae from those at risk of moderate severity outcome.

Project description:Interferon regulatory factor 4 (IRF4), a transcription factor recognized as a key regulator of lymphoid and myeloid cell differentiation, has recently been recognized as a critical mediator of macrophage activation. Previously we have reported that IRF4 signaling is closely correlated with anti-inflammatory polarization of microglia in adult mice after stroke. However, IRF4's role in the inflammatory response in the immature brain is unknown. Using a model of neonatal hypoxic ischemic encephalopathy (HIE) we investigated the regulatory action of IRF4 signaling in the activation of microglia and monocytes after HIE. IRF4 myeloid cell conditional knockout (CKO) postnatal day 10 (P10) male pups were subjected to a 60-min hypoxic-ischemic insult by the Rice-Vanucci model (RVM). IRF4 gene floxed mice (IRF4fl/fl) were used as controls. Brain atrophy and behavioral deficits were measured 7 days after HIE. Flow cytometry (FC) was performed to examine central (microglial activation) and peripheral immune cell responses by both cell membrane and intracellular marker staining. Serum levels of cytokines were determined by ELISA. The results showed that IRF4 CKO pups had increased tissue loss and worse behavioral deficits than IRF4fl/fl mice seven days after HIE. FC demonstrated significantly more infiltration of monocytes and neutrophils in the ischemic brains of IRF4 CKO vs IRF4fl/fl pups. IRF4 CKO ischemic microglia were more pro-inflammatory as evidenced by higher expression of the pro-inflammatory marker CD68, and increased intracellular TNF? and IL-1? levels compared to controls. In addition, IRF4 deletion from myeloid cells resulted in increased levels of circulating pro-inflammatory cytokines and higher endothelial MMP9 expression after HIE. These data indicate that IRF4 signaling in myeloid cells plays a regulatory role in neuroinflammation and that deletion of myeloid IRF4 is detrimental to HIE injury, suggesting that IRF4 could serve as a potential therapeutic target for neonatal ischemic brain injury.

Dataset Information

Practice variation in anti-epileptic drug use for neonatal hypoxic-ischemic encephalopathy among regional NICUs.

Publications

Practice variation in anti-epileptic drug use for neonatal hypoxic-ischemic encephalopathy among regional NICUs.

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