Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures.
Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures.
复制标题
DOI：
10.1001/jamaneurol.2021.1437
复制
发表时间：
2021-07-01
期刊：
影响因子：
29
通讯作者：
Shellhaas RA
中科院分区：
文献类型：
--
作者：
Glass HC;Soul JS;Chang T;Wusthoff CJ;Chu CJ;Massey SL;Abend NS;Lemmon M;Thomas C;Numis AL;Guillet R;Sturza J;McNamara NA;Rogers EE;Franck LS;McCulloch CE;Shellhaas RA
在新生儿急性症状性癫痫发作消退后和出院前停用抗癫痫药物（ASM）是否与24个月时的功能性神经发育或癫痫相关？在这项来自9个中心的303名新生儿癫痫发作儿童的比较有效性研究中，64%的儿童在出院时保持ASM。ASM维持组和中止组在功能性神经发育或癫痫方面没有差异; 13%的儿童发生癫痫，其中超过三分之一患有婴儿痉挛症。这些结果支持大多数急性症状性癫痫发作的新生儿在出院前停止ASM，这种方法可能代表许多临床医生在实践中的循证变化。抗癫痫药物（ASM）治疗急性症状性新生儿癫痫发作的持续时间是可变的。一项在急性症状性癫痫发作消退后比较苯巴比妥与安慰剂的随机临床试验由于入组人数少而提前结束。评估急性症状性新生儿癫痫发作消退后和出院前ASM停药是否与24个月龄时的功能性神经发育或癫痫风险相关。这项比较有效性研究纳入了来自9个美国新生儿癫痫登记中心的303名患有急性症状性癫痫发作的新生儿（282名有随访数据，270名有主要结局指标），这些新生儿出生于2015年7月至2018年3月。这些中心均设有IV级新生儿重症监护室和全面的儿科癫痫项目。数据分析时间为2020年6月至2021年2月。主要暴露是ASM治疗的持续时间，分为ASM停药与新生儿癫痫发作入院出院时维持的ASM。为了加强因果关系，每种结局风险都根据出院时接受ASM的倾向进行了调整。ASM维持倾向通过logistic回归模型定义，包括癫痫发作原因、胎龄、治疗性低温、最差脑电图背景、脑电图癫痫发作天数和出院检查（除原因外，联合模型中所有P ≤ .10，其被纳入表面有效性）。在24个月时，通过华纳适应性和功能性技能初步发育评价（WIDEA-FS）评估功能性神经发育，并对早期ASM停药的倾向调整非劣效性进行评估。根据国际抗癫痫联盟的标准定义新生儿后癫痫，预先规定的次要结局，通过父母访谈确定，并通过医疗记录证实。大多数新生儿（194/303 [64%]）在出院时保持ASM。在24个月时评估的270名儿童中，（平均[SD]，23.8 [0.7]个月; 147例[54%]为男性），停用ASM的婴儿的WIDEA-FS评分相似（101/270 [37%]）与维持ASM的婴儿相比（169/270 [63%]）（中位评分，165 [四分位距，150-175] vs 161 [四分位距，129-174]; P = 0.09）。倾向调整的平均差异为4分（90% CI，-3至11分），符合-12分的先验非劣效性限值。癫痫风险相似（11% vs 14%; P = 0.49），倾向调整比值比为1.5（95%CI，0.7-3.4; P = 0.32）。在这项有效性比较研究中，在急性症状性新生儿癫痫发作消退后，停用ASM与出院时维持ASM的儿童在24个月时的功能性神经发育或癫痫方面无差异。这些结果支持大多数患有急性症状性新生儿癫痫发作的婴儿在出院前停止ASM。这项比较有效性研究评估了急性症状性新生儿癫痫发作消退后出院前停用抗癫痫药物是否与24个月时功能性神经发育受损或癫痫风险相关。
Is discontinuation of antiseizure medication (ASM) after resolution of acute symptomatic neonatal seizures and prior to discharge from the hospital associated with functional neurodevelopment or epilepsy at 24 months? In this comparative effectiveness study of 303 children with neonatal seizures from 9 centers, 64% had ASM maintained at hospital discharge. No difference was found between ASM maintenance and discontinuation groups in functional neurodevelopment or epilepsy; 13% of children developed epilepsy, including more than one-third with infantile spasms. These results support discontinuing ASMs for most neonates with acute symptomatic seizures prior to discharge from the hospital, an approach that may represent an evidence-based change in practice for many clinicians. Antiseizure medication (ASM) treatment duration for acute symptomatic neonatal seizures is variable. A randomized clinical trial of phenobarbital compared with placebo after resolution of acute symptomatic seizures closed early owing to low enrollment. To assess whether ASM discontinuation after resolution of acute symptomatic neonatal seizures and before hospital discharge is associated with functional neurodevelopment or risk of epilepsy at age 24 months. This comparative effectiveness study included 303 neonates with acute symptomatic seizures (282 with follow-up data and 270 with the primary outcome measure) from 9 US Neonatal Seizure Registry centers, born from July 2015 to March 2018. The centers all had level IV neonatal intensive care units and comprehensive pediatric epilepsy programs. Data were analyzed from June 2020 to February 2021. The primary exposure was duration of ASM treatment dichotomized as ASM discontinued vs ASM maintained at the time of discharge from the neonatal seizure admission. To enhance causal association, each outcome risk was adjusted for propensity to receive ASM at discharge. Propensity for ASM maintenance was defined by a logistic regression model including seizure cause, gestational age, therapeutic hypothermia, worst electroencephalogram background, days of electroencephalogram seizures, and discharge examination (all P ≤ .10 in a joint model except cause, which was included for face validity). Functional neurodevelopment was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) at 24 months powered for propensity-adjusted noninferiority of early ASM discontinuation. Postneonatal epilepsy, a prespecified secondary outcome, was defined per International League Against Epilepsy criteria, determined by parent interview, and corroborated by medical records. Most neonates (194 of 303 [64%]) had ASM maintained at the time of hospital discharge. Among 270 children evaluated at 24 months (mean [SD], 23.8 [0.7] months; 147 [54%] were male), the WIDEA-FS score was similar for the infants whose ASMs were discontinued (101 of 270 [37%]) compared with the infants with ASMs maintained (169 of 270 [63%]) at discharge (median score, 165 [interquartile range, 150-175] vs 161 [interquartile range, 129-174]; P = .09). The propensity-adjusted average difference was 4 points (90% CI, −3 to 11 points), which met the a priori noninferiority limit of −12 points. The epilepsy risk was similar (11% vs 14%; P = .49), with a propensity-adjusted odds ratio of 1.5 (95% CI, 0.7-3.4; P = .32). In this comparative effectiveness study, no difference was found in functional neurodevelopment or epilepsy at age 24 months among children whose ASM was discontinued vs maintained at hospital discharge after resolution of acute symptomatic neonatal seizures. These results support discontinuation of ASM prior to hospital discharge for most infants with acute symptomatic neonatal seizures. This comparative effectiveness study assesses whether discontinuation of antiseizure medication prior to discharge from the hospital after resolution of acute symptomatic neonatal seizures is associated with impaired functional neurodevelopment or the risk of epilepsy at 24 months.
登录
查看更多内容
影响因子：
2
作者：
Le VT;Abdi HH;Sánchez PJ;Yossef L;Reagan PB;Slaughter LA;Firestine A;Slaughter JL
通讯作者：
Slaughter JL
DOI：
10.1136/archdischild-2019-318612
发表时间：
2020-11
期刊：
Archives of disease in childhood. Fetal and neonatal edition
影响因子：
--
作者：
Lemmon M;Glass H;Shellhaas RA;Barks MC;Bailey B;Grant K;Grossbauer L;Pawlowski K;Wusthoff CJ;Chang T;Soul J;Chu CJ;Thomas C;Massey SL;Abend NS;Rogers EE;Franck LS;Neonatal Seizure Registry
通讯作者：
Neonatal Seizure Registry
影响因子：
8
作者：
Guillet, Ronnie;Kwon, Jennifer M.
通讯作者：
Kwon, Jennifer M.
影响因子：
3.5
作者：
Glass, Hannah C.;Bonifacio, Sonia L.;Peloquin, Susan;Shimotake, Thomas;Sehring, Sally;Sun, Yao;Sullivan, Joseph;Rogers, Elizabeth;Barkovich, A. James;Rowitch, David;Ferriero, Donna M.
通讯作者：
Ferriero, Donna M.
影响因子：
5.1
作者：
Franck, Linda S.;Shellhaas, Renee A.;Glass, Hannah C.
通讯作者：
Glass, Hannah C.