Moderate hypothermia to treat perinatal asphyxial encephalopathy. [Preventive treatment of convulsions in perinatal asphyxia]. High-dose phenobarbital therapy in term newborn infants with severe perinatal asphyxia: a randomized, prospective study with three-year follow-up. Use of barbiturate therapy in severe perinatal asphyxia: a randomized controlled trial. Mild hypothermia via selective head cooling as neuroprotective therapy in term neonates with perinatal asphyxia: an experience from a single neonatal intensive care unit. Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study. Do prophylactic anticonvulsant drugs alter the pattern of seizures after craniotomy? Discontinuing anti-epileptic medication(s) in epileptic children: 18 versus 24 months. Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents.
Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.
                We performed a randomized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy. We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone. The primary outcome was death or severe disability at 18 months of age. Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes.
                Of 325 infants enrolled, 163 underwent intensive care with cooling, and 162 underwent intensive care alone. In the cooled group, 42 infants died and 32 survived but had severe neurodevelopmental disability, whereas in the noncooled group, 44 infants died and 42 had severe disability (relative risk for either outcome, 0.86; 95% confidence interval [CI], 0.68 to 1.07; P=0.17). Infants in the cooled group had an increased rate of survival without neurologic abnormality (relative risk, 1.57; 95% CI, 1.16 to 2.12; P=0.003). Among survivors, cooling resulted in reduced risks of cerebral palsy (relative risk, 0.67; 95% CI, 0.47 to 0.96; P=0.03) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II (P=0.03 for each) and the Gross Motor Function Classification System (P=0.01). Improvements in other neurologic outcomes in the cooled group were not significant. Adverse events were mostly minor and not associated with cooling.
                Induction of moderate hypothermia for 72 hours in infants who had perinatal asphyxia did not significantly reduce the combined rate of death or severe disability but resulted in improved neurologic outcomes in survivors. (Current Controlled Trials number, ISRCTN89547571.)
                2009 Massachusetts Medical Society A double blind randomized study has been performed in 17 newborn infants bearing a diagnosis of perinatal asphyxia and treated with phenobarbital (FB) or phenytoin (DPH) to prevent the onset of seizures. The initial dose for both drugs was 12 m/kg IM the first day, followed by 6 mg/kg/day through the seventh day. Patients were clinically assessed daily and drug blood levels were also determined daily by enzyme immunoassay (EMIT). Mean FB levels along the seven days were 17.6, 23.7, 25.6, 31.6, 31.4, 36.7, and 44.6 micrograms/ml. One child treated with FB exhibited seizures on the second day and six children showed drowsiness and bradycardia on the last two days, that were attributable to high levels of FB. Mean (DPH) levels along the study were: 4.6, 7.0, 9.7, 6.5, 4.5, and 5.2 micrograms/ml. Seizures occurred in one of the DPH-treated patients and signs of therapeutic inefficacy such as hypertonus and abnormal movements appeared in four children. To determine whether 40 mg/kg phenobarbital given to term infants with severe asphyxia would result in a lower incidence of seizures in the newborn period and an improved neurologic outcome.
                We conducted a randomized, controlled, prospective study. Entry criteria included (1) an initial arterial pH less than or equal to 7.0 with a base deficit 15 mEq/L or more, (2) Apgar score less than or equal to 3 at 5 minutes of age, or (3) failure to initiate spontaneous respiration by 10 minutes of age. Sample size was calculated to detect a 50% reduction in the incidence of neonatal seizures.
                No differences were present between treatment and control groups with respect to severity of asphyxia assessed by initial arterial pH, base excess, cerebrospinal fluid lactate dehydrogenase concentration or detection of CSF creatine kinase of its BB isoenzyme. Seizures occurred in 9 of 15 infants in the treatment group and 14 of 16 infants in the control group (p = 0.11). No adverse effects were observed from phenobarbital on heart rate, respiratory rate, blood pressure, or arterial blood gas values. Three-year follow-up revealed normal outcome in 11 of 15 infants in the treatment group and 3 of 16 in the control group (p = 0.003).
                Phenobarbital, when administered in a dose of 40 mg/kg intravenously over 1 hour in term, severely asphyxiated newborn infants appeared to be safe and was associated with a 27% reduction in the incidence of seizures and a significant improvement in neurologic outcome at 3 years of age. The possible cerebral sparing effect of thiopental was evaluated in 32 severely asphyxiated neonates randomly assigned to either a thiopental treatment or control group. All infants had neurologic manifestations of asphyxia and required assisted ventilation. Thiopental was begun at a mean age of 2.3 hours and was given as a constant infusion that delivered 30 mg/kg over 2 hours. Treatment was continued at a lower dose for 24 hours. Seizure activity occurred in 76% of infants given thiopental and 73% of control infants at a mean age of 1.5 and 2.5 hours, respectively. Although initial arterial blood pressure was similar in both groups, hypotension occurred in 88% of treated and 60% of control infants. The amount of blood pressure support required was significantly greater (P less than 0.005) in the thiopental treatment group. Three infants died in the control group, and five in the treatment group. Developmental assessment was performed at a minimum of 12 months of age in 22 infants. There were no significant differences in neurologic, cognitive, or motor outcome between groups. Deteriorating performance over time was a consistent trend in both groups. These findings indicate that treatment of severe perinatal asphyxia with thiopental does not appear to have a cerebral sparing effect and may be associated with significant arterial hypotension. The objective of this study was to determine the efficacy of mild hypothermia via selective head cooling as a neuroprotective therapy in term infants with perinatal asphyxia.
                Full-term newborns who had 5 min Apgar scores <6, first arterial blood gas pH<7.10 or BD>15 mEq/l, and with the clinical signs of encephalopathy were enrolled within 6 h after birth. Patients were randomized to receive mild hypothermia treatment via selective head cooling for a total of 72 h or receive routine treatment as a control. Brain hypoxic-ischemic injury was quantified based on the head computed tomographic scan (CT scan) at postnatal age 5-7 days and a Neonatal Behavioral Neurological Assessment (NBNA) score at 7-10 days of life.
                A total of 58 patients (30 hypothermia, 28 control) completed the study. Hypothermia was well tolerated in this study and attenuated the hypoxic-ischemic brain injury due to perinatal asphyxia. Head CT scan demonstrated moderate to severe hypoxic-ischemic changes in only 4/30 cases from the hypothermic group. In contrast, 18/28 cases in the control group showed moderate to severe hypoxic-ischemic changes (chi (2)=15.97, P<0.01). Brain hypothermia also significantly improved the NBNA score (32+/-2 in the hypothermic group vs 28+/-3 in the control group, P<0.01).
                Our results suggest that selective head cooling may be used as a neuroprotective therapy in term neonates with perinatal asphyxia. A long-term follow-up study is needed to further validate the results of this study. The authors conducted a randomized trial of second-line anticonvulsant treatments for neonates. The response to treatment was assessed using continuous video-EEG because the clinical diagnosis of seizure in neonates is known to be unreliable. Of 27 neonates with EEG-confirmed seizures, 5 were excluded because of protocol violations, and 11 responded to phenobarbitone in a dose of 40 mg/kg as first line. Three of five neonates treated with lignocaine responded. Six neonates were treated with benzodiazepines as second line: None responded, and their neurodevelopmental outcome was poor. A total of 276 patients with a high risk of developing postoperative seizures were randomised to treatment with carbamazepine or phenytoin for six or 24 months, or to no treatment. No significant differences were found (though the confidence limits were fairly wide) between the regimes in respect of the incidence of seizures or death. In a substantial proportion of the patients postoperative epilepsy remained a continuing disability. A high incidence of drug-related side effects was found in the treatment groups. Prophylactic anticonvulsants cannot therefore be recommended routinely following supratentorial craniotomy. For a period of slightly over 4 years, 80 children who had been seizure-free for at least 18 months while on anti-convulsant medication were prospectively collected. These 80 children were randomly assigned to either the 18-months seizure-free group (n = 41) or to the group where anti-convulsant medications were continued for another 6 months before they were gradually tapered off and stopped, i.e. the 24-months seizure-free group (n = 39). Twelve (29%) of the 41 children who had been seizure-free for 18 months and 14 (36%) of the 39 children who had been seizure-free for 24 months had seizure recurrence during the follow-up period. Log-rank test of the recurrence experience of the two groups of patients showed no statistically significant difference between the groups (p > 0.50). Similarly, when both groups were combined and other risk variables likely to influence the rate of seizure recurrence were tested, only EEG abnormality at discontinuation of anti-convulsant medication had a significant association with the risk of seizure recurrence (p < 0.001). Antiepileptic drugs (AEDs) are potential teratogenic agents. The purpose of this study was to examine the long-term effects of intrauterine AED exposure on neurologic and psychological functioning.
                Of a prospective study, "Epilepsy, pregnancy, and child development," children could be retraced at school age and adolescence. Sixty-seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects.
                Type of maternal epilepsy and type and kind of AED therapy, but not maternal seizures during pregnancy correlated with an increase in abnormal EEG patterns. Minor neurologic dysfunction was diagnosed, with increased frequency from the control to the risk/no drug or monotherapy to the polytherapy group. The compromised intelligence score of the polytherapy group was primarily due to those children who had been exposed to primidone (PRM). Level of IQ was negatively associated with PRM dosage.
                Maternal epilepsy and AED therapy during pregnancy appear to have long-term effects on the offspring well into adolescence, as evinced in EEG patterns, minor neurologic dysfunction, and intellectual performance. Severity of effects increased from control group to epilepsy/no-drug group to monotherapy group and was most marked in the polytherapy group. These group differences are assumed to reflect differential neural vulnerability to social and family factors.
At the present time, anticonvulsant therapy to term infants in the immediate period following perinatal asphyxia cannot be recommended for routine clinical practice, other than in the treatment of prolonged or frequent clinical seizures. Any future studies should be of sufficient size to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability.