Mark S. Scher

Phenobarbital compared with phenytoin for the treatment of neonatal seizures.

BACKGROUND Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly. METHODS From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 microg per milliliter for phenobarbital and 3 microg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria. RESULTS Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment. CONCLUSIONS Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates.

Depressive symptoms in mothers of prematurely born infants

Objective: This longitudinal, descriptive study described the level of depressive symptoms in mothers of preterm infants from birth through 27 months corrected age and examined factors associated with depressive symptoms. The framework for the study was guided by an ecological developmental systems perspective and an adaptation of the Preterm Parental Distress Model. Methods: In this model, we hypothesize that a mothers emotional distress to the birth and parenting of a prematurely born child is influenced by personal and family factors, severity of the infants health status, and illness-related stress and worry. Participants were 102 mothers of preterm infants who were off the ventilator and not otherwise dependent on major technology at enrollment. Results: Mean depressive symptoms scores on the Center for Epidemiologic Studies Depression Scale (CES-D) during hospitalization were high and more than half the mothers (63%) had scores of ≥16 indicating risk of depression. Depressive scores declined over time until 6 months and then were fairly stable. Unmarried mothers, mothers of infants who were rehospitalized, and mothers who reported more maternal role alteration stress during hospitalization and worry about the childs health had more depressive symptoms through the first year. Mothers who reported more parental role alteration stress during hospitalization (odds ratio [OR] = 1.570, 95% confidence interval [CI]: 1.171–2.104) and more worry about the childs health (OR = 2.350, 95% CI: 1.842–2.998) were more likely to experience elevated CES-D scores that put them at risk of depression. Also, mothers of rehospitalized infants had decreasing odds of elevated CES-D scores over time (OR = 0.982 per week, 95% CI: 0.968–0.996). Conclusions: Findings have implications for the support of mothers during hospitalization and in the early years of parenting a preterm infant.

The effects of prenatal alcohol and marijuana exposure: disturbances in neonatal sleep cycling and arousal.

ABSTRACT: Neonatal EEG and sleep findings are presented from a longitudinal study of the effects of maternal alcohol and marijuana use during pregnancy. Infant outcome has been examined relative to the trimester(s) of pregnancy during which use occurred. Disturbances in sleep cycling, motility, and arousals were noted that were both substance and trimester specific. Alcohol consumed during the first trimester of pregnancy was associated with disruptions in sleep and arousal, whereas marijuana use affected sleep and motility regardless of the trimester in which it was used. Although these findings are preliminary and based on a small sample of women exhibiting only moderate substance use during pregnancy, they do suggest that specific neurophysiological systems may be differentially affected by prenatal alcohol or marijuana exposure even in the absence of morphological abnormalities.

The American clinical neurophysiology society's guideline on continuous electroencephalography monitoring in neonates

This article offers the preferred methods and indications for longterm, conventional electroencephalography (EEG) monitoring for selected, high-risk neonates of postmenstrual age less than 48 weeks. The authors recognize that there may be significant practical barriers to the implementation of these recommendations for many caregivers and institutions, particularly with regard to the availability of equipment, and technical and interpretive personnel. A wide range of clinical circumstances dictates the implementation of EEG monitoring, frequency of EEG review, and the subsequent treatment of seizures or EEG background abnormalities detected by neonatal EEG. Consequently, this article should be considered as an expression of idealized goals and not as a mandated standard of care.

Uncoupling of EEG-clinical neonatal seizures after antiepileptic drug use

A prospective study of the efficacy of seizure cessation by phenobarbital versus phenytoin administration utilized both clinical and electroencephalographic expressions of seizure behaviors. The phenomenon of uncoupling was defined as the persistence of electrographic seizures despite the suppression of >or=50% clinical seizures after either one or both antiepileptic drugs use. Fifty-nine neonates (25 to 43 weeks estimated gestational age) with electrically-confirmed seizures were assigned to either of two drugs and continuously monitored over a 24-hour period. Nine of the fifty-nine patients had only electrographic seizure expression both before and after drug administration. Of the remaining 50 patients who had both electrical and clinical seizure expression before treatment, 24 infants responded to the first choice of an antiepileptic drug with no further seizures. Fifteen of the remaining 26 infants (58%) with persistent seizures after treatment had uncoupling of electrical and clinical expressions of seizures; no difference in the uncoupling effect was noted for neonates who were treated with either antiepileptic drug or based on prematurity or gender. Serial electroencephalographic monitoring helps document continued electrographic seizure expression after antiepileptic drug use, following complete or partial suppression of clinical seizure behaviors.

Ictal and interictal electrographic seizure durations in preterm and term neonates.

Summary: The effect of gestational age on neonatal ictal and interictal durations has not been investigated. Sixty‐eight neonates with 644 electrographic seizures were identified retrospectively. Thirty‐five full‐term (FT) neonates were compared with 33 preterm (PT) neonates. Eighteen older preterm infants (OPT) [>31 weeks estimated gestational age (EGA)] were also compared with 15 young preterm infants (YPT) of ≤31 weeks EGA. Ictal/ interictal durations were calculated for the total cohort with and without status epilepticus (SE). Statistical analyses were two‐tailed t tests, chi‐square calculations, and one‐way analysis of variance (ANOVA) with Duncans multiple‐range test. Eleven of 35 (33%) FT had SE as compared with 3 of 33 (9%) PT (chi‐square = 7.8, p < 0.05). The mean ictal duration was 14.2 min for FT infants as compared with 3.1 min for PT infants (p < 0.01); only borderline differences were noted after those with SE were excluded. Interictal durations were longer for OPT than YPT (p < 0.05). By ANOVA and Duncans multiple‐range tests, group differences included longer mean ictal durations for FT infants as compared with OPT infants (p = 0.06, ANOVA; p < 0.05, Duncans), and longer mean interictal durations for FT infants versus OPT and OPT versus YPT (p = 0.02, ANOVA; p < 0.05, Duncans). More developed neuronal networks result in longer ictal durations in FT than in PT neonates, including FT infants with SE. Inhibitory networks responsible for longer interictal periods are more dominant in OPT infants than in YPT infants, reflecting maturational changes that suppress seizure activity during the latter part of the third trimester before the infant reaches an FT corrected age.

Neurophysiologic Assessment of Neonatal Sleep Organization: Preliminary Results of a Randomized, Controlled Trial of Skin Contact With Preterm Infants

BACKGROUND. Sleep is important to brain organization, but few strategies to promote sleep among premature infants have been tested. Behaviorally based measures of sleep have shown increased quiet sleep (QS) and decreased active sleep (AS) during skin-to-skin contact (SSC) with the mother, but these results have not been confirmed with objective electroencephalographic/polysomnographic measures of sleep organization. Important differences exist between behavioral and electroencephalographic/polysomnographic definitions of sleep state. METHODS. Data for the first 28 relatively healthy, preterm subjects of an ongoing randomized trial of one 2- to 3-hour session of SSC or incubator care between feedings are reported here. Infants were positioned prone, inclined, and nested in an incubator during the 2- to 3-hour pretest period, were fed, and then went into the test period of SSC or incubator care. Infants were left largely undisturbed throughout testing. A mixed-model regression analysis compared the test-pretest differences in outcome measures within and between groups. RESULTS. Results showed that arousals were significantly lower in the SSC group, compared with the control group, for the entire study period and for test-pretest matched segments of QS and AS. Rapid eye movement was significantly lower for the SSC group for the study period and AS segments. Indeterminate sleep was significantly lower for the SSC group when confounding environmental variables were included in the regression analysis. When 4 subjects who experienced excessive ambient light levels during SSC were removed from analysis, QS increased during SSC. CONCLUSIONS. The patterns demonstrated by the SSC group are analogous to more-mature sleep organization. SSC may be used as an intervention to improve sleep organization in this population of preterm infants.

Prenatal marijuana use and neonatal outcome.

In a longitudinal study of marijuana and other substance use during pregnancy, women were interviewed at each trimester of pregnancy. Growth parameters, morphological abnormalities and gestational age were assessed for the 519 liveborn singletons. There were few significant effects of marijuana use during pregnancy on birth weight, head or chest circumference, gestational age, or growth retardation after adjustment for covariates using a regression model for analysis. There was a small but significant negative effect of marijuana use during the first two months of pregnancy on birth length and a positive effect of marijuana use during the third trimester on birth weight.

Neurophysiologic assessment of brain maturation after an 8-week trial of skin-to-skin contact on preterm infants

OBJECTIVE Skin-to-skin contact (SSC) promotes physiological stability and interaction between parents and infants. Analyses of EEG-sleep studies can compare functional brain maturation between SSC and non-SSC cohorts. METHODS Sixteen EEG-sleep studies were performed on eight preterm infants who received 8 weeks of SSC, and compared with two non-SSC cohorts at term (N=126), a preterm group corrected to term age and a full-term group. Seven linear and two complexity measures were compared (Mann-Whitney U test comparisons p<.05). RESULTS Fewer REMs, more quiet sleep, increased respiratory regularity, longer cycles, and less spectral beta were noted for SSC preterm infants compared with both control cohorts. Fewer REMs, greater arousals and more quiet sleep were noted for SSC infants compared with the non-SSC preterms at term. Three right hemispheric regions had greater complexity in the SSC group. Discriminant analysis showed that the SSC cohort was closer to the non-SSC full-term cohort. CONCLUSIONS Skin-to-skin contact accelerates brain maturation in healthy preterm infants compared with two groups without SSC. SIGNIFICANCE Combined use of linear and complexity analysis strategies offer complementary information regarding altered neuronal functions after developmental care interventions. Such analyses may be helpful to assess other neuroprotection strategies.

VISUAL AND NEUROLOGICAL OUTCOME OF INFANTS WITH PERIVENTRICULAR LEUKOMALACIA

Visual acuity, visual fields and neurological status were assessed in 10 infants with periventricular leukomalacia (PVL), tested at 16, 36, 48 and 72 weeks from the expected date of confinement. Monocular acuity development was normal in eight of the 10 infants, but was below normal in one infant at eight months and in another at 18 months. Over half the infants tested at 16, 36 and 48 weeks had smaller visual fields than those of 95 per cent of healthy preterm infants tested at the same ages, but by 72 weeks only two of six infants tested had restricted visual fields. Nine of the 10 infants were neurologically abnormal at ages under one year, but only four remained so beyond one year. These results indicate more favourable outcomes for visual acuity and neurological status in infants with non‐cavitary PVL than have been reported in infants with cavitary PVL. The most compromised infants were one with cavitary PVL and another with extensive non‐cavitary PVL who had the longest‐lasting EEG abnormalities of all 10 infants.