Neonatal Seizure Management: Is the Timing of Treatment Critical?

OBJECTIVE: To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden and describe overall seizure management in a large neonatal cohort. STUDY DESIGN: Newborns (36-44 weeks of gestation) requiring electroencephalographic (EEG) monitoring recruited to 2 multicenter European studies were included. Infants who received antiseizure medication exclusively after electrographic seizure onset were grouped based on the time to treatment of the first seizure: antiseizure medication within 1 hour, between 1 and 2 hours, and after 2 hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures, and antiseizure medication dose over the first 24 hours after seizure onset. RESULTS: Out of 472 newborns recruited, 154 (32.6%) had confirmed electrographic seizures. Sixty-nine infants received antiseizure medication exclusively after the onset of electrographic seizure, including 21 infants within 1 hour of seizure onset, 15 between 1 and 2 hours after seizure onset, and 33 at >2 hours after seizure onset. Significantly lower seizure burden and fewer seizures were noted in the infants treated with antiseizure medication within 1 hour of seizure onset (P = .029 and .035, respectively). Overall, 258 of 472 infants (54.7%) received antiseizure medication during the study period, of whom 40 without electrographic seizures received treatment exclusively during EEG monitoring and 11 with electrographic seizures received no treatment. CONCLUSIONS: Treatment of neonatal seizures may be time-critical, but more research is needed to confirm this. Improvements in neonatal seizure diagnosis and treatment are also needed.

A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia.

OBJECTIVE: To assess the predictive value of a novel magnetic resonance imaging (MRI) score, which includes diffusion-weighted imaging as well as assessment of the deep grey matter, white matter, and cerebellum, for neurodevelopmental outcome at 2 years and school age among term infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia. STUDY DESIGN: This retrospective cohort study (cohort 1, The Netherlands 2008-2014; cohort 2, Sweden 2007-2012) including infants born at >36 weeks of gestational age treated with therapeutic hypothermia who had an MRI in the first weeks of life. The MRI score consisted of 3 subscores: deep grey matter, white matter/cortex, and cerebellum. Primary adverse outcome was defined as death, cerebral palsy, Bayley Scales of Infant and Toddler Development, third edition, motor or cognitive composite scores at 2 years of <85, or IQ at school age of <85. RESULTS: In cohort 1 (n = 97) and cohort 2 (n = 76) the grey matter subscore was an independent predictor of adverse outcome at 2 years (cohort 1, OR, 1.6; 95% CI, 1.3-1.9; cohort 2, OR, 1.4; 95% CI, 1.2-1.6), and school age (cohort 1, OR, 1.3; 95% CI, 1.2-1.5; cohort 2, OR, 1.3; 95% CI, 1.1-1.6). The white matter and cerebellum subscore did not add to the predictive value. The positive predictive value, negative predictive value, and area under the curve for the grey matter subscore were all >0.83 in both cohorts, whereas the specificity was >0.91 with variable sensitivity. CONCLUSION: A novel MRI score, which includes diffusion-weighted imaging and assesses all brain areas of importance in infants with therapeutic hypothermia after perinatal asphyxia, has predictive value for outcome at 2 years of age and at school age, for which the grey matter subscore can be used independently.

Sex differences in outcome and associations with neonatal brain morphology in extremely preterm children.

OBJECTIVE: To investigate sex differences in neurologic and developmental outcomes in extremely preterm (EPT) children and explore associations with neonatal brain morphology. STUDY DESIGN: A population-based cohort of infants born at <27 weeks gestation underwent magnetic resonance imaging (MRI) at term equivalent age (n = 107). Voxel-based morphometry (n = 27) and tract-based spatial statistics (n = 29) were performed in infants with normal MRI findings. Neurologic and developmental assessment (using the Bayley Scales of Infant and Toddler Development-Third Edition [BSITD-III]) was performed at 30 months corrected age (n = 91). RESULTS: EPT boys had lower mean cognitive composite scores (P = .03) and lower mean language composite scores (P = .04) compared with EPT girls. Rates of cerebral palsy were similar in the 2 sexes. No perinatal factor explained the variance in outcomes. Visual inspection of T1- and T2-weighted MRI images found that delayed myelination was found more frequently in boys, whereas cerebellar abnormalities were more common in girls. In the subgroup of children with normal MRI findings (n = 27), boys had poorer cognitive function (P = .015) and language function (P = .008), despite larger volumes of cerebellar tissue (P = .029). In boys, cerebellar volume was positively correlated with BSITD-III cognitive and motor scores (P = .04 for both). In girls, white matter volume (P = .02) and cortical gray matter volume (P = .03) were positively correlated with BSITD-III language score. At the regional level, significant correlations with outcomes were found only in girls. CONCLUSION: Cognitive and language outcomes at age 30 months were poorer in boys. Sex-related differences were observed on neonatal structural MRI, including differences in the patterns of correlations between brain volumes and developmental scores at both global and regional levels.

Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants.

OBJECTIVE: To examine associations between brain white matter abnormalities, including diffuse excessive high signal intensities, detected on neonatal magnetic resonance imaging (MRI) with neurodevelopmental outcome at age 30 months. STUDY DESIGN: This was a prospective, population-based study of infants born at <27 weeks gestation (n=117) undergoing conventional MRI at term equivalent age (n=107). At age 30 months corrected, 91 of the preterm infants (78%) and 85 term-born controls were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS: Cerebral palsy (CP) was present in 7% of the preterm group. On the BSID-III, mean composite scores were 96±9.5 for the cognitive scale, 97±14 for language scales, and 103±15 for motor scales, all within the normal range for age. Compared with the term-born controls, however, the preterm infants did not perform as well on all 3 scales, also when MRI was normal. Significant associations were seen between moderate to severe white matter abnormalities and CP (P<.001). The presence of diffuse excessive high signal intensities was not associated with performance on the BSID-III or with CP. CONCLUSION: This 3-year cohort of extremely preterm infants had low rates of major brain injury and impaired outcome. Neonatal MRI provides useful information, but this information needs to be treated with caution when predicting outcome.

Continuous feeding promotes gastrointestinal tolerance and growth in very low birth weight infants.

OBJECTIVE: To compare the effects of continuous versus intermittent feeding on gastrointestinal tolerance and growth in very low birth weight (VLBW) infants. STUDY DESIGN: In a randomized, controlled trial conducted at 3 neonatal units, 70 premature infants with a gestational age 24 to 29 weeks and birth weight < 1200 g were assigned to 1 of 3 feeding methods: continuous nasogastric feeding, intermittent nasogastric feeding, or intermittent orogastric feeding. Feeding was initiated within 30 hours of birth. Daily enteral and parenteral volumes, caloric and protein intakes, growth, enteral intolerance, and clinical complications were recorded. Cox regression analysis was used to determine primary outcome, the time to achieve full enteral feeding. RESULTS: The continuously fed infants achieved full enteral feeding significantly faster than the intermittently fed infants (hazard ratio [HR] = 1.86; 95% confidence interval [CI] = 1.07 to 3.22). In stratified analysis according to birth weight, the improvement was even more pronounced in the smallest infants, those with birth weight < or = 850 g (adjusted HR = 4.13; 95% CI = 1.48 to 11.53). Growth rate was significantly faster in the continuously fed infants ( P = .002). CONCLUSION: In VLBW infants, continuous feeding seems to be better than intermittent feeding with regard to gastrointestinal tolerance and growth.