Effects of prenatal antiepileptic drug exposure on newborn brain activity

Abstract

SUMMARYObjective: Prenatal exposure to antiepileptic drugs (AEDs) is associated with an increased risk of cognitive dysfunction at early school age. Our aim was to investigate whether signs of adverse drug effects on brain function could be detected already during the first 2 weeks of life. Methods: We studied prospectively 56 full-term newborns with prenatal exposure to AEDs and 67 unexposed newborns for the following characteristics: Background information, AED exposure data, pregnancy outcome, neuropsychological evaluation of the mothers, clinical neurologic status with Hammersmith Neonatal Neurological Examination and early cortical activity using electroencephalography (EEG). For EEG assessment, we developed and provide automated quantitation algorithms of several earlier described features: oscillatory bouts at theta and alpha frequencies, frequency spectra, interhemispheric synchrony, and interburst intervals (IBIs). Results: The AED-exposed newborns had lower limb and axial tone and were less irritable than the unexposed newborns. EEG assessment disclosed significant differences in alpha bouts, in the frequency spectra, as well as in the spatial distributions of interhemispheric synchrony and IBIs. Significance: The results indicate that fetal AED exposure may affect early neonatal neurologic status and several features of early cortical activity. The findings suggest that interference of activity-dependent network development may be a possible mechanism to explain the link from fetal AED exposure to later neurocognitive sequelae. KEY WORDS: Epilepsy, Pregnancy, Neonatal, EEG.Epilepsy affects about 0.3-0.7% of pregnant women.

Evidence for spared attention to faces in 7-month-old infants after prenatal exposure to antiepileptic drugs

“…Supporting the hypothesis that AED exposure may alter the development of activity-dependent neural networks, we recently found significant differences in the newborn cortical activity after prenatal exposure to AEDs [20]. These findings suggested that prenatal AED exposure might interfere with temporal occurrence and spatial coordination of the developing brain, possibly leading to functional effects that emerge behaviorally in later infancy.…”

“…One of the proposed mechanisms at cellular level has been altered apoptosis [11][12][13][14] contributing to structural changes in the cerebellum [15], hippocampus, and cortex [16]. Functional changes have been suggested to be due to alterations in synaptic maturation, in organization of neuronal networks, and in electric brain activity [13,[17][18][19][20].…”

Design and optimisation of time-frequency analysis for multichannel neonatal EEG background features in term neonates with hypoxic ischaemic encephalopathy: characterisation, classification and neurodevelopmental outcome prediction

“…Table 5.3 provides a list of composite features used. [148,195] Higuchi fractal dimension, algorithmic entropy [163] Renyi, Shannon and Tsaillis entropy [164,230] Approximate and Sample entropy [166] Hurst exponent [168,230] Frequency( ) Spectral and relative powerbased features ( ) Spectral Flatness, Flux and Entropy [35] Spectral Edge frequency at 80, 90 and 95% [169,195,222] Spectral Edge power at 80, 90 and 95% [169,195,222] Total power in delta, theta and alpha bands [222] Relative power in delta, theta and alpha bands w.r.t total EEG power [170,222] Delta to theta power ratio (DTR) [231] Delta to alpha power ratio (DAR) [222,232] Mean bout in delta, alpha and theta band [229] Bout percentage in delta, alpha and theta band [229] Time-frequency ( , ) ( , ) -signal based features…”

“…Low activity duration and Low activity density High activity duration and High activity density Global mean (IBI) [229] Global median (IBI) [229] …”

“…Similarly, high activity duration density is defined as the high activity duration per hour. Global IBI is the IBI calculated from the whole 2-h EEG signal [229]. Like low voltage, IBI is also one of the predictors of outcome [86].…”