Perinatal antibiotics alter preterm infant EEG and neurobehavior in the Family Nurture Intervention trial

Abstract

Early exposure to antibiotics has been shown to increase risk for poor neurobehavioral development, particularly with regard to attention deficit disorders. Clinically, electroencephalography (EEG) is increasingly used as a biomarker of these deficits. Less is known about the effects of antibiotics on neurobehavioral and neurophysiological outcomes in preterm infants, a population at particularly high risk for attention deficits and perinatal antibiotic exposure. This study examines the effects of perinatal antibiotic exposure on neonatal EEG and attention deficits as measured by the Child Behavior Checklist in 4‐ to 5‐year‐old children who were enrolled in an NICU‐based randomized controlled trial comparing Family Nurture Intervention (FNI) to standard care. Antibiotic‐exposed infants had increased attention problems and there was a main effect of antibiotic exposure such that exposed infants had higher EEG power. This effect was fourfold greater in infants who received standard NICU care compared to those who received the intervention, suggesting a buffering effect of the intervention. We hypothesize that the relationship between antibiotic exposure and altered neurodevelopment may be due to effects of antibiotics on the microbiome, and that FNI may buffer these adverse consequences.

Neonatal quantitative electroencephalography and long‐term outcomes: a systematic review

“…61,62 Furthermore, vigilance state, including quiet, active, and intermediate sleep, affects quantitative EEG analysis, 14,63,64 a factor that was considered in only seven of the 24 studies included in this review. 22,23,27,28,37,40,41 A major limitation of this review is the lack of a quantitative synthesis (meta-analysis), which was impeded by heterogeneity in study design. The studies included in this review investigated different study populations, for example, infants born preterm, infants with asphyxia, or infants with tuberous sclerosis complex.…”

“…In addition, previous research showed that a spectral edge frequency at 90% and relative powers differed between males and females 61,62 . Furthermore, vigilance state, including quiet, active, and intermediate sleep, affects quantitative EEG analysis, 14,63,64 a factor that was considered in only seven of the 24 studies included in this review 22,23,27,28,37,40,41 …”

Annual Research Review: Critical windows – the microbiota–gut–brain axis in neurocognitive development

“…However, again, this study had several limitations; there was no justification provided for the choice of probiotic strains, the doses, or the methods of administration, nor was there a measure of the microbiota across treatment (problems that are common in this area of research). Finally, a recent study of premature infants in a Neonatal Intensive Care Unit (NICU) also examined the effect of perinatal antibiotics administered either to the mother during gestation or to the infant during the NICU stay (Firestein et al, ). In this study, which excluded cases of confirmed sepsis to reduce the confounding effect of infection, perinatal antibiotic exposure was associated with increased attentional problems at 4–5 years of age.…”

“…Antibiotic‐exposed children also exhibited higher delta power on an electroencephalogram (EEG), a pattern observed in ADHD and interpreted as a delay in maturation. Finally, an intervention that encouraged physical contact (and therefore transmission of microbes) between parent and infant during the NICU stay reduced the risk for both behavioral and neural alterations (Firestein et al, ). In addition to this preliminary evidence for microbiota modulation of developmental outcomes in humans, there have been many more studies using animal models to explore different aspects of cognitive and behavioral development.…”

Antibiotics Prescription Over Three Years in a French Benchmarking Network of 23 Level 3 Neonatal Wards

“…Prescription of antibiotics in neonatal intensive care units (NICUs) poses a unique challenge as prescription of antibiotics in excess is a risk factor for late-onset neonatal sepsis, abnormal digestive microbiota, necrotizing enterocolitis, candidemia, retinopathy of prematurity, bronchopulmonary dysplasia, and neonatal death (Alexander et al, 2011;Cotten, 2016;Esaiassen et al, 2018;Fjalstad et al, 2018;Firestein et al, 2019;Ting et al, 2019). Antibiotics overuse in neonatal wards (NWs) originates from the fear of overwhelming sepsis in an untreated infected baby, the lack of specific clinical and biological signs of neonatal infection, and the difficulty in obtaining efficient routine bacteriological examinations.…”