Abstract
BackgroundSeveral studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment.MethodsThis prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months.ResultsThe I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score − 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months.ConclusionsSystemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment.
Highlights
Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants
The objective of this study is two-fold: first, to investigate whether preterm infants who experienced systemic inflammation induced by clinical infection and necrotizing enterocolitis (NEC) are more susceptible to impaired short-term neurological and corrected age (CA) of 18 months neurodevelopmental outcomes in our study population, and second, to examine the association of laboratory markers including inflammatory cytokines and brain injury markers and amplitude-integrated electroencephalography (aEEG) at the time of systemic inflammation in the neonatal intensive care unit (NICU) and neurodevelopmental outcomes
Study population and data collection Of the 100 preterm infants enrolled in the study, five infants who died before 35 weeks of postmenstrual age (PMA) and one infant with intraventricular hemorrhage (IVH) grade IV were excluded
Summary
Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment. Preterm infants are at a high risk for infection, and infection-induced inflammation was found to contribute to adverse neurodevelopment in several clinical and animal studies [4,5,6,7,8]. The magnitude of systemic inflammation is possibly reflected in the level of blood inflammatory markers and these markers could indicate the high-risk preterm infants for brain injury and poor neurodevelopment at a later stage. There have been few studies on the association between adverse neurodevelopment and inflammatory markers or aEEG findings during systemic inflammatory episodes that preterm infants experience during neonatal intensive care unit (NICU) admission
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