Association of Circulating Proinflammatory and Anti-inflammatory Protein Biomarkers in Extremely Preterm Born Children with Subsequent Brain Magnetic Resonance Imaging Volumes and Cognitive Function at Age 10 Years

Abstract

Objectives-To examine elevated neonatal inflammatory and neurotrophic proteins from children born extremely preterm in relation to later childhood brain Magnetic Resonance Imaging volumes and cognition.Study design-We measured circulating inflammation-related proteins and neurotrophic proteins on postnatal days 1, 7, and 14 in 166 children at 10 years of age (73 males; 93 females). Top quartile levels on ≥2 days for ≥3 inflammation-related proteins and for ≥4 neurotrophic

Serelaxin activates eNOS, suppresses inflammation, attenuates developmental delay and improves cognitive functions of neonatal rats after germinal matrix hemorrhage

“…It has been demonstrated that the development of GMH leads to inflammation damaging the periventricular white matter, apoptosis and arresting maturation of oligodendrocyte precursor cells, and hypomyelination 47 . Negative effects of inflammation, resulting in the white matter loss have been observed in both preclinical and clinical studies [48][49][50] . Infants suffering GMH are prone to disrupted white matter www.nature.com/scientificreports www.nature.com/scientificreports/ maturation and impaired cognitive development 51 .…”

In-line filtration in very preterm neonates: a randomized controlled trial

“…The 20% change in pro-inflammatory cytokines serum concentrations has been decided after a consensus had been obtained from a panel of neonatologists and from the scientific committee of the trial asked about the minimal threshold they considered as clinically relevant and important. Indeed, the median levels of IL-1β, IL-8, and TNFα were previously reported to be about twice as high as those previously described for term infants 5 . Based on these data, we hypothesized that a reduction in cytokine level closer to the one measured in term newborn might be beneficial to prevent prematurity-related co-morbidities.…”

“…Regarding brain damage, intermittent or sustained systemic inflammation has been shown to contribute to brain damage in extremely preterm infants 3,4 . Elevated blood levels of inflammation-related proteins has been also shown to be associated with later brain volumes and cognition 5 and associated with an attention problem at age 24 months in extremely preterm infants 6 . Increased risk of BPD was associated with elevated blood concentrations of a variety of proinflammatory cytokines 9 .…”

Placental programming, perinatal inflammation, and neurodevelopment impairment among those born extremely preterm

“…48 In the ELGAN Study, elevated levels in neonatal blood of multiple inflammation biomarkers, most prominently IL-8, were associated with neonatal brain ultrasound indicators of white matter damage, 49 cognitive impairment, 50 cerebral palsy, 51 autism spectrum disorder, 52 and attention deficit hyperactivity disorder symptoms, 53 as well as decreased cortical and deep gray matter, cerebellar, and brainstem volumes as measured with magnetic resonance at 10 years of age. 54 A detailed description of the cellular and molecular events that could explain a causal relationship between perinatal inflammation and neurodevelopmental impairments is beyond the scope of this review, and the interested reader is referred to several excellent reviews of this topic. [55][56][57] Briefly, systemic inflammation disrupts the blood-brain barrier and allows movement of molecular inflammation mediators into the brain or by stimulating secretion from endothelial cells of inflammatory mediators into the brain parenchyma.…”