Executive Dysfunction Early Postnatal Biomarkers among Children Born Extremely Preterm

Leviton, Alan; Joseph, Robert M.; Fichorova, Raina N.; Allred, Elizabeth N.; Taylor, H. Gerry; Dammann, Olaf

doi:10.1007/s11481-018-9804-7

Cited by 18 publications

(12 citation statements)

References 50 publications

(55 reference statements)

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“…However, within the PT population, outcomes are highly variable (Anderson, Doyle, and Victorian Infant Collaborative Study, 2003; Bright et al, 2017). Many studies have documented that children who experience serious inflammatory complications during the neonatal period are at higher risk for poor cognitive outcomes than children spared these conditions (Mitha et al, 2013; Schlapbach et al, 2012; Stoll et al, 2004; Leviton et al, 2018). Adverse outcomes in PT children have been attributed, at least in part, to injury to the white matter of the brain (Back and Miller, 2014; Volpe et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

White matter microstructure and cognitive outcomes in relation to neonatal inflammation in 6-year-old children born preterm

Dubner

Dodson

Marchman

et al. 2019

NeuroImage: Clinical

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Background Cognitive outcomes in preterm (PT) children have been associated with microstructural properties of white matter. PT children who experienced neonatal inflammatory conditions have poorer cognitive outcomes than those who did not. The goal of this study was to contrast white matter microstructure and cognitive outcomes after preterm birth in relation to the presence or absence of severe inflammatory conditions in the neonatal period. Methods PT children ( n = 35), born at gestational age 22–32 weeks, were classified as either PT+ ( n = 12) based on a neonatal history of inflammatory conditions, including bronchopulmonary dysplasia, necrotizing enterocolitis or culture positive sepsis, or PT- ( n = 23) based on the absence of the three inflammatory conditions. Full term (FT) children ( n = 43) served as controls. Participants underwent diffusion MRI and cognitive testing (intelligence, reading, and executive function) at age 6 years. The corpus callosum was segmented into 7 regions using deterministic tractography and based on the cortical projection zones of the callosal fibers. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for each segment. General linear models with planned contrasts assessed group differences in FA, MD and cognitive outcomes. Pearson correlations assessed associations of white matter metrics and cognitive outcome measures. Results FA was significantly lower and MD was significantly higher in PT+ compared to PT- or FT groups in multiple callosal segments, even after adjusting for gestational age. Executive function scores, but not intelligence or reading scores, were less favorable in PT+ than in PT- groups. Among the entire sample, occipital FA was significantly correlated with IQ ( r = 0.25, p < 0.05), reading ( r = 0.32, p < 0.01), and executive function ( r = −0.28, p < 0.05) measures. Anterior frontal FA and superior parietal FA were significantly correlated with executive function ( r = −0.25, r = 0.23, respectively, p < 0.05). Conclusions We observed differences in the white matter microstructure of the corpus callosum and in the cognitive skills of 6-year-old PT children based on their history of neonatal inflammation. Neonatal inflammation is one medical factor that may contribute to variation in long-term neurobiological and neuropsychological outcomes in PT samples.

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Section: Introductionmentioning

confidence: 99%

White matter microstructure and cognitive outcomes in relation to neonatal inflammation in 6-year-old children born preterm

Dubner

Dodson

Marchman

et al. 2019

NeuroImage: Clinical

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“…Prematurity, placental dysfunction and fetal growth restriction have all been associated with reduced levels of BDNF (29,(35)(36)(37) which may have important implications for long-term brain health. Reduced BDNF in the neonatal period has been associated with increased risk of developing autism spectrum disorder (38) whilst elevated BDNF in the weeks after preterm birth is associated with better cognitive performance in childhood (39,40). C3 was identified as a novel postnatal marker of exposure to intrauterine inflammation.…”

Section: Discussionmentioning

confidence: 99%

Preterm Birth Is Associated With Immune Dysregulation Which Persists in Infants Exposed to Histologic Chorioamnionitis

et al. 2021

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IntroductionPreterm infants are at increased risk of exposure to histologic chorioamnionitis (HCA) when compared to term-born controls, and this is associated with several neonatal morbidities involving brain, lungs and gut. Preterm infants could benefit from immunomodulatory therapies in the perinatal period, but development of rational treatment strategies requires improved characterization of the perinatal response to HCA. We had two objectives: The first, to characterize the umbilical cord blood immune profile in preterm infants compared to term-born controls; the second, to investigate the postnatal immune response in preterm infants exposed to HCA versus those who were not.PopulationFor objective one 59 term infants [mean gestational age (GA) 39+4 (37+3 to 42+0)] and 55 preterm infants [mean GA29+0(23+3 to 32+0)] with umbilical cord samples available were included; for objective two we studied 96 preterm infants [mean GA29+1(23+2 to 32+0)] for whom placental histology and postnatal blood samples were available.MethodsPlacental histopathology was used to identify reaction patterns indicative of HCA, and a customized immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group.ResultsThe umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242x10-14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 8 immune proteins on postnatal day 5 (BDNF, C3, C5a, C9, IL-8, MCP-1, MIP-1β and MMP-9) when compared to preterm infants who were not exposed.ConclusionPreterm birth is associated with a distinct immune profile in umbilical cord blood and preterm infants exposed to HCA with evidence of a fetal inflammatory response have specific alterations in immune function that are apparent on day 5 of postnatal life.

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“…Prematurity, placental dysfunction and fetal growth restriction have all been associated with reduced levels of BDNF 29, 36-38 which may have important implications for long-term brain health. Reduced BDNF in the neonatal period has been associated with increased risk of developing ASD 39 whilst elevated BDNF in the weeks after preterm birth is associated with better cognitive performance in childhood 40, 41 .…”

Section: Discussionmentioning

confidence: 99%

Preterm birth is associated with immune dysregulation which persists in infants exposed to histologic chorioamnionitis: a descriptive study

Sullivan

Galdi

Borbye-Lorenzen

et al. 2021

Preprint

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ObjectiveTo characterise the umbilical cord blood immune profile in preterm infants compared to term-born controls and the postnatal immune response following exposure to histologic chorioamnionitis (HCA) in preterm infants.DesignDescriptive, observational cohort study.SettingEdinburgh, UK.Population118 preterm infants (mean gestational age 29+0 weeks, range 23+2 to 32+0) and 59 term-born controls.MethodsPlacental histopathology was used to identify reaction patterns indicative of HCA, and a customised immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group.ResultsThe umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242×10−14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 5 immune proteins on postnatal day 5 (BDNF, C3, IL-8, MIP-1β and MMP-9) when compared to preterm infants who were not exposed.ConclusionPreterm birth is associated with a distinct immune profile in umbilical cord blood and infants exposed to HCA experience specific alterations in immune function that persist to day 5 of postnatal life.

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Executive Dysfunction Early Postnatal Biomarkers among Children Born Extremely Preterm

Cited by 18 publications

References 50 publications

White matter microstructure and cognitive outcomes in relation to neonatal inflammation in 6-year-old children born preterm

White matter microstructure and cognitive outcomes in relation to neonatal inflammation in 6-year-old children born preterm

Preterm Birth Is Associated With Immune Dysregulation Which Persists in Infants Exposed to Histologic Chorioamnionitis

Preterm birth is associated with immune dysregulation which persists in infants exposed to histologic chorioamnionitis: a descriptive study

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