Early Inflammatory Measures and Neurodevelopmental Outcomes in Preterm Infants (original) (raw)
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Carolina Digital Repository (University of North Carolina at Chapel Hill), 2017
Background-Preterm newborns exposed to intrauterine inflammation are at increased risk of neurodevelopmental disorders. We hypothesized that adverse outcomes are more strongly associated with a combination of antenatal and postnatal inflammation than with either of them alone. Methods-We defined antenatal inflammation as histologic inflammation in the placenta. We measured the concentrations of seven inflammation-related proteins in blood obtained on postnatal days 1, 7, and 14 from 763 infants born before 28 weeks of gestation. We defined postnatal inflammation as a protein concentration in the highest quartile on at least 2 days. We used logistic regression models to evaluate the contribution of antenatal and postnatal inflammation to the risk of neurodevelopmental disorders. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Inflammation at Birth is Associated With Subnormal Development in Very Preterm Infants
Pediatric Research, 2008
Preterm birth carries a risk for impaired developmental outcome. We have previously described an association between increased levels of proinflammatory cytokines during the first 72 postnatal hours and cerebral damage as detected by ultrasound in a cohort of 74 very preterm infants. Sixty-seven of 71 surviving children with a mean gestational age of 27.1 (2.0) wk were examined at 2 y corrected age with a standardized neurologic examination and with Bayley Scales of Infant Development. We hypothesized that proinflammatory cytokine concentrations at or shortly after birth would be associated with an adverse developmental outcome. Increased concentrations of TNF-␣ in cord blood odds ratio (95% confidence interval) 3.3 (1.1-10.2), p ϭ 0.013 and at 6 h 7.8 (0.9 -71.8), p ϭ 0.015 and of IL-6 in cord blood 1.7 (1.0 -2.9), p ϭ 0.048 were associated with psychomotor developmental index Ͻ85. Increased concentrations of TNF-␣ in cord blood odds ratio (95% confidence interval) 3.6 (1.002-12.8), p ϭ 0.044 and of IL-8 in cord blood 3.5 (1.2-10.6), p ϭ 0.023 were associated with cerebral palsy. Associations of TNF-␣ and IL-8 in cord blood with the respective outcome measures remained significant after adjustment for other clinical variables. Proinflammation at birth is associated with impaired functional outcome at 2 y of corrected age in children with very preterm birth.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2017
To provide a systematic review investigating the role of inflammatory molecules and neurotrophic factors as biomarkers of neuropsychomotor development in preterm neonates. Databases including PubMed, BIREME, and Scopus were systematically searched. Observational studies, as well as transversal, and cohort studies using human subjects published from 1990 to September 2017 were eligible for inclusion. Two authors independently identified eligible studies and analyzed their characteristics, quality, and accuracy in depth. 11 eligible studies clearly investigated the association between peripheral inflammation and motor and/or cognitive development in preterm infants. However, the selected populations differed in relation to the events associated with prematurity and the risk factors to abnormal motor and/or cognitive development. These studies measured circulating levels of cytokines, chemokines, adhesion molecules, acute phase proteins, and growth factors. The most commonly analyzed p...
Early Human Development, 2011
Controversy exists regarding association of high levels of proinflammatory cytokines, neonatal morbidities and poor neurodevelopment outcome in very low birth weight infants. To determine association between severity of early inflammatory response and neurodevelopment outcome in high risk very low birth weight infants. Sixty-two very preterm infants with high risk for early-onset sepsis were followed up to 24 months corrected age. Blood sample was collected for IL-6, IL-8, IL-10, IL-1β, and TNF-α analysis. Neurodevelopment outcome by Bayley Scales of Infant Development II was assessed at 22 to 24 months. Magnetic Resonance Image was performed at least once during the first 12 months. In 24 (38.7%) MDI was <85, and 16 (25.8%) had PDI<85. Low birth weight was significantly associated with low MDI, and birth weight and periventricular leukomalacia were significantly associated with low PDI by multiple regression analysis. After controlling for birth weight and gestational age, none of the studied variables was associated with low MDI, and only periventricular leukomalacia with low PDI. Each additional 100g in the birth weight reduced the probability of low MDI and PDI scores in 14%. There was no association of high cytokines plasma levels with poor neurodevelopment outcome at 22 to 24 months' corrected age, suggesting that elevations of plasma proinflammatory cytokines early in life do not play an important role in pathophysiology of brain injury in high risk preterm infants.
Brain Behavior and Immunity, 2013
Neonatal inflammation is associated with perinatal brain damage. We evaluated to what extent elevated blood levels of inflammation-related proteins supplement information about the risk of impaired early cognitive function provided by inflammation-related illnesses. From 800 infants born before the 28 th week of gestation, we collected blood spots on days 1, 7 and 14, for analysis of 25 inflammation-related proteins, and data about culture-positive bacteremia, necrotizing enterocolitis (Bell stage IIIb), and isolated perforation of the intestine, during the first two weeks, and whether they were ventilated on postnatal day 14. We considered a protein to be persistently or recurrently elevated if its concentration was in the top quartile (for gestational age and day blood was collected) on two separate days one week apart. We assessed the children at 2 years of age with the Bayley Mental Development Index (MDI). The combinations of NEC and ventilation on day 14, and of bacteremia and ventilation on day 14 consistently provided information about elevated risk of MDI <55, regardless of whether or not a variable for an elevated protein concentration was included in the model. A variable for a persistently or recurrently elevated
American Journal of Obstetrics and Gynecology, 2008
OBJECTIVE-To determine the association between in utero exposure to acute inflammation and long-term major neurodevelopmental disability at age 6 years among children born prior to 32 weeks' gestation. STUDY DESIGN-This was a follow-up investigation of a cohort of maternal-infant dyads delivered between 23 and <32 weeks' gestation. Surviving infants (and their mothers or caregivers) underwent a battery of psychological and neurodevelopmental tests between 5 and 8 years of age. Pregnancy and neonatal data were analyzed among children with versus those without major neurodevelopmental disability (including IQ <70 [n=41], cerebral palsy [CP, n=11] and a composite major disability [n=52]).
PLOS ONE, 2019
The main objective of this study was to evaluate the relationship between mother's socioeconomic disadvantage and blood concentrations of inflammation-related proteins among extremely preterm newborns (<28 weeks gestation), a group at heightened risk of cognitive impairment when exposed to systemic inflammation. We measured the concentrations of 27 inflammatory and neurotrophic proteins in blood specimens collected a week apart during the first postnatal month from 857 extremely preterm newborns in the United States. We classified children according to 3 indicators/correlates of socioeconomic disadvantage, mother's eligibility for government-provided medical care insurance (Medicaid), mother's formal education level, and mother's IQ approximated with the Kaufman Brief Intelligence Test-2. The risks of a top-quartile concentration of each protein on each of 5 days a week apart, on two occasions during the first two postnatal weeks, and during the next two weeks were modeled as functions of each indicator of socioeconomic disadvantage. The risks of top quartile concentrations of multiple (2-5) inflammation-related proteins on multiple days during the first two weeks were increased for each of the 3 indicators of socioeconomic disadvantage, while the risks of top quartile concentrations of selected neurotrophic proteins were reduced. Adjustment for socioeconomic disadvantage did not alter the relationships between protein concentrations and both low IQ and low working memory 10 years later. Among extremely preterm newborns, indicators of socioeconomic disadvantage are associated with modestly increased risk of systemic inflammation in postnatal blood during the first postnatal month and with a slightly reduced risk of a neurotrophic signal, but do not confound relationships between protein concentrations and outcomes.
Pediatric research, 2014
Extremely preterm birth is associated with subsequent behavioral problems. We hypothesized that perinatal systemic inflammation, a risk factor for cerebral white matter injury and cognitive impairment, is associated with behavior problems observed at 2 y. In a cohort of 600 children born before 28 wk gestation, we measured 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14, and identified behavior problems using parent responses to the Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5) at 2 y of age. A persistent or recurrent protein elevation was defined as a concentration in the highest quartile (for gestational age and postnatal age) on at least 2 d ~1 wk apart. Behavior problems were defined by CBCL/1.5-5 subscale scores at or above the 93 rd percentile. A single-day elevation of intercellular adhesion molecule-3 was associated with an increased risk of an attention problem, as were persistent or recurrent elevations of myeloperoxidase, interleu...