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Hierarchical maturation of innate immune defences in very preterm neonates.

ABSTRACT: Preterm neonates are highly vulnerable to infection.To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on the maturation of neonatal microbial pathogen recognition responses.Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1?, IL-6, TNF-? and IL-12/23p40) to three prototypic Toll-like receptor (TLR) agonists, i.e. TLR4 (lipopolysaccharide), TLR5 (flagellin) and TLR7/8 (R848), and to the non-TLR retinoic acid-inducible gene I (RIG-I)-like receptor agonist, in cord blood mononuclear cells from neonates born before 33 weeks of gestation and at term.TLR responses develop asynchronously in preterm neonates, whereby responses to TLR7/8 were more mature and were followed by the development of TLR4 responses, which were also heterogeneous. Responses to TLR5 were weakest and most immature. Maturity in TLR responses was not influenced by sex. Overall, we detected no significant contribution of ANS and chorioamnionitis to the developmental attenuation of either TLR or RIG-I responses.The maturation of anti-microbial responses in neonates born early in gestation follows an asynchronous developmental hierarchy independently of an exposure to chorioamnionitis and ANS. Our data provide an immunological basis for the predominance of specific microbial infections in this age group.

SUBMITTER: Sharma AA

PROVIDER: S-EPMC4556450 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Hierarchical maturation of innate immune defences in very preterm neonates.

Sharma Ashish Arunkumar AA Jen Roger R Brant Rollin R Ladd Mihoko M Huang Qing Q Skoll Amanda A Senger Christof C Turvey Stuart E SE Marr Nico N Lavoie Pascal M PM

Neonatology 20140306 1

<h4>Background</h4>Preterm neonates are highly vulnerable to infection.<h4>Objectives</h4>To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on the maturation of neonatal microbial pathogen recognition responses.<h4>Methods</h4>Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1β, IL-6, TNF-α and IL-12/23p40) to three prototypic Toll-like receptor (TLR) agonists, i.e. TLR4 (lipopolysaccharide), TL ...[more]

PMID: 24603545

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Project description:ContextNo consensus exists regarding the association between maternal chorioamnionitis and neurodevelopmental outcomes in preterm and very preterm neonates.ObjectivesTo investigate whether maternal chorioamnionitis affects neurodevelopmental outcomes and to identify the factors that may explain these effects.Data sourcesWe used Ovid Medline, EMBASE and Web of Science to conduct a meta-analysis of studies published in English before August 25, 2017, with titles or abstracts that discussed an association between maternal chorioamnionitis and mental/motor development.Study selectionAmong the 603 initially identified studies, we selected those that addressed an association between maternal chorioamnionitis and mental/motor development according to our preselected inclusion criteria as follows: (1) the study compared infants with and without exposure to maternal chorioamnionitis and (2) the neurodevelopmental outcome was followed up using the Bayley Scales of Infant Development 2nd edition.Data synthesisOur meta-analysis included 10 studies. According to a random effect model, infants with maternal chorioamnionitis exposure had poorer mental development (d = -2.25 [95%CI, -4.33, -0.17], p<0.05) than infants without maternal chorioamnionitis, and infants with maternal clinical chorioamnionitis exposure had poorer motor development (d = -2.37 [95%CI, -4.62 to -0.12], p<0.05) than infants without maternal clinical chorioamnionitis exposure. Factors in the meta-analysis that showed differences between the two patient groups included an MDI assessment blinded to medical history, MDI assessment at the correct age, and time of the MDI assessment.ConclusionThis study suggests that maternal chorioamnionitis may affect mental development in preterm and very preterm neonates, and that maternal clinical chorioamnionitis may affect motor development in offspring. Further studies are required to confirm these results and to detect the influence of variables across studies.

Dataset Information

Hierarchical maturation of innate immune defences in very preterm neonates.

Publications

Hierarchical maturation of innate immune defences in very preterm neonates.

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