Dataset Information

Histological chorioamnionitis shapes the neonatal transcriptomic immune response.

ABSTRACT: Histologic chorioamnionitis (HCA) is commonly associated with preterm birth and deleterious post-natal outcomes including sepsis and necrotizing enterocolitis. Transcriptomic analysis has been used to uncover gene signatures that permit diagnosis and prognostication, show new therapeutic targets, and reveal mechanisms that underlie differential outcomes with other complex disease states in neonates such as sepsis.To define the transcriptomic and inflammatory protein response in peripheral blood among infants with exposure to histologic chorioamnionitis.Prospective, observational study.Uninfected preterm neonates retrospectively categorized based on placental pathology with no HCA exposure (n=18) or HCA exposure (n=15).We measured the transcriptomic and inflammatory mediator response in prospectively collected whole blood.We found 488 significant (p<0.001), differentially expressed genes in whole blood samples among uninfected neonates with HCA exposure that collectively represented activated innate and adaptive immune cellular pathways and revealed a potential regulatory role for the pleotropic microRNA molecule miR-155. Differentially secreted plasma cytokines in patients with HCA exposure compared to patients without HCA included MCP-1, MPO, and MMP-9 (p<0.05).Exposure to HCA distinctively activates the neonatal immune system in utero with potentially long-term health consequences.

SUBMITTER: Weitkamp JH

PROVIDER: S-EPMC4947555 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Histological chorioamnionitis shapes the neonatal transcriptomic immune response.

Weitkamp Jörn-Hendrik JH Guthrie Scott O SO Wong Hector R HR Moldawer Lyle L LL Baker Henry V HV Wynn James L JL

Early human development 20160616

<h4>Background</h4>Histologic chorioamnionitis (HCA) is commonly associated with preterm birth and deleterious post-natal outcomes including sepsis and necrotizing enterocolitis. Transcriptomic analysis has been used to uncover gene signatures that permit diagnosis and prognostication, show new therapeutic targets, and reveal mechanisms that underlie differential outcomes with other complex disease states in neonates such as sepsis.<h4>Aims</h4>To define the transcriptomic and inflammatory prote ...[more]

PMID: 27318328

Similar Datasets

Project description:Background: Elevated intrapartum temperature has been widely proven to be associated with adverse clinical outcomes in both mothers and neonates. Histological chorioamnionitis (HCA), the inflammation of chorion and amniotic membranes, is commonly observed in those with elevated intrapartum temperature. Thus, we aimed to explore whether the combination of HCA would further affect the pregnancy outcomes in those with intrapartum temperature ≥ 37.5°C. Methods: This retrospective cohort study was conducted at the International Peace Maternity and Child Health Hospital (IPMCH), including all full-term women with intrapartum temperature ≥ 37.5°C from Jan 2017 to Jan 2019. Patients were divided in to HCA group or control group according to placental pathology results, and we used 1:1 propensity score matching (PSM) to reduce the effects of potential confounding factors between the two groups. Univariate and multivariable logistic regression were used to identify the association between HCA and different adverse maternal and neonatal outcomes. Results: We formed a propensity-score matched cohort containing 464 women in each group. Higher positive rate of mycoplasma (14.01% vs. 7.33%, p = 0.001) was found in the vaginal secretion culture of women in the HCA group. After adjusting for various baseline clinical characteristics, women with HCA were more likely to end their delivery by cesarean section (AOR = 1.55, 95% CI: 1.05-2.28), and puerperal morbidity (AOR = 2.77, 95% CI: 1.44-5.33) as well as prolonged hospitalization (AOR = 1.56, 95% CI: 1.12-2.17) were more likely to be observed in the HCA group. The existence of HCA might also be associated with neonatal sepsis (AOR = 2.83, 95% CI: 1.14-7.04) and NICU admission (AOR = 1.40, 95% CI: 1.04-1.87) in newborns. In the study on the impact of different stages of HCA, we found that both maternal and neonatal outcomes would not be affected by mild HCA (stage I), while HCA of stage III was associated with increased need for neonatal respiratory support and elevated likelihood of prolonged hospitalization in neonates. Conclusions: Elevated intrapartum temperature complicated by HCA might be related to the elevated occurrence of several adverse maternal and neonatal outcomes, except those with HCA of stage I. Advanced HCA stage correlated with a worse prognosis.

Project description:Chorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA.Gestational age-, birth weight-, delivery mode- and sex- matched (1:2) preterm neonates (< 35 weeks' gestation) born to mothers with or without HCA were enrolled from an observational study. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic analysis was performed on urine samples non-invasively collected in the first 24 hours of life. Univariate analysis, partial least square discriminant analysis (PLS-DA) and its associated variable importance in projection (VIP) score were performed. The most affected metabolic pathways were examined by Metabolite Sets Enrichment Analysis (MSEA).Fifteen cases (mean GA 30.2 ± 3.8 weeks, mean BW 1415 ± 471.9 grams) and 30 controls (mean GA 30.2 ± 2.9 weeks, mean BW 1426 ± 569.8 grams) were enrolled. Following univariate analysis, 29 metabolites had a significantly different concentration between cases and controls. The supervised PLS-DA model confirmed a separation between the two groups. Only gluconic acid, an oxidation product of glucose, was higher in cases than in controls. All other VIP metabolites were more abundant in the control group. Glutamate metabolism, mitochondrial electron transport chain, citric acid cycle, galactose metabolism, and fructose and mannose degradation metabolism were the most significantly altered pathways (P < 0.01).For the first time, urinary metabolomics was able to discriminate neonates born to mothers with and without HCA. The identification of specifically altered metabolic pathways may be helpful in understanding metabolic derangement following chorioamnionitis.

Project description:OBJECTIVES:No information exists about whether fetal inflammatory-response(FIR), early-onset neonatal sepsis(EONS) and chorioamnionitis(an advanced-stage of maternal inflammatory-response in extraplacental membranes) continuously increase according to the progression of inflammation in umbilical-cord(UC). The objective of current-study is to examine this-issue. METHODS:Study-population included 239singleton pregnant-women(gestational-age[GA] at delivery: 21.6~36weeks) who had inflammation in extraplacental membranes or chorionic plate (CP) and either preterm-labor or preterm-PROM. We examined FIR, and the frequency of fetal inflammatory-responses syndrome(FIRS), proven-EONS, suspected-EONS and chorioamnionitis according to the progression of inflammation in UC. The progression of inflammation in UC was divided with a slight-modification from previously reported-criteria as follows: stage0, inflammation-free UC; stage-1: umbilical phlebitis only; stage-2: involvement of at least one UA and either the other UA or UV without extension into WJ; stage-3: the extension of inflammation into WJ. FIR was gauged by umbilical-cord-plasma(UCP) CRP concentration(ng/ml) at birth, and FIRS was defined as an elevated UCP CRP concentration at birth(?200ng/ml). RESULTS:Stage-0, stage-1, stage-2 and stage-3 of inflammation in UC were present in 48.1%, 15.5%, 6.7%, and 29.7% of cases. FIR continuously increased according to the progression of inflammation in UC(Kruskal-Wallis test,P<0.001; Spearman-rank-correlation test,P<0.000001,r = 0.546). Moreover, there was a significant and stepwise increase in the frequency of FIRS, proven-EONS, suspected-EONS and chorioamnionitis according to the progression of inflammation in UC(each for P<0.000005 in both chi-square test and linear-by-linear-association). Multiple logistic-regression analysis demonstrated that the more advanced-stage in the progression of inflammation in UC(i.e., stage-1 vs. stage-2 vs. stage-3), the better predictor of suspected-EONS (Odds-ratio[OR]3.358, 95%confidence-interval[CI]:1.020-11.057 vs. OR5.147, 95%CI:1.189-22.275 vs. OR11.040, 95%CI:4.118-29.592) and chorioamnionitis(OR6.593, 95%CI:2.717-15.999 vs. OR16.508, 95%CI:3.916-69.596 vs. OR20.167, 95%CI:8.629-47.137). CONCLUSION:FIR, EONS and chorioamnionitis continuously increase according to the progression of inflammation in UC among preterm-gestations with inflammation in extraplacental membranes or CP. This finding may suggest that funisitis(inflammation in UC) is both qualitatively and quantitatively histologic-counterpart of FIRS, and a surrogate-marker for chorioamnionitis.

Dataset Information

Histological chorioamnionitis shapes the neonatal transcriptomic immune response.

Publications

Histological chorioamnionitis shapes the neonatal transcriptomic immune response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets