Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep

Kramer, Boris W.; Ladenburger, A; Kunzmann, Steffen; Speer, Christian P.; Been, Jasper V; Iwaarden, J. Freek van; Zimmermann, Luc J. I.; Gantert, Markus; Garnier, Yves

doi:10.1016/j.ajog.2008.09.009

Cited by 42 publications

(32 citation statements)

References 39 publications

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“…Persistent exposure to LPS did not only result in less elastin foci but also increased collagen deposition along the alveolar wall. These observations of dysregulated elastin and collagen deposition in the fetal lung are consistent with ventilation-induced (1, 9, 12) and inflammation-induced (25,27) animal models of BPD and histology reports of BPD patients (46,48). Although Shh signaling has been implicated in the activation of fibroblasts and production Fig.…”

Section: Lps Exposure Leads To Changes In Shh Signaling In the Fetal supporting

confidence: 80%

LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling in the ovine fetal lung

Collins

Kuypers

Nitsos

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chorioamnionitis and antenatal corticosteroids mature the fetal lung functionally but disrupt late-gestation lung development. Because Sonic Hedgehog (Shh) signaling is a major pathway directing lung development, we hypothesized that chorioamnionitis and antenatal corticosteroids modulated Shh signaling, resulting in an altered fetal lung structure. Time-mated ewes with singleton ovine fetuses received an intra-amniotic injection of lipopolysaccharide (LPS) and/or maternal intramuscular betamethasone 7 and/or 14 days before delivery at 120 days gestational age (GA) (term = 150 days GA). Intra-amniotic LPS exposure decreased Shh mRNA levels and Gli1 protein expression, which was counteracted by both betamethasone pre- or posttreatment. mRNA and protein levels of fibroblast growth factor 10 and bone morphogenetic protein 4, which are important mediators of lung development, increased 2-fold and 3.5-fold, respectively, 14 days after LPS exposure. Both 7-day and 14-day exposure to LPS changed the mRNA levels of elastin ( ELN) and collagen type I alpha 1 (Col1A1) and 2 (Col1A2), which resulted in fewer elastin foci and increased collagen type I deposition in the alveolar septa. Corticosteroid posttreatment prevented the decrease in ELN mRNA and increased elastin foci and decreased collagen type I deposition in the fetal lung. In conclusion, fetal lung exposure to LPS was accompanied by changes in key modulators of lung development resulting in abnormal lung structure. Betamethasone treatment partially prevented the changes in developmental processes and lung structure. This study provides new insights into clinically relevant prenatal exposures and fetal lung development.

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Section: Lps Exposure Leads To Changes In Shh Signaling In the Fetal supporting

confidence: 80%

LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling in the ovine fetal lung

Collins

Kuypers

Nitsos

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Some studies have reported an increased risk of BPD among infants exposed to chorioamnionitis, but many others have reported little or no difference. A maturational effect of prenatal inflammation may be accompanied by structural changes in the lungs [12,13], and an alteration in the response to exogenous surfactant has also been suggested as a possible cause of prolonged mechanical ventilation in patients with histological evidence of fetal inflammatory response syndrome [14,15]. …”

Section: Discussionmentioning

confidence: 99%

Outcomes of Very-Low-Birth-Weight Infants Exposed to Maternal Clinical Chorioamnionitis: A Multicentre Study

Rodrigo

Henríquez²,

Aloy³

et al. 2014

Neonatology

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Background: Chorioamnionitis is a recognized risk factor of preterm delivery; however, controversy still persists concerning the relationship between maternal inflammation and neonatal morbidity and mortality. Objective: To determine the incidence of clinical chorioamnionitis and its relationship to morbidity and mortality among very-low-birth-weight (VLBW) infants. Methods: This was a retrospective analysis of prospectively collected data of VLBW neonates ≤32 weeks' gestational age (GA) admitted to collaborating units in the Spanish SEN1500 Network between January 2008 and December 2011. Clinical chorioamnionitis was defined by obstetricians based on clinical findings, and neonatal outcomes were compared between exposed and non-exposed infants by multivariate logistic regression analysis. Results: During the study period, 11,464 VLBW newborns were admitted to our units and 10,026 were ≤32 weeks' GA. Among them, 8,330 (83.1%) had complete data and were included. Of these, 1,480 (17.8%) were exposed to maternal clinical chorioamnionitis. The incidence was higher at lower GA and, after adjusting for confounding factors, exposed infants had higher risks of early-onset neonatal sepsis (EONS) (10.0 vs. 2.8%; aOR 3.102; 95% CI 2.306-4.173; p < 0.001) and necrotizing enterocolitis (NEC) (11.2 vs. 7.7%; aOR 1.300; 95% CI 1.021-1.655; p < 0.033), but lower risks of patent ductus arteriosus (PDA) (43.2 vs. 34.9%; aOR 0.831; 95% CI 0.711-0.971; p < 0.02) and late-onset bacterial sepsis (LONS) (36.6 vs. 32.5%; aOR 0.849; 95% CI 0.729-0.989; p < 0.035). There were no differences in mortality between the groups. Conclusions: The incidence of maternal clinical chorioamnionitis is inversely related to GA at delivery, and in VLBW infants ≤32 weeks' GA it is associated with higher risks of EONS and NEC, but lower risks of PDA and LONS. We did not found differences in survival.

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“…91 All these studies support the hypothesis that HCA could stimulate lung maturation, reducing the incidence of acute RDS but, at the same time, increasing the lung susceptibility to postnatal damage, which finally leads to BPD. The maturational effect of prenatal inflammation may be accompanied not only by structural changes in the lungs, 92 but also by an alteration in the response to exogenous surfactant and the need of prolonged mechanical ventilation. 93 Nevertheless, it is important to remember that prematurity itself is characterized by lungs with a smaller number of alveoli, a slow microvascular development, and thickening of the arteriolar walls.…”

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confidence: 99%

Chorioamnionitis and neonatal morbidity: current perspectives

Henríquez¹,

Rodrigo²

2017

RRN

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Abstract:The term chorioamnionitis (CA) is commonly used to refer to different clinical or pathological conditions characterized by an infectious and/or inflammatory process that affects primarily the chorioamniotic membranes, but also the amniotic fluid, vessels of the chorionic plate, and, eventually, the umbilical cord (funisitis) and the fetus. Its incidence is higher at lower gestational ages, and the main mechanism is believed to be the ascending bacterial infection from the maternal genital tract. It can be diagnosed by clinical criteria, amniotic fluid examination for inflammatory mediators, and/or isolation of microorganisms, or by histopathological examination of the placenta. CA is an important cause of stillbirth and is related to an increased incidence of premature rupture of membranes, preterm delivery, and adverse maternal and neonatal outcomes such as early-onset neonatal sepsis and necrotizing enterocolitis. An independent causal association to other neonatal morbidities is more controversial. The heterogeneity in the diagnostic criteria and in the operative definitions for morbidity makes comparison of studies difficult, and results are inconsistent. In addition, the intensity and duration of the process are usually not considered. For all these reasons, evidence-based recommendations for the management of mother and infant under these circumstances are difficult to establish, and clinical practice varies widely.

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Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep

Cited by 42 publications

References 39 publications

LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling in the ovine fetal lung

LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling in the ovine fetal lung

Outcomes of Very-Low-Birth-Weight Infants Exposed to Maternal Clinical Chorioamnionitis: A Multicentre Study

Chorioamnionitis and neonatal morbidity: current perspectives

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