Lipopolysaccharide-Induced Chorioamnionitis Is Confined to One Amniotic Compartment in Twin Pregnant Sheep

Abstract

Background: Chorioamnionitis is a major risk factor for preterm birth in multifetal pregnancies. However, there is little clinical data whether chorioamnionitis is restricted to one amniotic compartment in multifetal pregnancies. Objective: To explore whether chorioamnionitis is confined to the exposed compartment and does not cross to the unaffected fetus in twin pregnancy. Methods: In twin pregnant sheep, one of the twins was exposed to either 2 or 14 days of intra-amniotic lipopolysaccharide (LPS) while the co-twin was exposed to either 2 or 14 days of intra-amniotic saline (n = 3 for each exposure). Singletons were included in this study to compare the grade of inflammation with twins. All fetuses were delivered at 125 days of gestation (term = 150 days). Chorioamnionitis was confirmed by histological examination. Lung inflammation was assessed by cell count in bronchoalveolar lavage. Lung compliance was assessed at 40 cm H₂O. Results were compared using analysis of variance (ANOVA) with a post-hoc Tukey analysis. Results: Inflammation in placenta, membranes and lung of LPS-exposed twins was significantly higher after 2 and 14 days of exposure when compared to the saline-exposed co-twins. Lung compliance in LPS-exposed twins was significantly increased after 14 days when compared to saline-exposed co-twins. Intrauterine LPS exposure increased lung compliance and inflammation in the membranes, placenta and lung to the same extent in twins as in singletons. Conclusion: In twin pregnant sheep, inflammation of the membranes, placenta and fetal lung was strictly limited to the exposed fetus in the amniotic compartment in which the LPS was injected.

Pulmonary Morbidity in Infancy after Exposure to Chorioamnionitis in Late Preterm Infants

“…In our final modeling for adjustments, sex, race, and gestational age were included as initial covariates. In a preterm sheep model of chorioamnionitis induced by intraamniotic injection of LPS in one of the twin amniotic sacs, fetal inflammation did not transfer from one twin to the other (24). However, to account for possible nonindependence of twins due to genetic factors (25) or possible maternal-fetal transfer of inflammation to the other twin when one of the twins had inflammation, all models with significant associations were reanalyzed adding twin as a random effect.…”

Fetal inflammation associated with minimal acute morbidity in moderate/late preterm infants

“…Statistical significance was accepted at p<0.05. Adjustment for twins was not performed since animal experiments demonstrate that fetal inflammation does not transfer from one twin to the other 34. Selected clinical outcomes were included in logistic regression models with fetal inflammation status as the main effect.…”

Intrauterine inflammation alters fetal cardiopulmonary and cerebral haemodynamics in sheep

“…Ewes were randomized to receive intraamniotic LPS (Escherichia coli 055:B5, 20 mg; Sigma Aldrich, NSW, Australia; n = 7) or saline (controls; 4 ml; n = 6) via the amniotic catheter. It has been demonstrated previously that in twin pregnant sheep the response to intra-amniotic LPS exposure is confined to the LPS-exposed fetus (Gantert et al 2012). Fetal blood gas measurements were taken at 2, 4, 8, 12 and 24 h, and then at daily intervals for 6 days after intra-amniotic LPS or saline.…”