Preterm Birth, Infection, and Inflammation Advances From the Study of Animal Models

Abstract

Inflammation is a protective response mediated by both innate and adaptive arms of the immune system following exposure to a range of harmful stimuli. Although inflammation is an essential mechanism in response to challenges including tissue injury and microbiological insult, inappropriate or excessive induction of the inflammatory response is itself a well-characterized cause of morbidity and mortality in adult populations. There is currently a growing appreciation of the potential for inflammation to play an adverse role in fetal health. The expression of cytokines (notably interleukin 1beta [IL-1beta], IL-6, IL-8, and tumor necrosis factor alpha [TNF-alpha]) by either the fetal or maternal tissues has been demonstrated to upregulate the activity of a number of uterine and cervical factors (eg, prostaglandin hormones and their receptors, matrix metalloproteinases, vascular endothelial growth factor [VEGF]), leading to premature initiation of the parturition process. Herein, we review important developments in our understanding of the link between preterm birth and fetal inflammation subsequent to infection, gained from studies undertaken in animal models.

Influence of lactoferrin in preventing preterm delivery: A pilot study

“…Inflammatory cytokines are thought to play an important role in preterm delivery pathogenesis with infection occurring via the uterine cervix (17,18).…”

Maternal dietary omega-3 fatty acids and placental function

“…Pregnancy-related inflammation is proposed to play a key role in maternal tolerance of the semi-allogenic fetus (Paulesu et al 2010), and induce maternal insulin resistance thereby enhancing glucose passage to the developing fetus (Parsons et al 1992). Although pregnancy-related inflammation is considered adaptive, excessive placental inflammation is associated with a number of pregnancy disorders including preterm birth (Kemp et al 2010), PE ( …”

Inflammation of the Fetal Ovine Skin Following in utero Exposure to Ureaplasma parvum

“…10,[31][32][33] Ureaplasma species (notably U parvum and U urealyticum) are among the microorganisms most commonly identified in association with preterm birth. 16,[33][34][35] Due to the observation that a number of the microorganisms implicated in the etiology of preterm birth are fastidious with respect to nutrient and atmospheric culture conditions, there potentially exists a negative culture bias in the data relating to preterm birth and infection. 36 Indeed, there is growing evidence that the utilization of dual culture-PCR-based screening methodologies for amniotic infections-may provide a more accurate picture of infection status than culture alone.…”

“…10 A large body of experimental evidence now exists to support the association between in utero infection and preterm birth. [14][15][16] Utilizing a noninfectious ovine model of inflammation (induced by the intrauterine administration of lipopolysaccharides [LPS] from gram-negative Escherichia coli), we demonstrated previously that in utero exposure to bacterial agonist precipitates a robust, time-dependent, and modifiable inflammatory response. 6,17 This response is evident in fetal (lung, gut, brain, and chorioamnion) and maternal (placenta and decidua) tissues and involves elevated cytokine/chemokine expression, and neutrophil influx.…”