Sterile inflammation and pregnancy complications: a review (original) (raw)
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Nutrition Reviews, 2007
Fetal development and growth occur in a sterile amniotic cavity while first exposure to microorganisms happens at birth. However, at least 25% of all preterm births, the leading cause of perinatal morbidity and mortality worldwide, occur in mothers with microbial invasion of the amniotic cavity. Microbial attack of the fetus takes place in approximately 10% of pregnancies with intra-amniotic infection, and the human fetus is capable of deploying an inflammatory response (cellular and humoral) in the mid-trimester of pregnancy. The onset of premature labor in the context of infection is mediated by pro-inflammatory cytokines, such as interleukin (IL)-1 and tumor necrosis factor alpha (TNF-␣), as these cytokines are produced by intrauterine tissues in response to microbial products, can stimulate prostaglandin production, and induce labor in animals. Moreover, knockout experiments suggest that infection is less likely to lead to premature labor when the IL-1 and TNF signaling pathways are disrupted. A fetal inflammatory systemic response occurs in a fraction of fetuses exposed to microorganisms in utero, and is associated with the impending onset of labor as well as multisystem organ involvement. Neonates born with funisitis, the histologic marker of such inflammation, are at increased risk for neurologic handicap and cerebral palsy. Evidence has begun to accumulate that geneenvironment interactions determine the likelihood of preterm labor and delivery and, probably, the risk of fetal injury. Fetal inflammation has emerged as a major mechanism of disease responsible for complications in the perinatal period (in utero and in the first 28 days of life), as well as in infancy. Moreover, reprogramming of the fetal immune response may predispose to diseases in adulthood.
Reproductive Sciences, 2009
Inflammation is a process by which tissues respond to various insults. It is characterized by upregulation of chemokines, cytokines, and pattern recognition receptors that sense microbes and tissue breakdown products. During pregnancy, the balance of Th1 (cell-mediated immunity) and Th2 (humoral immunity) cytokines is characterized by an initial prevalence of Th2 cytokines, followed by a progressive shift toward Th1 predominance late in gestation, that when is abnormal, may initiate and intensify the cascade of inflammatory cytokine production involved in adverse pregnancy outcomes. Maternal and placental hormones may affect the inflammatory pathway. Hypoxia and the innate immune response are 2 adaptive mechanisms by which organisms respond to perturbation in organ function, playing a major role in spontaneous abortion, intrauterine growth restriction, preeclampsia, and preterm delivery. The interaction between tissue remodeling factors, like matrix metalloproteinases, and vasoactive/hemostatic factors, like prostaglandin and coagulation factors, mediates this adaptive response.
Specific inflammatory profile in each pregnancy complication: A comparative study
American Journal of Reproductive Immunology, 2020
Problem: Preeclampsia (PE), preterm birth (PTB) and intra-uterine growth restriction (IUGR) affect 5-12% of pregnancies. They have been associated with placental inflammation, although the detection of inflammatory mediators in the maternal circulation is still controversial. Our goal was to determine the inflammatory changes occurring in the second part of pregnancy to identify profiles distinguishing pathological pregnancies from each other.
Investigation of systemic inflammatory response in first trimester pregnancy failure
Human reproduction (Oxford, England), 2012
background: The contribution of local and systemic inflammation to the pathophysiology of sporadic first trimester miscarriages remains unclear. The objective of this study was to investigate the inflammatory response in the circulation of women presenting with first trimester miscarriage. methods: Levels of tumour necrosis factor alpha (TNFa), TNF receptors 1 and 2, interferon gamma (IFNg), interleukin (IL)-6 and IL-10 were assayed using cytometric bead arrays in plasma samples from 29 euploid and 21 aneuploid missed miscarriages, 35 normal pregnant controls and 31 non-pregnant women (NPW). Whole blood flow cytometry was carried out with samples from 17 euploid and 16 aneuploid miscarriages, 18 pregnant controls and 13 NPW.
Involvement of inflammation in normal pregnancy
Acta Obstetricia et Gynecologica Scandinavica, 2013
To study the role of inflammation throughout normal pregnancy and postpartum, 37 women with normal pregnancies, including normal neonatal outcome, participated. Blood and urine samples were collected from each woman at least six times during pregnancy and postpartum. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) and urinary levels of a prostaglandin-F 2a (PGF 2a ) metabolite were measured. Median, 25th to 75th centile and average change per gestational week of IL-6, TNF-a and the PGF 2a metabolite were measured. Levels of IL-6 increased significantly throughout pregnancy and remained high postpartum. No change in TNF-a could be seen. The PGF 2a metabolite levels increased significantly throughout pregnancy and decreased postpartum. These results suggest that mild but significant inflammatory activity is involved in the development of normal pregnancy, which might have important physiological roles.
A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition
American Journal of Obstetrics and Gynecology, 1998
OBJECTIVE: There is no evidence for the participation of the human fetus in the mechanisms responsible for the onset of preterm labor. We propose that preterm labor in the setting of infection results from the actions of proinflammatory cytokines secreted as part of the fetal and/or maternal host response to microbial invasion. The objective of this study was to determine whether a systemic fetal inflammatory response, defined as an elevation of fetal plasma interleukin-6 concentrations, has a temporal relationship with the commencement of labor.STUDY DESIGN: After informed consent was obtained, amniocentesis and cordocentesis were performed in 41 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for both aerobic and anaerobic bacteria, as well as for mycoplasmas. Fetal plasma interleukin-6 was assayed by a sensitive and specific immunoassay. Statistical analyses included contingency tables and survival analysis with time-dependent Cox regression hazard modeling.RESULTS: Microbial invasion of the amniotic cavity was present in 58.5% (24/41) of patients. Fetuses with fetal plasma interleukin-6 concentrations >11 pg/mL had a higher rate of spontaneous preterm delivery within 48 and 72 hours of the procedure than those with fetal plasma interleukin-6 levels ≤11 pg/mL (88% vs 29% and 88% vs 35%, respectively; P < .05 for all comparisons). Moreover, patients with initiation of labor and delivery within 48 hours of the procedure had a higher proportion of fetuses with plasma interleukin-6 values >11 pg/mL than patients delivered >48 hours (58% [7/12] vs 8% [1/13], respectively; P < .05). Survival analysis indicated that fetuses with elevated fetal plasma interleukin-6 levels had a shorter cordocentesis-to-delivery interval than those without elevated fetal plasma interleukin-6 concentrations (median 0.8 days [range 0.1 to 5] vs median 6 days [range 0.2 to 33.6], respectively; P < .05). Time-dependent Cox regression hazard modeling indicated that fetal plasma interleukin-6 level was the only covariate significantly associated with the duration of pregnancy after we adjusted for gestational age, amniotic fluid interleukin-6 level, and the microbiologic state of the amniotic cavity (P < .01).CONCLUSION: A systemic fetal proinflammatory cytokine response is followed by the onset of spontaneous preterm parturition in patients with preterm premature rupture of membranes. (Am J Obstet Gynecol 1998;179:186-93.)
Neutrophil-Derived Inflammation and Pregnancy Outcomes
NEWPORT INTERNATIONAL JOURNAL OF SCIENTIFIC AND EXPERIMENTAL SCIENCES, 2023
Inflammation, orchestrated by immune cells like neutrophils, plays a crucial role in maintaining homeostasis and protecting against pathogens. However, during pregnancy, the delicate balance of immune responses is paramount to support fetal development while safeguarding maternal health. Neutrophils, as pivotal contributors to the innate immune system, significantly influence the inflammatory milieu, yet excessive or dysregulated neutrophil-derived inflammation can impact pregnancy outcomes. This paper aims to dissect the multifaceted role of neutrophil-derived inflammation in shaping pregnancy outcomes. It delves into the mechanisms by which neutrophils orchestrate inflammatory responses during gestation and scrutinizes the implications of heightened inflammation on maternalfetal health. Specifically, it explores the association between increased neutrophil-driven inflammation and adverse outcomes such as preterm birth, preeclampsia, intrauterine growth restriction, and fetal developmental abnormalities. Examining the intricate balance between protective and detrimental roles of neutrophil-derived inflammation, this review assesses alterations in neutrophil functions, activation pathways, and the release of inflammatory mediators during normal and pathological pregnancies. Additionally, it evaluates potential regulatory mechanisms governing neutrophil-derived inflammation and identifies putative biomarkers indicative of heightened inflammatory responses linked to adverse pregnancy outcomes. The clinical implications of understanding the impact of neutrophil-derived inflammation on pregnancy outcomes are highlighted, emphasizing its significance in obstetric care, prenatal monitoring, and potential therapeutic interventions. Furthermore, this review delineates the