Inflammation in preterm and term labour and delivery

European cytokine network, 2007

Our aim was to compare maternal serum concentrations of interleukin(IL)-1alpha IL-1beta, IL-6 and IL-8 in pregnancies complicated by preterm labor (PTL), with the levels in healthy controls at comparable gestational age, and to determine if these assays have any value in the prediction of early-onset neonatal infection or histological chorioamnionitis. The study population consisted of 65 women with new-onset PTL, and 31 healthy controls. Maternal serum concentrations of IL-6 (8.40 versus 3.30 pg/mL; p = 0.002) and IL-1beta (2.20 versus 0.50 pg/mL; p = 0.003) were significantly higher in patients with PTL as compared to healthy pregnant women. The IL-1beta concentration (13.60 versus 1.20 pg/mL; p = 0.02) was significantly higher in the serum of mothers whose babies developed early-onset infections, than in mothers of newborns that were healthy. However, its predictive value, and the value of the other cytokines studied, was poor. In addition, IL-1beta levels (28.79 versus 5.19 pg/m...

American Journal of Reproductive Immunology, 2003

Journal of Reproductive Immunology, 2016

Preterm birth (PTB) is the leading cause of childhood mortality in children under 5 and accounts for approximately 11% of births worldwide. Premature babies are at risk of a number of health complications, notably cerebral palsy, but also respiratory and gastrointestinal disorders. Preterm deliveries can be medically indicated/elective procedures or they can occur spontaneously. Spontaneous PTB is commonly associated with intrauterine infection/inflammation. The presence of inflammatory mediators in utero has been associated with fetal injury, particularly affecting the fetal lungs and brain. This review will outline (i) the role of inflammation in term and PTB, (ii) the effect infection/inflammation has on fetal development and (iii) recent strategies to target PTB. Further research is urgently required to develop effective methods for the prevention and treatment of PTB and above all, to reduce fetal injury.

Cytokine, 2001

To establish levels of mediators of inflammation in cord blood and postnatal serum from extremely low gestational age newborns (ELGANs, c28 weeks), we measured sixteen markers of inflammation by recycling immunoaffinity chromatography in 15 ELGANs who had serum sampled at days 2-5. Median levels of IL-1, IL-6, IL-8, IL-11, IL-13, TNF-, G-CSF, M-CSF, GM-CSF, MIP-1 , and RANTES were considerably higher than published values of these inflammatory mediators from term newborns. In three of eight ELGANS who had serial measurements taken, levels of IL-1, IL-6, IL-8, IL-11, TNF-, G-CSF, and MIP-1 declined from initially very high levels to reach an apparent baseline towards the end of the first postnatal week. In these same three infants, GM-CSF and TGF-1 levels increased continuously during the first week. In the other five ELGANs, no consistent changes were observed. We speculate, that in some ELGANs, a fetal systemic inflammatory response is characterized by an antenatal wave of pro-inflammatory cytokines, followed by a second, postnatal wave of anti-inflammatory cytokines. Large epidemiologic studies are needed to clarify relationships among inflammation markers and their expression in the fetal and neonatal circulation over time. Such studies would also add to our understanding of the possible role of inflammatory mediators in the pathophysiology of the major complications of extreme prematurity.

Journal of Leukocyte Biology, 2015

Preterm birth is the leading cause of neonatal morbidity and mortality. Although the underlying causes of pregnancy-associated complication are numerous, it is well established that infection and inflammation represent a highly significant risk factor in preterm birth. However, despite the clinical and public health significance, infectious agents, molecular trigger(s), and immune pathways underlying the pathogenesis of preterm birth remain underdefined and represent a major gap in knowledge. Here, we provide an overview of recent clinical and animal model data focused on the interplay between infection-driven inflammation and induction of preterm birth. Furthermore, here, we highlight the critical gaps in knowledge that warrant future investigations into the interplay between immune responses and induction of preterm birth.

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2009

Premature rupture of membranes (PROM) is a normal event during labor that occurs prior to labor onset. When it occurs before 37 weeks of gestation, it is referred to as preterm premature rupture of membranes (PPROM) [1]. Multiple epidemiological and clinical factors have been associated with PPROM. These include race, smoking, sexually transmitted diseases [2,3], maternal vitamin C deficiency [4], obstetric complications [1,2,5], maternal lower genital tract infection [6], and infection and inflammation of the amniochorion which play primary or secondary roles in PPROM pathogenesis [7,8]. Intra-amniotic infection activates a host inflammatory response characterized by cytokine production. Interleukin (IL)-1b, IL-6, IL-8 and tumor necrosis factor-a (TNF-a) have been shown to be present in high concentrations in the amniotic fluid [9,10], the chorion, and fetal membranes [11] of pregnant women with intra-amniotic infection and PPROM. According to Menon et al. [11], membranes are a site of inflammatory cytokine production. These cytokines are thought to play an important role because TNF bioavailability, apoptosis in the chorion, and increased metalloproteinase (MMP) activity may lead to PPROM [12,13]. Several studies have described mechanisms through which pro-inflammatory cytokines lead to labor onset. The main effect appears to be through the up-regulation of prostaglandin production by reproductive tissues. In the presence of intrauterine infection, leukocytes that are recruited into gestational membranes increase cytokine production (reviewed by Bowen et al. [14]). The effect of chorioamnionitis in preterm tissues and the presence of pro-inflammatory cytokines in chorioamniotic membranes have been investigated. Laham et al. [15] showed that IL-8 release from amnion, chorioadecidual, and placental explants did not significantly differ in the absence or presence of chorioamnionitis. These findings are consistent with a previous study showing no difference in the pattern of inflammatory cytokine mRNA expression in women with or without clinically evident intrau

American Journal of Obstetrics and Gynecology, 2006

Journal of Physiology and Pathophysiology

Available therapeutic interventions for managing preterm labour have not been consistently successful due to controversies related to its etiology. Multiple mechanisms, including inflammation play a significant role in the pathogenesis of preterm labour. The connective tissue extracellular matrix of the amniochorion contains collagen fibres that maintain the tensile strength of the amniochorion, resisting mechanical stress and preventing rejection of the fetal allograft. Expression of pro-inflammatory mediators in the amniochorion triggers production of prostaglandins in the uterus and enzymatic degradation of the resilient extracellular matrix of the fetal membranes by matrix metalloproteinases leading to uterine contractions and cervical remodelling resulting in preterm labour. This review appraises the pathophysiological mechanisms of pro-inflammatory mediators in spontaneous preterm labour and their associations with multi-factorial etiological pathways. The physiological pathways and biological mechanisms of uterine activity during pregnancy and parturition are also discussed. Finally, the review provides an overview of the biological basis of common therapeutic agents for treating preterm labour. In this review, keywords related to pathophysiological mechanisms of maternal proinflammatory mediators in preterm labour and clinical management were used in the literature search from the PubMed and Google Scholar databases. The snowball sampling methodology was further employed to obtain a comprehensive literature search.

BJOG: An International Journal of Obstetrics and Gynaecology, 2002

Preterm Birth - Mother and Child, 2012