Pathophysiology Of Preterm Birth Research Articles

The prevalence of preterm birth and season of conception

Preterm birth is a major obstetric problem. An exploration of the season of conception in relation to preterm birth may provide direction in the search for risk factors. We conducted a retrospective cohort study of 82 213 singleton livebirths (20-45 weeks' gestation) to 61,630 women at Magee-Womens Hospital, Pittsburgh, PA, from 1995 to 2005. Conception was estimated based on gestational age determined by best obstetric estimate. Fourier series analysis was used to model seasonal trends. Spontaneous preterm birth at <37 weeks was associated with conception season (P < 0.05). The peak prevalence occurred among conceptions in winter and spring (peaking February 23 at 6.9%), with an average trough among late summer/early autumn conceptions (August 25 at 6.2%). The pattern for spontaneous preterm birth <32 weeks was similar (P < 0.05), with the peak on March 13 (1.7%), and nadir on September 12 (1.4%). Results were similar when indicated preterm births were included. These seasonal changes may increase our insight into the role of exposures with seasonal periodicity in the pathophysiology of preterm birth.

Iron-Dependent Oxidative Stress as a Pathogenesis for Preterm Birth

Preterm birth (PTB) is an oxidative stress-related disease that lacks effective therapies partly because of the poor understanding of disease pathogenesis. The aim of this manuscript was to review molecular pathways that could be responsible for the pathogenesis of PTB. Genomic and proteomic studies have started to delineate the wide array of mediators involved in this disorder. Understanding the mechanisms of the development of PTB and elucidating pathogenesis and pathophysiology are intrinsic to prevention and effective therapies for this disorder. This article reviews the English language literature for pathogenesis and pathophysiological studies on PTB. Several recent genomic and proteomic studies are discussed in the context of PTB biology. Decidual hemorrhage has been identified histologically in the placentas of patients with PTB, which may result in high levels of free heme and iron. Several important PTB-specific genes and proteins overlap with those known to be regulated by iron. Others were genes involved in oxidative stress and detoxification. Free iron oxidatively modifies lipid and protein, leading to DNA and cell damage. This signaling pathway of PTB will be discussed as it provides new insights into regulation of inflammation, oxidative stress, and detoxification. This review summarizes recent advances in heme/iron-mediated signaling, the target genes thereof, and the potential challenges to the understanding of pathogenesis and pathophysiology of PTB. A novel model is proposed. Collectively, decidual hemorrhage and inflammation are considered to be major contributors to the pathogenesis of PTB. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader should be able to paraphrase the role of oxidative stress in pathogenesis of preterm birth, explain the idea of preterm birth as a "syndrome," and summarize the potential role of early uterine bleeding in pathophysiology of preterm birth.

Impact of clinical and histologic correlates of maternal and fetal inflammatory response on gestational age in preterm births

Objective. To evaluate the impact of clinical and histopathologic correlates related to maternal and fetal inflammatory responses (MIR and FIR) on degree of preterm birth.Methods. Pathology reports and clinical data from 577 singleton preterm births (<37 weeks of gestation) that took place between 1998 and 2004 were analyzed according to decreasing gestational age (≥33 weeks, 29–32 weeks, and <29 weeks). MIR was defined by presence of subchorionitis, chorioamnionitis, deciduitis, or free membranitis; FIR was defined by presence of funisitis or chorionic plate vasculitis. The associations between MIR alone and MIR with FIR and gestational age subgroups were assessed using logistic regression.Results. The presence of FIR in addition to MIR was more strongly associated with degree of prematurity than the presence of MIR alone, especially for those born at <29 weeks (OR = 10.1 (95% CI 4.3–23.7) and OR = 5.3 (95% CI 2.3–12.5), respectively). These associations remained significant after adjusting for maternal race, clinical signs of chorioamnionitis, medically indicated birth, and intrapartum corticosteroid, tocolysis and antibiotic use, and after stratification by clinical signs of chorioamnionitis and medically indicated birth.Conclusions. The combined presence of MIR and FIR is associated with a higher risk of extreme preterm birth (<29 weeks) than MIR alone, suggesting a contributory role of FIR in the pathophysiology of preterm birth.

Effect of progesterone on toll-like receptor (TLR)-2 and toll-interacting protein (tollip) gene expression in monocytes stimulated by heat-killed bacteria

Inflammation and immune responses play important roles in parturition and may be key in the pathophysiology of preterm birth (PTB). Progesterone (P4), a recommended intervention to reduce impending preterm birth, may affect immune responses. The objective of this investigation was to determine if P4 limits the ability of monocytes to respond to pathogens by increasing the gene expression of Tollip, a negative regulator of TLR signaling, and/or decreasing the gene expression of TLR-2.

Macrophage inhibitory cytokine 1 in fetal membranes and amniotic fluid from pregnancies with and without preterm labour and premature rupture of membranes.

The placenta and fetal membranes are the site of expression of macrophage inhibitory cytokine (MIC-1), a member of the transforming growth factor (TGF)-beta superfamily. We hypothesized that MIC-1 may act as an immune regulator in pregnancy complications associated with intrauterine inflammation. Decidual cells, chorionic trophoblasts and amnion epithelial cells were identified by immunohistochemistry as the predominant MIC-1-containing cell type in term membranes. Amnion and choriodecidual explants all produced MIC-1 in culture, the latter having the greatest production rate (206 +/- 74.5 pg/mg tissue/24 h, n=6; mean +/- SEM). Production was not responsive to stimulation by pro-inflammatory cytokines. MIC-1 was detectable in 217 transabdominal amniotic fluid (AF) samples taken from 15 to 41 weeks gestation, concentrations ranging from 0.9-51.1 ng/ml. AF MIC-1 concentrations in pregnancies with premature rupture of membranes (PROM) or preterm labour, either with or without microbial invasion of the amniotic cavity, were not significantly different from those delivered at term either with or without labour. Treatment with MIC-1 (0.25-25 ng/ml) did not alter production of interleukin-6 or -8 by amnion or choriodecidual cells in vitro. We conclude that AF MIC-1 is derived from the fetal membranes and decidua, but that MIC-1 is unlikely to be involved in the pathophysiology of preterm birth or PROM.