Bacteria and Inflammatory Cells in Fetal Membranes Do Not Always Cause Preterm Labor

Abstract

Intrauterine infection has been frequently linked with preterm labor before 30 wk of human pregnancy. Many different species of organisms have been detected, leading to the suggestion that infection-induced preterm labor is a generic inflammatory response to organisms rather than a specific response to a limited number of pathogens. The detection of organisms by microbiological culture is a laborious and unreliable process, so the aim of this study was to harness modern molecular techniques to detect organisms in tissues from human pregnancy. A DNA probe specific for conserved regions of bacterial 16S ribosomal RNA sequence was designed and labeled with fluorescein for fluorescence in situ hybridization. Organisms were detected in the great majority (Ͼ80%) of fetal membranes after prolonged premature rupture of the fetal membranes and after preterm labor, which was consistent with previous data. Organisms were also detected in fetal membranes after preterm delivery without labor and in term deliveries (with or without labour). Inflammatory cells were found frequently in the amnion or chorion of preterm fetal membranes but not in term tissues. Our primary finding is that fluorescence in situ hybridization is an appropriate method to detect organisms in human fetal membranes. In addition, our data show that bacteria may be present in fetal membranes without necessarily causing an inflammatory response, so the mere presence of bacteria may not be sufficient to cause preterm labor. Human labor at all gestational ages involves an inflammatory response, being characterized by increased levels of prostaglandins and cytokines (1,2). This inflammation is presumed to be initiated by physiological mediators, including corticotrophin-releasing hormone (3) or platelet-activating factor (4), or by pathological processes (5-7).At 23-32 wk of pregnancy, preterm labor is most frequently associated with micro-organisms within the uterus (8). These organisms are thought to activate inflammatory responses within intrauterine tissues and cause the recruitment of leukocytes to the fetal membranes (chorioamnionitis) (9,10). This is so thoroughly accepted that in some studies, chorioamnionitis has been used as being diagnostic of intrauterine infection, without determination of the presence of bacteria (11). However, the precise relation between the presence of bacteria and an inflammatory response has not been clearly defined. This is an important issue as it is not known whether the presence of bacteria always causes chorioamnionitis or whether chorioamnionitis is always linked to infection.Many different organisms have been identified from intrauterine tissues after preterm labor using various sampling and culture techniques (12-14), but no clear pattern has emerged from these studies, so it has not been possible to implicate one particular organism or family of organisms as the main causes of preterm labor. Furthermore, it has not been proved that the bacteria present in the vagina are those that have caused chorioamnionitis in pre...

Chorioamnionitis and neonatal morbidity: current perspectives

“…On the other hand, it is also important to point out that the presence of bacteria and/or inflammatory cells in the fetal membranes does not always cause premature labor. 52 The inflammatory response associated with CA leads to the rupture of membranes or preterm labor by different mechanisms, including cytokine and MMP activation causing direct rupture of membranes, triggering apoptosis of the fetal membranes cells, activation of the extrinsic pathway in response to toxins and/or cytokines (TNF-α, IL-1ß, etc. ), or activating cell mediators, such as prostaglandins, that directly induce uterine contractions.…”

TLR9 Provokes Inflammation in Response to Fetal DNA: Mechanism for Fetal Loss in Preterm Birth and Preeclampsia

“…Although bacterial and viral factors may incite the inflammatory process without evidence of infection by cultures or histology, it is possible that another more sterile process might be at work. Notably, samples of amniotic fluid and placenta were examined for bacterial products at elective section of term pregnancies, and 70% had evidence of the presence of microbial products by fluorescence in situ hybridization without infection or symptoms of labor or PEC (14). This presents an incongruity with respect to factors from an infective source being the sole cause of inflammatory disorders of pregnancy even at a local level.…”

Hyperleukocytosis in a premature infant with intrauterine herpes simplex encephalitis

“…Non-culture molecular technologies have demonstrated bacteria in 70% of fetal membranes at the time of elective Caesarean section at term. 9 These and similar findings in premature pregnancies suggest that ascending invasion of the amniotic fluid from the vagina is common. 10 Intrauterine HSV infection can occur because of either transplacental or ascending infection.…”