Maternal Inflammation and/or Infection

Both maternal psychological stress and smoking habits are associated with increased levels of inflammatory mediators. Pregnant women experiencing psychosocial stress have demonstrated an increase (usually less than 2-fold) in preterm birth rates55-57 and demonstrate increased levels of corticotropin releasing hormone as well as C-reactive protein (CRP).58 Smoking is similarly associated with a significant increase in the systemic inflammatory response and has been proposed to increase preterm birth through that pathway.59,60

Maternal infections have also been demonstrated to increase the maternal inflammatory response and affect preterm birth. Microorganisms are recognized by immune cell receptors, which in turn release inflammatory chemokines and cytokines, such as interleukin-8 (IL-8), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). These pro inflammatory cytokines and microbial endotoxins stimulate the production of prostaglandins, other inflammatory mediators, and matrix-degrading enzymes. Prostaglandins, in turn, stimulate uterine contractility and degradation of the extracellular matrix within the uterine environment and can lead to PPROM.53,61

Microbiologic studies suggest that intrauterine infections may account for 25-40% of preterm births;61 however, this may be an underestimate as intrauterine infection is difficult to detect with conventional culture techniques.62 Early preterm births are most highly associated with intrauterine infections when compared to late preterm births.63 A variety of microorganisms have been associated with intrauterine infection, and these infections have been found to be most often of a chronic nature.61 Microorganisms can gain access to the intrauterine environment through a variety of means: (1) ascending through the genitourinary tract from the vagina, (2) bloodborne organisms traveling through the placenta, (3) accidental introduction at the time of invasive procedures, and (4) retrograde spread through the fallopian tubes.61,64 Bacterial vaginosis, which has been shown to ascend into the uterus, has been associated with a 1.5 to 3-fold increase in preterm birth rates.65