Dr. E. Albert Reece: How important is infection as a mechanism of disease in premature labor?
Dr. Roberto Romero: Intrauterine and systemic infections are a leading cause of spontaneous preterm labor and delivery. Indeed, infections and inflammation are the only mechanisms of disease for which a clear causal link with prematurity has been established. Moreover, a clear molecular pathophysiology has been described.
EAR: How frequent is intrauterine infection in spontaneous preterm birth?
RR: It has been estimated that one of every four preterm births occurs to mothers with intraamniotic infection (defined as a positive amniotic fluid culture for microorganisms). Under normal circumstances, the amniotic cavity does not contain bacteria, just as cerebrospinal fluid does not. However, approximately 12% of women presenting with an episode of preterm labor will have a positive amniotic fluid culture for microorganisms. The organisms most frequently isolated are genital mycoplasmas, particularly Ureaplasma urealyticum. Among women with preterm premature rupture of membranes (PROM), one of every three will have a positive amniotic fluid culture for microorganisms at the time of presentation. U. urealyticum is the most common microorganism isolated from the amniotic cavity.
EAR: Is there a particular subgroup of women in whom intrauterine infection is more prevalent?
RR: The earlier the gestational age at which a patient presents with preterm labor and intact membranes or preterm PROM, the higher the likelihood of a positive amniotic fluid culture. For example, infection and/or inflammation is present in close to 70% of women presenting around 24 weeks of gestation, but is much rarer in patients presenting after 34 weeks.
EAR: Among women who present with a clinical picture of acute cervical insufficiency, also known as an “incompetent cervix,” how common are infections?
RR: Studies by our group and others indicate that approximately 50% of women presenting with a dilated cervix and bulging membranes before 24 weeks of gestation will have a positive amniotic fluid culture for microorganisms. It is important to realize that rupture of membranes after a cervical cerclage may be the result of a subclinical infectious process, rather than the consequence of cerclage placement.
EAR: What proportion of intrauterine infections manifest themselves with clinical chorioamnionitis?
RR: Most intrauterine infections are subclinical in nature. Our work indicates that among women with intraamniotic infection and preterm labor with intact membranes, only 12% will have a positive amniotic fluid culture. Among women with preterm PROM, only 20% will have clinical signs of chorioamnionitis when a positive amniotic fluid culture is present.
EAR: If most infections are subclinical in nature, how can they be detected?
RR: The most accurate method to detect the presence of intraamniotic infection is analysis of amniotic fluid. Amniotic fluid is normally sterile for bacteria. It is possible to isolate some viruses from amniotic fluid, but generally, cultures for viruses are not performed in patients with preterm labor and preterm PROM. Amniotic fluid should be cultured for aerobic and anaerobic bacteria, as well as for Mycoplasma species. Detection of mycoplasmas is important, because they are the most common organisms found in the amniotic fluid. Commercially available systems exist that can be implemented in U.S. laboratories.
EAR: The results of cultures take several days to become available. Thus, rapid tests are required to assess the likelihood of infection or inflammation. What tests would you recommend for this purpose?
RR: A positive Gram stain has 99% specificity, but 20% sensitivity in the detection of intraamniotic infection. The low sensitivity is because the Gram stain cannot detect mycoplasmas since these organisms are too small to be seen with light microscopy. However, the take-home message is that a positive Gram stain is virtually always associated with a positive culture and that false positives are rare. The current approach to the detection of infection and/or inflammation in the amniotic fluid includes other tests that are routinely performed for the analysis of cerebrospinal fluid in all hospitals in the United States. Such tests include a white blood cell (WBC) count of amniotic fluid, and a glucose determination.
EAR: How can the clinician interpret the results of an amniotic fluid WBC and an amniotic fluid glucose determination?
RR: White blood cells—such as neutrophils, monocytes, or eosinophils—are not normally present in the amniotic fluid. Therefore, a high count of white blood cells is an indicator that intraamniotic inflammation is present. We recommend that an amniotic fluid sample be sent to the clinical hematology laboratory, that a WBC count be performed in the standard hemacytometer chamber, and that this be followed by a differential count. When the WBC count is greater than 50 cells/L in patients with intact membranes—or greater than 30 in patients with preterm PROM—the likelihood of a positive amniotic fluid culture is high.