Which lab studies on amniotic fluid and urogenital secretions are indicated in the diagnosis of chorioamnionitis?

Updated: May 08, 2018
  • Author: Fayez M Bany-Mohammed, MD; Chief Editor: Ted Rosenkrantz, MD  more...
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Culture of amniotic fluid remains the "gold standard" and most specific test for documentation of intraamniotic infection, but this study is limited by the fact that it may take days to obtain definitive results. More rapid results can be obtained from several other tests, including Gram stain, glucose concentration, white blood cell (WBC) concentration, and leukocyte esterase level. [7] Amniotic fluid, obtained with amniocentesis, may be screened for leukocyte count; Gram stain; pH; glucose concentration; and levels of endotoxin, lactoferrin, and cytokines (eg, interleukin [IL]-6, IL-8, or tumor necrosis factor [TNF]), or a combination of these markers.

Maternal endotoxin activity appears to show promise as a marker in pregnancies complicated by PPROM; however, more data and larger studies are needed to evaluate its potential in predicting the clinical evolution of preterm birth. [159]  Similarly, findings from a study of 47 women with PPROM suggested that maternal levels of IL-6 in combination with maternal characteristics hold the potential to be good noninvasive predictors of histologic chorioamnionitis. [160]

Cytokines commonly quantified in either amniotic fluid or blood include IL-6, TNF-alpha, IL-1, and IL-8. [31, 105, 161] No consensus has been reached regarding which cytokine offers the best sensitivity, specificity, and positive versus negative predictive accuracy. However, IL-6, a key mediator of the acute phase response to infection and tissue injury, is one of the most studied markers and a bedside, point-of-care (POC) testing has been developed to test for IL-6 in amniotic fluids and vaginal secretions. [136, 162, 31, 163] Elevated IL-6 levels in cord blood and amniotic fluid have been related to adverse long-term neurologic outcomes in the neonate. [163, 164, 165]  This testing has not become routine yet. However, Chaemsaithong et al reported the potential utility of a rapid IL-6 bedside test (20 minutes) (lateral flow-based immunoassay, or POC test) for measuring IL-6 concentrations in amniotic fluid. Their goal was to identify women with intraamniotic inflammation and/or infection and those who might deliver spontaneously before 34 weeks' gestation among women with preterm labor and intact membranes. [165]

Data from 136 women with singleton pregnancies who presented with symptoms of preterm labor and underwent amniocentesis showed that the POC test for amniotic fluid IL-6 concentrations had a 93% sensitivity, 91% specificity, and a positive likelihood ratio of 10 for the identification of intraamniotic inflammation by using a threshold of 745 pg/mL. [165] Moreover, the POC test performed similarly to enzyme-linked immunosorbent assay (ELISA) for IL-6 levels and identification of microbial invasion of the amniotic cavity (MIAC), acute inflammatory lesions of the placenta, and patients at risk of impending spontaneous preterm delivery. [165] These investigators found similar results in the setting of PPROM. [163] Other investigators reported similar findings. [162] More recently, matrix metalloproteinase (MMP)-8, a neutrophil collagenase enzyme, has been shown to be a sensitive marker for intraamniotic inflammation that compares well to IL-6 and was developed into rapid POC test as well. [166, 167]

The rapid development of polymerase chain reaction (PCR) as a diagnostic aid has allowed its use in identifying microbes such as human immunodeficiency virus, cytomegalovirus, herpes simplex, parvovirus, toxoplasmosis, and bacterial DNA in amniotic and other body fluids. PCR has been used for the diagnosis of amniotic fluid infection caused by bacterial pathogens [168] ; however, only university or major academic centers have this relatively expensive technology available to caregivers.

Amniocentesis to obtain amniotic fluid carries the risk of rupturing the fetal membranes and initiating preterm labor. For this reason, screening tests that use cervicovaginal secretions to indicate chorioamnionitis have been reported. Potential markers of cervical or chorionic inflammation include cervical or vaginal concentrations of fetal fibronectin, insulinlike growth factor binding protein-1, and sialidase. Significant association is noted among levels of cervical IL-6, fetal fibronectin, and amnionitis. Conversely, a positive midgestational fetal fibronectin assay was not associated with acute histologic placental inflammation at birth. [169] Proteomic profiling of amniotic fluid detects intrauterine inflammation and/or infection and predicts subsequent neonatal sepsis. [8] Caregivers should follow this research, because in the next 5 to 10 years, proteomic profiling for inflammation or nonculture-based molecular detection of microbes may become routine in obstetric samples.

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