Role of Waddlia chondrophila Placental Infection in Miscarriage

David Baud1, Geneviève Goy1, Maria-Chiara Osterheld, Antony Croxatto, Nicole Borel, Yvan Vial, Andreas Pospischil, and Gilbert Greub

Author affiliations: University of Lausanne, Lausanne, Switzerland (D. Baud, G. Goy, A. Croxatto, G. Greub); University Hospital, Lausanne (D. Baud, Y. Vial); University Hospital Centre, Lausanne (M.-C. Osterheld); University of Zürich, Zürich, Switzerland (N. Borel, A. Pospischil)

Abstract

Waddlia chondrophila is an intracellular bacterium suspected to cause human and bovine abortion. We confirmed an association between antibodies against W. chondrophila and human miscarriage and identified this organism in placenta or genital tract of women who had had miscarriages. These results suggest a possible role of W. chondrophila infection in miscarriage.

Approximately 25% of pregnant women will experience at least 1 miscarriage (1,2). However, a cause is identified for only 50% of cases (3,4). Intracellular bacteria, which do not grow on media routinely used to isolate human pathogens from clinical samples, represent possible agents of miscarriage of unexplained etiology (4,5).

Waddlia chondrophila, a Chlamydia-related bacterium first identified in samples of bovine abortion tissues, has been associated with human miscarriages (6,7). In a study of 438 serum samples from women attending a recurrent-miscarriage clinic, seroprevalence of W. chondrophila was higher for women who had sporadic (31.9%) and recurrent (33.0%) miscarriages than for women who had uneventful pregnancies (7.1%; p<0.001) (6).

To further investigate the role of W. chondrophila in human miscarriage, we studied 386 women who had had miscarriages or uneventful pregnancies. In addition to serologic analysis, we used PCR and immunohistochemical analysis to detect W. chondrophila in placenta and vaginal samples.

The Study

During 2006–2009, a total of 386 women were prospectively enrolled from the obstetrical ward of the University Hospital of Lausanne (Table 1) (8). The miscarriage group was composed of 125 women given a diagnosis of an acute episode of miscarriage in the emergency gynecology unit. The control group was composed of 261 women attending a labor ward, having uneventful pregnancies, and having no history of miscarriage, stillbirth, or preterm labor. Age, black race, and number of lifetime sex partners were different between both groups.

Immunofluorescence testing was performed by using W. chondrophila as antigen as described (6). Eighty-four women had antibodies against W. chondrophila as demonstrated by positive immunofluorescence against total immunoglobulin (Table 1). Among them, 67 women had IgG titers ≥1:64 and 6 women had IgM titers ≥1:32 against W. chondrophila (FluolineG or FluolineM; BioMérieux, Marcy l'Etoile, France). IgG seroprevalence was higher among women who experienced miscarriage (23.2%) than among women who experienced an uneventful pregnancy (14.6%; p = 0.044) (Table 2). When women with and without antibodies against W. chondrophila were compared, their age, contact with animals, education, number of previous sex partners, previous contraceptive use, and place of residence (countryside/city) were not associated with a positive serologic result for W. chondrophila. However, a multivariate logistic regression model indicated that black women were more likely to have antibodies against W. chondrophila (odds ratio [OR] 3.15, 95% CI 1.39–7.16).