Abnormal inflammation in a rat model of spontaneous fetal loss leads to maternal coagulopathies associated with placental haemostatic alterations

Thumbnail Image
Falcon, Bani Jadiel
Rat , Fetal loss , Coagulopathy , Inflammation
Spontaneous foetal loss is the most common complication of pregnancy, affecting up to 20% of recognized pregnancies and recurring in 1-3% of cases. Abnormal maternal inflammation and systemic maternal coagulopathies are associated with foetal loss; however, the causal role of inflammation in the development of obstetric coagulopathies has not been determined. Further, questions remain as to whether maternal systemic coagulopathies are associated with placental haemostatic alterations and what role these local alterations play in foetal outcome. We hypothesized that abnormal maternal inflammation during pregnancy is causally linked to maternal coagulopathies and that these coagulopathies are associated with impaired utero-placental blood flow preceding foetal death. To induce inflammation-mediated fetal death, we administered lipopolysaccharide (LPS; 100-µg/kg) to Wistar rats on gestational day 14.5 and characterized the systemic maternal coagulation status 1hr post LPS administration using thromboelastograpy. Utero-placental haemostatic alterations were analyzed by periodic acid Schiff staining (PAS) and immunohistochemistry for fibrin/fibrinogen. Spiral arteriole peak flow velocity was determined by Doppler ultrasound. To determine causality between abnormal maternal inflammation, coagulopathies, and placental hemodynamics, the TNF -inhibitor etanercept (Enbrel®) was administered six hours prior to LPS administration. Systemic maternal coagulopathies were evident in 82% of LPS-treated dams and were associated with specific placental haemostatic alterations as well as reduced utero-placental blood flow. Etanercept administration prevented the development of systemic coagulopathies and placental haemostatic alterations. Furthermore, etanercept maintained normal spiral arteriole peak flow velocity. This study demonstrated that abnormal maternal inflammation is causally linked to systemic coagulopathies specific to pregnancy. Moreover, we showed that inflammation-induced systemic coagulopathies are associated with placental haemostatic alterations and reduced utero-placental blood flow preceding foetal death. Modulation of maternal inflammation may thus be useful in the prevention of coagulopathies associated with complications of pregnancy.
External DOI