Placental malperfusion in response to intrauterine inflammation and its connection to fetal sequelae.

Exposure to intrauterine inflammation (IUI) is associated with short- and long-term adverse perinatal outcomes. However, little data exist on utilizing placenta to prognosticate fetal injury in this scenario. Our study aimed to utilize imaging modalities to evaluate mechanisms contributing to placental injury following IUI exposure and correlated it to concomitant fetal brain injury. CD1 pregnant dams underwent laparotomies and received intrauterine injections of either lipopolysaccharide (LPS; a model of IUI) or phosphate-buffered saline (PBS). In utero ultrasound Doppler velocimetry of uterine and umbilical arteries and magnetic resonance imaging (MRI) of placental volumes with confirmatory immunohistochemical (vimentin) and histochemistry (fibrin) analyses were performed. ELISA for thrombosis markers, fibrinogen and fibrin was performed to analyze thrombi in placenta. Fetal brain immunohistochemistry was performed to detect microglial activation (ionized calcium-binding adaptor molecule 1, Iba1). On ultrasound, LPS group demonstrated elevated resistance indices, pulsatility indices and a greater occurrence of absent end-diastolic flow in the umbilical and uterine arteries. In the fetus, there was an increased cardiac Tei indices in the LPS group. MRI revealed decreased volume of placenta in the LPS group associated with placental thinning and placental endothelial damage on immunohistochemistry. Decreased fibrinogen content and more thrombi staining in placenta exposed to maternal LPS indicated the hypercoagulability. Furthermore, the expression of Iba1was significantly associated with placental thickness (r = -0.7890, Pearson correlation coefficient). Our data indicate that IUI can trigger events leading to maternal placental malperfusion and fetal vessel resistance, as well as predispose the developing fetus to cardiac dysfunction and brain damage. Furthermore, our data suggest that prenatal ultrasound can be a real-time clinical tool for assessing fetal risk for adverse neurologic outcomes following the potential IUI exposure.

Prenatal Effects of Zika Virus and Management of the Pregnant Woman.

The identification of Zika virus as a significant teratogen has raised international concern, causing the World Health Organization to declare a Public Health Emergency of International Concern. This has allowed a global mobilization of experts in tropical infectious diseases, obstetrics, pediatrics, virology, public health policy, reproductive health, bioethics, and germ cell research to name just a few. This worldwide crisis has also raised awareness of health care disparities and concerns regarding the ability of families and societies to shoulder the long-term financial burden that the follow-up of affected children will require. There is now strong biologic evidence of causality between Zika virus and microcephaly and other neurologic abnormalities identified. Multiple national and international organizations have collaborated to develop guidelines for the management of pregnant women who reside in or who are exposed to Zika virus, whether from travel to affected areas or via sexual contact with an infected individual. These guidelines are updated frequently as data are made available. Testing algorithms are available and though testing is fraught with interpretation issues, the development of better diagnostic tests is ongoing.