The Contribution of an Infectious Workup in Understanding Stillbirth.

OBJECTIVE: This study was aimed to assess the utility of diagnostic tests of maternal and fetal infection in the evaluation of stillbirth. STUDY DESIGN: A single-center retrospective study from January 2011 to December 2016 of all women presenting to the hospital with intrauterine fetal death at or after 20 weeks of gestation. Standard evaluation included review of medical records, clinical and laboratory inflammatory workup, maternal serologies, fetal autopsy, placental pathology, and fetal and placental cultures. A suspected infectious etiology was defined as meeting at least two diagnostic criteria, and only after exclusion of any other identifiable stillbirth cause. RESULTS: During the 7-year study period, 228 cases of stillbirth were diagnosed at our center. An infectious etiology was the suspected cause of stillbirth in 35 cases (15.3%). The mean gestational age of infection-related stillbirth was 28 1/7 (range: 22-37) weeks, while for a noninfectious etiology, it was 34 0/7 (range: 25-38) weeks (p = 0.005). Placental histological findings diagnostic of overt chorioamnionitis and funisitis were observed in 31 (88.5%) cases. In 16 (45.7%) cases the placental and fetal cultures were positive for the same pathogen. Serology of acute infection was positive in three (8.5%) of the cases. CONCLUSION: Maternal and fetal infectious workup is valuable in the investigation of stillbirth, particularly before 30 weeks of gestation and should be considered a part of standard evaluation.

Placental vascular tree characterization based on ex-vivo MRI with a potential application for placental insufficiency assessment.

INTRODUCTION: Understanding regarding the whole placental vascular network structure is limited. Our aim was to quantitatively characterize the human placental vascular tree ex-vivo using high-resolution MRI. METHODS: 34 normal placentas were rinsed and injected with a solution of gelatin and contrast agent through the umbilical vessels. A sample of six placentas taken from pregnancies with intrauterine-growth-restriction (IUGR) was used to demonstrate the potential application to cases with placental insufficiency. Structural ex-vivo MR scans of the placenta were performed using high resolution T1 weighted images. A semi-automatic method was developed to segment and characterize the placental vascular architecture: placental volume and cord insertion location; number of bifurcations, generations and vessels diameters. RESULTS: Different vascular patterns were found in placentas with central versus marginal cord-insertion. Based on the placental volume and number of bifurcations we were able to predict birth weight. Furthermore, preliminary results on IUGR sample demonstrated the potential of this method to differentiate between small newborns with suspected IUGR from small normal newborns who reached their full growth potential. Results obtained using the automatic method were validated against manual values demonstrating no significant differences or bias. Histopathology supported the imaging findings. DISCUSSION: This is the first study to quantitatively characterize the human placental vascular architecture using high resolution ex-vivo MRI. Different patterns of vascular architecture may be related to different functioning of the placenta and affect fetal development. This method is simple, relatively fast, provides detailed information of the placental vascular architecture, and may have important clinical applications.

Placental vascular tree characterization based on ex-vivo MRI with a potential application for placental insufficiency assessment.

INTRODUCTION: Understanding regarding the whole placental vascular network structure is limited. Our aim was to quantitatively characterize the human placental vascular tree ex-vivo using high-resolution MRI. METHODS: 34 normal placentas were rinsed and injected with a solution of gelatin and contrast agent through the umbilical vessels. A sample of six placentas taken from pregnancies with intrauterine-growth-restriction (IUGR) was used to demonstrate the potential application to cases with placental insufficiency. Structural ex-vivo MR scans of the placenta were performed using high resolution T1 weighted images. A semi-automatic method was developed to segment and characterize the placental vascular architecture: placental volume and cord insertion location, number of bifurcations, generations and vessels diameters. RESULTS: Different vascular patterns were found in placentas with central versus marginal cord-insertion. Based on the placental volume and number of bifurcations we were able to predict birth weight. Furthermore, preliminary results on IUGR sample demonstrated the potential of this method to differentiate between small newborns with suspected IUGR from small normal newborns who reached their full growth potential. Results obtained using the automatic method were validated against manual values demonstrating no significant differences or bias. Histopathology supported the imaging findings. DISCUSSION: This is the first study to quantitatively characterize the human placental vascular architecture using high resolution ex-vivo MRI. Different patterns of vascular architecture may be related to different functioning of the placenta and affect fetal development. This method is simple, relatively fast, provides detailed information of the placental vascular architecture, and may have important clinical applications.

Can We Prevent Stillbirth?

OBJECTIVE: This study aimed to identify the frequency of potentially preventable causes of stillbirth in a large heterogeneous population. STUDY DESIGN: This is a retrospective study of all stillbirth cases between January 2011 and December 2016 at a single tertiary medical center. Deliveries resulting from a nonviable fetus prior to 24 weeks of gestation, intrapartum fetal death, and incomplete stillbirth workup were excluded. Potentially preventable stillbirth was defined as that of a nonanomalous fetus that most likely resulted from one or more of the following: (1) placental-mediated complications, (2) postterm pregnancy, (3) monochorionicity-associated complications, (4) cholestasis of pregnancy, (5) preventable or treatable infections, and (6) isoimmunization. RESULTS: During the study period, 312 stillbirths were identified, 228 of which met the inclusion criteria. Of the 110 cases with a recognized cause, 47 (20.6%) were potentially preventable. The most common causes were placental-mediated complications and preventable or treatable infections, accounting for 75 and 9% of all potentially preventable causes, respectively. There were no recognizable maternal risk factors for potentially preventable stillbirth. CONCLUSION: One-fifth of all causes of stillbirth are potentially preventable. Due to the significant contribution of placental-mediated complications to preventable stillbirth, close sonographic surveillance and timely delivery may decrease risk substantially.

Absence of peroxisome proliferator-activated receptor-alpha abolishes hypertension and attenuates atherosclerosis in the Tsukuba hypertensive mouse.

Peroxisome proliferator-activated receptor-alpha is widely distributed in the vasculature where it is believed to exert pleiotropic antiatherogenic effects. Its role in the regulation of blood pressure is still unresolved; however, some evidence suggests that it may affect the renin-angiotensin system. We investigated its role in angiotensin II-induced hypertension in the Tsukuba hypertensive mouse (THM). This is a model of hypertension and atherosclerosis because of high angiotensin II and aldosterone levels as a result of the transgenic expression of the entire human renin-angiotensin system. Making the THM animals deficient in Peroxisome proliferator-activated receptor-alpha (THM/PPARKO) totally abolished hypertension and myocardial hypertrophy. This was accompanied by a reduction in plasma human active renin in THM/PPARKO mice compared with THM animals from 3525+/-128 mU/L to 1910+/-750 mU/L (P<0.05) and by a normalization of serum aldosterone (1.6+/-0.29 nmol/L versus 3.4+/-0.69 nmol/L; P=0.003). In the THM/PPARKO mice, the extent of atherosclerosis at the aortic sinus after a 12-week period on an atherogenic diet was decreased by >80%. In addition, the spontaneous formation of foam cells from peritoneal macrophages, a blood pressure-independent event, was reduced by 92% in the THM/PPARKO mice, suggesting protection from the usual oxidative stress in these animals, possibly because of lower prevailing angiotensin II levels. Finally, chronic fenofibrate treatment further elevated blood pressure in THM animals but not in THM/PPARKO animals. Taken together, these data indicate that peroxisome proliferator-activated receptor-alpha may regulate the renin-angiotensin system. They raise the possibility that its activation may aggravate hypertension and hasten atherosclerosis in the context of an activated renin-angiotensin system.