A real-life prospective blinded evaluation of placental biometry and macroscopic morphology from 1008 unselected consecutive pregnancies.

INTRODUCTION: The study of the macroscopic appearance of the placenta may represent a useful tool to understand the pathophysiology of adverse pregnancy outcomes. The aim of this study was to evaluate biometry and morphology of placentas in relation to maternal, neonatal and pregnancy course characteristics. METHODS: Clinical and placental data (biometry and macroscopic features of chorionic disk and adnexa) from unselected consecutive singleton pregnancies were recorded at the same Institution. Placental efficiency was approximated as ratio between fetal and placental weight (FPR). The total population was grouped according to the presence of any maternal comorbidity or pregnancy complication (group 1), neonatal complications diagnosed only at birth (2) and absence of any comorbidity (3). Multi-adjusted general linear and logistic regression models were performed to analyze associations between groups and placental biometry and morphology. RESULTS: The study population counted 1008 pregnancies: 576 (57.2 %) classified as group 1, 76 (7.5 %) as group 2 and 356 (35.3 %) uncomplicated controls (group 3). In multivariate models adjusted for confounding factors, no significant differences in placental biometry and macroscopic features were observed among the three groups. Maternal BMI was significantly associated with higher placental and birth weight and lower FPR; moreover FPR was significantly higher in pregnancies carrying males compared to female neonates. DISCUSSION: Maternal comorbidity or pregnancy disease was not associated with significant changes in placental macroscopic biometry and morphology. Conversely, maternal pregestational BMI and fetal sex impact on placental biometry and efficiency, suggesting different intrauterine adaptations in obese mothers and in male and female fetuses.

Evidence-Based View of Safety and Effectiveness of Prokineticin Receptors Antagonists during Pregnancy.

Endocrine gland derived vascular endothelial growth factor (EG-VEGF) is a canonical member of the prokineticin (PROKs) family. It acts via the two G-protein coupled receptors, namely PROKR1 and PROKR2. We have recently demonstrated that EG-VEGF is highly expressed in the human placenta; contributes to placental vascularization and growth and that its aberrant expression is associated with pregnancy pathologies including preeclampsia and fetal growth restriction. These findings strongly suggested that antagonization of its receptors may constitute a potential therapy for the pregnancy pathologies. Two specific antagonists of PROKR1 (PC7) and for PROKR2 (PKRA) were reported to reverse PROKs adverse effects in other systems. In the view of using these antagonists to treat pregnancy pathologies, a proof of concept study was designed to determine the biological significances of PC7 and PKRA in normal pregnancy outcome. PC7 and PKRA were tested independently or in combination in trophoblast cells and during early gestation in the gravid mouse. Both independent and combined treatments uncovered endogenous functions of EG-VEGF. The independent use of antagonists distinctively identified PROKR1 and PROKR2-mediated EG-VEGF signaling on trophoblast differentiation and invasion; thereby enhancing feto-placental growth and pregnancy outcome. Thus, our study provides evidence for the potential safe use of PC7 or PKRA to improve pregnancy outcome.

Fetal-Maternal Exposure to Endocrine Disruptors: Correlation with Diet Intake and Pregnancy Outcomes.

Endocrine-disrupting chemicals (EDCs) are exogenous substances able to mimic or to interfere with the endocrine system, thus altering key biological processes such as organ development, reproduction, immunity, metabolism and behavior. High concentrations of EDCs are found in several everyday products including plastic bottles and food containers and they could be easily absorbed by dietary intake. In recent years, considerable interest has been raised regarding the biological effects of EDCs, particularly Bisphenol A (BPA) and phthalates, on human pregnancy and fetal development. Several evidence obtained on in vitro and animal models as well as by epidemiologic and population studies strongly indicated that endocrine disruptors could negatively impact fetal and placental health by interfering with the embryonic developing epigenome, thus establishing disease paths into adulthood. Moreover, EDCs could cause and/or contribute to the onset of severe gestational conditions as Preeclampsia (PE), Fetal Growth Restriction (FGR) and gestational diabetes in pregnancy, as well as obesity, diabetes and cardiovascular complications in reproductive age. Therefore, despite contrasting data being present in the literature, endocrine disruptors must be considered as a therapeutic target. Future actions aimed at reducing or eliminating EDC exposure during the perinatal period are mandatory to guarantee pregnancy success and preserve fetal and adult health.

Immune Cells in the Uterine Remodeling: Are They the Target of Endocrine Disrupting Chemicals?

Sufficient uterine remodeling is essential for fetal survival and development. Pathologies related to poor remodeling have a negative impact on maternal and fetal health even years after birth. Research of the last decades yielded excellent studies demonstrating the key role of immune cells in the remodeling processes. This review summarizes the current knowledge about the relevance of immune cells for uterine remodeling during pregnancy and further discusses immunomodulatory effects of man-made endocrine disrupting chemicals on immune cells.

Maternal Body Mass Index and Gestational Weight Gain and Their Association with Pregnancy Complications and Perinatal Conditions.

This study aimed to evaluate the impact of selected pregnancy pathologies statistically depending on overweight/obesity and excessive maternal weight gain during pregnancy on women who gave birth in the years 2013-2015 at the Second Department of Gynecology and Obstetrics at the University Hospital in Bratislava, Slovakia. In a retrospective study, we analyzed data gathered from the sample, which consisted of 7122 women. Our results suggest a statistically significant, higher risk for the groups of women with overweight and obesity and gestational hypertension (adjusted odds ratio (AOR) = 15.3; 95% CI 9.0-25.8 for obesity), preeclampsia (AOR = 3.4; 95% CI 1.9-6.0 for overweight and AOR = 13.2; 95% CI 7.7-22.5 for obesity), and gestational diabetes mellitus (AOR = 1.9; 95% CI 1.2-2.9 for overweight and AOR = 2.4; 95% CI 1.4-4.0 for obesity). A higher incidence of pregnancies terminated by cesarean section was observed in the group of obese women. Gestational weight gain above IOM (Institute of Medicine) recommendations was associated with a higher risk of pregnancy terminated by C-section (AOR = 1.2; 95% CI 1.0-1.3), gestational hypertension (AOR = 1.7; 95% CI 1.0-2.7), and infant macrosomia (AOR = 1.7; 95% CI 1.3-2.1). Overweight and obesity during pregnancy significantly contribute to the development of pregnancy pathologies and increased incidence of cesarean section. Systematic efforts to reduce weight before pregnancy through prepregnancy dietary counseling, regular physical activity, and healthy lifestyle should be the primary goal.

The Role of Decidual Macrophages During Normal and Pathological Pregnancy.

Macrophages perform many specific functions including host defense, homeostasis, angiogenesis, and tissue development. Macrophages are the second most abundant leukocyte population in the non-pregnant endometrium and pregnant decidua and likely play a central role in the establishment and maintenance of normal pregnancy. Importantly, aberrantly activated uterine macrophages can affect trophoblast function and placental development, which may result in various adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth restriction or demise. Only by fully understanding the roles of macrophage in pregnancy will we be able to develop interventions for the treatment of these various pregnancy complications. This review discusses the general origin and classification of monocytes and macrophages and focuses on the phenotype and functional roles of decidual macrophage at the maternal-fetal interface in normal pregnancy, as well as discussing the potential contribution of the abnormal state of these cells to various aspects of pregnancy pathologies.