Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations

Fetal sex impacts birth to placental weight ratio and umbilical cord oxygen values with implications for regulatory mechanisms

Background: We determined the effect of fetal sex on birth/placental weight and umbilical vein and artery oxygen values with implications for placental efficiency and regulatory mechanisms underlying fetal–placental growth differences. Methods: A hospital database was used to obtain birth/placental weight, cord PO2 and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA \u3e 34 weeks (N = 69,836). Oxygen saturation was calculated from the cord PO2 and pH data, while fractional O2 extraction was calculated from the oxygen saturation data. The effect of fetal sex on birth/placental weight, cord PO2, O2 saturation, and fractional O2 extraction was examined in all patients adjusting for pregnancy and labor/delivery covariates, and in a subset of low-risk patients. Results: Birth/placental weights were lower in females indicating decreased placental efficiency. Umbilical vein oxygen values were higher in females attributed to increased uterine blood flow, while artery oxygen values were lower in females attributed to decreased hemoglobin and umbilical blood flow, and increased oxygen consumption. Fetal O2 extraction was increased in females confirming increased O2 consumption relative to delivery. Conclusions: Sex-related differences in uterine/umbilical blood flows, placental development, and fetal O2 consumption can be linked to the differences observed in cord oxygen. The lower umbilical artery oxygen in females as a measure of systemic oxygenation signaling growth could account for their decreased birth weights, while slower development in female placentae could account for their lower placental weights, which could be differentially effected contributing to their lower birth/placental weights

Maternal obesity reduces placental autophagy marker expression in uncomplicated pregnancies

AIM: Obesity has been associated with changes in autophagy and its increasing prevalence among pregnant women is implicated in higher rates of placental-mediated complications of pregnancy such as pre-eclampsia and intrauterine growth restriction. Autophagy is involved in normal placentation, thus changes in autophagy may lead to impaired placental function and development. The aim of this study was to investigate the connection between obesity and autophagy in the placenta in otherwise uncomplicated pregnancies. METHODS: Immunohistochemistry and western blot analysis were done on placental and omental samples from obese (body mass index [BMI] ≥30 kg/m RESULTS: As pre-pregnancy BMI increased, there was an increase in both placental and fetal weight as well as decreased levels of LC3B in the central region of the placenta (P = 0.0046). Within the obese patient group, LC3B levels were significantly decreased in the placentas of male fetuses compared to females (P \u3c 0.0001). Adipocytes, compared to milky spots and vasculature, had lower levels of p62 (P = 0.0127) and LC3B (P = 0.003) in obese omenta and lower levels of LC3B in control omenta (P = 0.0071). CONCLUSION: Obesity leads to reduced placental autophagy in uncomplicated pregnancies; thus, changes in autophagy may be involved in the underlying mechanisms of obesity-related placental diseases of pregnancy

Highlighting the Mechanistic Relationship Between Perinatal Depression and Preeclampsia: A Scoping Review

Background: Although there is scientific literature supporting an association between depression and preeclampsia (PE), little is known about the underlying mechanistic pathways that may explain these observed associations. Thus, this study aimed to outline the relationship between depression and PE, and to highlight the underlying cardiovascular and metabolic risk factors that are common to both. Methods: A scoping review of the literature was conducted in Medline, Scopus, and Web of Science. Results: From 706 articles initially identified, 23 articles met the inclusion criteria and were included in this review. Although some studies reported a positive association between PE and postpartum depressive symptoms, challenges comparing different methodologies, measurement instruments and when measurements were administered, and patient populations do not permit a decisive conclusion. In addition, very few studies addressed potential underlying mechanisms that may be contributing to observed associations; thus, a secondary search was conducted to identify cardiovascular and metabolic risk factors that are common to both depression and PE. Conclusion: The cardiovascular and metabolic risk factors (i.e., increased inflammation and oxidative stress and decreased vascular and endothelial function) common to both depression and PE suggest that these factors may contribute as underlying mechanisms in both conditions. These similarities underscore the importance to better understand these mechanisms so preventative and therapeutic strategies could be developed to improve maternal health

Adrenal Cushing Syndrome Diagnosed during Pregnancy: Successful Medical Management with Metyrapone

Adrenal Cushing syndrome during pregnancy is rare, and there is limited information on the effect and safety of metyrapone treatment both for mother and fetus. We present a 24-year-old woman diagnosed with adrenal Cushing syndrome at the end of the second trimester. We elected treatment with metyrapone titrated to 250 mg 3 times daily, resulting in good clinical response and maternal serum and saliva cortisol levels in the upper half of the normal pregnancy range. A healthy male infant was born at 35 weeks\u27 gestation, with no clinical signs of adrenal insufficiency, this despite a low cortisol of 5 nmol/L on the first day of life. We measured metyrapone in maternal and umbilical cord blood samples, demonstrating fetal venous metyrapone levels similar to maternal venous concentration, and a fetal arterial cord concentration at about 60% of the fetal venous cord concentration. This case demonstrates that salivary cortisol levels may be used to monitor the effect of metyrapone on adrenal Cushing syndrome during pregnancy. We show, for the first time in humans, that metyrapone does cross the placenta and may suppress fetal cortisol production without necessarily causing clinical signs of adrenal insufficiency

Adrenal Cushing Syndrome Diagnosed during Pregnancy: Successful Medical Management with Metyrapone

Adrenal Cushing syndrome during pregnancy is rare, and there is limited information on the effect and safety of metyrapone treatment both for mother and fetus. We present a 24-year-old woman diagnosed with adrenal Cushing syndrome at the end of the second trimester. We elected treatment with metyrapone titrated to 250 mg 3 times daily, resulting in good clinical response and maternal serum and saliva cortisol levels in the upper half of the normal pregnancy range. A healthy male infant was born at 35 weeks\u27 gestation, with no clinical signs of adrenal insufficiency, this despite a low cortisol of 5 nmol/L on the first day of life. We measured metyrapone in maternal and umbilical cord blood samples, demonstrating fetal venous metyrapone levels similar to maternal venous concentration, and a fetal arterial cord concentration at about 60% of the fetal venous cord concentration. This case demonstrates that salivary cortisol levels may be used to monitor the effect of metyrapone on adrenal Cushing syndrome during pregnancy. We show, for the first time in humans, that metyrapone does cross the placenta and may suppress fetal cortisol production without necessarily causing clinical signs of adrenal insufficiency

Maternal, pregnancy and fetal outcomes in de novo anti-glomerular basement membrane antibody disease in pregnancy: A systematic review

Background Outside of pregnancy, anti-glomerular basement membrane (GBM) antibody disease is associated with significant morbidity and mortality. However, there is limited knowledge regarding de novo anti-GBM disease in pregnancy. Methods A systematic review was performed to identify maternal, pregnancy and fetal outcomes in de novo anti-GBM disease in pregnancy. Studies were selected from PubMed, EMBASE, Cochrane Library databases and conference proceedings, without language restriction. Results Data from eight patients were derived from seven case reports and one unpublished case. Most (6/8) patients presented after the first trimester. During pregnancy, acute kidney injury (5/8), anemia (5/8), hematuria (8/8) and proteinuria (8/8) were common. When hemodialysis was required antepartum (5/8), renal function recovery to independence of renal replacement was unlikely (2/5). While pulmonary involvement was common (5/8), no permanent damage was reported (0/8). The majority of cases ended in live births (6/8) although prematurity (6/6), intrauterine growth restriction (2/6), small for gestational age (4/6) and complications of prematurity (1/6) were common. When anti-GBM levels were tested in the living newborn, they were detectable (2/5), but no newborn renal or lung disease was reported (0/6). Complications in pregnancy included gestational diabetes (3/8), hyperemesis gravidarum (2/8) and preeclampsia (2/8). Conclusions Live births can be achieved in de novo anti-GBM disease in pregnancy, but are commonly associated with adverse maternal, pregnancy and fetal outcomes. Only with awareness of common presentations, and management strategies can outcomes be optimized