Search Results (40)

The developmental origins of adult disease theory support the concept that undernourished fetuses are at risk of developing metabolic syndrome due to the energy-saving ‘Thrifty Phenotype’. This metabolic plasticity represents an evolutionary adaptation that allows individuals to resist the intense pressure caused by cyclically recurring periods of nutritional deprivation. A comprehensive review was conducted following an extensive literature search in the PubMed/Medline and EMBASE databases concerning reports on fetal/intrauterine growth restriction and its metabolic-related long-term outcomes. We only included articles written in English that were published before 1 July 2024. There are several underlying mechanisms and metabolic and endocrine adjustments shaped by the perinatal environment, and they all contribute to progression towards adult disease. From in utero malnutrition or other insults during the fetal period to fetal programing and postnatal catch-up growth, it is difficult to identify the exact moment when this adaptative phenomenon meant to assure fetal survival and to set children on their own physiological growth curves lose its beneficial effect, establishing the trajectory to obesity, insulin resistance, and other hallmarks of metabolic syndrome. With clinical correspondence to an altered body mass, composition, and eating behaviors, it is evident that the metabolic complications linked to FGR are intricate and arise from disturbances in several pathways and organs, but the underlying processes responsible for the long-term consequences are just starting to be understood. The lack of continuity in perinatal-to-pediatric FGR research sets the challenge of exploring new directions in future scientific opportunities. These will hopefully represent a cornerstone in the management of FGR-related metabolic disorders in children, preventing these disorders from evolving into adult disease. Full article

Intrauterine growth restriction (IUGR) is a risk factor for postnatal cardiovascular, metabolic, and psychiatric disorders. In most IUGR models, placental dysfunction that causes reduced 11β-hydroxysteroid dehydrogenase 2 (11βHSD2) activity, which degrades glucocorticoids (GCs) in the placenta, resulting in fetal GC overexposure. This overexposure to GCs continues to affect not only intrauterine fetal development itself, but also the metabolic status and neural activity in adulthood through epigenetic changes such as microRNA change, histone modification, and DNA methylation. We have shown that the IUGR model induced DNA hypomethylation in the paraventricular nucleus (PVN) in the brain, which in turn activates sympathetic activities, the renin–angiotensin system (RAS), contributing to the development of salt-sensitive hypertension. Even in adulthood, strong stress and/or exogenous steroids have been shown to induce epigenetic changes in the brain. Furthermore, DNA hypomethylation in the PVN is also observed in other hypertensive rat models, which suggests that it contributes significantly to the origins of elevated blood pressure. These findings suggest that if we can alter epigenetic changes in the brain, we can treat or prevent hypertension. Full article

Intrauterine growth restriction (IUGR), the failure of the fetus to achieve his/her growth potential, is a common and complex problem in pregnancy. Clinically, IUGR is usually monitored using Doppler ultrasound of the umbilical artery (UA). The Doppler waveform is generally divided into three typical patterns in IUGR development, from normal blood flow (Normal), to the loss of end diastolic blood flow (LDBF), and even to the reversal of end diastolic blood flow (RDBF). Unfortunately, Doppler ultrasound hardly provides complete UA hemodynamics in detail, while the present in silico computational fluid dynamics (CFD) can provide this with the necessary ultrasound information. In this paper, CFD is employed to simulate the periodic UA blood flow for three typical states of IUGR, which shows comprehensive information on blood flow velocity, pressure, and wall shear stress (WSS). A new finding is the “hysteresis effect” between the UA blood flow velocity and pressure drop in which the former always changes after the latter by 0.1–0.2 times a cardiac cycle due to the unsteady flow. The degree of hysteresis is a promising indicator characterizing the evolution of IUGR. CFD successfully shows the hemodynamic details in different development situations of IUGR, and undoubtedly, its results would also help clinicians to further understand the relationship between the UA blood flow status and fetal growth restriction. Full article

Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee’s index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee’s index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits. Full article

Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process that is disrupted in preeclampsia, which is characterized by elevated vascular resistance, reduced utero-placental blood flow, and intrauterine growth restriction. This study investigated PP13’s role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries, isolated from both pregnant and non-pregnant women, were precontracted with the thromboxane analogue U46619 and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated, using specific inhibitors for nitric oxide synthase (L-NAME+LNNA at 10⁻⁴ M) and guanylate cyclase (ODQ at 10⁻⁵ M). The results showed that PP13 induced vasodilation in uterine arteries, but not in subcutaneous arteries. Additionally, PP13 counteracted U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13’s mechanism of action is dependent on the activation of the nitric oxide–cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine arteries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest that PP13 may be a promising candidate for improving utero-placental blood flow in conditions such as preeclampsia. Further research and clinical studies are warranted to validate PP13’s efficacy and safety as a therapeutic agent for managing preeclampsia. Full article

Postpartum hypertension (PPHT) is hypertension that persists or develops after delivery and is a frequent cause of readmission, affecting 10% of pregnancies. This interim analysis aims to describe the cohort and to determine the feasibility and acceptance of a home-based telemonitoring management strategy (HBTMS) in PPHT patients. Enrollment at the University Hospital Basel began during the 2020 SARS-CoV-2 pandemic. Maternity-ward patients were screened for preexisting hypertension, hypertensive disorders of pregnancy, and de novo PPHT. In this pragmatic non-randomized prospective trial, the participants chose the HBTMS or standard of care (SOC), which consisted of outpatient hypertension clinic appointments. The HBTMS was a smartphone application or a programmed spreadsheet to report blood pressure (BP), followed by telephone consultations. Three months postpartum, the participants underwent a 24 h BP measurement and a blood, biomarker, and urine analysis. A total of 311 participants were enrolled between 06/20 and 08/23. The mean age was 34 (±5.3) years. The current pregnancy history demonstrated the following (≥1 diagnosis possible): 10% had preexisting hypertension, 27.3% gestational hypertension, 53% preeclampsia (PE), 0.3% eclampsia, 6% HELLP (hemolysis, elevated liver enzymes, and low platelets), and 18.3% de novo PPHT. A family history of cardiovascular disease and PE was reported in 49.5% and 7.5%, respectively. In total, 23.3% were high-risk for PE. A total of 68.5% delivered via c-section, the mean hospitalization was 6.3 days (±3.9), and newborn intrauterine growth restriction occurred in 21%. A total of 99% of the participants chose the HBTMS. This analysis demonstrated that the HBTMS was accepted. This is vital in the immediate postpartum period and pertinent when the exposure of hospital visits should be avoided. Full article

Exposure to cigarette smoke is known to induce disease during pregnancy. Recent evidence showed that exposure to secondhand smoke (SHS) negatively impacts fetal and placental weights, leading to the development of intrauterine growth restriction (IUGR). Electronic cigarettes (eCigs) represent a phenomenon that has recently emerged, and their use is also steadily rising. Even so, the effects of SHS or eCigs during gestation remain limited. In the present study, we wanted to characterize the effects of SHS or eCig exposure at two different important gestational points during mouse pregnancy. C57/Bl6 mice were exposed to SHS or eCigs via a nose-only delivery system for 4 days (from 14.5 to 17.5 gestational days (dGA) or for 6 days (from 12.5 dGA to 17.5 dGA)). At the time of necropsy (18.5 dGA), placental and fetal weights were recorded, maternal blood pressure was determined, and a dipstick test to measure proteinuria was performed. Placental tissues were collected, and inflammatory molecules in the placenta were identified. Treatment with SHS showed the following: (1) a significant decrease in placental and fetal weights following four days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. Treatment with eCigs showed the following: (1) a significant decrease in placental weight and fetal weight following four or six days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. We also observed different inflammatory markers associated with the development of IUGR or PE. We conclude that the detrimental effects of SHS or eCig treatment coincide with the length of maternal exposure. These results could be beneficial in understanding the long-term effects of SHS or eCig exposure in the development of placental diseases. Full article

Obstructive sleep apnea (OSA) is a prevalent yet underdiagnosed condition in pregnancy, associated with various maternal and fetal complications. This review synthesizes the current evidence on the epidemiology, pathophysiology, and neurological consequences of OSA in pregnancy, along with the potential management strategies. Articles were sourced from the PubMed, EMBASE, and Cochrane databases until 2023. Our comprehensive review highlights that the incidence of OSA increases during pregnancy due to physiological changes such as weight gain and hormonal fluctuations. OSA in pregnancy is linked with gestational hypertension, pre-eclampsia, gestational diabetes, and potential adverse fetal outcomes such as intrauterine growth restriction and preterm birth. Continuous positive airway pressure (CPAP) therapy remains the most effective management strategy for pregnant women with OSA. However, adherence to CPAP therapy is often suboptimal. This comprehensive review underscores the importance of the early recognition, timely diagnosis, and effective management of OSA in pregnancy to improve both maternal and fetal outcomes. Future research should focus on enhancing screening strategies and improving adherence to CPAP therapy in this population. Full article

Exposure to secondhand smoke (SHS) during fetal development results in negative postnatal effects, including altered organ development, changes in metabolism, and increased risk of respiratory illness. Previously, we found the induction of intrauterine growth restriction (IUGR) dependent on the expression of the receptor for advanced glycation end-products (RAGE) in mice treated with SHS. Furthermore, antenatal SHS exposure increases RAGE expression in the fetal lung. Our objective was to determine the postnatal effects of antenatal SHS treatment in 4- and 12-week-old offspring. Pregnant animals were treated with SHS via a nose-only delivery system (Scireq Scientific, Montreal, Canada) for 4 days (embryonic day 14.5 through 18.5), and offspring were evaluated at 4 or 12 weeks of age. Animal and organ weights were measured, and lungs were histologically characterized. Blood pressure and heart rates were obtained, and RAGE protein expression was determined in the lungs of control and treated animals. We observed the following: (1) significant decreases in animal, liver, and heart weights at 4 weeks of age; (2) increased blood pressure in 4-week-old animals; and (3) increased RAGE expression in the lungs of the 4-week-old animals. Our results suggest an improvement in these metrics by 12 weeks postnatally such that measures were not different regardless of RA or SHS exposure. Increased RAGE expression in lungs from 4-week-old mice antenatally treated with SHS suggests a possible role for this important smoke-mediated receptor in establishing adult disease following IUGR pregnancies. Full article

Emerging evidence indicates a previously unrecognized, clinically relevant spectrum of abnormal aldosterone secretion associated with hypertension severity. It is not known whether excess aldosterone secretion contributes to hypertension during pregnancy. We quantified aldosterone concentrations and angiotensin peptides in serum (using liquid chromatography with tandem mass spectrometry) in a cohort of 128 pregnant women recruited from a high-risk obstetrics clinic and followed prospectively for the development of gestational hypertension, pre-eclampsia, superimposed pre-eclampsia, chronic hypertension, or remaining normotensive. The cohort was grouped by quartile of aldosterone concentration in serum measured in the first trimester, and blood pressure, angiotensin peptides, and hypertension outcomes compared across the four quartiles. Blood pressures and body mass index were greatest in the top and bottom quartiles, with the top quartile having the highest blood pressure throughout pregnancy. Further stratification of the top quartile based on increasing (13 patients) or decreasing (19 patients) renin activity over gestation revealed that the latter group was characterized by the highest prevalence of chronic hypertension, use of anti-hypertensive agents, pre-term birth, and intrauterine growth restriction. Serum aldosterone concentrations greater than 704 pmol/L, the 75th percentile defined within the cohort, were evident across all categories of hypertension in pregnancy, including normotensive. These findings suggest that aldosterone excess may underlie the development of hypertension in pregnancy in a significant subpopulation of individuals. Full article

Doppler findings of persistent reverse end-diastolic flow (PREDF) in a fetal middle cerebral artery (MCA) are a very rare sonographic finding and are a marker of poor fetal condition. This finding often leads to intrauterine fetal death or early neonatal death. Reverse end-diastolic flow in the middle cerebral artery is an advanced hemodynamic event. Fetal cerebral circulation normally has a high impedance; in the event of fetal hypoxemia, impedance decreases, resulting in the central redistribution of blood flow to vital organs, which maintains the oxygen delivery to the brain. Reverse flow in the middle cerebral arteries describes the loss of this autoregulatory process. PREDF is a sequence that occurs due to increased extracranial or intracranial pressure. Previous case reports mentioned intracranial hemorrhage, fetal growth restriction, fetal anemia, and fetal hepatic abnormalities as problems leading to PREDF. This condition presumably arises due to cerebral edema associated with severe hypoxemia. We reported Doppler findings of PREDF MCA in a 33-year-old female patient at 30 weeks gestation who was referred to the hospital with severe preeclampsia accompanied by fetal growth restriction and oligohydramnios. A cesarean section was performed due to severe preeclampsia and a low bishop score. Hypotheses on various etiologies and their association with intrauterine/neonatal death as well as the best management still require further investigation. Full article

Assisted reproductive technologies (ART) significantly increase the chance of successful pregnancy and live birth in infertile couples. The different procedures for ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), and gamete intrafallopian tube transfer (GIFT), are widely used to overcome infertility-related problems. In spite of its inarguable usefulness, concerns about the health consequences of ART-conceived babies have been raised. There are reports about the association of ART with birth defects and health complications, e.g., malignancies, high blood pressure, generalized vascular functional disorders, asthma and metabolic disorders in later life. It has been suggested that hormonal treatment of the mother, and the artificial environment during the manipulation of gametes and embryos may cause genomic and epigenetic alterations and subsequent complications in the health status of ART-conceived babies. In the current study, we aimed to review the possible long-term consequences of different ART procedures on the subsequent health status of ART-conceived offspring, considering the confounding factors that might account for/contribute to the long-term consequences. Full article

Adipokines are signaling proteins involved in metabolic, endocrinological, vascular and immunogenic processes. Associations of various adipokines with not only insulin resistance but also with increased insulin sensitivity, increased systolic blood pressure, and atherosclerosis highlight the significance of adipokines in several components of metabolic syndrome and metabolic diseases in general. As pregnancy presents a unique metabolic state, the role of adipokines in pregnancy, and even in various pregnancy complications, appears to be key to elucidating these metabolic processes. Many studies in recent years have attempted to clarify the role of adipokines in pregnancy and gestational pathologies. In this review, we aim to investigate the changes in maternal adipokine levels in physiological gestation, as well as the association of adipokines with pregnancy pathologies, such as gestational diabetes mellitus (GDM) and preeclampsia (PE). Furthermore, we will analyze the association of adipokines in both maternal serum and cord blood with parameters of intrauterine growth and various pregnancy outcomes. Full article

Fetal heart failure (FHF) is a condition of inability of the fetal heart to deliver adequate blood flow for tissue perfusion in various organs, especially the brain, heart, liver and kidneys. FHF is associated with inadequate cardiac output, which is commonly encountered as the final outcome of several disorders and may lead to intrauterine fetal death or severe morbidity. Fetal echocardiography plays an important role in diagnosis of FHF as well as of the underlying causes. The main findings supporting the diagnosis of FHF include various signs of cardiac dysfunction, such as cardiomegaly, poor contractility, low cardiac output, increased central venous pressures, hydropic signs, and the findings of specific underlying disorders. This review will present a summary of the pathophysiology of fetal cardiac failure and practical points in fetal echocardiography for diagnosis of FHF, focusing on essential diagnostic techniques used in daily practice for evaluation of fetal cardiac function, such as myocardial performance index, arterial and systemic venous Doppler waveforms, shortening fraction, and cardiovascular profile score (CVPs), a combination of five echocardiographic markers indicative of fetal cardiovascular health. The common causes of FHF are reviewed and updated in detail, including fetal dysrhythmia, fetal anemia (e.g., alpha-thalassemia, parvovirus B19 infection, and twin anemia-polycythemia sequence), non-anemic volume load (e.g., twin-to-twin transfusion, arteriovenous malformations, and sacrococcygeal teratoma, etc.), increased afterload (intrauterine growth restriction and outflow tract obstruction, such as critical aortic stenosis), intrinsic myocardial disease (cardiomyopathies), congenital heart defects (Ebstein anomaly, hypoplastic heart, pulmonary stenosis with intact interventricular septum, etc.) and external cardiac compression. Understanding the pathophysiology and clinical courses of various etiologies of FHF can help physicians make prenatal diagnoses and serve as a guide for counseling, surveillance and management. Full article

The endometrium undergoes repeated proliferation and shedding during the menstrual cycle. Significant changes to this environment include fluctuations in the partial pressure of oxygen, exposure to a high-cytokine environment associated with intrauterine infection, and inflammation. Chronic endometritis is a condition wherein mild inflammation persists in the endometrium and is one of the causes of implantation failure and miscarriage in early pregnancy. It is thought that the invasion of embryos into the endometrium requires epithelial–mesenchymal transition (EMT)-associated changes in the endometrial epithelium. However, the effects of inflammation on the endometrium remain poorly understood. In this study, we investigated the effects of the intrauterine oxygen environment, hypoxia-inducible factor (HIF), and inflammation on the differentiation and function of endometrial epithelial cells. We elucidated the ways in which inflammatory cytokines affect HIF activity and EMT in an immortalized cell line (EM-E6/E7/TERT) derived from endometrial epithelium. Pro-inflammatory cytokines caused significant accumulation of HIF-1α protein, increased HIF-1α mRNA levels, and enhanced hypoxia-induced accumulation of HIF-1α protein. The combined effect of inflammatory cytokines and hypoxia increased the expression of EMT-inducing factors and upregulated cell migration. Our findings indicate that pro-inflammatory factors, including cytokines and LPS, work synergistically with hypoxia to activate HIF-1 and promote EMT in endometrial epithelial cells. Full article