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Biochimica Et Biophysica Acta.... Dec 2023Gestational diabetes mellitus (GDM) and maternal obesity (MO) increase the risk of adverse fetal outcomes, and the incidence of cardiovascular disease later in life.... (Review)
Review
Gestational diabetes mellitus (GDM) and maternal obesity (MO) increase the risk of adverse fetal outcomes, and the incidence of cardiovascular disease later in life. Extensive research has been conducted to elucidate the underlying mechanisms by which GDM and MO program the offspring to disease. This review focuses on the role of fetoplacental endothelial dysfunction in programming the offspring for cardiovascular disease in GDM and MO pregnancies. We discuss how pre-existing maternal health conditions can lead to vascular dysfunction in the fetoplacental unit and the fetus. We also examine the role of fetoplacental endothelial dysfunction in impairing fetal cardiovascular system development and the involvement of nitric oxide and hydrogen sulfide in mediating fetoplacental vascular dysfunction. Furthermore, we suggest that the L-Arginine-Nitric Oxide and the Adenosine-L-Arginine-Nitric Oxide (ALANO) signaling pathways are pertinent targets for research. Despite significant progress in this area, there are still knowledge gaps that need to be addressed in future research.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Placenta; Nitric Oxide; Cardiovascular Diseases; Obesity, Maternal; Arginine
PubMed: 37541330
DOI: 10.1016/j.bbadis.2023.166834 -
The Journal of Maternal-fetal &... Dec 2022Maternal age, maternal obesity and neonatal sex dimorphism are known to affect pregnancy and neonatal outcome. However, the effects of these factors on specific...
OBJECTIVE
Maternal age, maternal obesity and neonatal sex dimorphism are known to affect pregnancy and neonatal outcome. However, the effects of these factors on specific placental pathology are less well-documented.
STUDY DESIGN
Clinical information, placental pathology and neonatal data from singleton delivery were collected at our hospital in March 2020 to October 2021 and correlation studies were performed.
RESULTS
A total 3,119 singleton placentas were examined between March 2020 and October 2021 in conjunction with clinical information and neonatal birth data. Advanced maternal age (>35) was significantly associated with a variety of pregnancy complications and placental pathology including preeclampsia/pregnancy induced hypertension (Pre/PIH), gestational diabetes mellitus (GDM2), intrauterine growth restriction (IUGR), and increased maternal body mass index (BMI) at delivery. Maternal obesity (BMI >30 at the time of delivery) was significantly associated with a variety of clinical features and placental pathology including PRE/PIH, GDM2 and decidual vasculopathy (mural arterial hypertrophy). No specific placental pathology was associated with neonatal sex except for more maternal inflammatory response (MIR, chronic deciduitis) in neonates of male sex.
CONCLUSION
Maternal age and maternal obesity were associated with not only clinical complications of pregnancy and neonatal birth weight but also specific placental pathology. Understanding the effects of maternal and environmental factors will help improve pregnancy outcome.
Topics: Infant, Newborn; Pregnancy; Female; Male; Humans; Placenta; Maternal Age; Obesity, Maternal; Pregnancy Outcome; Fetal Growth Retardation; Diabetes, Gestational
PubMed: 35225123
DOI: 10.1080/14767058.2022.2044777 -
International Journal of Molecular... May 2020Inflammation is often equated to the physiological response to injury or infection. Inflammatory responses defined by cytokine storms control cellular mechanisms that... (Review)
Review
Inflammation is often equated to the physiological response to injury or infection. Inflammatory responses defined by cytokine storms control cellular mechanisms that can either resolve quickly (i.e., acute inflammation) or remain prolonged and unabated (i.e., chronic inflammation). Perhaps less well-appreciated is the importance of inflammatory processes central to healthy pregnancy, including implantation, early stages of placentation, and parturition. Pregnancy juxtaposed with disease can lead to the perpetuation of aberrant inflammation that likely contributes to or potentiates maternal morbidity and poor fetal outcome. Maternal obesity, a prevalent condition within women of reproductive age, associates with increased risk of developing multiple pregnancy disorders. Importantly, chronic low-grade inflammation is thought to underlie the development of obesity-related obstetric and perinatal complications. While diverse subsets of uterine immune cells play central roles in initiating and maintaining healthy pregnancy, uterine leukocyte dysfunction as a result of maternal obesity may underpin the development of pregnancy disorders. In this review we discuss the current knowledge related to the impact of maternal obesity and obesity-associated inflammation on uterine immune cell function, utero-placental establishment, and pregnancy health.
Topics: Animals; Female; Humans; Inflammation; Models, Biological; Obesity, Maternal; Placenta; Pregnancy; Uterus
PubMed: 32471078
DOI: 10.3390/ijms21113776 -
Biochimica Et Biophysica Acta.... Feb 2020In recent years, the vascular endothelium has gained attention as a key player in the initiation and development of pregnancy disorders. Endothelium acts as an endocrine... (Review)
Review
In recent years, the vascular endothelium has gained attention as a key player in the initiation and development of pregnancy disorders. Endothelium acts as an endocrine organ that preserves the homeostatic balance by responding to changes in metabolic status. However, in metabolic disorders, endothelial cells adopt a dysfunctional function, losing their normal responsiveness. During pregnancy, several metabolic changes occur, in which endothelial function decisively participates. Similarly, when pregnancy metabolic disorders occur, endothelial dysfunction plays a key role in pathogenesis. This review outlines the main findings regarding endothelial dysfunction in three main metabolic pathological conditions observed during pregnancy: gestational diabetes, hypertensive disorders, and obesity and hyperlipidemia. Organ, histological and cellular characteristics were thoroughly described. Also, we focused in discussing the underlying molecular mechanisms involved in the cellular signaling pathways that mediate responses in these pathological conditions.
Topics: Animals; Diabetes, Gestational; Eclampsia; Endothelial Cells; Endothelium, Vascular; Female; Homeostasis; Humans; Hyperlipidemias; Hypertension, Pregnancy-Induced; Lipids; Metabolic Diseases; Obesity, Maternal; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Signal Transduction
PubMed: 30794867
DOI: 10.1016/j.bbadis.2019.02.009 -
The Australian & New Zealand Journal of... Oct 2022
Topics: Female; Humans; Obesity; Obesity, Maternal; Pregnancy; Pregnancy Complications
PubMed: 36250401
DOI: 10.1111/ajo.13610 -
The American Journal of Clinical... Apr 2021
Topics: Body Mass Index; Child; Female; Humans; Milk, Human; Obesity, Maternal; Pediatric Obesity; Pregnancy; Regression Analysis
PubMed: 33742200
DOI: 10.1093/ajcn/nqab009 -
Associations of maternal obesity, frozen embryos, and offspring adverse cardiometabolic alterations.Fertility and Sterility Dec 2022To evaluate the long-term cardiometabolic health of offspring conceived by frozen embryo transfer and born to mothers with overweight/obesity.
OBJECTIVE
To evaluate the long-term cardiometabolic health of offspring conceived by frozen embryo transfer and born to mothers with overweight/obesity.
DESIGN
Retrospective cohort study.
SETTING
Center for Reproductive Medicine.
PATIENT(S)
A total of 2,741 offspring born to mothers who underwent in vitro fertilization/intracytoplasmic sperm injection treatment were followed between June 2014 and August 2021. The offspring were singletons aged 4-11 years at follow-up.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Age-specific z-scores of cardiometabolic parameters were examined, including adiposity, systolic/diastolic blood pressure, glucose, and lipid profiles, and the metabolic sum score of different cardiometabolic characteristics.
RESULTS
Of 2,741 offsprings, 965 (35.21%) were born to mothers with overweight/obesity, including 396 (41.04%) offspring who were conceived by frozen embryo transfer. After adjusting for paternal and maternal age, paternal body mass index (BMI), offspring age, offspring sex, and offspring postnatal energy intake, offspring born to mothers with overweight/obesity and conceived by frozen embryo transfer showed a significantly higher BMI z-score, systolic blood pressure z-score, metabolic sum score-1, and metabolic sum score-2 compared with those conceived by fresh embryo transfer (BMI z-score: adjusted mean difference, 0.17; 95% confidence interval [CI], 0.04-0.30; systolic blood pressure z-score: adjusted mean difference, 0.16; 95% CI, 0.02-0.29; metabolic sum score-1: adjusted mean difference, 0.54; 95% CI, 0.15-0.94; metabolic sum score-2: adjusted mean difference, 0.45; 95% CI, 0.07-0.83). However, in offspring of mothers with normal weight, offspring conceived by frozen embryo transfer showed a significantly lower low-density lipoprotein-cholesterol z-score compared with those conceived by fresh embryo transfer (adjusted mean difference, -0.12; 95% CI, -0.22 to -0.02). Other cardiometabolic parameters were comparable between offspring with frozen and fresh embryo transfers after adjusting for multivariate confounder variables.
CONCLUSIONS
This study found that among offspring from mothers who were overweight/obese, those offspring conceived by frozen embryo transfer were associated with higher systolic blood pressure z-scores and adverse metabolic changes compared with those conceived by fresh embryo transfer. The changes show that the association between frozen embryo transfer and offspring adverse cardiometabolic changes is apparent only among those born to mothers who are overweight/obese.
Topics: Male; Female; Pregnancy; Humans; Obesity, Maternal; Retrospective Studies; Semen; Embryo Transfer; Obesity
PubMed: 36283861
DOI: 10.1016/j.fertnstert.2022.09.004 -
The Journal of Maternal-fetal &... Sep 2021To determine the effect of preexisting maternal obesity and gestational diabetes mellitus (GDM) on the circulating levels of Metrnl in cord and maternal plasma.
OBJECTIVE
To determine the effect of preexisting maternal obesity and gestational diabetes mellitus (GDM) on the circulating levels of Metrnl in cord and maternal plasma.
DESIGN
Metrnl levels were measured on maternal and cord plasma from women with normal glucose tolerance (NGT) (19 non-obese and 20 obese), GDM controlled by diet (18 non-obese and 17 obese) and GDM controlled by insulin (19 non-obese and 18 obese) at the time of term elective cesarean section. Metrnl concentrations were determined by enzyme-linked immunoassay. Correlations of Metrnl levels with anthropometric parameters and laboratory measurements were also assessed.
RESULTS
There was no effect of maternal obesity or GDM on maternal plasma Metrnl concentrations. In cord plasma, Metrnl concentrations were significantly lower in NGT obese compared to NGT non-obese women and in non-obese GDM women compared to non-obese NGT women. Significant positive correlations were observed between maternal plasma Metrnl and cord plasma Metrnl. In cord plasma, significant positive correlations were observed between Metrnl levels and GWG and maternal and cord plasma glucose levels at delivery.
CONCLUSIONS
At the time of term cesarean section, preexisting maternal obesity and GDM are associated with lower Metrnl levels in cord plasma. Alterations in cord plasma Metrnl levels may lead to alterations in fetal growth trajectory and be a determinant for metabolic disorders later in life.
Topics: Cesarean Section; Diabetes, Gestational; Female; Humans; Obesity; Obesity, Maternal; Pregnancy; Pregnancy Complications
PubMed: 31608723
DOI: 10.1080/14767058.2019.1676713 -
Current Vascular Pharmacology 2021The incidence of obesity is rising rapidly worldwide with the consequence that more women are entering pregnancy overweight or obese. This leads to an increased... (Review)
Review
The incidence of obesity is rising rapidly worldwide with the consequence that more women are entering pregnancy overweight or obese. This leads to an increased incidence of clinical complications during pregnancy and of poor obstetric outcomes. The offspring of obese pregnancies are often macrosomic at birth although there is also a subset of the progeny that are growth-restricted at term. Maternal obesity during pregnancy is also associated with cardiovascular, metabolic and endocrine dysfunction in the offspring later in life. As the interface between the mother and fetus, the placenta has a central role in programming intrauterine development and is known to adapt its phenotype in response to environmental conditions such as maternal undernutrition and hypoxia. However, less is known about placental function in the abnormal metabolic and endocrine environment associated with maternal obesity during pregnancy. This review discusses the placental consequences of maternal obesity induced either naturally or experimentally by increasing maternal nutritional intake and/or changing the dietary composition. It takes a comparative, multi-species approach and focusses on placental size, morphology, nutrient transport, metabolism and endocrine function during the later stages of obese pregnancy. It also examines the interventions that have been made during pregnancy in an attempt to alleviate the more adverse impacts of maternal obesity on placental phenotype. The review highlights the potential role of adaptations in placental phenotype as a contributory factor to the pregnancy complications and changes in fetal growth and development that are associated with maternal obesity.
Topics: Animals; Blood Glucose; Diabetes, Gestational; Energy Metabolism; Female; Humans; Maternal Nutritional Physiological Phenomena; Maternal-Fetal Exchange; Nutritional Support; Obesity, Maternal; Phenotype; Placenta; Placentation; Pregnancy; Pregnancy Outcome; Risk Factors
PubMed: 32400334
DOI: 10.2174/1570161118666200513115316 -
Best Practice & Research. Clinical... Jun 2024Venous thrombosis and thromboembolism (VTE) remain the leading cause of direct maternal deaths, occurring within 42 days of the end of pregnancy in the UK. Pregnancy is... (Review)
Review
Venous thrombosis and thromboembolism (VTE) remain the leading cause of direct maternal deaths, occurring within 42 days of the end of pregnancy in the UK. Pregnancy is associated with an overall 10-fold higher incidence of VTE than in the non-pregnant state and has been reported to reach up to 30-fold higher in the puerperium. This increased risk is further exacerbated by maternal obesity in a relationship that appears to be proportional with increasing Body Mass Index (BMI). Maternal obesity is the most common health problem in women of reproductive age with clinically significant health risks to women during pregnancy and after delivery. It is associated with poor perinatal and maternal outcomes, The incidence of maternal obesity has increased significantly worldwide over the last few decades and increasingly, pregnancy is being complicated by extreme or morbid obesity. In this review we discuss the challenges associated with the diagnosis and management of VTE in obese pregnant women and provide a review of the available current evidence.
Topics: Humans; Pregnancy; Female; Venous Thromboembolism; Obesity; Body Mass Index; Risk Factors; Pregnancy Complications, Cardiovascular; Anticoagulants; Obesity, Maternal; Obesity, Morbid; Pregnancy Complications
PubMed: 38452607
DOI: 10.1016/j.bpobgyn.2024.102471