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Endocrine Feb 2024During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use... (Review)
Review
During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the offspring. Metformin has been validated for maternal efficacy and safety, achieving comparable glycemic control with insulin. Additionally, it reduces maternal weight gain and possibly the occurrence of hypertensive disorders. During the early neonatal period, metformin administration does not increase the risk of congenital anomalies or other major adverse effects, including lower APGAR score at 5 min, neonatal intensive care unit admissions, and respiratory distress syndrome. Several studies have demonstrated a reduction in neonatal hypoglycemia. Metformin has been associated with an increase in preterm births and lower birth weight, although this effect is controversial and depends on the indication for which it was administered. Evidence indicates possible altered fetal programming and predisposition to childhood obesity and metabolic syndrome during adulthood after use of metformin in pregnancy. With critical questions still requiring a final verdict, ongoing research on the field must be conducted.
Topics: Child; Pregnancy; Infant, Newborn; Female; Humans; Adult; Metformin; Hypoglycemic Agents; Pediatric Obesity; Diabetes, Gestational; Insulin; Pregnancy Outcome
PubMed: 37798604
DOI: 10.1007/s12020-023-03550-0 -
Frontiers in Endocrinology 2023During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an... (Review)
Review
During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Metformin; Hypoglycemic Agents; Insulin Resistance; Diabetes Mellitus, Type 2; Breast Feeding; Polycystic Ovary Syndrome; Diabetes, Gestational; Abortion, Spontaneous; Obesity
PubMed: 37409227
DOI: 10.3389/fendo.2023.1176623 -
Frontiers in Endocrinology 2023Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and... (Review)
Review
Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and child. Children of mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease and GDM when they themselves become pregnant, perpetuating a multigenerational increased risk of metabolic disease. The negative effect of GDM is exacerbated by maternal obesity, which induces a greater derangement of fetal adipogenesis and growth. Multiple factors, including genetic, epigenetic and metabolic, which interact with lifestyle factors and the environment, are likely to contribute to the development of GDM. Genetic factors are particularly important, with 30% of women with GDM having at least one parent with T2D. Fetal epigenetic modifications occur in response to maternal GDM, and may mediate both multi- and transgenerational risk. Changes to the maternal metabolome in GDM are primarily related to fatty acid oxidation, inflammation and insulin resistance. These might be effective early biomarkers allowing the identification of women at risk of GDM prior to the development of hyperglycaemia. The impact of the intra-uterine environment on the developing fetus, "developmental programming", has a multisystem effect, but its influence on adipogenesis is particularly important as it will determine baseline insulin sensitivity, and the response to future metabolic challenges. Identifying the critical window of metabolic development and developing effective interventions are key to our ability to improve population metabolic health.
Topics: Child; Female; Humans; Pregnancy; Biomarkers; Diabetes Mellitus, Type 2; Diabetes, Gestational; Hyperglycemia; Insulin Resistance; Mothers; Extended Family
PubMed: 38288471
DOI: 10.3389/fendo.2023.1245899 -
Seminars in Reproductive Medicine Jul 2023Obesity is a highly prevalent chronic disease with a significant effect on reproductive-age women. The clinical implications of obesity on fertility and pregnancy are... (Review)
Review
Obesity is a highly prevalent chronic disease with a significant effect on reproductive-age women. The clinical implications of obesity on fertility and pregnancy are well studied citing ovulatory dysfunction, hormonal imbalances, higher miscarriage rates, and increased maternal and neonatal risks. For this reason, many patients with obesity seek reproductive specialists to help build their families. Despite this literature base, the effect of weight loss interventions prior to assisted reproductive technology (ART) is lacking. This review aims to outline the impact of obesity on ART, specifically in vitro fertilization (IVF). Response differences to treatment protocols compared with normal weight counterparts, limitations of access to care, and the mixed results of weight-reduction strategies prior to fertility treatment will be addressed. The known data surrounding benefits of lifestyle modification, pharmacologic therapies, and surgical interventions for obesity prior to IVF are outlined and found to emphasize a need for further research to determine the optimal approach for infertility patients with obesity.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Obesity; Fertilization in Vitro; Infertility; Fertility; Abortion, Spontaneous
PubMed: 37913788
DOI: 10.1055/s-0043-1776420 -
Frontiers in Medicine 2023In this review, we provide a comprehensive overview of common sleep disorders during pregnancy, including their characterization, prevalence, risk factors, and possible... (Review)
Review
In this review, we provide a comprehensive overview of common sleep disorders during pregnancy, including their characterization, prevalence, risk factors, and possible contribution to maternal and fetal outcomes. We conducted a quasi-systematic literature search of the MEDLINE database and identified 744 studies from 1991 through 2021, inclusive, that met our inclusion criteria. We synthesized the existing literature on sleep disorders during pregnancy and highlighted controversies, research gaps, and needed clinical developments. Our review covers a range of sleep disorders, including insomnia, obstructive sleep apnea, restless legs syndrome, and circadian rhythm disorders. We discuss the prevalence of these disorders in pregnancy and their potential impact on maternal and fetal health outcomes. We also explore the relationship between sleep disorders, pre-pregnancy comorbidities such as obesity, and pregnancy-related conditions such as gestational diabetes mellitus and preeclampsia. In addition to summarizing the existing literature on sleep disorders during pregnancy, we also highlight opportunities for further research in this area. We suggest that future studies should strive to employ validated and objective measurement tools for sleep disorders and prioritize utilization of longitudinal methods with participant follow-up through postpartum, mid-life, menopause, and beyond. We also put forward investigation into the impact of circadian rhythm disruption on reproductive physiology and early pregnancy outcomes as an area of important work. Overall, our review provides valuable insights on sleep and reproduction and into common sleep disorders during pregnancy and their potential impact on maternal and fetal health outcomes.
PubMed: 37671402
DOI: 10.3389/fmed.2023.1235252 -
Current Nutrition Reports Sep 2023Childhood obesity is a growing health problem in many populations, hence the urgent need to unravel the underlying mechanisms. Some evidence suggests that exposure to... (Review)
Review
PURPOSE OF REVIEW
Childhood obesity is a growing health problem in many populations, hence the urgent need to unravel the underlying mechanisms. Some evidence suggests that exposure to suboptimal intrauterine environments can program foetal metabolic health, with adverse consequences in later life, including susceptibility to childhood obesity.
FINDINGS
Factors such as high and low foetal birth weight, excessive gestational-weight-gain, maternal stress and smoking are all associated with increased risk of childhood obesity in observational studies. Animal models, where both genetic background and the postnatal environment can be carefully controlled, suggest that several different mechanisms, including epigenetic changes, dysregulation of adipose tissue development and programming of appetite, may be key drivers of developmental programming of childhood obesity. However, the influence of genetics and the post-natal environment are much more difficult to disentangle as independent effects in human studies, which are also complicated by low follow-up rates. Suboptimal intrauterine environments interact with maternal and foetal genetics and with the postnatal environment to contribute to the risk of childhood obesity. Maternal metabolic challenges, for example obesity and insulin resistance, contribute to the risk of foetal overgrowth and subsequent adiposity in childhood. To protect the long-term health of populations, research focusing on effective means of identifying and intervening in the transgenerational cycle of childhood obesity is required.
Topics: Animals; Child; Humans; Pediatric Obesity; Birth Weight; Adiposity; Weight Gain
PubMed: 37338777
DOI: 10.1007/s13668-023-00482-z