Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

Aims: Although preeclampsia (PE) has been attributed to excessive oxidative stress (OS) in the placenta, mild antioxidants failed to prevent PE in clinical trials. As mitochondria are a major source of OS, this study assessed the potential of a potent mitochondria-targeting antioxidant MitoQ in the prevention of PE. Results: Placentas from women with PE and from reduced uterine perfusion pressure (RUPP) mice demonstrated significantly higher OS, along with increased mitochondrial damage and compromised glutathione peroxidase (GPx) activities. MitoQ administration during late gestation alleviated RUPP-induced PE; whereas early-pregnancy MitoQ treatment not only exacerbated blood pressure, fetal growth restriction, and proteinuria but also reduced the labyrinth/spongiotrophoblast ratio and blood sinuses in the labyrinth. Invasion (Matrigel transwell) and migration (wound healing assay) of trophoblasts were greatly improved by 1 μM hydrogen peroxide (H₂O₂), but this improvement was abolished by MitoQ or MitoTempo. Mild OS enhanced the expression of miR-29b-3p, which regulates five genes involved in viability and mobility, in HTR8-S/Vneo cells. Innovation and Conclusions: Although the potent mitochondrial-targeting antioxidant MitoQ protects against hypertension and kidney damage induced by RUPP in mice when administered in late gestation, it exacerbates the PE-like phenotype when given in early gestation by interfering with placenta formation because mild OS is required to stimulate trophoblast proliferation, invasion, and migration. Eliminating trophoblastic OS during early pregnancy may lead to compromised placentation and a risk of diseases of placental origin. Therefore, antioxidant therapy for pregnant women should be carefully considered.

Hypertensive disorders of pregnancy (HDP) are the most common medical complication in pregnancy, affecting approximately 10–15% of pregnancies worldwide. HDP are a major cause of maternal and perinatal morbidity and mortality, and each year, worldwide, around 70,000 mothers and 500,000 babies die because of HDP. Up-to-date high-quality systematic reviews quantifying the role of exercise and the risks of developing HDP are currently lacking. Physical exercise is considered to be safe and beneficial to pregnant women. Supervised exercise has been shown to be safe and to be more beneficial than unsupervised exercise in the general population, as well as during pregnancy in women with obesity and diabetes. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of women performing supervised exercise during pregnancy compared to a control group (standard antenatal care or unsupervised exercise) on the development of HDP. We searched Medline, Embase, CINHAL, and the Cochrane Library, which were searched from inception to December 2021. We included only randomized controlled trials (RCTs) investigating the development of HDP compared to a control group (standard antenatal care or unsupervised exercise) in pregnant women performing supervised exercise. Two independent reviewers selected eligible trials for meta-analysis. Data collection and analyses were performed by two independent reviewers. The PROSPERO registration number is CRD42020176814. Of 6332 articles retrieved, 16 RCTs met the eligibility criteria, comparing a total of 5939 pregnant women (2904 pregnant women in the intervention group and 3035 controls). The risk for pregnant women to develop HDP was significantly reduced in the intervention compared to the control groups, with an estimated pooled cumulative incidence of developing HDP of 3% in the intervention groups (95% CI: 3 to 4) and of 5% in the control groups (95% CI: 5 to 6), and a pooled odds ratio (OR) comparing intervention to control of 0.54 (95% CI:0.40 to 0.72, p < 0.001). A combination of aerobic and anaerobic exercise, or yoga alone, had a greater beneficial effect compared to performing aerobic exercise only (mixed-OR = 0.50, 95% CI:0.33 to 0.75, p = 0.001; yoga-OR = 0.28, 95% CI:0.13 to 0.58, p = 0.001); aerobic exercise only-OR = 0.87, 95% CI:0.55 to 1.37, p = 0.539). Pregnancy is an opportunity for healthcare providers to promote positive health activities, thus optimizing the health of pregnant women with potential short- and long-term benefits for both mother and child. This systematic review and meta-analysis support a beneficial effect of either structured exercise (combination of aerobic, strength, and flexibility workouts) or yoga for preventing the onset of HDP. Yoga, considered a low-impact physical activity, could be more acceptable and safer for women in pregnancy in reducing the risk of developing HDP.

Background: Gestational diabetes mellitus (GDM) has been associated with several fetal complications, such as macrosomia and fetal growth restriction (FGR). Infants from GDM associated FGR are at increased risk for adult-onset obesity and associated metabolic disorders. However, the underlying mechanisms of GDM associated FGR remain to be explored. Methods: We analyzed placentas from GDM patients with FGR for ferroptosis markers and GLUT1 expression. High glucose conditions were established by adding different concentrations of D-Glucose to the 1640 cell culture medium. RSL3 were used to test ferroptosis sensitivity in trophoblast cells. GLUT1 was inhibited using siRNA or its inhibitor WZB117 to assess its impact on ferroptosis inhibition in HTR8/SVneo cell line. Mechanistic studies explored the effects of GLUT1 on AMPK and ACC phosphorylation, which in turn impacted lipid metabolism and ferroptosis. In mouse models, streptozotocin (STZ)-induced GDM was treated with WZB117 and the ferroptosis inhibitor liproxstatin-1 (Lip-1). Finally, AMPK and ACC phosphorylation levels were evaluated in GDM patient samples. Results: In this study, placentas from GDM patients with FGR showed signs of ferroptosis and upregulation of GLUT1. In cell models, high glucose conditions sensitized trophoblast cells to ferroptosis and induced GLUT1 expression. Interestingly, GLUT1 inhibition significantly suppressed ferroptosis in trophoblast cells under high glucose conditions. Mechanistically, elevated GLUT1 inhibited AMPK phosphorylation and reduced ACC phosphorylation, thereby promoting lipid synthesis and facilitating ferroptosis. In pregnant mice, STZ-induced hyperglycemia led to FGR, and treatment with either the GLUT1 inhibitor WZB117 or the ferroptosis inhibitor Lip-1 alleviated the FGR phenotype. Moreover, in vivo elevation of GLUT1 increased ferroptosis markers, decreased AMPK/ACC phosphorylation, and resulted in altered lipid metabolism, which likely contributed to the observed phenotype. Finally, placental samples from GDM patients showed reduced AMPK and ACC phosphorylation. Conclusions: Our findings suggest a potential role of ferroptosis in GDM associated FGR and indicate that the dysregulated GLUT1-AMPK-ACC axis may be involved in the pathogenesis of GDM associated FGR in clinicals.

Background: Prediction of preeclampsia is a challenge to overcome. The vast majority of prospective studies in large general obstetric populations have failed in the purpose of obtain a useful and effective model of prediction, sometimes based on complex tools unavaible in areas where the incidence of preeclampsia is the highest. The goal of this study was to assess mean arterial blood pressure (MAP) levels at 19–21, 27–29 and 37–39 weeks of gestation and performance of screening by MAP for the prediction of preeclampsia in a Brazilian cohort of healthy nulliparous pregnant women. Methods: This was a cohort approach to a secondary analysis of the Preterm SAMBA study. Mean arterial blood pressure was evaluated at three different time periods during pregnancy. Groups with early-onset preeclampsia, late-onset preeclampsia and normotension were compared. Increments in mean arterial blood pressure between 20 and 27 weeks and 20 and 37 weeks of gestation were also calculated for the three groups studied. The accuracy of mean arterial blood pressure in the prediction of preeclampsia was determined by ROC curves. Results: Of the 1373 participants enrolled, complete data were available for 1165. The incidence of preeclampsia was 7.5%. Women with early-onset preeclampsia had higher mean arterial blood pressure levels at 20 weeks of gestation, compared to the normotensive group. Women with late-onset preeclampsia had higher mean arterial blood pressure levels at 37 weeks of gestation, than the normotensive groups and higher increases in this marker between 20 and 37 weeks of gestation. Based on ROC curves, the predictive performance of mean arterial blood pressure was higher at 37 weeks of gestation, with an area under the curve of 0.771. Conclusion: As an isolated marker for the prediction of preeclampsia, the performance of mean arterial blood pressure was low in a healthy nulliparous pregnant women group. Considering that early-onset preeclampsia cases had higher mean arterial blood pressure levels at 20 weeks of gestation, future studies with larger cohorts that combine multiple markers are needed for the development of a preeclampsia prediction model.

Objective: This study explores the basic demographic characteristics of expectant mothers in the context of their intentions regarding mode of delivery, in particular, the preference for caesarean delivery, and analyzes the social and psychological factors that influence delivery preference. Method: A cross-sectional survey of pregnant women was conducted during June to August in 2015. This study adopted a stratified sampling method, and 16 representative hospitals in five provinces of China were included. Results: 1755 and 590 of expectant mothers in their first and second pregnancies, respectively, were enrolled in this study. 354 (15.10%) intended to deliver by caesarean section and 585 (24.95%) participants were uncertain prior to delivery. 156 (8.89%) of expectant mothers in their first pregnancy and 198 (33.56%) expectant mothers in their second pregnancy intended to deliver by caesarean section. Ordinal logistic regression analysis found that nationality, parity, trimester of pregnancy, and advanced maternal age were factors associated with intention to deliver by caesarean (ordered logistic regression/three-level caesarean delivery intention criterion; odds ratios p < 0.05). Conclusions: 8.89% of first pregnancy expectant mothers and 33.56% of second pregnancy expectant mothers intended to deliver by caesarean section. Any intervention program to reduce the rate of Caesarean delivery should focus on the Han population, older pregnant women, and expectant mothers in their second pregnancy, at an early gestation.