Improved neonatal outcomes in pregnancies with coexisting gestational diabetes and preeclampsia in normal birthweight neonates- insights from a retrospective cohort study.

INTRODUCTION: We aimed to assess neonatal and maternal outcomes in appropriate-for-gestational-weight (AGA) neonates of mothers with both gestational diabetes mellitus (GDM) and preeclampsia (PET). METHODS: Medical records of women diagnosed with GDM or PET were reviewed. Women with AGA neonates were divided into three groups- GDM, PET, and GDM + PET and maternal neonatal and placental outcomes were compared. The primary outcome was a composite of adverse neonatal outcomes, including intensive care unit admission (NICU), neurological morbidity, hypoglycemia, ventilation, respiratory distress syndrome (RDS), phototherapy, sepsis, blood transfusion, and neonatal death. Post-hoc analysis was performed to determine between-group significance. RESULTS: Composite adverse neonatal outcomes are significantly lower in women with multiple morbidities compared to women with confined PET (p = 0.015), and a similar trend is observed when comparing neonatal outcomes between women with GDM to those with GDM + PET, yet these results are underpowered (18.9 % vs. 12.8 % respectively, p = 0.243). Placentas of women with GDM + PET were larger, with a lower rate of placentas below the 10th percentile as compared to placentas of women with isolated PET (p < 0.001), but with similar rates of MVM lesions. DISCUSSION: While maternal and placental outcomes in patients of the GDM + PET group resemble the characteristics of the PET group, surprisingly, the neonatal outcomes in this group are significantly better compared to isolated morbidities. The paradoxical benefit attributed to the coexistence of GDM + PET may be explained by a balance of the opposing trends characterizing these morbidities-the reduced blood and nutrient supply characterizing PET vs. chronic overflow and abundance typical of GDM. CLINICAL TRIAL REGISTRATION: approval of local ethics committee WOMC-19-0152.

Weight Loss Prior to Pregnancy and Early Gestational Glycemia: Prepare, a Randomized Clinical Trial.

CONTEXT: Women with elevated body mass index are encouraged to lose weight before pregnancy, but no trials have tested the effects of prepregnancy weight loss on risk of developing gestational diabetes. OBJECTIVE: This work aims to determine whether prepregnancy weight loss improved the early metabolic environment as measured by early gestational diabetes diagnosis. METHODS: This was a secondary analysis of a pragmatic randomized clinical trial conducted between May 2015 and October 2019 in an integrated health system that encouraged first-trimester gestational diabetes screening for high-risk women, including those with obesity. Women aged 18 to 40 years with a body mass index (BMI) greater than or equal to 27 who were planning pregnancy were randomly assigned to a behavioral weight loss intervention or usual care. Clinical care decisions and data collection were blind to condition assignment. We compared rates of diagnosis with gestational diabetes in early pregnancy between the groups using logistic regression. RESULTS: Of 326 participants, 168 (89 in the intervention and 79 in usual care) had singleton pregnancies during the study period. At baseline, mean age was 31.3 ±â€…3.5 years and BMI was 34.8 ±â€…5.8. Fifty-nine (66%) intervention participants and 57 (72%) usual care participants underwent early screening. Among those, intervention participants were 73% less likely to be diagnosed with gestational diabetes than usual care participants (adjusted odds ratio [aOR], 0.27; 95% CI, 0.09-0.80). There was no difference in diagnosis of gestational diabetes in later pregnancy (aOR, 1.08; 95% CI, 0.41-2.81). CONCLUSION: Participation in a prepregnancy weight loss intervention led to lower rates of gestational diabetes diagnosis in early pregnancy. This suggests positive effects of prepregnancy weight loss on the early metabolic environment, a critical factor in offspring metabolic risk.

The Effect of Dietary Supplements on Oxidative Stress in Pregnant Women with Gestational Diabetes Mellitus: A Network Meta-Analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) exacerbates the oxidative stress status of the pregnant women. Τo improve the oxidative stress status, several therapeutic interventions have been suggested. The aim of this network meta-analysis is to assess the effect of different dietary supplements on the oxidative stress status in pregnant women with GDM. METHODS: A network meta-analysis of randomized control trials was performed comparing the changes delta (Δ) in total antioxidant capacity (TAC) and concentration of malondialdehyde (MDA) as primary outcomes, following different therapeutic interventions with dietary supplements in pregnant women with GDM. Four electronic databases and grey literature sources were searched. The secondary outcomes were other markers of oxidative stress. RESULTS: The meta-analysis included 16 studies of 1173 women with GDM. Regarding ΔTAC: probiotics and omega-3 with vitamin E were superior to placebo/no intervention. Regarding ΔMDA: vitamin D with calcium, omega-3, vitamin D, omega-3 with vitamin E, magnesium with zinc and calcium, and probiotics were superior to placebo/no intervention. CONCLUSIONS: Administration of dietary supplements in women with GDM can be helpful in limiting the oxidative stress which develop in these pregnancies.

Bioenergetics adaptations and redox homeostasis in pregnancy and related disorders.

Pregnancy is a challenging physiological process that involves maternal adaptations to the increasing energetics demands imposed by the growing conceptus. Failure to adapt to these requirements may result in serious health complications for the mother and the baby. The mitochondria are biosynthetic and energy-producing organelles supporting the augmented energetic demands of pregnancy. Evidence suggests that placental mitochondria display a dynamic phenotype through gestation. At early stages of pregnancy placental mitochondria are mainly responsible for the generation of metabolic intermediates and reactive oxygen species (ROS), while at later stages of gestation, the placental mitochondria exhibit high rates of oxygen consumption. This review describes the metabolic fingerprint of the placental mitochondria at different stages of pregnancy and summarises key signs of mitochondrial dysfunction in pathological pregnancy conditions, including preeclampsia, gestational diabetes and intrauterine growth restriction (IUGR). So far, the effects of placental-driven metabolic changes governing the metabolic adaptations occurring in different maternal tissues in both, healthy and pathological pregnancies, remain to be uncovered. Understanding the function and molecular aspects of the adaptations occurring in placental and maternal tissue's mitochondria will unveil potential targets for further therapeutic exploration that could address pregnancy-related disorders. Targeting mitochondrial metabolism is an emerging approach for regulating mitochondrial bioenergetics. This review will also describe the potential therapeutic use of compounds with a recognised effect on mitochondria, for the management of preeclampsia.

Association of circulating omega 3, 6 and 9 fatty acids with gestational diabetes mellitus: a systematic review.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased risks of disease for mother and child during pregnancy and after that. Early diagnosis of GDM would promote both maternal and fetal health. Metabolomics can simplify and develop our understanding of the etiology, manifestation, or pathophysiology of the disease. This systematic review investigates the association of circulating omega 3, 6, and 9 fatty acids with GDM. METHODS: We conducted a systematic search of PubMed, Scopus, Web of Science, and EMBASE databases up to May 8, 2020, using the key term combinations of all types of omega fatty acids with gestational diabetes mellitus. Additional articles were identified through searching the reference lists of included studies. RESULTS: This systematic review included 15 articles. Five were cohort studies, four included nested case-control studies and four were case-control studies. The results of this study demonstrate an increasing trend in the amount of oleic acid and palmitoleic acid in the second trimester and an increase in decosahexanoic acid in the third trimester of GDM mothers. The changes in other fatty acids of interest are either not significant or if significant, their results are inconsistent with the other existing articles. CONCLUSIONS: Omega fatty acids, as potential biomarkers, are considered to be associated with GDM risk and thus provide useful information regarding the prevention and early diagnosis of GDM. Moreover, existing metabolomic studies on GDM are shown to provide conflicting results about metabolite profile characteristics. This systematic review was registered at PROSPERO ( www.crd.york.ac.uk/PROSPERO ) as CRD42020196122.

Gestational Diabetes History and Glucose Tolerance After Pregnancy Associated With Coronary Artery Calcium in Women During Midlife: The CARDIA Study.

BACKGROUND: Gestational diabetes (GD) leads to earlier onset and heightened risk of type 2 diabetes, a strong risk factor for cardiovascular disease (CVD). However, it is unclear whether attaining normoglycemia can ameliorate the excess CVD risk associated with GD history. This study sought to evaluate GD history and glucose tolerance after pregnancy associated with coronary artery calcification (CAC) in women, a manifestation of atherosclerotic CVD and a predictor of CVD clinical events. METHODS: Data were obtained from the CARDIA study (Coronary Artery Risk Development in Young Adults), a US multicenter, community-based prospective cohort of young Black (50%) and White adults aged 18 to 30 years at baseline (1985-1986). The sample included 1133 women without diabetes at baseline, who had ≥1 singleton births (n=2066) during follow-up, glucose tolerance testing at baseline and up to 5 times during 25 years (1986-2011), GD status, and CAC measurements obtained from 1 or more follow up examinations at years 15, 20, and 25 (2001-2011). CAC was measured by noncontrast cardiac computed tomography; dichotomized as Any CAC (score>0) or No CAC (score=0). Complementary log-log models for interval-censored data estimated adjusted hazard ratios of CAC and 95% confidence intervals for GD history and subsequent glucose tolerance groups (normoglycemia, prediabetes, or incident diabetes) on average 14.7 years after the last birth adjusted for prepregnancy and follow-up covariates. RESULTS: Of 1133 women, 139 (12.3%) reported GD and were 47.6 years of age (4.8 SD) at follow-up. CAC was present in 25% (34/139) of women with GD and 15% (149/994) of women with no GD. In comparison with no GD/normoglycemia, adjusted hazard ratios (95% CIs) were 1.54 (1.06-2.24) for no GD/prediabetes and 2.17 (1.30-3.62) for no GD/incident diabetes, and 2.34 (1.34-4.09), 2.13 (1.09-4.17), and 2.02 (0.98-4.19) for GD/normoglycemia, GD/prediabetes, and GD/incident diabetes, respectively (overall P=0.003). CONCLUSIONS: Women without previous GD showed a graded increase in the risk of CAC associated with worsening glucose tolerance. Women with a history of GD had a 2-fold higher risk of CAC across all subsequent levels of glucose tolerance. Midlife atherosclerotic CVD risk among women with previous GD is not diminished by attaining normoglycemia.

The Impacts of Fish Oil and/or Probiotic Intervention on Low-Grade Inflammation, IGFBP-1 and MMP-8 in Pregnancy: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

BACKGROUND: We investigated the impact of fish oil and/or probiotics on serum and vaginal inflammatory and metabolic proteins and their relation to the onset of gestational diabetes mellitus (GDM). METHODS: Overweight/obese pregnant women received fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo from early pregnancy until six months postpartum (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid; probiotics: Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). Serum high sensitivity C-reactive protein (hsCRP) and serum/vaginal (s/v) phosphorylated insulin-like growth factor binding-protein-1 (phIGFBP-1), IGFBP-1 and matrix metalloproteinase 8 (MMP-8) were analyzed. GDM was diagnosed according to 2 h 75 g OGTT. RESULTS: The intervention had no impact on the change in proteins during pregnancy. Nevertheless, s-MMP-8 decreased and s-IGFBP-1 increased more in obese than in overweight women in the fish oil + probiotics group, while a decrease in s-MMP-8 was seen in obese women and an increase was seen in overweight women in the probiotics + placebo group. The late pregnancy s-phIGFBP-1 was higher in women who developed GDM in fish oil + probiotics-group compared to fish oil + placebo-group. The concentrations of s-phIGFBP-1 (635.9 ± 315.3 ng/mL vs. 753.2 ± 335.1 ng/mL, p = 0.005) and s-IGFBP-1 (3.78 ± 0.72 ng/mL vs. 3.96 ± 0.69 ng/mL, p = 0.042) were lower in early pregnancy in women who developed GDM than in women remaining healthy. CONCLUSIONS: The intervention per se had no impact on the proteins, but obesity and GDM may modify the effect. IGFBPs may affect the development of GDM.

Multiple Micronutrient Supplementation during Pregnancy and Increased Birth Weight and Skinfold Thicknesses in the Offspring: The Cambridge Baby Growth Study.

Multiple micronutrient supplementation (MMS) in pregnancy has previously been associated with positive effects on fetal growth, but its value in high-income countries remains controversial. In this study, we investigated effects of pregnancy MMS on offspring size at birth and adiposity, along with risks of various maternal outcomes of pregnancy, using the prospective Cambridge Baby Growth Study. Maternal MMS was reported in 528 out of 970 women who completed pregnancy questionnaires. Gestational diabetes (GDM) was assessed using results from 75 g oral glucose tolerance tests at week 28 of pregnancy. Offspring size at birth was assessed using standard anthropometric measurements and adiposity using skinfold calipers. MMS was associated with increased risk of developing GDM (risk ratio = 1.86 (1.13-3.08), p = 0.02), as well as increased offspring size at birth in terms of weight (p = 0.03), head circumference (p = 0.04), and flank, and subscapular and triceps skinfold thicknesses (p = 0.04, 0.03, and 0.003, respectively). There was no association with quadriceps skinfold thickness (p = 0.2), suggesting that the increased adiposity was partially regionalized. In women who underwent oral glucose tolerance testing, nearly all of these associations were attenuated by adjusting for GDM. These results suggest that the increased offspring size at birth, including (regionalized) adiposity associated with pregnancy, and MMS may be partially related to the development of GDM.

Exploring the role of LC-PUFA metabolism in pregnancy complications.

Maternal nutrition during pregnancy plays a significant role in growth and development of the placenta and influencing pregnancy outcome. Suboptimal nutritional status during early gestational period compromises the normal course of pregnancy leading to adverse maternal and fetal outcomes. Omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFA) are important for the growth and development of the placenta. Maternal fatty acids and their metabolites influence the normal course of pregnancy by regulating cell growth and development, cell signaling, regulate angiogenesis, modulate inflammatory responses and influence various structural and functional processes. Alterations in LC-PUFA and their metabolites may result in inadequate spiral artery remodeling or placental angiogenesis leading to structural and functional deficiency of the placenta which contributes to several pregnancy complications like preeclampsia, gestational diabetes mellitus, intrauterine growth restriction, and results in adverse birth outcomes. In this review, we summarize studies examining the role of fatty acids and their metabolites in pregnancy. We also discuss the possible molecular mechanisms through which LC-PUFA influences placental growth and development. Studies have demonstrated that omega-3 fatty acid supplementation lowers the incidence of preterm births, but its effect on reducing pregnancy complications are inconclusive.

Dietary Total Antioxidant Capacity and Gestational Diabetes Mellitus: A Case-Control Study.

BACKGROUND: Elevated oxidative stress status has been reported among pregnant women with gestational diabetes mellitus (GDM). In diabetic condition, glucose and lipid peroxidation, and alteration in antioxidant defense lead to increased free radicals. The objective of this study was to investigate the association between dietary total antioxidant capacity (DTAC) and GDM. METHODS: This hospital-based case-control study was conducted in 463 pregnant women (healthy, n = 263; GDM, n = 200). Anthropometric indices, blood pressure, and biochemical analyses were measured. Dietary intake was assessed by the average of three 24-hour dietary intake records. DTAC was calculated by three indices: ferric reducing ability of plasma (FRAP), total radical-trapping antioxidant parameter (TRAP), and Trolox equivalent antioxidant capacity (TEAC). Multivariable logistic regression was performed to examine the relationship between DTAC and GDM risk in crude and adjusted models. RESULTS: The mean age and BMI were 28.33 ± 6.23 years and 29.67 ± 4.73 kg/m2, respectively. Total energy, protein, and selenium intakes were significantly higher in cases than controls (P < 0.05). Moreover, intakes of carbohydrate, vitamins C, B6, and A, manganese, fruits, fruit juices, vegetables, legumes, and FRAP were significantly lower in cases than controls (P < 0.05). The risk of gestational diabetes mellitus was 85% lower among those in the highest tertile of FRAP (OR: 0.15; 95% CI: 0.08-0.29). There was no significant association between the risk of GDM and TRAP (OR: 1.62; 95% CI: 0.94-2.79) as well as TEAC (OR: 1.56; 95% CI: 0.89-2.72). CONCLUSION: Pregnant women who were in the highest tertile of FRAP were at lower risk of GDM. However, larger prospective studies are needed to confirm our findings.

Leptin and Nutrition in Gestational Diabetes.

Leptin is highly expressed in the placenta, mainly by trophoblastic cells, where it has an important autocrine trophic effect. Moreover, increased leptin levels are found in the most frequent pathology of pregnancy: gestational diabetes, where leptin may mediate the increased size of the placenta and the fetus, which becomes macrosomic. In fact, leptin mediates the increased protein synthesis, as observed in trophoblasts from gestational diabetic subjects. In addition, leptin seems to facilitate nutrients transport to the fetus in gestational diabetes by increasing the expression of the glycerol transporter aquaporin-9. The high plasma leptin levels found in gestational diabetes may be potentiated by leptin resistance at a central level, and obesity-associated inflammation plays a role in this leptin resistance. Therefore, the importance of anti-inflammatory nutrients to modify the pathology of pregnancy is clear. In fact, nutritional intervention is the first-line approach for the treatment of gestational diabetes mellitus. However, more nutritional intervention studies with nutraceuticals, such as polyphenols or polyunsaturated fatty acids, or nutritional supplementation with micronutrients or probiotics in pregnant women, are needed in order to achieve a high level of evidence. In this context, the Mediterranean diet has been recently found to reduce the risk of gestational diabetes in a multicenter randomized trial. This review will focus on the impact of maternal obesity on placental inflammation and nutrients transport, considering the mechanisms by which leptin may influence maternal and fetal health in this setting, as well as its role in pregnancy pathologies.

Association between plasma irisin and glucose metabolism in pregnant women is modified by dietary n-3 polyunsaturated fatty acid intake.

AIMS/INTRODUCTION: The role of irisin in maternal glucose metabolism and how it would respond to dietary n-3 polyunsaturated fatty acid (n-3 PUFA) intake remains unclear. This study aimed to explore whether maternal plasma irisin is associated with glucose metabolism and whether this association is modified by dietary n-3 PUFA. MATERIALS AND METHODS: A total of 932 pregnant women (20-28 weeks' gestation) aged 20-45 years were recruited. Dietary n-3 PUFA was estimated using a validated quantitative food frequency questionnaire. Plasma irisin and insulin were tested by enzyme-linked immunosorbent assay, and insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA). Gestational diabetes mellitus was diagnosed with a 75-g oral glucose tolerance test. Adjusted multivariable linear regression and logistic regression were carried out to examine the associations between plasma irisin and glucose metabolism. The moderating effect of dietary n-3 PUFA intake was determined by fully multiplicative models by including the interaction term. RESULTS: Maternal plasma irisin was negatively associated with HOMA-IR and oral glucose tolerance test 0 h glucose level (ß -0.250, -0.067; corrected P-value for false discovery rate = 0.012, 0.018, respectively), positively associated with HOMA of insulin sensitivity (ß 0.028; corrected P-value for false discovery rate = 0.012), but not associated with postprandial glucose or the risk of gestational diabetes mellitus. Furthermore, we found a moderating effect of dietary n-3 PUFA on the relationships of plasma irisin with HOMA-IR and HOMA of insulin sensitivity; these associations were strengthened with increased n-3 PUFA intake (ß -0.037, 0.004; P = 0.014, 0.041, respectively). CONCLUSIONS: Plasma irisin was negatively associated with HOMA-IR and fasting glucose, whereas it was positively associated with HOMA of insulin sensitivity in pregnant women. We first showed that these associations were modified by dietary n-3 PUFA intake.

Risk factors for congenital heart disease: The Baby Hearts Study, a population-based case-control study.

We investigated the role of maternal environmental factors in the aetiology of congenital heart disease (CHD). A population-based case-control study (242 CHD cases, 966 controls) was conducted using an iPad questionnaire for mother with linkage to maternity and first trimester prescription records. Risk of CHD was associated with low maternal education (OR adjusted for confounders 1.59; 95% confidence interval [CI], 1.02-2.49), pregestational diabetes (OR 4.04; 95% CI 1.00-16.28), self-reported maternal clotting disorders (adjOR 8.55, 95%CI 1.51-48.44), prescriptions for the anticlotting medication enoxaparin (adjOR 3.22, 95%CI 1.01-10.22) and self-reported vaginal infections (adjOR 1.69, 95%CI 1.01-2.80). There was no strong support for the hypothesis that periconceptional folic acid supplements have a protective effect, but there was a protective effect of frequent consumption of folate rich fruits (adjOR 0.64, 95%CI 0.47-0.89). Compared to the most common pre-pregnancy dietary pattern, CHD risk was associated with a poor diet low in fruit and vegetables (adjOR 1.56, 95%CI 1.05-2.34). Mothers of cases reported more pregnancy related stress (adjOR 1.69; 95% CI 1.22-2.34) and multiple stressors (adjOR 1.94, 95%CI 0.83-4.53). We found no supportive evidence for CHD risk being associated with obesity, smoking, depression or antidepressant use in this population. Our findings add to the previous evidence base to show potential for public health approaches to help prevent CHD in future by modifying environmental factors. Independent confirmation should be sought regarding elevated CHD risk associated with maternal blood clotting disorders and their treatment, since we are the first to report this.

Maternal Choline and Betaine Supplementation Modifies the Placental Response to Hyperglycemia in Mice and Human Trophoblasts.

Gestational diabetes mellitus (GDM) is characterized by excessive placental fat and glucose transport, resulting in fetal overgrowth. Earlier we demonstrated that maternal choline supplementation normalizes fetal growth in GDM mice at mid-gestation. In this study, we further assess how choline and its oxidation product betaine influence determinants of placental nutrient transport in GDM mice and human trophoblasts. C57BL/6J mice were fed a high-fat (HF) diet 4 weeks prior to and during pregnancy to induce GDM or fed a control normal fat (NF) diet. The HF mice also received 25 mM choline, 85 mM betaine, or control drinking water. We observed that GDM mice had an expanded placental junctional zone with an increased area of glycogen cells, while the thickness of the placental labyrinth zone was decreased at E17.5 compared to NF control mice (p < 0.05). Choline and betaine supplementation alleviated these morphological changes in GDM placentas. In parallel, both choline and betaine supplementation significantly reduced glucose accretion (p < 0.05) in in vitro assays where the human choriocarcinoma BeWo cells were cultured in high (35.5 mM) or normal (5.5 mM) glucose conditions. Expression of angiogenic genes was minimally altered by choline or betaine supplementation in either model. In conclusion, both choline and betaine modified some but not all determinants of placental transport in response to hyperglycemia in mouse and in vitro human cell line models.

How safe is metformin when initiated in early pregnancy? A retrospective 5-year study of pregnant women with gestational diabetes mellitus from India.

BACKGROUND: The initiation of metformin in early pregnancy in Gestational Diabetes mellitus (GDM) remains controversial. The aim of our study was to assess the influence of Metformin on maternal and fetal outcomes when initiated within the first trimester of pregnancy in GDM. METHODS AND MATERIALS: A retrospective analysis of 540 women with diabetes complicating pregnancy (IADPSG criteria) over five years (January 2011 to May 2016) was done. The study population comprised of patients initiated on (a) metformin within the first trimester (Group A:n = 186), (b) metformin after the first trimester (Group B:n = 203) and (c) insulin at any time during their pregnancy (Group C:n = 151). The primary outcomes compared were prematurity, respiratory distress, birth trauma, 5-min APGAR score, neonatal hypoglycaemia and need for phototherapy, while secondary outcomes compared were neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance. RESULTS: Individual and composite primary or secondary outcomes in group A were similar to Groups B and C, though numerically higher premature births were seen in Group A. There was a 1.3% overall incidence of stillbirths/IUD, while 1.11% congenital anomalies were noted of which 2.15% were in group A and 1.32% were in Group C (p = .16). CONCLUSIONS: The initiation of metformin within the first trimester of pregnancy has no significant adverse maternal or fetal outcomes. However, vigilance for premature births is recommended in women exposed to metformin in early pregnancy.

Pregnancy outcome and placental pathology differences in term gestational diabetes with and without hypertensive disorders.

OBJECTIVE: To compare pregnancy outcome and placental pathology in pregnancies complicated by gestational diabetes mellitus (GDM A1 and A2), with and without hypertensive disorders. METHODS: Pregnancy outcome and placental pathology from term deliveries of women complicated with GDM with (GDM + H) and without (GDM - H) hypertensive disorders were compared. Results of the GDM + H group were compared also with the non-diabetic patients but with hypertensive disorders (non-GDM + H). Composite neonatal outcome was defined as one or more of early complications: respiratory distress or need of ventilation support, sepsis, phototherapy, transfusion, seizure, hypoxic-ischemic encephalopathy. Placental lesions were categorized to lesions related to maternal and fetal vascular supply abnormalities, and maternal and fetal inflammatory responses. RESULTS: Of the 192 women with GDM, the GDM + H group (n = 41) were more obese, p < 0.001, with higher rate of placental maternal and fetal vascular supply lesions, p = 0.008, p = 0.03, respectively, but similar neonatal outcome, compared to the GDM - H (n = 151) group. Compared to the non-GDM + H group (n = 41), the GDM + H group had higher birth weights, similar neonatal outcome and similar rate of placental vascular lesions. CONCLUSIONS: Higher rate of placental maternal and fetal vascular supply lesions express underlying placental pathology in women with diabetes and hypertensive disorders, similar to women without DM and with hypertensive complications.

Centella asiatica and lipoic acid, or a combination thereof, inhibit monocyte adhesion to endothelial cells from umbilical cords of gestational diabetic women.

BACKGROUND AND AIMS: Diabetes mellitus is associated with inflammatory endothelial activation and increased vascular leukocyte adhesion molecule expression, both playing a prominent role in the development of vascular complications. Centella asiatica (CA) and Lipoic Acid (LA) have shown anti-inflammatory and anti-oxidant properties in a variety of experimental models; however, their action on human umbilical vein endothelial cells (HUVECs), chronically exposed to hyperglycemia and pro-inflammatory environment during pregnancy, is still unknown. METHODS AND RESULTS: In HUVECs from umbilical cords of gestational diabetic (GD) or healthy (C) women, both CA and LA affected tumor necrosis factor-α (TNF-α)-induced inflammation, being associated with a significant decrease in vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression (western blot) and exposure (flow cytometry), as well as monocyte-HUVECs interaction (adhesion assay). Notably, this was associated with a significant reduction of an index of nitro-oxidative stress, such as the intracellular peroxynitrite levels (fluorescence detection by cytometric analysis), Mitogen-Activated Protein kinase (p44/42 MAPK) expression/phosphorylation levels and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB p65) cytoplasm-nucleus translocation (flow cytometry). Overall our results indicate that both CA and LA used separately, and even better when combined, are effective to reduce the inflammatory response in TNF-α-treated HUVECs. Notably, this was more significant in GD than in C-HUVECs and also evident at baseline. CONCLUSION: In conclusion, our in vitro study demonstrates that both CA and LA, or a combination thereof, are able to mitigate the potentially dangerous effects on the endothelium of chronic exposure to hyperglycemia in vivo.

Vitamin D rescues dysfunction of fetal endothelial colony forming cells from individuals with gestational diabetes.

INTRODUCTION: Gestational diabetes (GDM) is associated with long-term cardiovascular and metabolic diseases in offspring. However, the mechanisms are not well understood. We explored whether fetal exposure to a diabetic environment is associated with fetal endothelial progenitor cell dysfunction, and whether vitamin D can reverse the impairment. METHODS: Nineteen women with uncomplicated pregnancies and 18 women with GDM were recruited before delivery. Time to first appearance of endothelial colony forming cell (ECFC) colonies and number of ECFC colonies formed from culture of cord peripheral blood mononuclear cells were determined. Angiogenesis-related functions of ECFCs in vitro were tested in the presence or absence of vitamin D. RESULTS: Fetal ECFCs from GDM pregnancies formed fewer colonies in culture (P = 0.04) and displayed reduced proliferation (P = 0.02), migration (P = 0.04) and tubule formation (P = 0.03) compared to uncomplicated pregnancies. Fetal ECFCs exposed to hyperglycemia in vitro exhibited less migration (P < 0.05) and less tubule formation (P < 0.05) than normoglycemic control. Vitamin D significantly improved the dysfunction of fetal ECFCs from pregnancies complicated by GDM or after exposure of healthy ECFCs to hyperglycemia. DISCUSSION: Fetal ECFCs from GDM pregnancies or ECFCs exposed to hyperglycemia in vitro exhibit reduced quantity and impaired angiogenesis-related functions. Vitamin D significantly rescues these functions. These findings may have implications for vascular function of infants exposed to a diabetic intrauterine environment.

Pituitary stalk Langerhans cell histiocytosis treated with CyberKnife radiosurgery.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare idiopathic disease that is characterized by clonal proliferation of Langerhans histiocytes in various parts of the body. These atypical cells have been found to infiltrate single or multiple organs, including bone, lungs, liver, spleen, lymph nodes, and skin. Central nervous system invasion in LCH patients has rarely been reported, especially in the adult population. METHODS AND RESULTS: We describe three histopathologically confirmed cases of adult LCH that involves both the pituitary stalk and hypothalamus, and report our limited experience of such cases in this location that has been treated with CyberKnife radio surgery. CONCLUSION: The treatment goal of controlling lesion growth is achieved by CyberKnife radiosurgery in this case series. All patients tolerated the treatment well without obvious complications.

Suplementação de ferro e sua associação com a incidência de diabetes mellitus gestacional / Iron supplementation and its association with the incidence of gestational diabetes mellitus

Iron requirements are significantly increased during pregnancy, which makes the daily dietary reference intake difficult to achieve through diet. Because iron deficiency may cause iron-deficiency anemia, which increases perinatal mortality, iron supplementation has been broadly adopted as a standard procedure during pregnancy. However, caution should be exercised as recent evidence suggests that iron excess may hamper fetus development and increase the risk for gestational diabetes mellitus (GDM). Literature is still scarce and it is inconclusive on this matter as the risks and benefits of prophylactic iron supplementation during pregnancy are still a source of controversy. However, it is imperative that a greater attention be given to the iron circulating levels individually. This practice would provide a better evaluation of the necessity and dosage determination of iron supplementation during pregnancy, being, therefore, potentially less likely to trigger the excess of iron-induced deleterious effects.

La demanda nutricional de hierro aumenta significativamente durante el embarazo siendo difícil alcanzar las dosis diarias recomendadas solamente a través de la alimentación. Dado que la deficiencia de hierro puede causar anemia y aumento de la mortalidad perinatal, la suplementación con hierro ha sido ampliamente utilizada como procedimiento estándar en las mujeres embarazadas. Sin embargo esta práctica debe usarse con cautela porque evidencias recientes sugieren efectos adversos de los niveles altos de hierro, que pueden perjudicar el desarrollo fetal y aumentar el riesgo de la diabetes mellitus gestacional (DMG). Aún no existe acuerdo, en la literatura, sobre la mejor manera de abordar el problema. Los riesgos y beneficios de la suplementación con hierro todavía son materia de debate. Sin embargo, es necesario que se preste más atención, de forma individual, a los niveles de hierro circulante Esta práctica permitiría una mejor evaluación de la necesidad de suplementación con hierro y de la determinación de la dosis a ser administrada, siendo de esta manera menos factible que se desencadenen los efectos deletéreos causados por el exceso de hierro.

A demanda nutricional de ferro aumenta significativamente durante a gestação, sendo difícil alcançar a ingestão diária recomendada apenas via alimentação. Como a deficiência de ferro pode ocasionar anemia ferropriva, aumentando a mortalidade perinatal, sua suplementação tem sido amplamente utilizada como procedimento padrão em gestantes. No entanto, tal prática deve ser vista com cautela, pois novas evidências sugerem efeitos adversos dos altos níveis férricos, que podem comprometer o desenvolvimento fetal e aumentar o risco para o diabetes mellitus gestacional (DMG). A literatura não é conclusiva sobre a melhor abordagem ao problema. Os riscos e benefícios da suplementação profilática de ferro ainda são motivo de controvérsia. Entretanto, é imperativo que maior atenção seja dada aos níveis circulantes de ferro de forma individualizada. Essa prática permitiria melhor avaliação da necessidade e da determinação da dosagem da suplementação de ferro durante a gestação, sendo então potencialmente menos passível de desencadear os efeitos deletérios induzidos pelo excesso de ferro.