The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial.

OBJECTIVE: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. DESIGN: Multicentre randomised controlled trial. SETTING: Hospitals in nine European countries. POPULATION: A cohort of 112 pregnant women with placental tissue. METHODS: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. MAIN OUTCOME MEASURES: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. RESULTS: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05). CONCLUSIONS: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. TWEETABLE ABSTRACT: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

AIMS: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. METHODS: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. RESULTS: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. CONCLUSIONS: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

Adropin as a potential protective factor of metabolic complications in obese pregnant women with hyperglycaemia diagnosed in early pregnancy.

Adropin is a hormone which increases insulin sensitivity. It enhances the oxygenation of glucose in the muscles. The 91 obese pregnant women (BMI >30 kg/m2) with gestational diabetes mellitus (GDM) diagnosed in the first half of pregnancy has been recruited to the study group. The control group consisted of 10 age matched and homogeneous pregnant women with BMI <25 kg/m2. Blood samples were collected on visit V1 - between the 28th and 32nd week and on visit V2 - between the 37th and 39th week of gestation. The ELISA test was used to measure the adropin level. The results in the study group and the control group were compared. Blood samples were collected at the same visits. The median concentration of adropin was 442.2 pg/ml on V1 and 453.1 pg/ml on V2. The increase was significant (p<0.05). Results were significantly lower in the control group's patients, i.e. 57.0 pg/ml (p<0.001) on V1 and 107.9 pg/ml on V2 (p<0.001). The higher adropin level on the V1 and V2 visits were related to patients' lower BMI and better metabolic control. The increase in the adropin level in the third trimester may have been involved in the weight gain reduction, whereas better dietary adherence might have had a compensatory effect on increasing insulin resistance. However, the small control group is a limitation of this study.

Significance of multiple myeloma oncogene 1 immunohistochemistry in chronic endometritis detection in patients with recurrent pregnancy losses: an observational study.

The most reliable chronic endometritis diagnosis is based on immunohistochemistry plasma cell identification in endometrial samples. Our study aimed to compare multiple myeloma oncogene 1 (MUM1) and syndecan-1/CD138 immunohistochemistry staining for chronic endometritis diagnosis among patients with recurrent pregnancy loss. We evaluated the presence of endometrial stromal changes. Fifty-four patients with a history of at least two intrauterine pregnancy losses underwent diagnostic hysteroscopy in the follicular phase of the cycle with endometrial aspiration biopsy. In all 54 cases, three successive sections were cut from each paraffin-embedded tissue block for hematoxylin and eosin (H&E), CD138 and MUM1 staining. The goal was to evaluate the level of agreement between the MUM1 and CD138 results and plasma cell detection rate in assessing the endometrial stromal changes. The concordance analysis between CD138 and MUM1 immunohistochemistry staining showed consistent results in 43 of 54 (79.6%) cases. The level of agreement was moderate, based on a Kappa value of 0.60. MUM1 immunostaining was positive for CE in more cases than CD138 staining, and this difference was statistically significant, showing a higher sensitivity of MUM1 in plasma cell detection (p=0.01). Endometrial stromal changes were observed in the majority of cases - 49/54 (90%). Samples without stromal changes were consistently negative for plasma cells using both CD138 and MUM1 staining. We demonstrated that MUM1 staining, used in conjunction with assessing endometrial stromal changes, contributes to a more accurate and comprehensive diagnosis of chronic endometritis.

Leptin and vascular endothelial growth factor A: a cross-talk in obese women with gestational diabetes and with diabetes in pregnancy - a cohort study.

Vascular endothelial growth factor A (VEGF A) synthesis is intensified by leptin in: hypoxia-inducible factor 1 alpha (HIF-1A) and nuclear factor kappa-light-chain-enhancer of activated B cells (NfκB)-dependent manners. The study aimed to investigate the association between leptin and VEGF A serum levels in obese women with hyperglycaemia in the third trimester of pregnancy. Sixty obese pregnant women with hyperglycaemia were divided into groups according to body mass index (BMI): group 1: BMI 30.0-34.9 kg/m2; group 2: BMI 35.0-39.9 kg/m2; group 3: BMI ≥40 kg/m2. On the enrolment visit, waist circumference, body mass and height were measured. At visit 1 (V1; gestational week (GW) 28-32) and visit 2 (V2; GW 36-38), anthropometric, blood pressure and heart rate measurements, and blood sample collection were performed. Blood levels of leptin, VEGF A, VEGF receptor 2, HIF-1A, NfκB, interleukin 1 alpha, protein delta homolog 1, nitric oxide and glycated haemoglobin were determined. To analyse the predictors of the biochemical parametres involved in leptin and VEGF A cross-talk, multivariate logistic regression was implemented. Positive correlations between serum levels of leptin and VEGF A were found. Serum level of HIF-1A at V1 was a predictor for the highest quartile of the serum levels of VEGF A at V1 and V2. Leptin serum level at V1 was a predictor for the highest quartile of HIF-1A serum concentration at V2. In group 3 HIF-1A level was higher at V2 compared to V1. We conclude that in obese women with hyperglycaemia in the third trimester of pregnancy there is a significant positive influence of serum leptin on VEGF A synthesis and serum level and HIF-1A seems to play more important role in leptin and VEGF A cross-talk than NfκB.

Low placental angiotensin-converting enzyme expression is related to fetal small for gestational age but not to metabolic control in type 1 diabetic pregnancies.

The maternal renin-angiotensin system is involved in blood pressure control and plays a crucial role in fetoplacental nutrition. Pre-gestational type 1 diabetes (PGDM) leads to serious pregnancy complications. We thus performed a longitudinal study to analyse the association of maternal angiotensin-converting enzyme (ACE) serum levels and placental mRNA expression with fetal newborns gestational weight in type 1 diabetes mellitus (T1DM) women. We recruited 65 singleton pregnant women with T1DM. Placental mRNA ACE gene expression was examined using quantitative real-time PCR. Serum ACE levels were measured in the first, second and third trimesters of pregnancy by ELISA commercial kits. Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers (0.55±0.06 vs 0.78±0.06 and 0.85±0.07 respectively, p=0.003). In the SGA group, the mRNA expression of ACE positively correlated with maternal body mass index (BMI) in the third trimester (r=0.49; p=0.04). In all study groups maternal ACE level was significantly higher in the third trimester (mean 139.91±SD 69.64) compared to the first and second trimesters of pregnancy (13.57±4.32 and 15.69±15.92 respectively). Our data suggest that lower placental ACE gene mRNA expression may have a vital role in the etiology of SGA babies.

Maternal endothelial dysfunction and its association with abnormal fetal growth in diabetic pregnancy.

AIMS: Some authors consider the vascular endothelium to be a target organ in diabetes. However, there have only been a few studies of the function of the maternal endothelium during pregnancy in women with diabetes. We analysed the relationship between maternal vascular endothelial dysfunction and fetal growth in such pregnancies. METHODS: Markers of endothelial dysfunction (serum concentration of sE-selectin and sVCAM-1) were measured at admission (baseline) and before delivery in 97 women with pregestational diabetes and a singleton pregnancy,. After delivery, the group with pregestational diabetes was divided retrospectively according to neonatal birthweight into three groups-appropriate, small and large for gestational age- and the maternal variables were analysed in relation to birthweight. RESULTS: The baseline concentration of sE-selectin was significantly higher in the large-for-gestational-age group vs. the small-for-gestational-age group (median: 53.1 vs. 39.0 ng/ml, P<0.05). The concentration of sVCAM-1 at baseline was significantly higher in the small-for-gestational-age vs. the appropriate- and large-for-gestational-age groups (median: 846.2 vs. 576.8 and 524.1 ng/ml, respectively; P<0.01 and P<0.001, respectively). The concentration of sE-selectin at baseline and gestational changes in the concentration of sVCAM-1 were related to birthweight. The baseline concentrations of sE-selectin and sVCAM-1 and the gestational change in sVCAM-1 concentration were predictive factors for large for gestational age (cut-off values: 45.0, 644.6 and 38.4 ng/ml; sensitivity: 67.7, 89.3 and 34.4%; specificity: 65.5, 39.7 and 85.5%, respectively). CONCLUSIONS: Our study showed a relationship between maternal endothelial dysfunction and fetal growth disturbances during pregnancy in women with diabetes that was not associated with maternal metabolic control. Higher levels of maternal sE-selectin in early pregnancy were associated with increased risk of the large-for-gestational-age condition. High levels of maternal sVCAM-1 in early pregnancy were characteristic of gestation complicated by the small-for-gestational-age condition. Further studies in larger groups are warranted to determine whether markers of maternal endothelial dysfunction are of use in the prediction of abnormal birthweight (large or small for gestational age) in pregnant women with diabetes.

Concentration of chemokines in peripheral blood in first trimester of diabetic pregnancy.

BACKGROUND: Several types of regulators (i.e. chemokines and metalloproteinases) are considered to play a crucial role in pregnancy by local modulation of the immune system at the level of peripheral leukocytes. The aim of this study was to determine whether changes in chemokines (interferon-gamma-inducible protein (IP-10), monocyte chemotactic peptide-1(MCP-1), cytokines regulated upon activation normal T cell expressed and secreted (RANTES) and matrix metalloproteinase-9 (MMP-9)) concentrations in diabetic patients could affect the course of pregnancy. METHODS: The study group consisted of 65 diabetics in the first trimester of pregnancy. Some 47 pregnancies were successfully continued to delivery, 18 were terminated with spontaneous miscarriages. Twenty healthy women matched for gestational age served as a control group. RESULTS: Glycated haemoglobin (HbA1C), vascular complications and lipoproteins (cholesterol, HDL-cholesterol, low density lipoprotein (LDL)-cholesterol and triglicerides) concentrations in maternal blood did not influence the chemokines concentrations. Lower RANTES level and higher MMP-9 concentrations were found in diabetic women. MCP-1 and RANTES levels differed significantly between pregnancies with good and poor perinatal outcome. A logistic regression model revealed that not only duration of diabetes, age of patients, HbA1C and insulin requirements, but also MMP-9,RANTES, MCP-1 and LDL-cholesterol levels seem to be involved in first trimester metabolism. CONCLUSIONS: Our results suggest the possible role of chemokines in early pregnancy development, especially in well-controlled diabetic patients, when hyperglycaemia is unlikely to be the main reason for an unfavourable outcome. Our results show that MCP-1 and RANTES might serve as predictive factors for an unfavourable outcome in diabetic pregnancy, whereas MMP-9 seems to be a marker of immunological changes related to mild hyperglycaemia. However, the open question of how the modulation of chemokines concentrations might be applied to prevent miscarriage in diabetic patients remains.

Low placental visfatin expression is related to impaired glycaemic control and fetal macrosmia in pregnancies complicated by type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is still related to altered fetal growth and severe maternal complications. We studied the possible role of placental visfatin/nicotinamide phosphoribosyltransferase (NAMPT) in fetal development in T1DM pregnancies, the possible role of placental visfatin in fetal macrosomia. Sixty five pregnant women with T1DM and singleton pregnancy were qualified into the study. Placental visfatin expression was by analysed by RT-PCR. We demonstrated the lowest expression of placental visfatin in women who delivered neonates with birth weight NBW > 4000 g (0.76 ± 0.05, P < 0.055). The highest placental visfatin/nicotinamide phosphoribosyltransferase (NAMPT) expression was found in the women who delivered small for gestational age (SGA) and large for gestational age (LGA) newborns (1.09 ± 0.95 vs. 0.87 ± 0.67, P < 0.05, respectively). There was also significant negative correlation between placental visfatin (NAMPT) expression and metabolic status in the 3rd trimester of pregnancy in T1DM LGA group, defined as long-term glycaemic control (3rd trimester HbA1C) - Pearson rank R - 08667654, P < 0.034. We conclude that the low placental visfatin (NAMPT) expression and poor metabolic control in the 3rd trimester of pregnancy may have a role in stimulating fetal overgrowth in T1DM pregnancy.

Maternal first trimester parameters in the prediction of excessive fetal growth in pregnant women with metabolic syndrome.

Metabolic syndrome (MS) and obesity is an important risk factor for fetal complications like excessive fetal growth manifested by large for gestational age (LGA) and macrosomia, which is a consequence of metabolic disturbances present in the first trimester of pregnancy. The aim of this prospective observational study is to analyze the relationship between the first trimester biochemical and anthropometric parameters of fetuses with the incidence of their macrosomia and LGA so to early predict such complications in women with symptoms of MS. A total of 124 Caucasian women in singleton pregnancies who fulfilled MS criteria were enrolled into the study group and compared to 30 healthy pregnant controls. Patients' blood was drawn and sampled for analysis at 11 - 13+6 weeks of gestation. Specific factors were analyzed in terms of influence on fetal growth and perinatal morbidity in both pregnancy groups. The maternal parameters obtained at first trimester that with respect to controls proved influential towards macrosomia defined as > 4000 g were: BMI and weight (28.0 versus 22 m/kg2; P < 0.001), (77.9 kg versus 60.8 kg; P < 0.001), fasting glucose (87.2 versus 82.1 mg/dl; P < 0.042), significantly higher s-E-selectin concentration (32.0 versus 24.5 ng/ml; P < 0.011) and lower adiponectin: (5.6 versus 9.1 µg/ml; P < 0.001). Similarly, the parameters for LGA fetuses were found to be: maternal weight (80.3 versus 60.8 kg; P < 0.001), BMI (28.7 versus 21.6 kg/m2; P < 0.001), fasting glucose (87.2 versus 82.4mg/dl; P < 0.022), increased s-E-selectin (30.8 versus 24.5 ng/ml; P < 0.022) and decreased adiponectin (6.3 versus 8.2 µg/ml; P < 0.024). We concluded that: 1) first trimester BMI with cut-off of 25.5 was significant risk factor for excessive fetal growth; 2) maternal glycemia, as well as adiponectin and soluble E-selectin serum concentration in the first trimester of pregnancy could be predictive of LGA and fetal macrosomia; 3) maternal weight at 11 - 13+6 weeks of pregnancy cut-off 67 kg had high sensitivity and specificity in detecting LGA and fetal macrosomia.

Short-term antidiabetic treatment with insulin or metformin has a similar impact on the components of metabolic syndrome in women with gestational diabetes mellitus requiring antidiabetic agents: results of a prospective, randomised study.

Gestational diabetes mellitus (GDM) is associated with an increased prevalence of fetal and maternal complications primarily caused by maternal hyperglycemia, which results in abnormal fetal growth. Diet modification is a common first step in the treatment of GDM, followed by antidiabetic pharmacotherapy if this approach fails. Insulin therapy is generally accepted; however, oral hypoglycemic agents have been used in this population. In this prospective, randomised study, we compared maternal metabolic status after treatment with insulin or metformin. Pregnant women (gestational age: ≥ 20 weeks) with GDM requiring medical hypoglycemic treatment were randomly allocated to the Metformin (n = 35) or Insulin (n = 43) Groups. Maternal metabolic status - assessed by glycated hemoglobin (HBA1c) level, glycemic profile, insulin concentration, Homeostatic Model Assessment - Insulin Resistance index, and lipids - was recorded at booking and throughout pregnancy. The characteristics of the study group were: maternal age 33.5 ± 5.9 years, gestational age at baseline 28.5 ± 3.5 weeks, prepregnancy body mass index (BMI) 32.2 ± 3.5 kg/m(2), HbA1c at baseline 5.6 ± 0.6%, and average daily glycemia 5.9 ± 0.6 mmol/dl. Fasting glycemia at term was significantly lower in the Insulin Group but there were no significant differences in mean daily glycemia, HbA1c and BMI at term between the groups. Longitudinally, there was a small but significant increase in BMI and a significant increase in high-density lipoprotein-cholesterol in the Insulin Group and a significant increase in the atherogenic index of plasma (AIP) and a trend towards higher triglycerides in the Metformin Group. Both fasting and average daily glycemia were significantly reduced following treatment in both groups. No such change was evident for HbA1c. In a relative risk analysis, metformin treatment was associated with an insignificant elevated risk of HbA1c, triglycerides and lipid indices falling within the highest quartile at term. The risk of gestational weight gain and total cholesterol falling within the highest quartile at term was insignificantly reduced in the Metformin Group. In conclusion, short-term antidiabetic treatment with insulin or metformin has a similar impact on markers of metabolic syndrome in women with GDM requiring antidiabetic treatment. Secondly, treatment with metformin is associated with increased triglyceride levels and higher AIP in the third trimester in pregnant women with GDM.

Changes of oxidative stress parameters in diabetic pregnancy.

BACKGROUND: The molecular aetiology of disturbed embryogenesis and other unfavourable outcomes in offspring of diabetic mothers is not fully understood. Experimental studies have suggested an involvement of radical oxygen species (ROS) in the teratological process. THE AIM OF OUR STUDY: To investigate if maternal diabetes in humans is capable of inducing alterations in vascular oxidative stress parameters and whether such changes are associated with disturbances in foetal development. METHODS: Seventy patients with pre-gestational diabetes (PGDM) were chosen for the study: 29 (41.4%) belonged to class B according to White, 15 (21.4%) to class C, 8 (11.4%) to class D, 3 (4.3%) to class F, 3 to class R and 12 (17.1%) to class F/R. In 20 (28.6%) patients from this group an unfavourable outcome was noted. All patients were subjected to intensive insulin therapy. Glycaemia was estimated by daily self-monitoring, and diurnal glucose profiles and glycated haemoglobin (HbA1c) concentrations were measured monthly. Oxidative stress was evaluated as changed superoxide dismutase, catalase and glutathione peroxidase activities as well as of malondialdehyde (MDA) and peroxides concentrations in maternal erythrocytes and blood serum. RESULTS: Prior to conception, the mean glycaemia in the group that had a planned pregnancy was 6.6mmol/l and HBA1c was 9.35%. Throughout the course of pregnancy, these parameters were maintained at a level of 6.7 mmol/l and 7.85%, respectively. The activity of all antioxidative enzymes was lower before than during pregnancy, and so was the concentration of MDA. The MDA concentrations were higher in patients with elevated glycaemia and with an unfavourable outcome. The investigated ROS, the glycaemia level, as well as the concentration of HBA1c did not show any significant differences between pregnancies with and without vascular complications. Patients with a favourable perinatal outcome presented a higher activity of antioxidant enzymes, than those with unfavourable outcome, throughout the whole course of pregnancy. The appearance of unfavourable perinatal outcomes in relation to parameters of oxidative stress was assessed by logistic regression. Both SOD and GPX activities, as well as peroxides' concentration, showed significant correlations (p < 0.005) with foetal complications. However, after mean glucose levels in the studied group were included into these analyses, this relationship was only evident with SOD and GPX activity (p < 0.0016). CONCLUSION: Oxidative stress is one of several important factors contributing to unfavourable outcome of human diabetic pregnancy.

[Brain tumor and imminent premature labor: a case report]. / Guz mózgu a zagrozenie porodem przedwczesnym. Opis przypadku.

A pregnant woman with cerebral tumour of right hemisphere is reported. In the 30th week of pregnancy intracranial pressure was increased and imminent premature delivery were diagnosed. The patient was operated on for cerebral tumour and immediately after this cesarean section was performed. We conclude that in this case neurosurgical operation followed by cesarean section saved the life of the mother and child.

[Analysis of unsuccessful outcomes in a group of pregnancies with diabetes from the intensive care clinic of the Institute of Obstetrics and Gynecology in Poznan during the years 1988-1993]. / Analiza niepowodzen polozniczych w grupie ciezarnych z cukrzyca w KIN IGIP AM w Poznaniu w latach 1988-1993.

In the present paper we analysed 416 diabetic pregnant women, treated in the Intensive Care Clinic--Poznan, between 1988-93. We found in this period 8 (1.93%) stillbirth, 6 (1.44%) perinatal deaths and 4 (0.96%) deaths in neonatal period. It was together 18 fetal and neonatal deaths, which gives 4.33 per cent of perinatal and neonatal mortality rate. Four newborns died because of RDS, 2 with congenital anomalies (pulmonary hypoplasia), 3 with heart defects and 1 with oesophagus anomaly. Only 3 diabetic pregnant women of the total 18, were under special care from the I trimester, and almost all been difficult to normalize the glycemia. Only in 6 cases this group glycemia profile was below 100 mg/dl, in other 8 cases this value was above 120 mg/dl. Unsuccessful outcomes mostly occurred in women with long--lasting diabetes and with vascular complications. This study prove, that despite substantial reduction of perinatal mortality rate in children of diabetic mothers, diabetes still is a cause of congenital anomalies, as well as fetal anoxia. Special adverse impact of diabetes on the development of the fetus is observed in long--lasting diabetes and uncontrolled metabolism.

[Glycemia control in diabetic pregnancies under intensive insulin treatment with and without the aid of the Camit-Diacomp system]. / Kontrola wyrównania glikemii u ciezarnych z cukrzyca leczonych intesywna insulinoterapia przy pomocy oraz bez systemu Camit-Diacomp.

The efficiency of glycemia control was compared in two groups of insulin dependent diabetic pregnancies treated with insulin, with and without the aid of the Camit-Diacomp system. The efficiency of glycemia control was analysed in all three trimesters of pregnancy. Mean diurnal fluctuations of glycemia levels in both study groups were compared. The clinical state of newborns, their glycemia and insulin levels in cord blood were analysed as well. No statistically significant differences of glycemia levels between the two compared groups of patients were found, however the observed significant differences of the HbA1C levels between these groups can speak in favour of the efficiency of treatment under the Camit-Diacomp system, which enables a more precise self control of the treatment and dosage of insulin.

[Influence of the degree of carbohydrate metabolism imbalance in gestational diabetes on pregnancy and newborns condition]. / Wplyw stopnia nasilenia zaburzen metabolizmu weglowodanów w momencie rozpoznania cukrzycy ciazowej na przebieg ciazy i stan noworodków.

UNLABELLED: The aim of our study was the evaluation of the correlation between carbohydrate metabolism imbalance at the moment of gestational diabetes mellitus (GDM) diagnosis and regulation of glycemia during pregnancy, pregnancy complications, time and mode of delivery and conditions of the newborns. MATERIAL: 231 women with GDM delivered in our hospital between 1993-1996 were investigated. This population was divided into 6 groups, according to glycemia levels. METHOD: The term of diagnosis of the GDM, medical treatment (diet or diet and insulin), the degree of metabolic regulation archived, mode and time of delivery, as well as state of newborns were analysed. RESULTS: In groups I and VI we noticed the greatest percentage of patients treated with insulin (68%, 67%), versus 26% in group II and 17% in group III. In group VI in all cases treated with insulin we begun this therapy shortly after marking GDM. Glycemia in 24 hrs period after GDM diagnosis in group I were 122.7 +/- 28.6 mg/dl, in group VI 112.0 +/- 23.6 mg/dl, while we noticed 90.3 +/- 15.6 mg/dl in group II and 87.7 +/- 15.9 mg/dl in group III. Blood glucose level < 100 mg/dl in first determination of 24 hrs profiles we noticed in 5% in group I, 2% in group VI while 20% in group II and 51% in group III. Average levels of glycemia in last 24 hrs profiles before delivery in group I were 93.0 +/- 15.8 mg/dl, in group VI 96.2 +/- 21.1 mg/dl while 87.8 +/- 13.5 mg/dl in group II and 86.8 +/- 14.1 mg/dl in group III. Blood glucose level < 100 mg/dl of daily profile before the end of pregnancy was discovered in 8% in group I, 47% in group III. The greatest amount of complications (pregnancy induced hypertension and imminent premature delivery) was diagnosed in group VI-75% and in group III-55%. Surgical delivery took place in group I in 50%, in group V in 46%, in group VI in 67% while 17% in group II, 35% in group III and 30% in group IV. Macrosomy of newborns (> 4000 g) was diagnosed in group I in 36% in group V in 23% and in group VI in 42% while 9%, 6% and 15% in groups, II, III and IV respectively. The condition of newborns in the 1st minute of life was determined as good (8-10 points in Apgar scale) in significant percentage, in 87%, 75%, 70% in groups II, III, IV while only 59%, 62%, 58% in groups I, V, VI respectively. CONCLUSION: Serious intensification of carbohydrates metabolism disorders at the moment of diagnosing GDM, such as fasting glycemia > 140 mg/dl and the result after 2 hours > 200 mg/dl in 75 g OGTT more often requires insulin treating connect with numerous difficulties both in pregnancy monitoring and also has inadventageous influence on obstetrics outcomes-increasing percentage of surgery deliveries and macrosomies, that change the condition of newborns for worse.

Concentrations of endothelial nitric oxide synthase, angiotensin-converting enzyme, vascular endothelial growth factor and placental growth factor in maternal blood and maternal metabolic status in pregnancy complicated by hypertensive disorders.

Hypertensive disorders of pregnancy (HDPs) are associated with altered maternal metabolism, impaired perinatal outcome and increased risk for remote maternal complications. The aim of our study was to analyse associations between circulating levels of angiogenic factors and markers of oxidative stress and metabolic status in women with HDP. Forty-six women in singleton pregnancies complicated by HDP and 30 healthy controls were enrolled in a prospective observational study. Serum concentrations of endothelial nitric oxide synthase (eNOS), angiotensin-converting enzyme, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were measured in the third trimester and correlated with maternal anthropometrics and metabolic status. We found significantly lower eNOS levels in patients with severe hypertension vs controls, a strong association between eNOS and PlGF in the study group, a significant association between maternal prepregnancy body mass index (BMI) and VEGF levels and an inverse correlation between VEGF and PlGF. Maternal prepregnancy BMI was the only independent predictor for VEGF concentrations. We noted reduced levels of PlGF and eNOS and increased VEGF levels in women with severe hypertension/preeclampsia. First, different forms of HDP are associated with different alteration patterns in concentrations of angiogenic factors and markers of oxidative stress. Second, maternal prepregnancy BMI, but not body weight, is a significant predictor for VEGF levels in late pregnancy.

Placental vascular endothelial growth factor expression in pregnancies complicated by type 1 diabetes.

UNLABELLED: Type 1 diabetes mellitus (T1DM) is still associated with increased risk of severe maternal and foetal complications but their pathomechanism remains unclear. OBJECTIVES: we investigated the possible role of placental vascular endothelial growth factor (VEGF) and VEGF single nucleotide polymorphisms (SNP) in foetal development in T1DM pregnancies. Sixty seven pregnant women with T1DM and singleton pregnancy were enrolled into the study. Results demonstrated higher expression of placental VEGF in women who delivered neonates with birth weight (NBW)>4000g. No such correlation was found in the overall T1DM group and in women who delivered appropriate for gestational age (AGA) and small for gestational age (SGA) newborns. We also demonstrated a significant correlation between 3(rd) trimester mean blood glucose, HbA1C and placental VEGF. No such correlation was found for the 1(st) and 2(nd) trimesters. Top placental VEGF expression and placental mass were found in women who delivered large for gestational age (LGA) newborns. We also found a statistically significant difference in homozygous and heterozygous frequency variants of VEGF SNPs in study groups. We conclude that the increased placental VEGF together with impaired metabolic control may have a role in stimulating foetal overgrowth in T1DM pregnancy.

Placental leptin and its receptor genes expression in pregnancies complicated by type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is still associated with increased risk for severe maternal and fetal complications but their pathomechanism remains unclear. We investigated into possible role of placental leptin (LEP) and its receptor gene (LEPR) in T1DM pregnancies. Fourty nine pregnant women with T1DM and singleton pregnancy were enrolled into the study. Control group consisted of 15 healthy pregnant women in uncomplicated, singleton gestation. We observed higher expression of LEP and LEPR in T1DM placentas in comparison to healthy subjects. We also noticed greater expression of LEP and LEPR in T1DM pregnancies with large for gestational age (LGA) and appropriate for gestational age (AGA) fetuses in comparison to small for gestational age (SGA) diabetic fetuses and controls. We found a significant positive correlation between placental LEP and LEPR expression and neonatal birthweight in overweight T1DM subjects. No such a correlation was found in T1DM subjects with normal weight and controls. We conclude that increased placental LEP and LEPR expression may have a role in stimulating fetal overgrowth in T1DM pregnancy.