Maternal Plasma Glucose Levels Research Articles

Effect of preoperative oral rehydration before cesarean section on ultrasound assessment of gastric volume and intraoperative hemodynamic changes: a randomized controlled trial

BackgroundCesarean section often requires an urgent transfusion load due to decreased blood pressure after spinal anesthesia. This prospective randomized study aimed to investigate whether a preoperative oral rehydration solution (ORS) stabilized perioperative circulatory dynamics.MethodsSixty-three parturients scheduled for cesarean section under combined spinal epidural anesthesia (CSEA) were randomly allocated to one of three groups: Group O received 500 mL ORS before bedtime and 500 mL 2 h before CSEA; Group M received mineral water instead of ORS; and Group C had no fluid intake (controls). After entering the operating room, stomach size was measured using ultrasound. Blood samples were obtained, and CSEA was induced. Vasopressors were administered when systolic blood pressure was < 90 mmHg or decreased by > 20%. As a vasopressor, phenylephrine (0.1 mg) was administered at ≥ 60 beats/min heart rate or ephedrine (5 mg) at < 60 beats/min heart rate. The primary outcome was the total number of vasopressor boluses administered. Secondary outcomes were the cross-sectional area of the stomach antrum, maternal plasma glucose levels, serum sodium levels, total intravenous fluid, bleeding volume, urine volume, operative time, and cord blood gas values after delivery.ResultsThe total number of vasopressor boluses was lower in Group O than in Group C (P < 0.05). Group O had lower total dose of phenylephrine than Group C (P < 0.05). There were no significant differences between Group M and other groups. No differences were detected regarding secondary outcomes.ConclusionsIn women scheduled for cesarean section, preoperative ORS stabilized perioperative circulatory dynamics. Neither ORS nor mineral water consumption increased the stomach content volume.Trial RegistrationThis trial is registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000019825: Date of registration 17/11/2015).

Evaluation of fetal myocardial performance index in gestational diabetes mellitus.

This study aimed to compare fetal myocardial performance index (MPI) between fetuses of pregnant women with gestational diabetes mellitus (GDM) and healthy controls and to evaluate the relationship between MPI and maternal glucose levels. This was a prospective study of 90 pregnant women, including 50 pregnancies with GDM (27 pregnancies with insulin-regulated GDM and 23 pregnancies with diet-regulated GDM) and 40 healthy controls. Isovolumetric contraction time (ICT) + isovolumetric relaxation time (IRT)/ejection time (ET) were used to calculate the MPI (MPI = [ICT + IRT]/ET). Fetal MPI, PR interval, E/A ratio, maternal plasma glucose levels on the day of MPI measurement, and neonatal outcomes were compared. The fetal left-MPI was significantly higher in the GDM group than healthy controls (0.43 ± 0.04 vs. 0.40 ± 0.06, p = 0.007). The best cut-off level for MPI was >0.41 to predict adverse perinatal outcomes (sensitivity: 70%, specificity: 68%, area under the curve: 0.715, 95% confidence interval: 0.5143-0.8205, p < 0.001). The fetal MPI values showed no correlation with maternal plasma fasting, postprandial glucose, and hemoglobin A1c (HbA1c) levels. Reduced E/A ratio, higher neonatal intensive care unit admissions, and the need for cesarean delivery were detected in the GDM group. Fetal MPI is impaired in women with GDM, and the need for insulin therapy is associated with higher MPI values and adverse neonatal outcomes. Fetal MPI can help detect fetuses with potential adverse outcome risks, owing to impaired fetal cardiac function.

Maternal fasting glucose levels throughout the pregnancy and risk of adverse birth outcomes in newborns: a birth cohort study in Foshan city, Southern China

We aimed to investigate the associations between maternal fasting plasma glucose (FPG) levels and glycemic fluctuations during different trimesters and adverse birth outcomes among newborns. This cohort study used data from 63 213 pregnant women and their offspring in Foshan city from November 2015 to January 2019. Associations between maternal FPG and glycemic fluctuations during different trimesters and adverse birth outcomes [congenital heart defect (CHD), macrosomia, small/large for gestational age (SGA/LGA), and preterm birth (PTB)] in newborns were estimated using mixed-effects logistic regression models. A total of 45 516 participants accepted at least one FPG test throughout pregnancy, and 7852 of whom had glycemic trajectory data. In the adjusted model, higher maternal FPG throughout the pregnancy was associated with an increased risk of adverse birth outcomes (except for SGA). Each 1 mmol/L increase in maternal FPG during trimester 1 was associated with higher odds of CHD (OR = 1.14 (95% CI: 1.02, 1.26)). The same increase in maternal FPG during trimester 3 was associated with a higher risk of PTB (OR = 1.05 (95% CI: 1.01, 1.10)). Increment of maternal FPG during trimester 2 and trimester 3 was associated with a higher risk of macrosomia and LGA. Increase in FPG throughout the pregnancy was associated with slightly lower odds of SGA. Similar results were observed when analyzing the associations between glycemic fluctuations during different trimesters and adverse birth outcomes. Our findings indicate higher maternal FPG levels during different trimesters were associated with different adverse birth outcomes, which suggests the importance of glycemic management throughout the pregnancy.

Low-dose antenatal betamethasone treatment achieves preterm lung maturation equivalent to that of the World Health Organization dexamethasone regimen but with reduced endocrine disruption in a sheep model of pregnancy

The intramuscular administration of antenatal steroids to women at risk of preterm delivery achieves high maternal and fetal plasma steroid concentrations, which are associated with adverse effects and may reduce treatment efficacy. We have demonstrated that antenatal steroid efficacy is independent of peak maternofetal steroid levels once exposure is maintained above a low threshold. This study aimed to test, using a sheep model of pregnancy, whether the low-dose antenatal steroid regimen proposed as part of the Antenatal Corticosteroids for Improving Outcomes in Preterm Newborns trial would achieve preterm lung maturation equivalent to that of the existing World Health Organization dexamethasone treatment regimen, but with reduced risk of adverse outcomes. Following ethical review and approval, date-mated ewes with single fetuses received intramuscular injections of either (1) four 6-mg maternal intramuscular injections of dexamethasone phosphate every 12 hours (n=22), (2) 4 2-mg maternal intramuscular injections of betamethasone phosphate every 12 hours (n=21), or (3) 4 2-mL maternal intramuscular injections of saline every 12 hours (n=16). Of note, 48 hours after first injection, (124±1 day), lambs were delivered, ventilated for 30 minutes, and euthanized for sampling. Arterial blood gas, respiratory, hematological, and biochemical data were analyzed for between-group differences with analysis of variance according to distribution and variance, with P<.05 taken as significant. After 30 minutes of ventilation, lambs from both steroid-treated groups had significant and equivalent improvements in lung function relative to saline control (P<.05). There was no significant difference in arterial blood pH, pO2, pCO2, lung compliance, ventilator efficiency index, or lung volume at necropsy with a static pressure of 40 cmH2O. The messenger RNA expression of surfactant protein (Sp)a, Spb, Spc, Spd, aquaporin (Aqp)1, Aqp5, and sodium channel epithelial 1 subunit beta (Scnn1b) was equivalent between both steroid groups. Maternal and fetal plasma neutrophil, glucose, and fetal plasma C-peptide levels were significantly elevated in the dexamethasone group, relative to the betamethasone group. Fetal plasma insulin-like growth factor 1 was significantly reduced in the dexamethasone group compared with the betamethasone group (P<0.05). Fetal adrenocorticotropic hormone (r=0.53), maternal glucose value (r=-0.52), and fetal glucose values (r=-0.42) were correlated with maternal weight in the betamethasone group (P<.05), whereas fetal pCO2 and pO2 were not correlated. There was no significant difference between male and female lamb outcomes in any groups for any of the items evaluated. This study reported that in preterm lambs, a low-dose treatment regimen of 8 mg betamethasone achieves lung maturation equivalent to that of a 24-mg dexamethasone-based regimen, but with smaller perturbations to the maternofetal hypothalamic-pituitary-adrenal axis. These data suggested that given steroid pharmacokinetic differences between sheep and humans, a betamethasone dose of 2 mg may remain above the minimum dose necessary for robust maturation of the preterm lung. Maternal weight-adjusted betamethasone doses might also be a key to reducing perturbations to the maternofetal hypothalamic-pituitary-adrenal axis.

Prenatal exposure to phthalates and maternal metabolic outcomes in a high-risk pregnant Latina population

BackgroundPhthalates are a group of endocrine disrupting chemicals that are heavily used throughout industry in flexible plastic and personal-care products. As a result, detectable levels of their metabolites are readily found in humans. Some studies have shown associations of phthalates with diabetes, but associations with gestational diabetes mellitus (GDM) are less clear. ObjectiveTo investigate the association of 11 prenatal urinary phthalate metabolites and development of GDM, impaired glucose tolerance (IGT), continuous plasma glucose level, and excessive gestational weight gain (GWG) in a population of pregnant Latina women (N = 415) enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study. MethodsPhthalate metabolite levels were measured via mass spectrometry from two urine samples collected in the end of the first and second trimester. Maternal plasma glucose levels, prior diabetes diagnosis, GDM diagnosis, and weight gain were abstracted from medical records. Multiple regression was used to evaluate the association between the average of the two urinary phthalate metabolites levels and maternal metabolic outcomes. In our sensitivity analysis, phthalate levels were categorized by level (as quartiles of exposure) and by timing of urine sample collection (as taken in first and second half of pregnancy). ResultsConsistent with findings from a nationally representative sample, all of the individual phthalate metabolites were detected in majority of mothers. Thirty-one mothers (7.5%) were diagnosed with GDM, 49 mothers (14.7%) displayed IGT, and 223 mothers (55.1%) gained an excessive amount of weight during their pregnancy. MEP concentrations were associated with an increased odds of excessive GWG (OR: 1.1, 95% CI: 1.0 to 1.3). We did not find an association between any phthalate metabolite and any maternal glucose outcome. ConclusionContrary to previous studies, our findings do not support an association of prenatal phthalate levels and increased odds for hyperglycemia, IGT, or GDM. But, we did find an increased odds of excessive GWG, a well-known risk factor for GDM.

The effect of 75-g oral glucose tolerance test on maternal and foetal Doppler parameters in healthy pregnancies: a cross-sectional observational study

Hyperglycaemia can alter placental resistance to blood flow and hyperglycaemia has adverse perinatal outcomes. Oral glucose tolerance testing (OGTT) increases the maternal plasma glucose levels temporarily and mimics metabolic hyperglycaemia. The blood flow of the uterine artery (UtA), umbilical artery (UA), middle cerebral artery (MCA) were assessed before, 1 and 2 h following the OGTT by using Doppler ultrasonography. Z-score of cerebroplacental ratio (CPR), pulsatility index (PI) for three vessels were evaluated separately. All measurements of the MCA, UA, UtA Doppler parameters were not statistically different for fasting, and 1 and 2 h following the 75 g OGTT in the 53 pregnant women with a singleton gestation in the low-risk group. This study results show that acute hyperglycaemia induced by OGTT has no effect on maternal and foetal Doppler parameters in healthy pregnancies. IMPACT STATEMENT What is already known on this subject? Foetal glucose is affected by maternal blood glucose concentrations and placental blood flow. Acute hyperglycaemia may have an effect on maternal, and foetal Doppler parameters among healthy pregnancies What do the results of this study add? Our findings indicate that blood flow velocity metric measurements in the UA, MCA and UtA were not affected by the OGTT in healthy pregnant women. What are the implications of these findings for clinical practice and/or further research? Acute hyperglycaemia induced by OGTT does not have any effect on fetomaternal circulation, especially foetal brain blood flow. Other foetal vessels including ductus venosus, renal artery, etc. may be affected by maternal blood glucose levels during the OGTT or in diabetic patients. Future prospective studies consisting of diabetic patients are warranted to verify the exact effect of glucose levels on foetal and maternal circulation.

Comparison of postprandial 90th-minute plasma glucose level with 60th- and 120th-minute levels in patients with gestational diabetes: a prospective cohort study.

The objective of the present study is to compare postprandial 90th-minute plasma glucose measurement with fasting, postprandial 60 and 120 min in gestational diabetes mellitus (GDM). One hundred and thirty-one pregnant women with GDM were hospitalized for regulation of maternal plasma glucose levels. Plasma glucose levels were daily recorded for every patient and treatment option arranged without considering the 90th-minute plasma glucose level. All patients were followed up until birth and pregnancy results were compared. At the admission, 69% of our patients were on diet and 31% were on insulin with diet therapy. The highest postprandial mean plasma glucose was seen at 90 min after breakfast (137.50 mg/dl), at 60 min after lunch (137.80 mg/dl), and 60 min after dinner (134.50 mg/dl). The cut-off level for postprandial glucose at 90th minute was determined as 130 mg/dl. The upper limit plasma glucose levels were most frequently exceeded at 90th minute for each meal. High plasma glucose levels and the need for neonatal intensive care unit were correlated (p < 0.05). The highest plasma glucose level was seen at 90 min after breakfast, 60 min after lunch, and 60 min after dinner. The upper limit plasma glucose levels were most frequently exceeded at the 90 min.

Maternal obesity and gestational diabetes decrease Metrnl concentrations in cord plasma

Objective To determine the effect of preexisting maternal obesity and gestational diabetes mellitus (GDM) on the circulating levels of Metrnl in cord and maternal plasma. Design Metrnl levels were measured on maternal and cord plasma from women with normal glucose tolerance (NGT) (19 non-obese and 20 obese), GDM controlled by diet (18 non-obese and 17 obese) and GDM controlled by insulin (19 non-obese and 18 obese) at the time of term elective cesarean section. Metrnl concentrations were determined by enzyme-linked immunoassay. Correlations of Metrnl levels with anthropometric parameters and laboratory measurements were also assessed. Results There was no effect of maternal obesity or GDM on maternal plasma Metrnl concentrations. In cord plasma, Metrnl concentrations were significantly lower in NGT obese compared to NGT non-obese women and in non-obese GDM women compared to non-obese NGT women. Significant positive correlations were observed between maternal plasma Metrnl and cord plasma Metrnl. In cord plasma, significant positive correlations were observed between Metrnl levels and GWG and maternal and cord plasma glucose levels at delivery. Conclusions At the time of term cesarean section, preexisting maternal obesity and GDM are associated with lower Metrnl levels in cord plasma. Alterations in cord plasma Metrnl levels may lead to alterations in fetal growth trajectory and be a determinant for metabolic disorders later in life.

Pre-pregnancy maternal fasting plasma glucose levels in relation to time to pregnancy among the couples attempting first pregnancy

STUDY QUESTIONWhat is the relationship between pre-pregnancy maternal glucose levels and fecundability in Chinese couples?SUMMARY ANSWERElevated pre-pregnancy maternal glucose levels were associated with fecundability, as reflected by prolonged time to pregnancy (TTP) among the couples with no prior gravidity.STUDY DESIGN, SIZE, DURATIONBased on the National Free Pre-conception Check-up Projects supported by the Chinese government, 2 226 048 eligible couples attempting first pregnancy and participating in the project from 2015 to 2016 were included. They were followed-up for 1 year or until they reported pregnancy.PARTICIPANTS/MATERIALS, SETTINGS, METHODSThe Kaplan–Meier method was used to estimate the cumulative pregnancy rate in each menstrual cycle, and the discrete-time analogue of the Cox models was used to estimate the fecundability odds ratios (FORs) and 95% CIs by different pre-pregnancy maternal glucose levels (impaired fasting glucose (IFG) or diabetes as compared to normal).MAIN RESULTS AND THE ROLE OF CHANCEThe cumulative pregnancy rate for 12 cycles of the normal fasting plasma glucose (FPG) level group was 42.29%, significantly higher than that of the IFG (35.52%) and diabetes groups (31.52%). After adjusting for confounding factors, the FORs were 0.82 (95% CI: 0.81–0.83) and 0.74 (95% CI: 0.72–0.76) for the IFG and diabetes groups, respectively, as compared to the normal group. The association between pre-pregnancy maternal FPG levels and the FORs was non-linear, and the optimal FPG level for greatest fecundability (shortest TTP) was 3.90–4.89 mmol/L.LIMITATIONS, REASONS FOR CAUTIONThe findings from this register-based cohort study require cautious interpretation given that information bias would be inevitable for single FPG measurements and for TTP calculations that were based on telephone follow-up information. Additionally, because couples who achieved pregnancy during their first menstrual cycle in the study were excluded, the pregnancy rates reported were low and possibly biased.WIDER IMPLICATIONS OF THE FINDINGSThe current report suggests that elevated pre-pregnancy maternal glucose levels were associated with prolonged TTP. Early evaluation and preventive treatment for female partners with IFG or diabetes in a pre-pregnancy examination are necessary.STUDY FUNDING/COMPETING INTEREST(S)Funding was provided by the National Key Research and Development Program of China (grants No. 2016YFC1000300 and 2016YFC1000307), the National Natural Science Foundation of China (grant No. 81872634), the CAMS Innovation Fund for Medical Sciences (grant No. 2018-I2M-1-004), the National Human Genetic Resources Sharing Service Platform (grant No. 2005DKA21300) and the National Population and Reproductive Health Science Data Center (grant No. 2005DKA32408), People’s Republic of China. The authors have no conflicts of interest to declare.TRIAL REGISTRATION NUMBERN/A

Influence of maternal adiposity, preterm birth and birth weight centiles on early childhood obesity in an Indigenous Australian pregnancy-through-to-early-childhood cohort study.

Childhood obesity rates are higher among Indigenous compared with non-Indigenous Australian children. It has been hypothesized that early-life influences beginning with the intrauterine environment predict the development of obesity in the offspring. The aim of this paper was to assess, in 227 mother-child dyads from the Gomeroi gaaynggal cohort, associations between prematurity, Gestation Related-Optimal Weight (GROW) centiles, maternal adiposity (percentage body fat, visceral fat area), maternal non-fasting plasma glucose levels (measured at mean gestational age of 23.1 weeks) and offspring BMI and adiposity (abdominal circumference, subscapular skinfold thickness) in early childhood (mean age 23.4 months). Maternal non-fasting plasma glucose concentrations were positively associated with infant birth weight (P=0.005) and GROW customized birth weight centiles (P=0.008). There was a significant association between maternal percentage body fat (P=0.02) and visceral fat area (P=0.00) with infant body weight in early childhood. Body mass index (BMI) in early childhood was significantly higher in offspring born preterm compared with those born at term (P=0.03). GROW customized birth weight centiles was significantly associated with body weight (P=0.01), BMI (P=0.007) and abdominal circumference (P=0.039) at early childhood. Our findings suggest that being born preterm, large for gestational age or exposed to an obesogenic intrauterine environment and higher maternal non-fasting plasma glucose concentrations are associated with increased obesity risk in early childhood. Future strategies should aim to reduce the prevalence of overweight/obesity in women of child-bearing age and emphasize the importance of optimal glycemia during pregnancy, particularly in Indigenous women.

Fetal sex influences maternal fasting plasma glucose levels and basal β-cell function in pregnant women with normal glucose tolerance.

Fetal sex has recently emerged as a new factor that is related to maternal glucose homeostasis during pregnancy. The present study aimed to investigate the effect of fetal sex on maternal glucose metabolism in women with normal glucose tolerance (NGT) during pregnancy in the Chinese population. A total of 877 pregnant women with NGT were recruited at 24-28weeks of gestation and underwent a 75-g oral glucose tolerance test (OGTT). Pregnant women were divided into two groups according to fetal sex. Physical examinations and laboratory tests were performed. Pancreatic β-cell function and insulin sensitivity were evaluated using OGTT-derived indices. Compared with women bearing female fetuses, women who delivered male fetuses had higher fasting plasma glucose (FPG) concentrations [4.5 (4.2-4.8) vs. 4.4 (4.2-4.7) mmol/L, P<0.05], but lower HOMA-β [161.9 (118.2-238.8) vs. 181.0 (131.7-260.9), P<0.05] and Stumvoll first phase of insulin secretion [1230.2 (1077.9-1433.7) vs. 1290.9 (1134.0-1493.2), P<0.05]. Multiple linear regression analysis indicated that the sex of the fetus was independently associated with maternal FPG and HOMA-β. Further binary logistic regression analyses revealed that the presence of a male fetus was significantly associated with elevated FPG [odds ratio (OR) 1.50; 95% confidence interval (CI) 1.12-2.00; P=0.006] and lower HOMA-β (OR 0.70; 95% CI 0.52-0.94; P=0.018) even after adjustment for potential confounders. This study provided evidence that maternal glucose metabolism could be affected by fetal sex even in NGT pregnant women. Our results suggest that the presence of male fetuses was independently associated with maternal elevated FPG and lower basal β-cell function.

Epigenetic adaptation of the placental serotonin transporter gene (SLC6A4) to gestational diabetes mellitus.

We tested the hypothesis that gestational diabetes mellitus (GDM) alters the DNA methylation pattern of the fetal serotonin transporter gene (SLC6A4), and examined the functional relevance of DNA methylation for regulation of the SLC6A4 expression in the human placenta. The study included 50 mother-infant pairs. Eighteen mothers were diagnosed with GDM and 32 had normal glucose tolerance (NGT). All neonates were of normal birth weight and born at term by planned Cesarean section. DNA and RNA were isolated from samples of tissue collected from the fetal side of the placenta immediately after delivery. DNA methylation was quantified at 7 CpG sites within the SLC6A4 distal promoter region using PCR amplification of bisulfite treated DNA and subsequent DNA sequencing. SLC6A4 mRNA levels were measured by reverse transcription—quantitative PCR (RT-qPCR). Functional SLC6A4 polymorphisms (5HTTLPR, STin2, rs25531) were genotyped using standard PCR-based procedures. Average DNA methylation across the 7 analyzed loci was decreased in the GDM as compared to the NGT group (by 27.1%, p = 0.037) and negatively correlated, before and after adjustment for potential confounder/s, with maternal plasma glucose levels at the 24th to 28th week of gestation (p<0.05). Placental SLC6A4 mRNA levels were inversely correlated with average DNA methylation (p = 0.010) while no statistically significant association was found with the SLC6A4 genotypes (p>0.05). The results suggest that DNA methylation of the fetal SLC6A4 gene is sensitive to the maternal metabolic state in pregnancy. They also indicate a predominant role of epigenetic over genetic mechanisms in the regulation of SLC6A4 expression in the human placenta. Longitudinal studies in larger cohorts are needed to verify these results and determine to which degree placental SLC6A4 changes may contribute to long-term outcomes of infants exposed to GDM.

Relationship between fasting plasma glucose levels and maternal food group and macronutrient intakes in pregnancy

AbstractAimIncreased maternal body mass index (BMI) has been consistently associated with elevated blood glucose levels during pregnancy. Studies to date investigating the relationship between maternal blood glucose levels and dietary intake have shown mixed results. We investigated the association between maternal fasting plasma glucose (FPG) levels and food group and macronutrient intakes in the first trimester of pregnancy, after adjustment for maternal bodyweight.MethodsWomen were recruited after sonographic confirmation of an ongoing singleton pregnancy in the first trimester. Dietary information was collected using the validated Willett Food Frequency Questionnaire. Maternal height and weight were measured and BMI calculated. Body composition was measured using advanced bioelectrical impedance analysis. FPG levels were obtained for women who were selectively screened with a 75 g oral glucose tolerance test.ResultsNo associations were observed between maternal FPG levels and food group or macronutrient intakes but higher energy and starch intakes were found in obese subjects (P = 0.009 and P = 0.03 respectively). On univariate analysis, higher FPG levels were associated positively with higher maternal bodyweight, BMI, body fat, fat free mass and visceral fat (all P &lt; 0.001). However, on multivariate regression analysis, higher FPG levels remained associated only with maternal BMI &gt; 29.9 kg/m2 (OR 7.4, P = 0.01).ConclusionsOur findings indicate that maternal BMI is the key determinant of maternal glycaemia. Interventions which focus on overall energy restriction and especially the limitation of dietary starch to optimise prepregnancy maternal bodyweight are likely to be useful in improving glycaemic control in higher risk pregnancies.

Diabetes and the breast

Diabetes and the breast

Fructose intake during pregnancy up-regulates the expression of maternal and fetal hepatic sterol regulatory element-binding protein-1c in rats

Excess fructose consumption is associated with the development of type 2 diabetes and obesity. However, the impact of fructose intake on maternal and fetal lipid metabolism during pregnancy is not known. The aim of this study was to examine whether maternal fructose intake during pregnancy would affect fetal and maternal hepatic lipid metabolism. Pregnant Wistar rats were randomly divided into untreated control and fructose-treated groups; the fructose-treated group received fructose via drinking water throughout pregnancy. On gestational day 20, glucose and insulin concentration in the maternal plasma were measured. The mRNA expression of sterol regulatory element-binding protein (SREBP)-1c and its target genes in the liver of dams and fetuses were analyzed by real-time PCR. Significantly higher maternal plasma glucose levels, indicating hyperglycemia, was observed in the fructose-treated group than in the control group. Furthermore, the fructose-treated group showed significantly higher expression levels of both maternal and fetal SREBP-1c mRNA and protein and significantly elevated expression of fatty acid synthase; the group also showed reduced acyl-CoA oxidase levels in the maternal liver. Thus, our results suggest that maternal fructose intake during pregnancy causes maternal hyperglycemia and up-regulates hepatic SREBP-1c expression in both fetuses and dams. This may lead to defects in carbohydrate and lipid metabolism in the adult offspring.

The interleukins IL-6 and IL-1Ra: a mediating role in the associations between BMI and birth weight?

The biological mechanisms in the association between maternal body mass index (BMI) and birth weight are not well understood, but are likely to involve maternal plasma glucose levels and nutrient transport across the placenta, both important modulators of fetal growth. Adipose tissue contributes to circulating levels of interleukins that may affect glucose metabolism and possibly also placental transport of nutrients. We investigated possible mediating roles of Interleukin 6 (IL-6) and Interleukin 1 Receptor antagonist (IL-1Ra) in 208 pregnant women. Known and hypothesized dependencies between BMI in early pregnancy and fasting glucose, IL-1Ra and IL-6 at gestational weeks 30-32, and birth weight were specified in a path diagram. Standardized regression coefficients, expressing direct, indirect and total effects, were estimated by Bayesian path analysis. Mean (s.d.) BMI was 24.9 kg/m2 (4.2) and mean (s.d.) birth weight 3748 g (454). The total effect of BMI on birth weight was 0.24 (95% credibility interval (CrI) [0.12, 0.36]). The direct effect of IL-1Ra on birth weight was not statistically significant, but significant effects of BMI on IL-1Ra (0.61, 95% CrI [0.51, 0.72]), of IL-1Ra on fasting glucose (0.17, 95% CrI [0.01, 0.34]) and of fasting glucose on birth weight (0.14, 95% CrI [0.01, 0.27]) implied an indirect pathway from BMI via IL-1Ra on birth weight. Approximately 20% of the effect of BMI on birth weight was mediated through IL-1Ra. For IL-6, no such effects were found. Our results indicate that IL-1Ra may be a mediator in the association between BMI and birth weight.

Metabolic effects of ritodrine hydrochloride in the pregnant sheep.

The effects of ritodrine hydrochloride on maternal and fetal arterial blood pH and pCO2, plasma electrolytes and maternal plasma glucose and free fatty acid levels were investigated in the third-trimester pregnant sheep. Ritodrine produced a slight fall in the maternal and fetal arterial pH without changes in the arterial pC02. The pH values were, however, within a normal range. Increases in the maternal plasma glucose and free fatty acid levels were also observed. Although maternal and fetal plasma sodium and chloride concentrations did not change, the potassium decreased in a dose-dependent manner both in the ewe and in the fetus following sequential ritodrine infusion. Constant infusion of ritodrine (3 mcg/kg/min), which is a sufficient dose to inhibit uterine contractions, also resulted in a significant decrease in the maternal plasma potassium concentration. It appears to be necessary to give attention to the metabolic effects of ritodrine in long-term therapy of premature labor.

Arsenate-induced maternal glucose intolerance and neural tube defects in a mouse model

Background Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic's teratogenicity in early neurodevelopment. Methods We evaluated maternal intraperitoneal (IP) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selected compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), l-methionine (L-Met), N-tert-Butyl-α-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate's effects. Results Arsenate caused significant glucose elevation during an IP glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams ( p = 0.0260). Arsenate caused NTDs (100%, p < 0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin's success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role.

Determinants of birth weight in boys and girls

AbstractBoys are heavier at birth than girls, but girls have higher fat mass at birth than boys. Insulin action may play an important role of this different distribution. Animal models have shown that female offspring are more sensitive to maternal feeding and glucose values during pregnancy and weaning than male offspring. Newborn girls have higher insulin and proinsulin concentrations and total proinsulin‐to‐insulin ratios in cord blood than boys, despite lighter birth weight. In a cohort of 522 newborn above 37 gestational weeks we split between the sexes and studied associations between birth weights, parental anthropometrics and fasting maternal plasma glucose and insulin levels. Boys weighed 184g more than girls, they were 1.1 cm longer and head circumference differed by 0.86 (all p values &lt;0.01). Multiple linear regressions showed that parity, maternal body mass index, gestational age and maternal birth weight were associated with birth weight for both sexes, whereas maternal weight gain in pregnancy and maternal fasting plasma glucose at week 30‐32 were significantly associated with birth weight for girls only. The effect of fasting plasma glucose on birth weight in girls was twice as high as in boys (B=162, 95% CI 33.4‐291, p=0.01). Paternal birth weight was significantly associated with birth weight of boys, but no such association was seen for girls. This supports the notion that there is a genetic regulation along the male line. Girls may be more sensitive to intrauterine environment and maternal glucose values, as these have a stronger influence on birth weight of girls.

AMP‐activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over‐nourished sheep

Maternal obesity and over-nutrition give rise to both obstetric problems and neonatal morbidity. The objective of this study was to evaluate effects of maternal obesity and over-nutrition on signalling of the AMP-activated protein kinase (AMPK) pathway in fetal skeletal muscle in an obese pregnant sheep model. Non-pregnant ewes were assigned to a control group (Con, fed 100% of NRC nutrient recommendations, n = 7) or obesogenic group (OB, fed 150% of National Research Council (NRC) recommendations, n = 7) diet from 60 days before to 75 days after conception (term 150 days) when fetal semitendinosus skeletal muscle (St) was sampled. OB mothers developed severe obesity accompanied by higher maternal and fetal plasma glucose and insulin levels. In fetal St, activity of phosphoinositide-3 kinase (PI3K) associated with insulin receptor substrate-1 (IRS-1) was attenuated (P < 0.05), in agreement with the increased phophorylation of IRS-1 at serine 1011. Phosphorylation of AMP-activated protein kinase (AMPK) at Thr 172, acetyl-CoA carboxylase at Ser 79, tuberous sclerosis 2 at Thr 1462 and eukaryotic translation initiation factor 4E-binding protein 1 at Thr 37/46 were reduced in OB compared to Con fetal St. No difference in energy status (AMP/ATP ratio) was observed. The expression of protein phosphatase 2C was increased in OB compared to Con fetal St. Plasma tumour necrosis factor alpha (TNFalpha) was increased in OB fetuses indicating an increased inflammatory state. Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) was higher in OB St, indicating enhanced adipogenesis. The glutathione: glutathione disulphide ratio was also lower, showing increased oxidative stress in OB fetal St. In summary, we have demonstrated decreased signalling of the AMPK system in skeletal muscle of fetuses of OB mothers, which may play a role in altered muscle development and development of insulin resistance in the offspring.