Maternal Metabolic Parameters Research Articles

Changes in the shape and function of the fetal heart of pre- and gestational diabetes mothers

BackgroundHyperglycemia during pregnancy can affect fetal heart in many ways, including causing cardiac malformation, leading to hypertrophic cardiomyopathy and cardiac dysfunction. Echocardiographic evaluation can assist identify alterations in heart structure, morphology and function, enabling prompt monitoring and management. However, according to earlier research, the cardiac alterations are modest in hyperglycemic mothers’ fetuses, and might not be detectable using conventional methods and it is also unclear whether these changes are related to the metabolism of mothers. Fetal Heart Quantification (Fetal HQ) can assess ventricular geometry and function more sensitively and thoroughly, and identify sub-clinical cardiac dysfunction. The purpose of this study was to evaluate fetal heart by Fetal HQ in fetuses of hyperglycemic mothers who either had pre-gestational or gestational diabetes and to correlate them with maternal metabolic indices.MethodsThe fetuses of 25 gestational age-matched control mothers, 48 women with gestational diabetes mellitus (GDM), and 11 women with diabetes mellitus (DM) were included in the prospective case-control research. Using fetal echocardiography and speckle tracking echocardiography (STE), the heart of the fetus was evaluated. Differences in the groups’ anthropometric, metabolic, and cardiac parameters were examined. It was assessed whether maternal features, prenatal glucose, lipids, and maternal hemoglobin A1c (HbA1c) correlated with fetal cardiac parameters.ResultsThe LV EDV and ESV were significantly higher in the GDM group as compared to the DM group (p < 0.05). The GSI% was significantly lower in the GDM group compared with the control (p < 0.05). The LV SV and CO of the GDM group were both significantly higher compared with the DM group (p < 0.05). There was a significant decrease in RV FS for segments 1–7 in GDM fetuses compared to the control (p < 0.05) and for segments 5–10 compared to DM (p < 0.05). Fetal cardiac morphology and function indices correlate with maternal pregestational weight, BMI, early pregnancy fast glucose, lipids, and glycemic control levels.ConclusionsFetuses exposed to gestational diabetes have altered heart morphology and function that is linked to maternal metabolic parameters, which presents a special indication for performing geometry and function cardiac assessment. Fetal HQ can be employed to evaluate the fetal cardiac shape and function in fetuses exposed to gestational diabetes.

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

BackgroundSerotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters—pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)—and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database.ResultsNone of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites.ConclusionsMethylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.

Maternal and fetal predictors of anthropometry in the first year of life in offspring of women with GDM.

Gestational Diabetes Mellitus (GDM) carries an increased risk for adverse perinatal and longer-term cardiometabolic consequences in offspring. This study evaluated the utility of maternal anthropometric, metabolic and fetal (cord blood) parameters to predict offspring anthropometry up to 1 year in pregnancies with GDM. In this prospective analysis of the MySweetheart study, we included 193/211 women with GDM that were followed up to 1 year postpartum. Maternal predictors included anthropometric (pre-pregnancy BMI, gestational weight gain (GWG), weight and fat mass at the 1st GDM visit), and metabolic parameters (fasting insulin and glucose, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Quantitative insulin-sensitivity check index (QUICKI), HbA1c, triglycerides, and high-density lipoprotein (HDL) at the 1st visit and HbA1c at the end of pregnancy). Fetal predictors (N=46) comprised cord blood glucose and insulin, C-Peptide, HOMA-IR, triglycerides and HDL. Offspring outcomes were anthropometry at birth (weight/weight z-score, BMI, small and large for gestational age (SGA,LGA)), 6-8 weeks and 1 year (weight z-score, BMI/BMI z-score, and the sum of 4 skinfolds). In multivariate analyses, birth anthropometry (weight, weight z-score, BMI and/or LGA), was positively associated with cord blood HDL and HbA1c at the 1st GDM visit, and negatively with maternal QUICKI and HDL at the 1st GDM visit (all p ≤ 0.045). At 6-8 weeks, offspring BMI was positively associated with GWG and cord blood insulin, whereas the sum of skinfolds was negatively associated with HDL at the 1st GDM visit (all p ≤0.023). At 1 year, weight z-score, BMI, BMI z-score, and/or the sum of skinfolds were positively associated with pre-pregnancy BMI, maternal weight, and fat mass at the 1st GDM visit and 3rd trimester HbA1c (all p ≤ 0.043). BMI z-score and/or the sum of skinfolds were negatively associated with cord blood C-peptide, insulin and HOMA-IR (all p ≤0.041). Maternal anthropometric, metabolic, and fetal metabolic parameters independently affected offspring anthropometry during the 1st year of life in an age-dependent manner. These results show the complexity of pathophysiological mechanism for the developing offspring and could represent a base for future personalized follow-up of women with GDM and their offspring.

Lipoprotein lipase concentration in umbilical cord blood reflects neonatal birth weight.

Insulin resistance (IR) is exacerbated during pregnancy via increases in insulin counterregulatory hormones. Maternal lipids are strong determinants of neonatal growth, although triglyceride-rich lipoproteins (TGRLs) cannot be transferred directly to the fetus through the placenta. The catabolism of TGRLs under physiological IR and the reduced synthesis of lipoprotein lipase (LPL) are poorly understood. We examined the association of maternal and umbilical cord blood (UCB)-LPL concentrations with maternal metabolic parameters and fetal development. Changes in anthropometric measures and lipid-, glucose-, and insulin-related parameters, including maternal and UCB-LPL concentrations, were examined in 69 women during pregnancy. The relationship between those parameters and neonatal birth weight was assessed. Parameters reflecting glucose metabolism did not change during pregnancy, whereas those associated with lipid metabolism and IR changed markedly, particularly in the second and third trimesters. In the third trimester, the maternal LPL concentration gradually decreased, by 54%, whereas the UCB-LPL concentration was∼2-fold higher than the maternal LPL concentration. Univariate and multivariate analyses showed that the UCB-LPL concentration was a significant determinant of neonatal birth weight, together with placental birth weight. The LPL concentration in UCB reflects neonatal development under a decreased LPL concentration in maternal serum.

Serum lipid profile in relation to free thyroxine and the effect of levothyroxine treatment on lipids in patients with isolated hypothyroxinemia during pregnancy: a single-center retrospective study

BackgroundThyroid function is widely considered a lipid metabolism regulator. However, studies on lipid metabolism in pregnant women with low free thyroxine (FT4) levels are limited and inconclusive. Furthermore, the association between maternal FT4 deficiency and adverse lipid metabolic parameters is unknown. Therefore, we aimed to investigate this association and the effects of levothyroxine (L-T4) treatment on these metabolic indicators.MethodsThis retrospective study included 164 patients with isolated hypothyroidism (IH) (FT4 levels below the 5th percentile with normal thyroid stimulating hormone levels according to the gestational-specific reference range) and 407 euthyroidism patients (control group who had regular antenatal examinations at Zhejiang Provincial People's Hospital, Hangzhou, China) between January 1, 2019, and December 31, 2020. Patients with IH were divided into levothyroxine (L-treatment group, n = 77) and dietary iodine supplement treatment groups (dietary treatment group, n=87) according to the hospital’s treatment policy and clinical experience. The intervention lasted for at least 8 weeks. Metabolic indicators, including thyroid function and lipid parameters, were collected at least twice before and after the intervention. Other data collected included maternal age, history of abortion, prepregnancy BMI, and gestational weight gain (Fig. 1).ResultsCompared with the control group, Patients with IH had a higher degree of dyslipidemia, reflected in elevated total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) levels. In IH patients, an inverse correlation was found between FT4 and TG levels, which remained after adjusting for prepregnancy BMI. The L-treatment group demonstrated a significantly slower rate of hypercholesterolemia progression during pregnancy than the dietary treatment group. In addition, there was a relationship between the therapeutic effect and the degree of disease, with the main factors being FT4, TSH and TG levels prior to starting treatment.ConclusionsLow FT4 levels were associated with elevated blood lipid levels. Serum FT4 and lipid levels in patients could be improved by medical intervention.

Associations between maternal metabolic parameters during pregnancy and fetal and child growth trajectories from 20 weeks' gestation to 5 years of age: Secondary analysis from the ROLO longitudinal birth cohort study.

To examine the association between maternal metabolic parameters in pregnancy and growth trajectories up to 5 years of age. Data from mother-child pairs who participated in the ROLO study, a randomized trial examining the impact of a low glycaemic index diet on the recurrence of macrosomia, were analysed. Fetal and child growth trajectories were developed from longitudinal measurements from 20 weeks gestation up to 5 years of age. We examined associations between maternal fasting glucose, insulin, HOMA-IR and leptin, taken in early pregnancy (14-16 weeks) and late pregnancy (28 weeks), and weight (kg) and abdominal circumference (cm) trajectories using linear spline multilevel models. We found no strong evidence of associations between any maternal metabolic parameters and fetal to childhood weight and abdominal circumference trajectories from 20 weeks gestation to 5 years. In a cohort of women with obesity with infants at risk of macrosomia, maternal metabolic markers were not strongly associated with trajectories of weight or abdominal circumference from 20 weeks gestation to 5 years of age.

An mHealth-Supported antenatal lifestyle intervention may be associated with improved maternal sleep in pregnancy: Secondary analysis from the PEARS trial.

To investigate the effect of an antenatal diet and exercise intervention during pregnancy on sleep duration. As a secondary objective, associations between sleep duration and gestational weight gain (GWG), maternal metabolic parameters and pregnancy outcomes were assessed. Secondary analysis. Large tertiary Maternity Hospital in Dublin, Ireland. 326 women with overweight or obesity who participated in the Pregnancy Exercise And Nutrition Research Study (PEARS) randomised controlled trial between March 2013 and August 2016. Secondary analysis of a randomised trial. Impact of the PEARS intervention on sleep duration, and association of sleep duration and maternal metabolic parameters, and pregnancy outcomes. Participants had a mean age of 32.5 ± 4.5 years and median (interquartile range [IQR]) body mass index of 28.3 (26.6-31.2) kg/m2 . The intervention group had a longer sleep duration in late pregnancy (mean difference 17.1 minutes (95% confidence interval [CI] 0.5-33.7) and a higher proportion achieving optimum sleep duration of 7-9 h (54.3 vs. 42.9%, relative risk [RR] 1.28 (95% CI 1.01-1.62). In late pregnancy, sleep duration of <6 h was associated with lower breastfeeding rates on discharge (RR 0.74, 95% CI 0.57-0.95) and higher triglyceride levels (mean difference 0.24, 95% CI 0.10-0.38). There were no significant associations between sleep and incidence of gestational diabetes mellitus or pre-eclampsia/toxaemia, or other metabolic parameters assessed (insulin, fasting glucose, HOMA-IR). A diet and exercise intervention from early pregnancy may promote longer and optimal sleep duration, with maternal benefits such as lower triglyceride levels and higher breastfeeding rates.

Impact of Risk Factors on Short and Long-Term Maternal and Neonatal Outcomes in Women With Gestational Diabetes Mellitus: A Prospective Longitudinal Cohort Study.

AimsUniversal screening of gestational diabetes mellitus (GDM) in women with no risk factors (RF) for GDM remains controversial. This study identified the impact of the presence of RF on perinatal and postpartum outcomes.MethodsThis prospective cohort study included 780 women with GDM. GDM RF included previous GDM, first grade family history of type 2 diabetes, high-risk ethnicity and pre-pregnancy overweight/obesity (OW/OB). Outcomes included obstetrical, neonatal and maternal metabolic parameters during pregnancy and up to 1 year postpartum.ResultsOut of 780 patients, 24% had no RF for GDM. Despite this, 40% of them needed medical treatment and they had a high prevalence of glucose intolerance of 21 and 27% at 6-8 weeks and 1-year postpartum, respectively. Despite similar treatment, women with RF had more neonatal and obstetrical complications, but they had especially more frequent adverse metabolic outcomes in the short- and long-term. The most important RF for poor perinatal outcome were previous GDM and pre-pregnancy OW/OB, whereas high-risk ethnicity and pre-pregnancy OW/OB were RF for adverse postpartum metabolic outcomes. Increasing number of RF were associated with worsened perinatal and long-term postpartum outcomes except for pregnancy-induced hypertension, C-section delivery and neonatal hypoglycaemia.ConclusionWomen with no RF had a high prevalence of adverse perinatal and postpartum outcomes, while the presence of RF particularly increased the risk for postpartum adverse metabolic outcomes. This calls for a RF-based long-term follow-up of women with GDM.

Metformin in pregnancy: a re-examination of its safety.

Metformin in pregnancy: a re-examination of its safety.

Zinc, selenium and chromium co-supplementation improves insulin resistance by preventing hepatic endoplasmic reticulum stress in diet-induced gestational diabetes rats

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and results in adverse outcomes for pregnant women and their offspring. Endoplasmic reticulum (ER) stress is associated with insulin resistance and implicates in the development of GDM. Zinc, selenium and chromium have been shown to maintain glucose homeostasis via multiple mechanisms, but how these trace elements affect the insulin resistance and ER stress in GDM are largely unknown. To address this, a GDM rat model was induced by feeding female Sprague-Dawley rats a high-fat (45%) and sucrose diet, while zinc (10 mg/kg.bw), selenium (20 ug/kg.bw), chromium (20 ug/kg.bw) were daily supplemented alone or in combination from 6 weeks before mating to the end of lactation period. Maternal metabolic parameters, hepatic ER stress and insulin signaling were analyzed. The results showed that zinc, selenium and chromium co-supplementation dramatically alleviated high-fat and sucrose-induced glucose intolerance and oxidative stress during entire experiment period. Hepatic ER stress as well as the unfolded protein response was activated in GDM dams, characterized by the up-regulation of glucose-regulated protein 78, phosphorylated the protein kinase RNA-like endoplasmic reticulum kinase, and the inositol-requiring enzyme 1α. Zinc, selenium and chromium supplementation significantly prevented this activation, by which contributes to the promotion of the phosphorylated protein kinase B related insulin signaling and maintenance of glucose homeostasis. In conclusion, zinc, selenium and chromium supplementation may be a promising way to prevent the development of GDM by alleviating hepatic ER stress.

Different Protein Sources in the Maternal Diet of the Rat during Gestation and Lactation Affect Milk Composition and Male Offspring Development during Adulthood.

Protein sources in maternal diet are important for mammary gland differentiation and milk protein; however, few studies have examined the metabolic and cellular adaptations of mothers based on protein source diets during pregnancy and lactation, and leptin concentration in offspring. We evaluated metabolic parameters and maternal key organs and milk components in mothers at the end of lactation, who were fed different sources of proteins. In postnatal day 110 and 250, we studied development parameters and leptin in male offspring. Female rats received a Vegetal (V) or Animal (A) diet during pregnancy and lactation. After weaning, male offspring ate V diet until postnatal day 250, which yielded two groups: Vv and Av. Milk dry, protein and fat were analyzed. Maternal metabolic parameters, leptin, and liver, adipose tissue and mammary gland histological analyses were studied. Body weight, food intake and leptin were analyzed in offspring at two ages. Adipose tissue weight and cells size and liver fat, mammary gland apoptosis, weight, milk protein and leptin were higher in A vs V. Maternal liver and milk dry were lower in A vs V. All offspring parameters were higher in Av vs Vv at postnatal day 110; however, at postnatal day 250, leptin was higher in Av vs Vv. Maternal serum and milk leptin had a positive correlation with offspring serum leptin at both ages. Consumption of animal protein-based diets by mothers during developmental periods affects specific maternal organs and changes milk composition during lactation, leading to a hyperleptinemic phenotype in male offsprings.

Zinc, Selenium and Chromium Supplementation Improves Insulin Resistance by Preventing Hepatic Endoplasmic Reticulum Stress in Diet-Induced Gestational Diabetes Rats

Abstract Objectives Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and results in adverse outcomes for pregnant women and their offspring. Endoplasmic reticulum (ER) stress is associated with insulin resistance and implicates in the development of GDM. Zinc, selenium and chromium have been shown to maintain glucose homeostasis via multiple mechanisms, but how these trace elements affect the insulin resistance and ER stress in GDM are largely unknown. Methods A GDM rat model was induced by feeding female Sprague-Dawley (SD) rats a high-fat (45%) and sucrose (HFS) diet, while zinc (10 mg/kg.bw), selenium (20 ug/kg.bw), chromium (20 ug/kg.bw) were daily supplemented alone or in combination from 6 weeks before mating to the end of lactation period. Maternal metabolic parameters, hepatic ER stress and insulin signaling were analyzed. Results The results showed that zinc, selenium and chromium supplementation dramatically alleviated HFS-induced glucose intolerance and oxidative stress during entire experiment period. Hepatic ER stress as well as the unfolded protein response (UPR) was activated in GDM rats, characterized by the up-regulation of glucose-regulated protein 78 (GRP78), phosphorylated the protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), and the inositol-requiring enzyme 1α (p-IRE1α). Zinc, selenium and chromium supplementation significantly prevented this activation, by which contributes to the promotion of the phosphorylated protein kinase B (p-AKT) related insulin signaling and maintenance of glucose homeostasis. Conclusions Zinc, selenium and chromium supplementation may be a promising way to prevent the development of GDM by alleviating hepatic ER stress. Funding Sources This work was financially supported by the Angel Nutritech Nutrition Fund (AF2017003) and the National Natural Science Foundation of China (NSFC, 81373006 and 81973043).

Maternal malnutrition and anaemia in India: dysregulations leading to the 'thin-fat' phenotype in newborns.

Maternal and child malnutrition and anaemia remain the leading factors for health loss in India. Low birth weight (LBW) offspring of women suffering from chronic malnutrition and anaemia often exhibit insulin resistance and infantile stunting and wasting, together with increased risk of developing cardiometabolic disorders in adulthood. The resulting self-perpetuating and highly multifactorial disease burden cannot be remedied through uniform dietary recommendations alone. To inform approaches likely to alleviate this disease burden, we implemented a systems-analytical approach that had already proven its efficacy in multiple published studies. We utilised previously published qualitative and quantitative analytical results of rural and urban field studies addressing maternal and infantile metabolic and nutritional parameters to precisely define the range of pathological phenotypes encountered and their individual biological characteristics. These characteristics were then integrated, via extensive literature searches, into metabolic and physiological mechanisms to identify the maternal and foetal metabolic dysregulations most likely to underpin the 'thin-fat' phenotype in LBW infants and its associated pathological consequences. Our analyses reveal hitherto poorly understood maternal nutrition-dependent mechanisms most likely to promote and sustain the self-perpetuating high disease burden, especially in the Indian population. This work suggests that it most probably is the metabolic consequence of 'ill-nutrition' - the recent and rapid dietary shifts to high salt, high saturated fats and high sugar but low micronutrient diets - over an adaptation to 'thrifty metabolism' which must be addressed in interventions aiming to significantly alleviate the leading risk factors for health deterioration in India.

Intrauterine Exposure to Diabetic Milieu Does Not Induce Diabetes and Obesity in Male Adulthood in a Novel Rat Model.

Several studies show an association of maternal diabetes during pregnancy with adverse offspring metabolic health. Other studies, however, suggest that this effect might be biased by obesity, which is independently associated with offspring metabolic disease and often coexistent to maternal diabetes. We performed a prospective study in a rat model to test the hypothesis that the burden of a diabetic pregnancy without obesity deteriorates metabolic health in male offspring. We generated maternal type 2 diabetes before conception that persisted during pregnancy by knockdown of the insulin receptor in small hairpin RNA-expressing transgenic rats. Male WT (wild type) offspring were followed up until adulthood and metabolically challenged by high-fat diet. Blood glucose was measured continuously via a telemetry device. Glucose and insulin tolerance tests were performed, and body composition was analyzed. Weight gain and glucose levels during adolescence and adulthood were similar in male offspring of diabetic and control pregnancies. Body weight and fat mass after high-fat diet, as well as glucose and insulin tolerance tests, were unaltered between male adult offspring of both groups. Glycemic control consisting of up to 49 000 individual glucose measures was comparable between both groups. Intrauterine exposure to maternal hyperglycemia and hyperinsulinemia without obesity had no impact on male offspring metabolic health in our model. We conclude that the intrauterine exposure itself does not represent a mechanism for fetal programming of diabetes and obesity in our model. Other maternal metabolic parameters during pregnancy, such as obesity, might impact long-term offspring metabolic health.

Celiac Disease and Pregnancy Outcomes in Patients with Gestational Diabetes Mellitus.

Aim Gestational diabetes mellitus (GDM) and celiac disease, if not diagnosed and properly treated, are associated with adverse outcomes of pregnancy. The aim of our study was to examine pregnancies complicated by GDM in celiac and nonceliac women in terms of their metabolic parameters and maternal and fetal outcomes. Methods The study involved 60 women with GDM, 20 with and 40 without celiac disease. Maternal clinical and metabolic parameters (glucose and insulin levels in the oral glucose tolerance test (OGTT), fasting plasma glucose, HbA1c, lipid profile, prepregnancy BMI, gestational weight gain, and chronic diseases), pregnancy outcomes (gestational hypertension, pre-eclampsia, eclampsia, time, and mode of delivery), and fetal parameters (weight and length at birth, and neonatal complications) were recorded. Results The two groups did not differ significantly in maternal parameters other than blood glucose levels at 120′ in the diagnostic OGTT (141.2 ± 35.2 vs 161.2 ± 35.4, mg/dl, p=0.047), prepartum cLDL (127.2 ± 43.5 vs 179.6 ± 31.7 mg/dl, p ≤ 0.001), and total cholesterol (229.0 ± 45.9 vs 292.5 ± 42.1 mg/dl, p ≤ 0.001), which were significantly lower in celiac women than in nonceliac controls. Children born from celiac women had a significantly higher birth weight (3458.1 ± 409.8 vs 3209.0 ± 432.7 g, p=0.044) and ponderal index (2.89 ± 0.32 vs 2.66 ± 0.25 g/cm3, p=0.006) and were more likely to be large for gestational age (27.8% vs 2.5%, p=0.012). Analyzing the composition of the celiac and nonceliac women's diet showed that, for the same amount of kilocalories, the gluten-free diet was associated with a slight increase in the amount of carbohydrates (49.75% vs 48.54%) and a reduction in the amount of protein (21.10% vs 23.31%) and especially of fiber (9.84% vs 12.71%). Conclusions Celiac women with GDM have much the same pregnancy outcomes as nonceliac women with GDM, except for fetal overgrowth. Gluten-free food, being richer in carbohydrates and less rich in fiber and protein, could have a role in fetal growth in celiac women.

Main Fetal Predictors of Adverse Neonatal Outcomes in Pregnancies with Gestational Diabetes Mellitus.

The objectives of this study were to (a) assess the utility of fetal anthropometric variables to predict the most relevant adverse neonatal outcomes in a treated population with gestational diabetes mellitus (GDM) beyond the known impact of maternal anthropometric and metabolic parameters and (b) to identify the most important fetal predictors. A total of 189 patients with GDM were included. The fetal predictors included sonographically assessed fetal weight centile (FWC), FWC > 90% and <10%, and fetal abdominal circumference centile (FACC), FACC > 90% and < 10%, at 29 0/7 to 35 6/7 weeks. Neonatal outcomes comprising neonatal weight centile (NWC), large and small for gestational age (LGA, SGA), hypoglycemia, prematurity, hospitalization for neonatal complication, and (emergency) cesarean section were evaluated. Regression analyses were conducted. Fetal variables predicted anthropometric neonatal outcomes, prematurity, cesarean section and emergency cesarean section. These associations were independent of maternal anthropometric and metabolic predictors, with the exception of cesarean section. FWC was the most significant predictor for NWC, LGA and SGA, while FACC was the most significant predictor for prematurity and FACC > 90% for emergency cesarean section. In women with GDM, third-trimester fetal anthropometric parameters have an important role in predicting adverse neonatal outcomes beyond the impact of maternal predictors.

An extra virgin olive oil-enriched diet improves maternal, placental, and cord blood parameters in GDM pregnancies.

To address the effect of a diet enriched in extra virgin olive oil (EVOO) on maternal metabolic parameters and placental proinflammatory markers in Gestational diabetes mellitus (GDM) patients. Pregnant women at 24-28 weeks of gestation were enrolled: 33 GDM patients which were randomly assigned or not to the EVOO-enriched group and 17 healthy controls. Metabolic parameters were determined. Peroxisome proliferator activated receptor (PPAR) γ and PPARα protein expression, expression of microRNA (miR)-130a and miR-518d (which respectively target these PPAR isoforms) and levels of proinflammatory markers were evaluated in term placentas. Matrix metalloproteinases (MMPs) activity was evaluated in term placentas and umbilical cord blood. GDM patients that received the EVOO-enriched diet showed reduced pregnancy weight gain (GDM-EVOO:10.3 ± 0.9, GDM:14.2 ± 1.4, P = .03) and reduced triglyceridemia (GDM-EVOO:231 ± 14, GDM:292 ± 21, P = .02) compared to the non-EVOO-enriched GDM group. In GDM placentas, the EVOO-enriched diet did not regulate PPARγ protein expression or miR-130a expression, but prevented the reduced PPARα protein expression (P = .02 vs GDM) and the increased miR-518d expression (P = .009 vs GDM). Increased proinflammatory markers (interleukin-1β, tumour necrosis factor-α and nitric oxide overproduction) in GDM placentas were prevented by the EVOO-enriched diet (respectively P = .001, P = .001 and P = .01 vs GDM). MMPs overactivity was prevented in placenta and umbilical cord blood in the EVOO-enriched GDM group (MMP-9: respectively P = .01 and P = .001 vs GDM). A diet enriched in EVOO in GDM patients reduced maternal triglyceridemia and weight gain and has antiinflammatory properties in placenta and umbilical cord blood, possibly mediated by the regulation of PPAR pathways.

Temporal relationships between maternal metabolic parameters with neonatal adiposity in women with obesity differ by neonatal sex: Secondary analysis of the DALI study.

SummaryObjectivesTo investigate the importance of time in pregnancy and neonatal sex on the association between maternal metabolic parameters and neonatal sum of skinfolds.MethodsThis was a longitudinal, secondary analysis of the vitamin D and lifestyle intervention for gestational diabetes mellitus study, conducted in nine European countries during 2012 to 2015. Pregnant women with a pre‐pregnancy body mass index (BMI) of ≥29 kg/m2 were invited to participate. We measured 14 maternal metabolic parameters at three times during pregnancy: <20 weeks, 24 to 28 weeks, and 35 to 37 weeks of gestation. The sum of four skinfolds assessed within 2 days after birth was the measure of neonatal adiposity.ResultsIn total, 458 mother‐infant pairs (50.2% female infants) were included. Insulin resistance (fasting insulin and HOMA‐index of insulin resistance) in early pregnancy was an important predictor for boys' sum of skinfolds, in addition to fasting glucose and maternal adiposity (leptin, BMI and neck circumference) throughout pregnancy. In girls, maternal lipids (triglycerides and fatty acids) in the first half of pregnancy were important predictors of sum of skinfolds, as well as fasting glucose in the second half of pregnancy.ConclusionsAssociations between maternal metabolic parameters and neonatal adiposity vary between different periods during pregnancy. This time‐dependency is different between sexes, suggesting different growth strategies.

Limited Impact of Fetal Sex and Maternal Body Mass Index on Fetal and Maternal Insulin Resistance and Lipid Metabolism: Findings from the PEARs Study.

The intrauterine environment can have a significant impact on fetal and maternal well-being, both during pregnancy and in later life. We aimed to identify how fetal sex and maternal body mass index (BMI) influence insulin resistance and metabolic function during pregnancy with maternal BMI > 25kg/m2. This secondary analysis assessed data from the PEARS-randomized controlled trial that recruited pregnant women with body mass indexes 25-39.9kg/m2. Longitudinal measurements of maternal and fetal insulin resistance and metabolic function were recorded throughout pregnancy. Regression models tested the effects of fetal sex and maternal BMI on markers of metabolic function and insulin regulation. A total of 484 women and their newborns (252 (52%) males vs. 232 (48%) females) were included in the analysis. A total of 333 (69%) women were overweight and 151 (31%) were obese. Male newborns were heavier and larger than females, and had a higher rate of instrumental delivery. Males had a lower LDL, but no other markers of insulin resistance or metabolic function were affected by fetal sex. Women with obesity had elevated markers of insulin resistance and metabolic dysfunction compared with women that were overweight, but maternal BMI did not impact these variables in the fetus. Fetal sex did not impact maternal and fetal metabolic parameters in women with BMI > 25kg/m2. However, a higher BMI caused increasingly deranged maternal blood lipid concentrations and markers of insulin resistance as pregnancy progressed. Lipid monitoring and interventions to reduce lipids during pregnancy therefore require further evaluation.

Maternal diets enriched in olive oil regulate lipid metabolism and levels of PPARs and their coactivators in the fetal liver in a rat model of gestational diabetes mellitus

In a rat model of gestational diabetes mellitus (GDM) programmed in the offspring of neonatal streptozotocin-induced (nSTZ) diabetic rats, lipids are accumulated in the fetal liver in a sex-dependent way. Here, we evaluated whether maternal diets enriched in olive oil in rats that will develop GDM ameliorate lipid metabolic impairments in the fetal livers. Pregnant offspring of control and nSTZ diabetic rats (F0) were fed a 6% olive oil-supplemented diet throughout the F1 gestation. We evaluated maternal metabolic parameters as well as lipid content, expression of lipid metabolizing enzymes and protein expression of PLIN2, PPARs and PPAR coactivators in the fetal livers. The offspring of nSTZ diabetic rats developed GDM regardless of the maternal treatment. Hypertriglyceridemia in GDM rats was prevented by the olive oil-enriched maternal treatment. In the livers of male fetuses of GDM rats, the maternal olive oil-supplemented diet prevented lipid overaccumulation and prevented the increase in PPARγ and PPARδ levels. In the livers of female fetuses of GDM rats, the maternal olive oil supplementation prevented the increase in PPARδ levels and the reduction in PGC1α levels, but did not prevent the reduced lipid content. Control and GDM rats showed a reduction of lipid metabolic enzymes in the fetal livers, which was associated with reduced levels of the PPAR coactivators PGC-1α and SRC-1 in males and of SRC-1 in females. These results suggest powerful effects of a maternal olive oil-supplemented diet in the fetal liver, possibly providing benefits in the fetuses and offspring from GDM rats.