Gestational hypertension and high-density lipoprotein function : an explorative study in overweight/obese women of the DALI cohort

Gestational hypertension (GHTN) is associated with an increased cardiovascular risk for mothers and their offspring later in life. High-density lipoproteins (HDL) are anti-atherogenic by promoting efflux of cholesterol from macrophages and suppression of endothelial cell activation. Functional impairment of HDL in GHTN-complicated pregnancies may affect long-term health of both mothers and offspring. We studied functional parameters of maternal and neonatal HDL in 192 obese women (pre-pregnancy BMI ≥ 29), who were at high risk for GHTN. Maternal blood samples were collected longitudinally at <20 weeks, at 24–28 and 35–37 weeks of gestation. Venous cord blood was collected immediately after birth. Maternal and cord blood were used to determine functional parameters of HDL, such as HDL cholesterol efflux capacity, activity of the vaso-protective HDL-associated enzyme paraoxonase-1, and levels of the HDL-associated anti-inflammatory apolipoprotein (apo)M. In addition, we determined serum anti-oxidative capacity. Thirteen percent of the women were diagnosed with GHTN. While we found no changes in measures of HDL function in mothers with GHTN, we observed impaired HDL cholesterol efflux capacity and paraoxonase-1 activity in cord blood, while serum antioxidant capacity was increased. Of particular interest, increased maternal paraoxonase-1 activity and apoM levels in early pregnancy were associated with the risk of developing GHTN. GHTN significantly impairs HDL cholesterol efflux capacity as well as HDL PON1 activity in cord blood and could affect vascular health in offspring. Maternal paraoxonase-1 activity and apoM levels in early pregnancy associate with the risk of developing GHTN

The Association of Physical Activity and Sedentary Behavior with Maternal and Cord Blood Anti-Oxidative Capacity and HDL Functionality: Findings of DALI Study

Obesity is one of the most common health issues in pregnancy with short and long-term consequences for both mother and her offspring. Promoting moderate to vigorous physical activity (MVPA) and decreasing sedentary time (ST) could have a positive impact on weight and obesity management, and therefore adiposity-induced oxidative stress, inflammation, and atherogenesis. However, the effects of MVPA and ST on anti-oxidative and anti-atherogenic markers in pregnancy have not been studied to date. This study aimed to assess the association of longitudinally and objectively measured MVPA and ST in 122 overweight/obese women (BMI ≥ 29 kg/m2) with maternal and cord blood markers of oxidative stress measured by advanced oxidation protein products (AOPP), anti-oxidative capacity, as well as high-density lipoproteins (HDL) related paraoxonase-1 (PON-1) activity and cholesterol efflux. Linear regression models showed no associations of MVPA and ST with outcomes in maternal blood. In contrast, MVPA at <20 weeks and 24–28 weeks of gestation were positively associated with anti-oxidative capacity, as well as PON-1 activity of HDL in cord blood. MVPA at 35–37 weeks correlated with higher AOPP, as well as higher anti-oxidative capacity. ST <20 weeks was also positively associated with inhibition of oxidation in cord blood. We speculate that increasing MVPA of overweight/obese women during pregnancy attenuates the oxidative stress state in the new-born

Intima-Media Thickness Measurements in the Fetus and Mother During Pregnancy: A Feasibility Study.

Fetal intima-media thickness (IMT) has been suggested as a marker of pre-clinical atherosclerosis, and maternal IMT could be altered through dynamic circumstances related to pregnancy. We investigated the feasibility of measurement of IMT at four pre-defined fetal and four pre-defined maternal arterial locations to determine vascular changes that could be associated with impaired vascular function. IMT was measured from the first to third trimester (12-34 wk), in 38 low-risk pregnancies. We imaged a 10-mm region of interest using a Mindray (Shenzhen, China) high-resolution ultrasound machine with automated IMT measurement software. Fetal abdominal aorta IMT was measurable during the second trimester in 71% and during the third trimester in 100% of the case, and umbilical artery IMT was measurable in 50% and 82% of cases during the second and third trimesters, respectively. Fetal IMT measurements were not possible during the first trimester. It was not often feasible to measure the IMT of the fetal common carotid artery, fetal renal artery and maternal iliac artery (maximal 20% of cases). Maternal common carotid artery, abdominal aorta and uterine artery IMTs were measurable throughout pregnancy. There was a significant relation between gestational age and IMT in the umbilical artery (p = 0.03) and a significant relation between body mass index and IMT in the maternal common carotid artery (p = 0.01). IMT measurements are feasible in some maternal and fetal vessels of interest. Further studies are underway to obtain more insight into vascular development during normal and pathologic pregnancies

Gestational Hypertension and High-Density Lipoprotein Function: An Explorative Study in Overweight/Obese Women of the DALI Cohort

Gestational hypertension (GHTN) is associated with an increased cardiovascular risk for mothers and their offspring later in life. High-density lipoproteins (HDL) are anti-atherogenic by promoting efflux of cholesterol from macrophages and suppression of endothelial cell activation. Functional impairment of HDL in GHTN-complicated pregnancies may affect long-term health of both mothers and offspring. We studied functional parameters of maternal and neonatal HDL in 192 obese women (pre-pregnancy BMI ≥ 29), who were at high risk for GHTN. Maternal blood samples were collected longitudinally at <20 weeks, at 24–28 and 35–37 weeks of gestation. Venous cord blood was collected immediately after birth. Maternal and cord blood were used to determine functional parameters of HDL, such as HDL cholesterol efflux capacity, activity of the vaso-protective HDL-associated enzyme paraoxonase-1, and levels of the HDL-associated anti-inflammatory apolipoprotein (apo)M. In addition, we determined serum anti-oxidative capacity. Thirteen percent of the women were diagnosed with GHTN. While we found no changes in measures of HDL function in mothers with GHTN, we observed impaired HDL cholesterol efflux capacity and paraoxonase-1 activity in cord blood, while serum antioxidant capacity was increased. Of particular interest, increased maternal paraoxonase-1 activity and apoM levels in early pregnancy were associated with the risk of developing GHTN. GHTN significantly impairs HDL cholesterol efflux capacity as well as HDL PON1 activity in cord blood and could affect vascular health in offspring. Maternal paraoxonase-1 activity and apoM levels in early pregnancy associate with the risk of developing GHTN

The role of early pregnancy maternal pGCD59 levels in predicting neonatal hypoglycaemia- sub-analysis of the DALI study

The aim of this study was to assess the association between early pregnancy maternal levels of plasma glycated CD59 (pGCD59) and neonatal hypoglycaemia (NH)

Obesity Affects Maternal and Neonatal HDL Metabolism and Function

Pregravid obesity is one of the major risk factors for pregnancy complications such as gestational diabetes mellitus (GDM) and an increased risk of cardiovascular events in children of affected mothers. However, the biological mechanisms that underpin these adverse outcomes are not well understood. High-density lipoproteins (HDLs) are antiatherogenic by promoting the efflux of cholesterol from macrophages and by suppression of inflammation. Functional impairment of HDLs in obese and GDM-complicated pregnancies may have long-term effects on maternal and offspring health. In the present study, we assessed metrics of HDL function in sera of pregnant women with overweight/obesity of the DALI lifestyle trial (prepregnancy BMI ≥ 29 kg/m2) and women with normal weight (prepregnancy BMI 2), as well as HDL functionalities in cord blood at delivery. We observed that pregravid obesity was associated with impaired serum antioxidative capacity and lecithin–cholesterol acyltransferase activity in both mothers and offspring, whereas maternal HDL cholesterol efflux capacity was increased. Interestingly, functionalities of maternal and fetal HDL correlated robustly. GDM did not significantly further alter the parameters of HDL function and metabolism in women with obesity, so obesity itself appears to have a major impact on HDL functionality in mothers and their offspring

The Temporal Profile of Circulating miRNAs during Gestation in Overweight and Obese Women with or without Gestational Diabetes Mellitus

Circulating non-coding microRNAs (miRNAs) are important for placentation, but their expression profiles across gestation in pregnancies, which are complicated by gestational diabetes mellitus (GDM), have not been fully established. Investigating a single time point is insufficient, as pregnancy is dynamic, involving several processes, including placenta development, trophoblast proliferation and differentiation and oxygen sensing. Thus, the aim of this study was to compare the temporal expression of serum miRNAs in pregnant women with and without GDM. This is a nested case-control study of longitudinal data obtained from a multicentric European study (the 'DALI' study). All women (n = 82) were overweight/obese (BMI &gt;= 29 kg/m(2)) and were normal glucose tolerant (NGT) at baseline (before 20 weeks of gestation). We selected women (n = 41) who were diagnosed with GDM at 24-28 weeks, according to the IADPSG/WHO2013 criteria. They were matched with 41 women who remained NGT in their pregnancy. miRNA (miR-16-5p, -29a-3p, -103-3p, -134-5p, -122-5p, -223-3p, -330-3p and miR-433-3p) were selected based on their suggested importance for placentation, and measurements were performed at baseline and at 24-28 and 35-37 weeks of gestation. Women with GDM presented with overall miRNA levels above those observed for women remaining NGT. In both groups, levels of miR-29a-3p and miR-134-5p increased consistently with progressing gestation. The change over time only differed for miR-29a-3p when comparing women with GDM with those remaining NGT (p = 0.044). Our findings indicate that among overweight/obese women who later develop GDM, miRNA levels are already elevated early in pregnancy and remain above those of women who remain NGT during their pregnancy. Maternal circulating miRNAs may provide further insight into placentation and the cross talk between the maternal and fetal compartments

Physical Activity and Sedentary Time in Pregnancy: An Exploratory Study on Oxidative Stress Markers in the Placenta of Women with Obesity

Regular moderate-to-vigorous physical activity (MVPA) and reduced sedentary time (ST) improve maternal glucose metabolism in pregnancy. More MVPA and less ST outside pregnancy increase antioxidant capacity, hence, are beneficial in preventing oxidative stress. The placenta is the first line of defense for the fetus from an adverse maternal environment, including oxidative stress. However, effects of MVPA and ST on oxidative stress markers in the placenta are unknown. The purpose of this study was to assess the association of MVPA and ST in pregnancy with oxidative stress markers in placentas of overweight/obese women (BMI &gt;= 29 kg/m(2)). MVPA and ST were objectively measured with accelerometers at &lt;20 weeks, 24-27 and 35-37 weeks of gestation. Using linear Bayesian multilevel models, the associations of MVPA and ST (mean and changes) with mRNA expression of a panel of 11 oxidative stress related markers were assessed in 96 women. MVPA was negatively correlated with HSP70 mRNA expression in a sex-independent manner and with GCLM expression only in placentas of female fetuses. ST was positively associated with HO-1 mRNA expression in placentas of male neonates. None of the other markers were associated with MVPA or ST. We speculate that increasing MVPA and reducing ST attenuates the oxidative stress state in placentas of obese pregnant women

Physical activity and sedentary time across pregnancy and associations with neonatal weight, adiposity and cord blood parameters : a secondary analysis of the DALI study

Background/Objectives Obesity during pregnancy is associated with neonatal adiposity, which is a risk factor for childhood obesity. Maternal physical activity (PA) and sedentary behaviours during pregnancy might modify this risk. We therefore studied associations between maternal PA and sedentary time (ST) during pregnancy and neonatal anthropometry and cord blood parameters and investigated whether associations differed by offspring sex.Subjects/Methods Participants of the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention (DALI) study with a BMI & GE; 29 kg/m(2) were analysed as a cohort. Maternal moderate-to-vigorous PA (MVPA) and ST were measured repeatedly with accelerometers across pregnancy. Associations between mean levels and changes in MVPA and ST and birthweight, neonatal adiposity (fat mass (FM)%) and cord blood parameters, including C-peptide, leptin and lipids, were analysed in 213 mother-child pairs with Bayesian multilevel models. Interactions with offspring sex were considered.Results Almost all women decreased MVPA levels and increased ST throughout gestation. Both higher maternal mean MVPA and increasing MVPA were associated with lower offspring FM% in males (-0.520%; 95% CI: -1.011%, -0.031% and -4.649%; -7.876%, -1.432% respectively). In female offspring, mean ST was associated with lower cord blood C-peptide (-0.145 & mu;g/l; -0.279 & mu;g/l, -0.005 & mu;g/l). No associations were found with birthweight or other cord blood parameters.Conclusions Maternal MVPA is associated with neonatal fat mass, but not birthweight, in male offspring. Our findings underline the importance of physical activity throughout pregnanc