Perinatal and childhood periods are sensitive windows of development wherein adversity exposure can result in disadvantageous outcomes. Data-driven dimensional approaches that appreciate the co-occurrence of adversities allow for extending beyond specificity (individual adversities) and cumulative risk (non-specific summation of adversities) approaches to understand how the type and timing of adversities affect outcomes.

With evolving recommendations on what should be important in adversity research, we sought to establish a data-driven framework that accounts for both type and timing of adversity by (1) replicating dimensions of childhood adversities, (2) determining whether perinatal adversities form unique dimensions and (3) identifying whether adversities during the perinatal and childhood periods overlap or remain distinct.

Using 6815 9-10-year-olds from the baseline Adolescent Brain Cognitive Development (ABCD) study, mixed graphical models were fit independently to childhood adversities and perinatal adversities, and simultaneously to perinatal and childhood adversities, to model relationships among adversities.

Data-driven clustering approaches estimated dimensions of adversity within networks. Six dimensions of childhood adversities and five dimensions of perinatal adversities were observed. When considered simultaneously, dimensions of perinatal and childhood adversities both merged (e.g., parental circumstances during perinatal and socioeconomic status during childhood) and stayed independent (e.g., obstetric complications during perinatal and neglect during childhood) underscoring the importance of considering both type and timing when studying early life adversity.

These results highlight that it may be appropriate to study certain adversity dimensions independently, whereas for others considering the impact of timing and potential continuity in exposure is critical. Recommendations for adversity research are discussed.

The coexistence of gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) amplifies the risk of maternal and perinatal mortality and complications, leading to more severe adverse pregnancy outcomes. This systematic review and meta-analysis aimed to assess the double burden of GDM and PIH (GDM/PIH) among pregnant women in Ethiopia.

A comprehensive systematic search was conducted in the databases of PubMed, Cochrane Library, Science Direct, Embase, and Google Scholar, covering studies published up to May 14, 2023. The analysis was carried out using JBI SUMARI and STATA version 17. Subgroup analyses were computed to demonstrate heterogeneity. A sensitivity analysis was performed to examine the impact of a single study on the overall estimate. Publication bias was assessed through inspection of the funnel plot and statistically using Egger's regression test.

Of 168 retrieved studies, 15 with a total of 6391 participants were deemed eligible. The pooled prevalence of GDM/PIH co-occurrence among pregnant women in Ethiopia was 3.76% (95% CI; 3.29-4.24). No publication bias was reported, and sensitivity analysis suggested that excluded studies did not significantly alter the pooled prevalence of GDM/PIH co-occurrence. A statistically significant association between GDM and PIH was observed, with pregnant women with GDM being three times more likely to develop PIH compared to those without GDM (OR = 3.44; 95% CI; 2.15-5.53).

This systematic review and meta-analysis revealed a high dual burden of GDM and PIH among pregnant women in Ethiopia, with a significant association between the two morbidities. These findings emphasize the critical need for comprehensive antenatal care programs in Ethiopia to adequately address and monitor both GDM and PIH for improved maternal and perinatal health outcomes.

Pre-eclampsia (PE) is one of the leading causes of maternal and perinatal health morbidity, producing more than 4.6% of complications in pregnancy worldwide. This systematic review was conducted to determine the significance of specific biomarkers in predicting PE in gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM). The review measured and explained the significant abnormalities in lipids, blood glucose, cytokines, inflammatory markers, placental proteins, urinary proteins, and other serum biomarkers that contribute to the development of PE in GDM and type 2 DM populations. We searched CINAHL, EMBASE, Medline, Maternity and Infant care, Scopus, and Web of Science. Studies were included if they had a measurable component in the blood serum or urine of women who developed PE and suffered from GDM or pre-existing type 2 DM. A narrative synthesis was conducted instead of a meta-analysis due to the high heterogeneity of data from the studies. A total of 2,593 studies were screened, producing eight relevant studies. Twenty-seven different biomarkers were investigated from the study group of 40 to 1,344 participants. No single biomarker was identified; however, there is a need for further research on specific biomarkers of PE, especially in CRP, FABP4, and microalbuminuria in the GDM-PE group and calprotectin in the type 2 DM population. Many biomarkers were identified as practical in predicting PE when combined with other biomarkers and more data are required to verify the predictability of the diagnostic markers in pregnant women.

Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM.

Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA).

A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers.

Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.

Women with gestational diabetes (GDM) have an increased risk of preeclampsia and postpartum diabetes. Inflammation associates with both GDM and preeclampsia. This study examined specialized proresolving mediators (SPM) that direct inflammation resolution and eicosanoids that are involved in inflammation, in relation to the development of preeclampsia and ongoing postpartum glucose intolerance in GDM.

Participants were selected from a prospective study examining the development of preeclampsia in women with GDM. Four groups of age-matched women were studied: GDM ( n  = 20), GDM who developed preeclampsia (GDM+PE, n  = 21), GDM who remained glucose-intolerant postpartum (GDM+PPIGT, n  = 20), or pregnancies with glucose tolerance within the normal range (NGT, n  = 21). Measurement of SPM (E-series resolvins and D-series resolvins), SPM pathway intermediates (14-HDHA, 18-HEPE and 17-HDHA), 20-hydroxyeicosatetraenoic acid (20-HETE), and the urinary metabolite of the vasodilator prostacyclin 2,3-dinor-6-Keto-PGF 1α , were made at 28, 32 and 36 weeks gestation and at 6 months postpartum.

Compared with GDM, GDM+PE had elevated levels of 20-HETE and the SPM pathway intermediates 14-HDHA, 18-HEPE, 17-HDHA, at 32 weeks, and the SPM RvE1 at 32 and 36 weeks gestation. Compared with NGT and regardless of whether they developed preeclampsia or PPIGT, GDM had lower levels of 2,3-dinor-6-Keto-PGF 1α during pregnancy.

Reduced levels of the prostacyclin metabolite 2,3-dinor-6-Keto-PGF 1α may contribute to the increased risk of preeclampsia in women with GDM. The increase in 20-HETE, a vasoconstrictor and mediator of inflammation, and SPM that contribute to inflammation resolution, prior to the onset of preeclampsia require further investigation to clarify their clinical significance.

Pregestational type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and gestational diabetes mellitus (GDM) are associated with increased rates of adverse maternal and neonatal outcomes. Adverse outcomes are more common in women with pregestational diabetes compared to GDM; although, conflicting results have been reported. This systematic review aims to summarise and synthesise studies that have compared adverse pregnancy outcomes in pregnancies complicated by pregestational diabetes and GDM. Three databases, Pubmed, EBSCOhost and Scopus were searched to identify studies that compared adverse outcomes in pregnancies complicated by pregestational T1DM and T2DM, and GDM. A total of 20 studies met the inclusion criteria and are included in this systematic review. Thirteen pregnancy outcomes including caesarean section, preterm birth, congenital anomalies, pre-eclampsia, neonatal hypoglycaemia, macrosomia, neonatal intensive care unit admission, stillbirth, Apgar score, large for gestational age, induction of labour, respiratory distress syndrome and miscarriages were compared. Findings from this review confirm that pregestational diabetes is associated with more frequent pregnancy complications than GDM. Taken together, this review highlights the risks posed by all types of maternal diabetes and the need to improve care and educate women on the importance of maintaining optimal glycaemic control to mitigate these risks.

Women with gestational diabetes mellitus (GDM) and/or hypertensive disorders of pregnancy (HDP) are at increased long-term cardiovascular risk. Mild cardiac functional alterations have been detected in women with GDM or HDP in midgestation, prior to clinical onset of the disease, but these functional alterations have not been found to be useful as screening tools. In contrast, increased impedance to peripheral blood flow, measured by echocardiography or ophthalmic artery Doppler, has been shown to provide incremental value to maternal characteristics for the prediction of pre-eclampsia. However, it is unknown whether similar changes can be detected in women at risk of GDM. In this study, we performed detailed cardiovascular phenotyping in a large, unselected population of women in midgestation to identify similarities and differences in cardiovascular adaptation in women who are at risk of GDM and/or HDP.

This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included assessment of flow velocity waveforms from the maternal ophthalmic arteries, echocardiography for assessment of maternal cardiovascular function and measurement of uterine artery pulsatility index and serum placental growth factor (PlGF) for assessment of placental perfusion and function. The measured indices were converted to either multiples of the median (MoM) values or deviation from the median (delta) after adjusting for maternal characteristics and elements of medical history. Biomarker delta or MoM values in the GDM and HDP groups were compared with those in the unaffected group using 95% CI and t-tests.

The study population of 5214 pregnancies contained 4429 (84.9%) that were unaffected by GDM or HDP, 509 (9.8%) complicated by GDM without HDP, 41 (0.8%) with GDM and HDP, and 235 (4.5%) with HDP without GDM. In HDP cases, with or without GDM, there was evidence of impaired placentation, with a decrease in PlGF, and increased impedance to flow in the peripheral circulation, suggested by an increase in ophthalmic artery peak systolic velocity (PSV) ratio, peripheral vascular resistance assessed on echocardiography and mean arterial pressure. In the GDM group without HDP, there was no evidence of altered placental perfusion or function and ophthalmic artery PSV ratio was not significantly different from that in the unaffected group; peripheral vascular resistance and mean arterial pressure were increased but to a lesser degree than in the HDP group. In the HDP group, there was an increase in global longitudinal systolic strain and slight increase in isovolumic relaxation time, while in the GDM group, there was an increase in mitral valve E/e', myocardial performance index and global longitudinal systolic strain.

In midgestation, women who subsequently develop HDP or GDM have a mild subclinical reduction in left ventricular function. In HDP cases, with or without GDM, there is evidence of impaired placentation and all biomarkers of impedance to peripheral blood flow are consistently increased. In contrast, in the GDM group without HDP, biomarkers of placental function are normal and those of impedance to peripheral blood flow are either marginally increased or not significantly different from those in normal pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common pregnancy complications with similar risk factors and pathophysiological changes. Evidence from previous studies suggests that the incidence of PE is significantly increased in women with GDM, but whether GDM is independently related to the occurrence of PE has remained controversial. GDM complicated by PE further increases perinatal adverse events with greater impact on the future maternal and offspring health. Identify factors associated with PE in women with GDM women, specifically those that are controllable, is important for improving pregnancy outcomes. This paper provides the findings of a review on the correlation between GDM and PE, factors associated with PE in women with GDM, possible mechanisms, and predictive markers. Most studies concluded that GDM is independently associated with PE in singleton pregnancy, and optimizing the treatment and management of GDM can reduce the incidence of PE, which is very helpful to improve pregnancy outcomes.

Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

Pre-eclampsia (PE) is a serious disease of pregnancy and one of the major causes of morbidity and mortality for both the mother and baby. This systematic review aims to detect the role of high-sensitivity C-reactive protein (CRP) in the detection of PE.

Thirty-four articles published between 2001 and 2019 were included in this review. The articles were extracted from OVID Medline and Embase. The study designs of these articles are randomized controlled, cohort, case-control, and cross-sectional studies evaluating CRP as a marker to predict or early diagnose PE. The quality assessment of these articles is made by the modified Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-analysis was not done because of clinical and statistical heterogeneity.

A positive association between CRP levels and the development of PE was confirmed in 18 studies. This positive effect was addressed in patients with normal BMI (<25 kg/m2) in 3 studies and in overweight patients in 2 studies. One study addressed this positive association in patients with a BMI ranging between 28 and 31 kg/m2. Three studies determined a cutoff level of CRP above which a significant risk of PE development should be suspected. These levels ranged between 7 and 15 mg/L.

CRP is a promising cost-effective biomarker that may be used in the prediction of PE. A CRP level higher than 15 mg/L may suggest initiation of low-dose aspirin in low-risk pregnancies.

Preeclampsia is a severe pregnancy complication with high potential for adverse effects on maternal and fetal health during the perinatal period. It is also associated with an increased risk of maternal cardiovascular disease later in life. Development of preeclampsia can be decreased by prescribing low-dose aspirin to high-risk women. At present, maternal and pregnancy factors are used to assess the risk of preeclampsia. One additional factor that could add to the assessment of risk is a family history of hypertension, cardiovascular disease, or diabetes, especially for nulliparous women who do not have a pregnancy history to inform treatment decisions. Therefore, we conducted a systematic review to assess the association between family history of the aforementioned conditions and preeclampsia. Four databases including MEDLINE, EMBASE, the Cochrane Library, and CINAHL/pre-CINAHL were searched for observational studies that examined a family history of hypertension, cardiovascular disease, or diabetes in women with preeclampsia and in a control population. Studies were evaluated for quality using the Newcastle-Ottawa Scale. A total of 84 relevant studies were identified. A meta-analysis was not conducted due to suspected heterogeneity in the included studies. Most studies reported a positive association between a family history of hypertension or cardiovascular disease and the development of preeclampsia. The majority of studies examining family history of diabetes reported non-significant associations. Overall, family history of hypertension or cardiovascular disease is associated with a higher risk for developing preeclampsia and should be considered when assessing women in the first trimester for low-dose aspirin.

To examine the relative association between fasting plasma glucose vs post-load (1-h and 2-h) glucose levels based on the oral glucose tolerance test in pregnancy and large-for-gestational-age and hypertensive disorders of pregnancy outcomes.

All live singleton births between October 2008 and December 2014 in Alberta, Canada were included. Gestational diabetes mellitus was diagnosed using Diabetes Canada criteria. Logistic regression models were used to examine the association between fasting plasma glucose vs post-load values and large-for-gestational-age infants and hypertensive disorders of pregnancy after adjusting for maternal characteristics and pharmaceutical intervention in gestational diabetes pregnancies.

Among 257 547 pregnancies, 208 344 (80.9%) had negative 50-g glucose challenge tests, 36 261 (14.1%) had negative 75-g oral glucose tolerance tests, and 12 942 (5.0%) had gestational diabetes based on either elevated fasting plasma glucose (n=4130, 1.6%) or elevated 1-h and/or 2-h oral glucose tolerance test values (n=8812, 3.4%). Large-for-gestational-age and hypertensive disorders of pregnancy rates were 8.1% and 5.1% in negative glucose challenge test pregnancies, 11.0% and 7.0% in negative oral glucose tolerance test pregnancies, 22.4% and 11.9% in gestational diabetes pregnancies with elevated fasting plasma glucose, and 9.1% and 8% in gestational diabetes pregnancies with elevated post-load levels, respectively. Among gestational diabetes pregnancies, those with elevated fasting plasma glucose were at higher risk of large-for-gestational age (adjusted odds ratio 2.66, 95% CI 2.39-2.96) and hypertensive disorders of pregnancy (adjusted odds ratio 1.51, 95% CI 1.33-1.72) outcomes relative to pregnancies with post-load glucose elevations only. Fasting plasma glucose remained significantly associated with adverse outcomes in gestational diabetes pregnancies with and without pharmacological intervention.

Elevated fasting plasma glucose in women with gestational diabetes is a stronger predictor of large-for-gestational-age and hypertensive disorders of pregnancy outcomes than elevated post-load glucose.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder occurring in pregnancy. GDM plays an important role in the current diabetes epidemic: exposure to a high glycemic environment during the early stages of development increases the risk of the fetus to develop type two diabetes mellitus (T2DM) in adult life. Various cardiometabolic risk factors are linked to GDM. A thorough knowledge of the risk factors and genes involved in the development of GDM, along with an understanding of the underlying pathophysiological mechanisms are crucial to properly identify patients at risk of developing this condition. There is growing evidence showing that myo-inositol, combined with an appropriate therapeutic regimen for GDM, can provide additional benefits to the patient. The aim of this review is to analyze the role of inositol isomers - especially myo-inositol (MYO-INS) - in the treatment of patients with GDM.

This study was aimed at evaluating effect of Gestational diabetes mellitus (GDM) and maternal characteristics on pregnancy outcome. GDM has several risk factors including; advanced maternal age, ethnic background, obesity and family history of diabetes mellitus. These pregnancy complications are associated with fetal morbidity and mortality and may lead to macrosomia and shoulder dystocia. Others are stillbirth, miscarriages, preterm and small for gestational age babies.

This was a retrospective case-case control study which compared maternal characteristics and pregnancy outcome among pregnant women with and without GDM. Diagnosis of GDM was done in accordance with the American Diabetes Association (ADA) criteria. Weight and height were determined and Body mass index (BMI) calculated. Pregnancy outcome was determined at the end of pregnancy and information on maternal characteristics obtained using questionnaire and patient folders.

Those who developed GDM were significantly older (OR= 1.772; 95% CI =1.432-2.192; P<0.0001) and had higher BMI (OR=1.637; 95% CI=1.004-1.289; P=0.044) than those who did not. A significant number of those who developed GDM also had stillbirths OR= 5.188; 95% CI=1.093-24.613; p=0.038) and cesarean deliveries (OR=14.362; 95% CI=3.661-56.335; p= 0.001).

Women who develop GDM are more likely to deliver stillborn or macrosmic babies and may require surgical intervention in order to have normal deliveries.

Gestational diabetes mellitus (GDM) is associated to an increased risk of pregnancy-induced hypertension (PIH). Ambulatory blood pressure monitoring (ABPM) has been used to detect PIH and preeclampsia, but few data are currently available on its use in women with GDM. The aim of this study was to achieve early identification in women with GDM of BP profiles (detected by ABPM) that could define a population at greater risk of developing PIH and preeclampsia.

A prospective study of 93 normotensive women with GDM in whom 24-h ABPM was performed (using a Spacelabs 90207 monitor) at 28-32 weeks of pregnancy. Clinical and laboratory variable and obstetric and perinatal outcomes were analyzed.

Mean age was 34.8±4.39years, and 5.4% of patients developed PIH. Higher levels of HbA1c (P=.005) and microalbumin (P=.001) were seen in patients with PIH. Patients with non-dipper patterns (50.5%) had higher values of night-time systolic BP (106.7 vs 98.4mmHg) and night-time diastolic BP (64.8 vs 57.2mmHg) (P<.001). Lower birth weights (3,084.57 vs 3,323.7) (P=.021) and shorter gestational age at delivery (38.67 vs 39.27 weeks) (P=.04) were found in women with non-dipper pattern. High night-time systolic BP significantly increased the chance of developing PIH (OR: 1.18; 95%CI: 1.00-1.39; P=.043).

Patients with GDM have BP changes, with predominance of the non-dipper pattern and higher night-time systolic and diastolic BP, changes that could be useful predictors of PIH. High night-time systolic BP values increase the risk of developing PIH. Further studies are needed to ascertain the relationships between BP changes and obstetric and perinatal complications.

Gestational diabetes mellitus (GDM) is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy. This definition includes cases of undiagnosed type 2 diabetes mellitus (T2DM) identified early in pregnancy and true GDM which develops later. GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2DM to the mother and foetus later in life. In addition, GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities, hypertensive disorders and hyperinsulinemia. These might result in later development of cardiovascular disease and metabolic syndrome. The understanding of the different risk factors, the pathophysiological mechanisms and the genetic factors of GDM, will help us to identify the women at risk, to develop effective preventive measures and to provide adequate management of the disease. Clinical trials have shown that T2DM can be prevented in women with prior GDM, by intensive lifestyle modification and by using pioglitazone and metformin. However, a matter of controversy surrounding both screening and management of GDM continues to emerge, despite several recent well-designed clinical trials tackling these issues. The aim of this manuscript is to critically review GDM in a detailed and comprehensive manner, in order to provide a scientific analysis and updated write-up of different related aspects.

Gestational diabetes mellitus (GDM) is a risk factor for the development of endothelial dysfunction and cardiovascular disease. However, in vivo microvascular endothelial function in GDM has not been investigated. This study aimed to examine, using near-infrared spectroscopy (NIRS), whether: (1) there are differences in microvascular reactivity and skeletal muscle oxygen consumption (m[Formula: see text]) at rest and during exercise between GDM and uncomplicated pregnancies; and (2) there is an association of NIRS indices with macrovascular function and cardiovascular disease risk factors.

Twenty-nine pregnant women (13 with GDM and 16 women with uncomplicated pregnancy, 28 ± 2 gestational weeks) underwent arterial stiffness (pulse wave velocity [PWV]) and 24 h ambulatory BP (24 h BP) evaluation. NIRS continuously monitored, non-invasively, changes in muscle oxygenated and deoxygenated haemoglobin and tissue O₂ saturation index (TSI, %) during arterial occlusion/reperfusion and intermittent handgrip exercise. m[Formula: see text] and vascular reactivity indices were calculated.

During occlusion and reperfusion, women with GDM exhibited slower TSI response (occlusion slope: -0.06 ± 0.02 vs -0.10 ± 0.04, in GDM and controls, respectively; reperfusion slope: 0.65 ± 0.26 vs 1.05 ± 0.41, respectively), lower m[Formula: see text] (1.3 ± 1.2 vs 3.8 ± 2.3 μmol l^-1 min^-1) and blunted hyperaemia (ΔTSI 6.8 ± 2.9 vs 9.5 ± 3.4) compared with controls (p < 0.01). Despite similar handgrip strength in the GDM and control groups (29.1 ± 8.1 vs 26.2 ± 10.4 kg, respectively), during repeated forearm contractions, women with GDM presented a blunted TSI response (6.5 ± 3.9 vs 19.2 ± 10.9; p < 0.01) and a reduced capacity to maintain the predetermined handgrip (23.4 ± 2.9 vs 27.4 ± 3.8%, p < 0.05). NIRS indices correlated with PWV, 24 h BP and blood glucose concentration earlier in pregnancy (r = 0.40-0.60; p < 0.05).

Women with GDM exhibited a characteristic blunted TSI curve, showing alterations in muscle oxygenation and microvascular responsiveness compared with women with uncomplicated pregnancies. These alterations were manifested during exercise and possibly contribute to the reduced exercise tolerance in GDM. NIRS indices correlated with macrovascular indices (arterial stiffness) and 24 h BP.

Diabetes in rat pregnancy is associated with impaired vasodilation of the maternal uteroplacental vasculature. In the present study, we explored the role of endothelial cell (EC) Ca(2+)-activated K(+) channels of small conductance (SKCa channels) and intermediate conductance (IKCa channels) in diabetes-induced uterine vascular dysfunction. Diabetes was induced by injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with citrate buffer. Changes in smooth muscle cell intracellular Ca(2+) concentration, membrane potential, and vasodilation induced by SKCa/IKCa channel activators were studied in uteroplacental arteries of control and diabetic rats. The impact of diabetes on SKCa- and IKCa-mediated currents was explored in freshly dissociated ECs. NS309 evoked a potent vasodilation that was effectively inhibited by TRAM-34 but not by apamin. NS309-induced smooth muscle cell intracellular Ca(2+) concentration, membrane potential, and dilator responses were significantly diminished by diabetes; N-cyclohexyl-N-2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine (CyPPA)-evoked responses were not affected. Ca(2+)-activated ion currents in ECs were insensitive to paxilline, markedly inhibited by charybdotoxin (ChTX), and diminished by apamin. NS309-induced EC currents were generated mostly due to activation of ChTX-sensitive channels. Maternal diabetes resulted in a significant reduction in ChTX-sensitive currents with no effect on apamin-sensitive or CyPPA-induced currents. We concluded that IKCa channels play a prevalent role over SKCa channels in the generation of endothelial K(+) currents and vasodilation of uteroplacental arteries. Impaired function of IKCa channels importantly contributes to diabetes-induced uterine endothelial dysfunction. Therapeutic restoration of IKCa channel function may be a novel strategy for improvement of maternal uteroplacental blood flow in pregnancies complicated by diabetes.

Gestational diabetes mellitus (GDM), gingivitis, infection with specific periodontal pathogens and systemic inflammation each increase the risk for poor pregnancy outcome. We set out to monitor the interactions of gingivitis and GDM with respect to oral infection and the systemic inflammatory burden.

Four case-control groups (n = 117) were recruited, (1) No gingivitis, No GDM (n = 27); (2) Gingivitis, No GDM (n = 31); (3) No gingivitis, GDM (n = 21); and (4) Gingivitis, GDM (n = 38). Oral infection with three key periodontal pathogens was determined by PCR. Systemic inflammation was determined by quantification of CRP by EIA.

Gingivitis during pregnancy was associated with oral infection with Porphyromonas gingivalis, Filifactor alocis and Treponema denticola and combinations thereof (all p < 0.01). GDM was also associated with increased infection with individual and multiple oral pathogens (all p < 0.05). Gingivitis during pregnancy led to a 325% increase in systemic CRP (mean, 2495 versus 8116 ng/ml, p < 0.01).

Diabetes and gingivitis act in concert to increase risk biomarkers for poor pregnancy outcome.

We assessed the association of glycosylated fibronectin (GlyFn) with preeclampsia and its performance in a point-of-care (POC) test.

GlyFn, placental growth factor (PlGF), and soluble vascular endothelial growth factor receptor 1 (sFlt1) levels were determined in serum samples from 107 pregnant women. In all, 45 were normotensive and 62 were diagnosed with preeclampsia. The ability of GlyFn to assess preeclampsia status and relationships between GlyFn and maternal characteristics and pregnancy outcomes were analyzed.

GlyFn serum levels in the first trimester were significantly higher in women with preeclampsia (P < .01) and remained higher throughout pregnancy (P < .01). GlyFn, sFlt1, PlGF, and the sFlt1/PlGF ratio were significantly associated (P < .01) with preeclampsia status, and the classification performance of these analytes represented by area under the receiver operating characteristic curve was 0.99, 0.96, 0.94, and 0.98, respectively, with 95% confidence intervals of 0.98-1.00, 0.89-1.00, 0.86-1.00, and 0.94-1.00, respectively. Increased GlyFn levels were significantly associated with gestational age at delivery (P < .01), blood pressure (P = .04), and small-for-gestational-age neonates. Repeated-measures analysis of the difference in weekly GlyFn change in the third trimester demonstrated that mild preeclampsia was associated with a weekly change of 81.7 μg/mL (SE 94.1) vs 195.2 μg/mL (SE 88.2) for severe preeclampsia. The GlyFn POC demonstrated similar performance to a plate assay with an area under the receiver operating characteristic curve of 0.93 and 95% confidence interval of 0.85-1.00.

GlyFn is a robust biomarker for monitoring of preeclampsia in both a standard and POC format, which supports its utility in diverse settings.

Gestational diabetes mellitus is associated with adverse maternal and fetal outcomes during, as well as subsequent to, pregnancy, including increased risk of type 2 diabetes and cardiovascular disease. Because of the importance of early risk stratification in preventing these complications, improved first-trimester biomarker determination for diagnosing gestational diabetes would enhance our ability to optimise both maternal and fetal health. Metabolomic profiling, the systematic study of small molecule products of biochemical pathways, has shown promise in the identification of key metabolites associated with the pathogenesis of several metabolic diseases, including gestational diabetes. This article provides a systematic review of the current state of research on biomarkers and gestational diabetes and discusses the clinical relevance of metabolomics in the prediction, diagnosis and management of gestational diabetes.

We conducted a systematic search of MEDLINE (PubMed) up to the end of February 2014 using the key term combinations of 'metabolomics,' 'metabonomics,' 'nuclear magnetic spectroscopy,' 'mass spectrometry,' 'metabolic profiling' and 'amino acid profile' combined (AND) with 'gestational diabetes'. Additional articles were identified through searching the reference lists from included studies. Quality assessment of included articles was conducted through the use of QUADOMICS.

This systematic review included 17 articles. The biomarkers most consistently associated with gestational diabetes were asymmetric dimethylarginine and NEFAs. After QUADOMICS analysis, 13 of the 17 included studies were classified as 'high quality'.

Existing metabolomic studies of gestational diabetes present inconsistent findings regarding metabolite profile characteristics. Further studies are needed in larger, more racially/ethnically diverse populations.

Outcomes in pregnancies complicated by preexisting diabetes (type 1 and type 2) and gestational diabetes mellitus have improved, but there is still excess morbidity compared with normal pregnancy. Management strategies appropriately focus on maternal glycemia, which demonstrably improves pregnancy outcomes for mother and infant. However, we may be reaching the boundaries of obtainable glycemic control for many women. It has been acknowledged that maternal lipids are important in pregnancies complicated by diabetes. Elevated maternal lipids are associated with preeclampsia, preterm delivery, and large-for-gestational-age infants. Despite this understanding, assessment of management strategies targeting maternal lipids has been neglected to date. Consideration needs to be given to whether normalizing maternal lipids would further improve pregnancy outcomes. This review examines the dyslipidemia associated with pregnancy complicated by diabetes, reviews possible therapies, and considers whether it is time to start actively managing this aspect of maternal metabolism.

The purposes of this study were to explore whether the maternal-fetal outcomes differed among various types of hyperglycemia during pregnancy and whether the values of glycemic screening in the middle phase of pregnancy could predict maternal-fetal outcomes.

A retrospective study was conducted to study the incidence of maternal-fetal outcomes in 383 singleton pregnant women with diabetes or gestational diabetes admitted to our hospital from November 2007 to March 2013. Patients were divided into three groups: DM (Type 1 and Type 2 diabetes mellitus) group, mGDM (mild gestational diabetes mellitus) group and sGDM (severe gestational diabetes mellitus) group. Maternal basic characteristics, results of oral glucose tolerance test (OGTT), antenatal random glycemia and maternal-fetal outcomes were collected. Binary logistic regression was used to estimate the association of blood glucose with the maternal-fetal outcomes. Predictive accuracy was assessed by calculating the areas under the receiver operating characteristic curves.

The maternal basic characteristics, maternal complications and neonatal complications did not differ significantly between DM group and sGDM group, except neonatal intensive care units admission (NICU). Incidences of preterm, NICU and preeclampsia were significantly lower in the mGDM group than in the DM and sGDM groups (P < 0.05). After adjusted by confounding factors, the value of OGTT 0 h could predict pregnancy induced hypertension (PIH) (OR = 1.24, 95% CI [1.04 to 1.46], P = 0.015), preterm birth (OR = 1.23, 95% CI [1.03 to 1.47], P = 0.025) and stillbirth (OR = 1.55, 95% CI [1.14 to 2.10], P = 0.005); antenatal random glycemia could predict preterm birth (OR = 1.19, 95% CI [1.08 to 1.31], P < 0.001) and stillbirth (OR = 1.41, 95% CI [1.17 to 1.71], P < 0.001).

Pregnant women in the mGDM group have better outcomes than those in the DM and sGDM groups. The values of OGTT in the middle phase of pregnancy and antenatal random glycemia could predict PIH, preterm birth or stillbirth to some extent.

This study aims to determine whether high C-reactive protein (CRP) concentration during pregnancy is associated with later preeclampsia and whether weight status (BMI) is a potential modifier of the relation between CRP and preeclampsia.

Twenty-three studies were included in a systematic literature review and a subset of 18 in a meta-analysis. Weighted mean difference (WMD) [with their 95% confidence intervals (CI)] of CRP in preeclampsia and control groups was the estimator. A quality assessment was carried out using a scale specifically developed for this study. Meta-regression with estimates for study characteristics and inter-arm differences and sensitivity and subgroup analysis was employed. Statistical heterogeneity was investigated using I(2) statistic.

The pooled estimated CRP between 727 women, who developed preeclampsia and 3538 controls was 2.30 mg/l (95% CI: 1.27-3.34). The heterogeneity among studies was high (I(2) = 92.8). The WMD was found to be lower in studies comprising preeclampsia and control groups with similar BMI [WMD = 0.85 (95% CI: 0.10-1.61); I(2) = 25.3%] compared with studies among which BMI was significantly elevated in the preeclampsia group [2.01 (95% CI: 1.23-2.78); I(2) = 0.0%], which may explain the high heterogeneity of pooled data. Meta-regression results confirmed that difference in BMI between groups modifies the association of CRP and preeclampsia. High quality studies represented 30%.

The pooled WMD suggest that women with higher levels of CRP may have an increased risk of developing preeclampsia. This association seems to be modified by confounders, such as BMI. Further studies of high methodological quality are needed.

To evaluate whether abnormal endothelial function, a common finding in gestational diabetes mellitus (GDM) pregnancies, can be explained by inflammatory cytokines.

Forearm skin blood flow (FSBF), into response to acetylcholine (Ach) (endothelium-dependent vasodilatation), were measured in 24 pregnant control subjects and 28 gestational diabetes mellitus (GDM) women, in the third trimester of gestation. A fasting glycemic and lipidic panel was obtained, and inflammatory cytokines (TNF-α and IL-6) and adiponectin were also determined.

FSBF is significantly reduced in GDM group compared with control subjects (344.59 ± 57.791 vs.176.38 ± 108.52, P < 0.05). Among all subjects, FSBF showed a strong negative correlation with TNF-α and IL-6 (r = -0.426, P < 0.0001 and r = -0.564, P < 0.0001, respectively) and positive correlation with adiponectin (r = 0.468, P < 0.0001).

Endothelial function, an early marker of macrovascular disease, is present in non-obese pregnancies complicated by GDM. This alteration seems to be directly related to inflammatory status, which may represent a patho-physiological link between GDM and type 2 diabetes and, later on, metabolic syndrome.

Diabetes mellitus in pregnancy is associated with impaired endothelium-mediated dilatation of maternal arteries, although the underlying cellular mechanisms remain unknown. In this study, we hypothesized that diabetes during rat gestation attenuates agonist-induced uterine vasodilation through reduced endothelial cell (EC) Ca(2+) elevations and impaired smooth muscle cell (SMC) hyperpolarization and SMC intracellular Ca(2+) concentration ([Ca(2+)]i) responses. Diabetes was induced by an injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with a citrate buffer. Fura-2-based measurements of SMC [Ca(2+)]i or microelectrode recordings of SMC membrane potential were performed concurrently with dilator responses to ACh in uteroplacental arteries from control and diabetic pregnant rats. Basal levels of EC [Ca(2+)]i and ACh-induced EC [Ca(2+)]i elevations in pressurized vessels and small EC sheets were studied as well. Diabetes reduced ACh-induced vasodilation due to a markedly impaired EDHF-mediated response. Diminished vasodilation to ACh was associated with attenuated SMC hyperpolarization and [Ca(2+)]i responses. Basal levels of EC [Ca(2+)]i and ACh-induced EC [Ca(2+)]i elevations were significantly reduced by diabetes. In conclusion, these data demonstrate that reduced endothelium-mediated hyperpolarization contributes to attenuated uteroplacental vasodilation and SMC [Ca(2+)]i responses to ACh in diabetic pregnancy. Impaired endothelial Ca(2+) signaling is in part responsible for endothelial dysfunction in the uterine resistance vasculature of diabetic rats. Pharmacological improvement of EC Ca(2+) handling may provide an important strategy for the restoration of endothelial function and enhancement of maternal blood flow in human pregnancies complicated by diabetes.

To assess and compare alterations in the morphology and function of platelets occurring in gestational diabetes and healthy pregnancies.

A retrospective study was performed of 77 pregnant women: 42 cases with gestational diabetes and 35 healthy controls. The two groups were compared in terms of demographics and platelet parameters derived from complete blood counts.

The mean platelet volume (p=0.001) and HbA1c (p<0.001) were significantly increased in the patients with gestational diabetes. The mean platelet volume was well correlated with the platelet distribution width (rs=0.404, p<0.001) and the platelet count (rs=0.355, p=0.002).

The mean platelet volume and other platelet parameters may significantly aid the identification of diabetic pregnants at risk for vascular complications. The role and possible clinical relevance of these changes during diabetic pregnancy need to be investigated in further studies.

We examined associations of age at menarche and menstrual characteristics with the risk of preeclampsia among participants (n = 3,365) of a pregnancy cohort study. Data were collected using in-person interviews and medical record abstraction. Logistic regression was used to estimate adjusted odds ratio (OR) and 95% confidence interval (95% CI). There was a significant inverse association between age at menarche and risk of preeclampsia (P value for trend < 0.05). Association of long cycle length (>36 days) with higher risk of preeclampsia was present only among women who had prepregnancy body mass index <25 kg/m(2) (interaction P value = 0.04). Early menarche is associated with higher risk of preeclampsia. Prepregnancy weight may modify associations of long menstrual cycles with risk of preeclampsia.

Hypertensive pregnancy disorders complicate 10% of all pregnancies. In this article we discuss the spectrum of hypertensive conditions that may occur during pregnancy. Recent studies have consistently shown that hypertensive disorders in pregnancy implicate a two-fold higher risk for the development of hypertension and cardiovascular disease later in life. To optimise preventive management of cardiovascular disease in women with previous complicated pregnancies, we therefore recommend monitoring of hypertension and other cardiac risk factors at an early stage in life. Furthermore, the obstetric history should be routinely incorporated in cardiovascular risk assessment in women who seek medical attention for hypertension and/or cardiac symptoms. (Neth Heart J 2007;15:415-7.).

To estimate maternal outcome of treated or untreated gestational diabetes mellitus (GDM).

French and English publications were searched using PubMed and the Cochrane library.

The diagnosis of GDM includes a high risk population for preeclampsia and Caesarean sections (EL3). The risks are positively correlated with the level of hyperglycaemia in a linear way (EL2). Intensive treatment of mild GDM compared with routine care reduces the risk of pregnancy-induced hypertension (preeclampsia, gestational hypertension). Moreover, it does not increase the risk of operative vaginal delivery, Caesarean section and postpartum haemorrhage (EL1). Being overweight, obesity and maternal hyperglycaemia are independent risk factors for preeclampsia (EL2). Their association with GDM increases the risk of preeclampsia and Caesarean section compared to diabetic women with a normal body mass index (EL3). The association of several risk factors (such as advanced maternal age, pre-existing chronic hypertension, pre-existing nephropathy, obesity, suboptimal glycaemic control) increases the risk of preeclampsia. In that case, the classic follow-up (blood pressure measurement, proteinuria) should be more frequent than monthly (professional consensus). The risk of Caesarean section is increased by macrosomia, whether suspected prenatally or not, but this increased risk remains whatever the birth weight (EL3). Diagnosis and treatment of GDM do not reduce the risk of severe perineal lesions, operative vaginal delivery and postpartum haemorrhage (EL2). Some psychological symptoms, such as anxiety and alteration of self-perception, can occur upon diagnosis of GDM (EL3). The treatment of GDM appears to reduce the risk of postpartum depression symptoms (EL2).

Most of the information published on GDM covers the risks of preeclampsia and Caesarean section; intensive care of GDM reduces these risks. Pregnancy care should be adjusted to the risk factors.

The gestational period serves as a natural stress test that can be used to predict future cardiovascular health risks of female patients. Recent evidence confirms that mothers with hypertensive pregnancies have higher cardiovascular disease (CVD) risks compared to other women of similar age. In women with preeclampsia, those delivering before 37 weeks of gestation and mothers with recurring preeclampsia in subsequent pregnancies carry the greater risks. These sex-specific risks are of similar magnitude to traditional CVD risk factors, such as smoking and obesity. Unfortunately, none of the commonly used CVD risk stratification models make use of these sex-specific markers, which can powerfully predict future CVD outcomes. Because women have historically posed a greater diagnostic challenge than men in assessing CVD risks, better models for risk stratification in this sex group are needed. A history of hypertension in pregnancy should be included as a variable in cardiovascular risk stratification. In addition, screening women for a history of preeclampsia should become routine practice, with greater emphasis placed on therapies to modify adverse outcomes for these higher-risk women.

To examine the association between uric acid (UA) level during the first 20 weeks of pregnancy and the development of gestational diabetes mellitus (GDM) and preeclampsia in the second half of pregnancy.

The study population included registered births (n = 5507) between 2001 and 2007 in a tertiary medical center. The UA levels during the first 20 weeks of pregnancy were sorted by UA ≤ 2.4 mEq/L; UA = 2.5-4.0 mEq/L, UA = 4.1-5.5 mEq/L, and UA > 5.5 mEq/L. The linear-by-linear chi-square test and ROC curves were used to determine the association between UA level during the first 20 weeks and pregnancy complications. Multivariate analyses were performed to demonstrate whether UA level is an independent factor for the prevalence of preeclampsia and GDM.

Significant linear association was documented between UA level in the first 20 weeks and the prevalence of GDM and mild preeclampsia. The lowest and the highest prevalence of GDM were found in the UA ≤ 2.4 mEq/L group (6.3%) and in the UA > 5.5 mEq/L group (10.5%) (p < 0.001), respectively. Mild preeclampsia was diagnosed in 2.1% of the patients from the UA ≤ 2.4 mEq/L group, 3.3% from the UA = 2.5-4.0 mEq/L group, 5.3% from the UA = 4.1-5.5 mEq/L group, and 4.5% from the UA > 5.5 mEq/L group (p < 0.001). Three multiple logistic regression models controlling for maternal age showed that UA level is an independent risk factor for both GDM and mild preeclampsia.

UA levels in the highest quartile of the normal range during the first 20 weeks of pregnancy are associated with higher risk for the development of GDM and mild preeclampsia.

Hypertensive disorders in pregnancy can be chronic, pregestational or just diagnosed before the 20th week, or newly diagnosed in the second half of pregnancy. Any type of hypertension is more frequent in diabetic pregnancies with a different distribution among different types of diabetes. Most of the evidence is for pre-eclampsia associated with a marked increase in primary caesarean section, preterm birth and more need for neonatal intensive care. Different risk factors and pregnancy outcomes would support the hypothesis that pre-eclampsia and gestational hypertension might be largely separate entities, but this position is not unanimously accepted. Chronic hypertension increases with age and duration of diabetes, predicting increased rates of prematurity and neonatal morbidity, especially when associated with superimposed pre-eclampsia. Long-term consequences are observed in women whose pregnancy was complicated by hypertension such as chronic hypertension and cardiovascular diseases.

Preeclampsia is one of the leading causes of maternal and perinatal morbidity and mortality world-wide. The risk for developing preeclampsia varies depending on the underlying mechanism. Because the disorder is heterogeneous, the pathogenesis can differ in women with various risk factors. Understanding these mechanisms of disease responsible for preeclampsia as well as risk assessment is still a major challenge. The aim of this study was to determine the risk factors associated with preeclampsia, in healthy women in maternity hospitals of Karachi and Rawalpindi.

We conducted a hospital based matched case-control study to assess the factors associated with preeclampsia in Karachi and Rawalpindi, from January 2006 to December 2007. 131 hospital-reported cases of PE and 262 controls without history of preeclampsia were enrolled within 3 days of delivery. Cases and controls were matched on the hospital, day of delivery and parity. Potential risk factors for preeclampsia were ascertained during in-person postpartum interviews using a structured questionnaire and by medical record abstraction. Conditional logistic regression was used to estimate matched odds ratios (ORs) and 95% confidence intervals (95% CIs).

In multivariate analysis, women having a family history of hypertension (adjusted OR 2.06, 95% CI; 1.27-3.35), gestational diabetes (adjusted OR 6.57, 95% CI; 1.94 -22.25), pre-gestational diabetes (adjusted OR 7.36, 95% CI; 1.37-33.66) and mental stress during pregnancy (adjusted OR 1.32; 95% CI; 1.19-1.46, for each 5 unit increase in Perceived stress scale score) were at increased risk of preeclampsia. However, high body mass index, maternal age, urinary tract infection, use of condoms prior to index pregnancy and sociodemographic factors were not associated with higher risk of having preeclampsia.

Development of preeclampsia was associated with gestational diabetes, pregestational diabetes, family history of hypertension and mental stress during pregnancy. These factors can be used as a screening tool for preeclampsia prediction. Identification of the above mentioned predictors would enhance the ability to diagnose and monitor women likely to develop preeclampsia before the onset of disease for timely interventions and better maternal and fetal outcomes.

We sought to investigate whether uric acid concentrations are increased in pregnant women with insulin resistance and to correlate both with fetal growth.

Uric acid, glucose, and insulin were measured in plasma at 20.4 (+/-2.0) weeks' gestation in 263 women. The association between uric acid and insulin resistance, as estimated using the homeostasis model assessment (HOMA), was analyzed and related to birthweights.

In 212 (80.6%) women who remained normotensive throughout pregnancy, HOMA increased 1.23 U per 1-mg/dL increase in uric acid (95% confidence interval, 1.07-1.42; P=.003). Infants born to normotensive women in the upper quartile of uric acid and lowest HOMA quartile weighed 435.6 g less than infants of women with highest uric acid and HOMA quartiles (P<.005).

Increasing uric acid concentrations were associated with insulin resistance in midpregnancy. Hyperuricemia was associated with lower birthweight in normotensive women, and this effect was attenuated by insulin resistance.

This study assesses whether the adipokine adiponectin is a useful marker in pregnant women who subsequently develop preeclampsia (PE).

A retrospective case-control study was conducted to measure the total serum levels of adiponectin, measured by radioimmunoassay kit, in serum samples stored in serological biobanks.

Total serum adiponectin concentrations between the groups were not significantly different (p = 0.22). There were no obvious clinical signs of the preeclamptic inflammatory process at the time when samples were drawn.

Using this design, total adiponectin appeared not be a useful pre-clinical marker of PE.

Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, resolves on delivery of the placenta. Normal pregnancy is itself characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. This is exacerbated in preeclampsia with an associated breakdown of compensatory mechanisms, eventually leading to placental and vascular dysfunction. The underlying pathology of preeclampsia is thought to be a relatively hypoxic or ischemic placenta. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can interact to produce peroxynitrite a powerful prooxidant that covalently modifies proteins by nitration of tyrosine residues, to possibly alter vascular function in preeclampsia. The linkage between placental hypoxia and maternal vascular dysfunction has been proposed to be via placental syncytiotrophoblast basement membranes shed by the placenta or via angiogenic factors which include soluble flt1 and endoglin secreted by the placenta that bind vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in the maternal circulation. There is also abundant evidence of altered reactivity of the maternal and placental vasculature and of the altered production of autocoids in preeclampsia. The occurrence of preeclampsia is increased in women with preexisting vascular disease and confers a long-term risk for development of cardiovascular disease. The vascular stress test of pregnancy thus identifies those women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia. Preexisting maternal vascular dysfunction intensified by placental factors is possibly responsible for the individual pathologies of preeclampsia.

The purpose of this study was to compare pregnancy outcomes in women with diet-treated gestational diabetes mellitus (GDM) that was diagnosed at < 24 weeks of gestation to those women who received the diagnosis at > or = 24 weeks of gestation.

This was a retrospective cohort study of 2596 women with diet-treated GDM who delivered between December 1999 and June 2005 at Parkland Hospital. Women with risk factors for GDM underwent immediate glucose screening; women without risk factors underwent universal glucose screening between 24 and 28 weeks of gestation. Women with diet-treated GDM that was diagnosed at < 24 weeks of gestation (n = 339; 13.1%) were compared with those women who received the diagnosis at > or = 24 weeks of gestation.

Women with an earlier diagnosis of diet-treated GDM were at increased risk of preeclampsia and the delivery of large infants. Even after adjustment for differences in maternal characteristics and glycemic control, the risk of preeclampsia persisted (odds ratio, 2.4; 95% CI, 1.5, 3.8).

Women with an early diagnosis of diet-treated GDM have a 2-fold increased risk of preeclampsia.

To investigate the incidence and risk factors for pre-eclampsia in pregnant Chinese women with abnormal glucose metabolism.

A retrospective cohort study was performed on 1499 pregnant women with abnormal glucose metabolism at Peking University First Hospital from January 1995 to December 2004.

The overall prevalence of pre-eclampsia in women with abnormal glucose metabolism was 9.4% (141/1499). The prevalence of pre-eclampsia in women diagnosed with diabetes mellitus prior to pregnancy was higher than that of gestational diabetes mellitus and gestational impaired glucose tolerance patients (29.1% vs 8.7% and 7.8%, P<0.01). Pre-pregnancy body mass index was significantly higher in women with pre-eclampsia than in those without. A higher rate of pre-eclampsia was found in women with chronic hypertension and those with poor glucose control. The independent risk factors for pre-eclampsia were chronic hypertension and elevated pre-pregnancy body mass index.

The type of diabetes, chronic hypertension, and elevated pre-pregnancy body mass index are high risk factors for pre-eclampsia in pregnant women with abnormal glucose metabolism.

The complexity of the several pathogenic pathways that cause hypertension and vascular disease and the prolonged interval that appears to predate clinical morbidity have hindered inquiry into the association between GDM and vascular disorders. As a forme fruste of later type 2 diabetes, GDM-affected gravidas are identified as at risk of diabetes-related atherosclerosis, glomerular disruption, and pathogenic retinal angio-genesis. That GDM is evidence for underlying chronic conditions such as dysregulation of innate immune response that, independent of the diabetic state, produces vascular disease is difficult state, produces vascular disease is difficult to assert with the present published literature. Cross-sectional studies of patients with established gestational hypertension or preeclampsia are ambiguous as to the possible pathogenic effect of insulin resistance. Cohort studies initiated in early and mid-pregnancy show evidence that both gestational hypertension and preeclampsia may be more prevalent in gravidas with greater insulin resistance. The association of gestational glucose intolerance with gestational hypertension appears to be independent of obesity and ambient glycemia but explained in part by insulin resistance. Late pregnancy preeclampsia is associated with elevated mid-pregnancy BMI, blood pressure, fasting glucose and insulin, urate, and C-reactive protein, suggestive of metabolic and immune dysregulation. GDM appears to be associated with overexpressed innate immune response, which, in turn, is associated with vascular dysfunction and vascular disease. Among women with GDM, markers of insulin resistance do not appear to correlate with hypertension in short-term cohort studies. However, when non-GDM subjects are compared with subjects with GDM, postpregnancy studies do show an associated with vascular dysfunction and vascular disease. Among women with GDM, markers of insulin resistance do not appear to correlate with hypertension in short-term cohort studies. However, when non-GDM subjects are compared with subjects with GDM, postpregnancy studies do show an association of insulin resistance with both inflammatory dysregulation and vascular dysfunction. Cohort studies that have used population-based pregnancy databases consistently identify a clinically significant association of both gestational hypertension and preeclampsia with later hypertensive disorders. Associations with coronary artery disease or stroke are less consistent, requiring further investigation. Preventing the evolution of diabetes and lipid and immune dysregulation of the metabolic syndrome has become a silent public health issue because of the epidemic of childhood and early adulthood obesity and the opportunity at hand to treat insulin resistance by behavioral and pharmacological interventions. However, limited available literature highlights the need for long-term cohort studies of women with well-characterized metabolic and vascular profiles during pregnancy and decades later. Our present knowledge suggests that screening for GDM provides an opportunity of pregnancy outcome improvement. Limited studies of diabetes prevention in at-risk patient groups suggest that we may have the opportunity to reduce the risk of later diabetes. Additional investigation is required to determine if interventions that prevent or postpone diabetes also delay the onset of vascular disease.

The etiology of preeclampsia is unknown. It is controversial whether insulin resistance (IR) is present in preeclamptic patients, and it is unclear if hyperinsulinemia is dependent upon being overweight during pregnancy or on preeclampsia per se.

We performed a cross-sectional study in 140 pregnant patients and compared serum insulin concentrations. These women, 18-40 years old, were classified into four groups: 1) overweight patients with mild preeclampsia (n = 21), 2) overweight patients without preeclampsia (n = 23), 3) non-overweight patients with mild preeclampsia (n = 48), and 4) non-overweight patients without preeclampsia (n = 48). An oral glucose tolerance test (OGTT) was performed in all patients between 29 and 40 weeks of gestation. Blood samples were taken at 0, 60, 120 and 180 min after 100 g oral glucose to measure serum glucose and insulin levels.

Basal and postload OGTT glucose values and basal insulin levels were similar in all groups. However, insulin levels at 60, 120 and 180 min were significantly higher (p = 0.009, p = 0.009, p = 0.046, respectively) in overweight patients with preeclampsia than in those without. Insulin levels at 60 and 180 min were also higher (p = 0.024, p = 0.023, respectively) in non-overweight patients with preeclampsia than in those without. The area under the curve (AUC) for glucose was not significantly different between both groups of overweight patients or between non-overweight patients with or without preeclampsia. In contrast, the AUC of insulin was significantly higher in preeclamptic patients in both overweight (p = 0.004) and non-overweight (p = 0.024) groups than in overweight and non-overweight groups without preeclampsia, respectively.

Increased insulin levels observed in mild preeclamptic patients were independent of overweight-related hyperinsulinemia.

In previously apparently healthy women, glucose intolerance and high blood pressure during pregnancy are common and frequently occur together. This article reviews the role of these gestational disorders as markers of vascular dysfunction and its pathophysiology. Mechanisms include alterations to function of large arteries and resistance vessels and to capillary blood flow. Much of the vessel pathology is seen in both gestational diabetes and hypertension. In women who have had transient diabetes during pregnancy and later redeveloped overt diabetes, cardiovascular risk is already elevated nearly fourfold before diagnosis, which is almost as high as the average risk after a clinical diagnosis of diabetes is made. This key finding suggests that vascular risk in such women is at least partly independent of overt hyperglycemia.

1. Pre-eclampsia is a serious complication of pregnancy that is potentially life threatening for both the mother and baby. It encompasses a number of abnormalities that may be present in other clinical conditions. 2. A placenta is essential for the development of pre-eclampsia and can be important in the pathogenesis of pre-eclampsia. Normal pregnancy is associated with remodelling of the maternal spiral arteries, which deliver blood to the placental villous space. Remodelling involves invasion by placental cytotrophoblasts that cause the maternal spiral arteries to lose their smooth muscle and become capacitance vessels; this process, known as placentation, is complete by 20 weeks of pregnancy. Poor placentation is associated with small-for-gestational-age fetuses and some cases of pre-eclampsia. It is thought that poor placentation can result in a hypoxic placenta that releases 'toxic substances' into the maternal circulation, contributing to the maternal syndrome. A number of candidate 'toxic substances' have been proposed, but none is universally raised in pre-eclampsia. 3. Although the placenta is necessary for the development of pre-eclampsia, the extent to which placental abnormalities contribute to the condition varies. It is becoming apparent that maternal constitutional factors may also be important in this syndrome. Underlying hypertension, diabetes and obesity strongly predispose to pre-eclampsia. However, a continuum of risk may exist for blood pressure, bodyweight, glucose and lipids, which, in combination with each other and some degree of placental abnormalities, may lead to the development of pre-eclampsia. 4. The present review will focus on the maternal constitutional factors that define the metabolic syndrome and examine their contribution to pre-eclampsia and the long-term consequences for cardiovascular health.