Metabolic abnormalities and obesity’s impact on the risk for developing preeclampsia

Abstract

Preeclampsia (PE), a hypertensive disorder of pregnancy, is increasing as a major contributor to perinatal and long-term morbidity of mother and offspring. PE is thought to originate from ischemic insults in the placenta driving the release of prohypertensive anti-angiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1)] and proinflammatory [tumor necrosis factor-α (TNF-α)] factors into the maternal circulation. Whereas the increased incidence of PE is hypothesized to be largely due to the obesity pandemic, the mechanisms whereby obesity increases this risk are unknown. The maternal endothelium is targeted by placental and adipose tissue-derived factors like sFlt-1 and TNF-α that promote hypertension during pregnancy, resulting in vascular dysfunction and hypertension. Interestingly, not all obese pregnant women develop PE. Data suggest that obese pregnant women with the greatest metabolic abnormalities have the highest incidence of PE. Identifying obesity-related mechanisms driving hypertension in some obese pregnant women and pathways that protect normotensive obese pregnant women, may uncover novel protocols to treat PE. Metabolic abnormalities, such as increased circulating leptin, glucose, insulin, and lipids, are likely to increase the risk for PE in obese women. It is not only important to understand whether each of these metabolic factors contribute to the increased risk for PE in obesity, but also their cumulative effects. This is particularly relevant to obese pregnant women with gestational diabetes mellitus (GDM) where all of these factors are increased and the risk for PE is highest. It is speculated that these factors potentiate the anti-angiogenic and proinflammatory mechanisms of placental ischemia-induced vascular dysfunction thereby contributing to the increasing incidence of PE.

The Area under the Curve (AUC) of Oral Glucose Tolerance Test (OGTT) Could Be a Measure Method of Hyperglycemia in All Pregnant Women

“…Metabolic abnormalities, such as increased circulating leptin, glucose, insulin, and lipids, are likely to increase the risk of preeclampsia in obese women. This is particularly relevant for obese pregnant women with GDM, for whom all of these factors are increased [20]. In Group 4, in which the AUC was ≥14.20; the prevalence of hypertensive diseases was higher in the GDM group even though they were undergoing intervention.…”

Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia

“…Although not statistically different, our preeclamptic cohort did tend to have slightly elevated total cholesterol, LDL, and BMI compared to our control group and these differences may reflect an increased risk of developing preeclampsia, and/or may contribute to increased risk of CVD post-partum. Classical CVD risk factors such as hypertension 57 , obesity 58 , and hyperlipidemia 59 have all been implicated in the development of preeclampsia and elevated CVD risk postpartum. Recent evidence suggests that women who have had preeclampsia demonstrate increased cardiovascular reactivity to sympathetic stressors, which may also contribute to increased risk of cardiovascular morbidity and mortality 60 .…”

The fetus at the tipping point: modifying the outcome of fetal asphyxia

“…). Maternal obesity is often accompanied by an increased risk for gestational diabetes and both are also associated with poor placental perfusion and conditions such as pre‐eclampsia that are associated with fetal inflammation, hypoxia and IUGR (Spradley, ). The factors that mediate the impact of obesity during development and which may interact with HI insults are multifactorial and include chronic neuroinflammation, oxidative stress, as well functional changes in maternal and perinatal insulin, glucose and leptin signalling (Edlow, ).…”