Epidemiology of preeclampsia: impact of obesity
TL;DR: Exploring common features may provide insight into the pathophysiologic mechanisms underlying preeclampsia among obese and overweight women, which is a leading cause of maternal and perinatal morbidity and mortality worldwide.
Abstract: Preeclampsia is a pregnancy-specific disorder that affects 2–8% of all pregnancies and remains a leading cause of maternal and perinatal morbidity and mortality worldwide. Diagnosis is based on new onset of hypertension and proteinuria. Multiple organ systems can be affected, with severe disease resulting. The wide range of risk factors reflects the heterogeneity of preeclampsia. Obesity, which is increasing at an alarming rate, is also a risk factor for preeclampsia as well as for later-life cardiovascular disease. Exploring common features may provide insight into the pathophysiologic mechanisms underlying preeclampsia among obese and overweight women.
Citations
More filters
TL;DR: In 2012, the cost of preeclampsia within the first 12 months of delivery was $2.18 billion in the United States ($1.03 billion for mothers and $1.15 billion for infants), and was disproportionately borne by births of low gestational age.
183 citations
TL;DR: Vitamin D supplementation initiated in weeks 10-18 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm, however, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeClampsia.
Abstract: BACKGROUND. Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia.
METHODS. We assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (10–18 weeks), on the development of preeclampsia. The effects of serum vitamin D (25-hydroxyvitamin D [25OHD]) levels on preeclampsia incidence at trial entry and in the third trimester (32–38 weeks) were studied. We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin D–associated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia.
RESULTS. Of 881 women randomized, outcome data were available for 816, with 67 (8.2%) developing preeclampsia. There was no significant difference between treatment (N = 408) or control (N = 408) groups in the incidence of preeclampsia (8.08% vs. 8.33%, respectively; relative risk: 0.97; 95% CI, 0.61–1.53). However, in a cohort analysis and after adjustment for confounders, a significant effect of sufficient vitamin D status (25OHD ≥30 ng/ml) was observed in both early and late pregnancy compared with insufficient levels (25OHD <30 ng/ml) (adjusted odds ratio, 0.28; 95% CI, 0.10–0.96). Differential expression of 348 vitamin D–associated genes (158 upregulated) was found in peripheral blood of women who developed preeclampsia (FDR <0.05 in the Vitamin D Antenatal Asthma Reduction Trial [VDAART]; P < 0.05 in a replication cohort). Functional enrichment and network analyses of this vitamin D–associated gene set suggests several highly functional modules related to systematic inflammatory and immune responses, including some nodes with a high degree of connectivity.
CONCLUSIONS. Vitamin D supplementation initiated in weeks 10–18 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm. However, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia. Differentially expressed vitamin D–associated transcriptomes implicated the emergence of an early pregnancy, distinctive immune response in women who went on to develop preeclampsia.
TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00920621","term_id":"NCT00920621"}}NCT00920621.
FUNDING. Quebec Breast Cancer Foundation and Genome Canada Innovation Network. This trial was funded by the National Heart, Lung, and Blood Institute. For details see Acknowledgments.
145 citations
Cites background from "Epidemiology of preeclampsia: impac..."
...Divorced/separated, n (%) 12 (3) 10 (2)...
[...]
...org Volume 126 Number 12 December 2016 Introduction Preeclampsia is a multisystem complex disease of pregnancy with grave maternal-fetal and neonatal consequences that complicates up to 8% of pregnancies (1, 2)....
[...]
TL;DR: Current knowledge on the present and future use of EVs not only as biomarkers, but also as therapeutic targeting agents, mainly as vectors for drug or compound delivery into target cells and tissues are provided.
Abstract: Extensive evidence suggests that the release of membrane-enclosed compartments, more commonly known as extracellular vesicles (EVs), is a potent newly identified mechanism of cell-to-cell communication both in normal physiology and in pathological conditions. This review presents evidence about the formation and release of different EVs, their definitive markers and cargo content in reproductive physiological processes, and their capacity to convey information between cells through the transfer of functional protein and genetic information to alter phenotype and function of recipient cells associated with reproductive biology. In the male reproductive tract, epididymosomes and prostasomes participate in regulating sperm motility activation, capacitation, and acrosome reaction. In the female reproductive tract, follicular fluid, oviduct/tube, and uterine cavity EVs are considered as vehicles to carry information during oocyte maturation, fertilization, and embryo-maternal crosstalk. EVs via their cargo might be also involved in the triggering, maintenance, and progression of reproductive- and obstetric-related pathologies such as endometriosis, polycystic ovarian syndrome, preeclampsia, gestational diabetes, and erectile dysfunction. In this review, we provide current knowledge on the present and future use of EVs not only as biomarkers, but also as therapeutic targeting agents, mainly as vectors for drug or compound delivery into target cells and tissues.
134 citations
TL;DR: The current knowledge of placental ageing in the aetiology of adverse pregnancy outcomes is summarized and the hallmarks of ageing which could be potential markers for preeclampsia and fetal growth restriction are discussed.
Abstract: Preeclampsia is a multisystemic pregnancy disorder and a major cause of maternal and neonatal morbidity and mortality worldwide. The exact pathophysiology of preeclampsia remains unclear; however, it is speculated that the various pathologies can be attributed to impaired vascular remodelling and elevated oxidative stress within the placenta. Oxidative stress plays a key role in cell ageing, and the persistent presence of elevated oxidative stress precipitates cellular senescence and mitochondrial dysfunction, resulting in premature ageing of the placenta. Premature ageing of the placenta is associated with placental insufficiency, which reduces the functional capacity of this critical organ and leads to abnormal pregnancy outcomes. The changes brought about by oxidative insults are irreversible and often lead to deleterious modifications in macromolecules such as lipids and proteins, DNA mutations, and alteration of mitochondrial functioning and dynamics. In this review, we have summarized the current knowledge of placental ageing in the aetiology of adverse pregnancy outcomes and discussed the hallmarks of ageing which could be potential markers for preeclampsia and fetal growth restriction.
105 citations
TL;DR: The mouse has proven to be a useful animal model for investigating molecular mechanisms that may hold the key to unraveling the mysteries of PE in women and will aid in the ability to accurately prevent, manage, and treat PE to avoid maternal and fetal losses.
Abstract: Preeclampsia (PE) is a devastating disorder of pregnancy that affects up to 8% of pregnant women in the United States The diagnosis of PE is made by the presentation of new-onset hypertension, ≥140 mmHg systolic blood pressure (BP) or ≥90 mmHg diastolic BP, and either proteinuria or another accompanying sign/symptom, such as renal insufficiency, thrombocytopenia, hepatic dysfunction, pulmonary edema, or cerebral/visual These signs can occur suddenly and without warning PE that presents before 34 wk of gestation is considered early onset and carries a greater risk for perinatal morbidity/mortality than late-onset PE that occurs at or after 34 wk of gestation At this time there is no cure for PE, and the only effective treatment is delivery of the baby and placenta If allowed to progress to eclampsia (PE with neurologic involvement), seizures will occur and possibly death through stroke PE also carries the risk of significant fetal and neonatal morbidity/mortality in addition to long-term health risks for mother and child Despite significant research efforts to accurately predict, diagnose, and treat PE, a cure eludes us Elucidating the pathophysiological mechanisms that can cause PE will aid in our ability to accurately prevent, manage, and treat PE to avoid maternal and fetal losses Intense research efforts are focused on PE, and the mouse has proven to be a useful animal model for investigating molecular mechanisms that may hold the key to unraveling the mysteries of PE in women
91 citations
Cites background from "Epidemiology of preeclampsia: impac..."
...Also, with the increased incidence of obesity worldwide, we see more women of childbearing age that have higher BMIs, diabetes, and hypertension as well as subfertility (24)....
[...]
...In fact PE is responsible for 15–20% of preterm births per year (24)....
[...]
..., new paternity, limited sperm exposure, barrier contraception), multifetal gestation, and hydatidiform mole (24)....
[...]
..., antiphospholipid antibody syndrome and systemic lupus erythematosus), family or personal history of PE, and lack of smoking (24)....
[...]
...A 24 to 36 yr follow-up of maternal health status in PE-affected women in Jerusalem reported a twofold increase in mortality rate from cardiovascular-related causes (1, 24)....
[...]
References
More filters
TL;DR: It is confirmed that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of VEGF and placental growth factor (PlGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt 1 that fall after delivery, and observations suggest that excess circulating sFelt1 contributes to the pathogenesis of preeClampsia.
Abstract: Preeclampsia, a syndrome affecting 5% of pregnancies, causes substantial maternal and fetal morbidity and mortality. The pathophysiology of preeclampsia remains largely unknown. It has been hypothesized that placental ischemia is an early event, leading to placental production of a soluble factor or factors that cause maternal endothelial dysfunction, resulting in the clinical findings of hypertension, proteinuria, and edema. Here, we confirm that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of VEGF and placental growth factor (PlGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt1 that fall after delivery. We demonstrate that increased circulating sFlt1 in patients with preeclampsia is associated with decreased circulating levels of free VEGF and PlGF, resulting in endothelial dysfunction in vitro that can be rescued by exogenous VEGF and PlGF. Additionally, VEGF and PlGF cause microvascular relaxation of rat renal arterioles in vitro that is blocked by sFlt1. Finally, administration of sFlt1 to pregnant rats induces hypertension, proteinuria, and glomerular endotheliosis, the classic lesion of preeclampsia. These observations suggest that excess circulating sFlt1 contributes to the pathogenesis of preeclampsia.
3,613 citations
TL;DR: Haemorrhage and hypertensive disorders are major contributors to maternal deaths in developing countries and these data should inform evidence-based reproductive health-care policies and programmes at regional and national levels.
3,593 citations
TL;DR: Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeClampsia was associated with a small-for-gestational-age infant.
Abstract: Background The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascul...
3,148 citations
2,562 citations