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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary embolism is the most common cause of maternal death during pregnancy and the puerperium in the industrialized world. The risk of venous thromboembolism (VTE) in pregnancy is 0.05%-1.8%, 6 times greater than in the non-pregnant state. The risk is increased in women over 35 years and those with obesity, previous VTE, operative delivery, or underlying thrombophilia. Women presenting with recurrent miscarriages, preeclampsia, intrauterine growth restriction, abruptio placentae, or stillbirth (all associated with microvascular thrombosis in placental blood vessels) have high incidence (65%) of thrombophilia. About 70% of the women who present with VTE during pregnancy are carriers of hereditary or acquired thrombophilia. Treatment of women with VTE during pregnancy, and especially those with thrombophilia, requires individualized dosing and duration of antithrombotic therapy and the formulation of thromboprophylactic strategies for future pregnancies. Warfarin is contraindicated during the first trimester due to fetotoxicity; unfractionated heparin (UFH) is associated with practical disadvantages and the risk of heparin-induced thrombocytopenia (HIT) and osteoporosis with long-term use. Low molecular weight heparins (LMWHs) are convenient to use, do not cross the placenta, carry a lower risk of HIT and osteoporosis, and are safe and effective. LMWHs are replacing UFH as the anticoagulant of choice during pregnancy and improve pregnancy outcome in women with a history of obstetric complications and confirmed thrombophilia.
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PMID:Thrombophilia and its treatment in pregnancy. 1171 85

Leptin is an endocrine and a growth factor which is important for regulation of body fat, feeding, and energy homeostasis. The anti-obesity function of leptin has been recently extended to reproduction, puberty and pregnancy as an endocrine signal to the hypothalamus. Leptin controls the functional integrity of the feto-placental unit thereby maintaining pregnancy by virtue of its immunomodulatory property via T lymphocytes or other proto-oncogenes. Dysregulation of autocrine/paracrine function of leptin at feto-placento-maternal interface may be implicated in the pathogenesis of recurrent miscarriage gestational diabetes, pre-eclampsia and intra-uterine fetal growth retardation including disturbance of fetal bone turnover. This review will focus on the role of leptin in normal and abnormal pregnancy and fetal growth.
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PMID:Prospective function of placental leptin at maternal-fetal interface. 1194 77

Leptin is an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. In rodents, it also modulates glucose metabolism by increasing insulin sensitivity. We previously reported that leptin is produced by human placental trophoblasts. We also revealed that leptin gene expression in the placenta was augmented in severe pre-eclampsia, and suggested that placental hypoxia may play a role in this augmentation. Maternal plasma leptin levels correlated well with mean blood pressure, but not with body mass index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than those without IUGR (P< 0.05). We further examined the effects of hyperleptinemia on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin. In pregnant Tg mice, food intake was significantly less than non-Tg, and the fetal body weights were reduced to approximately 70 per cent of those of non-Tg. Resistin is a novel adipocyte-derived hormone that decreases insulin sensitivity and increases plasma glucose concentration, thus contributing the development of obesity-related type II diabetes mellitus. We recently found that resistin gene is expressed in the human placenta as well as adipose tissue. In this review, possible roles of placental leptin and resistin are discussed.
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PMID:Role of leptin in pregnancy--a review. 1197 63

Susceptibility genes present in both mother and fetus most likely contribute to the risk of pre-eclampsia. Placental biopsies were therefore investigated by high-density DNA microarray analysis to determine genes differentially regulated within chorionic villous tissue in pre-eclampsia and normal pregnancy. The pooled RNAs of pre-eclamptic and normotensive subjects were hybridized to the HuGeneFL array representing sequences from approximately 5600 full-length human cDNAs. The differentially expressed genes that were detected could be categorized into nine groups: adhesion molecules, obesity-related genes, transcription factors/signalling molecules, immunological factors, neuromediators, oncogenic factors, protease inhibitors, hormones and growth factor-binding proteins. Among those, the obesity-related genes included putative candidate genes associated with the pathogenesis of pre-eclampsia. One of the most up-regulated transcripts was the obese gene (43.6-fold change), and this was reflected by elevated leptin protein levels. In the case of feto-maternal contribution of polymorphic genes to pre-eclampsia, expression analysis of placental tissue has lead to numerous target genes waiting for large scale genetic linkage analyses.
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PMID:Microarray analysis of differentially expressed genes in placental tissue of pre-eclampsia: up-regulation of obesity-related genes. 1208 83

Ovarian and other hormones are major determinants of breast cancer risk. Particularly important is the accumulative exposure of the breast to circulating levels of the ovarian hormones estradiol and progesterone. A number of breast cancer risk factors can be understood in light of how they affect women's hormone profiles. Age is a marker for the onset and cessation of ovarian activity. Racial differences in hormone profiles correlate with breast cancer incidence patterns. Age at menarche not only serves as the chronological indicator of the onset of ovarian activity, but as a predictor of ovulatory frequency during adolescence and hormone levels in young adults, and has a long-lasting influence on risk. Age at menopause, another established breast cancer risk factor, marks the cessation of ovarian activity. Pregnancy history and lactation experience also are hormonal markers of breast cancer risk. Postmenopausal obesity, which is associated with higher levels of estrogen following cessation of ovarian activity, increases breast cancer risk, whereas physical activity, which can limit menstrual function, reduces risk. A relatively recent area of investigation is prenatal exposures like preeclampsia and low birth weight; both may be associated with lower in utero exposure to estrogen and also may predict lower breast cancer risk as an adult. Improved understanding of these exposures and their potential interactions with breast cancer susceptibility genes may, in the future, improve our prospects for breast cancer prevention.
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PMID:Epidemiology of endocrine-related risk factors for breast cancer. 1216 84

In a case-control study of 190 preeclamptic patients and 373 control subjects, we assessed maternal family history of chronic hypertension and type 2 diabetes in relation to preeclampsia risk. Participants provided information on first-degree family history of the 2 conditions and other covariates during postpartum interviews. Logistic regression was used to estimate odds ratios and 95% confidence intervals adjusted for confounding by age, race, and obesity. Compared with women with no parental history of hypertension, women with maternal only (odds ratio=1.9), paternal only (odds ratio=1.8), or both maternal and paternal history of hypertension (odds ratio=2.6) had a statistically significant increased risk of preeclampsia. The odds ratio for women with at least one hypertensive parent and a hypertensive sibling was 4.7 (95% confidence interval, 1.9 to 11.6). Both maternal only (odds ratio=2.1; 95% confidence interval, 0.9 to 4.6) and paternal only (odds ratio=1.9; 95% confidence interval, 1.0 to 3.2) history of diabetes was associated with an increased risk of preeclampsia. Women with a diabetic sibling had a 4.7-fold increased risk of preeclampsia (95% confidence interval, 1.1 to 19.8). For women with at least one hypertensive parent and at least one diabetic parent, relative to those with parents with neither diagnosis, the odds ratio for preeclampsia was 3.2 (95% confidence interval, 1.6 to 6.2). Our results are consistent with the thesis that family history of hypertension and diabetes reflects genetic and behavioral factors whereby women may be predisposed to an increased preeclampsia risk.
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PMID:Family history of hypertension and type 2 diabetes in relation to preeclampsia risk. 1262 36

Diabetes in pregnancy, whether the woman had diabetes prior to becoming pregnant or developed gestational diabetes, is associated with many complications and risks. In the first trimester, organogenesis can be disrupted by complications due to poor control of the mother's diabetes, leading to fetal malformations or perinatal mortality. Problems with glucose control in the remainder of the pregnancy can also have consequences for the child. These include macrosomia, shoulder dystocia, pre-eclampsia, hypoglycemia and an increased risk for obesity and diabetes in the future. Therefore, aggressive and prompt treatment of the high blood sugar levels, which cause these complications, is necessary. This review looks at the current treatments for pregnancies complicated by diabetes and evaluates the place of new and possible future treatments including diet, exercise, insulin, insulin analogs and oral and inhaled agents.
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PMID:New and future diabetes therapies: are they safe during pregnancy? 1268 46

The pathophysiology of pre-eclampsia is contested, but one hypothesis indicates that it is a heterogeneous condition in which only a subset of affected women bear small-for-gestational age (SGA) babies. In intrauterine growth-restricted (IUGR) infants, placental transport of amino acids is diminished and the resulting decrease in cord-blood amino acid concentrations is thought to contribute to their stunted growth. In contrast, the metabolic syndrome (dyslipidaemia, hyperinsulinaemia, hyperglycaemia, hypertension and obesity) which is associated with high amino acid concentrations is more prevalent in women with pre-eclampsia. The focus of this study was to compare maternal and fetal serum amino acid concentrations during normal pregnancy and pre-eclampsia and to evaluate the associations between the amino acid concentrations and fetal growth. The results indicate that maternal and cord-blood amino acid concentrations were significantly higher in women with pre-eclampsia compared with normal pregnant women and the concentrations were inversely associated with measures of infant growth. Maternal and cord-blood amino acid concentrations were also significantly higher in pre-eclamptic mothers with SGA infants compared with pre-eclamptic mothers whose babies were not SGA. These data indicate that, in contrast to IUGR, pre-eclampsia is associated with enhanced placental amino acid transport or reduced fetal amino acid utilization. Furthermore, the data are consistent with the hypothesis that pre-eclampsia is a heterogeneous disease associated with the metabolic syndrome.
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PMID:Maternal and fetal amino acid concentrations and fetal outcomes during pre-eclampsia. 1277

New-onset hypertension (which includes preeclampsia and gestational hypertension) is a common and morbid complication of pregnancy. Many features of the insulin resistance syndrome have been associated with this condition. These include hypertension, hyperinsulinemia, glucose intolerance, obesity, and lipid abnormalities. Other accompanying abnormalities may include elevated levels of leptin, TNFalpha, tissue plasminogen activator, plasminogen activator inhibitor-1, and testosterone. The documentation of these features before the onset of hypertension in pregnancy suggests that insulin resistance or associated abnormalities may have a role in this disorder. Furthermore, the recognition that features of the insulin resistance syndrome persist many years after pregnancy among women with this condition raises the possibility that these women may have increased risk for future cardiovascular disease. These observations suggest that interventions to reduce insulin resistance may reduce the risk of both hypertension in pregnancy and later life cardiovascular complications, and warrant further study.
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PMID:Insulin resistance and its potential role in pregnancy-induced hypertension. 1278 33

A leading theory of the pathophysiology of preeclampsia is that oxidative stress induces vascular endothelial cell dysfunction. Advanced glycation end products (AGEs) form when aldose sugars react nonenzymatically with proteins under conditions of oxidative stress. AGEs are circulating molecules and can generate reactive oxygen species and vascular dysfunction (in diabetes and atherosclerosis) through an association with cell surface receptors (RAGE). RAGE is a multiligand receptor, expressed in vascular tissue, which is upregulated by its own ligands. Insulin resistance and obesity are risk factors for developing preeclampsia, as well as being conditions that would increase RAGE levels. Thus, we hypothesized that women with preeclampsia will have elevated levels of RAGE protein compared with normal pregnant women. Biopsies of nonlaboring myometrium as well as omentum were taken from normal pregnant and preeclamptic women. Nonpregnant samples were obtained at the time of hysterectomy. Tissue sections were immunostained with anti-RAGE as well as anti-alpha-actin and anti-von Willebrand factor (to identify blood vessels and intact endothelial cells). Staining intensity was qualitatively described as well as given an intensity score, with the identity of the section concealed. Nonpregnant myometrial and omental vessels showed very low to undetectable levels of RAGE staining. Pregnancy induced a significant increase in RAGE protein levels in both myometrium and omental vasculature. Blood vessels from women with preeclampsia consistently had intense staining for RAGE in both vessel beds. Thus, our data suggest that since RAGE activation can induce similar pathophysiologic changes to those observed in women with preeclampsia (including NFkappaB activation, increased TNFalpha and endothelin), elevated RAGE protein may be contributing to the vascular dysfunction in preeclampsia.
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PMID:The receptor for advanced glycation end products (RAGE) is elevated in women with preeclampsia. 1290 2


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