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Ian A Greer

Publications and source records attributed to Ian A Greer.

At least 19 recordsLinked to original sources
PubMed2006

Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers.

BACKGROUND: Obesity in pregnancy is increasing and is a risk factor for metabolic pathology such as preeclampsia. In the nonpregnant, obesity is associated with dyslipidemia, vascular dysfunction, and low-grade chronic inflammation. AIM: Our aim was to measure microvascular endothelial function in lean and obese pregnant women at intervals throughout their pregnancies and at 4 months after delivery. Plasma markers of endothelial function, inflammation, and placental function and their association with microvascular function were also assessed. METHODS: Women in the 1st trimester of pregnancy were recruited, 30 with a body mass index (BMI) less than 30 kg/m(2) and 30 with a BMI more than or equal to 30 kg/m(2) matched for age, parity, and smoking status. In vivo endothelial-dependent and -independent microvascular function was measured using laser Doppler imaging in the 1st, 2nd, and 3rd trimesters of pregnancy and at 4 months postnatal. Plasma markers of endothelial activation [soluble intercellular cell adhesion molecule-1 (sVCAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), and plasminogen activator inhibitor (PAI)-1], inflammation (IL-6, TNFalpha, C-reactive protein, and IL-10), and placental function (PAI-1/PAI-2 ratio) were also assessed at each time point. RESULTS: The pattern of improving endothelial function during pregnancy was the same for lean and obese, but endothelial-dependent vasodilation was significantly lower (P < 0.05) in the obese women at each trimester (51, 41, and 39%, respectively). In the postpartum period, the improvement in endothelial-dependent vasodilation persisted in the lean women but declined to near 1st trimester levels in the obese (lean/obese difference, 115%; P < 0.01). There was a small but significant difference in endothelial-independent vasodilation between the two groups, lean response being greater than obese (P = 0.021), and response declined in both groups in the postpartum period. In multivariate analysis, time of sampling had the most impact on endothelial-independent function [18.5% (adjusted sum of squares expressed as a percentage of total means squared), P < 0.001 for sodium nitroprusside response; 9.8%, P < 0.001 for acetylcholine response], and obesity had the most impact on endothelial-dependent microvascular function (1.7%, P = 0.046 for sodium nitroprusside response; 19.3%, P < 0.001 for acetylcholine response). Time of sampling (11.2%, P < 0.001), IL-6 (4.0%, P = 0.002), and IL-10 (2.4%, P = 0.018) were significant independent contributors to variation in endothelial-dependent microvascular function. When obesity was entered into the model, the association with IL-6 and IL-10 was no longer significant, and obesity explained 6.8% (P < 0.001) of the variability in endothelial-dependent microvascular function. In the 1st trimester, obese women had a significantly higher PAI-1/PAI-2 ratio [obese median (interquartile range), 0.87 (0.54-1.21) vs. lean 0.30 (0.21-0.47), P < 0.001), reflecting the lower PAI-2 levels in obese pregnant women. In a multivariate analysis, 1st trimester BMI (7.6%, P = 0.012), IL-10 (8.2%, P < 0.001), and sVCAM-1 (0.73%, P = 0.007) contributed to the 1st trimester PAI-1/PAI-2 ratio. CONCLUSION: Obese mothers have a lower endothelium-dependent and -independent vasodilation when compared with lean counterparts. There was a higher PAI-1/ PAI-2 ratio in the 1st trimester in obese women, which improved later in pregnancy. Obese pregnancy is associated with chronic preexisting endothelial activation and impairment of endothelial function secondary to increased production of inflammatory T-helper cells-2 cytokines.

Acetylcholine↗
PubMed2006

Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: This study sought to determine whether metformin improves vascular function or myocardial ischemia in nondiabetic subjects. BACKGROUND: Metformin prevents diabetes and may reduce coronary events in patients with diabetes, but effects on microvascular function and angina are not clear. METHODS: We conducted an 8-week double-blind, randomized, placebo-controlled study of metformin 500 mg twice a day in 33 nondiabetic women with a prior history of normal coronary angiography but two consecutive positive (ST-segment depression > or =1 mm) exercise tolerance tests. All parameters were measured at baseline and at 8 weeks, together with an in vivo assessment of forearm (skin) microvascular function using laser Doppler imaging combined with iontophoresis. RESULTS: In comparison with placebo (n = 17), metformin recipients (n = 16) showed significant reductions in weight and in homeostatic model assessment for insulin resistance (p < 0.05, intention to treat). Endothelium-dependent microvascular responses improved significantly with metformin (2-way repeated analysis of variance, p = 0.0003), but responses with placebo were unchanged (p = 0.50). A comparison of change in acetylcholine responses between metformin and placebo recipients was significant, whether analyzed by a 2-way analysis of variance (p < 0.0001) or change in area under curves (mean change +392 perfusion units, 95% confidence interval [CI] 20 to 764). Endothelium-independent responses were not altered. Maximal ST-segment depression (-0.84 mm, 95% CI -1.49 to -0.20, p = 0.013), Duke score (6.1 U, 95% CI 1.8 to 10.5, p = 0.008), and chest pain incidence (-0.11 episodes/day, 95% CI -0.22 to 0.00, p = 0.056) improved in metformin relative to placebo recipients. CONCLUSIONS: Metformin may improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries. Larger controlled trials of longer duration are warranted.

Adult↗
PubMed2006

Microvascular function, metabolic syndrome, and novel risk factor status in women with cardiac syndrome X.

To characterize microvascular function, candidate risk pathways, and metabolic syndrome prevalence in women with cardiac syndrome X, 52 nondiabetic women with angiographically normal epicardial arteries but >1 mm of planar ST depression during exercise testing (patients) and 24 healthy controls of similar age were recruited. In addition to fasting blood samples and anthropometric measurements, forearm cutaneous microvascular function after iontophoresis of acetylcholine and sodium nitroprusside was assessed by laser Doppler imaging. Despite body mass index correction and a larger proportion on statin therapy, patients had high levels of insulin (p=0.016), triglycerides (p=0.018), intercellular adhesion molecule-1 (p=0.021), von Willebrand factor (p=0.005), and leptin (p=0.005) and lower levels of high-density lipoprotein cholesterol (p=0.042) compared with controls. Consistent with these data, 30% of patients but only 8% of controls fulfilled criteria for the metabolic syndrome as defined by the National Cholesterol Education Program (p=0.015). Endothelium-dependent and -independent microvascular functions were markedly impaired in patients (p<0.001), and the odds ratio for cardiac syndrome X was 7.38 (95% confidence interval 2.2 to 24.7) if the acetylcholine response was <8,710 flux units. In conclusion, women with cardiac syndrome X more commonly have metabolic syndrome and related adiposity, metabolic, and inflammatory derangements. They also have significantly impaired skin microvascular function as assessed by laser Doppler imaging, consistent with generalized vascular dysfunction, a finding with potential diagnostic implications.

Acetylcholine↗
PubMed2006

Anticoagulants in pregnancy.

Venous thromboembolic (VTE) complications are a leading cause of maternal mortality in the developed world. To reduce the incidence of VTE in pregnancy, and improve outcomes, a wider understanding of the risk factors involved and a better identification of women at risk of thrombosis coupled with effective thromboprophylaxis and treatment of VTE are required. As coumarin is unsuitable for use in pregnancy because of problems with embryopathy and risk of fetal bleeding, anticoagulation therapy in pregnancy centres on the use of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH). There is now extensive experience of the safety and efficacy of LMWH in pregnancy. LMWH's, such as enoxaparin and dalteparin, have clinical and practical advantages compared with UFH in terms of improved safety (significantly lower incidence of osteoporosis and heparin induced thrombocytopenia), and patient convenience with once daily dosing for the majority of women. Such therapy is not restricted only to prevention and treatment of VTE but is now being assessed in additional clinical situations such as the prevention of pregnancy complications.

Anticoagulants↗
PubMed2006

The "PRIM" study: a randomized comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety profile of prostaglandin E2 with isosorbide mononitrate for cervical ripening before the induction of labor at term. STUDY DESIGN: Primigravid women were assigned randomly to receive either 40 mg of isosorbide mononitrate or 2 mg of prostaglandin E2. Efficacy outcomes were the cervical ripening effect of each agent and the time from treatment initiation to delivery. Safety outcomes were the incidence and frequency of maternal side effects and events that would be potentially hazardous for mother and baby during outpatient cervical ripening. RESULTS: Prostaglandin E2 was more effective than isosorbide mononitrate in inducing a change in modified Bishop score. Mean duration from treatment initiation to delivery was greater for isosorbide mononitrate than prostaglandin E2. There were no adverse events in the isosorbide mononitrate group that would contraindicate outpatient treatment. However, in the prostaglandin E2 group, 7% of the pregnancies had abnormal fetal heart rate patterns (P = .0002). Maternal satisfaction was significantly higher in the isosorbide mononitrate group. CONCLUSION: Although isosorbide mononitrate was less effective, maternal satisfaction was significantly greater. The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate, but not prostaglandin E2, on an outpatient basis.

Adult↗
PubMed2006

Leukocyte density and proinflammatory mediator expression in regional human fetal membranes and decidua before and during labor at term.

OBJECTIVES: The region of fetal membranes overlying the cervix, known as the zone of altered morphology (ZAM), is considered to be the principle site of membrane inflammatory activity and extracellular matrix remodelling. We wished to quantify the relative contribution of each area of fetal membranes to the inflammatory process of parturition. Specifically, we aimed to quantify and compare (1) leukocyte densities in three regions of fetal membranes and decidua before and during spontaneous labor at term, and (2) mRNA expression of interleukin (IL)-1beta, IL-6, IL-8, cyclo-oxygenase type 1 (COX-1), and COX-2 in three regions of fetal membranes and decidua before and during spontaneous labor at term. METHODS: Biopsies of fetal membranes and decidua were obtained from pregnant women delivered by cesarean section at term both before and during spontaneous labor (n = 8 both groups). Fetal membranes were sampled from three areas, the ZAM, midzone (MZ), and periplacental (PP) regions. Leukocytes were identified by immunohistochemistry and their density quantified. Inflammatory mediator expression was quantified using TaqMan technology (Applied Biosystems, Foster City, CA). RESULTS: There was a significantly greater density of leukocytes in (1) the PP region of membranes compared with the ZAM, and (2) the decidua compared with amnion, amniotic connective tissue, and chorion. IL-1beta, IL-6, and IL-8 mRNA expression was significantly greater in all regions following spontaneous labor compared with nonlaboring tissues. There were no regional differences in cytokine expression within the fetal membranes. Choriodecidua expressed significantly more IL-1beta mRNA than amnion. Amnion expressed more COX-2 mRNA than choriodecidua. CONCLUSIONS: All regions of fetal membranes and decidua contribute to the inflammatory process of human parturition; however, their relative contributions differ in magnitude. Although the ZAM may be specifically important for membrane rupture, it does not appear to play a key or exclusive role in the other inflammatory processes of parturition. When studying fetal membranes, it is relevant to identify and define the area sampled for consistency and comparison with other studies.

Cyclooxygenase 1↗
PubMed2006

Thrombophilia and the risk for venous thromboembolism during pregnancy, delivery, and puerperium.

The main inherited thrombophilias (antithrombin deficiency, protein C and S deficiency, FVL, the prothrombin gene variant, and MTHFR C677T homozygotes) have a combined prevalence in Western European populations of 15% to 20%. One or more of these inherited thrombophilias is usually found in approximately 50% of women who have a personal history of VTE. Obstetricians must therefore be aware of the interaction between thrombophilias and the procoagulant state of pregnancy and should have an understanding of additional risk factors that may act synergistically with thrombophilias to induce VTE. Such knowledge combined with the appropriate use of thromboprophylaxis and treatment in women who have objectively confirmed VTE continue to improve maternal and perinatal outcomes.

Female↗
PubMed2005

Manifestations of chronic disease during pregnancy.

CONTEXT: Physiologic changes of pregnancy include insulin resistance, thrombophilia, immunosuppression, and hypervolemia. These changes may herald the development of disease in later life. OBJECTIVE: To summarize current evidence on how pregnancy reveals risk of chronic disease. EVIDENCE ACQUISITION: MEDLINE was searched for articles published between 1990 and 2005 relating pregnancy conditions to the development of chronic disease. Bibliographies and the Web sites of the International Society of Obstetric Medicine and International Society for the Study of Hypertension in Pregnancy were also reviewed. EVIDENCE SYNTHESIS: Pregnancy exaggerates atherogeniclike responses, including insulin resistance and dyslipidemia, manifesting as preeclampsia or gestational diabetes. These complications herald an increased risk of postpartum cardiovascular disease, with a 2-fold increased risk of coronary artery disease and stroke. Women with gestational diabetes mellitus can progress to type 2 diabetes mellitus. The rate of progression varies from 6% to 92% depending on diagnostic criteria, race/ethnicity, and duration of surveillance (from 6 months to 28 years). Pregnancy increases risk of venous thrombosis by 7- to 10-fold. Heritable thrombophilia is present in at least 15% of Western populations and underlies at least 50% of gestational venous thromboses. Thus, the procoagulant changes during pregnancy can unmask hereditary thrombophilia. An important adaptation leading to immunotolerance of the fetoplacental unit is a switch from helper T-cell (T(H)) 1 dominance to T(H)2 dominance. Patients with a T(H)1-dominant immune disease, such as rheumatoid arthritis or multiple sclerosis, improve during pregnancy. However, rheumatoid arthritis is 5 times more likely to develop after delivery than at any other time. During pregnancy, there is a 50% increase in plasma volume, which can unmask glomerulopathies, peripartum cardiomyopathy, arterial aneurysms, or arteriovenous malformations. Development of intrahepatic cholestasis of pregnancy predicts increased risk of later cholelithiasis. CONCLUSIONS: The physiologic changes of pregnancy can reveal risk of chronic diseases. Exaggerated responses reflective of the metabolic syndrome are seen in preeclampsia and gestational diabetes and can herald future cardiovascular and metabolic disease. Pregnancy is therefore an important screening opportunity for cardiovascular and metabolic disease risk factors, with the possibility of early intervention.

Autoimmune Diseases↗
PubMed2005

Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy.

To assess the safety and efficacy of low-molecular-weight heparins (LMWHs) for thromboprophylaxis and treatment of venous thromboembolism (VTE) in pregnancy, a systematic review of studies to the end of 2003 was undertaken. Data on VTE recurrence and side effects were extracted and cumulative incidences of VTE and adverse effects calculated. Of 81 reports identified, 64 reporting 2777 pregnancies were included. In 15 studies (174 patients) the indication for LMWH was treatment of acute VTE, and in 61 studies (2603 pregnancies) it was thromboprophylaxis or adverse pregnancy outcome. There were no maternal deaths. VTE and arterial thrombosis (associated with anti-phospholipid syndrome) were reported in 0.86% (95% confidence interval [CI], 0.55%-1.28%) and 0.50% (95% CI, 0.28%-0.84%) of pregnancies, respectively. Significant bleeding, generally associated with primary obstetric causes, occurred in 1.98% (95% CI, 1.50%-2.57%), allergic skin reactions in 1.80% (95% CI, 1.34%-2.37%), heparin-induced thrombocytopenia in 0%, thrombocytopenia (unrelated to LMWH) in 0.11% (95% CI, 0.02%-0.32%), and osteoporotic fracture in 0.04% (95% CI, < 0.01%-0.20%) of pregnancies. Overall, live births were reported in 94.7% of pregnancies, including 85.4% in those receiving LMWH for recurrent pregnancy loss. LMWH is both safe and effective to prevent or treat VTE in pregnancy.

Abortion, Habitual↗
PubMed2005

Human placental peroxisome proliferator-activated receptor delta and gamma expression in healthy pregnancy and in preeclampsia and intrauterine growth restriction.

OBJECTIVES: Human and animal studies have demonstrated that peroxisome proliferator-activated receptors (PPARs) are important in placental development and play key roles in metabolism and inflammation. We studied placental PPARdelta, PPARgamma, and retinoid X receptor alpha (RXRalpha) expression in healthy pregnancy and in preeclampsia (PET) and intrauterine growth restriction (IUGR). METHODS AND RESULTS: Using immunocytochemistry, PPARdelta, PPARgamma, and RXRalpha were localized to the cyto- and syncytiotrophoblast and invading trophoblast columns in first and second trimester placentas. Third trimester placentas from healthy pregnancy, and in PET and IUGR, demonstrated PPARdelta, PPARgamma, and RXRalpha staining within the syncytium, and localization within isolated cells in the stroma. In uncomplicated pregnancies, PPARdelta mRNA expression (PPARdelta:18s ratio, third trimester median 0.43 [interquartile (IQ) range 0.26-0.52] vs first trimester 0.20 [0.00-0.26], P = .03) and PPARdelta protein expression (third trimester 3.94 [2.45-4.68] vs first trimester 1.29 [0.78-2.29] optical densitometry [OD] mm(2), P = .04) were higher in the third trimester than in the first trimester. There were no consistent differences in PPARdelta, PPARgamma, or RXRalpha mRNA and protein expression among PET or IUGR placentas and controls. CONCLUSION: PPARdelta expression is up-regulated between the first and third trimester, indicating a role for this nuclear receptor in placental function. We found no evidence that placental PPARdelta, PPARgamma, and RXRalpha expression is changed in PET or IUGR. This suggests that changes in total placental PPAR expression are not involved in the pathophysiology of these conditions.

Case-Control Studies↗
PubMed2005

Venous thromboembolism and anticoagulant therapy in pregnancy.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of maternal mortality in western countries. Many of these deaths could be prevented by optimal prophylaxis and management. OBJECTIVE: The aim of this study was to examine the current literature to assess the risk of VTE in pregnant women and to identify the most effective and safe anticoagulant therapy. METHODS: A search was conducted using the major electronic databases of PubMed and MEDLINE 1996-October 2005 using the following key words: Pregnancy, venous thrombosis, thrombophilia, prosthetic heart valves, anticoagulants, heparin, low-molecular-weight heparin, coumarin, and warfarin. RESULTS: The common risk factors for VTE during pregnancy are age >35 years, obesity, operative delivery, thrombophilia, and a family or personal history of VTE. Coumarins are unsuitable for use during pregnancy because of embryopathy and risk of fetal bleeding. Low-molecular-weight heparins (LMWHs), such as enoxaparin and dalteparin, are safer and more convenient than unfractionated heparin (UFH). LMWH is now the agent of choice for pharmacologic thromboprophylaxis and treatment of VTE during pregnancy. Women with a suspected VTE should receive anticoagulant therapy until an objective diagnostic test is performed, unless there is a clear contraindication to anticoagulation. If a VTE is confirmed, anticoagulant treatment should be continued throughout pregnancy. These patients usually, require at least 6 months of anticoagulation, and treatment should be continued until at least 6 weeks postpartum. Management of women with prosthetic heart valves in pregnancy is controversial; while coumarin treatment is more effective than UFH for thromboprophylaxis in the mother, UFH is associated with a better outcome for the fetus. Coumarin embryopathy can be avoided if heparin is substituted by 6 weeks' gestation. The limited data on LMWH in women with prosthetic heart valves suggest that it compares favorably with UFH. CONCLUSIONS: LMWH is now the anticoagulant of choice for the treatment and prevention of VTE in pregnancy. However, the management of women with prosthetic heart valves requiring anticoagulation in pregnancy remains controversial as coumarins appear safer for the mother, but heparin is associated with less fetal morbidity and data on LMWH are limited.

Adult↗
PubMed2005

Changes in booking body mass index over a decade: retrospective analysis from a Glasgow Maternity Hospital.

Whether booking body mass index (BMI) in the UK is increasing is unknown but is of clinical interest since overweight or obese pregnant women face far greater risks of pregnancy complications including pre-eclampsia and gestational diabetes. We examined booking BMI in 1990 and 2002/2004, of women with singleton pregnancies. Our analyses indicate an increase of 1 U in mean BMI over this period despite lower parity in recent years. When the model was adjusted for maternal age, parity, smoking status and deprivation category the mean BMI was 1.37 U higher in 2002/2004 than in 1990. More striking was the significant increase in the proportion of women who were obese (BMI > or = 30 kg/m2) at booking--more than twofold higher in unadjusted analysis (18.9% vs 9.4%) rising to greater than threefold higher in multivariate analysis. These findings suggest that obesity-related pregnancy complications are likely to increase with implications for both mother and child.

Adult↗
PubMed2005

Outcomes of pregnancy complicated by thyroid disease.

AIMS: To perform a case note review of pregnancies complicated by thyroid dysfunction to determine management and therapeutic intervention in relation to pregnancy outcome. METHODS: A retrospective case note analysis of 81 ongoing pregnancies in 70 pregnant women with a history of thyroid dysfunction over a period of 5 years at the Glasgow Royal Maternity Hospital (GRMH), Glasgow, Scotland, United Kingdom. The results of thyroid function tests and whether a change in treatment was instituted were recorded. Thyroid function was assessed by standard laboratory reference ranges for free thyroxine (FT4) and thyroid stimulating hormone (TSH) in all trimesters. Other parameters were also noted. RESULTS: Medication levels needed to be increased in the hypothyroid group (45%), and decreased (38%) in the hyperthyroid group. CONCLUSION: Pregnancy outcome was good in majority of cases given appropriate replacement therapy for stated reference values.

Antithyroid Agents↗
PubMed2005

Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study.

Combined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47). Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.

Adult↗
PubMed2004

Short- and long-term changes in plasma inflammatory markers associated with preeclampsia.

Preeclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Low-grade chronic inflammation is a risk factor for cardiovascular disease. This study examined changes in inflammatory markers prospectively during pregnancy, the current inflammatory status of women who had a pregnancy complicated by preeclampsia 20 years previously against matched controls, and the association between inflammatory genes and risk of preeclampsia in a case (n=106) control (n=212) study. In control pregnancies (n=34), mean interleukin-10 (IL-10) levels increased 38% (P=0.012) and tumor necrosis factor-alpha (TNF-alpha) by 33% (P=0.024) between the first and third trimesters. The mean preeclampsia group IL-10 and TNF-alpha rose by 43% (P=0.013 and P=0.0065, respectively) from the first to the third trimester. In women with preeclampsia only, plasma IL-6 increased from the first to the third trimester (1.66 [2.04] to 2.94 [2.47] pg/mL; P=0.0004). Twenty years after the index pregnancy, women who had had preeclampsia demonstrated significantly higher IL-6 to IL-10 ratio (3.96 [6.07] versus 2.12 [1.89]; P=0.034) compared with a healthy index pregnancy 20 years previously, that persisted after adjustment for smoking and current body mass index. The IL-1beta (C-511T), IL-6 (G-174C), TNF-alpha (G-308A), E-selectin (S128R), intercellular adhesion molecule-1 (K469E), and C-reactive protein (C1059G) polymorphisms were not associated with risk of developing preeclampsia. In conclusion, preeclampsia is associated with short- and long-term changes in inflammatory status.

Adult↗
PubMed2004

Prevention of venous thromboembolism in pregnancy.

Venous thromboembolic complications (VTE) are a leading causes of maternal mortality in the developed World. To reduce the incidence VTE in pregnancy, and improve outcomes, a wider understanding of the risk factors involved and a better identification of women at risk of thrombosis coupled with effective thromboprophylaxis are required. The common risk factors for VTE in pregnancy are: age over 35 years; obesity; operative delivery (especially emergency Caesarean Section in labour); thrombophilia; and a family or personal history of thrombosis suggestive of an underlying thrombophilia. As warfarin is unsuitable for use in pregnancy because of problems with embryopathy and risk of fetal bleeding, optimal thromboprophylaxis in pregnancy centres on the use of low-molecular-weight heparin (LMWH). There is now extensive experience of the safety and efficacy of LMWH in pregnancy. LMWH's, such as enoxaparin and dalteparin, have clinical and practical advantages compared with unfractionated heparin in terms of improved safety (significantly lower incidence of osteoporosis and heparin induced thrombocytopenia), and patient convenience with once daily dosing for the majority of women. Thus LMWH is now the agent of choice in pharmacological thromboprophylaxis in pregnancy

Adult↗
PubMed2004

Inverse association between birth weight and C-reactive protein concentrations in the MIDSPAN Family Study.

OBJECTIVE: Inflammation markers and low birth weight each predict elevated risk of cardiovascular events and type 2 diabetes. However, potential associations between the low-grade inflammatory response as represented by C-reactive protein (CRP) concentrations and low birth weight have been sparsely examined. METHODS AND RESULTS: In the MIDSPAN Family Study, 1663 individuals had birth weight data and CRP concentrations measured as adults (age 30 to 59). The relationship between these parameters was examined after adjusting for factors known to influence CRP concentrations inclusive of age, body mass index, smoking, socio-economic deprivation, and hormone use in women. After adjusting for potential confounders, there was a negative association between birth weight and CRP, whereby a 1-kg increase in birth weight is associated with a 10.7% decrease in CRP (95% CI: 3.0% to 17.8% decrease). There was no strong evidence that the effects differed in men and women (P=0.32). CONCLUSIONS: Low birth weight contributes to elevated CRP concentration in adult life. Future studies are required to determine to what extent this association reflects catch-up centile crossing, in utero programming, or genetic factors.

Adult↗