Gestational diabetes is associated with the risk of offspring's congenital anomalies: a register-based cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy-related disorder and a well-known risk factor for adverse pregnancy outcomes. There are conflicting findings on the association of GDM with the risk of congenital anomalies (CAs) in offspring. In this study, we aimed to determine study whether maternal GDM is associated with an increased risk of major CAs in offspring. METHODS: This Finnish Gestational Diabetes (FinnGeDi) register-based study included 6,597 women with singleton pregnancies and a diagnosis of GDM and 51,981 singleton controls with no diabetes identified from the Finnish Medical Birth Register (MBR) in 2009. Data from MBR were combined in this study with the Register of Congenital Malformations, which includes the data of CAs. We used logistic regression to calculate odds ratios (OR) for CAs, together with their 95% confidence intervals (CIs), adjusting for maternal age, parity, pre-pregnancy body mass index (BMI), and maternal smoking status. RESULTS: The risk of major CAs was higher in the GDM-exposed (n = 336, 5.09%) than in the non-exposed group (n = 2,255, 4.33%) (OR: 1.18, 95% CI: 1.05-1.33, p = 0.005). The adjusted OR (aOR) was 1.14 (95% CI: 1.00-1.30, p = 0.047). There was a higher overall prevalence of CAs, particularly chromosomal abnormalities (0.52% vs. 0.21%), in the GDM-exposed group (OR: 2.49, 95% Cl: 1.69-3.66, p < 0.001). The aOR was 1.93 (95% Cl: 1.25-2.99, p = 0.003). CONCLUSIONS: Offspring exposed to GDM have a higher prevalence of major CAs. Of note, risk factors other than GDM, such as older maternal age and a higher pre-pregnancy BMI, diminished the between group differences in the prevalence of major CAs. Nevertheless, our findings suggest that offspring exposed to maternal GDM are more likely to be diagnosed with a chromosomal abnormality, independent of maternal age, parity, pre-pregnancy BMI, and smoking.

Associations of low sex hormone-binding globulin and androgen excess in early pregnancy with fasting and post-prandial hyperglycaemia, gestational diabetes, and its severity.

AIMS: We studied whether androgen excess and low sex hormone-binding globulin (SHBG) measured in early pregnancy are independently associated with fasting and post-prandial hyperglycaemia, gestational diabetes (GDM), and its severity. MATERIALS AND METHODS: This nationwide case-control study included 1045 women with GDM and 963 non-diabetic pregnant controls. We measured testosterone (T) and SHBG from biobanked serum samples (mean 10.7 gestational weeks) and calculated the free androgen index (FAI). We first studied their associations with GDM and secondly with the type of hyperglycaemia (fasting, 1 and 2 h glucose concentrations during the oral glucose tolerance test), early-onset GDM (<20 gestational weeks) and the need for anti-diabetic medication. RESULTS: After adjustments for gestational weeks at sampling, pre-pregnancy BMI, and age, women with GDM had 3.7% (95% CI 0.1%-7.3%) lower SHBG levels, 3.1% (95% CI 0.1%-6.2%) higher T levels, and 4.6% (95% CI 1.9%-7.3%) higher FAI levels than controls. SHBG was inversely associated with fasting glucose, whereas higher FAI and T were associated with higher post-prandial glucose concentrations. Women with early-onset GDM had 6.7% (95% CI 0.7%-12.7%) lower SHBG levels and women who needed insulin for fasting hyperglycaemia 8.7% (95% CI 1.8%-14.8%) lower SHBG levels than other women with GDM. CONCLUSIONS: Lower SHBG levels were associated especially with early-onset GDM, higher fasting glucose and insulin treatment, whereas androgen excess was associated with higher post-prandial glucose values. Thus, a low SHBG level may reflect the degree of existing insulin resistance, while androgen excess might impair post-prandial insulin secretion.

Increased Oral Care Needs and Third Molar Symptoms in Women with Gestational Diabetes Mellitus: A Finnish Gestational Diabetes Case-Control Study.

(1) Hyperglycemia and oral pathology accelerate each other in diabetes. We evaluated whether gestational diabetes mellitus (GDM) is associated with self-reported increased oral health care needs and oral symptoms, including third molar symptoms, during pregnancy. (2) Pregnant women with (n = 1030) and without GDM (n = 935) were recruited in this multicenter Finnish Gestational Diabetes study in 2009-2012. Of the women with GDM, 196 (19.0%) receiving pharmacological treatment, 797 (77.0%) receiving diet treatment and 233 (23.0%) with recurrent GDM were analyzed separately. Oral health was assessed using structured questionnaires and analyzed by multivariable logistic regression adjusted for background risk factors. (3) Women with GDM were more likely to report a higher need for oral care than controls (31.1% vs. 24.5%; odds ratio (OR) 1.39; 95% confidence interval (CI) 1.14-1.69), particularly women with recurrent GDM (38.1% vs. 24.5%; OR 1.90; 95% CI 1.40-2.58). Women with pharmacologically treated GDM (46.9%) more often had third molar symptoms than controls (36.1%; OR 1.57; 95% CI 1.15-2.15) than women with diet-treated GDM (38.0%; OR 1.47; 95% CI 1.07-2.02). (4) GDM is associated with perceived oral care needs. Third molar symptoms were associated with pharmacologically treated GDM.

Pregnancy outcomes according to the definition of gestational diabetes.

OBJECTIVE: To assess the frequency and perinatal outcomes of gestational diabetes mellitus (GDM) defined by the criteria according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the National Institute for Health and Care Excellence (NICE) diagnostic criteria for GDM. DESIGN: A retrospective cohort study. SETTING: Six secondary and tertiary delivery hospitals in Finland in 2009. POPULATION: Pregnant women (N = 4,033) and their offspring. METHODS: We used data on comprehensive screening of pregnant women with a 2-h 75-g oral glucose tolerance test (OGTT), performed between gestational weeks 24 and 40. OGTT glucose concentrations were used to identify women who fulfilled IADPSG and NICE criteria. While cut-offs according to Finnish national criteria partly overlapped with both criteria, a subgroup of IADPSG- or NICE-positive GDM women remained undiagnosed by Finnish criteria and hence non-treated. They were analysed as subgroups and compared to controls who were negative with all cut-offs. MAIN OUTCOME MEASURES: GDM prevalence, birth weight SD score (BWSDS), large for gestational age (LGA) and caesarean section (CS) rates. RESULTS: Among the 4,033 women screened for GDM, 1,249 (31.0%) and 529 (13.1%) had GDM according to the IADPSG and NICE criteria, respectively. The LGA rate was similar in both groups. Regardless of the diagnostic criteria, women with GDM had a higher risk of induced delivery and CSs than controls. In IADPSG-positive non-treated women, offspring's BWSDS and CS rate were higher than in controls. CONCLUSIONS: GDM prevalence was 2.4-fold higher according to the IADPSG compared with the NICE criteria but the LGA rate did not differ. BWSDS and CS rate were increased already with mild untreated hyperglycaemia.

Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The Finnish Gestational Diabetes Prevention Study (RADIEL): A Randomized Controlled Trial.

OBJECTIVE: To assess whether gestational diabetes mellitus (GDM) can be prevented by a moderate lifestyle intervention in pregnant women who are at high risk for the disease. RESEARCH DESIGN AND METHODS: Two hundred ninety-three women with a history of GDM and/or a prepregnancy BMI of ≥30 kg/m(2) were enrolled in the study at <20 weeks of gestation and were randomly allocated to the intervention group (n = 155) or the control group (n = 138). Each subject in the intervention group received individualized counseling on diet, physical activity, and weight control from trained study nurses, and had one group meeting with a dietitian. The control group received standard antenatal care. The diagnosis of GDM was based on a 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. RESULTS: A total of 269 women were included in the analyses. The incidence of GDM was 13.9% in the intervention group and 21.6% in the control group ([95% CI 0.40-0.98%]; P = 0.044, after adjustment for age, prepregnancy BMI, previous GDM status, and the number of weeks of gestation). Gestational weight gain was lower in the intervention group (-0.58 kg [95% CI -1.12 to -0.04 kg]; adjusted P = 0.037). Women in the intervention group increased their leisure time physical activity more and improved their dietary quality compared with women in the control group. CONCLUSIONS: A moderate individualized lifestyle intervention reduced the incidence of GDM by 39% in high-risk pregnant women. These findings may have major health consequences for both the mother and the child.

Prevention of gestational diabetes through lifestyle intervention: study design and methods of a Finnish randomized controlled multicenter trial (RADIEL).

BACKGROUND: Maternal overweight, obesity and consequently the incidence of gestational diabetes are increasing rapidly worldwide. The objective of the study was to assess the efficacy and cost-effectiveness of a combined diet and physical activity intervention implemented before, during and after pregnancy in a primary health care setting for preventing gestational diabetes, later type 2 diabetes and other metabolic consequences. METHODS: RADIEL is a randomized controlled multi-center intervention trial in women at high risk for diabetes (a previous history of gestational diabetes or prepregnancy BMI ≥30 kg/m2). Participants planning pregnancy or in the first half of pregnancy were parallel-group randomized into an intervention arm which received lifestyle counseling and a control arm which received usual care given at their local antenatal clinics. All participants visited a study nurse every three months before and during pregnancy, and at 6 weeks, 6 and 12 months postpartum. Measurements and laboratory tests were performed on all participants with special focus on dietary and exercise habits and metabolic markers.Of the 728 women [mean age 32.5 years (SD 4.7); median parity 1 (range 0-9)] considered to be eligible for the study 235 were non-pregnant and 493 pregnant [mean gestational age 13 (range 6 to 18) weeks] at the time of enrollment. The proportion of nulliparous women was 29.8% (n = 217). Out of all participants, 79.6% of the non-pregnant and 40.4% of the pregnant women had previous gestational diabetes and 20.4% of the non-pregnant and 59.6% of the pregnant women were recruited because of a prepregnancy BMI ≥30 kg/m2. Mean BMI at first visit was 30.1 kg/m2 (SD 6.2) in the non-pregnant and 32.7 kg/m2 (SD 5.6) in the pregnant group. DISCUSSION: To our knowledge, this is the first randomized lifestyle intervention trial, which includes, besides the pregnancy period, both the prepregnancy and the postpartum period. This study design also provides an opportunity to focus upon the health of the next generation. The study is expected to produce novel information on the optimal timing and setting of interventions and for allocating resources to prevent obesity and diabetes in women of reproductive age.

Perinatal characteristics and bone cancer risk in offspring--a Scandinavian population-based study.

BACKGROUND: We investigated perinatal factors in relation to bone cancer subtypes, osteosarcoma (OS), Ewing Sarcoma (ES) and chondrosarcoma (CS). MATERIALS AND METHODS: All cases in Norway (1970-2009), Sweden (1974-2009) and Denmark (1980-2010)<43 years were included (n=914); 10 controls per case were selected from birth registries (which provided information on pregnancies) matched on birth country, sex and birth year (n=9140). Unconditional logistic regression models including sex and birth year were used to compute relative risk (RR) and 95% confidence intervals (CI). RESULTS: Higher maternal education was associated with a 40% increase in OS risk (95% CI 1-93%). The RR for OS was 3.22 (95% CI 1.37-7.59) comparing offspring of hypertensive mothers with those of mothers with a normotensive pregnancy, and Cesarean section was associated with a 29% risk reduction (95% CI 0-50%). When gestational age, birth weight and birth length were assessed simultaneously, there were no associations with any of the bone tumor subtypes. CONCLUSION: These results provided little evidence of an important role of pregnancy factors in the etiology of bone cancers. Higher maternal education may be associated with factors, possibly early nutrition or other correlates of socioeconomic status, that increase OS risk in offspring. The elevated OS risk associated with gestational hypertension and reduced risk associated with Cesarean section warrant replication.

Hormonal and metabolic characteristics of premenopausal women with a history of preeclamptic pregnancy.

OBJECTIVE: To investigate whether women with a history of preeclampsia have more signs of hyperandrogenism and insulin resistance in the premenopausal period than women with history of normotensive pregnancies. DESIGN: Case-control study. SETTING: University Hospital. SAMPLE: Eighteen women with a history of preeclamptic first pregnancy and 19 women with prior normotensive first pregnancy studied 23-24 years after delivery. METHODS: Diagnosis of metabolic syndrome was based on the International Diabetes Federation (IDF) criteria. Matsuda's whole-body insulin sensitivity index, serum concentrations of follicle-stimulating hormone (FSH), sex hormone-binding globulin, and total and free calculated testosterone were assessed. Polycystic ovary syndrome (PCOS) phenotype was defined using Rotterdam criteria. MAIN OUTCOME MEASURES: Insulin sensitivity, metabolic syndrome and signs of hyperandrogenism. RESULTS: Insulin sensitivity and total and free testosterone were similar in the two groups. However, in women with prior preeclampsia and FSH below the median, calculated free testosterone levels were higher than in women with prior preeclampsia and FSH above the median (median 13.4 range (8.0-22.5) vs. 7.1 (5.1-20.5), p = 0.03). Of the women with previous preeclampsia, 17% (3/18) had metabolic syndrome and 11% (2/18) PCOS, versus 11% (2/19) and 0% of the controls, respectively. CONCLUSIONS: In women with prior preeclampsia, premenopause was not associated with insulin resistance, but signs of hyperandrogenism were present if FSH was within a premenopausal level.

Secular trend in the menopausal age in Finland 1997-2007 and correlation with socioeconomic, reproductive and lifestyle factors.

BACKGROUND AND AIMS: Only few studies have studied secular trend of menopausal age during last decade. The aim of our study is to analyze secular trend of menopausal age and to evaluate the role of socioeconomic, reproductive and lifestyle factors. MATERIAL AND METHODS: National FINRISK Study sample from years 1997 and 2007 was utilized. The sample size for 1997 was 4193 and during 2007 was 4253 women. Covariance analysis included menopausal age as dependent variable and covariates (age, study year, education, occupation, parity, age at first birth, smoking, use of alcohol, physical activity, body mass index, waist circumference and waist-hip ratio) as independent variables. RESULTS: Median of menopausal age was 50 years in 1997 and 51 years in 2007. Differences in menopausal age by covariate were largest in smoking, education and occupation. Difference in mean menopausal age between smokers and non-smokers was larger in 2007 than in 1997 (p<0.001). Lowest educated women had lower average menopausal age during 2007 than higher educated women (p<0.001), but not in 1997. When including sociodemographic, reproductive and lifestyle factors in a model, smoking was significantly related to earlier and physical activity to later menopausal age. Study year was not significant in any model. CONCLUSION: Education, smoking and physical activity have an important role in menopausal age determination when comparing 10-year differences in menopausal age.

Factor V Leiden as risk factor for unexplained stillbirth--a population-based nested case-control study.

INTRODUCTION: Stillbirth is a relatively uncommon pregnancy complication in developed countries yet causing strong emotional burden. Thrombophilia has been associated with stillbirth but population-based studies are few. We assessed selected genetic and acquired parameters for the risk of unexplained stillbirth, including FV Leiden. MATERIALS AND METHODS: We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers and accepted according to strict criteria after checking their medical records. Stillbirth was defined as intrauterine fetal death > or =22weeks of gestation. We excluded stillbirths due to lethal congenital developmental conditions, umbilical cord complications, and infections. We studied 44 cases of unexplained stillbirth and 766 controls. RESULTS: FV Leiden was associated with 3.8-fold (95% CI 1.2-11.6) risk for unexplained stillbirth, 3.9-fold (95% CI 1.1-13.9) risk for unexplained late stillbirth (> or =28weeks of gestation), and 10.8-fold (95% CI 2.1-55.3) risk for unexplained stillbirth with placental lesions. The same figures for singleton pregnancies were 3.1-fold (95% CI 0.9-10.9), 4.3-fold (95% CI 1.2-15.3), and 10.6-fold (95% CI 2.1-54.3). Slightly increased risk associated with blood group O was not statistically significant. We found a trend for increased risk in advanced maternal age and smoking during pregnancy. High pre-pregnancy BMI was not associated with increased risk, nor was low educational level or first pregnancy. CONCLUSIONS: Our population-based study from a country with comprehensive prenatal care confirms the association between FV Leiden and unexplained stillbirth.

Oral inflammatory burden and preterm birth.

BACKGROUND: Earlier studies on the association between oral inflammation and preterm birth limited the inflammation source to periodontal disease. This might have caused an underestimation of the total inflammatory burden from the oral cavity. METHODS: We conducted a postpartum cross-sectional study of 328 Finnish women with singleton births, of whom 77 had preterm births and 251 had full-term births. Gingival bleeding on probing, probing depth, and the presence of dental calculus and mouth ulcers were recorded; the oral inflammatory burden index (OIBI) was constructed based on these clinical findings. A data-driven oral inflammation score (OIS) was also created by stochastically combining the same parameters assessed independently. We used the t, Mann-Whitney, and chi(2) tests for univariate analyses and multivariate logistic regression methods to examine the association between OIBI/OIS and preterm birth. The confounders adjusted for were age, smoking (past, present, and never), diabetes (type 1, type 2, and gestational), primiparity, antimicrobial treatment as a proxy for systemic infection, infertility treatment, and weight gain during pregnancy. RESULTS: OIBI was significantly associated with preterm birth after adjusting for confounding factors (odds ratio [OR], 1.85; 95% confidence interval [CI]: 1.10 to 3.10; P = 0.02). Without adjusting for weight gain, OIS was significantly associated with preterm birth (OR, 1.97; 95% CI: 1.09 to 3.57; P = 0.03); however, this association became non-significant after adding weight gain to the model. CONCLUSION: The combined effects of multiple oral infections were significantly associated with preterm birth.

Study of p53 gene mutations and placental expression in recurrent miscarriage cases.

This study aimed to investigate the role of p53 in early human development by screening patients with recurrent miscarriages (RM) for mutations in the p53 gene and by studying p53 expression in placental tissue. A total of 46 women with RM and 191 control women were included in the study. A sample was also obtained from 40 male partners of RM patients. The samples were screened for p53 sequence variations using denaturing high-performance liquid chromatography, sequencing and allele-specific polymerase chain reaction. Placental tissue was available from 19 miscarriages. p53 expression in placental tissue was studied by immunohistochemical staining. The C11992A polymorphism in p53 was found to be associated with RM in Finnish patients. The C/A or A/A genotype was detected in 32.6% of the women with RM and in 18.9% of the controls (P = 0.0414, odds ratio 2.083, confidence interval 1.018-4.259). The results suggest that women carrying the C/A or A/A genotype have a two-fold higher risk for RM than women with the C/C genotype. Further studies are, however, necessary to define whether the intronic polymorphism has functional consequences. The immunohistochemical staining of placental tissues revealed no abnormal p53 expression patterns in the samples studied.

Central sympatholytic therapy has anti-inflammatory properties in hypertensive postmenopausal women.

OBJECTIVE: Postmenopausal phase expresses many unfavourable physiological changes that lead to increased risk for cardiovascular disease. We compared the effect of two sympatholytic antihypertensive drug treatments, the centrally acting imidazoline receptor-1 agonist moxonidine and peripherally acting beta-blocking agent atenolol on sensitive inflammatory markers in overweight postmenopausal women with diastolic hypertension. METHODS: This was a multicentre, multinational double-blinded, prospective study comparing moxonidine (0.3 mg twice daily) with atenolol (50 mg once daily) in 87 hypertensive postmenopausal overweight women who were not taking hormone therapy. Sensitive C-reactive protein, IL-6, TNFalpha, TNFalpha-RII and adiponectin were determined in the beginning of the study and after 8 weeks of medical treatment. RESULTS: TNFalpha increased in atenolol and decreased in moxonidine group (P = 0.0004 between the groups). Adiponectin concentration decreased dramatically in atenonol but did not change in moxonidine treatment group (P < 0.0001 between the groups). In logistic regression analysis only treatment group showed an independent effect on changes in adiponectin and TNFalpha concentrations. CONCLUSION: We believe that centrally acting sympatholytic agent moxonidine is beneficial in the treatment of postmenopausal women with hypertension by reducing inflammatory cytokine TNFalpha without changing protective adiponectin level.

Management of cardiovascular risk in the peri-menopausal woman: a consensus statement of European cardiologists and gynaecologists.

Cardiovascular risk is poorly managed in women, especially during the menopausal transition when susceptibility to cardiovascular events increases. Clear gender differences exist in the epidemiology, symptoms, diagnosis, progression, prognosis, and management of cardiovascular risk. Key risk factors that need to be controlled in the peri-menopausal woman are hypertension, dyslipidaemia, obesity, and other components of the metabolic syndrome, with the avoidance and careful control of diabetes. Hypertension is a particularly powerful risk factor and lowering of blood pressure is pivotal. Hormone replacement therapy is acknowledged as the gold standard for the alleviation of the distressing vasomotor symptoms of the menopause, but the findings of the Women's Health Initiative (WHI) study generated concern for the detrimental effect on cardiovascular events. Thus, hormone replacement therapy cannot be recommended for the prevention of cardiovascular disease. Whether the findings of WHI in older post-menopausal women can be applied to younger peri-menopausal women is unknown. It is increasingly recognized that hormone therapy is inappropriate for older post-menopausal women no longer displaying menopausal symptoms. Both gynaecologists and cardiovascular physicians have an important role to play in identifying peri-menopausal women at risk of cardiovascular morbidity and mortality and should work as a team to identify and manage risk factors such as hypertension.

Reproductive history and carotid intima-media thickness.

BACKGROUND: Intima-media thickness (IMT) of the carotid arteries is a valid measure of preclinical atherosclerosis which may predict cardiovascular outcomes. Metabolic and hormonal changes associated with the reproductive history of women may contribute to the development of cardiovascular disease (CVD). METHODS: In a population-based cross-sectional study comprising 746 Finnish women, aged 45-74 years, associations of reproductive history (assessed by questionnaire) and measures of subclinical atherosclerosis (by ultrasonographic detection) were studied. Statistical methods included linear and logistic regression models. RESULTS: Mean carotid IMT was positively associated with parity, but after adjustment for age its statistical significance disappeared. Women with a history of stillbirth tended to have higher IMT than other women. History of hysterectomy was an independent determinant of carotid plaque in models with age, blood pressure, fasting blood glucose and cholesterol, body mass index (BMI), education and smoking (odds ratio (OR): 0.32; 95% confidence interval (CI): 0.11-0.96). But when oophorectomy (yes/no) was included in the model, this association lost its statistical significance (adjusted OR: 0.36; 95% CI: 0.11-1.22). A history of stillbirth was associated with an increased age-adjusted risk of plaque (OR=3.43; 95% CI: 1.07-11.05), but in the fully adjusted model it lost its statistical significance (OR=3.61; 95% CI: 0.86-15.23). CONCLUSION: Stillbirth was associated with increased risk of atherosclerotic plaque. Atherosclerosis is a lifelong process to which stillbirth is related. However, due to the cross-sectional design of this study, the causality of this association remains unclear.

Pregnancy-related factors and the risk of isolated systolic hypertension.

BACKGROUND: Isolated systolic hypertension (ISH) is known to be a strong predictor of cerebrovascular and cardiac events, especially in women. Metabolic and hormonal changes associated with reproductive history may contribute to the development of cardiovascular diseases. The aim of this study was to identify associations between pregnancy-related factors and ISH. METHODS: A cross-sectional study based on a random sample of 3937 Finnish women aged 30-99 was carried out. Associations between pregnancy-related factors and ISH were analyzed using multivariate analyses. RESULTS: Of 3470 subjects, 26% had ISH. Younger age at first delivery predicted a higher risk of ISH (odds ratio after adjustment for age, education, smoking, height and weight = 1.31, 95% CI 1.07-1.61). Age at first and last delivery was significantly associated with age, education, marital status and use at any time of hormone replacement therapy (HRT); age at first delivery was also associated with toxemia in any pregnancy, weight and body mass index (BMI). In the univariate analyses, ISH was significantly associated with age, height, weight, BMI, education, marital status, oral contraceptive pills use at any time and HRT use at any time. CONCLUSION: This population-based study showed that early age at first delivery increased the risk of ISH, which may in turn increase cerebrovascular and cardiac events after menopause. Age at first delivery is heavily dependent on education, which may be linked to the risk of developing of cardiovascular disease throughout adulthood. The other plausible mechanism may be adiposity due to pregnancy.

Impaired vascular dilatation in women with a history of pre-eclampsia.

OBJECTIVE: The mechanisms underlying increased cardiovascular risk among women with a history of pre-eclampsia remain unclear. Impaired endothelial function has been observed in both pre-eclampsia and atherosclerosis, and provides a plausible link between the two conditions. We studied endothelial function and arterial compliance in non-pregnant, previously pre-eclamptic women. DESIGN: A study of 30 women with a history of pre-eclampsia and 21 women with a previous normotensive, uncomplicated pregnancy was carried out. METHODS: Changes in brachial artery blood flow, induced by intra-arterial infusions of an endothelium-independent (sodium nitroprusside) and an endothelium-dependent (acetylcholine) vasodilator, were measured by venous occlusion plethysmography. Arterial stiffness was assessed by pulse-wave analysis. RESULTS: Vasodilatation was impaired in women with previous pre-eclampsia; at low and high concentrations of endothelium-independent (P = 0.004 and P = 0.057, respectively) and endothelium-dependent (P = 0.045 and P = 0.02) vasodilators, respectively. There was no difference in arterial stiffness between the groups (P = 0.45). In multiple regression analyses both endothelium-independent and endothelium-dependent vasodilatations were independently associated with a history of pre-eclampsia and parity. There was no correlation with blood pressure, body mass index (BMI), smoking or age. CONCLUSIONS: The finding of impaired vascular dilatation several years after a pre-eclamptic pregnancy could contribute to the higher risk of cardiovascular disease in these women.

Insulin resistance and sympathetic overactivity in women.

Insulin sensitivity decreases for the first time in females at the time of menarche. A much more profound decrease in insulin sensitivity is observed at the end of pregnancy. This physiological insulin resistance is not accompanied by a rise in overall sympathetic activity as reflected in plasma noradrenaline levels, but there is evidence of moderate sympathetic overactivity in muscle and the heart. Pre-eclampsia is characterized by increased insulin resistance, sympathetic overactivity and a particular lipid profile. Thus it is the first manifestation of metabolic syndrome. Women with a history of pre-eclampsia have persistent insulin resistance after pregnancy associated with increased sympathetic activity of the cardiovascular system, and coronary artery disease later in life. Aging is accompanied by a greater increase in sympathetic traffic in women than in men, and inflammation (measured via C-reactive protein) seems to be more strongly related to metabolic syndrome in women than in men. The clinical relevance of these observations remains to be shown. As the key factors of metabolic syndrome, such as insulin resistance and sympathetic overactivity, are closely inter-related, treatment should be aimed at cutting the vicious circle at many points: lifestyle modification (diet, increasing exercise) as a basis of therapy, use of insulin sensitizers (e.g. metformin) to decrease insulin resistance, central sympatholytics (e.g. moxonidine), and AT-receptor blockers or angiotensin-converting enzyme (ACE) inhibitors to overcome sympathetic overactivity, hypertension and inflammation.