Cardiovascular disease in women: challenge of the middle years

Although heart disease remains the primary cause of death among women of all races and ethnic groups in the United States, many women are still unaware of these facts. Health care providers may also not be aware. Lack of awareness among providers may limit or delay the education and intervention to prevent future cardiovascular disease for women in their middle years. In addition, the metabolic syndrome may develop in these years of a woman's life because of today's lifestyle issues and the reported increases in obesity. The appearance of the metabolic syndrome already places a woman in a precarious position for the development of risk factors such as frank hypertension and diabetes. The metabolic syndrome presents an opportunity for providers to enhance surveillance and to educate their patients in the prevention of future events. Complications of pregnancy may also foreshadow the development of hypertension as well as type 2 diabetes mellitus later in life. Some investigators consider pregnancy as an excursion into the metabolic syndrome and as a failed "stress test," if complications such as gestational diabetes or preeclampsia develop. The emergence of those complications may give a more recognized prediction of future cardiovascular events. All primary care providers, including obstetricians and gynecologists, need to be alert as to the follow-up of these women, and incorporate continued vigilance within the standard office visit including waist measurement, annual lipid measurement, glucose monitoring, blood pressure assessment, and intense education and referrals when needed.     

Statins and the primary prevention of cardiovascular events

Cardiovascular disease remains the leading cause of death in both men and women in the United States. Treating elevated low-density lipoprotein (LDL) cholesterol has been shown to be very effective in reducing the rate of coronary heart disease (CHD) in primary prevention trials; however, the data are not as robust for treating individuals categorized at either lower risk for CHD or with below-average LDL cholesterol levels. The next frontier for investigation will include strategies to determine who in these lower risk categories should be treated with statins. The growing epidemics of obesity, diabetes, and metabolic syndrome also loom as major problems that need to be incorporated into any strategy that focuses on the prevention of cardiovascular disease. In individuals with multiple cardiovascular risk factors, combination therapies tailored to address each individual’s risk profile need to be considered to best decrease the likelihood of their first coronary event.     

Pregnancy to postpartum transition of serum metabolites in women with gestational diabetes

ContextGestational diabetes is commonly linked to development of type 2 diabetes mellitus (T2DM). There is a need to characterize metabolic changes associated with gestational diabetes in order to find novel biomarkers for T2DM.ObjectiveTo find potential pathophysiological mechanisms and markers for progression from gestational diabetes mellitus to T2DM by studying the metabolic transition from pregnancy to postpartum.DesignThe metabolic transition profile from pregnancy to postpartum was characterized in 56 women by mass spectrometry-based metabolomics; 11 women had gestational diabetes mellitus, 24 had normal glucose tolerance, and 21 were normoglycaemic but at increased risk for gestational diabetes mellitus. Fasting serum samples collected during trimester 3 (gestational week 32 ± 0.6) and postpartum (10.5 ± 0.4 months) were compared in diagnosis-specific multivariate models (orthogonal partial least squares analysis). Clinical measurements (e.g., insulin, glucose, lipid levels) were compared and models of insulin sensitivity and resistance were calculated for the same time period.ResultsWomen with gestational diabetes had significantly increased postpartum levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, and their circulating lipids did not return to normal levels after pregnancy. The increase in BCAAs occurred postpartum since the BCAAs did not differ during pregnancy, as compared to normoglycemic women.ConclusionsPostpartum levels of specific BCAAs, notably valine, are related to gestational diabetes during pregnancy.     

Pregnancy in women with type 2 diabetes: an uncertain prognosis

The increasing prevalence of type 2 diabetes in women of childbearing age leads to an increasing number of pregnant women with type 2 diabetes. Pregnancy complicated by type 2 diabetes is a high-risk pregnancy, associated with birth defects and high perinatal mortality to the same extent as in type 1 diabetes. Until now, most attention was directed toward women with type 1 diabetes. Recent data stresses the urgent need to develop better screening and efficient care strategies in women with type 2 diabetes, who also display many risk factors for adverse fetal outcome. Family physicians, diabetologists and gynaecologists must be aware of this growing concern. Improvement of pregnancy planning, adequate metabolic control from conception to delivery and a multi-disciplinary team approach to care should improve fetal and maternal outcomes. Furthermore, diabetes screening in high-risk women prior to pregnancy is warranted.     

Iron deficiency in pregnancy: effects on the newborn

Iron deficiency during pregnancy affects a significant portion of women in countries with low economic wealth and is not uncommon in pregnant women in industrialized countries. Inadequate intake of iron related to diets poor in bioavailable iron is often responsible for iron deficiency before pregnancy, and metabolic adjustments (such as mobilization of iron stores and increased absorption) are insufficient to meet increasing needs during pregnancy. The effects of iron deficiency on the fetus are still controversial. Numerous measures, including the evaluation of erythrocyte ferritin, favor the hypothesis that the level of iron stores in newborns is related to maternal iron status and that the materno-fetal unit is dependent on exogenous iron, which is necessary to prevent iron deficiency in both mothers and infants. In industrialized countries, iron supplements should be prescribed for pregnant women in the third trimester, when the need for iron is prominent. In developing countries, supplementation should be initiated as soon as possible after conception because of the high prevalence of iron deficiency at the onset of pregnancy. The results of studies comparing intermittent with daily supplementation remain controversial.     

The experiences of pregnancy in women with SSA/Ro52 autoantibodies

Objective: Congenital heart block may develop in the foetus during pregnancy in SSA/Ro52 autoantibody‐positive women. The aim of this study was to investigate how women with SSA/Ro52 autoantibodies experience their pregnancy in terms of the risk of developing foetal heart block, and in undergoing serial ultrasound Doppler echocardiography to detect early signs of congenital heart block. Methods: Data were collected through individual semi‐structured interviews with SSA/Ro52‐positive women post‐pregnancy (n = 14). The interviews were audio‐taped, transcribed verbatim and analysed according to qualitative content analysis. Results: Three categories emerged from the responses: information, emotional response and support. The information received prior to and during early pregnancy was focused on the need for attending a specialized antenatal clinic, and information on the risk for congenital heart block was scarce or missing. During gestational weeks 18–24, when the ultrasound/Doppler examinations were performed, all women described increased stress. However, the interaction with the caregivers made the women feel more safe and secure. Several women also said that they did not emotionally acknowledge the pregnancy until after gestational week 24. None had been offered psychological support. Conclusion: There is a need for structured information and organized programmes for the surveillance of women who are SSA/Ro52 positive during their pregnancy. Further, offering psychological support to the women and their families to manage the stress and to facilitate the early attachment to the child should be considered. Copyright © 2010 John Wiley & Sons, Ltd.     

Gonadotropins as pharmacological agents in assisted reproductive technology and polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy associated with subfertility/infertility and pregnancy complications. Most PCOS women opt for assisted reproductive technologies (ART) for successful conception; however, optimization of the relative doses of the gonadotropins [follicle-stimulating hormone (FSH), luteinizing hormone (LH)/human chorionic gonadotropin (hCG)] for appropriate steroidogenesis, without causing ovarian hyperstimulatory syndrome (OHSS), is challenging. Embryonic factors probably do not contribute to pregnancy loss in PCOS women, albeit hormonal imbalance impairs the metabolic microenvironment critical for oocyte maturation and endometrial receptivity. Certain clinical studies have confirmed the role of metabolic corrections in increasing the rate of pregnancy in PCOS women. This review focuses on the impact of untimely high LHCGR and/or LH levels on oocyte/embryo quality, pregnancy outcomes in ART, and exploring LHCGR as a potential drug target in PCOS women.     

Gestational diabetes: A link between OGTT,maternal-fetal outcomes and maternal glucose tolerance after childbirth

Background and aimThe relationship among distribution of pathological values at the Oral Glucose Tolerance Test (OGTT), metabolic risk factors and pregnancy outcomes in women with Gestational Diabetes (GDM), has not been clearly identified. We retrospectively compared metabolic and therapeutic parameters, maternal–fetal outcomes and post-partum OGTTs, with respect to the number and distribution of altered values of diagnostic OGTT in pregnancy. Secondly, we assessed whether insulin therapy predictive factors were identifiable.Methods and resultsThis analysis included 602 pregnant women with GDM, followed in Diabetes and Pregnancy Unit of Perugia Hospital from diagnosis to childbirth. All women were diagnosed diabetic upon 75g OGTT, according IADPSG criteria. Women were divided into 3 groups, respect to distribution of diagnostic blood glucose (BG) values at OGTT: Group 1: only fasting BG (OGTT0h); Group 2: 1 and/or 2h (OGTT1-2h); Group 3: both fasting and 1 h and/or 2h (OGTT0+1–2h) BG.Pregnant women with fasting hyperglycemia at OGTT (Groups 1 and 3) had similar metabolic characteristics (weight, prevalence of obesity, gestational weight gain, HbA1c), a greater need for insulin therapy, and a higher risk of impaired glucose tolerance persistence after childbirth, as compared to Group 2. No significant differences were observed in terms of maternal and neonatal outcomes (p > 0.05), except for a greater prevalence of caesarean sections in Group 3.ConclusionThe metabolic characteristics of GDM women are mirrored by OGTT values at diagnosis, but are not associated with adverse pregnancy outcomes. Intensive management and a tailored treatment of GDM improve maternal-neonatal outcomes, regardless of diagnostic values distribution and pre-gestational metabolic characteristics.     

Current controversies in the mechanisms and treatment of gestational diabetes

Gestational diabetes mellitus (GDM) is a heterogeneous entity, including carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Insulin resistance and a-cell dysfunction are thought to be major determinants of its development. Its pathomechanism in many ways resembles that of type 2 diabetes. There is an evolving body of evidence from the last decade presenting similarities between gestational diabetes and the metabolic (insulin resistance) syndrome. These new observations suggest that GDM might be an early manifestation of the metabolic syndrome. The desired treatment target of GDM is normoglycemia. It can be reached by dietary treatment; however, if it fails, maternal glycemic monitoring or combined fetalmaternal monitoring, or even insulin (if required) can help reach it. Multiple daily insulin regimens are becoming more widely accepted for the treatment of GDM. Insulin analogues, however, need some more evidence to support their usefulness and safety during pregnancy. The screening for GDM, the reclassification, regular care, and follow-up of these women after pregnancy are of the utmost importance to delay or prevent not only type 2 diabetes but cardiovascular complications as well.     

Shared constitutional risks for maternal vascular-related pregnancy complications and future cardiovascular disease

Maternal predisposition to vascular and metabolic disease may underlie both vascular-related pregnancy complications, such as preeclampsia and intrauterine growth restriction, as well as future maternal cardiovascular disease. We aimed to substantiate this hypothesis with biochemical and anthropometric evidence by conducting an intergenerational case-control study in a Dutch isolated population including 106 women after preeclampsia or intrauterine growth restriction (median follow-up: 7.1 years) and their fathers (n=43) and mothers (n=64), as well as 106 control subjects after uncomplicated pregnancies with their fathers (n=51) and mothers (n=68). Cardiovascular risk profiles were assessed, including fasting glucose, lipids, anthropometrics, blood pressure, intima-media thickness, and metabolic syndrome. We found significantly higher fasting glucose levels, larger waist circumferences, and a 5-fold increased prevalence of hypertension in women with a history of preeclampsia as compared with control subjects (P<0.001). Likewise, their parents had higher glucose levels than control parents (P<0.05). Their mothers had larger waist circumferences and higher blood pressures (P<0.05). Also, women after pregnancies complicated by intrauterine growth restriction had higher glucose levels and increased prevalence of hypertension (P<0.01). Their fathers showed higher glucose levels as well (P<0.05). Mean carotid intima-media thickness was increased in a subset of women after preeclampsia diagnosed with chronic hypertension as compared with those without hypertension (P<0.01). Metabolic syndrome was more prevalent both in women with a history of preeclampsia and their mothers (P<0.05). We demonstrated intergenerational similarities in cardiovascular risk profiles between women after preeclampsia or intrauterine growth restriction and their parents. These findings suggest shared constitutional risks for vascular-related pregnancy complications and future cardiovascular disease.     

Choosing the best contraceptive method for the adult with congenital heart disease

As women with congenital heart disease (CHD) approach childbearing age, issues such as pregnancy and contraception need to be addressed. Women with CHD represent a heterogeneous population. While some have simple cardiac lesions and thus have contraceptive risks that are no different from those of the general population, others have complex, multisystem disease such that incorrect contraception advice can be associated with serious health consequences. Choosing a contraceptive requires consideration of the risk of pregnancy; the available contraception options; their risks, failure rates, and benefits; and the preferences of the woman. This review focuses on contraceptive selection in women with CHD.     

Gender disparity in outcomes of care and management for diabetes and the metabolic syndrome

Although diabetes lies among the major risk factors for cardiovascular disease (CVD) in both men and women, current evidence suggests that it has a much stronger effect on the risk of coronary heart disease (CHD) in women than in men. Moreover, diabetic women have not experienced the decline in CHD mortality observed in diabetic men and individuals without diabetes over the past three decades. Apart from a more pronounced direct effect of diabetes on the vascular wall, this greater impact of diabetes on CHD risk in women could be associated with a heavier burden of other traditional cardiovascular risk factors within the context of the metabolic syndrome, a stronger effect of the metabolic syndrome on CVD, and a less aggressive management of the various risk factors in diabetic women compared with men. This article discusses the recent evidence on the gender differences in the outcomes of CVD and the management of risk factors associated with diabetes and the metabolic syndrome, highlighting the need for better treatment strategies of diabetes and the other components of the metabolic syndrome in diabetic women.     

Is a single definition of the metabolic syndrome appropriate?—A comparative study of the USA and Asia

The metabolic syndrome has been identified as an increasingly important precursor to cardiovascular diseases in many Asian populations. Our objective was to compare the contribution of component risk factors to the diagnosis of the metabolic syndrome, as defined by the Third report of the National Cholesterol Education Program Expert Panel Adult Treatment Panel (NCEP-ATPIII), in the US and selected Asian populations. Nationally representative survey data from Hong Kong, Taiwan, Thailand and the US were used. Analyses were restricted to men and women aged > or = 35 years. The age-standardized prevalence of the NCEP-ATPIII defined metabolic syndrome was highest in the US (31% in men, 35% in women), and lowest in Taiwan (11% in men, 12% in women). The component risk factors that defined the presence of the metabolic syndrome varied between countries. As expected, abnormal waist circumference was considerably more prevalent among individuals with the metabolic syndrome in the US (72% in men, 94% in women) compared with their Asian counterparts, but substantial variation was also observed between the Asian populations (13-22% in men, 38-63% in women). Furthermore, the relative contribution of other risk factors to the metabolic syndrome was also substantially different between countries. The NCEP-ATPIII definition identifies a heterogeneous group of individuals with the metabolic syndrome in different populations.     

Use of sapropterin dihydrochloride in maternal phenylketonuria. A European experience of eight cases

Sapropterin dihydrochloride (SD) is the first drug treatment for phenylketonuria (PKU), but due to the lack of data, its use in maternal PKU must be undertaken with caution as noted in the FDA and EMEA labels. We collected data from eight pregnancies in PKU women treated with SD and we analysed the phenotypes of these patients, their tetrahydrobiopterin (BH4) responsiveness, the indications for SD treatment, the efficacy (metabolic control, phenylalanine (Phe) tolerance and offspring outcome) and the safety data. Results showed that in the seven patients known to be responsive to BH4, the use of SD during pregnancy was efficient in terms of metabolic control and Phe tolerance. The indications for giving SD included the failure of the low-Phe diet (n?=?3), the fact that some of these women had never experienced the low Phe diet (n?=?2), one unexpected pregnancy in a woman currently on SD and one pregnancy where the foetus was known to have PKU. The offspring of these seven pregnancies were all normal babies with normal birth measurements and outcomes. No side effect related to SD was observed in these seven cases. In the eighth case, SD was prescribed as a rescue treatment without previous knowledge of the BH4 responsiveness to a woman who was already 8 weeks pregnant without diet. The birth occurred at 33 weeks of gestational age with Potter syndrome (probably related to the absence of metabolic control during the first trimester) and the baby died in the first hours of life. In conclusion, the data presented here provides the first evidence that treatment with pharmacological doses of SD appears to be efficient and safe in women with PKU during pregnancy. Its use should, however, be restricted to those women previously identified to be clear responders to BH4.     

A series of pregnancies in women with inherited metabolic disease

In this case series we report 12 pregnancies, in women treated at four centres, illustrating some of the issues that may be encountered during pregnancy by women with inherited metabolic disease. We discuss how specific pregnancy, labour and delivery issues for mothers with methylmalonic acidemia, homocystinuria, propionic acidemia, glutaric acidemia type 1, ornithine transcarbamylase (OTC) deficiency and 3-hydroxy-3-methylglutaric(HMG)-CoA lyase deficiency were managed and the outcome for the mother and child in each case. Eight of the 12 pregnancies resulted in the successful delivery of a liveborn infant. Several women experienced decompensation of their condition during pregnancy or the post-partum period. There was one maternal death in a women with 3-hydroxy-3-methylglutaric(HMG)-CoA lyase deficiency. Pre-pregnancy counselling and co-management of high risk medical patients by obstetricians and specialist physicians with an understanding of the relationship between pregnancy and inherited metabolic disease is essential.     

The Resource Mothers Study of Maternal Phenylketonuria: Preliminary findings

Women with phenylketonuria (PKU) must follow a strict low-phenylalanine diet during pregnancy in order to protect the fetus from the deleterious effects of high maternal blood phenylalanine. The Resource Mothers Study of Maternal PKU was undertaken to determine whether a home visitation programme was effective in helping women with PKU attain blood phenylalanine control earlier during pregnancy. Resource Mothers were trained to provide social support and practical assistance to women with PKU during pregnancy. Eight metabolic clinics in the United States participated in the study. Women with PKU who were planning pregnancy or already pregnant were enrolled in the study and were treated with a low-phenylalanine diet aimed at controlling blood phenylalanine to 120-360 micromol/L. They were randomly assigned to receive the services of a Resource Mother (RM group) or to a control group. Fifty women were enrolled, and accounted for 44 pregnancies which resulted in 28 live births, and 6 spontaneous abortions. Ten women are currently pregnant and another 6 have not become pregnant. Fifty-six percent of enrolled women began the diet prior to becoming pregnant. Fifty-three percent of women in the Resource Mother group were in metabolic control by 10 weeks gestation as compared to 39% in the control group. In addition, women who began diet after pregnancy and had a Resource Mother attained metabolic control earlier (mean gestational age of 22.4 weeks in the RM group vs 29.8 weeks in the control group). There was no difference in birth measurement z -scores of offspring born to women in the RM group compared to controls. All but 4 women rated themselves as feeling worse about the diet at the end of pregnancy than at the beginning, and few women in either group remained on diet after delivery.     

Is Pregnancy the Time to Change Alcohol Consumption Habits in France?

Background:  Although it is well known that France has a cultural history of alcohol use, no recent French data on alcohol consumption during pregnancy in a large sample are available.
Methods:  To determine the alcohol consumption patterns among pregnant women in France, we analyzed data from a 1-year multicenter self-survey. Sociodemographic profile, obstetrical history, neonatal data, and a self-report for assessing drinking patterns during pregnancy including AUDIT were recorded from women who delivered recently. Cases of fetal alcohol syndrome (FAS) were also reported.
Results:  A total of 837 pregnant women have described all parameters. The mean age at delivery of our sample was 29.7 years (SD = 4.8 years). A total of 52.2% of women indicated that they had consumed alcohol at least once during their pregnancy, and among abstainers 54.5% had a positive AUDIT score. Of the pregnant women who consumed alcohol, 13.7% reported at least one binge drinking episode (5 or more drinks on 1 occasion) during pregnancy. Binge drinking is significantly more frequent than regular alcohol consumption (at least 1 drink more than 1 time per week) during pregnancy. A prevalence rate of FAS of 1.8 per 1,000 live births was observed.
Conclusions:  There is a large population of women who still drink alcohol during pregnancy, particularly in binge drinking episodes. This underlines the need to clearly inform women of childbearing age about the dangers of alcohol during pregnancy as related to all types of consumption. Moreover, acting to prevent alcohol consumption prior to pregnancy may also greatly influence prenatal drinking.     

Helping young mothers with HIV

Adolescent pregnancy rates are dropping overall, but a significant number of adolescent pregnancies occur in women infected with HIV. Pregnancy and parenting issues are intensified and more complex in this group than in the uninfected. Newly diagnosed young women with HIV face important life decisions but they are poorly prepared to address them. The significance of pregnancy is so potent in impoverished communities that many women want to become pregnant at a very young age. A study of HIV-infected women with substance abuse histories shows that they identify childbearing with independence and hope. Young mothers and their children benefit from services that help them build on their strengths and encourage skills development. They need vocational support, health care, case management, and counseling. Providers need to be careful, however, to remain professional and not become overly involved.     

Impact of thyroxine-binding globulin on thyroid hormone economy during pregnancy.

Pregnancy-associated changes in thyroid hormone economy are well-established and are of significant clinical relevance to women with established hypothyroidism because they usually result in increased thyroxine dose requirements by these women. Studies suggest that elevations in serum thyroxine-binding globulin (TBG) have the most influence on this increased need for thyroxine, although the exact contributions by TBG rises and by other mechanisms is as yet unclear. We report the case of a 42-year-old woman, with both established primary hypothyroidism and TBG deficiency, who we have now managed through two full-term pregnancies. The patient was noted to have a baseline TBG that was approximately 30% of the average baseline level reported for non-TBG-deficient individuals. Her TBG levels were induced by pregnancy, although the absolute increase of 1.0 mg/dL was only half the increase usually associated with pregnancy. Despite the patient's low baseline TBG level and her blunted pregnancy-associated TBG induction, her absolute and relative pregnancy-associated increases in thyroxine replacement dosage mirrored those found in non-TBG-deficient, hypothyroid women. Thus, our limited study suggests that an increase in TBG concentration is not the key determinant for the increase in thyroxine requirement in pregnancy.     

Partner notification of pregnant women infected with syphilis in Nairobi, Kenya

We examined partner notification among syphilitic pregnant women in Nairobi. At delivery, 377 women were found to be rapid plasma reagin (RPR) reactive. Data were available for 94% of the partners of women who were tested during pregnancy; over 67% of the partners had received syphilis treatment while 23% had not sought treatment mainly because they felt healthy. Six per cent of the women had not informed their partners as they feared blame and/or violence. Adverse pregnancy outcome was related to lack of partner treatment during pregnancy (7% versus 19%, odds ratio (OR) 3.0, 95% confidence interval (CI) 0.9-10.0). Our data suggest that messages focusing on the health of the unborn child have a positive effect on partner notification and innovative and locally adapted strategies for partner notification need more attention.