Mathew Sermer

Risk and Predictors for Pregnancy-Related Complications in Women With Heart Disease

BACKGROUND The physiological changes of pregnancy can result in cardiovascular complications in the mother, which in turn may have fetal implications. Prior studies have focused on specific cardiac lesions or identified univariate predictors. There is a need to refine the risk stratification of women with heart disease so they can receive appropriate obstetrical counseling and care. METHODS AND RESULTS We examined the outcomes of 221 women with heart disease who underwent 276 pregnancies and received their obstetrical care at three Toronto hospitals from 1986 through 1994. Those who underwent therapeutic abortions were excluded. Among the study participants, there were 24 miscarriages and 252 completed pregnancies (pregnancies not ending in miscarriage). Maternal heart failure, arrhythmia, or stroke occurred in 45 completed pregnancies (18%). There were no maternal deaths. Poor maternal functional class or cyanosis, myocardial dysfunction, left heart obstruction, prior arrhythmia, and prior cardiac events were predictive of maternal cardiac complications. These predictors were incorporated into a point score that can be used to estimate the probability of a cardiac complication in the mother. The rate of cardiac complications for a patient with 0, 1, and >1 of the above factors was 3%, 30%, and 66%, respectively. Neonatal complications occurred in 42 completed pregnancies (17%). Neonatal events included death (2), respiratory distress syndrome (16), intraventricular hemorrhage (2), premature birth (35), and small-for-gestational-age birth weight (14). Poor maternal functional class or cyanosis was predictive of neonatal events. CONCLUSIONS Despite low maternal and neonatal mortality, pregnancy in women with heart disease is associated with significant cardiac and neonatal morbidity. The probability of maternal cardiac or neonatal events can be predicted from baseline characteristics of the mother.

Glucose Intolerance in Pregnancy and Future Risk of Pre-diabetes or Diabetes

OBJECTIVE—The purpose of this study was to test the hypothesis that any degree of abnormal glucose homeostasis detected on antepartum screening for gestational diabetes mellitus (GDM) should be associated with an increased risk of postpartum pre-diabetes or diabetes. RESEARCH DESIGN AND METHODS—In this prospective cohort study, 487 women underwent 1) antepartum GDM screening by a glucose challenge test (GCT) and a diagnostic oral glucose tolerance test (OGTT) and 2) postpartum metabolic characterization by OGTT at 3 months after delivery. Four baseline glucose tolerance groups were defined on the basis of the antepartum GCT/OGTT: 1) GDM (n = 137); 2) gestational impaired glucose tolerance (GIGT) (n = 91); 3) abnormal GCT with normal glucose tolerance on an OGTT (abnormal GCT NGT) (n = 166); and 4) normal GCT with NGT on an OGTT (normal GCT NGT) (n = 93). RESULTS—The prevalence of postpartum glucose intolerance (pre-diabetes or diabetes) increased across the groups from normal GCT NGT (3.2%) to abnormal GCT NGT (10.2%) to GIGT (16.5%) to GDM (32.8%) (Ptrend < 0.0001). On logistic regression analysis, all three categories of abnormal glucose homeostasis in pregnancy independently predicted postpartum glucose intolerance: abnormal GCT NGT odds ratio (OR) 3.6 (95% CI 1.01–12.9); GIGT OR 5.7 (1.6–21.1); and GDM OR 14.3 (4.2–49.1). Furthermore, both in pregnancy and at 3 months postpartum, insulin sensitivity (ISOGTT) and pancreatic β-cell function (insulinogenic index/homeostasis model assessment of insulin resistance) progressively decreased across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all Ptrend < 0.0001). CONCLUSIONS—Any degree of abnormal glucose homeostasis in pregnancy independently predicts an increased risk of glucose intolerance postpartum.

Adiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications.

Aims/hypothesisGestational diabetes mellitus (GDM) identifies a population of young women at high risk of developing type 2 diabetes and thus provides an excellent model for studying early events in the natural history of this disease. Adiponectin, a novel adipocyte-derived protein with insulin-sensitising properties, has been proposed as a factor linking insulin resistance and beta cell dysfunction in the pathogenesis of type 2 diabetes. We conducted the current investigation to determine whether adiponectin is associated with beta cell dysfunction in GDM.MethodsWe studied 180 women undergoing OGTT in late pregnancy. Based on the OGTT results, participants were stratified into three groups: (1) NGT (n=93); (2) IGT (n=39); and (3) GDM (n=48). First-phase insulin secretion was determined using a validated index previously proposed by Stumvoll. Insulin sensitivity was assessed using the validated OGTT insulin sensitivity index of Matsuda and DeFronzo (ISOGTT).ResultsTo evaluate beta cell function in relation to ambient insulin sensitivity, an insulin secretion-sensitivity index (ISSI) was derived from the product of the Stumvoll index and the ISOGTT, based on the existence of the predicted hyperbolic relationship between these two measures. Mean ISSI was highest in the NGT group (6,731), followed by that in the IGT group (4,976) and then that in the GDM group (3,300) (overall p<0.0001), compatible with the notion of declining beta cell function across these glucose tolerance groups. Importantly, adiponectin was significantly correlated with ISSI (r=0.34, p<0.0001), with a stepwise increase in mean ISSI observed per tertile of adiponectin concentration (trend p<0.0001). In multivariate linear regression analysis, ISSI was positively correlated with adiponectin and negatively correlated with GDM, IGT and C-reactive protein (r2=0.54).Conclusions/interpretationAdiponectin concentration is an independent correlate of beta cell function in late pregnancy. As such, adiponectin may play a key role in mediating insulin resistance and beta cell dysfunction in the pathogenesis of diabetes.

Glucose Intolerance in Pregnancy and Postpartum Risk of Metabolic Syndrome in Young Women

CONTEXT/OBJECTIVE Gestational diabetes mellitus (GDM) and even mild glucose intolerance in pregnancy are both associated with increased risks of developing type 2 diabetes and cardiovascular disease in the future. Because the metabolic syndrome also identifies patients at risk of type 2 diabetes and cardiovascular disease, we hypothesized that gestational dysglycemia may be associated with an unrecognized latent metabolic syndrome. Thus, we sought to evaluate the relationship between gestational glucose tolerance status and postpartum risk of metabolic syndrome. DESIGN/SETTING/PARTICIPANTS In this prospective cohort study, 487 women underwent oral glucose tolerance testing in pregnancy and cardiometabolic characterization at 3 months postpartum. The antepartum testing defined three gestational glucose tolerance groups: GDM (n = 137); gestational impaired glucose tolerance (GIGT) (n = 91); and normal glucose tolerance (NGT) (n = 259). MAIN OUTCOME MEASURE The primary outcome was the presence of the metabolic syndrome at 3 months postpartum, as defined by International Diabetes Federation (IDF) and American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) criteria, respectively. RESULTS The postpartum prevalence of IDF metabolic syndrome progressively increased from NGT (10.0%) to GIGT (17.6%) to GDM (20.0%) (overall P = 0.016). The same progression was observed for AHA/NHLBI metabolic syndrome (NGT, 8.9%; GIGT, 15.4%; and GDM, 16.8%; overall P = 0.046). On logistic regression analysis, both GDM (odds ratio, 2.05; 95% confidence interval, 1.07-3.94) and GIGT (odds ratio, 2.16; 95% confidence interval, 1.05-4.42) independently predicted postpartum metabolic syndrome. CONCLUSIONS Both GDM and mild glucose intolerance in pregnancy predict an increased likelihood of metabolic syndrome at 3 months postpartum, supporting the concept that women with gestational dysglycemia may have an underlying latent metabolic syndrome.

Use of Low Molecular Weight Heparin in Pregnant Women With Mechanical Heart Valves

There are a number of different anticoagulation options for pregnant women with mechanical heart valves. The purpose of this study was to examine maternal thromboembolic complications in women with mechanical valves treated with low-molecular weight heparin (LMWH) throughout pregnancy. This was a substudy of a larger prospective cohort study of pregnant women with heart disease followed from 1998 to 2008. All pregnant women with mechanical left-sided valves who were treated with LMWH throughout pregnancy were included. Maternal thromboembolic events were defined as valve thrombosis, need for valve replacement, or stroke during pregnancy or postpartum (up to 6 months). Twenty-three pregnancies (17 women) occurred in women treated with LMWH and low-dose aspirin: 15 in women with mechanical mitral valves, 9 in women with mechanical aortic valves, and 1 in a woman with both. There was 1 maternal thromboembolic event (4%), which resulted in maternal and fetal death. Five women (22%) developed other adverse cardiac events during pregnancy. Nine pregnancies (43%) had fetal or neonatal adverse events, 5 of which had favorable outcomes. Three pregnancies were complicated by postpartum hemorrhage. In conclusion, carefully monitored LMWH may be a suitable anticoagulation strategy in pregnant women with mechanical heart valves who are unwilling to use warfarin. However, this group of women remains at risk for maternal cardiac and fetal complications. The occurrence of valve thrombosis resulting in maternal death despite therapeutic anti-Xa levels highlights current limitations with anticoagulation in this population.

Congenital aortic stenosis and pregnancy—A reappraisal

OBJECTIVE This study was performed to determine the maternal and fetal outcome in pregnant patients with congenital aortic stenosis without previous valvular replacement. STUDY DESIGN A retrospective review of 25 pregnancies in 13 patients delivered at our centers from September 1976 to September 1992 was undertaken. RESULTS Five (38%) patients had associated congenital heart lesions, three (23%) had severe stenosis (echocardiographically estimated valve area < or = 0.7 cm2), two had prior open aortic valve commissurotomy, and one had balloon valvuloplasty during pregnancy. There were no maternal deaths. Of the 25 pregnancies, five (20%) resulted in therapeutic abortions. There was no perinatal mortality, preterm labor, or increased incidence of pregnancy complications or fetal growth retardation in the remaining 20 pregnancies. One infant (5%) had congenital heart disease. CONCLUSION Pregnancy outcome is generally satisfactory in patients with congenital aortic stenosis.

B-Type Natriuretic Peptide in Pregnant Women With Heart Disease

OBJECTIVES The objectives of this study were to examine: 1) B-type natriuretic peptide (BNP) response to pregnancy in women with heart disease; and 2) the relationship between BNP levels and adverse maternal cardiac events during pregnancy. BACKGROUND Pregnancy imposes a hemodynamic stress on the heart. BNP might be a useful biomarker to assess the ability of the heart to adapt to the hemodynamic load of pregnancy. METHODS This was a prospective study of women with structural heart disease seen at our center. Serial clinical data and plasma BNP measurements were obtained during the first trimester, third trimester, and after delivery (>6 weeks). RESULTS Seventy-eight pregnant women were studied; 66 women with heart disease (age 31 ± 5 years), and 12 healthy women (age 33 ± 5 years). During pregnancy, the median peak BNP level was higher in women with heart disease compared with control subjects (median 79, interquartile range 51 to 152 pg/ml vs. median 35, interquartile range 21 to 43 pg/ml, p < 0.001). In women with heart disease, those with subaortic ventricular dysfunction had higher BNP levels (p = 0.03). A BNP >100 pg/ml was measured in all women with events during pregnancy (n = 8). Sixteen women had increased BNP levels during pregnancy but did not have clinical events. None of the women with BNP ≤100 pg/ml had events. BNP ≤100 pg/ml had a negative predictive value of 100% for identifying events during pregnancy. CONCLUSIONS Many pregnant women with heart disease have increased BNP levels during pregnancy. Incorporating serial BNP levels in into clinical practice can be helpful, specifically in adjudicating suspected adverse cardiac events during pregnancy.

Pregnancy Outcomes in Women With Dilated Cardiomyopathy

OBJECTIVES The objectives of this study were to determine adverse outcomes during pregnancy in women with dilated cardiomyopathy (DCM) and to compare their cardiac outcomes with those of nonpregnant women with DCM. BACKGROUND Women with DCM are at risk for complications during pregnancy, but few studies have examined outcomes in this specific population. METHODS This was a substudy of a larger prospective cohort study of outcomes in women with heart disease. Maternal cardiac, obstetric, and fetal outcomes in pregnancy in women with DCM were examined. For comparison, cardiac outcomes in nonpregnant women with DCM (n = 18) matched by age and left ventricular (LV) systolic function were examined. A matched-pair survival analysis was used to compare groups. RESULTS Thirty-six pregnancies in 32 women with DCM were included. Thirty-nine percent (14 of 36) of the pregnancies were complicated by at least 1 maternal cardiac event. In the multivariate analysis, moderate or severe LV dysfunction and/or New York Heart Association functional class III or IV (p = 0.003) were the main determinants of adverse maternal cardiac outcomes during pregnancy. In the subset of women with moderate/severe LV dysfunction, 16-month event-free survival was worse in pregnant women compared with nonpregnant women (28 +/- 11% vs. 83 +/- 10%, p = 0.02). The adverse neonatal event rate was highest among women with obstetric and cardiac risk factors (43%). CONCLUSIONS In pregnant women with DCM the risk of adverse cardiac events is considerable, and pre-pregnancy characteristics can identify women at the highest risk. Pregnancy seems to have a short-term negative impact on the clinical course in women with DCM.

Cohort Profile: The Maternal-Infant Research on Environmental Chemicals Research Platform

BACKGROUND The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health. METHODS Women were recruited during the first trimester from 10 sites across Canada and were followed through delivery. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, occupation, life style, medical history, environmental exposures and diet. Information on the pregnancy and the infant was abstracted from medical charts. Maternal blood, urine, hair and breast milk, as well as cord blood and infant meconium, were collected and analysed for an extensive list of environmental biomarkers and nutrients. Additional biospecimens were stored in the studys Biobank. The MIREC Research Platform encompasses the main cohort study, the Biobank and follow-up studies. RESULTS Of the 8716 women approached at early prenatal clinics, 5108 were eligible and 2001 agreed to participate (39%). MIREC participants tended to smoke less (5.9% vs. 10.5%), be older (mean 32.2 vs. 29.4 years) and have a higher education (62.3% vs. 35.1% with a university degree) than women giving birth in Canada. CONCLUSIONS The MIREC Study, while smaller in number of participants than several of the international cohort studies, has one of the most comprehensive datasets on prenatal exposure to multiple environmental chemicals. The biomonitoring data and biological specimen bank will make this research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals.

Pregnancy and Contraception in Congenital Heart Disease: What Women Are Not Told

As increased numbers of patients with congenital heart disease (CHD) survive to adulthood more women with CHD are reaching reproductive age. Contraception and pregnancy have now become important issues in this population; however both can be associated with increased risks in women with CHD (1). Other issues such as adverse fetal outcomes in these women and transmission of CHD to offspring must be addressed. Current guidelines for the care of adults with CHD recommend proactive counseling regarding issues of contraception and pregnancy (2-5). The objective of this study was to evaluate whether women with CHD have adequate knowledge regarding risks of contraception and pregnancy. (authors)