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Biomedical subjects

M Sermer

Publications and source records attributed to M Sermer.

At least 19 recordsLinked to original sources
PubMed2005

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

AIMS/HYPOTHESIS: Gestational 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. METHODS: We 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 (IS(OGTT)). RESULTS: To 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 IS(OGTT), 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 (r(2)=0.54). CONCLUSIONS/INTERPRETATION: Adiponectin 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.

Adiponectin↗
PubMed2004

Hypoadiponectinaemia in South Asian women during pregnancy: evidence of ethnic variation in adiponectin concentration.

AIMS: People of South Asian descent face an increased risk of Type 2 diabetes mellitus (DM) and coronary artery disease (CAD) compared with other ethnic groups. One candidate factor underlying this risk may be adiponectin, as circulating levels of this adipocyte-derived protein are reduced in both Type 2 DM and CAD. In a recent study, we assessed the relationship between adiponectin and gestational diabetes (GDM), a potential model of early events in the natural history of Type 2 DM. Here, we report the impact of ethnicity on plasma adiponectin concentration in that study. METHODS: A cross-sectional study was performed in 180 women undergoing oral glucose tolerance testing in late second or early third trimester to investigate the relationship between adiponectin and glucose tolerance in pregnancy. Based on self-reported ethnicity, participants were stratified into three groups: (i) Caucasian (n = 116), (ii) South Asian (n = 31), and (iii) Asian (n = 28). RESULTS: Median adiponectin concentration was much lower in the South Asian group (9.7 micro g/ml) than in Caucasians (15.8 micro g/ml) or Asians (16.1 micro g/ml) (overall P < 0.0001). With adjustment for age, prepregnancy body mass index, weight gain in pregnancy, previous history of GDM, family history of DM, fasting insulin and glucose intolerance, mean adiponectin remained significantly lower among South Asians compared with either Caucasians (P < 0.0001) or Asians (P = 0.0034). CONCLUSIONS: Women of South Asian descent exhibit significantly reduced plasma concentrations of adiponectin in pregnancy compared with Caucasian and Asian counterparts. This observation raises the possibility of hypoadiponectinaemia as a potential factor contributing to the increased risk of diabetes and cardiovascular disease in South Asians.

Adiponectin↗
PubMed2001

Prospective multicenter study of pregnancy outcomes in women with heart disease.

BACKGROUND: The maternal and neonatal risks associated with pregnancy in women with heart disease receiving comprehensive prenatal care have not been well defined. METHODS AND RESULTS: We prospectively enrolled 562 consecutive pregnant women with heart disease and determined the outcomes of 599 pregnancies not ending in miscarriage. Pulmonary edema, arrhythmia, stroke, or cardiac death complicated 13% of pregnancies. Prior cardiac events or arrhythmia, poor functional class or cyanosis, left heart obstruction, and left ventricular systolic dysfunction independently predicted maternal cardiac complications; the cardiac event rate can be predicted using a risk index incorporating these predictors. Neonatal complications (20% of pregnancies) were associated with poor functional class or cyanosis, left heart obstruction, anticoagulation, smoking, and multiple gestations. CONCLUSIONS: Pregnancy in women with heart disease is associated with significant cardiac and neonatal complications, despite state-of-the-art obstetric and cardiac care. Maternal cardiac risk can be predicted with the use of a risk index.

Adolescent↗
PubMed2000

Obstetric outcome of adolescent pregnancies

Background: To determine if adolescent pregnancies are at increased risk of poor obstetrical outcome compared with a general obstetrical population.Methods: A five-year retrospective review of the Toronto Hospital for Sick Children's Teenage Pregnancy Unit was carried out. Information was available on 209 patients < 19 years age between January 1994 and December 1998. This was compared to information available from a database of all women delivering at the same hospital, The Toronto Hospital General Division, during the same time period (n = 13,557). The Chi-square test of independence was used to compare the data and is reported as adolescent group vs. hospital group.Results: Labour was induced in 25.5% vs. 21.8% (p = 0. 20). Epidural anaesthesia was received by 63.5% vs. 53% (p < 0.05). The incidence of preterm delivery (<37 wks) was 13.5% vs. 8.1% (p < 0.05), low-birth-weight babies (< 2500 g) 13.4% vs. 8.6% (p < 0.05) and small-for-gestational-age babies (<2 SD) 1.9%. The incidence of post-term delivery (>41 wks) was 12.5% vs. 4.3% (p < 0.001), macrosomia (>4000 g) 1.9% vs. 9.2% (p < 0.001) and large-for-gestational-age babies (>2 SD) 0.5%. Operative delivery (forceps or vacuum) occurred in 19.7% vs. 19.9% (p = 0.94) and caesarian section in 6.2% vs. 20.1% (p < 0.001). APGARs <7 at five minutes were found in 2.4% vs. 3.1% (p = 0.60). 12.0% of infants were admitted to the neonatal nursery. There were no stillbirths. Conclusions: Both preterm deliveries and low-birth-weight babies were more frequent in the adolescent group although the incidence of SGA babies was low. The low caesarian section rate also likely reflects these findings. Postterm delivery was also more common, yet macrosomia occurred less frequently.

Journal Article↗
PubMed2000

Successful twin pregnancy in a dual-transplant couple resulting from in-vitro fertilization and intracytoplasmic sperm injection: case report.

There are numerous reports of successful pregnancy following liver transplantation. Little information is available regarding the incidence and management of infertility in transplant recipients, particularly the use of artificial reproductive technologies. We present a case of a successful twin pregnancy resulting from in-vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) in a liver transplant recipient, whose partner was a renal transplant recipient with severe oligozoospermia. With careful evaluation and monitoring, and the involvement of appropriate consultants, artificial reproductive technologies can be safely used in transplant recipient couples experiencing infertility.

Adult↗
PubMed1999

RhD status of a fetus at risk for haemolytic disease with a discrepant maternal DNA-based RhD genotype.

The cloning of the RHD gene has made it possible to determine the RhD status of fetuses at risk for haemolytic disease due to RhD iso-immunization using amniotic fluid or chorionic villi-derived DNA and the polymerase chain reaction. However, some Rh haplotypes are associated with false-positive or negative DNA-based results with the potential for an adverse outcome. We determined the RhD status of a fetus using amniotic fluid-derived DNA for an anti-D iso-immunized woman. Initially, we obtained the ethnic background and the complete RhD and RhCcEe phenotypes of both parents. The mother was RhD negative (Cde/cde) but her DNA was positive for exon 10 of the RHD gene. The fetus was positive for both exons 4 5 and exon 10. Southern analysis confirmed that the maternal DNA contained a portion of the RHD gene with a restriction pattern that was similar to RhD-positive individuals. This report illustrates that, in addition to fetal DNA genotyping, the same PCR assays, complete with RhD and RhCcEe phenotypes, and ethnic background of the parents should be obtained to alert the molecular diagnostic laboratory to the presence of rare Rh haplotypes that are associated with DNA genotyping errors.

Adult↗
PubMed1999

Prenatal detection of cerebral lesions in a fetus with tuberous sclerosis.

We report a newborn, diagnosed prenatally with both cardiac rhabdomyomas and a brain tumor. To the best of our knowledge, this is the first report of central nervous system (CNS) lesions detected prenatally in a child with tuberous sclerosis with term follow-up. At 36 months, the child has normal growth and is developing appropriately. Thus the finding of CNS tumors on fetal ultrasound examination can help in the prenatal diagnosis of tuberous sclerosis but does not necessarily indicate a poor prognosis.

Adult↗
PubMed1998

The Toronto Tri-Hospital Gestational Diabetes Project. A preliminary review.

In this study, we assessed maternal-fetal outcomes in untreated patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes mellitus (GDM), examined the relationship between birth weight and mode of delivery among women with untreated borderline GDM, treated overt GDM, and normoglycemia, and established more efficient screening strategies for detection of GDM. This was a prospective analytic cohort study in which nondiabetic women aged > or = 24 years were eligible for enrollment. A 50-g glucose challenge test (GCT) and a 100-g oral glucose tolerance test (OGTT) were administered at 26 and 28 weeks gestational age, respectively. Risk factors for unfavorable maternal-fetal outcomes were recorded. Time since the last meal prior to the screening test was recorded, as well. Caregivers and patients were blinded to glucose values except when test results met the National Diabetes Data Group criteria for GDM. Maternal and fetal outcomes, including the mode of the delivery, were recorded in the postpartum period. Of 4,274 patients screened, 3,836 (90%) continued to the diagnostic oral glucose tolerance test. GDM was seen in 145 women. Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean section, preeclampsia, macrosomia, and need for phototherapy, as well as an increased length of maternal and neonatal hospital stay. Multivariate analysis showed that increasing carbohydrate intolerance remained an independent predictor for various unfavorable outcomes, but the strength of the associations was diminished. Compared with normoglycemic control subjects, the untreated borderline GDM group had increased rates of macrosomia (28.7 vs. 13.7%, P < 0.001) and cesarean delivery (29.6 vs. 20.2%, P = 0.03). Usual care of known GDM patients normalized birth weights, but the cesarean delivery rate was about 33%, whether macrosomia was present or absent. An increased risk of cesarean delivery among treated patients compared with normoglycemic control subjects persisted after adjustment for multiple maternal risk factors. As for the screening tests, time since the last meal had a marked effect on mean plasma glucose. Receiver operating characteristic curve analysis allowed the selection of the most efficient cut points for the GCT based on the time since the last meal. These cut points were 8.2, 7.9, and 8.3 mmol/l (1 mmol/l = 18.015 mg/dl) for elapsed postprandial time of < 2, 2-3, and > 3 h, respectively. With this change from the current threshold of 7.8 mmol/l, the number of patients with a positive screening test dropped from 18.5 to 13.7%. There was an increase in positive predictive value from 14.4 to 18.7%. The overall rate of patient misclassification fell from 18.0 to 13.1%. In conclusion, increasing maternal carbohydrate intolerance in pregnant women without GDM is associated with a graded increase in adverse maternal and fetal outcomes. Infant macrosomia is an important factor in high cesarean delivery rates for women with untreated borderline GDM. Although detection and treatment of GDM normalizes birth weights, rates of cesarean delivery remain inexplicably high. Recognition of GDM may lead to a lower threshold for surgical delivery. The efficiency of screening for GDM can be enhanced by adjusting the current GCT threshold of 7.8 mmol/l to new values related to time since the last meal before screening. Further analyses are underway to elucidate whether maternal risk factors can be used to achieve additional efficiency gains in screening.

Birth Weight↗
PubMed1997

Selective screening for gestational diabetes mellitus. Toronto Trihospital Gestational Diabetes Project Investigators.

BACKGROUND: The usual approach to detecting gestational diabetes mellitus is to screen all pregnant women by measuring their plasma glucose after a 50-g oral glucose load at 24 to 28 weeks' gestation. Women are referred for an oral glucose-tolerance test if the plasma glucose concentration one hour later is > or = 140 mg per deciliter (7.8 mmol per liter). We hypothesized that the efficiency of screening could be enhanced by considering women's risks of gestational diabetes on the basis of their clinical characteristics. METHODS: We studied 3131 pregnant women who underwent both the screening and the diagnostic tests. We randomly selected data on half the women and used them to derive new screening strategies. We categorized each woman's risk of gestational diabetes mellitus on the basis of her age, body-mass index before pregnancy, and race. We developed strategies that entailed no screening for low-risk women, usual care for intermediate-risk women, and universal screening with lower thresholds -- plasma glucose values of 130 mg per deciliter (7.2 mmol per liter) or 128 mg per deciliter (7.1 mmol per liter) -- for high-risk women. The strategies were validated with data on the other half of the women. RESULTS: The new strategies allowed a 34.6 percent reduction in the number of screening tests performed (95 percent confidence interval, 32.3 to 37.0) and detected 81.2 to 82.6 percent of the women with gestational diabetes as compared with the 78.3 percent detected through usual care. The percentage of false positive screening tests was significantly reduced, from 17.9 percent with usual care to 16.0 per cent (P=0.02) or 15.4 percent (P<0.001) with the new strategies, depending on the threshold values for high-risk women. CONCLUSIONS: Consideration of women's clinical characteristics allows efficient selective screening for gestational diabetes.

Adult↗
PubMed1997

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.

Adolescent↗
PubMed1997

Omphalocele in Miller-Dieker syndrome: expanding the phenotype.

We report on a patient prenatally diagnosed with omphalocele, mild cerebral ventriculomegaly, nuchal fold thickening, and cystic changes in the umbilical cord who was found postnatally to have lissencephaly type I. Prenatal chromosome analysis showed a normal male karyotype; however, postnatal high resolution banding and FISH analysis, using a probe for locus D17S379 in chromosome region 17p13.3, demonstrated a deletion at 17p13.3 consistent with Miller-Dieker syndrome (MDS). A review documented four more cases with MDS/isolated lissencephaly/17p-, with omphalocele. Because MDS is a contiguous gene disorder, we speculate that a gene or genes in this region have a major role in the closure of the lateral folds or the return of the midgut from the body stalk to the abdomen at 5-11 weeks of gestation. Prenatal diagnosis of omphalocele with mild ventriculomegaly should prompt FISH analysis for a deletion in 17p13.3.

Abnormalities, Multiple↗
PubMed1996

Cesarean delivery in relation to birth weight and gestational glucose tolerance: pathophysiology or practice style? Toronto Trihospital Gestational Diabetes Investigators.

OBJECTIVES: To examine the relationship between birth weight and mode of delivery among women with untreated borderline gestational diabetes mellitus (GDM), treated overt GDM, and normoglycemia. DESIGN: Prospective cohort study. SETTING: Three Toronto, Ontario teaching hospitals. PATIENTS: A total of 3778 volunteers aged 24 years or older. INTERVENTIONS: Subjects underwent a 3-hour long, 100-g oral glucose tolerance test at 28 weeks' gestation, regardless of screening test results. Usual care was provided to 143 women who met the National Diabetes Data Group criteria for GDM. Physicians were blinded to glucose tolerance test results for all others, including 115 untreated women with borderline GDM by the broader criteria of Carpenter and Coustan. MAIN OUTCOME MEASURES: Crude and adjusted rates of cesarean delivery and neonatal macrosomia (birth weight >4000 g). RESULTS: Compared with normoglycemic controls, the untreated borderline GDM group had increased rates of macrosomia (28.7% vs 13.7%, P<.001) and cesarean delivery (29.6% vs 20.2%, P=.02). Cesarean delivery in this subgroup was associated with macrosomia (45.5% vs 23.5%, P=.03). Usual care of known GDM normalized birth weights, but the cesarean delivery rate was about 33% whether macrosomia was present or absent. A clearly increased risk of cesarean delivery among treated patients compared with normoglycemic controls persisted after adjustment for multiple maternal risk factors (adjusted odds ratio, 2.1; 95% confidence interval, 1.3 to 3.6). CONCLUSIONS: Infant macrosomia was a mediating factor in high cesarean delivery rates for women with untreated borderline GDM. While detection and treatment of GDM normalized birth weights, rates of cesarean delivery remained inexplicably high. Recognition of GDM may lead to a lower threshold for surgical delivery that mitigates the potential benefits of treatment.

Adult↗
PubMed1996

Pregnancy after the fontan procedure for tricuspid atresia. A case report.

BACKGROUND: Pregnancy is contraindicated in uncorrected tricuspid atresia. Even following palliative surgery with the Fontan procedure, only four pregnancies have been reported. CASE: A 32-year-old female presented at 8 weeks' gestation in her first pregnancy with a history of the Fontan procedure performed seven years earlier for cardiac decompensation despite two previous palliative procedures for tricuspid atresia. She remained class I with no deterioration and required no medication throughout the pregnancy. Amniocentesis for positive maternal alpha-fetoprotein screening was normal. The pregnancy was complicated by antepartum hemorrhage at 29 weeks and premature rupture of membranes at 33 weeks, resulting in preterm labor and delivery of a 2.5-kg infant five days later. Apart from postpartum hemorrhage, the puerperium was uneventful, and the patient was well 20 weeks after delivery. CONCLUSION: Five similar pregnancies, including this one, have been reported. Although all were successful, three infants were preterm and two growth retarded. This observation suggests that for these patients, pregnancy must be monitored closely even though the mothers may be hemodynamically stable.

Adult↗
PubMed1996

Systemic lupus erythematosus and pulmonary hypertension during pregnancy: report of a case fatality.

The case of a 25-year-old pregnant woman with systemic lupus erythematosus and severe pulmonary hypertension is presented. The pregnancy was complicated by worsening right heart failure and pre-eclampsia, requiring a caesarian section at 29 weeks' gestation. On the fourth day postpartum, the patient's respiratory status worsened and she was transferred to the coronary care unit where she soon died from combined right heart failure and respiratory arrest. The presumed pathogenesis and etiology of lupus-related pulmonary hypertension are discussed, in addition to noninvasive tests and proposed management. Given that the mortality rate is very high during pregnancy and therapy is of limited value, women with lupus-associated pulmonary hypertension should avoid conceiving. Those who choose to become pregnant must be carefully managed by a multidisciplinary team.

Adult↗
PubMed1995

The prognostic factors in the prenatal diagnosis of the echogenic fetal lung.

The prenatal diagnosis of an echogenic fetal lung (EFL) is now often made in the early second trimester using high-resolution ultrasound. This ultrasound appearance is usually caused by a congenital cystic adenomatoid lung malformation (CCAM), an intrapulmonary lung sequestration or obstruction of a major airway. In order to provide prognostic guidelines to parents who may be considering termination of a fetus with these findings, we have analysed a series of 11 cases diagnosed in our centre over the past 2 years in conjunction with 60 cases from major published series. The data suggest that in the absence of non-immune hydrops fetalis (NIHF) or other anomalies, the outcome for the fetuses is excellent, with over 90 per cent survival. Neither early diagnosis (24 weeks) nor the presence of mediastinal shift is a poor prognostic indicator. In addition, it appears that if NIHF is absent at diagnosis, the chance that it will develop as the pregnancy continues is small (6 per cent). Furthermore, there is a significant (up to 30 per cent) chance that this ultrasound finding will resolve in utero. The development of in utero fetal surgical techniques may be the only hope for those hydropic fetuses who appear to have a dismal prognosis.

Bronchopulmonary Sequestration↗
PubMed1995

Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes Project.

OBJECTIVE: Our purpose was to assess maternal-fetal outcomes in patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes. STUDY DESIGN: We conducted a prospective analytic cohort study in which nondiabetic women aged > or = 24 years, receiving prenatal care in three Toronto teaching hospitals, were eligible for enrollment. A glucose challenge test and an oral glucose tolerance test were administered at 26 and 28 weeks' gestation, respectively; risk factors for unfavorable maternal-fetal outcomes were recorded. Caregivers and patients were blinded to glucose values except when test results met the current criteria for gestational diabetes. RESULTS: Of 4274 patients screened, 3836 (90%) continued to the diagnostic oral glucose tolerance test. The study cohort was formed by the 3637 (95%) patients without gestational diabetes, carrying singleton fetuses. Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean sections, preeclampsia, macrosomia, and need for phototherapy, as well as an increased length of maternal and neonatal hospital stay. Multivariate analysis showed that increasing carbohydrate intolerance is an independent predictor for various unfavorable outcomes. CONCLUSION: Increasing maternal carbohydrate intolerance in pregnant women without gestational diabetes is associated with a graded increase in adverse maternal-fetal outcomes.

Adult↗
PubMed1995

Pregnancy outcome after gestational exposure to amiodarone in Canada.

OBJECTIVE: Our purpose was to quantitate the risk of perinatal thyroid dysfunction and other amiodarone-induced adverse effects among infants exposed in utero to amiodarone. STUDY DESIGN: A historic cohort study of gestational exposure to amiodarone was conducted by contacting Canadian cardiac electrophysiologists. RESULTS: Twelve cases were identified. Of six with first-trimester exposure, one child had congenital nystagmus with synchronous head titubation. There was one case each of transient neonatal hypothyroidism (9%) and hyperthyroidism (9%). A fourth child, exposed to amiodarone from 20 weeks' gestation, had developmental delay, hypotonia, hypertelorism, and micrognathia. Four small-for-gestational-age infants were also exposed to beta-blockers, which in addition to maternal cardiac disease, have been recognized to cause growth restriction. beta-Blockers may also have contributed to bradycardia in one of the three fetuses in whom this was observed. CONCLUSIONS: Gestational exposure to amiodarone may be complicated by perinatal hypothyroidism or hyperthyroidism and possibly neurologic abnormalities, intrauterine growth retardation or fetal bradycardia. Concomitant beta-blocker therapy should probably be avoided. Full neonatal thyroid function tests and developmental follow-up are recommended.

Adrenergic beta-Antagonists↗