Differential impact of maternal and paternal ethnicity on the pattern of fat distribution in infants at age 3 months.

BACKGROUND: As ethnicity is typically recorded as a single demographic variable in clinical studies, little is known about the relative impact of maternal vs. paternal ethnicity on fat distribution. OBJECTIVES: The objective of this study was to determine whether there is a differential impact of maternal and paternal ethnicity on infant adiposity. METHODS: Three hundred fifty-five infants underwent anthropometric assessment at age 3 months, including skin-fold thickness (SFT) measurement at subscapular, suprailiac and triceps. Maternal (M) and paternal (P) ethnicity were classified as white (M = 241, P = 252), Asian (M = 50, P = 42) or other (M = 64, P = 61). RESULTS: Infants with either Asian mother (compared with white) or Asian father (compared with white) had increased subscapular, suprailiac and triceps SFT (all P < 0.05). On logistic regression analysis, however, only maternal Asian ethnicity (compared with white) independently predicted the likelihood of an infant being in the highest tertile for SFT at subscapular (odds ratio [OR] = 2.72, 95% confidence interval 1.17-6.34, P = 0.02), suprailiac (OR = 3.56, 1.51-8.42, P = 0.004) and triceps (OR = 3.26, 1.40-7.55, P = 0.005). In contrast, paternal Asian ethnicity was independently associated with sum of SFT only (OR = 2.46, 1.02-5.97, P = 0.04). CONCLUSION: Maternal and paternal Asian ethnicity have differential effects on infant fat distribution. Future clinical studies on obesity and fat composition should consider the distinct contributions of both parents to the ethnic classification of participants.

Lower dietary vitamin E intake during the second trimester is associated with insulin resistance and hyperglycemia later in pregnancy.

BACKGROUND/OBJECTIVES: Beneficial effects of vitamin E on insulin sensitivity have been reported in observational and short-term intervention studies in non-pregnant populations. We aimed to investigate whether dietary vitamin E intake during the second trimester would be associated with glucose metabolism later in pregnancy and whether this association would be influenced by an insulin-sensitizing hormone adiponectin. SUBJECTS/METHODS: Women with singleton pregnancies (n=205) underwent a 3-h oral glucose tolerance test at 30 weeks gestation and were asked to recall second trimester dietary intake. RESULTS: Higher dietary vitamin E intake was associated with lower fasting glucose, lower HOMA insulin resistance, and higher Matsuda insulin sensitivity index after covariate adjustment including serum adiponectin among women consuming daily multivitamin supplements (all P≤0.03). CONCLUSIONS: Lower dietary vitamin E intake during the second trimester is associated with hyperglycemia and insulin resistance later in pregnancy among women consuming daily multivitamin supplementations. Further, these associations are not influenced by adiponectin.

Effect of maternal gestational diabetes on the cardiovascular risk factor profile of infants at 1 year of age.

BACKGROUND AND AIM: Offspring of women with gestational diabetes (GDM) exhibit an adverse cardiovascular risk factor profile by as early as age 5 years. Recently, maternal glycemia has been associated with epigenetic modification of genes on the fetal side of the placenta, including those encoding emerging risk factors (adiponectin, leptin), suggesting that vascular differences may emerge even earlier in life. Thus, we sought to evaluate cardiovascular risk factors and determinants thereof in 1-year-old infants of women with and without GDM. METHODS AND RESULTS: Traditional (glucose, lipids) and emerging (C-reactive protein (CRP), adiponectin, leptin) risk factors were assessed in pregnancy in 104 women with (n = 36) and without GDM (n = 68), and at age 1-year in their offspring. In pregnancy, women with GDM had higher triglycerides (2.49 vs 2.10 mmol/L, p = 0.04) and CRP (5.3 vs 3.6 mg/L, p = 0.03), and lower adiponectin (7.3 vs 8.5 µg/mL, p = 0.04) than did their peers. At age 1-year, however, there were no differences in cardiovascular risk factors (including adiponectin) between the infants of women with and without GDM. Of note, maternal and infant adiponectin levels were associated in the non-GDM group (r = 0.39, p = 0.001) but not in the GDM group (r = 0.07, p = 0.67). Furthermore, on multiple linear regression analyses, maternal adiponectin emerged as an independent predictor of infant adiponectin in the non-GDM group only (beta = 776.1, p = 0.0065). CONCLUSION: Infants of women with and without GDM have a similar cardiovascular risk factor profile at age 1-year. However, there are differences in their early-life determinants of adiponectin that may be relevant to the subsequent vascular risk of GDM offspring.

Maternal pregravid weight is the primary determinant of serum leptin and its metabolic associations in pregnancy, irrespective of gestational glucose tolerance status.

CONTEXT: Several previous studies have investigated circulating levels of the adipokine leptin in relation to gestational diabetes mellitus (GDM). However, these studies have yielded markedly conflicting results, including increased, decreased, and unchanged leptin levels in women with GDM as compared with their peers. OBJECTIVE: We sought to evaluate the metabolic determinants of serum leptin in a well-characterized cohort reflecting the full spectrum of glucose intolerance in pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Metabolic characterization, including oral glucose tolerance test (OGTT) and measurement of serum leptin, insulin, lipids, adiponectin, and C-reactive protein, was performed in 817 pregnant women. The OGTT identified 198 women with GDM, 142 with gestational impaired glucose tolerance, and 477 with normal glucose tolerance. RESULTS: Median leptin (ng/ml) did not differ between the normal glucose tolerance (33.7), gestational impaired glucose tolerance (36.3), and GDM (36.4) groups (P = 0.085). On univariate correlation analysis, leptin was most strongly associated with prepregnancy body mass index (BMI) (r = 0.54, P < 0.0001), fasting insulin (r = 0.60, P < 0.0001), and C-reactive protein (r = 0.38, P < 0.0001) but only weakly associated with area under the glucose curve (AUC(glucose)) on the OGTT (r = 0.10, P = 0.0066). On multiple linear regression analysis, the strongest independent determinant of leptin was prepregnancy BMI (t = 11.55, P < 0.0001), whereas AUC(glucose) was not a significant predictor (t = -0.95, P = 0.34). Furthermore, although its respective associations with fasting insulin, triglycerides, and adiponectin varied across tertiles of prepregnancy BMI, leptin was not significantly associated with AUC(glucose) in any BMI tertile. CONCLUSIONS: Pregravid BMI, rather than gestational glucose tolerance, is the primary determinant of serum leptin concentration in pregnancy.

The postpartum cardiovascular risk factor profile of women with isolated hyperglycemia at 1-hour on the oral glucose tolerance test in pregnancy.

BACKGROUND AND AIMS: Women with gestational diabetes mellitus (GDM) have an enhanced cardiovascular risk factor profile at 3-months postpartum and an elevated risk of future cardiovascular disease, as compared to their peers. Recently, it has emerged that even mild dysglycemia on antepartum oral glucose tolerance test (OGTT) predicts an increased risk of future cardiovascular disease, although it is not known whether there exists an identifiable high-risk subgroup within this patient population. Since gestational impaired glucose tolerance (GIGT) due to isolated hyperglycemia at 1-h during the OGTT (1-h GIGT) bears metabolic similarity to GDM, we hypothesized that, like GDM, 1-h GIGT may predict a high-risk postpartum cardiovascular phenotype. METHODS AND RESULTS: In this prospective cohort study, 485 women underwent antepartum OGTT, followed by cardiovascular risk factor assessment at 3-months postpartum. The antepartum OGTT identified 4 gestational glucose tolerance groups: GDM (n = 137); 1-h GIGT (n = 39); GIGT at 2- or 3-h (2/3-h GIGT)(n = 50); and normal glucose tolerance (NGT)(n = 259). After adjustment for age, ethnicity, breastfeeding and waist circumference, mean levels of the following cardiovascular risk factors progressively increased from NGT to 2/3-h GIGT to 1-h GIGT to GDM: LDL cholesterol (p = 0.0026); total cholesterol:HDL (p = 0.0030); apolipoprotein B (p = 0.004); apolipoprotein B:apolipoprotein A1 (p = 0.026); leptin (p = 0.018); and C-reactive protein (p = 0.011). CONCLUSIONS: Amongst women without GDM, 1-h GIGT predicts an enhanced postpartum cardiovascular risk factor profile. It thus emerges, that amongst young women with mild dysglycemia in pregnancy, those with 1-h GIGT may comprise an unrecognized patient population at risk for future cardiovascular disease.

Anesthetic management of a consecutive cohort of women with heart disease for labor and delivery.

BACKGROUND: The cardiovascular changes of pregnancy may place additional stress upon women with pre-existing heart disease, increasing peripartum morbidity and mortality. The purpose of this descriptive study was to report the anesthetic management of a large cohort of pregnant women with heart disease. METHODS: The medical records of 522 consecutive parturients (657 pregnancies) with heart disease who delivered at Toronto General Hospital or Mount Sinai Hospital in Toronto, Ontario, Canada between 1986 and 2004 were reviewed. Obstetric, medical and anesthetic management data were collected and the women were stratified by New York Heart Association (NYHA) functional status at delivery. The main outcome of interest was the method of analgesia or anesthesia administered during labor and delivery. Univariate and multivariate analysis was performed to identify risk factors associated with the administration of general anesthesia. RESULTS: Of 657 pregnant women, 602 were NYHA 1/2 and 55 were NYHA 3/4 at time of delivery. Epidural analgesia was administered to 84% of NYH 1/2 women and 83% of NYH 3/4. The cesarean section rates were 29% and 31% respectively. The rate of general anesthesia for the entire cohort was 9%. Factors associated with the use of general anesthesia for operative delivery included cesarean delivery (adjusted O.R. 74; 95% CI 9.5, 573), delivering at Toronto General Hospital site (adjusted O.R. 5.5; 95% CI 2.3, 13.3), presence of complex congenital heart lesion (adjusted O.R. 2.3; 95% CI 1.0, 5.4) and each week of premature delivery (adjusted O.R. 1.3; 95% CI 1.1, 1.5). Three percent suffered intrapartum cardiac complications; there was one death. CONCLUSIONS: Pregnant women with heart disease managed within an organized program may undergo labor and delivery with acceptable rates of complications. Cesarean section, epidural analgesia/anesthesia and general anesthesia rates are similar to those in the general obstetric population.

Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia.

AIMS/HYPOTHESIS: The postpartum phase following gestational diabetes (GDM) is characterised by subtle metabolic defects, including the beta cell dysfunction that is believed to mediate the increased future risk of type 2 diabetes in this patient population. Low circulating levels of adiponectin and increased leptin and C-reactive protein (CRP) have recently emerged as novel diabetic risk factors, although their relevance to GDM and subsequent diabetes has not been characterised. Thus, we sought to determine whether adiponectin, leptin and CRP levels during pregnancy relate to the postpartum metabolic defects linking GDM with type 2 diabetes. METHODS: Metabolic characterisation, including oral glucose tolerance testing, was undertaken in 487 women during pregnancy and at 3 months postpartum. Based on the antepartum OGTT, there were 137 women with GDM, 91 with gestational impaired glucose tolerance and 259 with normal glucose tolerance. RESULTS: Adiponectin levels were lowest (p < 0.0001) and CRP levels highest (p = 0.0008) in women with GDM. Leptin did not differ between the glucose tolerance groups (p = 0.4483). Adiponectin (r = 0.41, p < 0.0001), leptin (r = -0.36, p < 0.0001) and CRP (r = -0.30, p < 0.0001) during pregnancy were all associated with postpartum insulin sensitivity (determined using the insulin sensitivity index of Matsuda and DeFronzo [IS(OGTT)]). Intriguingly, adiponectin levels were also related to postpartum beta cell function (insulinogenic index/HOMA of insulin resistance; r = 0.16, p = 0.0009). Indeed, on multiple linear regression analyses, adiponectin levels during pregnancy independently predicted both postpartum insulin sensitivity (t = 3.97, p < 0.0001) and beta cell function (t = 2.37, p = 0.0181), even after adjustment for GDM. Furthermore, adiponectin emerged as a significant negative independent determinant of postpartum fasting glucose (t = -3.01, p = 0.0027). CONCLUSIONS/INTERPRETATION: Hypoadiponectinaemia during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia, and hence may be relevant to the pathophysiology relating GDM with type 2 diabetes.

Decreased high-molecular-weight adiponectin in gestational diabetes: implications for the pathophysiology of Type 2 diabetes.

AIMS: Low serum concentrations of the insulin-sensitizing protein adiponectin predict the development of incident Type 2 diabetes (T2DM). It has recently emerged that the anti-diabetic activity of adiponectin may be mediated by its high-molecular-weight (HMW) isoform, circulating levels of which are decreased in T2DM. The relevance of decreased HMW adiponectin to incident T2DM, however, has not been assessed. Since gestational diabetes (GDM) identifies a population of young women at high risk of future T2DM (i.e. representing an early stage in the natural history of the disease), we sought to determine if decreased HMW adiponectin is a feature of GDM. METHODS: HMW and total adiponectin were measured in 121 women at the time of oral glucose tolerance testing (OGTT) in late pregnancy, following an abnormal glucose challenge test. Based on the OGTT, there were 41 women with and 80 without GDM. RESULTS: Median HMW adiponectin concentration was lower in women with GDM (3.5 microg/ml) than in those without GDM (5.5 microg/ml) (P < 0.0001). After full adjustment for covariates, mean HMW adiponectin remained significantly lower in women with GDM compared with their peers (3.6 vs. 5.3 microg/ml, P = 0.0035). HMW adiponectin was positively associated with insulin sensitivity (IS(OGTT)) (r = 0.38, P < 0.0001) and pancreatic B-cell function [insulin secretion-sensitivity index (ISSI)] (r = 0.33, P = 0.0002) and inversely related to blood glucose levels, including area-under-the-glucose-curve during the OGTT (AUC(glucose)) (r = -0.31, P = 0.0007). On separate multiple linear regression analyses, HMW adiponectin emerged as an independent determinant of AUC(glucose), IS(OGTT) and ISSI, respectively, mirroring the relationships of total adiponectin. CONCLUSIONS: HMW adiponectin is significantly decreased in women with GDM. Deficiency of HMW adiponectin may be an early event in the natural history of T2DM.

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.

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.

Pregnancy complicated by heart disease: a review of Canadian experience.

The physiological adaptations to pregnancy can potentially worsen the prognosis in women whose pregnancy is complicated by heart disease. A comprehensive systematic approach to risk identification is desirable. The ability to predict a subgroup of women that are at a particularly increased risk of pregnancy-related complications can enhance the obstetric care we provide to this population. A retrospective review of 276 pregnancies associated with pre-existing heart disease was undertaken in three Toronto teaching institutions. During the course of the pregnancy, 45 (18%) of 252 completed gestations were complicated by adverse cardiovascular events (congestive heart failure, arrhythmia and stroke). 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 converted into a point score. If a point score was 0, 1 or more than 1, the risk of a given patient running into cardiovascular complication was 3%, 30% and 66%, respectively. The Canadian Prospective Multicenter Study offered the validation of this prediction rule. In this study, 13 centres recruited prospectively 599 patients with completed gestations. Similar factors were identified in their ability to predict adverse cardiac events. In addition, neonatal complications (20% of pregnancies) were associated with poor functional class or cyanosis, left heart obstruction, anticoagulation, smoking and multiple gestation. A sample of this prospective cohort (302 pregnancies) was compared to 572 matched pregnancies with no underlying heart disease. The neonatal complication rate was higher in the study group when compared to controls, 18% versus 7%, respectively. The highest neonatal complication rate (33%) was seen in gravidas with underlying heart disease who had previously identified cardiac risk factors, were at both extremes of reproductive age, had obstetrical risk factors, smoked or received anticoagulants. Both maternal and neonatal morbidity are increased significantly in gravidas with pre-existing heart disease, although mortality is low. Factors that place the mother and the neonate at risk can be identified before pregnancy. This allows informed counselling and development of a patient-specific management plan.

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.

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.

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.

Congenital heart disease in pregnancy.

Care of pregnant patients with congenital heart disease requires understanding of the specific congenital defect, the nature of previous surgical correction, and the residua and sequelae. General risks and principles can be adduced in management decisions. In addition, lesion- and patient-specific details are important. There are only a few conditions that place patients at a high enough risk to advise that pregnancy be avoided under all circumstances (pulmonary vascular obstructive disease, Marfan syndrome with dilated aortic root, severe aortic stenosis, and severe systemic ventricular dysfunction). Preconception counseling, optimization of status, and meticulous multidisciplinary management during pregnancy and the postpartum period will improve outcomes.

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.

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.

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.