Obesity in pregnancy as a model to identify women at risk for later metabolic syndrome.

The aim of our study is to identify - in a cohort of obese women - cardiovascular and clinical risk factors in women with previous complicated pregnancies and protective factors in women with previous physiological pregnancies. A total of 135 nonpregnant obese women referring to Policlinico Gemelli in Rome were prospectively collected in 2009-2010. Thirty-two women matched inclusion criteria: 16 reported a previous physiological pregnancy and 16 reported previous obstetric complications. A clinical, instrumental and laboratory evaluation has been performed for each patient. Statistical analysis was performed using StatView Software. Values are expressed as mean ± standard error (SEM). All tests were two-tailed with a confidence level of 95% (p < .05). Statistically significant reduced flow-mediated dilatation (p = .0338), increased serum values of vascular cell adhesion molecule (p = .0154) and higher systolic blood pressure values (p = .0427) have been detected in obese women with previous complicated pregnancies due to gestational diabetes and/or hypertension. In conclusion, obese patients with previous complicated pregnancies develop signs of endothelial dysfunction in the postpartum period. Future research should focus on the early identification of possible molecular mechanisms implicated in the development of glyco-metabolic and cardiovascular diseases in obese patients, since they are at higher risk of metabolic syndrome.

Low adiponectin in overweight/obese women: association with diabetes during pregnancy.

BACKGROUND: Overweight/obese (OW/OB) women are at high risk to develop gestational diabetes mellitus (GDM) in pregnancy. AIM: To investigate, in pregnant OW/OB women, the longitudinal changes of adiponectin plasma levels, carbohydrate and lipid metabolism, and to identify if there is any association between adipokines and subsequent development of GDM. SUBJECTS AND METHODS: Thirty-two OW/OB normotensive normoglycaemic women at the beginning of pregnancy were studied. Adiponectin, insulin sensitivity (homeostasis model assessment, HOMA) and lipid panel were measured at 1st, 2nd and 3rd trimesters of pregnancy. The bioelectrical impedance to estimate the subject's body composition was also performed. RESULTS: Sixteen OW/OB women developed GDM. There were no significant differences with regard to age, BMI and body composition. Glycaemic and insulinaemic plasma levels, HOMA and lipid panel were comparable in the two groups. Systolic, diastolic and mean blood pressure at the 1st trimester were higher in OW/OB women with GDM (p < 0.05). GDM group showed adiponectin levels significantly lower than control group, at each trimester (p < 0.05). Adiponectin, fat mass, diastolic blood pressure and HOMA are independent predictors of GDM. CONCLUSIONS: OW/OB women who will develop GDM show lower adiponectin than euglycaemic group, across all pregnancy. Furthermore, at first trimester, they showed higher body fat and blood pressure levels than NGT group. Adiponectin, body fat, DBP and HOMA are independent predictors of GDM in OW/OB pregnant women. These results suggest the possibility of using adiponectin as early marker of GDM risk, at least in this cohort of women.

Bladder function after spinal anesthesia for cesarean section: an urodynamic evaluation.

BACKGROUND: This study evaluates the effects of spinal anesthesia with hyperbaric bupivacaine plus sufentanil on bladder function in women undergoing cesarean section. SUBJECTS AND METHODS: Thirty caucasian healthy pregnants scheduled for elective Cesarean section under spinal anesthesia performed with hyperbaric bupivacaine plus sufentanil were enrolled. Filling cystometry, proprioceptive bladder sensation during cystometry, rate of spontaneous voiding, post void residual volume, anocutaneous and bulbocavernosus reflex were analyzed at 4, 6 and 8 hours after spinal anesthesia. RESULTS: The proportion of women experiencing first sensation, first desire and strong desire at 4 hours was significantly different from that reported at 6 and 8 hours (p < 0.05 for first sensation and p < 0.01 for first and strong desire). Significant differences were also observed between volumes at which first sensation arose at first measurement (4 hours) and at second and third measurements (p < 0.01). There was a significant difference in rate of spontaneous micturition, with 80% of patients at 8 hours able to spontaneously void versus 40% at 6 hours, (p < 0.01). Moreover, a lower percentage of women had absent and/or light reflexes at 4 hour than at 6 and 8 hours (p < 0.01). CONCLUSIONS: Spinal anesthesia with bupivacaine plus sufentanil causes a clinically significant disturbance on bladder function in women undergoing cesarean section. Even thought recovery of proprioceptive bladder sensation is fast, a full recovery of spontaneous voiding requires a much longer time. A close monitoring of urinary function and of bladder distension is, therefore, advisable.

Effect of pravastatin on endothelial function and endothelial progenitor cells in healthy postmenopausal women.

PURPOSE: Coronary heart disease is the leading cause of morbidity and mortality in postmenopausal women. Among statins, pravastatin has been shown to significantly reduce fatal and non-fatal cardiovascular events in primary and secondary prevention trials. The aim of the present research was to investigate whether treatment with pravastatin can modify some indices of cardiovascular risk in healthy postmenopausal women such as significant reductions in total and LDL cholesterol and triglyceride levels. METHODS: 20 patients were randomized in double-blind fashion to treatment for eight weeks with either pravastatin 40 mg/day or placebo, and subsequently, after one-week wash-out, crossed-over to the alternative treatment (placebo or pravastatin) for the following eight weeks. We performed clinical and laboratory investigations, before and at the end of each treatment period, to evaluate patient response to the treatment with pravastatin. RESULTS: After eight weeks pravastatin therapy reduced the median low density lipoprotein (LDL) and total cholesterol (p < 0.01 in both cases). In contrast, insulin level and insulin sensitivity did not show any difference with regard to values observed after placebo treatment. The absolute number of endothelial progenitor cells-colony forming unit (EPC-CFU) was significantly increased by pravastatin treatment (30.6% increase, p < 0.05) and the number of senescent cells was significantly decreased. However pravastatin did not increase tube-like formation by EPC and did not improve endothelial function. CONCLUSIONS: Despite beneficial effect on lipids and EPC, short term pravastatin does not seem to improve other cardiovascular risk factors, at least in healthy postmenopausal women.

[Role of vaginal infection in fetal and neonatal mortality]. / Ruolo delle infezioni vaginali nella mortalità fetale e neonetale.

Preterm delivery is the chief problem in obstetrics today and the main determinant of infant mortality and morbidity. Despite the dramatic decrease in infant mortality rate during the past several years, the percentage of preterm (<37 weeks gestation) and low birth weight (LBW) (<2500) rates remain elevated. Approximately 10% of all births are preterm, with a rate of 1-2% of infant born before the end of the 32 weeks of gestation and with a weight <1500 g. Despite the importance of the problem, the majority of preterm live births remain unexplained, and programmatic attempts at reversing the high level of preterm births have not been successful. Numerous studies have linked bacterial vaginosis, chorioamniotitis and endometritis with preterm birth and LBW, especially among African women. The number of preterm live births among African women is twice the one among Caucasians. Bacterial vaginosis is an independent risk factor for preterm and LBW births and the mechanism by which bacterial vaginosis causes the preterm birth of an infant with LBW is unknown. The aim of this article was to underline the importance of the treatment and early identification of vaginal infection, in particular if due to bacterial vaginosis, as it can have a substantial affect on the incidence of preterm delivery with LBW.

Coronary artery disease: a study on the joint role of birth weight, adenosine deaminase, and gender.

An inverse relationship between birth weight and coronary artery diseases is well documented but it remains unclear which exposure in early life might underlie such association. Recently it has been reported an association between adenosine deaminase genetic polymorphism and coronary artery diseases. Gender differences in the degree of this association have been also observed. These observations prompted us to study the possible joint effects of BW, ADA, and gender on the susceptibility to coronary artery diseases. 222 subjects admitted to hospital for nonfatal coronary artery diseases, and 762 healthy consecutive newborns were studied. ADA genotypes were determined by DNA analysis. A highly significant complex relationship has emerged among ADA, birth weight, and gender concerning their role on susceptibility to coronary artery diseases in adult life. Odds ratio analysis suggests that low birth weight is more important in females than in males. ADA( *)2 allele appears protective in males, while in females such effect is obscured by birth weight.

Repeatability characteristics of simple indices of insulin resistance: implications for research applications.

The objectives of this study were to evaluate test characteristics, such as normality of distribution, variation, and repeatability, of simple fasting measures of insulin sensitivity and to use the results to choose among these measures. Duplicate fasting samples of insulin and glucose were collected before 4 h of euglycemic hyperinsulinemic clamping using insulin infusion rates ranging from 40-600 mU/m2 x min. Currently recommended estimates of insulin sensitivity, including the fasting insulin, 40/insulin, the homeostasis model assessment, the logarithmic transformation of the homeostasis model assessment, and the Quantitative Insulin Sensitivity Check Index, were evaluated. The normality of distribution and the variability of the tests (coefficient of variation and discriminant ratio) were compared between the measures and against the "gold standard" hyperinsulinemic clamp. Data from 253 clamp studies in 152 subjects were examined, including 79 repeated studies for repeatability analysis. In subjects ranging from lean to diabetic, the log transformed fasting measures combining insulin and glucose had normal distributions and test characteristics superior to the other simple indices (logarithmic transformation of the homeostasis model assessment coefficient of variation, 0.55; discriminant ratio, 13; Quantitative Insulin Sensitivity Check Index coefficient of variation, 0.05; discriminant ratio, 10) and statistically comparable to euglycemic hyperinsulinemic clamps (coefficient of variation, 0.10; discriminant ratio, 6.4). These favorable characteristics helped explain the superior correlations of these measures with the hyperinsulinemic clamps among insulin-resistant subjects. Furthermore, therapeutic changes in insulin sensitivity were as readily demonstrated with these simple measures as with the hyperinsulinemic clamp. The test characteristics of the logarithmic transformation of the homeostasis model assessment and the Quantitative Insulin Sensitivity Check Index are superior to other simple indices of insulin sensitivity. This helps explain their excellent correlations with formal measures both at baseline and with changes in insulin sensitivity and supports their broader application in clinical research.

Polycystic ovary syndrome is associated with endothelial dysfunction.

BACKGROUND: We recently reported endothelial dysfunction as a novel cardiovascular risk factor associated with insulin resistance/obesity. Here, we tested whether hyperandrogenic insulin-resistant women with polycystic ovary syndrome (PCOS) who are at increased risk of macrovascular disease display impaired endothelium-dependent vasodilation and whether endothelial function in PCOS is associated with particular metabolic and/or hormonal characteristics. METHODS AND RESULTS: We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) and to euglycemic hyperinsulinemia in 12 obese women with PCOS and in 13 healthy age- and weight-matched control subjects (OBW). LBF increments in response to MCh were 50% lower in the PCOS group than in the OBW group (P:<0.01). Euglycemic hyperinsulinemia increased LBF above baseline by 30% in the PCOS and 60% in OBW group (P:<0.05 between groups). Across all subjects, the maximal LBF response to MCh exhibited a strong inverse correlation with free testosterone levels (r=-0.52, P:<0.007). This relationship was stronger than with any other parameter, including insulin sensitivity. CONCLUSIONS: PCOS is characterized by (1) endothelial dysfunction and (2) resistance to the vasodilating action of insulin. This endothelial dysfunction appears to be associated with both elevated androgen levels and insulin resistance. Given the central vasoprotective role of endothelium, these findings could explain, at least in part, the increased risk for macrovascular disease in women with PCOS.

Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production.

The effect and time course of free fatty acid (FFA) elevation on insulin-mediated vasodilation (IMV) and the relationship of FFA elevation to changes in insulin-mediated glucose uptake was studied. Two groups of lean insulin-sensitive subjects underwent euglycemic-hyperinsulinemic (40 mU x m(-2) x min(-1)) clamp studies with and without superimposed FFA elevation on 2 occasions approximately 4 weeks apart. Groups differed only by duration of FFA elevation, either short (2-4 h, n = 12) or long (8 h, n = 7). On both occasions, rates of whole-body glucose uptake were measured, and changes in leg blood flow (LBF) and femoral vein nitric oxide nitrite plus nitrate (NOx) flux in response to the clamps were determined. Short FFA infusion did not have any significant effect on the parameters of interest. In contrast, long FFA infusion decreased rates of whole-body glucose uptake from 47.7 +/-2.8 to 32.2 +/- 0.6 micromol x kg(-1) x min(-1) (P < 0.01), insulin-mediated increases in LBF from 66 +/- 8 to 37 +/- 7% (P < 0.05), and insulin-induced increases in NOx flux from 25 +/- 9 to 5 +/- 9% (P < 0.05). Importantly, throughout all groups, FFA-induced changes in whole-body glucose uptake correlated significantly with FFA-induced changes in insulin-mediated increases in LBF (r = 0.706, P < 0.001), which indicates coupling of metabolic and vascular effects. In a different protocol, short FFA elevation blunted the LBF response to NG-monomethyl-L-arginine (L-NMMA), which is an inhibitor of NO synthase. LBF in response to L-NMMA decreased by 17.3 +/- 2.4 and 9.0 +/- 1.4% in the groups without and with FFA elevation, respectively (P < 0.05), which indicates that FFA elevation interferes with shear stress-induced NO production. Thus, impairment of shear stress-induced vasodilation and IMV by FFA elevation occurs with different time courses, and impairment of IMV occurs only if glucose metabolism is concomitantly reduced. These findings suggest that NO production in response to the different stimuli may be mediated via different signaling pathways. FFA-induced reduction in NO production may contribute to the higher incidence of hypertension and macrovascular disease in insulin-resistant patients.

Type II diabetes abrogates sex differences in endothelial function in premenopausal women.

BACKGROUND: Obesity is a more potent cardiovascular risk factor (CVRF) in men than in women. Because traditional CVRFs cannot fully account for this sex difference, we tested the hypothesis that compared with men, women exhibit more robust endothelial function independent of obesity and that this sex difference is abrogated by diabetes. METHODS AND RESULTS: We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) and the endothelium-independent vasodilator sodium nitroprusside (SNP) in groups of lean, obese (OB), and type II diabetic (DM) premenopausal women and age- and body mass index-matched men. LBF response to intrafemoral administration of L-NMMA, an inhibitor of nitric oxide synthase, was also assessed in normal men and women. Maximum LBF increments in response to Mch were 347+/-57% versus 231+/-22% in lean women versus men (P<0.05) and 203+/-25% versus 111+/-17% in OB women versus men (P<0.01), respectively. In DM, maximum LBF increments in response to Mch were 104+/-24% and 138+/-33% in women and men, respectively, (P=NS). LBF decrements in response to L-NMMA were 34.9+/-4.1% and 17.1+/-4.2% in women and men, respectively (P<0.01). The response to SNP was not different between sexes and groups. CONCLUSIONS: Premenopausal nondiabetic women exhibit more robust endothelium-dependent vasodilation owing to higher rates of nitric oxide release than men. Given the protective vascular action of nitric oxide, this difference may partially explain the lower incidence of macrovascular disease in women. In premenopausal women, DM causes impairment of endothelial function beyond that observed with obesity alone and leads to endothelial dysfunction similar to that observed in DM men. These findings may help explain the similar rates of coronary artery disease and mortality in diabetic men and women.

Emergency cerclage in the presence of protruding membranes: is pregnancy outcome predictable?

BACKGROUND: The aim of this retrospective study is to verify whether some maternal features are related to pregnancy outcome in cases of emergency mid-trimester cerclage when membranes are protruding through the dilated cervix. METHODS: Between 1988 and 1996 twenty-three pregnant patients with dilated cervix and protruding membranes were treated with emergency cerclage. At the time of cerclage, gestational age ranged from 17 to 27 weeks (median 22). RESULTS: Pregnancy was prolonged from 0 to 20 weeks (median 4). Eleven living infants were born (46%); median gestational age at delivery was 25 weeks (range 21-39) and median birth weight 700 g (range 350-3980 g). Obstetric histories, white blood cell count, and vaginal-cervical and urine cultures obtained on admission were analyzed in the two following groups: data from patients with good pregnancy outcome (live births) versus those from patients with poor outcome (stillbirths and neonatal deaths). No significant difference was found between the groups for the above mentioned maternal features. CONCLUSIONS: The possibility of 46% live births is considered a good result for mid-trimester emergency cerclage when the membranes are protruding. Success of the procedure remains unpredictable on the basis of the maternal features investigated.

Birth weight in pre-eclamptic and normotensive twin pregnancies: an analysis of discordance and growth restriction.

The aim of this study was to verify whether twin pregnancies complicated by pre-eclampsia were associated with a higher rate of inter-twin weight discordance or an increased prevalence of small for gestational age (SGA) neonates than in normotensive twin pregnancies. A 17 year retrospective study was undertaken by examining 76 twin pregnancies complicated by pre-eclampsia and comparing them with 400 normotensive twin pregnancies. The case notes were reviewed in reference to birth weight differences, birth order, pregnancy outcome and inter-twin birth weight discordance. Statistical analyses were performed with t-test, contingency tables, regression curves, rank sum test and non-parametric survival plots. Power analysis was also carried out. Pre-eclamptic twin pregnancies were delivered at similar weeks of gestation to normotensive. They resulted in a smaller size for the second twin the earlier the delivery week, while in normotensive twin pregnancies no significant difference occurred at any week. Twin pregnancies complicated by pre-eclampsia showed higher rates of SGA neonates among second twins than those with normal pressure. The >25% discordance was associated with lower gestational age at delivery in each group [mean (range) 33 weeks (27-38) versus 37 (29-41), P < 0.005 pre-eclampsia and 35 weeks (25-41) versus 38 (25-42), P < 0.001 normotensive]. In pre-eclampsia the concomitant occurrence of SGA second twin and the discordance >25% was associated with shorter gestation while the presence of SGA second twin alone was not.

Carbohydrate metabolism in gestational diabetes: effect of chronic hypertension.

OBJECTIVE: To evaluate whether the coexistence of chronic hypertension and gestational diabetes mellitus (GDM) is characterized by a greater impairment of carbohydrate metabolism than GDM alone. METHODS: Carbohydrate metabolism of eight women with chronic hypertensive GDM and 15 normotensive women with GDM was evaluated in the third trimester using the oral glucose tolerance test (GTT) and hyperinsulinemic-euglycemic clamp technique. Controls were ten normotensive, glucose-tolerant, pregnant women in the third trimester. RESULTS: Insulin sensitivity of women with chronic hypertension and GDM was approximately twofold lower than those with GDM only (1.54+/-0.35 versus 4.15+/-0.31, P < .001) and approximately fivefold lower than controls (1.54+/-0.35 versus 7.65+/-0.66, P < .001). Women with chronic hypertension and concomitant GDM had higher insulin levels in response to GTT than controls (P < .001 repeated measures analysis of variance). In all subjects, mean arterial pressure (MAP) had a strong negative correlation with maternal insulin sensitivity (r = -0.62, P < .001). Significant correlation was also found between percent of body fat and insulin sensitivity (r = -0.53, P < .002). Those regressions were still significant when adjusted for percent of body fat and MAP. CONCLUSION: Gravidas with chronic hypertension and GDM are more insulin resistant than those with GDM alone. Blood pressure, in a population of pregnant women with normal and abnormal carbohydrate metabolism, is a stronger predictor of insulin resistance than adiposity.

Dual energy X-ray absorptiometry assessment of fat mass distribution and its association with the insulin resistance syndrome.

OBJECTIVE: To determine which dual energy X-ray absorptiometry (DXA)-derived indices of fat mass distribution are the most informative to predict the various parameters of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 87 healthy men, 63 lean (% fat < or =26) and 24 obese (% fat >26), underwent DXA scanning to evaluate body composition with respect to the whole body and the trunk, leg, and abdominal regions from L1 to L4 and from L3 to L4. These regions were correlated with insulin sensitivity determined by the euglycemic-hyperinsulinemic clamp, insulin area under the curve after oral glucose tolerance test (AUC I); triglyceride; total, HDL, and LDL cholesterol; free fatty acids; and blood pressure. The analyses were performed in all subjects, as well as in lean and obese groups separately. RESULTS: Among the various indices of body fat, DXA-determined adiposity in the abdominal cut at L1-4 level was the most predictive of the metabolic variables, showing significant relationships with glucose infusion rate ([GIR], mg kg(-1) lean body mass x min(-1)), triglyceride, and cholesterol, independent of total-body mass (r = -0.267, P<0.05; r = 0.316, P<0.005; and r = 0.319, P<0.005, respectively). Upon subanalysis, these correlations remained significant in lean men, whereas in obese men, only BMI and the amount of leg fat (negative relationship) showed significant correlations with triglyceride and cholesterol (r = 0.438, P<0.05; r = 0.458, P<0.05; r = -0.439, P<0.05; and r = -0.414, P<0.05, respectively). The results of a multiple regression analysis revealed that 47% of the variance in GIR among all study subjects was predicted by AUC I, fat L1-4, diastolic blood pressure (dBP), HDL, and triglyceride as independent variables. In the lean group, fat L1-4 alone accounted for 33% of the variance of GIR, whereas in obese men, AUC I and dBP explained 68% of the variance in GIR. CONCLUSIONS: The DXA technique applied for the evaluation of fat distribution can provide useful information regarding various aspects of the insulin resistance syndrome in healthy subjects. DXA can be a valid, accurate, relatively inexpensive, and safer alternative compared with other methods to investigate the role of abdominal body fat distribution on cardiovascular risk factors.

Gestational hypertension but not pre-eclampsia is associated with insulin resistance syndrome characteristics.

The aim of this study was to assess whether the metabolic characteristics of insulin resistance syndrome are present in pre-eclamptic (PE), gestational (GH) and chronic hypertensive (CH) pregnancies. Glucose and insulin serum concentrations, both fasting and after oral administration of a glucose tolerance test, were evaluated in 26 hypertensive pregnant women (10 PE, 10 GH and six CH patients) and in 10 healthy controls during the third trimester of gestation. Insulin sensitivity was assessed using the hyperinsulinaemic-euglycaemic clamp technique. The plasma concentrations of triglyceride (TG), high density (HDL), low density (LDL), and very low density (VLDL) lipoprotein cholesterol, apolipoproteins AI and B, and non-esterified fatty acid (NEFA) were also measured. Women with GH exhibited approximately 40% lower steady-state insulin sensitivity index (ISI) compared to controls (3.75 versus 6.34, P < 0.03), as well as approximately 33% higher mean plasma TG (3.57 versus 2.68 mmol/l, P < 0.01), and approximately 69% higher mean NEFA (0.59 versus 0.35 mmol/l, P < 0.01). Women with PE showed similar ISI but reduced insulin and glucose areas under curve compared to controls (P < 0.006, P < 0.0005 respectively). Women with PE also had higher HDL-cholesterol and apo-AI than controls. Patients with CH had similar lipid and carbohydrate metabolism to control subjects. In conclusion, women with GH exhibit metabolic features similar to those of patients with insulin resistance syndrome, suggesting that similar abnormalities could be involved in the pathogenesis of these disorders. In contrast, our data do not support an association between insulin resistance syndrome and hypertension in pregnant women with PE and chronic hypertension.

Effect of maternal carbohydrate metabolism on fetal growth.

OBJECTIVE: To determine the effect of maternal carbohydrate metabolism and anthropometric characteristics on fetal growth. METHODS: Eight pregnant women in the third trimester with unexplained fetal growth restriction (FGR) and 11 women with normal pregnancies in the third trimester were evaluated for maternal carbohydrate metabolism, using oral glucose tolerance tests and hyperinsulinemic-euglycemic clamps. These data and maternal anthropometric characteristics subsequently were related to relative birth weight, defined as observed birth weight x 100/50th percentile birth weight. RESULTS: The women with FGR pregnancies were more insulin sensitive than were controls (21.6+/-4.4 versus 16.7+/-4.8 micromol/kg x min, P < .05) and showed reduced insulin and glucose areas under the curve (96,293+/-25,870 versus 145,291+/-49,356 pmol/L, P < .03; 1057.0+/-184.7 versus 1210.1 +/-85.9 mmol/L, P < .05, respectively). No differences were seen in fasting plasma glucose, insulin and human placental lactogen samples, age, height, pregravid weight, weight gain, and parity. In all patients, maternal insulin sensitivity and weight gain correlated well with relative birth weight (r =-.65, P < .002; r=.68, P < .001, respectively). When the same analysis was computed separately in the groups, insulin sensitivity exhibited a strong negative correlation with relative birth weight in the FGR group but not in controls (r=-.84, P < .007; r=-.54, P=.08, respectively). Conversely, in control women the best correlation between relative birth weight and the other variables studied was seen with maternal weight gain (r=.82, P < .002). CONCLUSION: Women with unexplained FGR have a different glucose metabolic pattern than do normals. We speculate that increased insulin sensitivity leads to a reduction in metabolic substrates for fetal growth.

Endocrino-metabolic features in women with polycystic ovary syndrome during pregnancy.

To elucidate the mechanism of metabolic adaptation of women with polycystic ovary syndrome (PCOS) during pregnancy, the endocrino-metabolic features of a group of PCOS patients with or without gestational diabetes were studied longitudinally during the three trimesters of gestation. Oral glucose tolerance test (OGTT, 100 g) and hyperinsulinaemic-euglycaemic clamp were performed throughout the study. Plasma concentrations of insulin and glucose were determined by radioimmunoassay and glucose oxidase technique, respectively. Five of 13 PCOS patients developed gestational diabetes (GD) at the third trimester (PCOS-GD), while the other eight patients did not develop any alteration of glucose metabolism (PCOS-nGD). Both fasting glucose and insulin plasma concentrations did not change significantly during pregnancy and no difference was seen between the two groups. On the contrary PCOS-GD group early exhibited higher values of area under the curve (AUC) for glucose and insulin response to OGTT with respect to those found in PCOS-nGD group. This difference was already significant in the first gestational trimester. Moreover insulin sensitivity value (M) was significantly lower in the first trimester of gestation in PCOS-GD as compared with that found in PCOS-nGD group. However, as gestation proceeded, M value decreased in PCOS-nDG group and the difference from PCOS patients developing gestational diabetes was not sustained into the second and third trimesters. Both groups had similar body mass index values and AUC insulin increase from first to third trimester of gestation. It is concluded that early alteration of insulin sensitivity and secretion constitute specific risk factors in PCOS patients for the development of abnormalities of glucose tolerance.

Pregnancy outcome in women with cardiac valve prosthesis.

Twenty-one pregnancies in 16 women who conceived after cardiac valve replacement were reviewed. Oral anticoagulants were discontinued before conception or as soon as possible for subcutaneous heparin treatment (8000-14,000 IU every 8-12 h) and resumed in the second trimester until the last period of pregnancy when oral anticoagulants were replaced again by heparin. No therapeutic abortion was performed. The spontaneous abortion rate was found to be 14.3% (3/21). Preterm delivery (< or = 37 weeks) and low birth weight babies (< 2500 g) were 29.4% (5/17) and 35.3% (6/17), respectively, significantly more frequent than those of the control group (P < 0.02 and P < 0.0005). No significant statistical difference was found when the rate of spontaneous abortion [14.3% (3/21)] and the rate of fetal growth retardation [11.8% (2/17)] were compared with the control group. The majority of thromboembolic events (6/7) occurred during heparin regimen in three mothers; one of them subsequently died. No coumarin embryopathy was observed and the physical and mental development in the 16 surviving children was good. This study confirms: (1) the increased rate of preterm delivery and infants weighing < 2500 g; (2) the increased risk of maternal thrombosis related to heparin use; and (3) the good follow-up in the surviving children.

Use of bispecific hybrid antibodies for the development of a homogeneous enzyme immunoassay.

Hybrid bispecific monoclonal antibodies reacting with carcinoembryonal antigen (CEA) and with the E. coli enzyme beta-galactosidase (GZ) were produced by fusion of hybridomas or chemical linkage of half-antibodies. Since the original anti-GZ antibody used in these experiments was capable of protecting GZ from thermal denaturation, it was possible, by hybridizing it with two different non-competitive anti-CEA antibodies, to design a homogeneous enzyme immunoassay for quantitation of CEA. In fact, a mathematical analysis of the reaction indicates that, under appropriate concentrations of the reactants, circular complexes can be formed which contain the two hybrid antibodies, the GZ enzyme and the CEA antigen. The stability of these complexes can be expected to be substantially greater than that of the more labile CEA-free GZ-antibody complexes, prompting a significant increase in the amount of enzyme molecules which are bound to antibody and are consequently protected from thermal denaturation. These expectations were supported by experimental results: under appropriate conditions, heat-resistant enzyme activity was indeed proportional to concentration of CEA in the range up to 75 ng/ml. As predicted by theory, however, in the presence of excess CEA - in fact at CEA concentrations which are higher than those of possible clinical relevance - circular complexes tended to open up, leading to a marked prozone effect.