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Objective: To investigate, in pregnant women without gestational diabetes mellitus (GDM), the relation among obstetric/demographic characteristics; fasting, 1-h, and 2-h plasma glucose values resulting from a 75-g glucose load; and the risk of abnormal neonatal anthropometric features and then to verify the presence of a threshold glucose value for a 75-g glucose load above which there is an increased risk for abnormal neonatal anthropometric characteristics.Research Design and Methods: The study group consisted of 829 Caucasian pregnant women with singleton pregnancy who had no history of pregestational diabetes or GDM, who were tested for GDM with a 75-g, 2-h glucose load, used as a glucose challenge test, in two periods of pregnancy (early, 16-20 weeks; late, 26-30 weeks), and who did not meet the criteria for a GDM diagnosis. In the newborns, the following abnormal anthropometric characteristics were considered as outcome measures: cranial/thoracic circumference (CC/TC) ratio /=90th percentile for GA, and macrosomia (birth weight >/=90th percentile for GA), on the basis of growth standard development for our population. For the first part of the objective, logistic regression models were used to identify 75-g glucose load values as well as obstetric and demographic variables as markers for abnormal neonatal anthropometric characteristics. For the second part, the receiver operating characteristic (ROC) curve was performed for the 75-g glucose load values to determine the plasma glucose threshold value that yielded the highest combined sensitivity and specificity for the prediction of abnormal neonatal anthropometric characteristics.Results: In both early and late periods, maternal age >35 years was a predictor of neonatal CC/TC ratio 35 years being an independent predictor for macrosomia. The 2-h, 75-g glucose load values were significantly associated in both periods with neonatal CC/TC ratio /=90th percentile, whereas maternal age >35 years was an independent predictor of both neonatal CC/TC ratio Conclusions: This study documented a significant association, seen even in the early period of pregnancy, between 1-h, 75-g glucose load values and abnormal neonatal anthropometric features, and provided evidence of a threshold relation between 75-g glucose load results and clinical outcome. Our results would therefore suggest the possibility of using a 75-g, 1-h oral glucose load as a single test for the diagnosis of GDM, adopting a threshold value of 150 mg/dl at 16-20 weeks and 160 mg/dl at 26-30 weeks. [ABSTRACT FROM AUTHOR]

Objective: To assess the 24-h glucose levels in a group of nondiabetic, nonobese pregnant women and to verify the presence of correlations between maternal glucose levels and sonographic parameters of fetal growth.Research Design and Methods: A total of 66 Caucasian nonobese pregnant women with normal glucose challenge tests (GCT) enrolled in the study; from this population, we selected 51 women who delivered term (from 37 to 42 weeks completed) live-born infants without evidence of congenital malformations. The women were requested to have three main meals and to perform daily glucose profiles fortnightly from 28-38 weeks without modifying their lifestyle or following any dietary restriction. All subjects were taught how to monitor their blood glucose by using a reflectance meter. Fetal biometry was evaluated by ultrasound scan according to standard methodology at 22, 28, 32, and 36 weeks of pregnancy.Results: The overall daily mean glucose level during the third trimester was 74.7 +/- 5.2 mg/dl. Daily mean glucose values increased between 28 (71.9 +/- 5.7 mg/dl) and 38 (78.3 +/- 5.4 mg/dl) weeks of pregnancy. We found a significant positive correlation at 28 weeks between 1-h postprandial glucose values and fetal abdominal circumference (AC). At 32 weeks, we documented positive correlations between fetal AC and maternal blood glucose levels 1 h after breakfast, 1 and 2 h after lunch, and 1 and 2 h after dinner. At 36 weeks, there was a positive correlation between fetal AC and 1- and 2-h postprandial blood glucose levels. In addition, there was a negative correlation between head-abdominal circumference ratio and 1-h postprandial blood glucose values.Conclusions: This longitudinal study first provides a contribution toward the definition of normoglycemia in nondiabetic, nonobese pregnant women; moreover, it reveals significant correlations of postprandial blood glucose levels with the growth of insulin-sensitive fetal tissues and, in particular, between 1-h postprandial blood glucose values and fetal AC. [ABSTRACT FROM AUTHOR]

Cerebrovascular diseases are rare in pregnancy and mostly caused by rupture of an arterial aneurysm. We present the case of a pregnant woman at 36 weeks of gestation who had a subarachnoid hemorrhage resulting from rupture of an unknown aneurysm, and who underwent a Cesarean section and an endovascular treatment to embolize the aneurysm. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the content and distribution of sugar residues in placentas from pregnancies complicated by hypertensive disorders. Placentas from women with uncomplicated pregnancies (group 1), pregnancies complicated by gestational hypertension (group 2), pregnancies complicated by pre-eclampsia (group 3), pregnancies complicated by pre-eclampsia with HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) (group 4) were collected. Lectins: ConA, WGA, PNA, SBA, DBA, UEA I, GNA, DSA, MAA, SNA, in combination with chemical and enzymatic treatments, were used. Data showed a decrease and/or lack of α-d-mannose, α-d-glucose and d-galactose-(β1-4)-N-acetyl-d-glucosamine in placentas from pre-eclampsia and pre-eclampsia with HELLP syndrome compared with control and hypertension cases. N-acetyl-d-galactosamine appeared and/or increased in placentas from hypertensive disorders. A different distribution of various types of sialic acid was observed in placentas from hypertensive disorders compared with the controls. In particular, placentas from pre-eclampsia, with and without HELLP syndrome, lacked the acetylated sialic acid side-chain. These findings demonstrate various alterations of the carbohydrate metabolism in the placentas from pregnancies complicated by different types of hypertensive disorders. This indicates correlation with the placental morpho-functional changes characteristic of these complications and with the degree of clinical severity., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

The "Barker hypothesis" suggests that low birth weight might predict future risk of developing obesity, cardiovascular disease, and type 2 diabetes. Identification of the causes of fetal growth restriction (FGR) is critical for preventive and management strategies. Some studies indicate that maternal carbohydrate metabolism might be involved in FGR development. We aimed to evaluate, in a large number of normotensive pregnant women with normal glucose tolerance, the effect of insulin sensitivity and β-cell function on unexplained fetal growth. A total of 1,814 Caucasian pregnant women with normal prepregnancy body mass index were tested with a 75-g, 2-h glucose load (24-28 gestation wk). Insulin sensitivity was evaluated with fasting (QUICKI) and dynamic index (OGIS) and β-cell function with a modified insulinogenic index as ΔAUC(insulin)/ΔAUC(glucose) and disposition index. FGR was a birth weight below the 5th percentile for gestational age. FGR developed in 99 (5.5%) pregnant women that showed significantly higher QUICKI, OGIS, insulinogenic, and disposition index with respect to women with normal-weight babies (P < 0.0001). By using multiple regression analysis in the FRG group, QUICKI and OGIS appeared as significant independent variables (P < 0.0001 and P < 0.0366, respectively). We conclude that elevated insulin sensitivity seems to be one of the factors involved in determining unexplained fetal growth retardation; its assessment, even only in the fasting state, could be useful to guide any possible monitoring and therapeutic strategies to reduce fetal complications.

Objective: This prospective study evaluated the impact of gestational diabetes on maternal and fetal outcome in a large cohort of women with gestational diabetes mellitus (GDM) followed up using standardized clinical criteria., Study Design: Between 1999 and 2003, we collected 3465 GDM women from 31 Italian regional obstetric or diabetes centers, recording the time and mode of delivery, gestational hypertension, pre-eclampsia, eclampsia, congenital malformations, and neonatal mortality, comparing findings with the Italian general pregnant population., Results: The rate of cesarean sections was 34.9% and macrosomia 8.7% (33.2 and 7.4%, respectively, in the general population, p=ns). The stillbirth and neonatal mortality rates were no different in GDM patients and normal pregnancies (0.34% vs. 0.30%, p=0.176 and 0.29% vs. 0.32%, p=0.748), but the former had twice as many newborn with congenital malformations (2.05% vs. 0.89%, p<0.01; CI 1.64-2.62). A prognostic model for the outcome of pregnancy was built and the concurrent occurrence of several conditions was deemed as a positive outcome. Pregnancies which did not meet one or more of the above criteria were classified as "complicated". On multivariate logistic analysis, only the week of gestation when GDM was diagnosed and prepregnancy BMI were independent predictors of a complicated pregnancy., Conclusion: When correctly diagnosed and treated during pregnancy, women with GDM have a pregnancy outcome similar to the general pregnant population, except for a greater likelihood of congenital malformations in the newborn, probably due to unrecognized prior diabetes. Prepregnancy obesity plays an important part in raising the risk of adverse perinatal outcomes in GDM patients.

Background and Aim: To determine pregnancy outcome in women with type 1 and type 2 diabetes., Methods and Results: A prospective study was conducted in 33 centers in Italy between 1999 and 2003, mainly recording preterm delivery, stillbirths, neonatal mortality, congenital malformations and birthweight. Of the 668 women examined, 504 had type 1 diabetes and 164 had type 2. Pre-pregnancy counseling had been provided to 43.9% of the women who had type 1 diabetes and 29.1% of the women who had type 2 diabetes and correlated with a better HbA1c value throughout pregnancy. The preterm delivery rate was significantly higher in type 1 and 2 diabetics than in normal pregnant women and was related to HbA1c values higher than 8%, gestational hypertension, pre-eclampsia and the presence of retinopathy before pregnancy. The stillbirth and neonatal mortality rates were also higher in diabetic pregnant women (1.26% and 0.63%, respectively) than in Italian pregnancies in general (0.30% and 0.32%), and the same was true for major congenital malformations (4.9% for diabetic pregnancies, 0.86% for normal Italian pregnancies)., Conclusions: In our population, pregnancy in diabetic women was still associated with a high rate of stillbirths, neonatal mortality and congenital malformations. Unplanned pregnancies and non-optimal glycemia control may help explain the high rates of maternal and neonatal complications.

Objective: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM)., Research Design and Methods: The oral glucose tolerance test (OGTT) was performed in 903 women at 16-20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26-30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and beta-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests., Results: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower beta-cell function than ND. During the late visit, GDM2 also showed impaired beta-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2., Conclusions: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. beta-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.

The aim of the present study was to determine the expression of vascular endothelial growth factor (VEGF) receptors VEGFR-1, VEGFR-2 and VEGFR-3 in placentas from pregnancies complicated by altered glycaemia. Placentas from women with physiological pregnancies (Group 1), pregnancies complicated by minor degree of glucose intolerance (MDGI, Group 2) and by gestational diabetes mellitus (GDM) treated with insulin (Group 3) were collected. Immunohistochemistry, RT-PCR and western blot were employed to evaluate receptor expression. In the three study groups, VEGFR-1 immunoreactivity was detected in all the placental components. VEGFR-2 immunoreactivity was observed in the vessels of all the placentas from Groups 1 and 2, but only in some placentas of Group 3. VEGFR-3 reactivity was observed in all the components of Group 1; in Groups 2 and 3 reactivity was observed in some portions of the trophoblast or the whole trophoblast, and in the stroma. VEGFR-1 and VEGFR-2 mRNA levels in Groups 2 and 3 were significantly higher compared with Group 1, whereas those of VEGFR-3 were significantly lower. Receptor protein levels were significantly lower in Groups 2 and 3 compared with Group 1. These findings demonstrated dysregulation of expression of the three placental receptors, both in GDM and in MDGI.

The aim of this study was to investigate the distribution of the oligosaccharides of the glycoconjugates in placentas from pregnancies complicated by different degree of altered glycaemia. Placentas from women with physiological pregnancies (group 1), with pregnancies complicated by minor degree of glucose intolerance (group 2) and with pregnancies complicated by gestational diabetes mellitus (GDM) treated with insulin (group 3) were collected. Ten lectins were used (ConA, WGA, PNA, SBA, DBA, LTA, UEA I, GSL II, MAL II and SNA) in combination with chemical and enzymatic treatments. The data showed a decrease of sialic acid linked alpha(2-6) to galactose/N-acetyl-D-galactosamine and an increase of N-acetyl-D-glucosamine in the placentas of the pathological groups, in particular the group 3, comparing to the group 1. A decrease of L-fucose (LTA) and D-galactose-(beta1-3)-N-acetyl-D-galactosamine, and an increase and/or appearance of L-fucose (UEA I) and N-acetyl-D-galactosamine were observed in both the pathological groups, particularly in the group 2, with respect to the group 1. In GDM, and even in pregnancies with a simple alteration of maternal glycaemia, the changes in the distribution of oligosaccharides could be related to alteration of the structure and functionality of the placenta.

Objective: Content and distribution of the oligosaccharides in the umbilical cord from pregnancies with altered glycemia were investigated., Study Design: A prospective cohort study was conducted in the Florence Policlinic of Careggi, Italy. Samples of cord from physiological pregnancies (n=20), from pregnancies with minor degree of glucose intolerance (n=20) and from pregnancies with gestational diabetes mellitus (GDM) treated with insulin (n=20) were collected. Eleven lectins were used (ConA, WGA, PNA, SBA, DBA, LTA, UEA I, OOA, GSL II, MAL II and SNA) in combination with chemical and enzymatic treatments., Results: Increase of N-acetyl-d-glucosamine and a loss of sialic acid in the umbilical cord of the cases with minor degree of glucose intolerance with respect to the other study groups was observed. d-Galactose(beta1-->3)-N-acetyl-d-galactosamine, N-acetyl-d-galactosamine and l-fucose were in less amount in both the pathological groups with respect to the control one., Conclusion: The increase of some glycoconjugates carbohydrates and the loss of others in the umbilical cord from pregnancies with minor degree of glucose intolerance might be related to its morphofunctional alterations in a not diabetic altered glycemia. Moreover, the treatment with insulin in the GDM might play a role in restoring partially the normal glycosilation in the cord components in the attempt to renew some their functions.

The aim of the present study was to determine the expression of vascular endothelial growth factor (VEGF) family receptors (VEGFR) in placentas from pregnancies complicated by hypertensive disorders of different clinical severity. Placental tissue from women with gestational hypertension, pre-eclampsia, pre-eclampsia with haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) and normotensive women, as a control group, was examined. Immunohistochemical techniques, reverse transcription-polymerase chain reaction and western blot were used to evaluate receptor expression. In cases with gestational hypertension, as well as in control cases, VEGFR-1 and VEGFR-3 immunoreactivity was detected in all placental components, whereas in placentas from the pre-eclampsia and pre-eclampsia with HELLP syndrome groups, VEGFR-1 and VEGFR-3 immunoreactivity was detected only in some portions of trophoblast and/or some vessels and/or clusters of stromal cells. In the control group, VEGFR-2 immunoreactivity was observed only in the vessels, whereas the hypertensive groups showed VEGF-2 immunoreactivity also in trophoblast and stromal cells. The mRNA levels of the three receptors in the group with gestational hypertension were higher with respect to those in the control group. Placentas from pregnancies with pre-eclampsia showed lowest mRNA expression levels, whereas placentas from women with pre-eclampsia plus HELLP syndrome showed higher mRNA expression levels with respect to the three other groups. Receptor protein levels were lower in pathological cases compared with levels in the control group. These findings demonstrate a dysregulation of placental expression of VEGF family receptors related to the degree of clinical severity of the hypertensive disorder.

Certain similarities between preeclampsia and insulin resistance syndrome suggest a possible link between the 2 diseases. The aim of our study was to evaluate 3 insulin sensitivity (IS) indexes (fasting homeostasis model assessment IS [ISHOMA], quantitative insulin sensitivity check index [ISQUICKI], and oral glucose IS [OGIS]) early and late in pregnancy in a large number of normotensive pregnant women with a normal glucose tolerance and to test the ability of these indexes to predict the risk of subsequent preeclampsia. In all, 829 pregnant women were tested with a 75-g, 2-hour oral glucose load in 2 periods of pregnancy: early (16 to 20 weeks) and late (26 to 30 weeks). In early and late pregnancy, respectively, IS(HOMA) was 1.23+/-0.05 and 1.44+/-0.05 (P<0.01), IS(QUICKI) was 0.40+/-0.002 and 0.38+/-0.002 (P<0.01), and OGIS was 457+/-2.4 mL min(-1) m(-2) and 445+/-2.2 (P<0.001), all confirming the reduction in insulin sensitivity during pregnancy. Preeclampsia developed in 6.4% of the pregnant women and correlated positively with the 75th centile of IS(HOMA) (P=0.001), with a sensitivity of 79% in the early and 83% in the late period and a specificity of 97% in both. IS(QUICKI) <25th centile was also related with preeclampsia (P=0.001), with a sensitivity of 85% in the early and 88% in the late period and a specificity of 97% in both. Judging from our findings, ISHOMA and ISQUICKI are simple tests that can pinpoint impaired insulin sensitivity early in the pregnancy. Given their high sensitivity and specificity, these indexes could be useful in predicting the development of preeclampsia in early pregnancy, before the disease become clinically evident.

The role of thrombophilia in the pathogenesis of preeclampsia is controversial. The aim of this case-controlled study was to determine whether thrombophilia increases the risk of preeclampsia or interferes with its clinical course. A total of 808 white patients who developed preeclampsia (cases) and 808 women with previous uneventful pregnancies (controls) matched for age and parity were evaluated for inherited and acquired thrombophilia (factor V Leiden; factor II G20210A; methylenetetrahydrofolate reductase C677T; protein S, protein C, and antithrombin III deficiency; anticardiolipin antibodies; lupus anticoagulant; and hyperhomocysteinemia). Odds ratios (ORs) with 95% confidence intervals (CIs) for risk of being carriers of thrombophilia in cases compared with controls and for risk of maternal life-threatening complications and adverse perinatal outcomes in preeclamptic patients with or without thrombophilia were calculated. Women with severe preeclampsia (406 cases) had a higher risk (OR, 4.9; 95% CI, 3.5 to 6.9) of being carriers of either an inherited or acquired thrombophilic factor, except for protein S, protein C, and antithrombin deficiency. In women with mild preeclampsia (402 cases), only prothrombin and homozygous methylenetetrahydrofolate reductase gene mutations were significantly more prevalent than in the controls. Thrombophilic patients with severe preeclampsia are at increased risk of acute renal failure (OR, 1.8; 95% CI, 1.5 to 2.2), disseminated intravascular coagulation (OR, 2.7; 95% CI, 1.1 to 6.4), abruptio placentae (OR, 2.6; 95% CI, 1.2 to 6.0) and perinatal mortality (OR, 1.7; 95% CI, 1.5 to 2.2) compared with nonthrombophilic preeclamptic patients. Our study demonstrates a significant association between maternal thrombophilia and severe preeclampsia in white women. Thrombophilia also augments the risk of life-threatening maternal complications and adverse perinatal outcomes in preeclamptic patients.

Data from literature report that angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the recurrence of preeclampsia and that low-molecular-weight heparin (LMWH) prevents adverse outcomes in thrombophilic women. We investigated the effect of LMWH on the pregnancy outcome, on maternal blood pressure values, and on uteroplacental flow in ACE DD nonthrombophilic women with history of preeclampsia. Eighty nonthrombophilic ACE DD women were randomized in 2 groups: 41 treated with dalteparin 5000 IU/day and 39 untreated (control group). Women underwent 24-hour automated blood pressure monitoring in the preconceptional period and every 2 weeks from weeks 8 to 36 and transabdominal color flow/pulsed Doppler examination at weeks 16, 20, and 24. LMWH reduced the risk of clinical negative outcomes (74.1% reduction of preeclampsia and 77.5% reduction of fetal growth restriction) and the severity (88.3% reduction of early onset of preeclampsia and 86.4% reduction of early onset of fetal growth restriction). In treated women, the relative risk for preeclampsia was 0.26 (P=0.02), and the relative risk for fetal growth restriction was 0.14 (P<0.001). Systolic (P=0.002) and diastolic (P=0.002) blood pressures, as well as awake (P=0.04) and asleep (P=0.01) period values, and the resistance indexes of both uterine arteries (P=0.002) were lower in the treated group. LMWH reduces the recurrence of preeclampsia, of negative outcomes, and the resistance of uteroplacental flow, and also prevents maternal blood pressure increase in ACE DD homozygote women with a previous history of preeclampsia.

Objective: To determine the expression of VEGF in the placental tissue from pregnancies complicated by hypertension disorders of different clinical severity., Design: Prospective cohort study., Setting: Polyclinic of Careggi, University of Florence, Italy., Sample: Placentas from women with gestational hypertension (n= 20), pre-eclampsia (n= 20) and pre-eclampsia with HELLP syndrome (n= 20) and from normotensive women (n= 20), as control group (gestational age comprised between 35 and 38 weeks)., Methods: An immunohistochemical technique and a quantitative analysis to measure mRNA levels (RT-PCR) were employed., Main Outcome Measures: Intensity of immunoreactivity and mRNA levels in the placental components. Differences between the data., Results: VEGF immunoreactivity was observable in all the placental components in the gestational hypertension cases as in the control ones. In the cases with pre-eclampsia and pre-eclampsia with HELLP syndrome, some placental components were not immunoreactive. However, the VEGF positive components of all the pathological groups showed a higher intensity of reactivity with respect to that of the control group. The levels of VEGF mRNA were higher in the gestational hypertension cases and lower in the cases of pre-eclampsia with HELLP syndrome with respect to the control ones; in the cases of pre-eclampsia, the levels were the same as the control ones., Conclusion: The different expression of VEGF in the placenta of the pathological cases is probably related to haemodynamic changes that take place in these disorders, in order to attempt restoration of a normal uteroplacental flow.

Objective: To compare maternal glucose levels and neonatal outcome, achieved in women with gestational diabetes (GDM) receiving either regular insulin or insulin lispro, with those of a control group of non-diabetic pregnant women., Study Design: We enrolled 49 pregnant women with GDM, randomly allocated to the treatment with either insulin lispro (n=25) or regular insulin (n=24), and 50 pregnant women with normal GCT, matched for age, parity, pre-pregnancy weight and BMI, who formed the control group. All the women were caucasian, non-obese, with a singleton pregnancy and delivered term live born infants. Women of both groups were requested to perform a blood glucose profile (consisting of nine determinations: fasting/pre-prandial, 1 and 2h post-prandial) every week from the time of diagnosis to 38 weeks (study subgroups) or every 2 weeks from 28 to 38 weeks' gestation (control group)., Results: Overall pre-prandial blood glucose values in diabetic women were significantly higher than those of controls; at the 1h post-prandial time point, blood glucose values of GDM women receiving insulin lispro were similar to those of controls, whereas in the regular group they were significantly higher. Overall, both the lispro and regular insulin obtained optimal metabolic control at the 2h post-prandial time point, although near-normal blood glucose levels 2h after lunch could be observed only in the lispro group. There were no statistically significant differences between the groups in neonatal outcome and anthropometric characteristics; however, the rate of infants with a cranial-thoracic circumference (CC/CT) ratio between the 10th and the 25th percentile was significantly higher in the group treated with regular insulin in comparison to the lispro and control groups., Conclusions: Fasting/pre-prandial and 1h post-prandial maternal blood glucose levels in non-diabetic pregnant women fell well below the currently accepted criteria of glycemic normality in diabetic pregnancies. In women with GDM, the use of insulin lispro enabled the attainment of near-normal glucose levels at the 1h post-prandial time point and was associated with normal anthropometric characteristics; the use of regular insulin was not able to blunt the 1h peak post-prandial response to a near-normal extent and resulted in infants with a tendency toward the disproportionate growth. Insulin lispro can be regarded as a valuable option for the treatment of gestational diabetes.

Objective: To investigate the maternal demographic and metabolic factors contributing to the growth of fetal lean and fat body mass in women whose degree of glucose intolerance is less than that defining gestational diabetes in comparison with women with normal glucose metabolism., Research Design and Methods: Longitudinal sonographic examinations of 66 singleton fetuses without anomalies of nonobese mothers with abnormal oral glucose challenge test (GCT) results and without gestational diabetes (group 1) were compared with those of 123 singleton fetuses without anomalies of nonobese mothers with normal GCT values (group 2). Lean body mass measurements included head circumference, femur length, mid-upper arm, and mid-thigh central areas. Fat body mass measurements included the anterior abdominal wall thickness, the subscapular thickness, and the mid-upper arm and mid-thigh subcutaneous areas. All the women performed a 24-h glucose profile on the day preceding the ultrasound scan. Multivariate logistic regression analysis established best-fit equations for fetal sonographic measurements of fat and lean body mass. Independent variables included groups 1 and 2, maternal age, parity, prepregnancy BMI, gestational age, weight gain during pregnancy, fetal sex, and the following averaged 24-h profile maternal capillary blood glucose values: preprandial, 1-h postprandial, and 2-h postprandial., Results: No difference was found between the two groups with respect to fetal lean body mass parameters; the factors that contributed significantly and most frequently were gestational age and fetal sex (male). With respect to fetal fat body mass, all the measurements were significantly higher in group 1 than in group 2. In all instances, the significantly contributing factors were gestational age and maternal 1-h postprandial glucose values, whereas another frequent contributor was prepregnancy BMI., Conclusions: Our study suggests the possibility of using sonographically determined fetal fat and lean mass measurements as indicators of body composition. The assessment of these parameters, achievable in a noninvasive and reproducible fashion in pregnancies complicated by glucose intolerance, might enable the real-time detection of fetal overgrowth and disproportion, thus opening the possibility of exploring interventions to limit fetal fat accretion, birth weight, and potential resulting morbidity.

The risk for an adverse pregnancy outcome is markedly higher in women with history of preeclampsia. This may stem from impaired placentation in early gestation and from high impedance to flow in uteroplacental circulation. The renin-angiotensin system is one of the mediators of the remodeling of spiral arteries throughout pregnancy. The D allele of the Insertion/Deletion (I/D) polymorphism in the ACE gene has been associated with higher ACE activity, accounting for 47% of the total phenotypic variance of serum enzyme levels. To investigate whether the ACE I/D polymorphism affects maternal uteroplacental and fetal umbilical circulation and the pregnancy outcome in women with a history of preeclampsia, 106 women underwent Doppler examination of uterine arteries resistance index and umbilical artery pulsatility index at the 16th, 20th, and 24th weeks of gestation and were genotyped for the I/D polymorphism. This study found a difference in genotype distribution (P=0.0002) and allele frequency (P<0.0001) between women with and those without preeclampsia recurrence and fetal growth restriction as well as an association (P=0.0007) between DD genotype and risk of recurrent preeclampsia or fetal growth restriction. At the 16th, 20th, and 24th weeks, uterine artery resistance indexes were significantly lower in II, higher in DD, and intermediate in ID genotype carriers, whereas the umbilical artery pulsatility index values were significantly higher in the DD group in comparison to ID and II genotypes. The current study shows that the ACE I/D polymorphism affects uteroplacental and umbilical flows and the recurrence of an adverse pregnancy outcome in women with history of preeclampsia.

Pregnancy-induced hypertensive disorders (PIHD) are common complications of pregnancy and are associated with increased maternal and fetal morbidity. In this study, artificial neural networks (aNN) and multivariate logistic regression (MLR) were applied to a set of clinical and laboratory data (urea, creatinine, uric acid, total proteins, hematocrit, iron and ferritin) collected at 16 and 20 weeks of gestation. The efficacy of the two approaches in predicting the development of PIHD in 303 consecutive normotensive pregnant women at high risk of pre-eclampsia and intrauterine fetal growth retardation was then compared. The aNN were trained with a randomly selected set of 187 patient records and evaluated on the remainder (n=116). MLR analysis was done with the same 116 patients. The performance of each model was assessed using receiver operator characteristic (ROC) curves. Pregnancies had a normal physiological course in 227 cases, whereas 76 (25.1%) women developed PIHD during the third trimester. The best aNN at 20 weeks yielded an area under the ROC curve of 0.952, the sensitivity of 86.2%, the specificity of 95.4%, the positive predictive value of 86.2% and the negative predictive value of 95.5% for PIHD. The corresponding values for the MLR at 20 weeks were 0.962, 79.3%, 97.7%, 92% and 93.4%, respectively. The computer-aided integrated use of these conventional tests seems to provide a useful means for and early prediction of PIHD development.

HELLP syndrome is a severe complication of pregnancy characterized by microangiopathic hemolytic anemia, hepatic dysfunction and thrombocytopenia. Though delivery is the ultimate therapeutic option, medical treatments, including the use of heparin or corticosteroids, have been employed in the attempt to improve maternal prognosis. The aim of this retrospective study was to compare the time course of recovery and the incidence of complications in women with HELLP syndrome receiving either heparin or dexamethasone. Between January 1990 and December 1998, 32 patients with HELLP syndrome were cared for at the Institute of Obstetrics and Gynecology of the University of Florence: 20 patients were treated with heparin, administered subcutaneously at a dose of 5000 IU every 12 h, whereas 12 women received dexamethasone, administered intravenously at a dose of 10 mg every 12 h. Categorical data were evaluated with chi-square and Fisher's exact test; continuous data were analyzed with Mann-Whitney U test; P < .05 was considered significant. In the subgroup treated with heparin the incidence of disseminated intravascular coagulation (DIC) (P < .02), the number of patients requiring blood transfusion (P < .05) and the length of stay at the Intensive Care Unit (ICU) (P < .04) were significantly increased as compared with the subgroup receiving dexamethasone; in this latter subgroup, significantly higher platelet count and hematocrit values, and significantly lower levels of lactate dehydrogenase (LDH) could be documented starting from day 2 after delivery. The results of our investigation suggest that the use of dexamethasone in patients with HELLP syndrome is associated with faster regression and lower incidence of complications in comparison to heparin.

Objective: To evaluate the cardiovascular response to active postural changes in pregnancy., Design: Prospective study., Setting: Outpatient Clinic, Fetal Maternity Unit., Participants: Sixteen healthy women referred prior to pregnancy., Methods: Heart rate, arterial pressure, echocardiographic end-diastolic and end-systolic left ventricular volumes (Teichholz' s formula) were measured in the three months before pregnancy, at the end of the first and second trimester, at mid third trimester, and six months after delivery in the supine and standing position, in thirteen women (mean age 33, range 25-38 years)., Results: Cardiac output (supine position) significantly increased (28%): it reached its maximum at the second trimester, remained steadily elevated in the mid third trimester, and returned to baseline after delivery. Cardiac output increased during pregnancy also in the active orthostatic position, the percentage increase being greater (70%) since the standing pre-conception value was lower. The postural stress induced similar changes in heart rate, arterial pressure and left ventricular ejection fraction before, during and after pregnancy. However, the reduction in cardiac output associated with early standing attenuated significantly at the second trimester and it was absent at mid third trimester (F = 3.13, P = 0.021). This was due to the interplay between the significantly lesser increase in systemic vascular resistance, occurring since the first trimester, and the significantly lesser decrease in left ventricular end-diastolic volume which was observed in the mid third trimester., Conclusion: These data indicate that the elevated cardiac output is adequately maintained in pregnancy during the postural challenge, due to optimisation of the responses of preload and afterload.

Complications of pregnancy have been found to be related with thrombophilic polymorphisms that explain about 30% of obstetric complications. We evaluated the angiotensin converting enzyme (ACE) and the angiotensin type 1 receptor (AT1R) gene polymorphisms in the renin-angiotensin system (RAS) as possible risk factors for fetal loss. Fifty-nine women with a history of three or more first-trimester fetal losses and 70 healthy women with a history of normal pregnancies were enrolled in this study. Thrombophilic factors, ACE insertion/deletion (I/D) and AT1R A1166C polymorphisms, prothrombin G20210A and factor V Leiden mutations were analyzed. At univariate and multivariate analysis, a significant association between ACE DD and AT1R CC genotype and fetal loss was observed. The effect of the ACE DD genotype on the risk of fetal loss was higher in AT1R C allele carriers. The prevalence of hyperhomocysteinemia (Hcy) (defined as baseline plasma levels higher than the 95% percentile; cut-off, 10.5 micromol/l per l) was significantly higher in women with fetal loss, and an association between Hcy and fetal loss was detected. All patients showed normal antithrombin, protein C, protein S, and plasminogen activator inhibitor-1 (PAI-1) values. The presence of one risk factor not associated with others was found in 33 out of 59 patients (56%); ACE DD genotype was the most prevalent risk factor. Our results identify new possible predictive markers for fetal loss in RAS polymorphisms and Hcy. Large-scale studies are warranted to attribute clinical relevance to these polymorphisms as risk factors for complicated pregnancies.

Objective: To assess what degree of maternal metabolic control in women with type 1 diabetes is associated with normal fetal growth and results in normal neonatal body proportions in a group of full-term infants., Research Design and Methods: We investigated the anthropometric characteristics of 98 full-term singleton infants born to 98 Caucasian women with type 1 diabetes enrolled within 12 weeks of gestation. The type 1 diabetic mother-infant pairs were divided into three groups on the basis of the daily glucose levels reached during the second and third trimesters of pregnancy (group 1: 37 mother-infant pairs with an average daily glucose level during the second and third trimesters of < or =95 mg/dl; group 2: 37 mother-infant pairs with an average daily glucose level during the second trimester of >95 mg/dl and during the third trimester of < or =95 mg/dl; group 3: 24 mother-infant pairs with an average daily glucose level during the second and third trimesters of >95 mg/dl; control group: 1,415 Caucasian mother-infant pairs with full-term singleton pregnancies and normal glucose challenge test screened for gestational diabetes., Results: Infants of diabetic mothers in group 1 were similar to those of the control group in birth weight and in other anthropometric parameters. In contrast, offspring of diabetic mothers of groups 2 and 3 showed an increased incidence of large-for-gestational-age infants, significantly greater means of ponderal index and thoracic circumferences, and significantly smaller cranial/thoracic circumference ratios with respect to the control group., Conclusions: The results of our study suggest that, in diabetic pregnancies, only overall daily glucose values < or =95 mg/dl throughout the second and third trimesters can avoid alterations in fetal growth.

In this study the authors describe a case of acute pericarditis occurring at 26 weeks' gestation in a woman affected by Wolff-Parkinson-White Syndrome and with a history of Hodgkin's Lymphoma and autoimmune hypothyroidism. The patient was first admitted to the 4th Medical Pathology Unit of the University of Florence, where moderate pericardic effusion with no evidence of heart tamponade was documented by ultrasound scan. Subsequently the patient was cared for on outpatient basis at the Centre of Perinatal Medicine of the Department of Obstetrics and Gynaecology of the University of Florence. Since all examinations and tests aimed at defining the etiology of pericardial effusion were negative, an idiopathic acute pericarditis was diagnosed. The patient was given prednisone at a dose of 75 mg per day; owing to episodes of paroxystic atrial fibrillation, propaphenon was also administered intravenously to treat acute episodes and orally as prophylaxis. The patient underwent close control of both heart function (by means of ultrasound scans of the heart and dynamic EKG) and pregnancy (blood tests, ultrasound scans and Doppler velocimetry). At 36.5 weeks' gestation a healthy fetus was spontaneously delivered. Three months after delivery, the patient underwent an ultrasound scan that demonstrated the complete reabsorption of the effusion.

Following the observation that non-organ-specific antibodies are related with pregnancy loss and preeclampsia, the role of organ-specific antibodies is currently being extensively investigated. The aim of this study was on the one hand to evaluate the incidence of antithyroid antibodies in a study group of 69 women with a history of early pregnancy loss (subgroup 1), foetal death (subgroup 2) or preeclampsia (subgroup 3) and in a control group, on the other hand to assess the possible association of these autoantibodies with non-organ-specific antibodies and subclinical alterations of thyroid function in the study group. Antithyroid antibodies were present in 26/69 (37.7%) women of the study group (37.9% in subgroup 1; 40.9% in subgroup 2; 33.3% in subgroup 3) and in 10/69 (14.5%) of controls, the difference being statistically significant. A significant difference in the distribution of antibodies to thyroglobulin and thyroid peroxidase was found in subgroup 2. In the study group, the incidence of antiphospholipid antibodies was not significantly different in women positive (26.9%) and negative (34.9%) for antithyroid antibodies. Also, the overall incidence of subclinical alterations of thyroid function in the study group was significantly different in women positive (53.8%) and negative (16.2%) for thyroid autoimmunity (P<0.02). The results of this study seem to confirm the association between thyroid autoimmunity and obstetric complications and suggest the usefulness of undertaking prospective studies in order to evaluate the reproductive outcome of women with a history of recurrent abortion, foetal death or preeclampsia and positivity for antithyroid antibodies.

Activated protein C resistance (APCR) is a common cause of familial thrombophilia and venous thrombosis. The aim of the study was to investigate the prevalence of APCR associated with factor V Leiden mutation and its relevance in comparison to other risk factors for thromboembolic disorders in women with a history of previous complicated pregnancies (history of fetal loss in the second and third trimester n = 34, preeclampsia n = 46). The frequency of APCR was significantly higher in women with a history of fetal loss and preeclampsia (23.5 and 26.1%, respectively) compared with a control group (3.8%). The prevalence of antithrombin, protein C and protein S deficiencies and the presence of antiphospholipid antibodies were also investigated: the prevalence of at least one disorder was 41.2% in the group with previous fetal loss, 37.0% in the group with previous preeclampsia and 7.5% in the control group., (Copyright 2000 S. Karger AG, Basel)

The aim of this study was to evaluate the extent to which the presence of a transplanted kidney conditions the physiological renal and maternal cardiocirculatory adaptation to pregnancy. For this purpose, we compared the trend of cardiocirculatory and renal hematochemical parameters in a kidney-transplant patient to a group of 100 physiological pregnant women followed longitudinally. M. G., aged 36, primigravida, who underwent renal transplantation ten years before, was carefully monitored throughout gestation. Pregnancy was free of complications and ended at 38 weeks with an elective caesarian section. The trend of the parameters mirrored the physiological pattern, even if the values for some renal parameters were completely different. This type of comparison enabled us to evaluate the adaptation of the transplanted organ and the body to pregnancy and to formulate a prognostic judgement halfway through pregnancy regarding the outcome.

Blood pressure (BP) differences between two consecutive 24-h monitoring periods (P1, P2) were analyzed in 159 hospitalized pregnant women. Reproducibility index, or twice the standard deviation of differences between individual systolic and diastolic means, was better for 24-h (7.8 and 5.8) and daytime (8.7 and 6.3) than for nighttime (12.2 and 9.7) BP means. It did not depend on BP level or gestation week. Alert reaction to monitoring procedure increased BP only in the first 2 h of P1. The high overall reproducibility of ambulatory BP in pregnancy supports the expanding use of the technique also in this condition.

Background and Aim: To correlate the perinatal outcome of insulin-dependent diabetic (IDDM) pregnant women with the quality of metabolic control defined as gestational age at initial visit, extent and duration., Materials and Methods: A total of 64 pregnant women classified from White's class B to class R were included in the study: 55 pregnant women joined the study before the 9th week (early control group), 9 after the 26th week (late control group). On the basis of perinatal outcome, the 55 pregnant women in the early control group were then subdivided into a further two groups: 34 patients with optimal outcome and 21 with non-optimal outcome., Results: In the early control group of pregnant women, overall mean daily glycemia was significantly lower in the group with optimal outcome compared to that with non-optimal outcome during the 1st and 2nd trimester, but not in the 3rd. Compared to the early control group, during the 3rd trimester patients in the late control group showed significantly higher levels of: overall mean daily glycemia, glycosylated hemoglobin and fructosamine. In the early control group maternal morbidity (p < 0.05), neonatal morbidity (p < 0.03) and perinatal mortality (p < 0.05) were significantly lower than in the late control group., Conclusions: The achievement of optimal glycometabolic control in the 2nd trimester appears to be a prerequisite for improving maternal-fetal outcome in the early control group compared to that in the late control group in which the attainment of good glycemic control during the 3rd trimester does not seem to be efficacious in reducing overall morbidity and mortality.

Background and Aim: To evaluate the hypothesis that insulin-dependent diabetic (IDDM) pregnant women have a threshold of glycemic control during the first trimester of pregnancy for an increased risk of spontaneous abortion., Materials and Methods: Seventy IDDM pregnant women were enrolled before the 9th week of gestation and monitored throughout pregnancy. Fifteen pregnancies (21.4%) led to spontaneous abortion within the first trimester (study group) and 55 (76%) continued until term (control group). In order to evaluate the differences between the study group and the control group variance analysis and Student's t-test were used for constant variables and chi 2 and Fisher's exact test for discrete variables; p < 0.05 was considered statistically significance., Results: Mean levels of glycosylated hemoglobin (HbA1c) and fructosamine at the initial prenatal visit were significantly higher in the study group (p < 0.03) compared to the control group. The threshold for an increased risk of spontaneous abortion in the first trimester was found to be initial concentrations > 8% for HbA1c and > 300 mmol/l for fructosamine., Conclusions: Pregnant women suffering from IDDM with initial HbA1c levels higher than 8% and fructosamine > 3 mmol/l have an increased risk of spontaneous abortion in the first trimester of pregnancy. Below this threshold the risk of spontaneous abortion during the first trimester of pregnancy is similar to that for non-diabetic pregnant women.

Background: Low plasma zinc concentrations in pregnant women have been associated with certain obstetric and foetal complications. However, there is no agreement in previous studies and mediterranean populations have not been extensively studied., Methods: The plasmatic zinc was tested in 73 mothers, within 24 hours post-partum, in order to evaluate an association between plasmatic zinc and various obstetric and fetal complications. The women were all from the Florence province and were admitted for delivery at the II Maternity Ward of the University of Florence (Third level Center); mothers of twins and foreign mothers were excluded. Subjects were consecutively included in the study. The values pointed out in a control group (n = 28) were compared with the hematic zinc of a) women who delivered by cesarean section (CS) for acute fetal distress or by operative delivery with vacuum extractor (n = 9), b,c) mothers whose children weighted over the 90th (LGA: n = 11) or under the 10th percentile (SGA: n = 13), and d) mothers who delivered prematurely (n = 12). The subjects included in two or more groups, were not considered., Results: The plasmatic zinc of the control group has been significantly higher than that of mothers who delivered by vacuum extractor or by urgent CS (p < 0.0001) and than that of mothers whose newborns were LGA (p < 0.0024). The hematic zinc of the control group is not higher than that of mothers with SGA or premature children., Conclusions: The conclusions is drawn that even a relative zinc deficiency may negatively potentiate certain obstetric abnormalities in fetal development or in delivering.

Objective: The aim of this study was to investigate whether minor abnormalities of glucose metabolism without gestational diabetes are a risk factor for fetal overgrowth., Design: A sample of 1883 unselected white mother-infant pairs were screened for gestational diabetes using a 50 g 1-h oral glucose challenge test (GCT) in two periods of pregnancy: early (16-20 weeks) and late (26-30 weeks)., Methods: The effects of risk factors (glucose metabolism, previous history of mothers, obesity, multiparity and age of mothers) were estimated using a multinomial logit model., Results: The level of risk was related to gestational age at the appearance of an abnormal GCT. Patients with an abnormal GCT in the early and late periods of pregnancy (Group 1) had a risk of delivering a large for gestational age (LGA) infant seven times higher than the control group (normal GCT in both periods), and patients with a normal GCT in the early period and an abnormal GCT in the late period (Group 2) showed a risk three times higher than the control group. Among the historical risk factors for LGA infants, such as maternal obesity, multiparity, previous gestational diabetes and previous delivery of an infant weighing 4000 g or more, only the latter was associated with fetal overgrowth with a risk level 4.7 higher than the control group. Group 1 patients had a significantly higher incidence of pregnancy-induced hypertension and preterm birth. There were no differences in the frequency of 5-min Apgar score < 7 and metabolic complications among the infants of all groups. We found a significantly higher rate of shoulder dystocia in Group 1 infants than in infants in the other groups., Conclusions: Our results suggest that a positive GCT at 26-30 weeks is the most important risk factor for fetal overgrowth. This result was strongly enforced in patients who had also shown a positive early GCT at 16-20 weeks.

We compared the effects of two treatment strategies (diet alone versus a combination of insulin and diet) on neonatal anthropometric measurements and the outcome of a full-term white infant sample born to mothers with gestational diabetes mellitus (GDM). Study subjects included 217 consecutive nonrandomized women with GDM with term singleton pregnancies. Insulin therapy was administered on the basis of anamnestic and maternal-fetal criteria. One hundred and twenty-one patients (group 1) received a combination of insulin and diet, and 96 (group 2) underwent diet alone. All 1,052 white patients with term singleton pregnancies without GDM, screened at the same time as the study group, formed the control group. The incidence of large-for-gestational-age (LGA) infants was significantly higher in group 2 (18.8%) compared with group 1 (9.9%) and the control group (8.3%). Male and female infants born to diabetic mothers of group 2 had significantly greater mean birth weights, ponderal indices, thoracic circumferences, weight/length ratios and significantly smaller mean cranial/thoracic circumference ratios than male and female infants in group 1 and the control group (p < 0.05, Scheffe test). Treatment of GDM mothers with insulin and diet has been shown to be able not only to normalize the incidence of LGA infants but also to influence the anthropometric characteristics of the infants born to these mothers to such an extent that they showed no significant differences compared to infants born to non-diabetic mothers.

The relationship between perinatal outcome and daily glucose profile throughout pregnancy was assessed in 31 White Class B through R pregnant diabetic women. The study population was divided into two groups on the basis of perinatal outcome: 20 patients (Group I) without neonatal complications; 11 patients (Group II) with at least one form of neonatal complications. The overall capillary blood glucose average levels of Group I (98.53 +/- 22.33 mg/dl) and of Group II (110.14 +/- 20.77 mg/dl) was significantly different (ANOVA p < 0.0001). From the first trimester of pregnancy Group I showed significantly lower mean glycemic levels for daytime, evening and night (Bonferroni test p < 0.05) than Group II and both presented daily glycemic profiles with very extensive excursions. During the second trimester the groups continued to maintain these differences in mean glycemic levels (Bonferroni test p < 0.05) but a daily glycemic rthythm with relative nocturnal hypoglycemia with closer fluctuations. In contrast, during the third trimester the two groups presented both a daily rhythm of glucose and glycemic values for daytime, evening and night not statistically different (Bonferroni test p < 0.06). The distribution of women according to glucose levels reached during the night showed a mode of distribution in both Group I and II collocated in a range 70-100 mg/dl. These findings suggest that an optimum perinatal outcome can be achieved only if the pre-pregnancy diabetic women can achieve a metabolic equilibrium during the second trimester which matches the daily excursions of glycemia present in a non-diabetic pregnant women avoiding individual episodes of night-time hypoglycemia.