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Objective To investigate the role of glycemic control in development of preeclampsia (PE) in women with type 1 diabetes mellitus (T1DM). Methods An observational case-control study comparing 244 women with type 1 diabetes and 488 controls was conducted. Among women with T1DM HbA1c, average daily glucose values, fasting, preprandial, 1-hour and 2-hour postprandial glucose levels, and daily 3 meals postprandial glucose areas were evaluated. Uterine artery pulsatility indices (PI) at 16, 20, 24 weeks‘ gestation were obtained. Data analysis included rates of PE in both groups, and association between glycemic control, uterine artery PI and development of PE among women with T1DM. Results PE developed in 13.1% of diabetic women and in 3.5% of women in the control group (odds ratio 4.2; 95% CI 2.2–8.1). In multivariate logistic regression analysis, HbA1c in the 1st trimester, mean daily glucose level in the 1st and 2nd trimester, daily 3 meal postprandial glucose area in the 1st and 2nd trimester, and the uterine arteries PI at 24 weeks’ gestation were found to be associated with development of PE. The uterine arteries PI showed a significant positive correlation with the 3 meal postprandial glucose area at 16, 20, 24 weeks. Conclusion In women with T1DM, poor glycemic control early in pregnancy is associated with an increased risk of subsequent PE. An association between poor placentation, as indicated by the increased PI of uterine arteries, and a maternal metabolic factor, that is the 3 meal post-prandial glucose area, has been shown, supporting the increased rate of PE among women with T1DM.

Problem The aim of this study was to investigate the prevalence of human leukocyte antigens (HLA) DQ2 and DQ8 haplotypes, two common polymorphisms associate with celiac disease (CD), in women with previous stillbirth, but not affected by CD. Method of study Women with history of unexplained term stillbirth referred to our Center for High-Risk Pregnancies for a preconception counseling, and women with previous uncomplicated pregnancies, were enrolled as cases and controls. Celiac women were excluded from the study. Genetic tests for HLA DQ2/DQ8 were performed, and patients' data were compared. Results The population included 56 women with a previous term stillbirth and 379 women with history of uncomplicated pregnancies. The prevalence of HLA-DQ2 or DQ8 positivity was significantly higher in cases than in controls (50% vs 29.5%) (P = 0.0031). Women with HLA DQ8 genotype have a significantly higher risk of stillbirth (OR: 2.84 CI: 1.1840-6.817) and in case of DQ2 genotype the OR for stillbirth was even higher (OR: 4.46 CI: 2.408-8.270). In the stillbirth group, SGA neonates were significantly more frequent in those with HLA-DQ2/DQ8 haplotypes than in those resulted negative to genetic testing (85.7% vs 42 .8%, P = 0.004). Conclusion In women with history of term stillbirth, a significantly higher prevalence of HLA DQ2/DQ8 haplotypes has been found compared to women with previous uneventful pregnancies. In addition, HLA DQ2/DQ8 positivity was significantly associated with suboptimal fetal growth in intrauterine fetal death cases, as shown by an increased prevalence of SGA babies.

Systemic lupus erythematosus (SLE) commonly affects women of childbearing age. Hypertension, antiphospholipid syndrome, and lupus nephritis are risk factors for adverse maternal/fetal outcome. The aim of this retrospective cohort study is to compare pregnancy outcomes in patients with and without SLE nephritis, using a multidisciplinary approach and a broad prophylaxis protocol.Data were collected from 86 pregnancies complicated by SLE. Twenty-seven women with nephropathy before pregnancy stated as the study group and 59 formed the control group. Each group received a prophylactic treatment based on their clinical characteristics. Results were expressed as mean ± SD, percentage and χThe prophylactic treatment (60.4% of the patients) significantly controlled the complications related to some risk factors, such as antiphospholipid antibodies (aPL) and nephritis. Preeclampsia occurred in 14.8% of patients. Patients with pregestational hypertension showed a 2.75 odds ratio of adverse events when compared to the group without chronic hypertension. The presence of proteinuria was associated with a risk of preeclampsia 2.45 times greater, as well as serum creatinine1.2 mg/dL, which was related to a risk 1.25 times higher than the risk observed in patients with serum creatinine1.2 mg/dL. A 6-month inactive disease was associated with a better outcome. A value of Estimated Glomerular Filtration Rate (eGFR) 90 mL/min/1.73 mA multidisciplinary approach in a tertiary care center and a broad prophylactic treatment protocol to patients affected by SLE and complicated by nephritis may definitively foster a successful pregnancy.

The aim is to investigate the proportion of multiple pregnancies with gestational diabetes mellitus (GDM) diagnosed using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria and to identify the impact of age, body mass index (BMI), and mode of conception on incidence of GDM. This is a single center, retrospective cohort study on 656 multiple pregnancies screened for GDM with 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation, between January 2010 and January 2016. The diagnosis of gestational diabetes mellitus (GDM) was reached through the IADPSG. The incidence of GDM in our population was 15.1%. When patients who conceived through heterologous assisted reproduction technology were compared with those who conceived spontaneously, there was a significant difference for GDM (31.1 vs 13.6%, p

To compare glycemic control, maternal-neonatal outcomes and fetal fat body mass growth of type 1 diabetic pregnant women treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with the long-acting insulin analogue detemir as basal insulin.Retrospective study of 53 women, attending the Unit of Prenatal Medicine of Careggi University Hospital, Florence, from 2009 to 2012: 35 treated with CSII, 18 with MDI-detemir. Each woman performed daily blood glucose self-monitoring, had an individualized nutritional therapy, weekly prenatal visits and ultrasound scans (US) according to the Tuscan guidelines. US were also performed every two weeks from 28 to 38 weeks of gestation to assess fetal fat body mass growth. Student's t-test and Chi-square test were performed to compare the groups' results.No significant differences were observed in metabolic control, in any maternal and neonatal outcome nor fetal fat body mass growth for either group. The MDI group needed higher daily doses of insulin (MDI: 1.00 ± 0.32 UI/kg versus CSII: 0.75 ± 0.29 UI/kg, p = 0.007) to reach results comparable to the CSII group.MDI therapy with detemir is a safe and effective alternative, with a good benefit-cost ratio compared to insulin pumps.

Objective: Maternal diabetes increases the risk of perinatal mortality and morbidity, but the maintenance of antenatal normal glucose serum prevents the majority of neonatal complications. The aim of our study is to compare the metabolomic profile of infants of gestational diabetic mothers (IGDMs) to that of infants of healthy mothers to evaluate if differences remain despite a strict control of gestational diabetes.Methods: We performed the metabolomics study in cord serum sampled from 30 term IGDMs and 40 controls recording the occurrence of the most frequent complications in IGDMs.Results: We demonstrated that IGDMs have lower level of glucose and higher level of pyruvate, histidine, alanine, valine, methionine, arginine, lysine, hypoxanthine, lipoprotein and lipid than controls, but we did not find any clinical differences.Conclusions: Our results suggest that prolonged fetal exposure to hyperglycemia during pregnancy can change neonatal metabolomic profile at birth without affecting the clini...

To confirm the role of fetal growth restriction (FGR) as a cause of stillbirth, and to compare diagnostic accuracy of customized fetal growth and population-based standards in identifying FGR within a pathological population of early and late stillbirths.Retrospective study on a cohort of 189 stillbirths occurred in single pregnancy between January 2006 and September 2011. Unexplained stillbirths, defined by Aberdeen-Wigglesworth and ReCoDe classifications, were evaluated on the basis of fetal birthweight with both Tuscany population and Gardosi customized standards. Unexplained stillbirths have been classified as early or late depending on the gestational age of occurrence.Aberdeen-Wigglesworth classification, applied to the 189 cases of stillbirth, left 94 unexplained cases (49.7%), whereas the ReCoDe classification left only 40 (21%). By applying population standards to the 94 unexplained stillbirths we have identified 31 FGRs (33% of sample), while customized standards identified 54 FGRs (57%). Customised standards identified a larger number of FGRs with respect to population standards during the third trimester (i.e. 51% vs. 25% respectively) than in the second trimester (73% vs. 54% respectively) (p = 0.05).Customized standards have a higher diagnostic accuracy in identifying FGRs especially during the third trimester.

La morte intrauterina č un evento tragico che ogni anno in Italia colpisce circa 2000 famiglie nella seconda metŕ della gravidanza. La perdita di un bambino in utero č un lutto paragonabile per intensitŕ, manifestazioni psicologiche e decorso, al lutto per la perdita di una persona adulta. Il vissuto dei genitori, nonostante questo, č purtroppo scarsamente riconosciuto a livello sociale. Si tende a minimizzare l'effetto di questa perdita, le cui caratteristiche rimangono ignorate dai piů. Il lutto perinatale č spesso ignorato anche dagli operatori, che nel loro corso di studi non vengono solitamente formati sul lutto, e dunque l'assistenza psicologica offerta č spesso insufficiente, o lasciata alla volontŕ del singolo operatore: studi condotti in proposito evidenziano come una cattiva o inadeguata assistenza sia responsabile di traumatizzazione secondaria nei genitori e possa ostacolare una buona elaborazione del lutto. Per questi motivi, l'associazione CiaoLapo ONLUS ha avviato nel 2007 una collaborazione con l'Azienda Ospedaliera Careggi, per lavorare sulla formazione degli operatori e sul sostegno ai genitori. Da questa esperienza sono nate alcune linee guida che descrivono i momenti salienti dell'assistenza alla coppia colpita da morte in utero e gli accorgimenti da adottare per migliorare la pratica clinica. Scopo di questo lavoro č presentare questa esperienza e descrivere le linee guida alla luce della piů recente letteratura sugli aspetti psicologici del lutto perinatale.

Objective:Pregnant women with systemic sclerosis (SSc; scleroderma) have an increased risk of premature delivery and small full-term infants. During placental development, angiogenesis and vascular remodelling are essential for a successful pregnancy outcome. An analysis was made of the pathological changes and expression of angiogenic factors in SSc placentas.Methods:Placenta biopsies were obtained from three patients with SSc and four healthy uncomplicated pregnancies after delivery at 34–38 weeks of gestation. The sections were stained with Masson’s trichrome and phosphotungstic-acid-haematoxylin and immunostained for connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and receptors VEGFR-1 and VEGFR-2.Results:The pathological findings were signs of decidual vasculopathy, increased syncytiotrophoblast knotting, placental infarcts and villous hypoplasia. Severe and diffuse perivascular and stromal fibrosis of decidua and chorionic villi, and extensive deposition of fibrinoid material around decidual vessels and in intervillous spaces were observed. Strong CTGF expression in the vessel wall, decidual cells and fibroblasts and α-SMA+ myofibroblasts were found. VEGF and VEGFR-2 expression was stronger in SSc than in healthy placentas, while VEGFR-1 expression was similar to controls. PlGF immunopositivity was weaker in SSc.Conclusion:In SSc placentas, severe fibrosis and abnormal vascular remodelling were detected. This may result in reduced blood flow leading to deep sufferance of maternal placenta and possible premature delivery.

Objective. Pregnant women affected by SLE are at high risk of gestational hypertension and pre-eclampsia (32-50%). This risk is particularly elevated if aPLs are dosable. The present study was planned to evaluate maternal-fetal outcomes of different groups of SLE pregnant patients characterized by diverse risk factors: patients affected by APS treated with a combination of low-dose aspirin (LDA) and low-molecular weight heparin (LMWH), nulliparous patients with dosable aPL treated by LMWH and SLE patients with no aPL administered no treatment during pregnancy. Methods. A retrospective description of maternal and fetal outcomes was made in a total of 62 pregnancies presenting APS in 8 cases (12.9%), aPL in 20 (32.2%) and no aPL in 34 (54.8%). Results. No statistically significant difference was found comparing fetal and maternal outcomes of the three groups despite differences in SLE activity: SLE aPL-positive pregnancies were associated with a higher incidence of nephritis and chronic hypertension than pregnancies treated for APS or not presenting with the added risk factor. The incidence of pre-eclampsia is 15% in aPL positive, 12.5% in APS and 14.7% in no aPL pregnancies, respectively. Conclusions. LMWH is rather a possible option of prophylaxis for SLE aPL-positive pregnancies with potential maternal-fetal outcomes similar to aPL-negative patients or to standard treated APS.

Here we report a case of a 25-year-old woman with mesenteric and hepatic sarcoidosis without lung involvement complicated by severe noncirrhotic portal hypertension. In 1992, at the clinical presentation, she had abdominal pain, asthenia, and weight loss. Splenomegaly, signs of flogosis, sideropenic anemia, and cholestasis were observed. Laparoscopic abdominal exploration and histological analysis demonstrated noncaseating granulomas of the liver, abdominal lymph nodes, and mesenteric connective tissue. The clinical course was severe with episodic remissions and recrudescences characterized by ascites (mild or moderate), elevation of bilirubin levels (mean: 1.1 mg/dl; range: 0.9-3.5 mg/dl), reduction of albumin levels (mean: 4 g/dl; range: 3.4-4.2 g/dl), and prolongation of elevated international normalized ratio (mean: 1; range: 0.9-1.4). In 1997, the patient had variceal bleeding. Complete hemostasis was obtained with band ligation. Liver function was preserved, and until 2000 the disease remained stable. In 2001, the patient became pregnant. At the 36th week of gestation, the patient delivered a healthy female infant and afterwards remained in clinical remission. This report stresses that sarcoidosis can have a hepatic and mesenteric involvement in absence of thoracic lymphadenopathy. Portal hypertension may be severe, and in absence of cirrhosis it may be associated with portal thrombosis. Finally, portal hypertension in patients with hepatic sarcoidosis and preserved liver function should not be considered as an absolute contraindication to pregnancy.

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(β1 → 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.

Introduction Compromised placental function and morphology found in early onset preeclampsia as well as a modified phenotype of the fetus may derive from a deviation in the normal gene expression pattern. Previous studies demonstrated by experimental animal models, that the gene HOXA13 plays an essential role in the arrangement of the placental vascular net, identifying direct and indirect target functions this gene has on the endothelial component. Research in model systems and now expanding to human studies has suggested that the causes and consequences of a variety of pregnancy-related pathologies are connected to epigenetic regulation. Objectives To evaluate the methylation status of the promoter region of HOXA13 within placental tissue and its association with specific clinical signs of severe early onset preeclampsia. Methods A prospective case - control study was performed to evaluate the methylation status of the promoter region of HOXA13 by pyrosequencing analysis within placental tissue and its association with specific clinical signs of severe early onset preeclampsia (EOSP). Results The group of preeclamptic patients reached a mean methylation degree of 27.06% (±8.94) and 30.56% (±8.08) on two CpG islands of HOXA13 5’ promoter respectively. Conversely in the group of physiologic controls the mean degree of methylation resulted 15.12%(±3.64) (p Conclusion This study firstly demonstrated that an hypermethylation of placental HOXA13 exists in preeclamptic placental tissues and concentrates only on the gene promoter. Additionally, the existence of a correspondence between themethylation process of the gene promoter HOXA 13 and the clinical manifestation of severe early onset preeclampsia supports the original hypothesis that this process may be at the base of the preeclamptic pathogenesis.

Introduction The occurrence of preeclampsia before the 20th week of gestation is rare and it has been associated with hydatidiform molar pregnancy. Objectives We describe a case of first trimester eclampsia which occurred in a patient with hydatidiform mole. Methods Case report. Results A 16-year-old woman came to emergency service for abdominal pain and vaginal bleeding. She had been suffering of vomiting after meals and complaining for abdominal mass for 2months, without consulting her physician. The last reported period was 1month before; the patient told her periods were regular and the only disease she reported was chronic HBV hepatitis. Vital parameters were all normal. Urine pregnancy test resulted always negative. The gynecological exam reported an increased uterus and a little bleeding, so serum bhCG was performed because of the exam findings and resulted 110,5317UI/L. The transvaginal ultrasound showed images consistent with gestational trophoblastic disease. Computed tomography (CT) scan revealed the presence of an uterine mass and three lung nodules, reported as possibly metastatic. A few days later, the patient underwent dilation and curettage (D&C). Second grade hydatiform mole was diagnosed by histology. After D&C, the serum bhCG was 202,511UI/L. The day after, the patient presented bilateral acute blindness, followed by incoming general seizures, concurrent hypertension and tachycardia. Intravenous diazepam, levetiracetam and mannitol controlled the seizures, but the conscious state of the patient remained critical. Temperature reached 40°C, with concurrent leukocytosis. Then, a lumbar puncture was performed but it resulted negative for inflammatory/infective processes. A head CT was performed the same day and showed a posterior reversible encephalopathy syndrome (PRES). Intravenous methylprednisolone was started. Long term therapy with methylprednisolone and levetiracetam was effective and the patient's status improved and stabilized. A subsequent chemotherapy with EMA/CO regimen (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine/oncovine) was performed for six cycles, until serum bhCG resulted negative and the abdomen/pelvis ultrasound, head NMR and chest X-ray resulted normal. Conclusion Preeclampsia and eclampsia are regarded as common causes of PRES, which is considered to be the result of vasogenic brain edema. Clinical and imaging findings are usually reversible. Early diagnosis and elimination of possible causes are important in order to avoid permanent visual or brain injury. Imaging (especially MRI) should be carried out in eclamptic patients with visual disturbance in order to exclude other causes of blindness. Molar pregnancy is a rare but important cause of eclampsia, and it has always to be considered in case of early manifestations.

the release of the IPG P-type has been described at placental level with acquired alterations in the activation of proteins involved in insulin signalling in preeclamptic specimens: this was proposed to explain the glycogen accumulation found in these placentas. This confirms that in preeclampsia the placenta is insulin resistant and this is known to extend to the mother with IPG-P as a unifying mediator. In fact, a very high concentration of IPG P-type was reported in the amniotic fluid under physiological conditions (suggesting a role in the maintenance of the carbohydrate metabolism in the fetal-placental unit) and a significant increase of its concentrations in maternal fluids during preeclampsia suggesting a leakage of IPG-P into the maternal blood that probably contributes to the disease syndrome of preeclampsia. The study of the relationship between the nutrients provided by endometrial glands during early pregnancy and how this matches the metabolic requirements of the fetus in its low oxygen environment may explain the bases of the pathophysiology of preeclampsia. In fact, if a disconnect occurs between the placental/fetal metabolism and oxygen tension this could lead to a preeclamptic type of syndrome via leakage of Wharburg/IPG mediators into the maternal circulation.

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 [IS HOMA ], quantitative insulin sensitivity check index [IS QUICKI ], 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 QUICKI was 0.40±0.002 and 0.38±0.002 ( P −1 m −2 and 445±2.2 ( P 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 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, IS HOMA and IS QUICKI 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.

Background We present a case of an atypical onset of antiphospholipid syndrome (APS). Case A woman in her 15th week gestation had a thrombosis of an unknown cerebral cavernoma, which was successfully removed. Twenty-six days after, she was admitted for a severe pain in right hypochondrium and a second class HELLP syndrome was diagnosed. Two days after, she had a fetal loss. After 1 month, laboratory tests revealed high level of antiphospholipid antibodies. At the same time, she developed a spontaneous thrombosis at her right arm. After 6 weeks, antiphospholipid antibodies, tested again, result positive. Conclusion Antiphospholipid antibodies often cause pregnancy complications, but, to our knowledge, this is the first report of an association of antiphospholipid antibodies, with cerebral cavernoma thrombosis and early onset HELLP syndrome.

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 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 reference values of fetal subcutaneous tissue thickness (SCTT) throughout gestation in a healthy population and to compare them with those from a population of pregnant women with gestational diabetes under standard therapy. Methods Three hundred and three women recruited from a high-risk pregnancy clinic were classified as being healthy (n = 218) or as having gestational diabetes (n = 85) on the basis of a negative or positive oral glucose tolerance test, respectively. They were enrolled into the cross-sectional study at 20 weeks' gestation. Ultrasound examinations were performed approximately every 3 weeks until delivery at term. The mid-arm fat mass and lean mass (MAFM, MALM), the mid-thigh fat mass and lean mass (MTFM, MTLM), the abdominal fat mass (AFM) and the subscapular fat mass (SSFM) were evaluated. Time-specific reference ranges were constructed from the 218 healthy women and a conventional Student's t-test was performed to compare SCTT values between the two study groups throughout gestation. Results Normal ranges, including 5th, 50th and 95th centiles of the distribution, were generated for each SCTT parameter obtained in each of the two groups of women. Significant differences were found between the two study groups at 37–40 weeks' gestation for MTFM, at 20–22 and 26–28 weeks for MTLM, at 31–34 and 35–37 weeks for MAFM, at 26–28 and 38–40 weeks for SSFM, and at 39–40 weeks for AFM, the mean residual values always being greater in gestational diabetic women than they were in the group of healthy pregnant women. Conclusions We provide gestational age-specific reference values for fetal SCTT. Fetal fat mass values, particularly in late gestation, are greater in women with gestational diabetes compared with healthy women. The reference values may have a role in assessing the influence of maternal metabolic control on fetal state. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

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 evaluate the performance, in the prediction of pre-eclampsia, of (1) an abnormal mean uterine artery resistance index (RI; cross-sectional index) at 24 weeks of gestation, (2) the individual longitudinal flow pattern of results observed at 16, 20 and 24 weeks of gestation and (3) a multiple logistic regression model including the individual longitudinal flow pattern and the mean RI at 24 weeks. Methods A total of 144 normotensive pregnant women with risk factors for pre-eclampsia were evaluated with uterine artery color Doppler at 16, 20 and 24 weeks' gestation. The following indices were obtained: (1) cross-sectional index: the mean RI of both uterine arteries at 24 weeks' gestation was calculated for each patient and considered abnormal when ≥ 0.58; (2) longitudinal indices: the individual longitudinal flow pattern of mean RI of both the main uterine arteries at 16, 20 and 24 weeks' gestation was derived for each subject and defined as (a) the typical physiological flow pattern, with a trend of decrease in values or (b) the non-physiological flow pattern. The probability of having a pregnancy complicated by pre-eclampsia was also calculated by means of a multivariate logit model. The log-odds was modeled as a function of variables related to maternal characteristics, the individual longitudinal flow pattern indicator, and of the mean RI at 24 weeks' gestation as a continuous variable. Results Pregnancies had a physiological course in 108 (75%) women, while 36 (25%) women developed pre-eclampsia during the third trimester. For the prediction of pre-eclampsia, the use of an abnormal uterine artery RI index (≥ 0.58) at 24 weeks showed a sensitivity of 77.8%, a specificity of 67.6%, a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 90.1%, with a likelihood ratio (LR) for an abnormal test of 2.4; with the longitudinal flow pattern indicator, sensitivity was 88.9%, specificity 82.4%, PPV 62.7% and NPV 95.7%, with a LR for an abnormal test of 4.9; the use of a logit model yielded a sensitivity of 72.2%, a specificity of 90.7%, a PPV of 72.2% and a NPV of 90.7%, with a LR for an abnormal test of 8.0. Conclusions In this study the use of an individual longitudinal flow pattern indicator resulted in improving accuracy in the prediction of pre-eclampsia as compared with the traditional cross-sectional mean RI at 24 weeks. A further increase in specificity and PPV was obtained using a logit model that includes the longitudinal flow pattern indicator and the cross-sectional RI at 24 weeks. Since both the longitudinal flow pattern indicator and the logit model showed a high performance in predicting pre-eclampsia in women with risk factors for impaired placentation, they might be used to identify a high-risk population in which preventive measures and/or therapeutic options might be tested. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

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 ≤10th percentile for gestational age (GA), ponderal index (birth weight/length3 × 100) ≥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 ≤10th percentile and macrosomia, with fasting 75-g glucose load values being independent predictors of neonatal CC/TC ratio ≤10th percentile. In both periods, 1-h values gave a strong association with all abnormal neonatal anthropometric characteristics chosen as outcome measures, with maternal age >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 ≤10th percentile and ponderal index ≥90th percentile, whereas maternal age >35 years was an independent predictor of both neonatal CC/TC ratio ≤10th percentile and macrosomia. In the ROC curves for the prediction of neonatal CC/TC ratio ≤10th percentile for GA in both early and late periods of pregnancy, inflection points were identified for a 1-h, 75-g glucose load threshold value of 150 mg/dl in the early period and 160 mg/dl in the late period. 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.

The aim of the study was to assess the outcome of pregnancies achieved by OD in vitro fertilization compared with those obtained by autologous IVF.This retrospective cohort study includes 136 consecutive patients who were referred to our centre between 2009 and 2011. According to the mode of conception, they were divided into two groups, whose pregnancy outcomes were analyzed by χ2 Test for unpaired data.Pregnancy-induced hypertension, cesarean section, complications after delivery resulted more frequent in pregnancies from donor oocyte IVF. The other outcomes considered were non-significantly different between the two groups.The risk of developing preeclampsia, cesarean section, and postpartum complications is higher in patients who conceived by donor oocyte IVF than in patients who underwent autologous IVF.

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.

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.

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

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.

to assess the prevalence of smoking in pregnancy and its changes after childbirth, and the characteristics associated with a greater likelihood of smoking during pregnancy in a sample of women attending three university hospitals in Tuscany (Central Italy).observational prospective multicentric study.1,036 women in ninth month of pregnancy were enrolled at the teaching hospitals of Careggi (Firenze), Pisa and Siena. Women filled a standardized, self-administered questionnaire at enrolment. A second questionnaire was administered by phone to the smoking, ex-smoking and abstinent-during-pregnancy women one year after the delivery.60.5% of women was never smoker, 17.4% was ex-smoker, 14% of women stopped smoking during pregnancy, and 8.4% were current smokers. Smoking in pregnancy was significantly associated with being younger than 31 years old (OR 1.75; 95%CI 1.01-1.84) and unmarried (OR 1.75; 95%CI 1.10- 2.78), having a low school degree (OR 2.31; 95%CI 1.58-3.36) and a smoking partner (OR 3.03; 95%CI 2.32-3.96). The absolute risk of smoking during pregnancy was 42%. One year after delivery, 44%of women who stopped smoking in pregnancy relapsed.a not negligible percentage of women residents in Tuscany Region smokes during pregnancy. Relapses after delivery are high. Even if recently in Italy a smoke free legislation was implemented, the study shows a low attention toward passive smoking during pregnancy. Smoking cessation interventions specifically tailored for pregnant women and relapses prevention need to be implemented in Tuscany by all health care professionals who care for women during pregnancy and after delivery.

Continuous glucose monitoring (CGM) gives a unique insight into magnitude and duration of daily glucose fluctuations. Limited data are available on glucose variability (GV) in pregnancy. We aimed to assess GV in healthy pregnant women and cases of type 1 diabetes mellitus or gestational diabetes (GDM) and its possible association with HbA1c. CGM was performed in 50 pregnant women (20 type 1, 20 GDM, and 10 healthy controls) in all three trimesters of pregnancy. We calculated mean amplitude of glycemic excursions (MAGE), standard deviation (SD), interquartile range (IQR), and continuous overlapping net glycemic action (CONGA), as parameters of GV. The high blood glycemic index (HBGI) and low blood glycemic index (LBGI) were also measured as indicators of hyperhypoglycemic risk. Women with type 1 diabetes showed higher GV, with a 2-fold higher risk of hyperglycemic spikes during the day, than healthy pregnant women or GDM ones. GDM women had only slightly higher GV parameters than healthy controls. HbA1c did not correlate with GV indicators in type 1 diabetes or GDM pregnancies. We provided new evidence of the importance of certain GV indicators in pregnant women with GDM or type 1 diabetes and recommended the use of CGM specifically in these populations.

Pregnancy is sometimes related to thromboembolic complications (1) and alterations in different hemostatic parameters have been reported in pregnancy (2–4). In particular, a progressive increase in fibrinogen and D-dimer levels occurs during normal pregnancy (5–9). D-dimer levels may be predictive for some complications such as preeclampsia (10) and they have been also reported to be useful for diagnosis of abruptio placentae (6). However, it remains to be established if common ELISA for D-dimer are able to discriminate pathologic samples in conditions such as intrauterine growth retardation (IUGR) or gestational hypertension (GH). Aim of the present study has been to evaluate the behavior of D-dimer in pregnant women with IUGR and GH.

Fetal overgrowth is the most important complication of gestational (GDM) and pregestational diabetes mellitus.We correlated maternal glucose profiles, as detected by continuous glucose monitoring (CGM), with fetal growth parameters for 80 pregnant women (32 with type 1 diabetes, 31 with GDM, and 17 healthy controls). Glucose profiles were monitored in the first, second, and third trimesters of pregnancy for type 1 diabetes women and in the second and third trimesters for GDM women and controls. To analyze glycemic variability, we considered the mean amplitude of glycemic excursion, mean glycemia, the continuous overlapping net glycemic action (CONGA), the SD, the High Blood Glucose Index (HBGI), the Low Blood Glucose Index, and the interquartile range (IQR).Mean age was the same for the three groups. Prepregnancy body mass index was higher for the women with diabetes (GDM and type 1) than for controls. The newborn's mean birth weight and ponderal index were higher, although not significantly so, for the women with diabetes than for controls. For the type 1 diabetes patients, ponderal index correlated with the HBGI in the first trimester, CONGA1 and IQR in the second, and mean glycemia and SD in the third. For GDM patients, ponderal index correlated with mean glycemia and the HBGI in the second trimester.Fetal exposure to glycemic variability and hyperglycemia seems to be important in determining fetal overgrowth in pregnant women with diabetes. Optimal glucose control and less glucose variability are needed as early as possible in both type 1 diabetes and GDM patients to ensure normal fetal growth.

Dalfra MG, Pacini G, Parretti E, Ragazzi E, Mello G, Lapolla A. Elevated insulin sensitivity and beta-cell function during pregnancy in mothers of growth-restricted newborns. Am J Physiol Endocrinol Metab 301: E25-E30, 2011. First published April 5, 2011; doi: 10.1152/ajpendo.00024.2011.-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 beta-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 beta-cell function with a modified insulinogenic index as Delta AUC(insulin)/Delta AUC(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.

Through the description of two high risk unplanned pregnancy cases and the subsequent interview of the patients, a few years after delivery, this article focuses on the following issues: 1. The importance of a planned pregnancy in a woman with diabetes or other chronic disease; 2. The ethical role of counselling and how it should not be influenced by the ethical belief of the obstetrician; 3. The legal aspect related to the knowledge and qualifications of the obstetrician in the management of a high-risk pregnancy to improve both maternal and fetal outcomes. Here, two cases of complicated type 1 diabetes in women with unplanned pregnancies and the importance of counselling in high-risk pregnancy are presented.