Double diabetes as an effect modifier for adverse perinatal outcome in pregnant women with type 1 diabetes mellitus - a retrospective multicenter cohort study.

Introduction: Double diabetes (DDiab) is defined as T1DM coexisting with insulin resistance (IR), metabolic syndrome (MetS), and/or obesity. Little evidence is available regarding how frequent DDiab is among T1DM pregnancies and whether it affects the perinatal outcome in this population. Aims of the study: To explore the prevalence of DDiab in early pregnancy in the cohort of pregnant women with T1DM and to examine the association between an early-pregnancy DDiab status and fetomaternal complications characteristic for T1DM in pregnancy. Material and methods: A retrospective data analysis of the multicenter cohort of N=495 pregnant women in singleton pregnancy complicated with T1DM followed from early pregnancy until delivery in three tertiary referral centers. DDiab status was defined as T1DM plus pre-pregnancy obesity defined as BMI≥30 kg/m2 measured at the first antenatal visit (DDiabOb), or T1DM plus pre-pregnancy IR defined as eGDR (estimated Glucose Disposal Rate) below the 25th centile for the cohort measured at the first antenatal visit (DDiabIR). Proportions of the adverse pregnancy outcomes were compared between DDiabOb and Non-DDiabOb and between DDiabIR and Non-DDiabIR patients. Characteristics of the study group: (data presented as mean(SD) or percentage): age: 30.0(5.1) years; age when T1DM diagnosed: 17.5(8.5) years; T1DM duration: 12.0(7,9) years; microvascular complications (White classes R,F,RF): 11.9%, pre-pregnancy counselling: 26.6%, baseline gestational age: 10.5(4.3) weeks, pre-pregnancy BMI: 23.7(4.3) kg/m2; chronic hypertension: 9.1%, gestational hypertension (PIH) 10.7%, preeclampsia (PET): 3.2%; nulliparity 53.8%, smoking in pregnancy: 4.8%, eGWG: 22.4%, DDiabOB: 10.1%; DdiabIR: 25.2%; LGA: 44.0%, and NICU admission: 20.8%. Results: (data from the univariate analysis given as OR(95%CI)): both DDiabOB and DDiabIR status increased the risk for eGWG [23.15 (10.82; 55.59); 3.03 (1.80; 5.08), respectively]. DDiabIR status increased the risk for PET [4.79 (1.68;14.6)], preterm delivery [1.84 (1.13; 3.21)], congenital malformation [2.15 (1.07;4.25)], and NICU hospitalization [2.2 (1.20;4.01)]. Both DDiabOB and DDiabIR accurately ruled out PET (NPV 97.3%/98.3%, accuracy: 88.3%/75.6%, respectively), congenital malformation (NPV 85.6%/88.4%, accuracy: 78.9/69.8, respectively), and perinatal mortality (NPV 98.7%/99.2%, accuracy: 88.8%/74.5%, respectively). Conclusions: Double diabetes became a frequent complication in T1DM pregnant population. Double diabetes diagnosed in early pregnancy allows for further stratification of the T1DM pregnant population for additional maternal risk.

Can redox imbalance predict abnormal foetal development?

OBJECTIVES: Based on the current state of knowledge, elevated levels of oxidative stress markers may be considered as risk factors for pregnancy complications. The aim of the research was to assess the correlation between selected oxidative stress biomarkers with the occurrence of foetal chromosomal aberration and congenital malformations. MATERIAL AND METHODS: This retrospective research lasted for two years. The purpose was to determine serum levels of selected oxidative stress markers, including total protein (TP), glutathione (GSH), S-nitrosothiols (RSNO), nitric oxide (NO), trolox equivalent antioxidant capacity (TEAC) and glutathione S-transferase (GST) at 11-13 + 6 gestational weeks in 38 women with confirmed foetal developmental abnormalities and in 34 healthy pregnancies in order to assess their utility as predictors of abnormal foetal development. RESULTS: Serum concentrations of TP (56.90 ± 5.30 vs 69.1 ± 15.30 mg/mL), TEAC (4.93 ± 0.82 vs 5.64 ± 0.74 µM/mL) and GST (15.94 ± 4.52 vs 21.72 ± 6.81 nM/min/mg) were statistically significantly (p < 0.05) lower in the group of patients with developmental abnormalities in the fetus, whereas GSH levels (6.43 ± 1.24 vs 4.98 ± 1.88 nM/mg) were significantly higher, compared to the group of healthy fetuses. There were no differences in the concentration of these markers between chromosomal aberrations and fetal dysmorphia in subjects. A significant difference in odds ratio obtained for GSH (OR = 0.57, 95% CL: 0.40-0.80) indicates that its higher concentration can relate to reduced risk of developmental abnormalities, whereas odds ratio for TP (OR=1.11, 95% CL: 1.04-1.17), TEAC (OR = 3.54, 95% CL: 1.56-8.05) and GST (OR = 1.18, 95% CL: 1.03-1.17) indicate that their elevation may increase the risk of developmental abnormalities CONCLUSIONS: Elevated levels of TP, GST, TEAC and low GSH level may be relevant to predict congenital defects.

A 646C > G (rs41423247) polymorphism of the glucocorticoid receptor as a risk factor for hyperglycaemia diagnosed in pregnancy-data from an observational study.

AIM: Hyperglycaemia diagnosed in pregnancy (HiP) is a serious and frequent complication of pregnancy, increasing the risk for adverse maternal and neonatal outcomes. Investigate whether allelic variations of the glucocorticoid receptor are related to an increased risk of HiP. METHOD: The following polymorphisms of the glucocorticoid receptor (GR) were investigated in the cohort study of N = 197 pregnant women with HiP and N = 133 normoglycemic pregnant controls: 646C > G (rs41423247), N363S (rs6195), ER23/22EK (rs6190, rs6189). RESULTS: A GG variant of the rs41423247 polymorphism was associated with a significantly higher risk for HiP: OR 1.94 (1.18; 3.18), p = 0.009. The relationship remained significant after controlling for maternal age and prepregnancy BMI: OR 3.09 (1.25; 7.64), p = 0.014. CONCLUSIONS: The allelic GG variant of the 646C > G (rs41423247) polymorphism is associated with an increased risk for hyperglycaemia in pregnancy.

Serum visfatin as a metabolic biomarker in obese patients with gestational diabetes mellitus.

BACKGROUND: Visfatin is an adipokine produced and secreted by the adipose tissue. It exerts an insulin-like effect by the insulin receptor-1 and has a hypoglycemic effect. We aimed to investigate how serum visfatin changes in women with gestational diabetes mellitus (GDM), and whether it is predictive of neonatal outcomes. METHODS: Visfatin levels were prospectively measured in peripheral blood serum by enzyme immunoassay in 210 pregnant women, 156 of which were diagnosed with GDM, 18 of which suffered from pregnancy-induced hypertension (PIH) and 36 healthy controls. RESULTS: Patients with obesity class II (median=2.562 ng/mL) and class III (median=6.2940 ng/mL) had higher serum visfatin than overweight patients (median=0.735 ng/mL); (Mann-Whitney U test, P=0.037 and P=0.023, respectively). In GDM patients with BMI above 30, serum visfatin was associated to glycosylated hemoglobin (Spearman correlation test, R=0.26, P=0.045). Women with BMI above 25 treated with insulin had lower serum visfatin levels than those treated with diet only (Mann-Whitney U test, P=0.045). No correlation was found between visfatin and parameters of lipid profile such as HDL, LDL, or triglycerides (Spearman correlation tests, R=-0.051, -0.1, 0.0019; P=0.54, 0.29, 0.98, respectively). We observed that visfatin was not associated with birth weight (Spearman correlation test, R=-0.014, P=0.86) or adverse neonatal outcome as measured by umbilical artery pH below 7.25 (Mann-Whitney U test, P=0.55) or Apgar score below 10 (Mann-Whitney U test, P=0.21). CONCLUSIONS: In GDM patients with higher BMI, serum visfatin was elevated, correlated positively with glycosylated hemoglobin, and decreased upon treatment with insulin therapy.

Association of Oxidative Stress on Pregnancy.

The pathophysiological mechanism underlying pregnancy complications such as congenital malformations, miscarriage, preeclampsia, or fetal growth restriction is not entirely known. However, the negative impact of the mother's body oxidative imbalance on the fetus and the course of gestation is increasingly discussed. This article is an integrative review of some original studies and review papers on the effects of oxidative stress on the adverse pregnancy outcomes mainly birth defects in fetuses. A systematic search for English language articles published from 2010 until 2020 was made, using MEDLINE data. Additionally, we analyzed the Cochrane and Scopus databases, discussions with experts, and a review of bibliography of articles from scientifically relevant and valuable sources. The main purposes are to assess the contribution of the existing literature of associations of oxidative stress on the etiology of the abovementioned conditions and to identify relevant information and outline existing knowledge. Furthermore, the authors aim to find any gaps in the research, thereby providing grounds for our own research. The key search terms were "oxidative stress in pregnancy," "oxidative stress and congenital malformations," and "oxidative stress and adverse pregnancy outcomes." Studies have confirmed that oxidative stress has a significant impact on pregnancy and is involved in the pathomechanism of adverse pregnancy outcomes.

How mother's obesity may affect the pregnancy and offspring.

One of the main reasons for the epidemic of obesity, which has already influenced the economic condition of health system worldwide, is our modern lifestyle having an unbalanced calorie intake and insufficient physical activity. Maternal-fetal nourishment and metabolism are the mechanisms of fetal programming of obesity-adiposity and non-communicable diseases that have been most extensively investigated. A mother's obesity is related to adverse outcomes for both mother and baby. Maternal overnutrition is also associated with a higher risk of gestational diabetes, preterm birth, large-for-gestational-age babies, fetal defects, congenital anomalies, and perinatal death. Women with obesity should be encouraged to reduce their body mass index (BMI) prior to pregnancy, and to limit weight gain during pregnancy. Obstetric ultrasound imaging in pregnant women is negatively affected by abdominal adipose tissue, having an adverse influence on congenital anomaly detection rates and the estimation of fetal weight.

Serum homocysteine and vitamin B12 levels in women with gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) is described as a glucose intolerance of variable severity which begun or was firstly recognized during gravidity. Two major metabolic disorders, insulin resistance and ß-cell dysfunction, currently play major role in pathogenesis of GDM. Our intention was to investigate total serum homocysteine and vitamin B12 levels in pregnant women with GDM and non-diabetic gravid women. MATERIAL AND METHODS: Serum homocysteine and vitamin B12 levels were prospectively measured in a total of 79 pregnant women, 60 of whom were diagnosed with GDM, and 19 of whom were healthy controls. Serum homocysteine levels were analyzed by ELISA. Vitamin B12 concentrations were determined by chemiluminescent immunoassay, and lipids were determined enzymatically. RESULTS: GDM and control groups did not differ in terms of the serum homocysteine levels (median 7.24 vs 7.97 umol/L, respectively, p = 0.15). Nor did we find any association between serum homocysteine levels and BMI (r = 0.06, p = 0.55, respectively). There was no correlation between serum homocysteine and fasting serum glucose (r = 0.3, p = 0.8, respectively). There was no relationship between serum homocysteine concentrations and glycosylated hemoglobin (HgbA1c) levels (r = 0.06, p = 0.67, respectively). Serum vitamin B12 concentrations did not differ between the GDM and control groups (median 286 vs 262 pg/mL, respectively, p = 0.17). We found that levels of Vitamin B12 correlated inversely with fasting serum glucose concentrations (r = -0.44, p = 0.0009). Vitamin B12 concentrations increased along with LDL (r = 0.27, p = 0.043) and HDL (r = 0.38, p = 0.004) levels, however were inversely correlated with serum triglycerides (r = -0.34, p = 0.009). CONCLUSIONS: GDM patients with low Vitamin B12 values tend to have higher fasting serum glucose and altered lipid profiles (high triglycerides, low HDL and LDL). In women with GDM, serum homocysteine levels are not associated with HbA1c level, fasting glycemia, or BMI.

Expression of Osteoblast-Specific Factor 2 (OSF-2, Periostin) Is Associated with Drug Resistance in Ovarian Cancer Cell Lines.

One of the main obstacles to the effective treatment of ovarian cancer patients continues to be the drug resistance of cancer cells. Osteoblast-Specific Factor 2 (OSF-2, Periostin) is a secreted extracellular matrix protein (ECM) expressed in fibroblasts during bone and teeth development. Expression of OSF-2 has been also related to the progression and drug resistance of different tumors. The present study investigated the role of OSF-2 by evaluating its expression in the primary serous ovarian cancer cell line, sensitive (W1) and resistant to doxorubicin (DOX) (W1DR) and methotrexate (MTX) (W1MR). The OSF-2 transcript (real-time PCR analysis), protein expression in cell lysates and cell culture medium (western blot), and expression of the OSF-2 protein in cell lines (immunofluorescence) were investigated in this study. Increased expression of OSF-2 mRNA was observed in drug-resistant cells and followed by increased protein expression in cell culture media of drug-resistant cell lines. A subpopulation of ALDH1A1-positive cells was noted for W1DR and W1MR cell lines; however, no direct co-expression with OSF-2 was demonstrated. Both drugs induced OSF-2 expression after a short period of exposure of the drug-sensitive cell line to DOX and MTX. The obtained results indicate that OSF-2 expression might be associated with the development of DOX and MTX resistance in the primary serous W1 ovarian cancer cell line.

Mutual Expression of ALDH1A1, LOX, and Collagens in Ovarian Cancer Cell Lines as Combined CSCs- and ECM-Related Models of Drug Resistance Development.

A major contributor leading to treatment failure of ovarian cancer patients is the drug resistance of cancer cell. CSCs- (cancer stem cells) and ECM (extracellular matrix)-related models of drug resistance are described as independently occurring in cancer cells. Lysyl oxidase (LOX) is another extracellular protein involved in collagen cross-linking and remodeling of extracellular matrix and has been correlated with tumor progression. The expression of LOX, COL1A2, COL3A1, and ALDH1A1 was performed in sensitive (A2780, W1) and resistant to paclitaxel (PAC) (A2780PR1 and W1PR2) and topotecan (TOP) (W1TR) cell lines at the mRNA (real-time PCR analysis) and protein level (Western blot and immunofluorescence analysis). The ALDH1A1 activity was measured with the ALDEFLUOR test and flow cytometry analysis. The protein expression in ovarian cancer tissues was determined by immunohistochemistry. We observed an increased expression of LOX and collagens in PAC and TOP resistant cell lines. Subpopulations of ALDH1A1 positive and negative cells were also noted for examined cell lines. Additionally, the coexpression of LOX with ALDH1A1 and COL1A2 with ALDH1A1 was observed. The expression of LOX, collagens, and ALDH1A1 was also detected in ovarian cancer lesions. In our study LOX, ALDH1A1 and collagens were found to be coordinately expressed by cells resistant to PAC (LOX, ALDH1A1, and COL1A2) or to TOP (LOX and ALDH1A1). This represents the study where molecules related with CSCs (ALDH1A1) and ECM (LOX, collagens) models of drug resistance are described as occurring simultaneously in ovarian cancer cells treated with PAC and TOP.

Myotilin, a New Topotecan Resistant Protein in Ovarian Cancer Cell Lines.

Background: Low effectiveness of chemotherapy in ovarian cancer results from development of drug resistance during treatment. Topotecan (TOP) is a chemotherapeutic drug used in second-line chemotherapy of this cancer. Unfortunately, during treatment cancer can develop diverse cellular and tissue specific mechanisms of resistance to cytotoxic drugs. Methods: We analyzed development of TOP resistance in ovarian cancer cell lines (A2780 and W1). On the base of our previous results where a set of "new genes" with different functions that can be related to TOP-resistance was described hereby we performed detailed analysis of MYOT expression. MYOT mRNA level (real time PCR analysis), protein expression in cell lysates and cell culture medium (western blot analysis) and protein expression in cancer cells (immunofluorescence analysis) were determined in this study. Results: We observed increased expression of MYOT in TOP resistant cell lines at both mRNA and protein level. MYOT, together with extracellular matrix molecules like COL1A2 and COL15A1 were also secreted to corresponding cell culture media. Conclusion: Our results suggest that upregulation of MYOT can be related to TOP resistance in ovarian cancer cell lines.

The role of visfatin in pathogenesis of gestational diabetes (GDM).

Gestational diabetes (GDM) is defined as a glucose intolerance of varying severity with onset or first recognition during pregnancy. Two major metabolic disorders: insulin resistance and ß-cells dysfunction, play currently major role in pathogenesis of GDM. Adipose tissue is an organ involved in production of adipokines, which have various influence on metabolism of glucose and lipids. Visfatin is an adipokine mainly produced and secreted by the fat tissue. It exerts an insulin-like effect by binding to the insulin receptor-1 and have hypoglycemic effect. Visfatin appears to be an important factor in the pathophysiology of GDM. The aim of this article is to review the literature concerning the relationship between the adipokine mentioned above and GDM, and to clarify its role in the pathophysiology of GDM.

The Role of Matrix Gla Protein (MGP) Expression in Paclitaxel and Topotecan Resistant Ovarian Cancer Cell Lines.

The major cause of ovarian cancer treatment failure in cancer patients is inherent or acquired during treatment drug resistance of cancer. Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. Recently, MGP expression was related to cellular differentiation and tumor progression. A detailed MGP expression analysis in sensitive (A2780) and resistant to paclitaxel (PAC) (A2780PR) and topotecan (TOP) (A2780TR) ovarian cancer cell lines and their corresponding media was performed. MGP mRNA level (real time PCR analysis) and protein expression in cell lysates and cell culture medium (Western blot analysis) and protein expression in cancer cells (immunofluorescence analysis) and cancer patient lesions (immunohistochemistry) were determined in this study. We observed increased expression of MGP in PAC and TOP resistant cell lines at both mRNA and protein level. MGP protein was also detected in the corresponding culture media. Finally, we detected expression of MGP protein in ovarian cancer lesions from different histological type of cancer. MGP is an important factor that might contribute to cancer resistance mechanism by augmenting the interaction of cells with ECM components leading to increased resistance of ovarian cancer cells to paclitaxel and topotecan. Expression found in ovarian cancer tissue suggests its possible role in ovarian cancer pathogenesis.

An observational study of the risk of neonatal macrosomia, and early gestational diabetes associated with selected candidate genes for type 2 diabetes mellitus polymorphisms in women with gestational diabetes mellitus.

OBJECTIVES: 1) to analyse the prevalence of selected candidate genes for type 2 diabetes mellitus polymorphisms (IRS1 G972R; ENPP1 K121Q; ADRB3 W64R) among women with gestational diabetes; and 2) to investigate any association between variants of these genes and risk of neonatal macrosomia. MATERIAL AND METHODS: We conducted a prospective observational study of a group of women (N = 140) in singleton pregnancies who delivered at term. Characteristics of the study group at enrolment: age: 32.0 ± 4.9 years; GA: 26.6 ± 7.5 weeks; HbA1c: 5.6 ± 0.6%; fasting blood glucose: 102.3 ± 16.3 mg/dL; insulin treatment (G2DM): 65.7%; chronic hypertension: 11.4%; gestational hypertension: 17.9%; preeclampsia: 1.4%; birth weight: 3590 ± 540 g; birth weight ≥ 4000 g (macrosomia): 18.6%; caesarean section: 44.3%; and female newborns: 57.1%. RESULTS: The maternal metabolic characteristics at the time of booking did not differ between polymorphisms. Macrosomia was insignificantly more frequent in females (22.5%) than in males (13.3%) (p = 0.193). Only maternal height and body weight at the time of booking significantly predicted birth weight (R = 0.27, p = 0.007; R = 0.25, p = 0.005, respectively). IRS1 G972R GR and ENPP1 K121Q KQ polymorphisms were associated with an insignificantly increased risk for macrosomia. Carriers of the heterozygotic variant of the IRS 1 gene were significantly more likely to be diagnosed with GDM/DiP in the first trimester: OR 5.2, 95% CI: 1.4; 19.2; p = 0.014. CONCLUSIONS: 1) having similar metabolic characteristics, carriers of specific variants of T2DM candidate genes might be at increased risk of delivery of macrosomic newborns; 2) any association between genetic variants and macrosomia in this population might be gender-specific; and 3) allelic variation in the IRS1 gene is associated with early GDM/DiP.

Maternal lipids associated with large-for-gestational-age birth weight in women with type 1 diabetes: results from a prospective single-center study.

INTRODUCTION: Despite improvement in diabetes care over the years, the incidence of macrosomia in type 1 diabetic mothers is still very high and even shows an increasing tendency. It is suggested that other factors that maternal hyperglycemia might be associated with excessive fetal growth in diabetic mothers. The aim of this study was to determine whether maternal lipids might contribute to high rates of large-for-gestational-age (LGA) newborns in women with type 1 diabetes (T1DM). MATERIAL AND METHODS: This prospective, single-center study was performed in a population of women with T1DM admitted to the perinatal center for women with diabetes. Data were collected in the first trimester (< 12th week), in mid-pregnancy (20th-24th weeks), and before delivery (34th-39th weeks). RESULTS: Among 114 women included in the analysis, 30 (26.3%) delivered LGA newborns. The remaining 84 (73.7%) newborns were appropriate for gestational age (AGA). Lower high-density lipoprotein (HDL) HDL concentration in the first trimester was significantly associated with LGA (p = 0.01). Similar associations were observed for the HDL concentrations in mid-pregnancy (p = 0.04) and before delivery (p = 0.03). Higher triglyceride concentrations in the first trimester (p = 0.02) and before delivery (p = 0.008) were associated with LGA. Higher glycated haemoglobin (HbA1c) levels in mid-pregnancy and before delivery were associated with LGA. The associations between maternal lipids and LGA were independent of maternal body mass index at onset of the study, gestational weight gain and HbA1c concentrations. CONCLUSIONS: Decreased HDL and increased triglycerides during pregnancy might contribute to the development of LGA in women with type 1 diabetes.

Chorionic thickness and PlGF concentrations as early predictors of small-for-gestational age birth weight in a low risk population.

OBJECTIVES: SGA is associated with higher incidence of postnatal complications, including suboptimal neurodevelopment and increased cardiovascular risk. Screening for SGA, carried out at 11-13 (+ 6d) gestational weeks enables to reduce or completely eliminate the above mentioned complications. The aim of this study was to assess the correlation between chorionic thickness, concentration of PIGF protein and foetal birth weight in a single low-risk pregnancy. MATERIAL AND METHODS: The study included 76 patients at 11-13 (+ 6d) gestational weeks, monitored throughout preg-nancy. Ultrasound examinations identified the location and thickness of the chorion by measuring it in its central part at its widest point in a sagittal section. Additionally, at each visit venous blood was collected to determine the level of PlGF, PAPP-A, and BhCG. RESULTS: A significant positive correlation (r = 0.37) was found between the foetal weight and chorionic thickness. This correlation was affected by the location of the chorion and a significant negative correlation was observed between the level of PLGF, FHR, weight and length of the newborn. Maternal early-pregnancy BMI did not affect neonatal weight and body length, FHR, chorionic thickness, and the levels of PlGF, PAPP-A, and BhCG. CONCLUSIONS: The preliminary analysis indicates an association between chorionic thickness assessed during ultrasound at 11-13 (+ 6d) gestational weeks, PIGF levels assayed at the same time and birth weight. Increasing chorion thickness was accompanied by increasing foetal birth weight. PlGF level showed an inversely proportional effect on the foetal weight. This correlation was significant for the posterior location of the chorion.

Chronic and gestational metabolic disorders have a different impact on late-pregnancy endothelial function in pregnant women.

OBJECTIVES: We investigated how maternal endothelial function is affected by pregestational (Type 1) diabetes mellitus (PGDM) or gestational diabetes mellitus (GDM) and/or chronic hypertension (chHT) or gestational hypertension (PIH). METHODS: We conducted a prospective, observational study involving 78 participants with GDM, PGDM and/or hypertension (PIH-16, GDM + PIH-14, PGDM + chHT-8, PGDM-20, GDM-20) in the third trimester of a singleton viable pregnancy. Twenty healthy women with uncomplicated pregnancies matched for gestational age served as controls. We analysed maternal data, disease history and serum concentrations of E-selectin and Vascular cell adhesion molecule 1 (sVCAM-1). RESULTS: Only the maternal serum concentration of sVCAM-1 differed significantly among the subgroups (p< 0.0001), with the highest levels evident in women with PIH or GDM + PIH and the lowest in women with PGDM alone or PGDM + chHT. CONCLUSIONS: Pregestational or pregnancy associated disorders, although sharing similar clinical symptoms, have a different impact on endothelial function in pregnant women.

Determinants of C-reactive protein concentrations in pregnant women with type 1 diabetes.

INTRODUCTION    Increased C-reactive protein (CRP) concentrations during pregnancy are associated with several perinatal complications. OBJECTIVES    The aim of the study was to assess serum CRP concentrations and identify its determinants in pregnant women with type 1 diabetes. PATIENTS AND METHODS    CRP concentrations were determined using a high-sensitivity assay (hs-CRP) in the first trimester (I, week <12 of gestation), in mid-pregnancy (II, weeks 20 to 24 of gestation), and in the late third trimester (III, weeks 34 to 39 of gestation) in a group of 73 patients with type 1 diabetes. RESULTS    There was a significant increase in CRP concentrations between the first trimester and mid­pregnancy (median [interquartile range], 2.5 mg/l [1.3-4.5 mg/l] and 5.6 mg/l [2.5-11.6 mg/l]; P = 0.0001), which then stabilized with no further change between mid-pregnancy and the late third trimester (5.7 mg/l [2.5-9.6 mg/l]). CRP concentrations in all 3 trimesters were positively correlated with the waist­to-hip ratio (I, P <0.0001; II, P = 0.0004; III, P = 0.0369) and body mass index (I, P = 0.015; II, P = 0.0025; III, P = 0.0048), measured in the first trimester. CRP concentrations during pregnancy were positively correlated with a measure of insulin resistance, namely, the estimated glucose disposal rate, assessed in the first trimester (I, P = 0.01; II, P = 0.0165; III, P = 0.0062). There was a positive correlation between the levels of hs-CRP and total cholesterol (P = 0.001), low-density lipoprotein cholesterol (P = 0.013), and triglycerides (P = 0.0014) in the first trimester. There was no significant correlation between CRP and hemoglobin A1c, daily insulin requirement/kg, high-density lipoprotein cholesterol levels, maternal age, and diabetes duration. CONCLUSIONS    Adiposity, abnormal body fat distribution, and insulin resistance are the major determinants of CRP concentrations in pregnant women with type 1 diabetes. Our results confirm the importance of weight control before pregnancy in women with type 1 diabetes.

Ballantyne Syndrome (Mirror Syndrome) associated with severe non-immune fetal hydrops--a case report.

OBJECTIVES: The aim of the study was to present a case of rapidly progressing non-immune fetal hydrops (NIHF) of unknown etiology in a normal-karyotype fetus, accompanied by severe maternal edema, anemia, and hypoproteinemia. After the differential diagnosis, Ballantyne Syndrome (BS, Mirror Syndrome) was diagnosed. MATERIAL AND METHODS: We present a case of a 31-year-old multipara at 22/24 weeks of pregnancy presenting severe symptoms of non-immune fetal hydrops: subcutaneous edema, hydrothorax, ascites and placental edema associated with maternal edema, anemia and hypoproteinemia. After cardiovascular infectious, immune and morphological causes were excluded, amniocentesis was performed and confirmed normal female 46, XX karyotype. Since 22 weeks of pregnancy increasing maternal edema and anemia were observed. No hematological, cardiac or nephrological causes of this condition were found. RESULTS: At 24 weeks of pregnancy intrauterine fetal demise was diagnosed and surgical evacuation (cesarean section) of the fetus was performed. Resolution of maternal edema, anemia, and hypoproteinemia was observed shortly after the delivery. CONCLUSIONS: Based on our findings, it seems safe to conclude that BS may develop in pregnancy complicated by NIHF of unknown origin.

Self-directed learning in high-quality antenatal screening.

OBJECTIVES: To compare first-trimester scan results between audited (AS), according to the Fetal Medicine Foundation criteria, and non-audited sonographers (NAS). MATERIAL AND METHODS: Retrospective observational study of N = 629 and N = 1290 NT and CRL measurements done by AS and NAS, respectively. RESULTS: For similar examined populations (similar CRL and maternal age at examination) NT values were significantly lower in NAS with NT of 1.0 mm or less in 26.9% of measurements taken by NAS (vs. 0.3% in AS). NT differed significantly between NAS and AS in all maternal age groups, except for patients below 24 years of age and in all CRL categories. CONCLUSIONS: Training of sonographic skills in fetal medicine needs to be complemented by a regular audit to ensure adequate quality of the measurements.