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Background: In addition to its neuroprotective effect, Brain-derived neurotrophic factor (BDNF) also plays a role in glucose and lipid metabolism. This study aims: a) to find changes in the BDNF concentration during pregnancy in type 1 diabetes. b) to prove the effect of DHA and EPA supplementation on changes in BDNF concentrations c) to investigate the impact of hypoglycemia on BDNF concentration. Subjects and methods: The data from this study were from the PRE-HYPO cohort study. Twenty-one of them were on a standard diabetic diet enriched with EPA and DHA (EPA 120 mg/day and DHA 616 mg/day; Exposed group), and nineteen pregnant diabetic women were on the standard diabetic diet without EPA and DHA supplementation (Non-exposed group). In the first trimester of pregnancy, fift􀁈􀁈􀁑􀀃 􀁓􀁕􀁈􀁊􀁑􀁄􀁑􀁗􀀃 􀁚􀁒􀁐􀁈􀁑􀀃 􀁇􀁈􀁙􀁈􀁏􀁒􀁓􀁈􀁇􀀃 􀁋􀁜􀁓􀁒􀁊􀁏􀁜􀁆􀁈􀁐􀁌􀁄􀀃 􀁈􀁓􀁌􀁖􀁒􀁇􀁈􀁖􀀃 􀀋􀂔􀀖.9 mmol/L; HYPO+ group), and twenty-five pregnant women did not have hypoglycemia episodes (HYPO- group). Results: BDNF concentration significantly decreased during pregnancy from the first to the third trimester, in Non-exposed from 25.1 (22.0-30.2) to 22.1 (16.3-28.2), P

The effort to reach the ideal glycemic control in type 1 diabetic pregnancy (T1DM) is often linked with increased risk of hypoglycemia. The aim of the study was to find the effect of C- peptide concentration on severe hypoglycemia prevalence in diabetic pregnancy and its impact on insulin doses and fetal macrosomia. Study participants. 90 women with T1DM and singleton pregnancy, who received insulin treatment for ≥ 24 months, were included in the study. The HbA1c was ≤ 8% at pregnancy confirmation. The study was conducted in Department of Obstetrics and Gynecology, School of Medicine University of Zagreb, as a part of scientific project PRE-HYPO No IP-2018-01-1284. Participants were divided into three groups according to duration of diabetes: 1. group 2-10 years (n=36) ; 2. group 11-20 years (n=36), and 3. group ≥ 20 years (n=18). Severe hypoglycemia was defined as glucose concentration below 3 mmol / L. Results. The percentage of severe hypoglycemia in the first trimester according the groups was 41.7%, 66.7% and 77.8%, respectively, and it declined in third trimester in all three groups (19.4% ; 38.9% and 66.7%, respectively). The C- peptide concentration in group 1 was significantly higher throughout pregnancy when compared with group 2 and 3 (P=0.011 ; P=0.015 ; P

Summary. According to the World Health Organization criteria, underweight, normal weight, overweight and obesity are defined by body mass index (BMI). Underweight, overweight and obesity in pregnancy increase the risk of unfavorable maternal and perinatal outcome. The aim of the study was to analyze the impact of maternal BMI before and during pregnancy, and the impact of gestational weight gain on the occurrence of maternal and neonatal morbidity. Subjects and methods. This retrospective study included 4646 pregnant women that underwent oral glucose tolerance test between 24th and 32nd week of gestation and gave birth to their children at Clinical Department of Gynecology and Obstetrics, Zagreb University Hospital Center during the 2013-2015 period. There were 136 (2.9%) underweight, 3066 (66%) normal weight, 949 (20.4%) overweight and 467 (10.01%) obese women. The following data were analyzed: maternal age, BMI, gestational weight gain, parity, prevalence of preeclampsia, method of delivery termination (cesarean section, vaginal delivery or vacuum extraction), and neonatal birth weight, ponderal index, fetal macrosomia, and Apgar index at 1 min and 5 min. Results were expressed as mean value and standard deviation. The SPSS ver. 17 statistical software was used on data analysis. The χ2-test and ANOVA were calculated. Study parameters were compared between study groups and control group. The level of statistical significance was set at p

Obesity affects mental, physical and emotional health, increases the prevalence of hypertension, diabetes, sexual dysfunction and cardiovascular disease, and reduces the quality of life. Every woman with body mass index greater than 30 kg/m2 is considered obese, which has negative sequels on her general and reproductive health. A higher prevalence of early habitual abortion, congenital anomalies, preterm delivery, preeclampsia, gestational diabetes, cesarean section, fetal growth retardation and thromboembolism has been reported in obese women. Obesity is associated with worse maternal and perinatal outcomes. Children born to obese mothers more frequently develop cardiovascular disease, type 2 diabetes and metabolic syndrome later in life. This review gives recommendations for preconception work- up, and antenatal, intrapartum and postpartum care of obese pregnant women and their newborns.

Insulin is the main hormone in the regulation of glucose metabolism. Insulin is synthesized in the Langerhans islet β-cells as the proinsulin precursor, from which C-peptide and insulin are formed by proteolytic cleavage. In patients with type 1 diabetes mellitus (DM-1), complex interplay of genetic, exogenous ad autonomic factors leads to selective destruction of pancreatic β-cells, thus compromising insulin synthesis and secretion. Patients with DM-1 can produce exogenous insulin to a certain extent, however, insulin secretion undergoes gradual reduction due to selective destruction of β-cell function. Both C-peptide and insulin are secreted to portal circulation in equimolar amounts. There is an association of elevated C-peptide concentration with great reduction of hypoglycemic episodes, HbA1c values and microvascular complications. Studies have demonstrated that vitamins D and E, nicotinamide and polyunsaturated fatty acids (omega-3 fatty acids) may have protective effects in DM-1. Our investigations showed C-peptide to increase in both healthy and DM-1 pregnant women. This review article describes the impact of pregnancy and diet on β-cell function in women with DM-1.

Aims. The aim of this study was to relate the levels of glucose, insulin, C-peptide, leptin and adiponectin in the maternal and umbilical vein serum to the birth weight in T1DM and healthy pregnancies. Methods. The study included 120 pregnant women divided into 4 groups: 30 suffering from type 1 diabetic pregnancy (T1DM) who gave birth to eutrophic and 30 who gave birth to macrosomic infants ; 30 from Control group (CTRL) who gave birth to eutrophic and 30 who gave birth to macrosomic infants. Serum insulin, C-peptide, leptin and adiponectin levels were quantified by ELISA. Results. Fetal macrosomia is associated with higher level of leptin in the fetal serum in both groups (T1DM: p=0.049 ; CTRL: p=0.031). Fetal levels of glucose and insulin have an influence on birth weight in the Control group (glucose: p=0.002 ; insulin: p=0.015). Adiponectin levels are higher in the maternal (p=0.001) and fetal serum (p

Introduction. Due to the stressful and sedentary lifestyle with the plenty of calorie-rich food obesity reaches pandemic proportions. It is increased interest of scientist to discovery previously unknown metabolic-endocrine effects on obesity. Aims. The aim of this study was to determine the influence of obesity of the mother and GDM as individual and combined factors on the levels of glucose, C-peptide, adiponectin and leptin in umbilical serum, and on insulin resistance in the child. Methods. This case control study included 160 pregnant women divided into four groups according to BMI and GDM. The concentration of C-peptide, adiponectin and leptin were determined using the ELISA method. Results. Obese women in both diabetic and healthy groups had higher concentrations of C-peptide. The concentration of adiponectin was positively correlated to newborn’s weight among women with normal BMI values in both diabetic and healthy groups and leptin concentrations and newborn’s weight only among obese diabetic women. Conclusion. This study has shown that the activities of increasingly common pathogenic factors in the mother - weight and increased insulin resistance - either independent or combined, alter the in utero metabolism of the child.

INTRODUCTION Diabetes-induced changes and poorly regulated glycemia in diabetic pregnant women are reflected on placental tissue and metabolism, and consequently induce a series of complications in both the embryo and later fetus, and the pregnant woman. For normal growth and development of the fetal central nervous system of particular importance is the availability and supplementation of essential long-chain polyunsaturated fatty acids. The purpose of this study was to determine how changes in carbohydrate metabolism can affect the lipid content of the placenta in pregnant women with type 1 diabetes mellitus (DM 1). MATERIALS AND METHODS Pregnant women (38 with DM 1, and 34 healthy) were recruited for the study at the Reference Center for Diabetes in Pregnancy, Department of Gynecology and Obstetrics, Clinical Hospital Center Zagreb. All pregnancies were finished by caesarean section at the expected term of birth. Samples were collected from placental tissue, homogenized and total lipids were extracted by solvent mixtures. Free fatty acids were separated by thin layer chromatography, trans-esterified to methyl esters and analyzed by gas chromatography. RESULTS The amounts of free fatty acids were significantly reduced in placental tissue of the pregnant women with DM1 than in the control group. In DM1 group the ratio of lauric acid (C12:0) was significantly lower and the ratios of miristoleic (14:1), palmitic (16:0), stearic (18:0), oleic (18:1), linoleic (18:2) and docosahexaenoic (22:6) fatty acids were significantly higher than in the control group. CONCLUSION Decreased amounts of free fatty acids in the placenta of pregnant women with DM1 might indicate an increased lipolytic activity. Well regulated DM1 results with stable metabolism of carbohydrates and lipids, and with the appropriate fatty acid composition.

A pregnant woman with inherited thrombophilia (factor II mutation – 20210A) had two late pregnancy losses. The first pregnancy was not well documented, but the second pregnancy was complicated by fetal thrombophilia and umbili- cal artery thrombosis, proven after fetal death. During the third pregnancy enoxaparine was introduced in the therapy and early amniocentesis was performed. Fetal thrombophilia was proven again. Early delivery was induced and per- formed with no complications, resulting in a live healthy infant. A history of miscarriages or recurrent fetal loss should raise suspicion of thrombophilia as a potential cause. It is debatable whether amniocentesis in pursuit of fetal thrombo- philia should be performed and whether this will lead to a better perinatal outcome. When fetal thrombophilia is diag- nosed, an earlier induction of delivery should be considered, taking into account the fetal extrauterine viability. The aforementioned approach of early delivery in cases of inherited fetal thrombophilia could be a possible solution for better perinatal outcomes.

Objective. Perinatal and neonatal hypoxic/ischemic (H/I) brain injury is a leading cause of perinatal mortality and morbidity [1]. Prolonged neuronal apoptosis plays an important role in the processes contributing to neuronal degeneration. The essential long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA), a major component of brain membrane phospholipids, prevents neuronal cell apoptosis and plays an important role as an anti-oxidant agent [2]. Some research has shown that omega-3 FAs protect against ischemic brain damage in adult stroke models [3]. One recent study has suggested the beneficial effect of DHA pretreatment on brain damage and functional outcomes at 7 days after H/I in neonatal rats [4]. In this study, it was found that dietary supplementation of omega-3 FAs to pregnant female rats resulted in robust and prolonged neuroprotection in the neonatal brain after H/I. Fetal concentration of DHA depends on the mother’s concentration, i.e. on their ingestion by food. During the pregnancy the maternal EFA status declines steadily. Therefore, it is recommended that this fatty acid must be added in food [5]. Previous studies showed that type 1 diabetes is associated with low DHA level of pregnant women [6, 7]. The aims of the study were: 1. To determine total FAs concentration (mg/L) in the maternal vein serum and in the serum of the umbilical vein in pregnant women suffering from Type 1 diabetes (T1DM) and in healthy pregnant women (Control group) and ; 2. To determine and analyze omega-3 FAs (ALA, EPA, DHA) concentrations (mg/L) in relation to the total FAs concentration in the mother’s vein serum and the serum of the umbilical vein in pregnant women suffering from T1DM compared to the Control group. Methods. The study included 63 pregnant women, 32 suffering from T1DM and 31 from Control group who gave birth to eutrophic children. Samples of a mother’s vein blood and the umbilical vein blood were taken immediately after the birth. The total lipid extraction was carried out by the mixture of chloroform: methanol solvent: a method of increasing polarity according to Folch [8]. Heptadecanoic acid (C17) was used as internal standard in order to determine the exact proportion of total lipids. Fatty acids from lipid extracts were converted to methyl esters by transesterification with methanolic HCl (ref: ISO standard) and their composition analyzed by GC-MS on Varian 3400 (Varian, USA) equipped with Saturn II ion trap mass spectrometer operating in the electron impact (EI) mode. Results. There was statistically significant difference in the total FAs concentration in the maternal vein serum and the umbilical vein serum between the two groups (p0.001 ; EPA: p>0.001 ; DHA: p

Objectives: Increased reactive oxygen species (ROS) production in diabetes causes increased oxidative stress. Consequently, gestational diabetes (GDM) increases expression of antioxidant enzymes in the placenta in the 3rd trimester. Whether the placenta compensates diabetes-induced oxidative stress also in the 1st trimester is unknown. Therefore, we determined expression of antioxidant enzymes as well as of ROS producing enzymes xanthine oxidase (XO) and NADPH oxidases 4 and 5 (NOX4, 5) in 1st trimester placentas from Type 1 diabetic (T1D) pregnancies compared to healthy pregnancies. Methods: 1st trimester placentas from normal (n=14) vs. T1D (n=16) pregnancies between gesta-tional week 6-12 were obtained after pregnancy interruption for psychosocial reasons and immediately frozen in liquid nitrogen. Total RNA was isolated, and mRNA expression of superoxide dismutases 1-3 (SOD1-3), glutathione peroxidases 1, 3, and 4 (GPX1, 3, 4), catalase (CAT) and glutathione reductase (GSR) measured by real time PCR. Also, expression of enzymes producing ROS ie, NOX4, 5 and XO was determined. Data were normalized to expression of the housekeeping gene HPRT1. Results: Expression of SOD2 was decreased by 38% (p=0.036) in T1D placentas from week 8-12, but not from week 6-7. GPX3 was reduced by 63% (p=0.006) in ali investigated gestational weeks. GPX1, GPX4 and CAT showed also lower expression in T1D placentas between weeks 8-12 but did not reach significance. Expression of the ROS producing enzymes NOX4, 5 and XO was unchanged. Conclusion: This is the first study measuring diabetes associated changes in placental antioxidant enzyme expression in early pregnancy. In contrast to GDM in the 3rd trimester, we found a down-regulation of placental antioxidant enzymes in the 1st trimester. This suggests that either 1) oxidative stress is reduced in T1D 1st trimester placentas causing reduced antioxidant enzyme expression, or 2) because of their lower expression, oxidative stress in T1D cannot be compensated by antioxidant enzymes. This would lead to even higher oxygen toxicity of T1D in the 1st trimester placenta.

Results: In the first trimester of pregnancy placental trophoblast cells invade the maternal uterine wall in order to anchor the placenta and to establish adequate utero-placental blood flow by remodelling of the uterine arteries. Therefore, trophoblasts are well equipped with matrix degrading enzymes i.e. matrix metalloproteinases (MMPs). Maternal T1D is associated with a higher risk for early pregnancy loss, pre-eclampsia and fetal growth restriction. As underlying reason we hypothesise impaired trophoblast invasion. Because placental changes in early gestation are difficult to determine, indirect evidence is needed to demonstrate changes in trophoblast invasion. The aim of the present study was to identify changes in MMP expression in first trimester placentas from healthy vs. T1D pregnancies. Additionally, the effect of low oxygen on MMP expression was determined in a first trimester trophoblast cell line (ACH-3P). First trimester placentas from normal (n=15) vs. T1D (n=12) pregnancies between gestational week 6 and 10 were obtained after pregnancy interruption for psycho-social reasons and immediately frozen in liquid nitrogen. Total RNA was isolated and mRNA expression of all 23 human MMPs was measured using sqRT-PCR and analyzed according to the gestational weeks. Expression signals were normalized to the trophoblast marker cytokeratin 7. ACH-3P cells were cultured under various oxygen concentrations (2.5, 5, 12, 21) for seven days and expression of MMPs was measured similarly. In the first trimester, the placenta expresses 14 MMPs. T1D was associated with a reduced expression of 11 MMPs in weeks 8-10. Hypoxia reduced expression of various MMPs in ACH-3P cells. This is the first study to demonstrate altered placental MMP expression during early human pregnancy as a result of maternal T1D. T1D is associated with a decrease of MMP expression which may hence impair the process of trophoblast invasion. Lower uterine oxygen concentrations as a result of diabetes may be involved in the impaired MMP expression. These results may explain the higher incidence of spontaneous abortions in T1D women and their higher risk for pre-eclampsia and IUGR in late pregnancy.

This paper reviews perinatal problems of autoimmune etiology of systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), immune thrombocytopenic purpura (ITP) and myasthenia gravis (MG) which are particularly associated with pregnancy loss and obstetric complications. SLE is disease of unknown etiology in which tissues and cells are damaged by deposition of pathogenic autoantibodies and immune complexis. Since SLE is predominantly a disease of young women, pregnancy is a frequent occurrence. Fertility rates are normal in patients with SLE, but the rate of spontaneous abortion and stillbirths is high (30-40 percent), especially in women with antiphospholipid antibodies. If severe renal or cardiac disease is absent and SLE is controlled, many patients complete pregnancy safely and deliver normal infants. Neonatal lupus occurs in infants but is rare, two syndromes are seen: a transient rash and congenital heart AV block. APS refers to the occurrence of thrombosis, recurrent miscarriage, or both in association with laboratory evidence of persistent antiphospholipid antibodies, either lupus anticoagulants (LAC) and/or anticardiolipin antibodies (ACA). It is designated as "primary" when it occurs in isolation, and "secondary" when it arises in association with other diseases such as SLE. Recurrent pregnancy loss is one of the defining diagnostic criteria of APS. ITP is an autoimmune disorder manifested by immune mediated thrombocytopenia. Neonatal alloimmune thrombocytopenia caused by movement of maternal alloantibodies directed against fetal platelet antigens across the placenta that is the most common cause of severe neonatal thrombocytopenia. These antibodies cause thrombocytopenia, which may result in intracranial hemorrhages. Myasthenia gravis (MG) often affects women in the second and third decade of life, overlapping with the childbearing years. The course of the disease is unpredictable during pregnancy ; however, worsening of symptoms occurs more likely during the first trimester and postpartum. MG can be well managed during pregnancy with relatively safe and effective therapies.

Information on the predictive value in normal and pregnancy complicated with type-1 diabetes mellitus outcome, of yolk sac (YS) measurement and YS morphology has been scanned. During first trimester, peripherally placed (within gestational sac) YS measuring 5 mm or less is likely to be normal. YS maybe smaller or larger of 5 mm in abnormal pregnancies, than in intact pregnancies of equal size. Aim: To compare the size and shape at transvaginal sonography (TVS) of YS in normal and type 1 diabetic pregnancies and to correlate these characteristics with perinatal outcome. Patient and methods: 60 healthy pregnancies and 60 pregnancies with type 1 DM underwent TVS in the first trimester to establish the normal size and shape: TVS was performed at least 2 times between 6-12 weeks of menstrual age (MA), and HCG was measured at he same day of TVS as well. We calculated the correlation coefficient between YS and MA, YS and crown-rump length, YS and gestational sac diameter, and YS and HCG. Student-t test and Mann-Whitney test were used for statistical analysis with SPSS 10 software. Results: The high statistical positive correlation was found between YS diameter and MA, crown-rump length and diameter of YS for both studied groups. The YS diameter in type-1 DM pregnancies was statistically significantly larger for MA, than that of healthy pregnant women. YS in type-1 DM showed slower regression after 10 weeks of MA than in healthy pregnancies. The unfavorable perinatal outcome in healthy pregnant women was connected with YS measuring 5 mm and less with hypoechogenic sonographic characteristics. YS measuring more than 6 mm were found in 30/60 of type-1 DM group. Perinatal outcome was favorable in 20/30 cytogenetic malformation occurred in type-1 DM group. It is unknown if abnormalities of YS are related primarily to YS or secondarily to embryonic maldevelopment. Gross change in its size and/or shape may indicate or reflect significant dysfunction of the maternal-fetal transport system in early pregnancy. The larger size of YS could be of maternal hyperglycemia and accumulation of nutritive secretions not used by embryo, resulting more frequently in diabetic embryopathy.

OBJECTIVE: The results of studies in type-1 diabetes mellitus pregnant patients (type-1 DM) for mid-trimester distribution of serum multiple of the median (MoM) concentrations of alpha-fetoprotein (AFP), unconjugated estriol (uE3) and human chorionic gonadothropin (hCG) are often conflicting. THE AIM OF THE STUDY: This study investigated the relationship between type-1 DM and maternal serum levels of AFP, uE3, and hCG. STUDY DESIGN: The serum markers AFP, uE3 and hCG during second trimester in 25 pregnant women with uncomplicated and well controlled type-1 DM have been compared with 327 healthy controls . METHODS: Competitive radio immunochemical procedures (2nd trimester Amerlax-M, Ortho Clinical Diagnostics, USA) were used. Serum markers were expressed as MoM concentration derived from the control samples, corrected for maternal weight. Gestational age was calculated by the last menstrual period (LMP) and verified by ultrasound not later than 10 weeks after LMP. Regression functions were used for adjustment of serum levels for weight . Mann Whitney test was used to calculate the statistical significance between two studied groups. RESULTS: Mean maternal weight in controls was 68.25± 10.31 kg, and in type-1DM group 72.16± 13.12 kg (p=0.3). There were no significant differences in the distribution of hCG, AFP and uE3 between these two cohorts. All three markers AFP, uE3 and hCG levels in well controlled type-1 DM pregnant patients were lower but not statistical significant when compared to the healthy controls. All pregnancies had favourable perinatal outcome. CONCLUSIONS In centres which offer appropirate medical facilities to their type-1 DM pregnant patients and reach optimal preconceptional and during pregnancy blood glucose surveillance, general adjustment of AFP, uE3 and hCG except for weight are no longer necessary.

Diabetes in pregnancy causes many problems both for a mother and a child. Patients and methods. In ten years period (1995 - 2004) 396 pregnant patients with type-1 diabetes mellitus were delivered. Following data were analyzed: age of patients, body mass index, weight gain during pregnancy, number and outcome of previous pregnancies, levels of HbA1c in each trimester of pregnancy, complications of labor and delivery, new born weight and height, perinatal mortality and morbidity, placental weight and patohistologycal findings. For statistical analyses we used statistical program SPSS vr. 10. The aim of the study was to analyze the mode of delivery, perinatal outcome in relation to gestational weeks, complications of diabetes mellitus and complications of pregnancy. Results. 396 type-I diabetic patients delivered 398 new born children (2 pregnancies with twins). 309 pregnant type-I patients were without diabetic complications, 29 pregnant patients with non proliferative retinopathy, 23 patients with proliferative retinopathy, 5 patients with peripheral neuropathy and 30 patients with clinically manifest nephropathy. Premature labor occurred in 81 out of 396 deliveries (21.5%) of type-1 diabetic women. Among premature delivered patients the rate of elective preterm delivery was 16.6% what is explained with increased incidence of other complications of pregnancy like fetal in compromise (n=35 ; 43.2%) and super-imposed pre eclampsia (n=31 ; 38.3%). In 15 (18.5%) out of 81 prematurely delivered pregnant diabetic patients pregnancy was terminated earlier than 37 week of gestation because of contractions. The incidence of respiratory distress syndrome in premature new born children was 14.8% (n=12). There were 93 (23.6%) spontaneous vaginal deliveries, 7 (1.8%) deliveries finished by vacuum extraction, and by cesarean section delivered 296 (74.7%) type-1 diabetic patients. There were 23 (5.8%) SGA newborns, 269 (67.6%) AGA newborns, and 106 (26.6%) LGA newborns. Perinatal mortality was 3.3% (n=13 ; 8 stillbirth and 5 neonatal death). Congenital malformations occurred in 10 (2.5%) newborns: one child with Potter' syndrome, 6 children with congenital heart malformation, one child with prosencephaly, and two children with multiple malformations. Four children with congenital malformations died in early neonatal period. During labor and delivery two complications were diagnosed: placental abruption and silent uterus [scare] rupture after previous cesarean section. In postpartum period 16% patients developed endometritis, and one patient developed deep venous thrombosis. Conclusion. The type-I diabetic pregnant patients must be considered a high risk obstetric patients and delivered in the unit that can provide experienced obstetric care, continuous fetal monitoring, and neonatal intensive care.

Introduction: The aim of investigation was to establish the medicaments use during pregnancy and to compare them with data from the year 1989. Material and Methods: In Department of Gynecology and Obstetrics, Division of Perinatal Medicine, during the first six months of 2001, 2158 pregnant women were delivered. By random 1000 deliveries were chosen and examined by immediate questionnaire. For each pregnant patient the following data were obtained: the use of each drug and duration of therapy (days). Patients were divided in 2 groups according to the weeks of pregnancy: the first up to 12 wks and the second > 12 wks. Standard demographic data were observed. All data were compared to the results of the same study designed in 1989. Results: The general review of the drug use in 2001 in comparison to the year 1989 is presented in table 1. It shows significant increase of pregnant patients without any drug in 2001, in comparison to 1989. The use of Iron+vitamins did not change. The use of others, different and possibly harmful drugs significantly decreased. In the group of 401 drug users, in comparison to 1989, the use of only one medicament increased from 12.9% to 41,6%. while users of 4 drugs decreased from 22,7% to 7.5% and of 5-7 drugs from 14,8% to 5,21,lo respectively. Among I 000 pregnant patients the most frequent use was of psychorelaxant Diazepam (182 cases), following by: antibiotics (159 cases). ritodrine (102), gestagens (94), vaginal anti-inflammatory drugs (41) and glucocorticoids (9). 34 pregnant patients used the additional 12 drugs. Congenital anomalies were registered in 9 newborns; 4 newborns were from mothers without drug use (0,85%), 5 from mothers with drug use (1,25%), 3 of them with drug use = 12 weeks. The differences are not significant. Table 1. The overview of the drug use in Zagreb in the year 2001 compared to the year 1989. Patients without any drug Patients with Iron+vitamins Patients with other drugs Numbers Percent Numbers Percent Numbers Percent All pregnancies 2001 *470 47,0 **129 12,9 *401 40,1 1989 * 197 19,7 **176 17,6 *627 62,7 < 1 2 weeks 2001 *799 79,9 ns2l 2,1 180 18,0 1989 *875 87,5 ns19 1,9 106 10,6 *p< 0, 001; **p

Objective. Heparin therapy is today very well established in pregnant women with antiphospholipid syndrome. Study design. This study was prospective clinical trial, and included 24 pregnant women with antiphospholipid syndrome in whom low-molecular heparin (Clivarin) was introduced in dose of 2 x 1750 IU/day, s.c. Therapy started from as early as sonogram demonstrated a live embryo and continued throughout the pregnancy until the end of puerperium. Results. All pregnancies terminated favourably at 38.4ą1.6 (meanąSD) weeks of gestation, with planned cesarean section in 13 cases and vaginal delivery 11. The newborns had mean birthweight of 3106.5ą775.7 grams and under 10th percentile were born 4 infants or 16.7%. Coagulation parameters changed during heparin therapy: fibrinogen values were increased significantly in comparison to its initial values (F=12.4; p

Objective. The autonomic neuropathy was recently recognised as a potential risk factor in pregnancy of IDDM diabetics. We wish to highlight a poorly recognised problem in the obstetric management of the diabetic mother. Study design. It was included 44 pregnant IDDM diabetics in the age of 20 to 35 with the minimum two years of diabetes. The normal population, e.g. 30 pregnant women without diabetes in the same age group, were evaluated, because there are no normal values for this population. Cardiovascular tests as well as structured clinical examination was monitored 3 times during pregnancy (once in each trimester). Cardiovascular tests were examined using ProSciCard system. The full battery of tests was performed and six basic tests were evaluated. HbA1c measured the diabetes regulation. Diabetic polyneuropathy were clinically assessed using Dyck's staging system. Results. The incidence of moderate and severe autonomic neuropathy in IDDM pregnant women was 11.4%. High perinatal morbidity and mortality associated with moderate and severe autonomic neuropathy, especially with gastropathy. Conclusion. The presence of moderate to severe symptomatic autonomic neuropathy in patients with IDDM is a relative contra-indication to pregnancy. If pregnancy is achieved then the patients should be monitored for the occurrence of significant vomiting.

Objective. Impaired metabolic control of diabetic pregnancy results in increased risk of spontaneous abortions, congenital malformations, preeclampsia, macrosomic fetuses and stillborn. HbA1c gives the best information about metabolic control ion the last eight weeks. Aims of the study: (1) HbA1c levels in the peripheral blood of pregnant women with IDDM, and GDM, with healthy controls; (2) Implications of HbA1c concentration on detection and the control of the decrease in pregnancy complicated by impaired metabolism of carbohydrate; (3) Comparison of HbA1c levels with appearance of spontaneous abortion, and premature deliveries. Study design. 290 pregnant women were studied out of which 46 were healthy pregnant women, 94 with GDM and 150 were IDDM pregnancies. Results. The highest value of HbA1c was in the group IDDM pregnant women (7.7%ą1.8%) and the lowest value of HbA1c was in the control group (4.1%ą0.5%). It was found statistically significant coefficient correlation between HbA1c and weight gain during pregnancy, and between weight deviation from ideal body weight and HbA1c; and between newborns weight and HbA1c. Conclusion. Macrosomic fetuses were born by mothers with higher concentrations of HbA1c.

At the Department of Obstetrics and Gynecology, Perinatal Unit for Diabetes and Fetal Growth, School of Medicine, Zagreb perinatal care of pregnancies complicated with insulin dependent diabetes mellitus (IDDM),has been performed for more than 36 years. The intention of this review is to show our own results in the management of IDDM pregnancies and the latest clinical advances in perinatal care of such pregnancies. Pregnancy complicated with IDDM is at risk because of numerous maternal, fetal and neonatal complications. Recent advances in medicine, especially in diabetology and perinatology, help clinician avoid or lessen antenatal or perinatal complications in IDDM pregnancies. The main result of improved perinatal care is that today fetal and neonatal mortality in IDDM pregnancy is almost equal to that of healthy pregnant population. Intensive preconceptual care and optimal regulation of IDDM have resulted not only in decreased perinatal mortality but also in a decreased rate of congenital malformation. Tight glycemia control during pregnancy has a beneficial effect on fetal growth. Intensive control of fetal growth, verification of lung maturation at term by amniocentesis, and control of fetal oxygenation will result in delivery of a mature eutrophic newborn with the lowest rate of neonatal complications possible. Perinatal mortality of less than 2% in IDDM pregnancy can be obtained by planned delivery between 38 and 39 weeks of gestation by either vaginal route or cesarean section, depending on indications. After delivery, intensive care of the newborn is necessary.

Intolerancija glukoze (IG) i gestacijski dijabetes (GD) dijagnosticirani su pomoću OGTT-a prema preporuci SZO, izmedu 20-28 tjedna gestacije. Proučavani su slijedeći rizični faktori: nasljeđe, pretilost, dob iznad 30 godina, anamneza spontanih pobačaja, mrtvorođenost, predhodni porodi novorođenčadi težine iznad 4000 g, prekomjeran porast tjelesne težine tijekom trudnoće, glukozurija u početnoj fazi trudnoće, gestacijski dijabetes u predhodnim trudnoćama. U studiju je bilo uključeno 158 trudnica, 124 s intolerancijom glukoze, te 34 s gestacijskim dijabetesom. U grupi žena mlađih od 20 godina 9 ih je imalo IG; u dobnoj skupini 20-24 god. 14 je imalo IG i 5 GD; u dobnoj skupini 25-29 god. 52 su imale IG, 14 je razvilo GD; u grupi 30-34 god. 34 trudnice je imalo IG, a 9 je razvilo GD. U starijoj dobnoj skupini (35-39 god.) 14 trudnice je imalo IG, a 5 GD. Važno je upozoriti da je 60.5% ttudnica s IG i 55.9% trudnica s GD bilo mlađe od 30 godina. Nije nađena statistički značajna razlika između porodne težine novorođenčadi trudnica na inzulinskoj terapiji odnosno samo na dijetnom režimu. Učestalost prijevremenih poroda je iznosila 13.9%. Nije bilo mrtvorođene niti neonatalno umrle djece. Prema dobivenim rezultatima zaključujemo da OGTT valja odrediti u svake trudnice ne samo u onih s poznatim rizičnim faktorima. Nizak perinatalni morbiditet novorođenčadi koja su rođena iz trudnoća opterećenih intolerancijom glukoze ili gestacijskim dijabetesom je rezultat poboljšane antenatalne i neonatalne skrbi.

Summary. Introduction. Gestational diabetes mellitus (GDM) refers to impaired glucose tolerance of various degrees first manifested during pregnancy, and is related to a significant risk of adverse pregnancy outcomes and complications during and after birth, as well as long-term health risks. The primary goal of treatment is to optimize glycaemic control and improve pregnancy outcomes. As part of treatment, exercise is recommended for pregnant women without contraindications. Aim. To summarize results of trials on the effects of exercise on GDM and to assess the possible efficacy of this approach in the treatment of GDM. Methods. Four databases were systematically reviewed along with reference lists of relevant articles up to August 2016. Included studies were prospective randomized and non randomized controlled trials which investigated effects of therapeutic exercise on the course and outcomes of GDM. Results. Nine trials have been found, 7 randomized and 2 non randomized which included a total of 544 pregnant women. Main outcomes measured included complications during pregnancy and birth, and glycemic control parameters. The type, frequency, intensity and duration of exercise programmes varied. Most trials reported significant difference in glycaemic control or the need for insulin therapy in favour of exercise group. Discussion and Conclusion. A definite clinical significance of exercise as additional therapy for GDM still cannot be established with certainty. More randomized controlled trials are necessary in order to determine the optimal exercise programme. Therapeutic exercise during pregnancy might be an effective method for improving course and outcomes of GDM.

Dijabetes je kronična metabolička bolest, to je stanje kronične hiperglikemije obilježeno poremećenim metabolizmom ugljikohidrata, proteina i masti. S obzirom na etiologiju razlikujemo četiri tipa, od kojih su najčešći dijabetes tip 1 i tip 2. U žena s pregestacijskim dijabetesom trudnoća se smatra rizičnom zbog mogućeg razvoja brojnih majčinih, fetalnih i neonatalnih komplikacija. Loša metabolička kontrola glikemije u takvih trudnica povezana je s povećanim rizikom spontanih pobačaja, preeklampsije, rađanja djece s kongenitalnim malformacijama, mrtvorođene, asfiktične, prematurne i makrosomne djece, te povećanom neonatalnom smrtnosti. Dobrom kontrolom glikemije učestalost komplikacija znatno se smanjuje, te se približava razini učestalosti u zdravoj populaciji trudnica. Optimalna metabolička kontrola trudnica postiže se intenzivnom inzulinskom terapijom, odgovarajućom prehranom, čestom kontrolom glikemije i dobrom antenatalnom skrbi. Trudnice oboljele od dijabetesa potrebno je nadzirati i liječiti u regionalnim centrima za liječenje dijabetesa u trudnoći, a u nadzoru i skrbi takvih trudnoća sudjeluje tim stručnjaka sastavljen od opstetričara, dijabetologa, neonatologa, dijetetičara, medicinske sestre i socijalnog radnika., Diabetes mellitus is a chronic metabolic disease which is characterized with chronic hyperglycemia and disturbed metabolism of carbohydrates, proteins and fats. There are four types of diabetes mellitus depending on the etiology. The most common are type 1 and type 2 diabetes mellitus. Women with pregestational diabetes mellitus have high-risk pregnancies due to the possible development of maternal, fetal and neonatal complications. Poor metabolic control of glucose levels in pregnant women is associated with an increased risk of miscarriage, preeclampsia, birth of children with congenital malformations, stillbirths, asphyctic, premature and macrosomic children, and increased neonatal mortality. Good metabolic control during pregnancy significantly reduces the incidence of complications and approaches the level of incidence in the normal population of pregnant women. The optimal metabolic control of pregnant women is achieved with intensive insulin therapy, adequate nutrition, frequent glucose control and good antenatal care. Pregnant women with diabetes should be monitored and treated in regional centers for the treatment of diabetes in pregnancy. The supervision and care of such pregnancies involve a team of experts composed of obstetricians, diabetologists, neonatologists, dietitians, nurses and social workers.

Background. Gestational diabetes mellitus (GDM) is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. Diagnose is obtained by 75g/2h oral glucose tolerance test. GDM poses a risk for mother and child, related to high blood glucose levels and its consequences. The main risks GDM imposes on the baby are growth abnormalities, linked to higher rate of Caesarean section (SC) and delivery trauma, and chemical imbalances after birth. Objective. To determine the impact of gestational diabetes on neonatal complications compared to healthy pregnancies. Study design. We retrospectively analyzed GDM pregnancies from 10-year period, delivered in our hospital, and compared the data to similar number of healthy pregnancies (Control group, C). A total of 3396 newborns from singleton pregnancies were enrolled in the study. Analyzed variables in newborns were: preterm birth, SC, birth weight, neonatal macrosomia (≥4000 g), perinatal asphyxia, transitory hypoglycaemia, transitory tachypnoea, RDS, perinatal infection, hyperbilirubinaemia, cephalhaematoma, clavicular fracture, brachial plexus paresis, and congenital malformations. Results. The statistically significant difference was found in following variables: preterm birth (GDM 14.5%, C 6.87%, p

Introduction. Obesity is one of risk factors for impaired glucose metabolism, preeclampsia and adverse pregnancy outcome. Prepregnancy body mass index correlates with perinatal outcome, but weight gain during pregnancy seems to have an important influence on birth weight. Aim. The aim of this study was to explore weather prepregnancy BMI or weight gain during pregnancy had bigger influence on perinatal outcome among GDM women vs. controls. Materials and methods. This is a historical cohort study. The data of one decade period till 2010 from our clinic was analyzed. It included 3741 singleton pregnancies. Women were divided into 4 subgroups according to their diagnosis and prepregnancy BMI. Results. Both BMI and maternal weight gain were positively correlated to neonatal birth weight, but weight gain had bigger correlation coefficient than BMI (r=0.256, r=0.158 ; p

This volume provides a comprehensive yet concise overview of the scientific and clinical characteristics of gestational diabetes as well as type 1 and type 2 diabetes mellitus during pregnancy. Throughout the book the authors adopt multidisciplinary approach and cover aspects such as etiology, physiology, molecular biology and genetics, immunology, pathogenesis, diagnosis, treatment and management, pathology and evidence-based medicine.