HORMONSKO NADOMJESNO LIJEČENJE CLIMENOM© I NJEGOV UČINAK NA TKIVO DOJKE

Objective. To evaluate the effect of the hormone replacement therapy on breast changes in postmenopausal women. Material and methods. The study includes 35 women with natural or surgical menopause who were treated with sequential estrogen/progestogen hormone replacement therapy (E/P HRT) during one year. The therapeutic program consisted of three weeks treatment with estradiol valerate 2 mg/day orally, combined with ciproterone acetate 1 mg/day in the last 10 days (Climen© – Schering) followed by one week pause. Before the start with E/P HRT basic mammography and ultrasound examination of the breast tissue was performed in all patients. At the end of the study after 12 therapeutic cycles, control mammography and ultrasonographic examination were done. Results. In the short-term study 18 patients (51.43%) showed regression of the finding, 15 (42.86%) stagnation, and only 2 (5.71%) progression of the finding (D=0.27, p<0.01). Conclusion. A clear consensus regarding the relationship between HRT and breast cancer risk cannot yet be drawn.Cilj rada je bio vrednovati učinak hormonskog nadomjesnog liječenja na promjene dojke u 35 žena u post¬menopauzi. Bolesnice i način istraživanja. 35 žena u prirodnoj ili kirurškoj postmenopauzi je kroz jednu godinu liječeno sekvencijskom hormonskom nadomjesnom terapijom (HNL). Terapijska shema je bila tri tjedna estradiol valerijanat 2 mg/dan peroralno, kombinirano s ciproteron acetatom 1 mg/dan posljednjih 10 dana (Climen© – Schering) te nakon toga sedam dana stanke. Prije početka HNL svima je pacijenticama učinjena mamografija i ultrazvučni pregled dojki. Na kraju studije, nakon 12 terapijskih ciklusa, učinjeni su kontrolna mamografija i pregled ultrazvukom. Rezultati. U kratkoročnoj studiji u 18 pacijentica (51,43%) nastupila je regresija nalaza, u 15 (42,86%) stagnacija i u 2 (5,71%) pacijentice progresija nalaza (D=0,27, p<0,01). Zaključak. Jasni dogovor u pogledu odnosa između hormonskog nadomjesnog liječenja i raka dojke još se ne može donijeti

Two Pregnancies with a Different Outcome in a Patient with Alport Syndrome

BACKGROUND: Alport syndrome is a genetic disease that progresses to chronic kidney failure, with X-linked, autosomal dominant or autosomal recessive type of inheritance. Women are generally carriers of the mutation and have a milder form of the disease. During pregnancy, they have an increased risk of impaired kidney function and preeclampsia.CASE PRESENTATION: A 27-year old woman, gravida 1, para 0, in her 23rd gestational week came to the outpatient unit of the University Clinic of Nephrology for the first time because of slowly progressing proteinuria and Alport syndrome. She was admitted to the gynaecological ward in her 29th gw for proteinuria which increased from 3.8 g/day up to 20 g/day and the serum creatinine increased to 120- 150 micromol/l. She was delivered in the 30th gestational week due to obstetrical indications with a cesarian section and delivered a baby with a birth weight of 880 g. After delivery, proteinuria decreased to 2 g/d within 2 months and an angiotensin-converting enzyme inhibitor (ACEI) was started. Her second pregnancy, after 2 years, had an uneventful course and she delivered a healthy baby weighing 3000 g in the 39th week. Six months after the second delivery, her renal function remained normal and her proteinuria was 2 g/d.CONCLUSIONS: Pre-pregnancy counselling and frequent controls during pregnancy are necessary for women with Alport syndrome, as well as regular monitoring after delivery. Recent reports are more in favour of good pregnancy and nephrological outcomes in women with Alport syndrome when renal disease is not advanced

Effect of lipid parameters on fetal growth in type 2 diabetes mellitus and gestational diabetes mellitus pregnancies

Background: During pregnancy,complex changes occur in lipid profiles. The aim of the study was to evaluate the effect of lipid parameters on fetal growth in type 2 diabetes mellitus (D.M) and gestational diabetes mellitus (GDM) pregnancies. Material and methods: In forty three type 2D.M. and two hundred GDM women pregnancies were analyzed: age, body mass index (BMI), lipid parameters, HbA1c in first, second and third trimester of pregnancy, preeclampsia, and baby birth weight. Results: D.M. tip 2 and GDM group were statistically significant different in the following variables: total lipids, triglycerides, total cholesterol, BMI, age, baby birth weight, and incidence of SGA (9.4±2,3 vs. 11,0±2,3mmol/L, 2,4±1,4 vs. 3,4±1,6mmol/L, 5,5±1,2 vs. 6,4±1,4mmol/L, 30,6±5,4 vs. 26,9±5,2 kg/m2, 34±7,8 vs. 31,5±5,6 years, 3183±972 vs. 3533±699 g., 20% vs. 7,5%, respectively, p<0,05). Statistically significant correlations were found between triglycerides and HbA1c (r=0,18, p<0,05), HDL-C and HbA1c (r=-0,19, p<0,05), HDL-C and large for gestational age (LGA) (r=-0,17, p<0,05), small for gestational age (SGA) and Hba1c (r=0,29, p<0,05). LinearmultipleregressionanalysisdemonstratedthatLDL-C,triglycerides, and total cholesterol were independent predictors of LGA (p<0,05). Conclusion:LDL-C and triglycerides are predictors for macrosomia in type 2 D.M and GDM pregnancies.Thus, with good regulation of lipid profile we can avoid macrosomia from type 2 D.M and GDM pregnancies. Key words: lipid parameters, gestational diabetes mellitus, type 2 diabetes mellitus, macrosomia

Clinical Importance of Low Level of PAPP-A in First Trimester of Pregnancy - An Obstetrical Dilemma in Chromosomally Normal Fetus

BACKGROUND: A variety of recent evidence exists about the clinical implication of low level of Pregnancy-associated plasma protein A (PAPP-A) in pregnancy. This glycoprotein is a protease, which releases the Insulin-like growth factor from IGFBP 4. Its role is a trophoblastic invasion of decidua, stimulation of cell mitosis and differentiation. It has an immunosuppressive effect in the placenta, inhibition of coagulation and complex role for integration of all these processes in the placenta. Level of PAPP-A (under 0.4 MoM-Multiple of Medians) in first-trimester screening in chromosomally and morphologically normal fetuses, could influence fetal weight, preeclampsia, premature birth and stillbirth. As a result of the complications mentioned above, there is implication on timing, mode of delivery and condition of the newborn. AIM: The study aims to evaluate the influence of low PAPP-A, measured in the first trimester on the outcome of pregnancy, with accent disorders which are the result of placental insufficiency. Also, gestational week, mode of delivery and condition of newborn secondary underlying conditions will be evaluated. MATERIAL AND METHODS: After given information and consultation about the expectation from the screening, pregnant women with a singleton pregnancy were tested for First Trimester Screening to estimate the risk for Trisomy 21, 13, 18- the most frequent chromosomopathies. After exclusion of chromosomopathies and congenital malformations, one hundred and fourteen patients enrolled in the study. The target group (n = 64) with PAPP-A below 0.4 MoM and control group (n = 50) with PAPP-A equal and above 0.4 MoM. An assessment of mode and time of delivery and presence of small for gestational age newborns, preeclampsia, premature birth and newborn condition at delivery was made. RESULTS: The percentage of the patients delivered in term was similar between the target group (n = 64) and the control group (n = 50), 82.81% vs 82.0% respectively. The rate of cesarean section was 29.7 % in the target group vs 32% in the control group. A significant difference was found about elective vs urgent cesarean section in favour of the target group. The difference was present about the complication in pregnancy before delivery, 56% vs 22%, p = 0.023, which were the main indication for cesarean section. The difference in newborn outcome was not significant. CONCLUSION: There is a difference in frequency of complications, in the cases with PAPP-A under 0.4 MoM, such as premature birth, preeclampsia compound with SGA fetuses versus the control group. The difference for SGA newborn and premature birth among the groups has statistical significance. The patients delivered with cesarean section were with the main indications SGA or elevated blood pressure, often occurred combined with prematurity. Apgar score and birth weight were similar in target and control group, but the newborns with a birth weight under 2500 g. were more frequent in the target group. Because these results did not show another significance among two groups, probably lower cut-off is needed, combining with another test (Doppler of uterine arteries in the first trimester, biochemical test). Presence of other diseases which could hurt placental function should be emphasised

Obstetric Outcome in Pregnant Patients with Low Level of Pregnancy-Associated Plasma Protein A in First Trimester

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A), is a protease which releases Insulin-like growth factor. The role of this factor is stimulation of cell mitosis, differentiation and trophoblastic invasion of deciduas. Identification of patients with low PAPP-A (under 0.4 MoM in the first trimester has an influence on birth weight, attenuation of fetal growth, preeclampsia, birth and fetal demise.AIM: The main issue in the study is evaluating an influence of PAPP-A, calculated in the first trimester on the unfavourable outcome of pregnancy.MATERIAL AND METHODS: Seventy pregnant women with singleton pregnancy underwent first-trimester biochemical screening. The target group were women with PAPP-A below 0.4 MoM, and in control group, PAPP-A were оver 0.4 MoM. There was an assessment of the influence on the mode of delivery, gestational week, the presence of intrauterine growth restriction, preeclampsia, temporary birth, intrauterine fetal demise and newborn condition.RESULTS: In target group, consisted of 35 patients, 16 were delivered at term. From 28 to 37 g.w.- were 7 patient, 22-28 g.w.- 4 and 8 patients were under the 22 g.w (all with fetal demise) there were 19 pretemporary deliveries - 9 with Cesarean Section (SC). In the target group: 5 newborn wеre with IUGR, 6 women had preeclampsia, 1 had placental abruption. In control group were 35 patients: 28 delivered at term, 9 with SC, 26 vaginal deliveries; with IUGR were 4 newborns. Two newborns were hypertrophic.CONCLUSION: There is a significant difference in unfavourable outcome in the cases with PAPP-A under 0.4 Mom, particular in the group, with a PAPP-A value under 0.2 MoM. The patients delivered with SC with the main indications in utero hypoxia, growth restriction and elevated blood pressure had PAPP-A between 0.3-0.4 MoM. The patients with intrauterine fetal death and placental abruption in the most of the cases have PAPP-A value under 0.2 MoM. There is a need to be aware in these pregnancies to achieve the preventions of adverse outcome, to decrease perinatal morbidity and mortality

Maternal and Neonatal Outcomes in Pregnant Women with Gestational Diabetes Mellitus Treated with Diet, Metformin or Insulin

AIM: Aim of the study was to compare outcomes of pregnancy in gestational diabetes mellitus (GDM) treated with metformin, insulin, or diet.MATERIAL AND METHODS: The study included 48 women with GDM treated with metformin, 101 with insulin, and 200 women on a diet from the Outpatient Department of Endocrinology and University Clinic of Obstetrics and Gynecology in Skopje.RESULTS: The groups were comparable in age, smoking cigarettes and positive family history of diabetes. Mean glycosylated haemoglobin (HbA1c) at 37 gestation week, mean fasting, postprandial glycaemia, and gestational age at delivery were lower in diet and metformin than insulin group. No differences in mode of delivery were observed between the metformin and insulin group. Women in metformin group had a significantly lower incidence of LGA newborns than diet and insulin groups. The percent of SGA new-borns was higher in insulin group than diet and metformin groups. The incidence of neonatal hypoglycemia was statistically significantly higher in the insulin group than in the metformin and diet group.CONCLUSION: Metformin in women with GDM can improve maternal and neonatal outcomes compared with those treated with diet or insulin

The outcome of Pregnancy with Fetal Primitive Neuroectodermal Tumor

BACKGROUND: Fetal intracranial tumours are very rare. The overall incidence is 0.34 per one thousand live birth newborns. According to the new classification of central nervous system tumour (2016), a primitive neuroectodermal tumour of (PNETs) is an embryonal tumour group; these are tumours with high malignancy and belong to group IV (WHO). In our case, we will present a case of PNETs in 28 gestation week old fetus, diagnosed antenatally and confirmed postnatally.CASE REPORT: We present the third pregnancy in 29 years old patient, with two previous term deliveries of healthy newborn. She came to University clinic at 27+3 gestational week for fetal hydrocephalus. After an ultrasound and MRI scan, possibilities were explained to the parents. During the medico-ethical counselling, explain to the parents the need for operation and the possibility of postoperative adjuvant therapy, quality of life with potential future disabilities. They choose to terminate the pregnancy. Postmortem the diagnosis was PNETs. Summary of analysis: peripheral neuroectodermal tumour with ganglion and neuronal differentiationCONCLUSION: Antenatal management depends on the gestational week in the time of diagnosis and the decision of parents. If the lesion is before viability fetus, it should be offered termination of pregnancy. Another important factor is the mode of delivery, because of increased intracranial pressure although this aggressive combined modality of treatment, recurrence is often. Tree year of survival is between 53% and 73% when the adjuvant radiotherapy is included. For that, they should be diagnosed as soon as possible before achieving fetal viability. Only 18% of those tumours presenting in the first year of life are diagnosed before or at delivery

Multidisciplinary approach to management of hypofibrinogenaemia in pregnancy: A case report

Inherited fibrinogen disorders introduce risk for recurrent abortions, sub-chorionic haematoma, placental abruption and postpartum haemorrhage. This is a case report of a successful pregnancy outcome in a 37-year old woman with hypofibrinogenaemia. She was referred to a coagulation test in the first trimester because of history of preeclampsia and HELLP syndrome in previous pregnancy. Hypofibrinogenaemia was diagnosed with fibrinogen level of 0.7 g/L. During the pregnancy she was regularly monitored for fibrinogen levels and multiple cryoprecipitate concentrates were given. She delivered at 39th gestation week, with elective caesarean section under general anaesthesia. There was one episode of postpartum haemorrhage treated with 2 units of red blood cells, repeated infusions of cryoprecipitate to obtain the level of fibrinogen of 2 g/L. She was discharged on the 6th postpartum day in a good condition. In these disorders levels of fibrinogen should be higher than 1 g/L during pregnancy or 2 g/L in case of caesarean section for successful prenatal and peripartal management

Association between Foetal Growth and Different Maternal Metabolic Characteristics in Women with Gestational Diabetes Mellitus

Abstract: Objective: The aim of the study was to investigate the association between foetal growth and different maternal metabolic characteristics in women with gestational diabetes mellitus (GDM). Methods: The study group included 200 consecutive pregnant women who attended the Endocrinology, Diabetes and Metabolic Disorders Outpatient Department in the period from 02.2006 to 02.2009 with singleton pregnancy and GDM diagnosed following ADA criteria. The following parameters were studied: pre-pregnancy maternal body mass index (BMI), 3-hours 100g oral glucose tolerance test (OGTT) results, glycosylated haemoglobin (HbA1c), total lipids (TL), total cholesterol (TH), triglycerides (TG), HDL- and LDL-cholesterol levels at admission. Neonatal birth weight and the prevalence of being large for gestational age (LGA) was an end-point. Results: We found a significant association between birth weight and pre-pregnancy BMI, HDL-C and birth weight of a large child born previously. Birth weight of a large child born previously was the strongest independent predictor for LGA. The prevalence of LGA (from 27% to 80%) was related to a number of altered maternal characteristics. Conclusion: Pre-pregnancy BMI, HDL-C and birth weight of a large child born previously are the independent predictors for LGA, but results of glucose levels during OGTT are not useful in the prediction of LGA in GDM pregnancies. Probably morefactors and other maternal metabolic parameters than glucose levels during OGTT are responsible for the risk of LGA. Key words: gestational diabetes, LGA, macrosomia, maternal characteristics, OGTT

Gestational Diabetes Mellitus – The Impact оf Maternal Body Mass Index аnd Glycaemic Control оn Baby’s Birth Weight

Abstract: Objectives. To asses the influence of the maternal BMI and glycaemic control in women with GDM on the baby's birth weight (BW). Material and methods: We analysed 180 women with GDM. Macrosomia has been defined as BW > 4000 gm, small for gestational age < 2700 gm and appropriate for gestational age between both. According to the baby´s BW the pregnant women were divided into three groups: group 1 (G1) with BW < 2700 gm (n = 26); group 2 (G2) with BW between 2700 to 4000 gm (n = 117), and group 3 (G3) with BW > 4000 gm (n = 37). We also analysed BMI (kg/m²), HbA1c (%), PPG (mmol/L) and time of delivery (WG). Results: Comparisons between G1 and G2 showed: BMI (30.7 ± 5 & 31 ± 5.2; p < 0.7), HbA1c (6.4 ± 0.8 & 5.1 ± 0.8, p < 0.002), PPG (8.2 ± 1.7 & 6.9 ± 1.5, p < 0.02), time of delivery (35.2 ± 3.8 & 38.6 ± 1.5, p < 0.0001) and BW (2289 ± 504 & 3474 ± 334, p < 0.0001). Comparisons between G2 and G3 showed: BMI (31 ± 5. 2 & 33.4 ± 6.1; p < 0.02), HbA1c (5.2 ± 1.1 & 6.4 ± 2.3, p < 0.02), PPG (6.9 ± 1.5 & 8.2 ± 1.9, p < 0.02), time of delivery (38.6 ± 1.5 & 39.3 ± 1.4, p < 0.01) and BW (3474 ± 334 & 4431 ± 302, p < 0.0001). Comparisons between G1 and G3 showed the difference at delivery time and the baby's BW (p < 0.0001). Conclusions: Maternal obesity and PPG contribute to macrosomia and also PPG to SGE. Key words: gestational diabetes, large for gestational age, small for gestational age, birth weight, postprandial glycaemia