Clinical Case of Parvovirus B19 Infection in Pregnant Woman with Β-Thalassemia in Bulgaria.

A pregnant 30-year-old female in the 34th gestational week was admitted at University "Maichin Dom" Hospital prior to childbirth. The patient is diagnosed with ß-thalassemia. During laboratory screening hemoglobin of 98 g/L was established. Blood smear shows mild microcytic hypochromic anemia: RBC 5.15 x 1012/L, HGB 98 g/L, MCV 65.8 fL, MCH 19.4 pg, MCHC 295 g/L. Serum iron concentration is 12.9 µmol/L and ferritin 17.5 µg/L. For the delivery process cesium was considered. Two days after procedure a rash presented on face, hands and breasts. Although the mother was positive for parvovirus B19 infection, the baby was negative. This was confirmed by se-rological and molecular investigations. We discovered only the mother's B19V IgG antibodies in the newborn. In connection to the main disease, namely ß-thalassemia, acute virus infection could cause aplastic crisis. After consultation with a hematologist, serum hepcidin concentration (an iron homeostasis regulator) was quantified: 19.4 µg/L. ELISA test was used to prove B19V IgM antibodies in the mother. PCR analysis shows the presence of B19V DNA. During infection, inflammatory cytokines increase hepcidin secretion, leading to iron deposition into cells.

Assessment of the impact of 10-day intermittent hypoxia on the autonomic control measured by heart rate variability.

PURPOSE: The purpose of this study is to establish the alterations in the activity of the autonomic nervous system (ANS) via heart rate variability (HRV) in subjects exposed to 1 h of exogenous hypoxia for 10 consecutive days. METHODS: Twelve healthy non-smoker males at mean age of 29.8 ± 7.4 (mean ± SD) breathed hypoxic air delivered through hypoxicator (FiО2 = 12.3% ± 1.5%) for 1 h in 10 consecutive days. Pulse oximetry and electrocardiography were monitored during the visit and HRV was calculated for the entire 1-h hypoxic period. RESULTS: Comparing the last hypoxic visit to the first, subjects had higher standard deviation of normal-to-normal interbeat intervals (SDNNs) (65.7 ± 32.5 vs. 81.1 ± 32.0 ms, p = 0.013) and root mean square of successive R-R interval difference (RMSSD) (58.1 ± 30.9 vs. 76.5 ± 34.6 ms, p = 0.029) as well as higher lnTotal power (8.1 ± 1.1 vs. 8.5 ± 0.9 ms2, p = 0.015) and high frequency (lnHF) (6.8 ± 1.3 vs. 7.5 ± 1.2 ms2, p = 0.05) and lower LF/HF (2.4 ± 1.4 vs. 1.5 ± 1.0, p = 0.026). Changes in saturation (87.0 ± 7.1 vs. 90.8 ± 5.0%, p = 0.039) and heart rate (67.1 ± 8.9 vs. 62.5 ± 6.0 beats/min, p = 0.040) were also observed. CONCLUSIONS: Intermittent hypoxic training consisting of 1-h hypoxic exposure for 10 consecutive days could diminish the effects of acute exogenous hypoxia on the ANS characterized by an increased autonomic control (SDNN and total power) with augmentation of the parasympathetic nervous system activity (increased RMSSD and HF and decreased LF/HF). Therefore, it could be applied as a pre-acclimatization technique aiming at an increase in the autonomic control and oxygen saturation in subjects with upcoming sojourn to high altitude.

[NEW APPROACH IN DIAGNOSTIC ALGORITHM OF AN INFECTIOUS AGENTS (PARVOVIRUS B19 AND CHLAMYDIA TRACHOMATIS) INVOLVED IN THE DEVELOPMENT OF PATHOLOGICAL PREGNANCY].

UNLABELLED: Viral infections during pregnancy, along with some form of accompanying pregnancy diseases such as diabetes, cardiovascular, gastrointestinal, kidney and others, are a major cause of arising complications and mortality of mother and fetus. AIM: To improved the laboratory diagnostic approach in the study of women with pathological pregnancy, including improve treatment and prognostic character of the outcome of pregnancy, with the inclusion of two infectious agent parvovirus B19 and Chlamydia trachomatis. To determine types of anemia in pregnant women with parvovirus B19 and Chlamydia trachomatis infection and to select the correct therapeutic approach. MATERIALS AND METHODS: A total 36 serum samples from pregnant women with anemia (n = 22), nonimmune hydrops fetalis (n = 8) and fetal ascites (n = 6) were tested. The study included three newborns (n = 3), tested on the occasion of a possible maternal-fetal infections. The serological (indirect ELISA tests) and molecular (B19V-PCR test) methods were used. In anemic pregnant women were evaluated iron homeostasis parameters with CLIA, AAS and NEPH methods. RESULTS: In 6/36 (16.66%) patients B19V-IgM positive result was detected. Among the study patients with anemia, non-immune hydrops fetalis and fetal ascites incidence of proven B19V-IgM antibodies was 18.18% (4/22), 12.5% (1/8) and 16.66% (1/6), respectively. Protective B19-IgG antibodies in 25/39 (64.10%) samples were found. A positive PCR signal was showed in all patients with positive B19V-IgM, and 1 patient with anemia and positive B19V-IgG result. The three newborns were positive for B19V-IgG antibodies (maternal) and negative for acute viral infection. Present Chlamydia trachomatis infection in 6/36 (16.66%) and past infection in 5/36 (13.89%) patients was demonstrated. The anemia was evaluated as iron-deficiency according to low hepcidin levels 2.54 ± 0.4 µg/I compared to pregnant control group which included women without anemia 25.9 ± 2.8 µg/I. CONCLUSION: In view of the varied transmission B19V and the wide range of complications arising as a result of chlamydia, screening for these viral agents of pregnant women and women of childbearing age is an important approach for monitoring of pregnancy.

[SERUM HEPCIDIN LEVELS IN ENDOMETRIOSIS].

OBJECTIVE: Endometriosis is a benign disease, which ranks third in mortality from gynecological morbidity after inflammatory conditions and myoma. We tried to evaluate serum iron and hepcidin levels and seek their connection with the development of endometriosis. METHODS: For quantification of serum hepcidin we use ELISA method. 53 women were included, average age 25.4 ± 4.3. They were divided into two groups--women with endometriosis (EM) and a control group. Samples were taken at the University hospital "Maichin dom" for a period of one year. We measure serum iron, ferritin and calculate transferrin saturation. We use the Pearson's correlation and Student's t-test for evaluating of statistical significance. RESULTS: We found statistically significant differences in serum hepcidin levels in the groups included: women with endometriosis have higher concentrations 64.3 ± 7.8 µg/L compared to the control group 19.4 ± 4.1 µg/L (r = -0.201, P < 0.001). Serum ferritin levels showed significant differences between the two groups in EM 17.9 ± 8.4 ng/ml vs control 79.5 ± 14.6 ng/ml (r = -0.249, P < 0.001). Statistically significant difference was found in serum iron levels: in EM 21.9 ± 3.2 µmol/L compared to 13.5 ± 1.9 µmol/L in the control group (P < 0.001). CONCLUSION: Our results support the idea that iron overload and increased serum levels of hepcidin plays an important role in the pathogenesis of endometriosis.

[Tocolysis with nifedipin; its use in current practice].

AIM: The aim of the study is to establish the safety and efficacy of calcium channel blocker- Nifedipin as tocolytic agents. A wide range of tocolytics have been utilized for the management of preterm labor Calcium channel blockers, namely nifedipine, gained popularity as tocolytics due to the oral route of administration, availability of immediate- and slow-release preparations, the low incidence of maternal adverse effects associated with their use, and the fact that they are inexpensive. METHODS: 88 pregnant women in preterm labor participated in a prospective longitudinal study Inclusion criteria were: gestational age between 24 and 34 weeks gestation; uterine contractions in 10-15 min interval; single pregnancy, lack of contraindications for tocolysis. In all cases the calcium antagonist Nifedipine was used in dosage 4 x 10 mg per os. The clinical response to tocolysis, gestational age at delivery and potential side effects were analyzed. RESULTS: 91 pregnant women participated in the study. Three were excluded because they refused to participate. 88 pregnancies were finally analyzed. In nine of them maternal contractions persisted despite of treatment. The other 79 pregnancies were delayed 48 hours to receive antenatal corticosteroids. From all these 79 pregancies 66 delayed 7 days. The most common adverse effects were tachycardia, hypotonia, headache, dizziness, but they escape soon after the first dose. CONCLUSION: Nifedipine is an effective oral tocolytic with few maternal side effects.

[Induced abortion--clinical problems, regulatory gaps, chaos. How much longer?].

Induced abortion is becoming more and more frequent in the contemporary clinical practice. Usually these are pregnant women with diagnosed foetal malformations. Most of them reach a final diagnose in the late second trimester and hence need a pregnancy termination at this gestational age. They are treated in accordance with The Artificial Pregnancy Termination Regulations and put on N 142 clinical-care pathway. The presentation describes the patients' journey form the diagnose through the induced abortion and to the discharge. Analyses the regulations, the multiple inaccuracies and striking omissions with regards to the procedure. Stimulates a discussion on the clinical problems and offers reasonable and realistic solutions.

[Preterm birth in Bulgaria--changes in aetiology and incidence in the last decade].

There is no decrease in the incidence of preterm birth in Bulgaria and in the world, despite of all the therapeutic and prophylactic efforts. The rate of prematurity in University Maternity Hospital 'Maichin dom' in the last decade has increased significantly- from 11.6% in 2003 to 17.5% in 2013. The numbers are higher than the national average due to the essence of the Hospital being a leading clinical and scientific center. Thorough analysis demonstrates significant increase in the first grade prematurity being 5.8% of all live births in 2003 and 10.2% of all live births in 2013. In fact 58% of all premature births result in first grade preterm newborn. There is no significant increase in the forth grade- severe prematurity in the last decade. We believe that this increase in preterm birth rate is due to several reasons: the success of assisted reproductive technologies, which in Bulgaria leads to a significant increase in the number of multiple pregnancies; destructive/ablative methods of treatment of cervical intraepithelial neoplasia, especially LLETZ (LEEP), postponing of first pregnancy, increase in the number of adult primiparous women and as a whole pregnancy at later age, pregnancy in puberty. All these impose changes in the protocol for pregnancy follow up. Furthermore, we believe it is high time to increase the effectiveness of this service, as lack of adequate follow up is a reason for preterm birth on its own.

[Plasma D-dimer levels in preeclampsia].

Preeclampsia is a multifactorial disease characterized by hypertension and proteinuria after 20 weeks of gestation of the pregnancy. Preeclampsia is characterized by the deposition of fibrin in the walls of small blood vessels. D-dimer was used as a marker for degradation/synthesis of fibrin in vivo. D-dimer has emerged as a useful indicator in the diagnosis of thrombotic conditions because its plasma concentration has a high predictive value for the assessment of venous thromboembolism. The purpose of this study was to evaluate plasma levels of D-dimer and preeclampsia compared to normal pregnancy occurs. We found that elevated levels of D-dimer is associated with the development of preeclampsia in the third trimester of pregnancy compared with normal pregnancy occurs. Preliminary findings highlight the need for further in-depth studies during pregnancy in order to fully clarify the diagnostic/prognostic role of D-dimer preeclampsia.

[The asphyxia of the fetus--cardiotocography and ultrasound methods of diagnosis].

The asphyxia of the fetus remains a main cause for neonatal morbility and mortality. And the possibility of it developing antenatal or intrapartal. The main objective of the antenatal fetus examination tests is the timely diagnosis of the signs of the asphyxia of the fetus.

[Pregnancy-induced haemolytic anaemia].

This is the clinical case of a primiparous eight month pregnant female, presenting with symptoms of pregnancy-induced acute haemolytic anaemia (haemolytic aneamia provoked by an immune mechanism, intra- and extra-erythrocyte defects, and HELLP syndrome were excluded). The anaemia progressed to become life-threatening for both the pregnant women and the foetus, which brought the following questions into consideration: diagnosis of anaemia during pregnancy; dosing of corticosteroid therapy; possibility of giving birth to a viable foetus and prognosis for next pregnancies. Owing to the inter-disciplinary efforts, the life and health of this pregnant woman were preserved, but the foetus was lost.

[Mastodynia. Premenstrual syndrome].

Mastodynia is defined as breast tenderness and pain, also called mastalgia. There are several types of cyclic, noncyclic and extramammary. The cyclic mastodynia is the most common one, and represents a clinical symptom of the premenstrual syndrome and of the more severe premenstrual dysphoric disorder. The article outlines different types of mastalgia with their typical clinical features, including the relatively rear Tietze's syndrome and MONDOR'S disease, as well as the PMS and the PMDD. The authors also offer a diagnostic algorithm and specific diagnostic criteria. There is also a discussion on the main treatment alternatives being symptomatic treatment of the most troublesome symptoms or alteration of the menstrual cycle and a brief discussion on the pharmaceutical preparations used for treatment including the administration of selective serotonin reuptake inhibitors (SSRI).

[PlGF and sFlt-1--diagnostic significance in preeclampsia prediction in pregnant women with gestational and chronic hypertension].

Preeclampsia (PE) is characterized with hypertension and proteinuria after 20 gestational weeks. and is the major reason for maternal and fetal mortality during pregnancy. Etiology of PE is still unclear. Clinical manifestation is connected to high levels of circulated anti-angiogenic proteins such as soluble Fms-like tyrosine kinase 1 (sFlt1) and soluble endolgin (sEng). Furthermore PE leads to low serum levels of Placental growth factor (PIGF). The change of these serum levels appears before clinical manifestation, which makes them useful for screening of pregnant women with high risk of PE. This opportunity for prediction of PE would significantly lower the mortality caused by PE. We measure serum sFlt-1 and PIGF levels in pregnant women with normal and pathological pregnancy including gestational and chronic hypertension without PE. Population included 23 pregnant women during a period of two years. Comparison between the groups was made with parametric Student's test. A level of p < 0.05 was accepted as statistically significant. Eight women were with PE (one of them with chronic hypertension). Six pregnant women were with isolated hypertension (four with chronic and 2 with gestational hypertension). Nine pregnant women were with normal pregnancy. Serum sFlt-1 and PIGF levels showed significant differences in pregnant women in between 25th and 28th gestational weeks: a) for sFlt-1--in PE (4859.88 pg/ml) and normal pregnancy (3125.53 pg/ml)--p = 0.0002 or isolated hypertension (2791.40 pg/ml)--p = 0.0054 and b) for PIGF--in PE (206.63 pg/ml) and normal pregnancy (667.87 pg/ml)--p = 0.0011 or isolated hypertension (560.20 pg/ml)--p =0.0125. Our study shows that serum sFlt-1 and PIGF levels significantly changes during pregnancy and before clinical manifestation of PE (minimum in 15.5 gestational weeks).

[Nonspecific immunomodulation in obstetrics and gynecology with Ecomer preliminary report].

UNLABELLED: The article gives a brief description of "Ecomer", preparation containing shark liver oil. Main immunoactive ingredient of the shark liver oil are the alkylglycerols. The main characteristics of alkylglycerols are noted together with their mechanism of action. There is also a list of indications for Ecomer administration. There is a summary of the authors' experience with Ecomer, its efficacy in ObGyn being the main aim of this study. METHODS AND MATERIALS: For the purpose of the study Ecomer is given to two main groups of patients: I-pregnant women between 27 and 36 weeks of gestation having two subgroups: 1--with 8 women with naso-pharyngeal complaints and 2--with 13 patients with urinary tract complaints, suggestive of cysto-pyelitic disorders and II main group of patients operated for cervical cancer in different stages with two subgroups--1 with 17 patients with Ecomer intake started at the beginning of the radiation therapy, and 2 with 6 patients who began taking Ecomer before the beginning of the radiation therapy, after having a histologically proved diagnose. The I group took two capsules of Ecomer three times a day for 15 days or less if asymptomatic earlier; in the II group Ecomer was taken two capsules three times a day for 2 months, then one capsule three times a day for a month, followed by a repetition of the scheme. RESULTS: In the pregnant women group, improvement was noticed in 75% in the first subgroup and in 76% in the second subgroup. In the second main group the interpretation of results is hindered by the insufficient time interval. Nevertheless, fewer side effects of the radiation therapy was noticed in both groups. Improvement in the survival rate is yet to be followed up. CONCLUSIONS: Administration of Ecomer in pregnant women with naso-pharyngeal problems led to improvement in their general condition and less frequent need to prescribe antibiotics. In pregnant women with urinary tract problems, Ecomer resulted in easing the pain faster and lowered the recurrence risk. In women with cervical cancer, the treatment is quite aggressive and the opportunity to diminish the side effects by administration of a natural and harmless preparation should not be omitted.

[Preterm birth--incidence and etiology].

Preterm birth is a major societal and economic problem. To him is accounting for 80 to 90% of neonatal morbidity and mortality worldwide. It is recognized as a complex multifactorial condition with different underlying etiologies. Paramount in the prevention of preterm birth is physician education regarding known risk factors, signs and symptoms of preterm labor and the role of close follow-up in the patients identified as high risk.

[Intraamniotic infection--cause and satellite of preterm birth].

Intraamniotic infection (IAI), most commonly presented as chorioamniotitis, plays a major role in the pathogenesis of preterm birth (PTB). In this study, we sought for signs of IAI through clinical and laboratory parameters (leukocyte count, CRP concentration and IL-6 in maternal blood), and compared those to the newborns' infectious condition. Using cervical and vaginal secretion cultures, we determined the probable causing agents of IAI. We also followed up the therapeutic effect from the use of corticosteroids, tocolitics and antibiotics for the treatment of PTB. The results demonstrated that over 46% of the pregnant women with PTB presented with evidence of IAI. The best diagnostic option to detect an IAI provides maternal blood IL-6, and the combination between leukocyte count and CRP is a must for routine examinations. We did not isolate a single vaginal pathogen but a combination of harmful microbes which provided evidence of a vaginal ecosystem disorder. The combination therapy in over 50% of women had a positive effect on PTB for the period of corticosteroid prophylaxis (72 hrs). From hour 84, antibiotic therapy can no longer control IAI development.

[HIV infection in pregnant women and risk of preterm birth].

According to estimates by WHO and UNAIDS, 34 million people were living with HIV at the end of 2011. Transmission of the human immunodeficiency virus (HIV) from mother to child can occur in utero, during labour or after delivery from breastfeeding. The majority of infants are infected during delivery. Clinical records have found more evidence of an increased rate of preterm delivery in HIV-positive women in low income countries.

[Pregnancy termination in Bulgaria ­ past, present and future perspectives. Drugs induced abortion ­ guidelines by WHO].

There are still too many unsafe abortions performed worldwide. Together with the efforts to reduce the abortion by choice, we note a rise in the need for mid trimester pregnancy termination for medical reasons. The article looks at the past present and future perspective of the abortion as a procedure in Bulgaria. States the fact that medical abortion is officially not widely performed. We reckon that with the existing guidelines by WHO and with Mifepriston and Misoprostol recently registered in Bulgaria, it is time for the medical abortion to become part of the clinical practice in Bulgaria. We believe that early medical abortion as well as mid trimester induced abortion is and adequate if not better alternative to the existing in Bulgaria procedures.

[Mid trimester pregnancy termination--review of the caseload for 2012 of Maternity University Hospital 'Maichin Dom', Sofia, Bulgaria].

Midtrimester pregnancy termination is yet an ongoing clinical issue in spite of the hard work on the matter in the recent years. There is a significant withdrawal from the surgical methods, absence of adequate drug preparations for medical termination and absence of guidelines for such form the Bulgarian Society of Obstetricians and Gynaecologists. In order to obtain a clear view on the current situation, we made a review on all the cases of midtrimester induced abortion in Maternity University Hospital 'Maichin dom' for the year of 2012. We found that the mid trimester abortions represent 11.7% of all abortions performed in the hospital in 2012. Most widely used are the following methods: vaginal application of prostaglandin E2 vag. tabl. 3 mg--33.5%, intrauterine balloon-catheter application after priming of the cervix with prostaglandin E2 3 mg--18%, prostaglandin F 2alpha as intrauterine extraamniotic continuous infusion through a balloon catheter, noweighton--9%, vaginal application of Prostaglandin E1--5.4%. Surgical termination was used in as little as 6% of the cases. The shortest interval for expulsion had been registered with the application of PG E1--19'55", compared with the most widely spread method of application of PG E2, which was more than twice longer--42'12". Application of balloon catheter, after priming of the cervix with 3 mg PG E2 vag. tabl. proved to be inefficient with mean interval for expulsion of 88'42". Surgical termination for midtrimester pregnancy is seen as the last alternative, it is rarely applied and mostly as anurgent procedure. In conclusion, the existing regimes for medical termination of midtrimester pregnancy are inefficient; application of 3 mg PG E2 is ineffective during the second trimester, insertion of balloon catheter attached to a weight is unacceptable. It is highly recommended that more attention is paid to the surgical termination with regards to residence training programmes and maintaining of qualification. This is needed as the procedure is usually performed to stop life threatening bleeding and is hence urgent. We underline the necessity of adequate guidelines for midtrimester medical termination. They should be based on Misoprostol as this is the gold standard for this gestational age. We believe there is enough clinical and scientific evidence for its safety and efficacy. Moreover, we are happy to announce that Misoprostol is already registered in Bulgaria.