Cadmium and Lead in Women Who Miscarried.

BACKGROUND: Cadmium (Cd) and lead (Pb) are toxic elements which, when ingested excessively in food and drinking water, accumulate in selected organs and pass through the placenta barrier to the foetus, showing teratogenic effects. The aim of the study was to determine the concentration of Cd and Pb in blood and placental tissue in women who miscarried. METHODS: The study group consisted of 83 women who miscarried. The control group included 35 women in the first trimester of pregnancy and after childbirth. The experimental materials consisted of whole blood and fragments of placental tissue. The concentrations of Cd and Pb were determined using atomic absorption spectrometry (AAS) with electrothermal atomization in a graphite furnace and by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in standard mode. RESULTS: The average concentration of Cd (2.730 ± 2.07 µg/L) and Pb (35.54 ± 11.0 µg/L) in the blood of women with miscarriage was higher in comparison to the level of these toxic metals in the blood of women from the control group (Cd 1.035 ± 0.59 µg/L; Pb 27.11 ± 4.6 µg/L). The average Cd (214.4 ± 514 µg/L) and Pb (199.6 ± 348 µg/L) content in the placenta of women with miscarriage was higher in comparison to the amount of these elements in the placenta of women from the control group (Cd 127.4 ± 85 ng/L; Pb 26.35 ± 7.9 ng/L). Tobacco smoking significantly affected cadmium blood levels and the placental tissue content in women who miscarried. CONCLUSIONS: Elevated Cd and Pb concentrations in the blood and placenta of pregnant women may be connected with the occurrence of miscarriage; therefore, the levels of these heavy metals should be monitored in women who plan pregnancy. It seems that determining the level of molar ratio between toxic metal and antioxidant elements can be analyzed as a marker for selection for control examinations as a valuable complement to existing diagnostic procedures in prevention, especially in early pregnancy. Additional diagnostic methods should be established as new tools in perinatal care in order to enable early diagnosis of pregnancy pathology and, especially, to prevent miscarriage.

Chemokines profiling of patients with preterm birth.

INTRODUCTION: Nowadays it is thought that the main cause of premature birth is subclinical infection. However, none of the currently used methods provide effective prevention to preterm labor. The aim of the study was to determine the concentration of selected chemokines in sera of patients with premature birth without clinical signs of infection (n = 62), threatened preterm labor (n = 47), and term births (n = 28). METHOD: To assess the concentration of chemokines in the blood serum, we used a multiplex method, which allows the simultaneous determination of 40 chemokines per sample. The sets consist of the following chemokines: 6Ckine/CCL21, Axl, BTC, CCL28, CTACK/CCL27, CXCL16, ENA-78/CXCL5, Eotaxin-3/CCL26, GCP-2/CXC, GRO (GRO α /CXCL1, GRO ß /CXCL2 and GRO γ /CXCL3), HCC-1/CCL14, HCC-4/CCL16, IL-9, IL-17F, IL18-BPa, IL-28A, IL-29, IL-31, IP-10/CXCL10, I-TAC/CXCL11, LIF, LIGHT/TNFSF14, Lymphotactin/XCL1, MCP-2/CCL8, MCP-3/CCL7, MCP-4/CCL13, MDC/CCL22, MIF, MIP-3 α /CCL20, MIP-3- ß /CCL19, MPIF-1/CCL23, NAP-2/CXCL7, MSP α , OPN, PARC/CCL18, PF4, SDF-1/CXCL12, TARC/CCL17, TECK/CCL25, and TSLP. RESULTS: We showed possible implication of 4 chemokines, that is, HCC-4, I-TAC, MIP-3 α , and TARC in women with symptoms of preterm delivery. CONCLUSION: On the basis of our findings, it seems that the chemokines may play role in the pathogenesis of preterm labor. Defining their potential as biochemical markers of preterm birth requires further investigation on larger group of patients.

Expression of selected genes in preterm premature rupture of fetal membranes.

OBJECTIVE: To analyse the expression of 15 genes encoding receptors and enzymes associated with the molecular mechanism of the tocolytic drugs atosiban (oxytocin receptor antagonist), nifedipine (calcium channel blocker) and celecoxib (selective cyclo-oxygenase-2 inhibitor) in preterm labor patients with premature rupture of fetal membranes in relation to symptoms of intrauterine infection and preterm labor risk factors. DESIGN: Experimental molecular study. SETTING: Tertiary obstetric care center. SAMPLE: Myometrial samples were obtained during cesarean sections from 35 patients who delivered preterm with unverified symptoms of intrauterine infection, 35 patients who delivered preterm without symptoms of intrauterine infection and 90 women who delivered at term. METHODS: The Micro Fluidic Profiling Card analytic system was used to evaluate mRNA expression of the genes of interest. MAIN OUTCOME MEASURES: The relative quantification values for mRNA expression. RESULTS: The median oxytocin receptor and cyclo-oxygenase-2 mRNA expression in preterm patients with clinical symptoms of intrauterine infection was significantly higher than in preterm patients without symptoms. The median mRNA expression of ß(1) , ß(3) and ß(4) subunits of the L-type calcium channel and prostaglandin E(2) receptor was significantly higher in preterm patients compared with term patients. CONCLUSIONS: The mRNA expression of hormones, enzymes and their receptors associated with tocolytic actions can differ in various clinical conditions. The expression of these genes is regulated at different levels and can be modified by inflammatory factors, which affect their functions.

Spontaneous rupture of unscarred uterus in the early second trimester: a case report of placenta percreta.

BACKGROUND: Prevalence of uterine rupture at delivery has been recently estimated at less than 1 in 2500 deliveries. Spontaneous uterine rupture in the early mid-trimester (16 weeks gestation or less), is far less frequent. We report a case of uterine rupture due to placenta percreta in otherwise uncomplicated pregnancy CASE: A 35-year-old, gravida 5, para 5, at 15wk 2d gestation (menstrual age) with negative history of uterine scarring suddenly developed symptoms of incipient hypovolemic shock while being hospitalized for imminent miscarriage. On exploratory laparotomy we found a midline uterine rupture infiltrated by the placenta. Supracervical hysterectomy was performed. Postoperative lab analysis confirmed the elevated serum AFP levels. CONCLUSION: Abnormal placentation and subsequent uterine rupture should be taken into consideration also in women in the second trimester who have no history of uterine instrumentation.

[Evaluation of carbetocin (pabal) efficacy in the prevention of the postpartum hemorrhage in women after cesarean section--preliminary report]. / Ocena skutecznosci stosowania karbetocyny w profilaktyce krwawien poporodowych u kobiet po cieciu cesarskim--doniesienie wstepne.

OBJECTIVES: The aim of this study was to evaluate the efficacy of carbetocin in prevention of PPH in women after cesarean section. MATERIAL AND METHODS: We enrolled 60 patients who had undergone cesarean section in tertiary referential center, Department of Perinatology, Medical University of Lodz, Poland, between January and June 2008. Each patient obtained a single 100 microg dose of carbetocin intravenously during cesarean section, immediately after the delivery of the baby and prior to the delivery of the placenta. We evaluated postoperative blood parameters in 2 and 12 hours after the operation, the proportion of patients requiring additional uterotonic agents and adverse events in the whole population and in the group of women with high risk of PPH. RESULTS: 58.1% of patients underwent emergency and 41.3% elective cesarean section delivery. The risk factor of PPH was identified in 38 women (63.3%). The results of this study indicate that carbetocin produces rapid and long-lasting uterine tone. A small drop in mean hemoglobin and hematocrit levels 2 and 12 hours after the operation was observed. 15% of patients required the use of additional uterotonic agents. In the group of women with high risk of PPH, carbetocin appeared to be effective in 79% of the patients. Only 11.4% of patients had minor adverse events. CONCLUSIONS: Carbetocin appears to be an effective new drug in the prevention of postpartum hemorrhage, not only among women undergoing cesarean section but also in the group of women with PPH risk factors.

Uterine contractility: visualization of synchronization measures in two simultaneously recorded signals.

The analysis of the uterine contraction signals in nonpregnant states gives information about physiological changes during the menstrual cycle. Spontaneous uterine activity was recorded directly by a dual microtip catheter. The device consisted of two ultra-miniature pressure sensors. One sensor was placed in the fundus, the other in the cervix. It was important to identify time delays between contractions in two topographic locations, which may be of potential diagnostic significance in various pathologies: dysmenorrhea, endometriosis, and fecundity disorders. In this study the following synchronization measures-the cross-correlation, the semblance, the mutual information-were used to visualize the time delay changes over time. These measures were computed in a moving window with a width corresponding to approximately two or three contractions. As a result, the running synchronization functions were obtained. The running synchronization functions visualize changes in the propagation of the two simultaneously recorded signals. The propagation% parameter assessed from these functions allows for quantitative description of synchronization. Finally, we illustrate the use of running synchronization functions to investigate the effect of treatment with tamoxifen on primary dysmenorrhea.

Reductionist and system approaches to study the role of infection in preterm labor and delivery.

A substantial number of patients with preterm labor and delivery do not show clinical signs of infection, however, it is the subclinical form which is the main causative factor and often results in premature delivery. The hitherto commonly applied methods of inflammation detection are based either on potentially hazardous amniocentesis or still insufficient inflammation-related protein measurement in the serum or other biological fluids. The advent of new "omics" technologies has led to a paradigm-shift in experimental approach which tends to primarily generate rather than form hypotheses. This has resulted in a surge of wealth of data composed of sets of individual or clusters of new genes and proteins that can be of potential importance as new markers of inflammation leading to preterm labor. It is hoped that as a result of those new methodologies the overall perception of medical research and practice would gradually change from reductionist to systems approach. Despite several successes of reductionism in the diagnosis and treatment of preterm labor it seems that system-based methodology would contribute to a more favorable personalized rather than one-for-all patient assistance. In this review we present the current knowledge on this new attractive field of medical studies with emphasis on early detection of infection related with preterm labor.

New research models and novel signal analysis in studies on preterm labor: a key to progress?

Preterm labor affects up to 20% of pregnancies, is considered a main cause of associated neonatal morbidity and mortality and is responsible for neonatal care costs of multimillion euros. In spite of that, the commercial market for this clinical indication is rather limited, which may be also related to high liability. Consequently, with only a few exceptions, preterm labor is not in the orbit of great interest of the pharmaceutical industry. Coordinated effort of research community may bring the change and help required to reduce the influence of this multifactorial syndrome on society. Between the novel techniques that are being explored in a SAFE (The Special Non-Invasive Advances in Fetal and Neonatal Evaluation Network) group, there are new research models of preterm labor as well as novel methodology of analysis of biological signals. In this article, we briefly describe new clinical and nonclinical human models of preterm labor as well as summarize some novel methods of data processing and analysis that may be used in the context of preterm labor.

[Serum cotinine level as a biomarker of tobacco smoke exposure during pregnancy]. / Stezenie kotyniny w osoczu jako biomarker czynnej i biernej ekspozycji kobiet ciezarnych na dym tytoniowy.

AIM: The aim of the study was to evaluate the reliability of self-reported smoking status and environmental tobacco smoke exposure (ETS) during pregnancy, assessing serum cotinine level. METHODS: The prospective cohort study was conducted in 2 antenatal care units in Lodz, Poland. Study population consisted of 183 pregnant women between 20-24 weeks of pregnancy. All of the women who agreed to participate in the study were interviewed to investigate certain socio-demographic, lifestyles, behavioural characteristics and obstetric background. Self-reported smoking status and ETS exposure were verified with the help of serum cotinine level. Cotinine level was analyzed by means of gas chromatography with mass spectroscopy (GC-MS). We choose more than 15 ng/ml as serum cotinine level for smokers, 2-15 ng/ml for ETS exposure and less than 2 ng/ml for non-smokers not exposed to ETS. RESULTS: Among non-smoking and not ETS-exposed women, 17% had cotinine level indicating active smoking and 74% ETS exposure. About 4% of the women who indicated ETS exposure during pregnancy had serum cotinine level higher than 15 ng/ml indicating active smoking. CONCLUSIONS: The information about active and passive smoking during pregnancy obtained from mothers and based on the questionnaire does not indicate objective maternal exposure to tobacco smoke.

Decreased serum level of macrophage inflammatory chemokine-3beta/CCL19 in preterm labor and delivery.

OBJECTIVE: Chemokines are small soluble molecules which mediate leukocyte migration and may be involved in the pathophysiology of preterm labor. We aimed to determine if serum concentrations of selected chemokines are changed in preterm labor and delivery. STUDY DESIGN: A novel array-based enzyme-linked immunosorbent assay was used to quantitate serum levels of nine chemokines from a single sample: MDC/CCL22, TARC/CCL17, ITAC/CXCL11, I-309/CCL1, IP-10/CXCL10, MIP-1alpha/CCL3, -1beta/CCL4, -3alpha/CCL20 and -3beta/CCL19. Women in preterm labor who delivered (n = 17), women at preterm pregnancy not in labor (n = 13) and women in labor at term (n = 8) participated. RESULTS: In the preterm delivery group of patients, the MIP-3beta/CCL19 concentration was in mean (+/-S.D.) 70.4+/-31.7 pg/mL, which was significantly lower than that in preterm gravidas not in labor of 123+/-34 pg/mL (p < 0.001) and those in labor at term of 118+/-25.6 pg/mL (p < 0.01). The other measured chemokines did not differ significantly. CONCLUSIONS: Of a small number of examined chemokines, we were able to show that one of them, MIP-3beta/CCL19 was significantly lower in women with preterm labor and delivery. Whether or not this chemokine has a potential as biochemical marker of preterm delivery remains to be determined.

Visualization of synchronization of the uterine contraction signals: running cross-correlation and wavelet running cross-correlation methods.

In physiological research, we often study multivariate data sets, containing two or more simultaneously recorded time series. The aim of this paper is to present the cross-correlation and the wavelet cross-correlation methods to assess synchronization between contractions in different topographic regions of the uterus. From a medical point of view, it is important to identify time delays between contractions, which may be of potential diagnostic significance in various pathologies. The cross-correlation was computed in a moving window with a width corresponding to approximately two or three contractions. As a result, the running cross-correlation function was obtained. The propagation% parameter assessed from this function allows quantitative description of synchronization in bivariate time series. In general, the uterine contraction signals are very complicated. Wavelet transforms provide insight into the structure of the time series at various frequencies (scales). To show the changes of the propagation% parameter along scales, a wavelet running cross-correlation was used. At first, the continuous wavelet transforms as the uterine contraction signals were received and afterwards, a running cross-correlation analysis was conducted for each pair of transformed time series. The findings show that running functions are very useful in the analysis of uterine contractions.

[Comparison between computerized cardiotocography analysis in triplet and singleton pregnancies]. / Porównanie wyników komputerowej analizy kardiotokogramów w ciazy trojaczej i pojedynczej.

OBJECTIVES: Triplet pregnancies have higher perinatal morbidity and mortality rates than singleton pregnancies. In modern perinatology computer cardiotocography is one of the best methods of fetus state assessment. DESIGN: The research was based on computer analysis of cardiotocograph printouts. MATERIALS AND METHODS: The studies were made on 39 pregnant women in 27-36 week of gestation. The women were hospitalized in the Clinic of Perinatology I Department of Gynecology and Obstetrics, Medical University of Lodz and divided into two groups. First consisted of 30 singleton, second of 9 triplet pregnancies. RESULTS: Computer analysis of cardiotocograph printouts was performed and compared between the triplet and singleton pregnancy groups and presented in forms of tables. CONCLUSIONS: In the studded group of triplet pregnancy statistically significant higher number of high episodes, accelerations, fetal movements and signal loss were observed. The Apgar score and arterial cord pH was not different between the both groups.

[Monitoring of labour and delivery in the presence of meconium stained amniotic fluid by pulse oximetry]. / Pulsoksymetryczne monitorowanie porodu w przypadku obecnosci smólki w plynie owodniowym.

OBJECTIVES: Evidence of meconium-stained amniotic fluid during labor suggests implementation of close monitoring of fetal well-being. DESIGN: Our purpose was to compare fetal oxygen saturation between cases with normal and meconium stained amniotic fluid. MATERIALS AND METHODS: Fetal oxygen saturation was continuously recorded with use of Nellcor N-400 fetal pulse oximeter in 30 control cases of term labour of normal, and 30 cases of meconium stained amniotic fluid. Distribution of fetal oxygen saturation values during 5 periods of labour was analyzed and compared between the examined groups, and presented in forms of Tables, together with neonatal umbilical artery pH values, Apgar score, birth weight and percentage of caesarian sections performed. RESULTS: No significant differences in fetal oxygen saturation, neonatal umbilical artery pH, birth weight and caesarian sections rate were observed between analyzed groups. Newborns 1-th minute Apgar score (mean value) and base excess was lower in meconium group compared to control group. CONCLUSIONS: Our data demonstrate, that fetal oxygen saturation trends to decrease during labour in fetuses in both groups.

[B lynch suture for post partum heamorrhage due to uterine atony]. / Zastosowanie szwu lyncha typu b w leczeniu krwotoku poporodowego w przebiegu atonii macicy.

Uterine atony and concomittant massive haemorrhage is one of the most dangerous complications of labour. Conventional, conservative treatment approach comprising of oxytocics such as oxytocin, methergin or prostaglandins may fail in some cases, mandating surgical techniques, including hysterectomy. B Lynch compression uterine suture may be a safe and effective method of treatment in post partum heamorrhage and in most of cases may replace more complicated techniques. In this article, together with referring the technical aspects of this procedure, we present a case of successful treatment.

Differences in permeability of preterm and term fetal membranes to calcium ions - Preliminary report.

The metabolic activity of amniochorion contributes to the control of activation of labor-type uterine contractions. The study presents an experimental model of transport of calcium ions across the human amniochorion sampled directly after cesarean section in patients delivering both at term and prematurely. Transmembrane transport of calcium ions was lower in preterm vs. term tissue samples. The differences in permeability were most pronounced in the first 60 min of experiments. The results of the study provide evidence for the existence of an active mechanism of calcium transport which can contribute to regulating the contractility of the uterus.

Antioxidant status in women who have had a miscarriage.

PURPOSE: During normal pregnancy there is an oxido-reductive balance between action of pro-oxidative factors. The aim of this study was to evaluate the total antioxidant status (TAS) and glutathione peroxidase (GSH-Px) activity, and the content of selenium (Se), zinc (Zn), copper (Cu) and manganese (Mn) in women who have had a miscarriage. PATIENTS AND METHODS: The study group consisted of 83 women who had had miscarriages. The control group included 35 women in the first trimester of pregnancy, and 35 pregnant women after childbirth. RESULTS: TAS activity and Cu concentration in serum in women who experienced a miscarriage were significantly lower, but Mn level - higher, than in women in the first trimester of pregnancy. The content of Se, Cu and Mn in placental tissue in patients who have had a miscarriage was significantly higher, while Zn content was lower than in pregnant women at full-term delivery. CONCLUSIONS: Our findings, provided in the research, enable us to claim that the total antioxidative status is significantly lower in women who have had a miscarriage. Low level of Zn but high of Mn in the examined biological material may be indicative to the incidence of miscarriage.

Inhibitory effect of barusiban and atosiban on oxytocin-induced contractions of myometrium from preterm and term pregnant women.

BACKGROUND: A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocin-induced activity of myometrium from term pregnant women. The responsiveness to vasopressin was not influenced by the compound. OBJECTIVE: To test the effect of barusiban and a reference compound, atosiban, on oxytocin-induced activity of myometrium from women at preterm pregnancy in comparison to myometrium from women at term. METHODS: Fifteen preterm (30-36 gestational weeks) and 12 term pregnant women (38-41 weeks) who underwent cesarean delivery donated myometrial tissue for the study. Concentration-response curves following oxytocin administration to isolated myometrial strips were recorded in control experiments, in the presence of barusiban at concentrations of 2.5, 25, and 250 nM, and of atosiban at concentrations of 25, 250, and 750 nM. Effective concentration 50% (EC50) and pA2 values were calculated. RESULTS: Both antagonists in higher concentrations increased the EC50 values to oxytocin. The median pA2 value for preterm myometrium with barusiban was 9.76 and with atosiban 7.86. For term myometrium the corresponding pA2 results were 9.89 and 7.81, respectively. None of these pA2 values differed to any statistically significant degree. CONCLUSION: The selective oxytocin antagonist, barusiban, concentration-dependently inhibits oxytocin-induced myometrial contractions of both preterm and term myometrium at least as potently as atosiban. It remains to be determined if the selectivity of barusiban for the oxytocin receptor confers an advantage over atosiban as a tocolytic in preterm labor.

Fractal analysis of the uterine contractions.

The fractal dimension D may be calculated in many ways, since its strict definition, the Hausdorff definition is too complicated for practical estimation. In this paper we perform a comparative study often methods of fractal analysis of time series. In Benoit, a commercial program for fractal analysis, five methods of computing fractal dimension of time series (rescaled range analysis, power spectral analysis, roughness-length, variogram methods and wavelet method) are available. We have implemented some other algorithms for calculating D: Higuchi's fractal dimension, relative dispersion analysis, running fractal dimension, method based on mathematical morphology and method based on intensity differences. For biomedical signals results obtained by means of different algorithms are different, but consistent.

[The evaluation of prevalence and the impact of pathological microflora of the lower genital tract among women at early pregnancy on the risk of preterm delivery]. / Ocena wystepowania i wplywu patologicznej mikroflory dróg rodnych kobiet ciezarnych we wczesnej ciazy na ryzyko wystapienia porodu przedwczesnego.

The main aim of this prospective study was to determine the prevalence and an association between pathological microflora of the lower genital tract diagnosed at early pregnancy and the risk of preterm delivery. The study group comprised 179 randomly selected pregnant women from Lodz region, between 8 and 16 week of pregnancy. For the qualitative and quantitative assessment of biocenosis of the lower genital tract vaginal and cervical swabs were collected from the pregnant women under study. The C. trachomatis antigen was detected by direct immunofluorescence assay. The vaginal swabs were tested for aerobic and anaerobic bacteria. Bacterial vaginosis was diagnosed by Gram stain according to Spiegel's criteria. To evaluate the risk factors odds ratios were calculated using EPI INFO software. 21 (11.7%) women delivered before 37th week of pregnancy. Bacterial vaginosis was diagnosed among 51 (28.5%) pregnant women while intermediate microflora was diagnosed by Gram stain in 62 (34.6%) women. The shortest mean gestational age at delivery was noted among women with BV. The rate of preterm delivery in BV group was 15.7% comparing to 9.1% among women with normal microflora. Among women with preterm delivery BV was diagnosed in 38.1% (OR = 1.86). Based on culture results only 84 (46.9%) women had normal microflora at early pregnancy. The pathological culture was associated with slightly increased preterm delivery rate (12.6%) as compare to 10.7% in control group. Positive culture for Bacteroides and Mobiluncus was connected with nonstatistical rise in the risk of preterm delivery. No association between C. trachomatis infection at early pregnancy and elevated risk of preterm delivery was found. Early pregnancy diagnosis of bacterial vaginosis and its treatment should lower the rate of prematurity in Poland.

[Evaluation of fetal oxygen saturation (FSpO2) during the course of underwater labor]. / Ocena wysycenia tlenem krwi plodowej (FSpO2) w przebiegu porodu podwodnego.

During controlled, randomized prospective trials, fetal arterial hemoglobin saturation (FSpO2) was estimated during 25 underwater labors and compared to results obtained from 34 classical deliveries. Mean fetal hemoglobin saturation during the first stage of labor was similar in both groups while a gradual decreasing trend in fetal FSpO2 was noticed throughout the progress of labor. In the second stage of labor higher mean FSpO2 values were observed in the group of fetuses born underwater. The author emphasized in discussion that underwater labor constitutes delicate and mild procedure particularly for the fetus.