Genetic modifications of cytokine genes and Toxoplasma gondii infections in pregnant women.

PURPOSE: Toxoplasma gondii causes one of the most common intrauterine infections worldwide, thus being a severe threat during pregnancy. IL1, IL6, IL10, IL12, and TNF-α cytokines were reported to be involved in immune responses to infections with T. gondii. The research was aimed to reveal relationships between genetic changes within the polymorphisms of these cytokine genes and the incidence of T. gondii infection among pregnant women, as well as congenital transmission of the parasite to the foetuses of their infected mothers. METHODS: The primary study was performed in 148 Polish pregnant women, including 74 T. gondii-infected patients and 74 age-matched uninfected individuals; and further analysis - among the additional 142 pregnant women. Genotypes within IL1A -889 C>T, IL1B +3954 C>T, IL6 -174 G>C, IL10 -1082 G>A, IL12B -1188 A>C and TNFA -308 G>A single nucleotide polymorphisms (SNPs) were determined, using self-designed nested PCR-RFLP assays. Randomly selected PCR products, representing distinct genotypes in the analyzed polymorphisms, were confirmed by sequencing, using the Sanger method. A statistical analysis was carried out of relationships between genetic alterations within studied SNPs and the occurrence of T. gondii infection, using the following tools: cross-tabulation, Pearson's Chi-square test and the logistic regression model to estimate genetic models of inheritance. A power analysis of statistically significant outcomes was performed by Cramér's V test. RESULTS: A multiple-SNP analysis showed TC haplotype for IL1A and IL1B SNPs to be significantly associated with a decreased risk of the parasitic infection (OR 0.41, P≤0.050). The association remained important after power analysis (Cramér's V = 0.39, χ2 = 7.73, P≤0.050), and the additional analysis with larger groups of patients (OR 0.47, P≤0.050). Moreover, the CCCAGA complex variants were for all the studied polymorphisms at an increased risk of T. gondii infection (OR 8.14, P≤0.050), although this strong relationship was not significant in the further analysis (Cramér's V = 0.76, χ2 = 26.81, P = 0.310). Regarding the susceptibility to congenital transmission of T. gondii from mothers to their foetuses among the infected pregnant women, the presence of GA heterozygotic status within IL10 polymorphism significantly increased the risk of parasitic transmission (OR 5.73 in the codominant model and OR 5.18 in the overdominant model; P≤0.050). The correlation stayed important in the power analysis (Cramér's V = 0.29, χ2 = 6.03, P≤0.050), although it was non-significant in larger groups of patients. Important relationships specific for the first study cohort remained non-significant in the second group of studied pregnant women. CONCLUSIONS: Within the analyzed cohort of Polish pregnant women, the genetic modifications from SNPs of genes, encoding both the proinflammatory IL1α, IL1ß, IL6, IL12 and TNF-α, and anti-inflammatory IL10 cytokines, may have been associated with susceptibility to T. gondii infection. It is the first study on the contribution of cytokine genes polymorphisms to the occurrence of T. gondii infection during pregnancy. Further studies for other populations of pregnant women would be justified to reveal a detailed role of the analyzed polymorphisms for the occurrence of T. gondii infections during pregnancy.

The role of single nucleotide polymorphisms, contained in proinflammatory cytokine genes, in the development of congenital infection with human cytomegalovirus in fetuses and neonates.

PURPOSE: The research project targeted the distribution of genotypes, alleles and haplotypes in single nucleotide polymorphisms (SNPs) within the interleukin (IL) 1A, IL1B, IL6, IL12B and TNFA genes, in fetuses and neonates, congenitally infected with human cytomegalovirus (HCMV), and among uninfected controls. METHODS: The study included 20 fetuses and neonates with congenital HCMV infection and 31 control individuals. The genotypes in SNPs of the studied cytokine genes were identified by a self-designed nested PCR-RFLP assays. Selected genotypes, representing distinct variants in analyzed polymorphisms, were confirmed by sequencing. The relationship between the genetic status of the studied polymorphisms and congenital infection development was estimated, using a logistic regression model. RESULTS: The CT haplotype, composed of C allele determined in IL1A -889 C > T and T allele in IL1B +3954 C > T SNP, increased the risk of congenital HCMV infection, as well as the onset of disease related symptoms (P ≤ 0.0001). Considering disease outcome, the risk of development of symptoms, was increased among the CT heterozygotes in IL1A -889 C > T polymorphism (OR 2.86, 95% CI 0.24-33.90; P = 0.045). Moreover, multiple-SNP variants CCGAG in the range of all the SNPs, analyzed in the study, increased the risk of congenital infection with HCMV (OR 7.94, 95% CI 1.38-45.69; P = 0.026). CONCLUSIONS: Polymorphisms within the proinflammatory cytokine genes may contribute to the development of congenital infection with HCMV.

TLR2 2258 G>A single nucleotide polymorphism and the risk of congenital infection with human cytomegalovirus.

BACKGROUND: Human cytomegalovirus (HCMV) is responsible for the most common intrauterine infections, which may be acquired congenitally from infected pregnant woman to fetus. The research was aimed to estimate the role of three single nucleotide polymorphisms (SNPs) located in TLR2 gene, and the common contribution of TLR2, and previously studied TLR4 and TLR9 SNPs, to the occurrence of congenital HCMV infection in fetuses and newborns. METHODS: The study was performed in 20 Polish fetuses and newborns, congenitally infected with HCMV, and in 31 uninfected controls, as well as with participation of pregnant women, the mothers of 16 infected and 14 uninfected offsprings. Genotypes in TLR2 SNPs were determined, using self-designed nested PCR-RFLP assays, and confirmed by sequencing. The genotypes were tested for Hardy-Weinberg (H-W) equilibrium, and for their relationship with the development of congenital cytomegaly, using a logistic regression model. The common influence of TLR2, TLR4 and TLR9 SNPs on the occurrence of congenital disease was estimated by multiple-SNP analysis. RESULTS: Distribution of the genotypes and alleles in TLR2 1350 T>C and 2029 C>T SNPs was similar between the studied groups of fetuses and neonates. In case of 2258 G>A polymorphism, the GA heterozygotic status was significantly more frequent in the infected cases than among the uninfected individuals (25.0% vs. 3.2%, respectively), and increased the risk of HCMV infection (OR 10.00, 95% CI 1.07-93.44; P ≤ 0.050). Similarly, the A allele within 2258 G>A polymorphism was significantly more frequent among the infected offsprings than in the uninfected ones (12.5% vs. 1.6%; P ≤ 0.050). Complex AA variants for both TLR2 2258 and TLR9 2848 G>A polymorphisms, were estimated to be at increased risk of congenital HCMV infection (OR 11.58, 95% CI 1.19-112.59; P ≤ 0.050). Additionally, significant relationships were observed between the occurrence of complex AA or GA variants for both TLR2 and TLR9 SNPs and the increased viral loads, determined in fetal amniotic fluids and in maternal blood or urine specimens (P ≤ 0.050). CONCLUSIONS: Among various TLR2, TLR4 and TLR9 polymorphisms, TLR2 2258 G>A SNP seems to be an important factor associated with increased risk of congenital HCMV infection in Polish fetuses and neonates.

Toll-like receptors genes polymorphisms and the occurrence of HCMV infection among pregnant women.

BACKGROUND: Human cytomegalovirus (HCMV) is the most common cause of intrauterine infections worldwide. The toll-like receptors (TLRs) have been reported as important factors in immune response against HCMV. Particularly, TLR2, TLR4 and TLR9 have been shown to be involved in antiviral immunity. Evaluation of the role of single nucleotide polymorphisms (SNPs), located within TLR2, TLR4 and TLR9 genes, in the development of human cytomegalovirus (HCMV) infection in pregnant women and their fetuses and neonates, was performed. METHODS: The study was performed for 131 pregnant women, including 66 patients infected with HCMV during pregnancy, and 65 age-matched control pregnant individuals. The patients were selected to the study, based on serological status of anti-HCMV IgG and IgM antibodies and on the presence of viral DNA in their body fluids. Genotypes in TLR2 2258 A > G, TLR4 896 G > A and 1196 C > T and TLR9 2848 G > A SNPs were determined by self-designed nested PCR-RFLP assays. Randomly selected PCR products, representative for distinct genotypes in TLR SNPs, were confirmed by sequencing. A relationship between the genotypes, alleles, haplotypes and multiple variants in the studied polymorphisms, and the occurrence of HCMV infection in pregnant women and their offsprings, was determined, using a logistic regression model. RESULTS: Genotypes in all the analyzed polymorphisms preserved the Hardy-Weinberg equilibrium in pregnant women, both infected and uninfected with HCMV (P > 0.050). GG homozygotic and GA heterozygotic status in TLR9 2848 G > A SNP decreased significantly the occurrence of HCMV infection (OR 0.44 95% CI 0.21-0.94 in the dominant model, P ≤ 0.050). The G allele in TLR9 SNP was significantly more frequent among the uninfected pregnant women than among the infected ones (χ2 = 4.14, P ≤ 0.050). Considering other polymorphisms, similar frequencies of distinct genotypes, haplotypes and multiple-SNP variants were observed between the studied groups of patients. CONCLUSIONS: TLR9 2848 G > A SNP may be associated with HCMV infection in pregnant women.

New criteria for gestational diabetes mellitus - do they impact the outcome?

OBJECTIVE: The aim of the study was to compare the perinatal outcome of pregnancies in mothers who were diagnosed with gestational diabetes mellitus (GDM) with previous versus current Polish Gynecological Society (PTG) criteria. METHODS: 475 patients were divided into three groups. In group A, the patients only met the previous PTG criteria for a GDM diagnosis, i.e., those with a blood glucose level of 140-152 mg/dl 2 hours after administration, a fasting glucose level <92 mg/dl, and a blood glucose level <180 mg/dl 1 hour after administration. Group B included patients complying with both the previous and current PTG criteria for a GDM diagnosis. Group C included patients who only met the current PTG criteria for a GDM diagnosis, i.e., those with a fasting blood glucose level of 92-99 mg/dl, a blood glucose level <180 mg/dl 1 hour and <140 mg/dl 2 hours after administration, respectively. RESULTS: Women from group C were characterized by the highest fasting glycaemia in the first trimester of pregnancy (93.0 mg/dL vs. 88.0 mg/dL vs. 83.5 mg/dL, p=0.012) and during the OGTT (p=0.001). Gestational diabetes was diagnosed significantly earlier in patients from group C (23 vs. 26 vs. 26 weeks, p=0.005). The patients from group A significantly less frequently required insulin therapy for proper glycemic control (p=0.035). Women from group A were characterized by lower pre-pregnancy BMI (p=0.001). CONCLUSIONS: Current PTG criteria for diagnosing GDM according to the IADPSG allow for identification of women who often require insulin therapy to achieve proper glycemic control.

Evaluation of the amoxicillin concentrations in amniotic fluid, placenta, umbilical cord blood and maternal serum two hours after oral administration.

OBJECTIVES: Amoxicillin is a broad-spectrum beta-lactam antibiotic. Due to its low toxicity, it is commonly used in obstetrics. The objective of this study was to assess amoxicillin concentrations in amniotic fluid, umbilical blood, placenta and maternal serum two hours following oral administration among pregnant women at term and to assess obstetric and non-obstetric factors that might affect amoxicillin's penetration of these tissues. MATERIALS AND METHODS: A total of 30 full-term pregnant women who qualified for elective Caesarean delivery were included in the study. Amoxicillin at a dose of 500 mg was administered prior to surgery. Amoxicillin levels were determined by diffusion microbial assay. RESULTS: The maternal serum, placental, umbilical blood and amniotic fluid levels of amoxicillin two hours after oral administration were 2.18±1.30 µg/g, 1.00±0.71 µg/g, 1.00±0.73 µg/g, and 0.67±0.59 µg/g, respectively (Table 2). Maternal serum levels of amoxicillin were significantly higher compared to other tissues (p<0.05). CONCLUSION: If the target tissues for the use of antibiotic drugs in pregnant patients are the fetus and/or the placenta, the drug should be administered in a higher-than-standard dose than that used to treat infections in non-pregnant patients. Considering that there is a maximum absorbable dose following oral administration, intravenous administration should be considered to prevent failure of antibiotic treatment. A higher dose of amoxicillin should be considered in obese mothers.

Cytological evaluation of the nasal mucosa in neonates exposed to tobacco smoke during fetal life.

OBJECTIVES: The objective of this study is to assess the cytological picture of the nasal mucosa of neonates born to mothers who are active smokers, passive smokers and non-smokers. METHODS: A prospective study was conducted in a group of 86 neonates born between 23 and 41 weeks of gestation. The assignation of neonates to one of the three aforementioned groups was based on a questionnaire concerning exposure to tobacco smoke, and on the concentration of cotinine in maternal urine. A cytological examination was performed using exfoliative cytology with a semi-quantitative evaluation of the cells present in the specimens. Hematological summation equipment was used to assess the number of neutrophils, eosinophils, columnar, goblet, basal and squamous cells out of 500 cells counted. The number of specific cells was expressed as a percentage and a cytogram was created. RESULTS: The most common type of cytogram contained neutrophils, columnar cells, and squamous cells. No significant differences were observed between the subgroups. Similarly, there was no correlation between the median of each type of cell and the cotinine concentration in the mothers' urine. CONCLUSION: Active and passive smoking during pregnancy do not influence the cytological picture of the nasal mucosa of neonates.

Emergency peripartum hysterectomy - a challenge or an obstetrical defeat?

OBJECTIVES: Peripartum hysterectomy remains an obstetric nightmare. Most obstetricians consider it a defeat. The aim of our study was to assess the prevalence, indications, procedures and complications of emergency peripartum hysterectomy (EPH) in the 2nd Department of Obstetrics & Gynecology, Medical University of Warsaw during a 7 year period (2007-2013). METHODS: A retrospective evaluation of 21,144 deliveries was performed. We analyzed all cases of EPH, including the maternal characteristics, obstetrical history, course of pregnancy and delivery, type of surgery and complications. RESULTS: Nineteen peripartum hysterectomies were performed between January 1, 2007 and October 30, 2013 (0.9/1000), including 16 EPH (0.76/1000). The rate of EPH was between 0.66 and 1.0 per 1000 deliveries. The majority of the patients were multiparous (79.0%), and EPH was performed after at least one cesarean section (75.0%). Fifteen women had a singleton pregnancy and one woman had a triplet pregnancy. The mean gestational age was 34.2 weeks. The delivery mode was cesarean section in 93.8% of the cases. The most common reason for peripartum hemorrhage and the indication for EPH was abnormal placentation (75.0%). All patients underwent a total hysterectomy, including 43.8% during the same operation and 50.0% during a reoperation. There was no maternal death. The serious maternal complication rates were relatively low in our study and included one case of cardiac arrest that required cardiopulmonary resuscitation and one case of sepsis with pulmonary embolism. CONCLUSIONS: EPH is typically performed as a result of massive hemorrhage associated with abnormal placentation, and it should be treated as a challenging, life-saving procedure.

Evaluation of the amoxicillin concentrations in amniotic fluid, placenta, umbilical cord blood and maternal serum two hours after intravenous administration.

OBJECTIVES: The aims of this study were to evaluate amoxicillin concentrations in amniotic fluid, placenta, umbilical cord blood and maternal blood two hours after intravenous administration to assess obstetric and non-obstetric factors that could have influences on the penetration of the antibiotic into the examined tissues and to analyze the sensitivity to amoxicillin of the most common pathogens isolated from the genital tract. METHODS: A total of 35 full-term pregnant women who qualified for elective Caesarean delivery were included in the study. Amoxicillin at a dose of 1000 mg was administered prior to surgery. Amoxicillin levels were determined by diffusion microbial assay. RESULTS: The drug concentration was highest in umbilical cord blood compared with amniotic fluid, maternal blood and placenta (4.20±1.06 µg/g versus 3.96±0.79 µg/g, 3.22±0.64 µg/g and 2.81±0.64 µg/g, respectively). Obstetric and non-obstetric factors had no influence on the amoxicillin concentration. The most common bacteria isolated from the genital tracts of pregnant women (Streptococcus agalactiae, Enterococcus faecalis, Escherichia coli) were sensitive to amoxicillin. The MIC for the sensitive strain of Streptococcus agalactiae was seen in the majority of tissues of all of the patients; however, the MICs for E. faecalis and E. coli were not observed in any compartment. CONCLUSIONS: Amoxicillin proved to have good penetration into the fetal tissues and placenta after intravenous administration. The most common bacteria isolated from the genital tracts of pregnant women were sensitive to amoxicillin. Pregnancy complications were not found to have an influence on the amoxicillin concentrations in the examined tissues.

Prenatal sonographic diagnosis of premature constriction of the fetal ductus arteriosus after maternal self-medication with benzydamine hydrochloride: report of 3 cases and review of the literature.

We report 3 cases of prenatal diagnosis of premature constriction of the ductus arteriosus after maternal benzydamine hydrochloride therapy (3-mg lozenges) in third-trimester pregnancies. In each case, fetal echocardiography revealed a dilated, hypocontractile right ventricle with severe tricuspid regurgitation and constriction of the ductus arteriosus. Although the effect of indomethacin and other nonsteroidal anti-inflammatory drugs on prenatal ductal constriction is well known, readily available over-the-counter nonsteroidal anti-inflammatory drugs such as benzydamine can have an equally deleterious effect and are best avoided in the third trimester of pregnancy.

DNA repair mechanisms and Toxoplasma gondii infection.

Lately, we can observe significant progress in understanding mechanism of DNA repair owing to fast methods of DNA sequence analysis from different organisms the revealing of structure and function of DNA repair proteins in prokaryota and eukaryota. The protozoan parasites survival depends on DNA repair systems. Better understanding of DNA repair systems can help in new antipathogen drug development. This review is aimed at updating our current knowledge of the various repair pathways by providing an overview of DNA repair genes regarding Toxoplasma gondii infections and the corresponding proteins, participating either directly in DNA repair, or in checkpoint control and signaling of DNA damage.

Elevated frequencies of micronuclei in pregnant women with type 1 diabetes mellitus and in their newborns.

Pregestational diabetes mellitus (type 1 and type 2) affects about 1% of the obstetric population. In diabetes, persistent hyperglycemia can be a source of DNA damage via overproduction of reactive oxygen species (ROS). Using the cytokinesis-block micronucleus (CBMN) test, we measured the frequencies of micronuclei (MN) per 1000 binucleated (BN) cells in pregnant women (mothers) with type 1 diabetes mellitus (T1DM) and in their newborns. Peripheral blood lymphocytes were collected from 17 pregnant women with T1DM and cord-blood lymphocytes from their 17 newborns. The control group included 40 pregnant women (mothers) without diabetes mellitus (DM) and their 40 newborns. In the group of pregnant women with T1DM, the mean number of MN per 1000 BN cells was 2.35 (±1.07), significantly (p<0.001) higher than in the control group of pregnant women (0.86±0.90). The frequency value in the group of newborns of T1DM mothers was 1.42 (±0.60), significantly (p<0.05) higher than in the corresponding control group (0.67±0.79). The value in the group of mothers with T1DM was significantly (p<0.05) higher than in their newborns. Comparing mothers without DM with their newborns, no significant frequency differences were observed. No significant correlations were observed between MN frequencies in mothers with T1DM and either the frequencies in their newborns, the duration of diabetes, or HbA1C levels. Our results indicate that T1DM is accompanied by increased frequencies of MN in pregnant women and their newborns.

Successful treatment of fetal bilateral primary chylothorax--report of the two cases.

Primary fetal chylothorax is an uncommon complication, associated with high perinatal morbidity and mortality. In our report, we describe two cases of fetal bilateral primary chylothorax successfully treated with pleuro-amniotic shunting. In both cases, ultrasound scans showed bilateral, hypoechoic fluid in the pleural space without any associated structural malformations and features of infection and aneuploidy Laboratory analysis of pleural fluids revealed 79% and 92% of lymphocytes, respectively confirming chylothorax in both fetuses. In the first case, pleuro-amniotic shunts were successfully inserted at 31 weeks and 6 days of gestation. Ultrasound scan after two weeks showed expansion of the left lung and lack of fluid in both pleural cavities. At 39 weeks of gestation, a 2660 g baby boy was delivered by cesarean section (Apgar score: 9). The child did not require surgical intervention and was discharged home on day 16 of life. In the second case, the insertion of shunts (at 24 weeks and 6 days of gestation) also significantly reduced the amount of the fluid in the pleural cavities, but one shunt had to be surgically removed after birth. At 30 weeks and 2 days of gestation, a cesarean section was performed due to maternal cholestasis. A female weighing 1400 g was delivered (Apgar score: 7). The chest X-ray revealed only a small amount of fluid in the left pleural cavity The infant was discharged on postnatal day 26, in good condition and with body weight of 2150 g. Pleuro-amniotic shunt insertion is a method of choice in the treatment of confirmed primary fetal chylothorax.

Preliminary report of 48-hours Atosiban administration in spontaneous preterm labor - Doppler blood flow assessment of placental and fetal circulation.

OBJECTIVES: The aims were to investigate whether there are any changes in placental and fetal circulation during Atosiban tocolysis within the first 48 hours of therapy. METHODS: Detailed Doppler evaluation of placental and fetal circulation was performed prior to Atosiban administration and thereafter at 24 and 48 hours. Maternal heart rate and the pulsatility index (PI) in both uterine arteries (R-UtA, L-UtA) were assessed. Fetal heart rate (FHR), the resistance (RI) and pulsatility index (PI) of umbilical (UA) and middle cerebral artery (MCA) were measured. Additionally cerebroplacental ratio was calculated. E-wave/A-wave ratio (E/A) for atrioventricular valves, the myocardial performance index (MPI) and shortening fraction (SF) for both ventricles were calculated for both ventricles independently. To determine changes over time in all study variables analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's post hoc test was used. The effects of additional clinical covariates were checked. RESULTS: Maternal heart rate and blood flow in (R-UtA/L-UtA) were not altered significantly during Atosiban administration. No significant changes in FHR as well as Doppler parameters (RI, PI, PSV) in UA and MCA were recorded after 24/48 hours of tocolytic treatment. The mean values of cerebroplacental ratio (CPR) remained unaltered during treatment. Detailed evaluation of fetal cardiac function parameters (E/A, SF, MPI) calculated independently for both ventricles, revealed no significant changes over the time. CONCLUSIONS: To our best knowledge this study has been first evaluation of placental and fetal circulation with assessment of cardiac hemodynamic function during 48-hours administration of Atosiban. This kind of tocolysis treatment seems not to alter uterine nor fetal arterial blood flow pattern seriously. Hemodynamic cardiac activity in fetuses has remained unaffected. We cannot conclude definitely that there are absolutely no changes in the fetal hemodynamic condition due to Atosiban. Further studies should be performed to verify its possible influence on fetal venous blood flow.

48-hours administration of nifedipine in spontaneous preterm labor - Doppler blood flow assessment of placental and fetal circulation.

OBJECTIVES: The aims were to assess the placental and fetal circulation during nifedipine tocolysis within the first 48 hours of therapy. METHODS: Placental and fetal circulation was assessed in Doppler ultrasound examination prior to nifedipine administration and then after 24 and 48 hours. Maternal heart rate and PI in uterine arteries were evaluated as well as FHR, RI and PI of UA and MCA. E/A-wave ratio for A-V valves, MPI and SF were calculated for both ventricles independently. To determine changes over time in all study variable analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked. RESULTS: Uterine and umbilical blood flow patterns were not altered significantly during administration of nifedypine tocolysis. While MCA Doppler indicies such as RI and PI were unchanged, the evaluation of MCA PSV revealed a transient significant decrease after 24 hours. A resolution of this distraction was observed within the following 24 hours. No significant changes were observed in direct fetal cardiac function parameters calculated separately for both ventricles. CONCLUSIONS: The decrease of MCA PSV after 24 hours of treatment was isolated and transient hemodynamic distraction observed during treatment. Neither fetal cardiac parameters nor other Doppler indices were changed. Therefore oral administration of nifedipine seems not to alter uterine nor fetal arterial blood flow pattern seriously. As significant changes were observed by different authors, further studies should be performed to verify the optimal total dose of nifedipine and its influence on hemodynamic conditions.

Doppler evaluation of blood flow in fetal inferior vena cava during 48-hours Atosiban administration in spontaneous preterm labor.

OBJECTIVES: The aims were to evaluate whether any changes in blood flow in fetal inferior vena cava (IVC) are observed during Atosiban tocolysis within the first 48 hours of therapy. METHODS: Detailed Doppler evaluation of blood flow in fetal IVC was performed prior to Atosiban administration and after 24 and 48 hours respectively. Maternal and fetal heart rate was assessed. IVC Doppler indices, such as, S/D (systole/diastole), PVIV (peak velocity index for the vein) and PLI (preload index) were calculated. To determine changes over time in all study variables, analysis of variance (ANOVA) for repeated measurements was used and followed by Tukey-Kramer's post hoc test. The effects of additional clinical covariates were checked. RESULTS: Maternal heart rate was not altered significantly during Atosiban administration. No significant changes in FHR (fetal heart rate) as well as following IVC Doppler parameters (S/D, PVIV) were recorded after 24/48 hours of tocolytic treatment. The fetal IVC PLI values were significantly reduced after 24 hours and 48 hours of treatment. The changes in PLI values when comparing 24 and 48 hours results were not statistically significant. CONCLUSIONS: As the questions about drug safety appeared after the animal study had been published about possible myocyte injury, detailed Doppler evaluation of IVC blood flow was performed. It revealed the changes in preload conditions which could be a reflection of successful Atosiban tocolytic treatment. No hemodynamic changes in IVC were noted, suggesting the presence of fetal acidemia due to possible heart damage was observed.

48-hours administration of fenoterol in spontaneous preterm labor - does it affect fetal preload?

OBJECTIVE: to investigate whether any changes in the preload index (PLI) occur within the first 48 hours of fenoterol intravenous tocolysis. MATERIAL AND METHODS: Doppler evaluation of placental and fetal circulation was performed in 36 pregnant women prior to fenoterol administration and after 24/48 hours. Measurements were obtained from a longitudinal section of the inferior vena cava (IVC) and preload index was calculated. To determine changes over time, an all study variable analysis of variance (ANOVA) for repeated measurements, followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked. RESULTS: The maternal heart rate values were significantly increased after 24 hours and 48 hours in comparison to pre-treatment values. No significant changes in fetal heart rate were observed during treatment. The fetal IVC PLI values were significantly reduced after 24 hours and 48 hours of treatment. The increase in PLI values when comparing 24 and 48 hours results were not statistically significant. These observations were consistent with ANOVA post-hoc analysis. CONCLUSIONS: 48 hours intravenous administration of fenoterol appears not to alter inferior vena cava blood flow by itself. The reduction in PLI values may reflect lower fetal preload conditions during the course of successful tocolytic treatment. Therefore, Doppler IVC PLI measurement should be considered as a possible additional assessment method of effectiveness of treatment. However, other Doppler venous blood flow parameters should be assessed to confirm the results and clarify whether maternal corticosteroids administration may be interfering with the results.

48-hours administration of fenoterol in spontaneous preterm labor - Doppler blood flow assessment of placental and fetal circulation.

OBJECTIVES: The aims were to investigate whether any changes in placental and fetal circulation were observed during fenoterol tocolysis within the first 48 hours of therapy. MATERIAL AND METHODS: Doppler evaluation of placental and fetal circulation was performed prior to fenoterol administration and then after 24 and 48 hours. Maternal heart rate and pulsatility index (PI) in uterine arteries were assessed. FHR, RI and PI of umbilical artery and middle cerebral artery were measured. E/A ratio for A-V valves, the myocardial performance index (MPI) and shortening fraction (SF) were calculated for both ventricles independently. The blood flow pattern in DV was assessed using PI, S/a ratio and peak velocity index for the vein. To determine changes over time in all study variable analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked. RESULTS: Uterine and fetal arterial blood flow patterns were not altered significantly during 48 hours of tocolysis. No significant changes were observed in fetal cardiac function parameters as well. The evaluation of Doppler parameters in the DV revealed a significant increase in PVIV after 48 hours. Additionally after 48 hours of successful tocolysis S/a ratio values were significantly lower. CONCLUSIONS: Short term intravenous administration of fenoterol seems not to alter uterine and fetal arterial blood flow pattern. Direct fetal cardiac function remained unaffected. However significant changes of selected Doppler parameters in DV may suggest further studies should be performed to assess more precisely fetal venous blood flow.

[Evaluation of the association between maternal HCMV viremia and the course of pregnancy and neonatal outcome]. / Ocena zwiqzku poziomu wiremii HCMV u matki z przebiegiem ciqzy i stanem urodzeniowym noworodków.

UNLABELLED: Congenital cytomegaly is caused by intrauterine mother-to-fetus HCMV transmission and constitutes the most common vertical infection. OBJECTIVES: The aim of the study was to analyze the viremia level in maternal blood and its influence on the course and duration of pregnancy as well as newborn condition. MATERIAL AND METHODS: The material included blood samples collected from 117 pregnant women with serological features of HCMV infection and from 29 neonates hospitalized at DFMMG in Lodz between 1999 and 2009. The presence of HCMV DNA in the maternal and fetal blood was tested using real-time PCR. RESULTS: Prevalence of maternal viremia was observed to increase the risk of viremia in neonates, as compared to children born to mothers with no viremia. However; lack of HCMV DNA in maternal blood does not exclude fetal infection in utero. Newborn condition assessed by Apgar scores was significantly lower in the group of infants born to mothers with serological features of acute cytomegaly (p < 0.05). CONCLUSION: The assessment of viremia level in maternal blood can be helpful in assessing the risk of intrauterine infection in the fetus as well as in predicting the neonatal outcome of newborn.

[Prevalence of uterine malformations and their impact on fertility]. / Czestosc wystepowania wad macicy i ich wplyw na plodnosc.

AIM: Uterine malformations belong to the most common congenital abnormalities within the female reproductive system. Their mean prevalence in the general population is 2-4%. The incidence of uterine malformation leads to impaired fertility and a number of obstetric complications such as threatening preterm delivery pelvic and transverse presentation, premature departure of amniotic fluid, intrauterine growth restriction, threatening rupture of the uterus, caesarean section. The aim of this review is to analyze the influence of an individual uterine malformation on female fertility. MATERIAL AND METHODS: The study involved 124 women hospitalized at Research Institute of the Polish Mothers Memorial Hospital in Lodz between the years 1994-2007. The patients were divided into 6 groups on the basis of the diagnosed defect. RESULTS AND CONCLUSION: In our study the most common defect was uterus bicornis, diagnosed in 46.7% of cases. The worst obstetric outcome was found among patients with septate uterus. The highest number of miscarriages and fertility problems occurs among those women. Nevertheless, there are positive data on the treatment of this defect. It would be recommendable to extend the diagnosis of the uterine malformations, especially in women with fertility problems, because early diagnosis and appropriate treatment allow to obtain satisfactory obstetric outcomes.