New Ideas for the Prevention and Treatment of Preeclampsia and Their Molecular Inspirations.

Preeclampsia (PE) is a pregnancy-specific disorder affecting 4-10% of all expectant women. It greatly increases the risk of maternal and foetal death. Although the main symptoms generally appear after week 20 of gestation, scientific studies indicate that the mechanism underpinning PE is initiated at the beginning of gestation. It is known that the pathomechanism of preeclampsia is strongly related to inflammation and oxidative stress, which influence placentation and provoke endothelial dysfunction in the mother. However, as of yet, no "key players" regulating all these processes have been discovered. This might be why current therapeutic strategies intended for prevention or treatment are not fully effective, and the only effective method to stop the disease is the premature induction of delivery, mostly by caesarean section. Therefore, there is a need for further research into new pharmacological strategies for the treatment and prevention of preeclampsia. This review presents new preventive methods and therapies for PE not yet recommended by obstetrical and gynaecological societies. As many of these therapies are in preclinical studies or under evaluation in clinical trials, this paper reports the molecular targets of the tested agents or methods.

Association of Single Nucleotide Polymorphisms from Angiogenesis-Related Genes, ANGPT2, TLR2 and TLR9, with Spontaneous Preterm Labor.

In this study, we hypothesized that the changes localized at angiopoietin-2 (ANGPT2), granulocyte-macrophage colony-stimulating factor (CSF2), fms-related tyrosine kinase 1 (FLT1) and toll-like receptor (TLR) 2, TLR6 and TLR9 genes were associated with spontaneous preterm labor (PTL), as well as with possible genetic alterations on PTL-related coagulation. This case-control genetic association study aimed to identify single nucleotide polymorphisms (SNPs) for the aforementioned genes, which are correlated with genetic risk or protection against PTL in Polish women. The study was conducted in 320 patients treated between 2016 and 2020, including 160 women with PTL and 160 term controls in labor. We found that ANGPT2 rs3020221 AA homozygotes were significantly less common in PTL cases than in controls, especially after adjusting for activated partial thromboplastin time (APTT) and platelet (PLT) parameters. TC heterozygotes for TLR2 rs3804099 were associated with PTL after correcting for anemia, vaginal bleeding, and history of threatened miscarriage or PTL. TC and CC genotypes in TLR9 rs187084 were significantly less common in women with PTL, compared to the controls, after adjusting for bleeding and gestational diabetes. For the first time, it was shown that three polymorphisms-ANGPT2 rs3020221, TLR2 rs3804099 and TLR9 rs187084 -were significantly associated with PTL, adjusted by pregnancy development influencing factors.

Prenatal exposure to neurotoxic metals and micronutrients and neurodevelopmental outcomes in early school age children from Poland.

Exposure to environmental factors, such as neurotoxic metals and micronutrients, during critical periods of development can contribute to long-term consequences in offspring's health, including neurodevelopmental outcomes. The aim of this study was to evaluate the association between simultaneous prenatal exposure to metals [lead (Pb), cadmium (Cd), mercury (Hg)] and micronutrients [selenium (Se), zinc (Zn), copper (Cu)] and neurodevelopmental outcomes in school-age children from the Polish Mother and Child Cohort (REPRO_PL). Metals and micronutrients concentrations were measured in cord blood (Pb, Cd, Se, Zn, Cu) and in maternal hair (Hg) collected during the 3rd trimester of pregnancy. Behavioral and emotional problems, as well as children's cognitive and psychomotor development, were assessed in 436 school-age children using the Strengths and Difficulties Questionnaire (SDQ, filled in by the mothers) and the Polish adaptation of the Intelligence and Development Scales (IDS, administered by trained psychologists). Multivariate regression models were applied after imputation of missing values, using two approaches: (i) a joint analysis taking into account all metals and micronutrients simultaneously, and (ii) an ExWAS study (single-exposure model). In the SDQ, Hyperactivity/Inattention problems and Total difficulties were associated with higher Hg concentrations in maternal hair (0.18, 95% CI: 0.05; 0.3; and 0.14, 95% CI: 0.01; 0.3, respectively), whereas Emotional symptoms were inversely associated with Se and Zn levels in cord blood (-0.13, 95% CI: -0.3; 0.004; and -0.10, 95% CI: -0.2; 0.02, respectively). In the IDS, cord blood Pb levels were found to be negatively associated with Fluid and Crystallized IQ (-0.12, 95% CI: -0.3; 0.02; and -0.14, 95% CI: -0.3; 0.007, respectively) as well as Mathematical skills (-0.15, 95% CI: -0.3; 0.01). The current research has been able to simultaneously assess the exposure to various interacting chemicals during the prenatal period. We demonstrate that prenatal co-exposures to Pb, Hg, Zn and Se have long-term influences on the neuropsychological outcome of school-age children.

Chromogranin A demonstrates higher expression in preeclamptic placentas than in normal pregnancy.

BACKGROUND: Although preeclampsia has long been recognized as a condition affecting late pregnancy, little is known of its pathogenesis or treatment. The placenta releases a number of hormones and molecules that influence the course of pregnancy, one of which is chromogranin A, a soluble protein secreted mainly from the chromaffin cells of the adrenal medulla. Its role in pregnancy and pregnancy-related disorders remains unclear. Therefore, the main aim of the proposed study is to determine whether chromogranin A is related with the occurrence of preeclampsia. METHODS: Placental samples were collected from 102 preeclamptic patients and 103 healthy controls, and Chromogranin A gene (CHGA) expression was measured using real-time RT-PCR, The RT-PCR results were verified on the protein level using ELISA. The normal distribution of the data was tested using the Shapiro-Wilk test. The clinical and personal characteristics of the groups were compared using the Student's t-test for normally-distributed data, and the χ2 test for categorical variables. The Mann-Whitney U test was used for non-normally distributed data. As the log- transformation was not suitable for the given outcomes, the Box- Cox Transformation was used to normalize data from ELISA tests and CHGA expression. Values of P < .05 were considered statistically significant. RESULTS: Chromogranin A gene expression was found to be significantly higher in the study group than in controls. Protein analyses showed that although the CgA concentration in placental samples did not differ significantly, the catestatin (CST) level was significantly lower in samples obtained from women with preeclampsia, according to the controls. CONCLUSIONS FOR PRACTICE: This study for the first time reveals that chromogranin A gene expression level is associated with preeclampsia. Moreover, the depletion in catestatin level, which plays a protective role in hypertension development, might be a marker of developing preeclampsia. Further studies may unravel role of Chromogranin A in the discussed disease.

The Preeclamptic Environment Promotes the Activation of Transcription Factor Kappa B by P53/RSK1 Complex in a HTR8/SVneo Trophoblastic Cell Line.

Preeclampsia is a pregnancy disorder associated with shallow placentation, forcing placental cells to live in hypoxic conditions. This activates the transcription factor kappa B (NFκB) in maternal and placental cells. Although the role of NFκB in preeclampsia is well documented, its mechanism of activation in trophoblastic cells has been never studied. This study investigates the mechanism of NFκB activation in a first trimester trophoblastic cell line (HTR8/SVneo) stimulated by a medium containing serum from preeclamptic (PE) or normotensive (C) women in hypoxic (2% O2) or normoxic (8% O2) conditions. The results indicate that in HTR8/SVneo cells, the most widely studied NFκB pathways, i.e., canonical, non-canonical and atypical, are downregulated in environment PE 2% O2 in comparison to C 8% O2. Therefore, other pathways may be responsible for NFκB activation. One such pathway depends on the activation of NFκB by the p53/RSK1 complex through its phosphorylation at Serine 536 (pNFκB Ser536). The data generated by our study show that inhibition of the p53/RSK1 pathway by p53-targeted siRNA results in a depletion of pNFκB Ser536 in the nucleus, but only in cells incubated with PE serum at 2% O2. Thus, the p53/RSK1 complex might play a critical role in the activation of NFκB in trophoblastic cells and preeclamptic placentas.

Subclinical thyroid dysfunction in the first trimester of pregnancy: 'Disease' versus physiological (pulsatile) variation in TSH concentrations.

BACKGROUND: There is no universal consensus regarding cut-off points for TSH in pregnancy, so concentrations of 2.5 or 4.0 mIU/L were suggested for first trimester (Endocrine Society [2012] and ATA [2017] guidelines, respectively). Yet, the impact of physiological variation in TSH secretion has not been assessed. SUBJECTS AND METHODS: We assessed baseline concentrations of free T4, free T3 and TSH at 30-minute intervals (between 7.00 and 9.00 hours) in 110 healthy pregnant women, age 30.2 ± 6.0 years, 9.9 ± 2.4 weeks of gestation, and in 19 female controls, age 28.9 ± 10.7. RESULTS: Mean TSH concentrations in pregnant women were 1.62 ± 1.26 mIU/L and on average varied by 39.5% (dispersion between the highest and the lowest TSH), with no difference in TSH variation between pregnant women and controls. Taking into account the highest TSH out of five consecutive measurements, TSH >2.5 mIU/L and TSH above 4.0 mIU/L were found in 23 (20.9%) and 10 (9.1%) pregnant women, respectively. In contrast, when the lowest TSH value was considered, then concentrations of TSH >2.5 mIU/L and >4.0 mIU/L were found in 14 (12.7%) and 4 (3.6%) women, respectively. This discrepancy was even more pronounced in aTPO-negative subjects (21 [21.2%] vs 8 [8.1%] women, for TSH >2.5 mIU/L, and six [6.06%] vs one [1.01%], for TSH >4.0 mIU/L). Furthermore, either six (5.4%) or 10 (9.1%) women had TSH concentrations below 0.1 mIU/L. CONCLUSIONS: In a significant number of patients, diagnosis of subclinical thyroid dysfunction could be erroneously made not as a result of 'disease', but as a result of physiological variation in TSH concentrations.

Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia.

Although higher nuclear factor κB (NFκB) expression and activity is observed in preeclamptic placentas, its mechanism of activation is unknown. This is the first study to investigate whether the canonical, non-canonical, or atypical NFκB activation pathways may be responsible for the higher activation of NFκB observed in preeclamptic placentas. The study included 268 cases (130 preeclamptic women and 138 controls). We studied the expression of the genes coding for NFκB activators (NIK, IKKα, IKKß, and CK2α) and inhibitors (IκBα and IκBß) using RT-PCR in real time. The RT-PCR results were verified on the protein level using ELISA and Western blot. To determine the efficiency of the pathways, the ratios of activator(s) to one of the inhibitors (IκBα or IκBß) were calculated for each studied pathway. The preeclamptic placentas demonstrated significantly lower IKKα and CK2α but higher IκBα and IκBß protein levels. In addition, the calculated activator(s) to inhibitor (IκBα or IκBß) ratios suggested that all studied pathways might be downregulated in preeclamptic placentas. Our results indicate that preeclamptic placentas may demonstrate mechanisms of NFκB activation other than the canonical, non-canonical, and atypical forms. In these mechanisms, inhibitors of NFκB may play a key role. These observations broaden the existing knowledge regarding the molecular background of preeclampsia development.

Identification of placental genes linked to selective intrauterine growth restriction (IUGR) in dichorionic twin pregnancies: gene expression profiling study.

A linkage of dichorionic (DC) twin pregnancies with selective intrauterine growth restriction (IUGR) to alterations in placental gene expression is unclear. The aim of the study was to identify placental genes related to hypoxia, adipogenesis and human growth which may contribute to IUGR development. The study group (IUGR/AGA) comprised dichorionic (DC) twin pregnancies, where the weight of the twins differed by > 15%; in addition, one twin was small for gestational age (< 10th percentile-SGA) (IUGR) while the other was appropriate for gestational age (> 10th percentile-AGA). In the control group (AGA/AGA), both fetuses were AGA and their weights differed by < 15%. In the first step (selection), placental expression of 260 genes was analysed by commercial PCR profiler array or qPCR primer assay between six pairs of IUGR/AGA twins. In the second stage (verification), the expression of 20 genes with fold change (FC) > 1.5 selected from the first stage was investigated for 75 DC pregnancies: 23 IUGR/AGA vs. 52 AGA/AGA. The expression of Angiopoetin 2, Leptin and Kruppel-like factor 4 was significantly higher, and Glis Family Zinc Finger 3 was lower, in placentas of SGA fetuses (FC = 3.3; 4.4; 1.6; and - 1.8, respectively; p < 0.05). The dysregulation of gene expression related to angiogenesis and growth factors in placentas of twins born from IUGR/AGA pregnancies suggest that these alternations might represent biological fetal adaptation to the uteral condition. Moreover, DC twin pregnancies may be a good model to identify the differences in placental gene expression between SGA and AGA fetuses.

"Y Sign" at the Level of the 3-Vessel and Trachea View: An Effective Fetal Marker of Aortic Dextroposition Anomalies in the First Trimester.

OBJECTIVES: The "Y sign" at the level of the 3-vessel and trachea view corresponds to thinning of main pulmonary artery and arterial duct and a dilated transverse aortic arch. The purpose of this study was to evaluate the Y sign for the diagnosis of aortic dextroposition anomalies at the time of the first-trimester scan and to assess the screening performance of only the Y sign, only abnormal left axis deviation (axis sign), and their combination for the diagnosis of aortic dextroposition anomalies. METHODS: A prospective evaluation of 6025 pregnant women undergoing first-trimester ultrasonography was conducted. The cardiac axis was measured in all examined patients and considered abnormal (positive axis sign) at greater than 57 °. The frequency of the Y sign and the axis sign was assessed for this population, and their screening performance for the diagnosis of aortic dextroposition anomalies was calculated. RESULTS: A total of 5775 patients fulfilled the inclusion criteria. Aortic dextroposition anomalies were diagnosed in 17 cases (tetralogy of Fallot in 8 and Fallot-like double-outlet right ventricle in 9). The Y sign was found in 18 of 5775 (0.3%) fetuses examined, of which 7 of 18 were confirmed with tetralogy of Fallot, 9 of 18 with a Fallot-like double-outlet right ventricle, and 2 of 18 with pulmonary stenosis. A positive axis sign of greater than 57 ° was found in 20 fetuses, including 4 with normal heart anatomy. The sensitivity values of the Y sign, the axis sign, and their combination were 94%, 76%, and 94%, respectively. CONCLUSIONS: Visualization of the Y sign should increase the suspicion of aortic dextroposition anomalies in the late first trimester. The screening performance of the Y sign alone and in combination with an abnormal cardiac axis was high and may aid in the early diagnosis of aortic dextroposition anomalies in the fetus.

Assessment of dietary intake and mineral status in pregnant women.

PURPOSE: To evaluate the dietary intake of pregnant women and their nutritional status of Ca, Mg, Fe, Zn, and Cu, as the nutritional status of pregnant women is an important factor for the proper progression of a pregnancy and the development and health of the foetus. METHODS: The study was conducted on 108 pregnant women ages 18-42, at 6-32 weeks of gestation. We used a questionnaire and a 24-h recall nutrition interview. Hair samples were taken for testing and the level of each mineral was assessed using atomic absorption spectrometry. The results were analysed using the Dietetyk and Statistica 10 software. RESULTS: Low levels of Fe, Zn, Ca, Mg, vitamin D, and folic acid intake were seen in the pregnant women, with the use of dietary supplements significantly increasing their intake of Fe, Zn, and folic acid. The concentration of zinc and magnesium in the women's hair was shown to be affected by their age and, in the case of magnesium, by the week of pregnancy. CONCLUSIONS: It was observed that the diet of pregnant women is characterised by low levels of Fe, Zn, Ca, Mg, vitamin D, and folic acid. Dietary supplementation with vitamins and minerals significantly increases the daily Fe and folic acid intake in pregnant women. The concentration of Zn and Mg in hair depends on the age of pregnant women and Mg level in the hair of women decreases during pregnancy.

Selected trace elements concentrations in pregnancy and their possible role - literature review.

The aim of this study was to review the role of selected trace elements in pregnancy and fetal development. Citations related to the role of iron (Fe), zinc (Zn), manganese (Mn), copper (Cu) and selenium (Se) during pregnancy were searched in PubMed, Medline, Web of Science, using keywords and MeSH terms. Inadequate supply of trace elements can cause abnormalities of fetal development and predispose a child to disorders later on in life. Trace elements are the key elements of complex enzymes responsible for the modulation of the antioxidant defense system of the organism. It has been suggested that there is a correlation between reduced levels of trace elements essential for antioxidant function in the body of pregnant women, and an increased risk of developing preeclampsia. Trace elements are components of numerous regulatory enzymes and hormones essential to the division and differentiation of fetal cells and their further development. Mineral deficiencies in pregnant women can cause birth defects of the central nervous system, and growth disorders. Future research should be directed to explain the interaction between trace elements, and establish the optimum levels of macro and micronutrients supplementation, as well as determine the reference values for trace elements in the maternal serum, umbilical cord blood and amniotic fluid.

The course of pregnancy and delivery in a patient with malaria.

Malaria is one of the most common lethal parasitic diseases. Infection is transmitted when an infected female mosquito bites a human introducing the sporozoites into human blood. The article presents the course of pregnancy and delivery in a patient complicated by Plasmodium infection. The patient had repetitive several trips to Tanzania over a short time period before she developed the condition. She had been taking antimalarial medication (proguanil-atovaquone) in a prophylactic dose during and after her first travel to Tanzania. Following her first return to Poland she experienced infection-related symptoms.

Wspólczesne metody monitorowania dobrostanu plodu w ciazy powiklanej wewnatrzmacicznym zahamowaniem wzrastania.

Intrauterine growth restriction (IUGR) is one of the most important problems in current perinatology. The number of complications such as intrauterine fetal hypoxia, preterm and operative labours, intrauterine demises and neonatal deaths are signifcantly higher among pregnant women with IUGR. The proper monitoring and assesement of the fetal well-being are crucial to make the right decision about optimal time and mode of delivery.

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.

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.

Epidural analgesia during labor: a retrospective cohort study on its effects on labour, delivery and neonatal outcome.

OBJECTIVES: to evaluate the impact of epidural analgesia (EA) on labor delivery and neonatal status. MATERIAL AND METHODS: retrospective, observational, cohort study comprising 5593 pregnant women who met the inclusion criteria (singleton pregnancy cephalic presentation, 37-42 weeks of gestation). Out of them, 2496 had EA and 3097 constituted the control group. MAIN OUTCOME MEASURES: incidence of labor complications and operativd deliveries in women who received EA, neonatal status assessed by Apgar score in 1- and 5-minute, and cord pH values. RESULTS: Labor complications were more frequently observed in the epidural group, with an almost 1.5-fold higher incidence in nulliparous (16.32% vs. 11.29%) and 1.4-fold in multiparous women (9.86% vs. 7.08%). Stepwise logistic regression confirmed that EA is a significant risk factor for labor complications in nulliparous women (OR 1.27, 95% CI 1.03-1.58) and for forceps delivery in multiparous women (5.20, 95% CI 3.31-8.177). Also, EA is an important risk factor for both, low cord arterial pH <7.10 (OR 1.98, 95% CI 1.28-3.09, p=0.0023) and low Apgar score at 7 minute (OR=4.55, 95% CI 2.35-8.80, p<0.0001). Crucially there was no difference in the incidence of a low Apgar score at 5 minutes. CONCLUSIONS: EA constitutes an independent risk factor for operative vaginal delivery in multiparous women, but has no effect on the incidence of cesarean sections, either in nulliparous or multiparous women. EA also increases the risk of labor complications, low 1-minute Apgar score and low umbilical cord pH, but is not associated with low 5-minute Apgar score.

Potential Impact of a Pregnant Woman's Microbiota on the Development of Fetal Heart Defects: A Review of the Literature.

Developments in medicine and biology in recent decades have led to a significant increase in our knowledge of the complex interactions between the microbiota and human health. In the context of perinatal medicine and neonatology, particular attention is being paid to the potential impact of the maternal microbiota on fetal development. Among the many aspects of this relationship, the question of the impact of dysbiosis on the development of fetal heart defects is an important one. In this article, we present an analysis of recent research and scientific evidence on the relationship between a pregnant woman's microbiota and the development of fetal heart defects. We also discuss potential intervention strategies, including the role of probiotics and diet in optimising the maternal microbiota.

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.