Skin disorders in women with poor obstetric history: MTHFR polymorphisms and importance of preconceptional counseling.

OBJECTIVES: This study focused on the link between skin disorders and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. METHODS: Study cases were taken from a pre-conceptional care program where patients with poor obstetric history were evaluated in terms of systemic disorders including skin diseases. This retrospective cohort (n = 472) consisted of 110 (23.3%) and 362 (76.7%) women with or without skin disorders, respectively. For ease of analysis, the history of skin diseases was classified into seven categories: (1) acne/rosacea/other acneiform disorders; (2) fungal disease; (3) pruritis/xerosis; (4) psoriasis vulgaris; (5) acrochordons and other benign skin growths; (6) urticaria/dermatitis; and (7) viral diseases. RESULTS: In this retrospective cohort of 472 women, we explored the impact of MTHFR A1298C and C677T polymorphisms on skin disorders. Despite similar allelic frequencies, our findings revealed a statistically significant association between the presence of MTHFR polymorphisms and skin disorders (p = .027). Subgroup analysis indicated significantly higher rates of MTHFR polymorphisms in patients with psoriasis vulgaris (p = .033) and acrochordons (p = .030), highlighting their potential relevance in specific skin disorder subtypes. CONCLUSIONS: The increased prevalence of psoriasis and acrochordons among women with MTHFR deficiency underscores the complex relationship between genetic factors and dermatological health. Our findings emphasized the critical role of MTHFR polymorphisms not only in poor obstetric history but also as significant contributors to skin disorders. This dual association highlights the importance of comprehensive preconception counseling, especially customized for women affected by skin disorders.

In vivo and in vitro effects of cord blood hematopoietic stem and progenitor cell (HSPC) expansion using valproic acid and/or nicotinamide.

BACKGROUND: High self-renewal capacity and most permissive nature of umbilical cord blood (CB) results with successful transplant outcomes but low hematopoietic stem and progenitor cell (HSPC) counts limits wider use. In order to overcome this problem ex vivo expansion with small molecules such as Valproic acid (VPA) or Nicotinamide (NAM) have been shown to be effective. To the best of our knowledge, the combinatory effects of VPA and NAM on HSPC expansion has not been studied earlier. The aim of this study was to analyze ex vivo and in vivo efficacy of VPA and NAM either alone or in combination in terms of expansion and engraftment. METHODS: A total of 44 CB units were included in this study. To determine the ex vivo and in vivo efficacy, human CB CD34+ cells were expanded with VPA and/or NAM and colony forming unit (CFU) assay was performed on expanded HSPC. Xenotransplantation was performed simultaneously by intravenous injection of expanded HSPC to NOD-SCID gamma (NSG) mice (n = 22). Significance of the difference between the expansion groups or xenotransplantation models was analyzed using t-test, Mann-Whitney, ANOVA or Kruskal-Wallis tests as appropriate considering the normality of distributions and the number of groups analyzed. RESULTS: In vitro CD34+ HSPC expansion fold relative to cytokines-only was significantly higher with VPA compared to NAM [2.23 (1.07-5.59) vs 1.48 (1.00-4.40); p < 0.05]. Synergistic effect of VPA+NAM has achieved a maximum relative expansion fold at 21 days (D21) of incubation [2.95 (1.00-11.94)]. There was no significant difference between VPA and VPA+NAM D21 (p = 0.44). Fold number of colony-forming unit granulocyte-macrophage (CFU-GM) colonies relative to the cytokine-only group was in favor of NAM compared to VPA [1.87 (1.00-3.59) vs 1.00 (1.00-1.81); p < 0.01]. VPA+NAM D21 [1.62 (1.00-2.77)] was also superior against VPA (p < 0.05). There was no significant difference between NAM and VPA+NAM D21. Following human CB34+ CB transplantation (CBT) in the mouse model, fastest in vivo leukocyte recovery was observed with VPA+NAM expanded cells (6 ± 2 days) and the highest levels of human CD45 chimerism was detectable with VPA-expanded CBT (VPA: 5.42 % at day 28; NAM: 2.45 % at day 31; VPA+NAM 1.8 % at day 31). CONCLUSION: Our study results suggest using VPA alone, rather than in combination with NAM or NAM alone, to achieve better and faster expansion and engraftment of CB HSPC.

Psychometric Properties and Cutoff Value of the Turkish Overactive Bladder Symptom Score.

IMPORTANCE: The Overactive Bladder Symptom Score (OABSS) measures all overactive bladder (OAB) symptoms with graded answers, evaluates urgency symptoms, and reveals the subjective bladder control. However, the Turkish version and the cutoff value of the questionnaire have not yet been studied. OBJECTIVE: The aims of this study were to determine the psychometric properties of the 7-item OABSS and to estimate the cutoff value of the scale. STUDY DESIGN: This was an observational study. The internal consistency (Cronbach α) and test-retest reliability were analyzed, and exploratory factor analysis was performed. For the criterion validity, the correlations between the OABSS, the Overactive Bladder Questionnaire, the Bristol Female Lower Urinary Tract Symptoms questionnaire, and outcomes of a bladder diary were used. The cutoff value of the OABSS was analyzed by the receiver operating characteristics curve analysis. RESULTS: Participants with (n = 49) and without (n = 38) OAB were included. The internal consistency was very strong (Cronbach α = 0.95). The test-retest reliability was very strong (intraclass correlation coefficients = 0.93-0.95, P = 0.001). The percentage of explanation of the total variance was calculated as 78%. There was a strong to very strong correlation between the OABSS and the Overactive Bladder Questionnaire and Bristol Female Lower Urinary Tract Symptoms scores and outcomes of the bladder diary. The cutoff value for the OABSS was determined as 10.5. CONCLUSIONS: The Turkish OABSS was found to be a valid and reliable scale to determine OAB symptoms and severity. Those who score more than 10.5 on the questionnaire can be considered as at risk of OAB syndrome.

Significance of Physical Exercise in Pregnancy: Comparison of Short and Long Exercise Programs.

BACKGROUND: Several musculoskeletal changes occur in pregnancy, particularly in the abdominal region. The aim of this study was to search and compare the effects of long (LEP) and short exercise programs (SEP) in terms of the satisfaction of the needs of pregnant women. METHODS: This study consisted of 2 groups: LEP (n=16) and SEP (n=16). Muscle thickness measurements determined by ultrasound, the 6 minute walk test, Pregnancy Physical Activity Questionnaire, Visual Analogue Scale, Oswestry Disability Index, and Short Form-36 Quality of Life Questionnaire were the study variables. Evaluations were done at the 16th (baseline), 24th, and 32nd gestational weeks. The LEP consisted of 20 and the SEP consisted of 9 exercises, which were applied for 16 weeks until the 32nd gestational week. RESULTS: Emotional role limitation and pain scores of quality of life, 6 minute walk test, and occupational physical activity were found to be better in the LEP group at the 24th gestational week (p=0.043, p=0.049, p=0.049, p=0.026). At the 32nd gestational week, the 6 minute walk test and occupational physical activity were found to be higher in the LEP group (p=0.006, p=0.017). Additionally, rectus abdominis and bilateral diaphragm muscle thicknesses, "moderate intensity and sports physical activity" and "vitality and emotional well-being" were increased over time with the LEP (p+<+0.05 for all). On the other hand, unilateral diaphragm muscle thickness, sports physical activity level, and vitality were improved with the SEP (p+<+0.05 for all). CONCLUSIONS: The SEP and LEP both have beneficial effects in pregnant women. However, the LEP increases physical activity level, functional capacity, and quality of life more than the SEP during the later stages of pregnancy.

Determination of Autophagy in Human Cervicovaginal Smears by Cytological and Immunocytochemical Methods.

Background: Autophagy is a catabolic process whereby organelles and long-lived proteins are recycled through lysosomes to maintain cellular homeostasis. This process is being widely studied using culture techniques and animal models; however, cervicovaginal smears have not been used to detect autophagy. Aims: Our study aims to detect and evaluate autophagy in normal, malignant, infectious, and atypical cells in cervicovaginal smears by using cytological and immunocytochemical methods. Materials and Methods: Papanicolaou-stained 200 cervicovaginal smears were examined and 55 of 200 (27.5%) smears containing negative for intraepithelial lesion or malignancy (NILM) with identifiable infections and/or reactive/reparative changes (INF); briefly, NILM-INF (n = 31, 56.4%), atypical (n = 4, 7.3%), and malignant cells (n = 20, 36.3%) were evaluated as a study group. One hundred forty-five of 200 (72.5%) normal smears were accepted as the NILM without any identifiable infections (control group). The autophagy marker protein Microtubule-associated protein 1 light chain 3 A (MAP1LC3A) was used for immunocytochemical examination. Results: The staining intensity of the MAP1LC3A protein and autophagy positivity were lower in the malignant cells; however, they were higher in the NILM-INF and atypical cells. A statistically significant correlation between the malignant and normal cells was obtained for the autophagy positivity (P = 0.012). In view of the staining intensity of MAP1LC3A protein by the H-score method, a significant correlation was found between the NILM-INF and the normal cells (P = 0.015). Conclusions: Autophagy was detected in various cervicovaginal smears for the first time in this study. Our findings indicate that an autophagy process is essential in infectious cells as well as in the transformation of atypical cells into malignant cells in carcinogenesis.

Impact of scoliosis on gestational outcome.

Objective: To demonstrate the impact of scoliosis on pregnancy and gestational outcome. Material and Methods: We retrospectively evaluated gestational outcomes of pregnant women with scoliosis at Hacettepe University Hospital between 2008 and 2018. Cases were grouped according to the presence of previous scoliosis surgery and compared in terms of gestational week at birth, birthweight, rate of neonatal intensive care unit admission, hospitalization during pregnancy, route of delivery, type of anesthesia at labor and postpartum intensive care unit admission rate. Ejection fraction (EF), functional vital capacity (FVC), forced expiratory volume (FEV1) and FEV1/FVC ratio values were also recorded. Results: A total of 23 women were included, of whom 12 (52.2%) had a prior scoliosis surgery. One of the 23 (4.3%) cases was terminated due to respiratory problems, while the remaining 22 cases resulted in deliveries. The median gestational week at birth was 38.2 and the median birth weight was 3150 g. Median (range) maternal height was 143 (80-160) cm while median (range) maternal weight was 51 (35-86) kg. Three (13.6%) were diagnosed with restrictive lung disease. No significant difference was found between operated and non-operated groups in terms of respiratory function test results, cardiac EF and other related demographic and clinical features. Overall cesarean delivery rate was 63.6% (14/22) and cesarean section rate was significantly higher in the operated group (83.3% versus 40%) (p=0.04). Conclusion: Cesarean section rate was increased in this cohort of pregnancies in women with scoliosis and who had previous scoliosis surgery.

Refusal of the hospitalization: a distressed dilemma in obstetric practice.

Background: Pregnant women are a special population in which hospitalizations are more recommended due to physiological changes mimicking pathologies and medico-legal concerns. Objectives: We aimed to assess the obstetric outcomes of expectant mothers who were admitted to the obstetrics emergency outpatient clinic and declined the hospitalization advised by doctors. Additionally, we examined the appropriateness of physicians' recommendations. Design: We have retrospectively evaluated the patients admitted to the 'Obstetric Emergency Outpatient Clinic' and refused hospitalization between 1 January 2019 and 31 December 2019. Methods: Cases were classified into three groups based on the trimester, considering the substantial variation between complaints and complications in each trimester. The complaints of pregnant women were categorized as psychosocial causes, obstetric complications, maternal systemic complaints, and suspicion of labor. We evaluated the compatibility of the hospitalization decision with the pregnancy outcome of patients. Results: A total of 958 pregnant women were included in the study. Leading causes for admissions were obstetric complications, maternal systemic complaints, and suspicion of labor in first, second, and third trimesters, respectively. Psychosocial causes were mostly observed in the second trimester. Readmission to the hospital within a week was highest in the third trimester group. According to pregnancy outcomes, 12.5% (94/753) of our recommendations were appropriate in all trimesters. Conclusion: Obstetricians seem overcautious in managing obstetric patients and willing to offer hospitalization more often than the actual requirements.

Impact of Increased Activated Protein-C Resistance, Decreased Antithrombin III Activity and Hypocomplementemia on the Gestational Outcomes of Pregnancies with MTHFR Polymorphisms.

OBJECTIVE: To evaluate the impact of increased Activated Protein C (APC) resistance, decreased antithrombin III activity and hypocomplementemia on the pregnancy outcomes of the patients with methylentetrahydrofolate reductase (MTHFR) polymorphisms. METHODS: This study was composed of 83 pregnancies with MTHFR polymorphisms. Increased APC resistance, decreased antithrombin III activity and hypocomplementemia were accepted as risk factors for poor gestational outcome. RESULTS: Having at least one risk factor resulted in significantly higher rates of "APGAR score of<7" at the first ten minutes (p=0.009). Composite adverse outcome rate was also higher in patients with at least one of the defined risk factors despite lack of statistical significance (p=0.241). Rate of newborn with an "APGAR score of<7" at first ten minutes was significantly higher at patients with hypocomplementemia (p=0.03). CONCLUSION: Hypocomplementemia is a risk factor for poor gestational outcome in pregnancies with MTHFR polymorphisms.

Association of single nucleotide polymorphisms (4G/5G) of plasminogen activator inhibitor-1 and the risk factors for placenta-related obstetric complications.

BACKGROUND: Placenta-related obstetric complications (PROCs) such as miscarriage, fetal growth restriction, preeclampsia, and preterm birth are the major causes of maternal and fetal morbidity and mortality. The objective of this study was to search the relevance of plasminogen activator inhibitor-1 (PAI-1) polymorphisms and co-morbidities and the risk factors for PROCs such as miscarriage, fetal growth restriction, preeclampsia, and preterm birth. METHOD: This retrospective study analyzed the PAI-1 genotype in a cohort of 268 multiparous women with poor obstetric history. Poor obstetric history was defined as the presence of at least one of the PROCs and/or poor gestational outcomes at the previous pregnancy/pregnancies. RESULTS: 5G allele frequency was higher than the 4G allele frequency in the cohort (0.767 vs. 0.233). The frequencies of having at least one risk factor are relatively similar among the different PAI-1 genotypes ( P  > 0.05). However, the presence of MTHFR polymorphisms (homozygous and compound heterozygous forms of C677T and A1298G) and hereditary thrombophilia (Factor V Leiden and prothrombin G20210A gene mutations, and FXIII deficiency) were found to be associated with PAI 4G/4G ( P  = 0.048) and 5G/5G ( P  = 0.022) genotypes, respectively. Significant differences were not observed in other risk factors and co-morbidities such as autoimmune disorders, chronic inflammatory diseases, history of venous thromboembolism, carbohydrate metabolism disorders, hyperlipidemia, cardiovascular and cerebrovascular diseases depending on PAI-1 genotypes ( P  > 0.05). CONCLUSION: MTHFR polymorphisms were found to be associated with PAI 4G/4G genotype, while 5G/5G genotype was observed more frequently in hereditary thrombophilia cases.

Cervicovaginal Bacillus velezensis Isolate: A Potential Probiotic and an Antagonist Against Candida and Staphylococcus.

The cervicovaginal microbiota is an essential aspect of women's reproductive and overall health. In this study, we aimed to evaluate the probiotic properties of a cervicovaginal isolate, obtained from a gynecologically healthy woman and assess its antagonistic effect against various microorganisms isolated from the vagina. Cytological examination was performed using Papanicolaou staining, and the isolated microorganism was identified via 16S Ribosomal RNA Gene Sequence Analysis. Probiotic characteristics were evaluated by determining the tolerance of the isolate to low pH, different NaCl concentrations, and bile salts. Bacterial adherence to stainless steel sheets, antibiotic susceptibility, and antimicrobial activity tests were also conducted and analyzed. Antimicrobial tests and antagonistic activities were assessed through disc diffusion assays. The cervicovaginal isolate was identified as B. velezensis ON116948 and was found to be tolerant to low pH, high NaCl and 0.3% bile salts. Additionally, it exhibited adherence. With the exception of amoxicillin/clavulanic acid (AMC) (30 µg) and oxacillin (OX) (1 µg), this isolate was susceptible to all the antibiotics tested. Candida species did not grow on B. velezensis spread media, while B. velezensis was able to grow on C. albicans, C. glabrata, C. tropicalis, S. condimenti and S. epidermidis spread media with growth zones of 13.7 ± 0.6, 13.3 ± 0.6, 14.2 ± 4.4, 10.5 ± 0.5 and 16.0 ± 1.0 (around discs), respectively. Our findings suggest that the cervicovaginal B. velezensis ON116948 isolate exhibits probiotic properties and antagonistic activity. These results provide important insights into the potential use of this isolate as a probiotic for the prevention of vaginal infections.

Association of lupus anticoagulants with risk factors for obstetric complications and adverse gestational outcome.

BACKGROUND: Lupus anticoagulant (LA) may be a cause of poor obstetric outcome. OBJECTIVE: To search the association of LA with risk factors for obstetric complications and adverse gestational outcome. METHODS: This retrospective cohort was consisted of 2 groups of pregnancies with poor obstetric history; 1) LA (+) gestations (Study Group, n= 20) and 2) LA (-) gestations (Control Group, 78). All patients were admitted to a special antenatal care program and were examined in terms of risk factors for thrombotic events, placenta-related obstetric complications, and poor gestational outcomes. Patients were administered low-dose low-molecular-weight heparin (LMWH), low-dose salicylic acid and low-dose corticosteroid (if necessary) within the framework of a prophylaxis protocol in addition to their already existing medications. RESULTS: We have shown that adverse gestational outcome was 1.7-fold more frequent in LA (+) pregnancies with poor obstetric history (p= 0.039, 70% vs. 41%). Higher rates of autoimmune diseases and hereditary thrombophilia were observed among LA (+) patients compared to LA (-) gestations (35% vs. 10.3%, p< 0.012 and 55% vs. 19.2%, p< 0.003, respectively). To identify the effectiveness of low-dose LMWH prophylaxis protocol, we compared gestational outcomes and demonstrated that the miscarriage rate was significantly decreased to half in current pregnancies compared to the previous gestations (73.6% vs. 35%, p= 0.003). CONCLUSIONS: Autoimmune diseases and hereditary thrombophilia are more frequent in LA (+) pregnancies, and these women are prone to obstetric problems. Low-dose LMWH and salicylic acid prophylaxis are critical in the management of LA (+) pregnant women.

Presence of fetal DNA in maternal exhaled breath condensate.

OBJECTIVES: Cell-free DNA has been found in all body fluids, but DNAs emerging from locations that are not in direct contact with breath in exhaled breath condensate (EBC) are yet to be found. The potential of EBC for prenatal and cancer screening prompted us to investigate whether fetal DNA is present in maternal EBC. METHOD: A total of 20 pregnant women's EBC and blood samples were collected. Four Y chromosome-specific assays were tested on all EBC and plasma samples by quantitative PCR (qPCR). The best-performing assay was used for digital droplet PCR (ddPCR) on all EBC and the six plasma samples. RESULTS: The sex of the fetuses was accurately determined from plasma samples. DNA sequences could not be properly amplified in EBC samples by the qPCR. By ddPCR, the Y chromosome sequence was amplified in two of the 11 EBC samples, from women carrying male fetuses (2/11), and the Y chromosome sequence was not amplified in the EBC of women carrying female fetuses (9/9). Exhaled breath condensate ddPCR result's specificity was 100%, the detection rate of Y chromosome was 18.18% (2/11), and the corrected accuracy was 59.09%. CONCLUSION: Our finding of "the presence of fetal DNA in maternal EBC", despite the low detection rate, might have a major impact on prenatal diagnosis and cancer screening.

Contributory effects of individual characteristics on pelvic floor distress in women with pelvic floor dysfunctions.

OBJECTIVE: To determine individual characteristics (i.e. sociodemographic and medical, obstetric and gynecological, and musculoskeletal and anthropometric parameters) for greater pelvic floor distress (PFD). METHODS: A cross-sectional study was performed in 253 women with pelvic floor dysfunction. PFD was assessed using the Pelvic Floor Distress Inventory-20 (PFDI-20). The score of Urogenital Distress Inventory-6 (UDI-6) was used to perform secondary analyses. Sociodemographic, medical, and obstetric & gynecological parameters were recorded. Waist and hip circumferences and pelvic diameters were measured as anthropometric parameters. Pearson test, t-test, and linear regression analyses were conducted with a significance level of 0.05. RESULTS: Education level (r = -0.23, p < .001; r = -0.24, p < .001), number of vaginal births (r = 0.15, p = .012; r = 0.12, p = .048), total vaginal birth weight (r = 0.15, p = .021; r = 0.16, p = .019), and Body Mass Index (r = 0.12, p = .043; r = 0.16, p = .007) were significantly correlated with the higher PFDI-20 and UDI-6 scores. The maternal age at the first vaginal birth (r = -0.13, p = .049) and pelvic antero-posterior diameter (r = 0.17, p = .013) were also significantly correlated with higher UDI-6 score. Linear regression analyses revealed that younger age (Beta coefficient (ß) = -1.10, p = .005), greater symptom duration (ß = 2.28, p = .001), the presence of chronic cough/constipation (ß = 25.72, p = .001), and increased total vaginal birth weight (ß = 2.38, p = .030) were associated with the greater PFDI-20 score. Increased pelvic antero-posterior diameter (ß = 0.88, p = .049) was a contributory factor for the greater UDI-6 score. CONCLUSION: This study showed that younger age, chronic cough/constipation, higher total vaginal birth weight, greater symptom duration, and pelvic antero-posterior diameter can be contributors of greater PFD. We suggest further longitudinal studies that better reveal the causal relationship between individual characteristics and PFD.

Impact of anti-thyroid peroxidase and anti-thyroglobulin antibodies on the gestational outcome of euthyroid pregnancies: A retrospective study.

BACKGROUND: Thyroglobulin (anti-TG) and/or thyroid peroxidase (anti-TPO) autoantibodies are associated with higher rates of poor gestational outcomes. OBJECTIVE: To demonstrate the impact of anti-TPO and anti-TG autoantibodies on the gestational outcomes of euthyroid pregnant women with a history of poor gestational outcome and thyroid gland disorders. METHODS: This retrospective study included totally 75 euthyroid pregnant, 30 of women with high thyroid autoantibodies (Anti-TPO/Thyroglobulin-positive group) and 45 of them without autoantibodies (control group). RESULTS: We could not demonstrate significant differences between two groups in terms of risk factors/co-morbidities, obstetric complications, gestational outcomes, and birth data (p> 0.05). However, enhanced miscarriage rates were observed among the Anti-TPO/Thyroglobulin-positive and control groups without significance (36.7% and 17.8% respectively, p= 0.116). High neonatal intensive care unit (NICU) admission rates were found for control and Anti-TPO/Thyroglobulin-positive groups (16.2% and 21.1%, respectively) (p= 0.720). Clinically, we compared the two groups in terms of the existence and the types of goiter (diffuse and nodular), and demonstrated that nodular goiter was statistically more frequent in the control group (40.0% vs. 8.7%, p= 0.015). Alongside, relatively high hereditary thrombophilia and type-2 diabetes mellitus rates were found in the Anti-TPO/Thyroglobulin-positive group (20.0% and 20.0%). CONCLUSION: Thyroid autoantibody positivity is likely a risk factor for early pregnancy loss and NICU admission.

Evaluation of umbilical cord immune cells in pregnancies with autoimmune disorders and/or methylenetetrahydrofolate reductase polymorphisms.

OBJECTIVES: To evaluate umbilical cord immune cells in pregnancies with autoimmune disorders (AID) and/or methylenetetrahydrofolate reductase (MTHFR) polymorphisms. METHODS: Umbilical cords were obtained from seven AID women without MTHFR polymorphisms, eight with AID and MTHFR polymorphisms, nine with MTHFR polymorphisms, and eight with neither. Umbilical cords were assessed immunohistologcally by anti-CD4, anti-CD8, anti-CD14, anti-CD19, anti-CD21, and anti-CD56 antibodies in six umbilical cord zones: 1) arterial wall 2) periarterial zone 3) venous wall 4) perivenous zone 5) intervascular zone, and 6) subamniotic zone. RESULTS: AIDs and MTHFR polymorphisms had an effect on the number and composition of CD4+ cells in the venous wall. The presence of a MTHFR polymorphism may affect the number and morphology of CD4+ cells in the subamniotic zone. CD8+ cell distribution is substantially influenced by the presence of maternal risk factors. The co-existence of AID with MTHFR polymorphism has a prominent effect on the number and morphology of CD14+ cells, especially in the arterial wall. CD19+ cells were only observed in the control group in the venous wall, perivenous zone, and intervascular zone. CD21+ cells were only observed in the arterial wall of the control group and the intervascular zone of the AID group with different morphologic features. The number and morphology of CD56+ cells is prominently affected by the presence of maternal risk factors. CONCLUSIONS: Umbilical cord stem cell and immune cell composition may be affected by the presence of risk factors like MTHFR polymorphisms and/or AID.

Impact of Human Papillomavirus on Wnt/Beta-Catenin Signaling in Morphological Inconspicuous Cervicovaginal Cells.

INTRODUCTION: The aim of this study was to identify early changes in the Wnt/beta-catenin signaling pathway in high-risk human papillomavirus (HPV) infected cervicovaginal cells and to correlate these changes with cell proliferation, apoptosis, and autophagic processes. METHODS: We evaluated 91 cervicovaginal smears of women with (n = 41) and without (n = 50) HPV-DNA. Smears were stained against beta-catenin, c-myc, secreted frizzled-related protein 4 (sFRP4), cleaved caspase-3, and the autophagy markers Beclin-1 and light chain 3B. In addition, sFRP-1, -2, -3, -4, -5 mRNA levels were determined by quantitative reverse transcription-PCR in primary keratinocytes and FaDu cells expressing HPV16-E6, -E7, or -E6E7. RESULTS: Our data indicated that the Wnt/beta-catenin signaling is activated in HPV (+) cervicovaginal cells that can already be detected in cells with no obvious changes in cellular morphology (HPV [+]/cyto [-]). These cells also had significantly higher sFRP4 levels when compared to HPV-negative samples. In primary keratinocytes, sFRP4 was found to be absent and sFRP1 and sFRP2 to be repressed in the presence of HPV16-E6 and E7. Interestingly, sFRP4 is expressed in FaDu cells and can be upregulated in the presence of E6E7. Curiously, SFRP4 expression correlated with an increase in the level of autophagic markers in HPV (+)/cyto (-) smears. CONCLUSION: In conclusion, the activation of the Wnt/beta-catenin signaling pathway and upregulation of sFRP4, paralleled by an activation of the autophagic pathway may represent predisposing cellular factors early after HPV infection which need to be further determined in larger study.

Singleton pregnancy losses before gestational week 22 among patients with autoimmune disorders and methylenetetrahydrofolate reductase polymorphisms.

BACKGROUND: The rates of pregnancy losses (PLs) are increased by maternal risk factors such as autoimmune disorders (AD) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. OBJECTIVE: To evaluate singleton PLs before gestational week (gw) 22 among patients with AD and MTHFR polymorphisms. METHODS: Totally, 1108 singleton pregnancies in 243 women were categorized as: 1) 148 pregnancies in 33 patients with AD, 2) 316 pregnancies in 66 patients with MTHFR polymorphisms, 3) 644 pregnancies in 144 patients with AD +MTHFR polymorphisms. PLs were classified into subgroups: a) Chemical Pregnancy(CP), b) Blighted Ovum(BO), c) gw ⩽ 10, d) gw11-14 e) gw15-22, f) Ectopic Pregnancy(EP), g) Trophoblastic Disease(TD). Obstetric histories were compared using Beksac Obstetrics Index (BOI): [number of living child + (π/10)]/gravida. RESULTS: PL rates before gw22 were 39.2% (58/148), 33.2% (105/316), and 36.3% (234/644) in AD, MTHFR, and AD +MTHFR groups, respectively (p= 0.421). The rate of Pre-Prenatal Screening Period fetal losses (CP + BO + gw ⩽ 10 fetal losses + EP + TD) were 84.8%, 75.9%, and 77.8% in AD, MTHFR, and AD +MTHFR, respectively (p= 0.264). Gravidity ⩽ 4 versus those with gravidity ⩾ 5 had statistically significant differences in BOI (p< 0.001). CONCLUSIONS: PL rate before gw22 among singleton pregnancies with AD and/or MTHFR polymorphisms was 35.8%. The clinical findings seem to be more complicated in patients with gravidity ⩾ 5.

Low-dose low-molecular-weight heparin prophylaxis against obstetrical complications in pregnancies with metabolic and immunological disorder-associated placental inflammation.

OBJECTIVE: We investigated the importance of prophylactic administration of low-dose low-molecular-weight heparin (LMWH) in women with risk factors associated with placental inflammation. MATERIALS AND METHODS: This retrospective cohort study included 300 pregnant women with a singleton pregnancy (30 primigravidas and 270 multigravidas) who received prophylactic low-dose LMWH to prevent placental inflammation. Based on maternal risk factors, patients were categorized into 3 groups as follows: Group 1: Patients with metabolic risk factors for placental inflammation (n = 205), Group 2: Patients with immunological risk factors for placental inflammation (n = 42), Group 3: Patients with metabolic and immunological risk factors for placental inflammation (n = 53). Obstetric histories, demographic features, clinical characteristics, and present pregnancy outcomes were compared between groups. Live birth rates, composite adverse obstetric outcomes, and the Beksac obstetric index were compared between present and previous pregnancies in multigravidas. RESULTS: Pregnancy outcomes were significantly better in the present pregnancy than in previous pregnancies. A significant increase was observed in live birth rates (33.4% vs. 69.9%, 27.5% vs. 60.5%, and 30.1% vs. 69.4% in groups 1, 2, and 3, respectively) and in the Beksac obstetric index (0.32 vs. 0.43, 0.33 vs. 0.47, and 0.38 vs. 0.57 in groups 1, 2, and 3 respectively) (p < .001 for all). A significant decrease in composite adverse pregnancy outcome rates was observed during the present pregnancy (23.5% vs. 100%, 28.9% vs. 100%, and 24.5% vs. 100% in groups 1, 2, and 3, respectively) (p < .001 for all). Live birth and composite adverse obstetric outcome rates were 70% and 33.3%, respectively in primigravidas. CONCLUSION: Low-dose low-molecular-weight heparin prophylaxis is useful to prevent metabolic and immunological disorders causing placental inflammation, which is the most likely pathophysiological mechanism contributing to various obstetrical complications.

Antenatal corticosteroids for women at risk of preterm delivery: the "Emperor's New Clothes" tale in medical practice.

OBJECTIVE: To introduce the effect of a single course of betamethasone for pregnant women at risk of preterm delivery (PTD). MATERIALS AND METHODS: In this study, a single course of 12 mg Bethamethasone was administered twice in 24 h (between 24-34 gestational weeks) for antenatal corticosteroid prophylaxis. Four hundred ninety-three neonates fulfilled the inclusion criteria and they were categorized (259 singletons, 192 twins and 42 triplets who met the inclusion criteria) into two groups according to the utilization of antenatal corticosteroid as control (n = 202) and study (n = 291) groups. We used respiratory distress syndrome (RDS), congenital pneumonia, intraventricular hemorrhage (IVH), neonatal sepsis, and bronchopulmonary dysplasia (BPD) as primary outcomes for the evaluation of neonatal morbidity. RESULTS: Study and control groups were similar in terms of clinical characteristics. RDS, congenital pneumonia, neonatal sepsis, and BPD rates were significantly higher in the study group (betamethasone) (p = .05, p = .007, 0.003, and 0.004, respectively) between 24-34 gestational weeks (when the neonates of multiple pregnancies were excluded from the analysis, we have demonstrated that congenital pneumonia (p = .033) and neonatal sepsis (p = .030) were still significantly higher in the betamethasone group). The neonates of 24-28 gestational weeks were compared separately and we demonstrated that RDS (p = .012), congenital pneumonia (p = .022), IVH (p = .044), neonatal sepsis (p = .023), and BPD (0.001) were also more frequent in the study group. When the 28-32 gestational week data were compared, IVH (p = .020) and neonatal sepsis (p = .017) were more frequent in the single course betamethasone users. However, we could not demonstrate a significant difference between the control and study groups between 32-34 gestational weeks in terms of the primary neonatal outcomes used in this study. CONCLUSION: Single course antenatal betamethasone administration may be ineffective on the respiratory complications of preterm and very preterm infants while it may be unfavorable for extremely preterm infants. WHAT IS NEW ABOUT THE PAPER, WHAT COULD ADD TO THE CURRENT KNOWLEDGE: Pregnant women at risk for preterm labor must be under intensive antenatal care programs, and if possible, necessary precautions must be undertaken to prevent fetal hypoxia together with etiology specific treatments. This approach might contribute to better perinatal outcomes than just administering antenatal corticosteroid therapy.

Musculoskeletal and anthropometric factors associated with urinary incontinence in pregnancy.

INTRODUCTION: Urinary incontinence (UI) is a common pelvic floor dysfunction in pregnancy. The relationship between biomechanical changes and pregnancy-related UI has not been fully elucidated. OBJECTIVE: To investigate the association of various musculoskeletal and anthropometric changes in pregnancy that affect gestational UI. METHODS: The study was conducted with 275 pregnant women. Ninety-three, 110 and 72 women were in first, second and third trimesters, respectively. Incontinence Impact Questionnaire for UI, Urogenital Distress Inventory-Short Form and Incontinence Severity Index were applied. Lumbar lordosis measurement was performed by Baseline Bubble Inclinometer while diastasis recti abdominis (DRA) measurement was carried out by finger-width method. Manual muscle test for rectus abdominis and right and left external oblique abdominal muscles, and Benign joint hypermobility test with Beighton scoring method were also applied as musculoskeletal measurements. Tape measurement at the waist, umbilical and hip levels, caliper with bi-iliac and bi-trochanteric diameters were also recorded as anthropometric measurements. RESULTS: Significant associated factors for UI were: umbilical DRA (OR = 1.57; p = .012); rectus abdominis muscle strength (values of 3 and below, OR = 1.2; p = .014); umbilical environment (OR = 1.1; p = .029); bi-iliac diameter (OR = 1.1; p = .05;) and bi-trochanteric diameter (OR = 1.3; p = .05), respectively. CONCLUSION: Changing musculoskeletal and anthropometric characteristics of pregnant women should be taken into consideration in UI follow-up during pregnancy.