Altered Transcriptome Response in PBMCs of Czech Adults Linked to Multiple PFAS Exposure: B Cell Development as a Target of PFAS Immunotoxicity.

While the immunomodulation effects of per- and polyfluoroalkyl substances (PFASs) are described on the level of clinical signs in epidemiological studies (e.g., suppressed antibody response after vaccination), the underlying mechanism has still not been fully elucidated. To reveal mechanisms of PFAS exposure on immunity, we investigated the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMCs) responding to PFAS exposure (specifically, exposure to PFPA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS). Blood samples and the chemical load in the blood were analyzed under the cross-sectional CELSPAC: Young Adults study. The overall aim of the study was to identify sensitive gene sets and cellular pathways conserved for multiple PFAS chemicals. Transcriptome networks related to adaptive immunity were perturbed by multiple PFAS exposure (i.e., blood levels of at least four PFASs). Specifically, processes tightly connected with late B cell development, such as B cell receptor signaling, germinal center reactions, and plasma cell development, were shown to be affected. Our comprehensive transcriptome analysis identified the disruption of B cell development, specifically the impact on the maturation of antibody-secreting cells, as a potential mechanism underlying PFAS immunotoxicity.

Time Patterns in Internal Human Exposure Data to Bisphenols, Phthalates, DINCH, Organophosphate Flame Retardants, Cadmium and Polyaromatic Hydrocarbons in Europe.

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000-2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011-2012, biobanked samples from the DEMOCOPHES project were used. For 2014-2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5-12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24-52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.

Impact of PFAS exposure on prevalence of immune-mediated diseases in adults in the Czech Republic.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are emerging environmental contaminants with multiple hazardous properties including immunomodulation potency. Human exposure to PFASs has been associated with various immune-mediated diseases and outcomes. This study aimed to investigate the association between PFAS exposure and immune-mediated diseases such as allergies, eczemas, and autoimmune diseases in a population of adults in the Czech Republic. METHODS: This study included 309 adults from the Central European Longitudinal Study of Parents and Children: Young Adults (CELSPAC: YA). 12 PFASs were measured in participants' serum by HPLC-MS/MS, 3 PFASs were removed from the subsequent analyses due to low detection frequency. The associations of 9 PFASs with 9 immune-mediated diseases were assessed by logistic regression. Furthermore, Bayesian kernel machine regression (BKMR) was used to estimate the effect of the PFAS mixture on immune-mediated diseases. All analyses were adjusted for sex, age, BMI, smoking, education, and family history of immune-mediated diseases. In cases of a statistically significant interaction of PFASs and sex, stratified analyses were performed for men and women. RESULTS: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) were negatively associated with both atopic eczema (OR per IQR increase 0.58 (95% CI 0.37-0.90) for PFOA and 0.56 (0.32-0.95) for PFOS) and contact dermatitis (0.37 (0.16-0.85) for PFOA and 0.33 (0.11-0.94) for PFOS). Perfluoroundecanoate (PFUnDA) was negatively associated with pollen, dust, and mite allergy (0.62 (0.43-0.89)). BKMR modelling showed a negative tendency in the overall effect of PFAS mixture on immune-health outcomes. Based on the stratified analysis, sex was suggested to be an effect modifier in the association of PFOS and atopic eczema. CONCLUSION: Our results contribute to the body of literature that observes the immunosuppressive effect of PFAS exposure during eczemas and allergies, both for PFASs individually and as a mixture.

Investigation of SARS-CoV-2 seroprevalence in relation to natural infection and vaccination between October 2020 and September 2021 in the Czech Republic: a prospective national cohort study.

OBJECTIVE: Examine changes in SARS-CoV-2 seropositivity before and during the national vaccination campaign in the Czech Republic. DESIGN: Prospective national population-based cohort study. SETTING: Masaryk University, RECETOX, Brno. PARTICIPANTS: 22 130 persons provided blood samples at two time points approximately 5-7 months apart, between October 2020 and March 2021 (phase I, before vaccination), and between April and September 2021 (during vaccination campaign). OUTCOME MEASURES: Antigen-specific humoral immune response was analysed by detection of IgG antibodies against the SARS-CoV-2 spike protein by commercial chemiluminescent immunoassays. Participants completed a questionnaire that included personal information, anthropometric data, self-reported results of previous RT-PCR tests (if performed), history of symptoms compatible with COVID-19 and records of COVID-19 vaccination. Seroprevalence was compared between calendar periods, previous RT-PCR results, vaccination and other individual characteristics. RESULTS: Before vaccination (phase I), seroprevalence increased from 15% in October 2020 to 56% in March 2021. By the end of phase II, in September 2021, prevalence increased to 91%; the highest seroprevalence was seen among vaccinated persons with and without previous SARS-CoV-2 infection (99.7% and 97.2%, respectively), while the lowest seroprevalence was found among unvaccinated persons with no signs of disease (26%). Vaccination rates were lower in persons who were seropositive in phase I but increased with age and body mass index. Only 9% of unvaccinated subjects who were seropositive in phase I became seronegative by phase II. CONCLUSIONS: The rapid increase in seropositivity during the second wave of the COVID-19 epidemic (covered by phase I of this study) was followed by a similarly steep rise in seroprevalence during the national vaccination campaign, reaching seropositivity rates of over 97% among vaccinated persons.

Titanium Dioxide Nanoparticles Modulate Systemic Immune Response and Increase Levels of Reduced Glutathione in Mice after Seven-Week Inhalation.

Titanium dioxide nanoparticles (TiO2 NPs) are used in a wide range of applications. Although inhalation of NPs is one of the most important toxicologically relevant routes, experimental studies on potential harmful effects of TiO2 NPs using a whole-body inhalation chamber model are rare. In this study, the profile of lymphocyte markers, functional immunoassays, and antioxidant defense markers were analyzed to evaluate the potential adverse effects of seven-week inhalation exposure to two different concentrations of TiO2 NPs (0.00167 and 0.1308 mg TiO2/m3) in mice. A dose-dependent effect of TiO2 NPs on innate immunity was evident in the form of stimulated phagocytic activity of monocytes in low-dose mice and suppressed secretory function of monocytes (IL-18) in high-dose animals. The effect of TiO2 NPs on adaptive immunity, manifested in the spleen by a decrease in the percentage of T-cells, a reduction in T-helper cells, and a dose-dependent decrease in lymphocyte cytokine production, may indicate immunosuppression in exposed mice. The dose-dependent increase in GSH concentration and GSH/GSSG ratio in whole blood demonstrated stimulated antioxidant defense against oxidative stress induced by TiO2 NP exposure.

Exposure to flame retardants in European children - Results from the HBM4EU aligned studies.

Many legacy and emerging flame retardants (FRs) have adverse human and environmental health effects. This study reports legacy and emerging FRs in children from nine European countries from the HBM4EU aligned studies. Studies from Belgium, Czech Republic, Germany, Denmark, France, Greece, Slovenia, Slovakia, and Norway conducted between 2014 and 2021 provided data on FRs in blood and urine from 2136 children. All samples were collected and analyzed in alignment with the HBM4EU protocols. Ten halogenated FRs were quantified in blood, and four organophosphate flame retardants (OPFR) metabolites quantified in urine. Hexabromocyclododecane (HBCDD) and decabromodiphenyl ethane (DBDPE) were infrequently detected (<16% of samples). BDE-47 was quantified in blood from Greece, France, and Norway, with France (0.36 ng/g lipid) having the highest concentrations. BDE-153 and -209 were detected in <40% of samples. Dechlorane Plus (DP) was quantified in blood from four countries, with notably high median concentrations of 16 ng/g lipid in Slovenian children. OPFR metabolites had a higher detection frequency than other halogenated FRs. Diphenyl phosphate (DPHP) was quantified in 99% of samples across 8 countries at levels ∼5 times higher than other OPFR metabolites (highest median in Slovenia of 2.43 ng/g lipid). FR concentrations were associated with lifestyle factors such as cleaning frequency, employment status of the father of the household, and renovation status of the house, among others. The concentrations of BDE-47 in children from this study were similar to or lower than FRs found in adult matrices in previous studies, suggesting lower recent exposure and effectiveness of PBDE restrictions.

Personal care product use and lifestyle affect phthalate and DINCH metabolite levels in teenagers and young adults.

Humans are widely exposed to phthalates and their novel substitutes, and considering the negative health effects associated with some phthalates, it is crucial to understand population levels and exposure determinants. This study is focused on 300 urine samples from teenagers (aged 12-17) and 300 from young adults (aged 18-37) living in Czechia collected in 2019 and 2020 to assess 17 plasticizer metabolites as biomarkers of exposure. We identified widespread phthalate exposure in the study population. The diethyl phthalate metabolite monoethyl phthalate (MEP) and three di (2-ethylhexyl) phthalate metabolites were detected in the urine of >99% of study participants. The highest median concentrations were found for metabolites of low-molecular-weight (LMW) phthalates: mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) and MEP (60.7; 52.6 and 17.6 µg/L in young adults). 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) metabolites were present in 68.2% of the samples with a median of 1.24 µg/L for both cohorts. Concentrations of MnBP and MiBP were similar to other European populations, but 5-6 times higher than in populations in North America. We also observed large variability in phthalate exposures within the study population, with 2-3 orders of magnitude differences in urinary metabolites between high and low exposed individuals. The concentrations varied with season, gender, age, and lifestyle factors. A relationship was found between high levels of MEP and high overall use of personal care products (PCPs). Cluster analysis suggested that phthalate exposures depend on season and multiple lifestyle factors, like time spent indoors and use of PCPs, which combine to lead to the observed widespread presence of phthalate metabolites in both study populations. Participants who spent more time indoors, particularly noticeably during colder months, had higher levels of high-molecular weight phthalate metabolites, whereas participants with higher PCP use, particularly women, tended to have higher concentration of LMW phthalate metabolites.

Nationwide increases in anti-SARS-CoV-2 IgG antibodies between October 2020 and March 2021 in the unvaccinated Czech population.

Background: The aim of the nationwide prospective seroconversion (PROSECO) study was to investigate the dynamics of anti-SARS-CoV-2 IgG antibodies in the Czech population. Here we report on baseline prevalence from that study. Methods: The study included the first 30,054 persons who provided a blood sample between October 2020 and March 2021. Seroprevalence was compared between calendar periods, previous RT-PCR results and other factors. Results: The data show a large increase in seropositivity over time, from 28% in October/November 2020 to 43% in December 2020/January 2021 to 51% in February/March 2021. These trends were consistent with government data on cumulative viral antigenic prevalence in the population captured by PCR testing - although the seroprevalence rates established in this study were considerably higher. There were only minor differences in seropositivity between sexes, age groups and BMI categories, and results were similar between test providing laboratories. Seropositivity was substantially higher among persons with history of symptoms (76% vs. 34%). At least one third of all seropositive participants had no history of symptoms, and 28% of participants with antibodies against SARS-CoV-2 never underwent PCR testing. Conclusions: Our data confirm the rapidly increasing prevalence in the Czech population during the rising pandemic wave prior to the beginning of vaccination. The difference between our results on seroprevalence and PCR testing suggests that antibody response provides a better marker of past infection than the routine testing program.

Copper Oxide Nanoparticles Stimulate the Immune Response and Decrease Antioxidant Defense in Mice After Six-Week Inhalation.

Copper oxide nanoparticles (CuO NPs) are increasingly used in various industry sectors. Moreover, medical application of CuO NPs as antimicrobials also contributes to human exposure. Their toxicity, including toxicity to the immune system and blood, raises concerns, while information on their immunotoxicity is still very limited. The aim of our work was to evaluate the effects of CuO NPs (number concentration 1.40×106 particles/cm3, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 µg CuO/m3 continuously for 6 weeks. After six weeks of CuO NP inhalation, the content of copper in lungs and liver was significantly increased, while in kidneys, spleen, brain, and blood it was similar in exposed and control mice. Inhalation of CuO NPs caused a significant increase in proliferative response of T-lymphocytes after mitogenic stimulation and basal proliferative activity of splenocytes. CuO NPs significantly induced the production of IL-12p70, Th1-cytokine IFN-γ and Th2-cytokines IL-4, IL-5. Levels of TNF-α and IL-6 remained unchanged. Immune assays showed significantly suppressed phagocytic activity of granulocytes and slightly decreased respiratory burst. No significant differences in phagocytosis of monocytes were recorded. The percentage of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD19+ cell subsets in spleen, thymus, and lymph nodes did not differ between exposed and control animals. No changes in hematological parameters were found between the CuO NP exposed and control groups. The overall antioxidant protection status of the organism was expressed by evaluation of GSH and GSSG concentrations in blood samples. The experimental group exposed to CuO NPs showed a significant decrease in GSH concentration in comparison to the control group. In summary, our results indicate that sub-chronic inhalation of CuO NPs can cause undesired modulation of the immune response. Stimulation of adaptive immunity was indicated by activation of proliferation and secretion functions of lymphocytes. CuO NPs elicited pro-activation state of Th1 and Th2 lymphocytes in exposed mice. Innate immunity was affected by impaired phagocytic activity of granulocytes. Reduced glutathione was significantly decreased in mice exposed to CuO NPs.

Tracking of anthropometric characteristics from childhood to adolescence: an 8-year follow-up findings from the Czech ELSPAC study.

BACKGROUND: Although evidence suggests that obesity track well from childhood to adolescence, most of the research has been done in Western and high-income countries. Moreover, most of the studies have tracked body-mass index, as a proxy of nutritional status, while tracking characteristics of circumferences and skinfold thicknesses have been less studies. Therefore, the main purpose of the study was to explore tracking characteristics of complete anthropometric data from childhood to adolescence. METHODS: This sub-study was part of the Czech ELSPAC study. In the present 8-year longitudinal study, we collected information from pediatrician's medical records at the ages of 8 y (n = 888), 11 y (n = 1065), 13 y (n = 811) and 15 y (n = 974), including circumferences (head, chest, waist, hips, and arm), indices (body-mass index, waist-to-hip ratio and waist-to-height ratio) and skinfold thicknesses (biceps, triceps, subscapula, suprailiaca, thigh and the sum of 5 skinfolds). Participants were recruited from the two selected regions of the Czech Republic (Brno and Znojmo). Linear generalized estimating equations were conducted to analyze tracking patterns over an 8-year follow-up period for all anthropometric measurements. RESULTS: Tracking coefficients were moderate to strong, ranging from 0.40 to 0.62 for circumferences, 0.41 to 0.74 for indices and 0.72 to 0.86 for skinfolds. According to body-mass index and waist circumference standards, overweight/obese children and children with abdominal obesity at the age of 8 y were 11.31 (95% CI = 8.41 to 15.22, p < 0.001) and 10.73 (95% CI = 7.93 to 14.52, p < 0.001) more likely to remain overweight/obese and to have abdominal obesity at the age of 15 y. CONCLUSIONS: Findings show moderate to strong tracking of anthropometric characteristics, i.e. circumferences track moderately well, while strong tracking for indices and skinfold thicknesses is observed. Moreover, strong tracking of general overweight/obesity and abdominal obesity between ages 8 y and 15 y indicates that the detection of these risk factors at the beginning of primary school should be advocated.

Longitudinal associations between sport participation and fat mass with body posture in children: A 5-year follow-up from the Czech ELSPAC study.

The main purpose of the study was to examine longitudinal associations between sport participation and fat mass with body posture in children. We used data from children recruited in the Czech European Longitudinal Study of Pregnancy and Childhood (CELSPAC) at the ages of 11 y (n = 1065), 13 y (n = 811) and 15 y (n = 974). Information on body posture, practicing sport in a club and at a competitive level, and skinfold thicknesses (biceps, triceps, subscapula, suprailiaca and thigh) from pediatrician's medical records were collected. Body posture was inspected by a pediatrician. The sum of 5 skinfolds was used as a proxy of fat mass. The 85th and 95th percentiles defined 'overfat' and 'obese'children. Practicing sport in a club and at a competitive level were included as 'yes/no' answers. General linear mixed models with risk ratios (RR) and 95% confidence intervals (95% CI) were calculated. Overall, 35.6% of children and adolescents had impaired body posture; the prevalence of 'incorrect' body posture increased by age (from 41.0% to 28.0%, p<0.001). Practicing sport in a club and at a competitive level decreased by follow-up (p<0.001), while the level of 'overfat' and 'obese' children increased (p<0.01). In separate models, 'incorrect' body posture was associated with non-practicing sport in clubs (RR = 1.68; 95% CI 1.43-1.97, p<0.001) or at competitive level (RR = 1.61; 95% CI 1.37-1.88, p<0.001) and with being 'overfat' (RR = 2.05; 95% CI 1.52-2.75, p<0.001) and 'obese' (RR = 2.15; 95% CI 1.68-2.75, p<0.001). When all variables were put simultaneously into the model additionally adjusted for sex, self-rated health and baseline body posture, similar associations remained. This study shows, that not participating in sport and being overfat/obese are longitudinally associated with 'incorrect' body posture. Therefore, the detection of these risk factors in childhood, through the development of school- and community-based interventions, should be advocated.

Maternal Pre-Pregnancy Nutritional Status and Physical Activity Levels and a Sports Injury Reported in Children: A Seven-Year Follow-Up Study.

OBJECTIVE: Our aim was to analyze dose-response associations between maternal pre-pregnancy body mass index and physical activity levels with childhood sports injury rates. METHODS: Participants included pre-pregnant mothers (n = 4811) and their children at the age of 7 years (n = 3311). Maternal anthropometry (height, weight, and body mass index), time spent in physical activity, and education level were recorded. All sports injuries were defined as injuries reported in the past year by the children at the age of 7 years. RESULTS: Children whose mothers were overweight/obese in the pre-pregnancy period were 2.04 (OR = 2.04, 95% CI = 1.12-3.71) times more likely to report a sports injury at the age of 7 years. Underweight mothers exhibited a 74% decrease in the odds of their children reporting a sports injury at follow-up (OR = 0.26, 95% CI = 0.10-0.68). Finally, an increase in maternal physical activity across the last three quartiles was associated with a lower odds of sports injuries. CONCLUSIONS: The risk of reporting a sports injury was greater for children whose mothers were overweight/obese in the pre-pregnancy period. However, there was a lower risk with both maternal underweight status and increasing minutes of physical activity.

Tracking of Maternal Physical Activity and Sport Participation over 11 Years: Findings from the Czech ELSPAC Study.

Purpose: Tracking of physical activity (PA) and sport participation (SP) during motherhood is poorly understood. The purpose of the study was to analyze the extent of tracking of maternal PA and SP. Methods: In this investigation, data were collected from the Czech ELSPAC study subsample of 4811 and 2609 women measured postnatally (1991-1992) and after 11 years of follow-up (2002-2003), respectively. The structured questionnaire was used to assess the participation and average weekly time spent in PA, and the frequency of engaging in different sports (running, cycling, strength training, racket sports, swimming, and team sports). Tracking was calculated using generalized estimating equations (GEE) with beta coefficients (ß), odds ratios (ORs), and 95% confidence intervals (95% CI). Results: Moderately high tracking coefficients were observed for cycling (ß = 0.69, 95% 0.67-0.72), strength training (ß = 0.59, 95% 0.56-0.63), and weekly time spent in PA (ß = 0.53, 95% 0.38-0.66); meanwhile, moderate tracking coefficients were generated for swimming (ß = 0.48, 95% 0.44-0.52), team sports (ß = 0.44, 95% 0.39-0.48), racket sports (ß = 0.44, 95% 0.39-0.48), and running (ß = 0.35, 95% 0.30-0.40). Mothers who did not participate in PA at baseline were 81% more likely not to participate in it at follow-up (OR = 1.81, 95% CI 1.53-2.13). Conclusion: Cycling- and strength-related activities and weekly PA were tracked moderately-to-moderately high during motherhood. Moreover, the strong tracking of physical inactivity indicates that the detection of this risk factor before pregnancy should be advocated.

Birth outcomes, puberty onset, and obesity as long-term predictors of biological aging in young adulthood.

Background: Biological aging and particularly the deviations between biological and chronological age are better predictors of health than chronological age alone. However, the predictors of accelerated biological aging are not very well understood. The aim was to determine the role of birth outcomes, time of puberty onset, body mass index (BMI), and body fat in accelerated biological aging in the third decade of life. Methods: We have conducted a second follow-up of the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ) prenatal birth cohort in young adulthood (52% male; age 28-30; n = 262) to determine the role of birth outcomes, pubertal timing, BMI, and body fat on biological aging. Birth outcomes included birth weight, length, and gestational age at birth. Pubertal timing was determined by the presence of secondary sexual characteristics at the age of 11 and the age of first menarche in women. Biological age was estimated using the Klemera-Doubal Method (KDM), which applies 9-biomarker algorithm including forced expiratory volume in one second (FEV1), systolic blood pressure, glycated hemoglobin, total cholesterol, C-reactive protein, creatinine, urea nitrogen, albumin, and alkaline phosphatase. Accelerated/decelerated aging was determined as the difference between biological and chronological age (BioAGE). Results: The deviations between biological and chronological age in young adulthood ranged from -2.84 to 4.39 years. Accelerated biological aging was predicted by higher BMI [in both early (R2 adj = 0.05) and late 20s (R2 adj = 0.22)], subcutaneous (R2 adj = 0.21) and visceral fat (R2 adj = 0.25), puberty onset (η p 2 = 0.07), birth length (R2 adj = 0.03), and the increase of BMI over the 5-year period between the two follow-ups in young adulthood (R2 adj = 0.09). Single hierarchical model revealed that shorter birth length, early puberty onset, and greater levels of visceral fat were the main predictors, together explaining 21% of variance in accelerated biological aging. Conclusion: Our findings provide comprehensive support of the Life History Theory, suggesting that early life adversity might trigger accelerated aging, which leads to earlier onset of puberty but decreasing fitness in adulthood, reflected by more visceral fat and higher BMI. Our findings also suggest that reduction of BMI in young adulthood slows down biological aging.

Association between Stress Urinary Incontinence and Depressive Symptoms after Birth: the Czech ELSPAC Study.

The study objectives were to (1) identify risk factors related to stress urinary incontinence (SUI) and postnatal depression (PD) after birth, and (2) investigate both possible directions of association between SUI and PD in population-based sample of Czech mothers. 3,701 nulliparous and multiparous women completed the self-reported questionnaires at 6 weeks and 6 months after birth and were included into the analyses of this prospective cohort study. Unadjusted and adjusted logistic regressions examined relationship between SUI a PD accounting for range of other risk factors. During the first 6 months after birth, 650 mothers (17.6%) developed SUI and 641 (17.3%) displayed signs of PD. The mode of delivery, parity and higher BMI were associated with SUI. The rate of PD symptoms was higher in mothers with positive history of prenatal depression, and in divorced or widowed mothers. Both conditions were associated with worse self-reported health, back pain and stop-smoker status. Initially, SUI at 6 weeks was slightly, but significantly associated with onset of PD at 6 months (OR 1.51, 95% CI 1.02-2.23) while PD at 6 weeks was not significantly related to new cases of SUI at 6 months (OR 1.48, 95% CI 0.91-2.39). After full adjustment these OR reduced to 1.41 and 1.38 (both non-significant), respectively. SUI and PD are common conditions in women postpartum that share some risk factors. Our study suggests that both directions of their relationship are possible although a larger study is needed to confirm our findings.

Identification of microRNA signatures in umbilical cord blood associated with maternal characteristics.

BACKGROUND: Umbilical cord blood could serve as useful source of blood markers enabling more efficient and reliable prenatal and neonatal diagnostics. MicroRNAs (miRNAs) are ubiquitous in body fluids where they were used for detecting and monitoring various physiological and pathological conditions. In this descriptive study, we aimed to identify changes in miRNA expression profiles associated with basic maternal somatic and epidemiological characteristics. METHODS: Study is based on 24 mothers from the Pilot phase of CELSPAC: TNG (Central European Longitudinal Studies of Parents and Children: The Next Generation) study. Cord blood was collected at time of delivery and global miRNA profiling was performed using microRNA Ready-to-use PCR Human Panel I+II TaqMan microarrays. Expression profiles were statistically evaluated in relation to maternal age, BMI, pregnancy weight gain, blood type, Rh factor status, allergies during pregnancy, addictive substance abuse and smoking status. RESULTS: We analyzed expression of 752 human mature miRNAs in 24 samples of umbilical cord blood. For all maternal characteristics tested we described a specific signature of significantly deregulated miRNAs (P < 0.05). Analysis revealed seven miRNA associated with maternal age (three increased and four decreased in women younger than 35 years), 14 miRNAs associated with BMI status (five miRNAs increased and nine miRNAs decreased in women with BMI > 25) and nine miRNAs associated with maternal weight gain during pregnancy (eight miRNAs increased, and one miRNA decreased in women with weight gain < 12 kg). Additionally, 17 miRNAs correlated to blood type (two miRNAs decreased in blood type A, 11 increased in blood type B, two miRNAs increased in blood type AB and two miRNAs increased in blood type 0) and 17 miRNAs to Rh status of mother. We also detected seven miRNAs deregulated in umbilical cord blood of women with allergy (four increased and three decreased in women with allergy), four miRNAs associated to addictive substance abuse status (two up- and two downregulated in women with addictive substance abuse) and eight miRNAs associated with maternal cigarette smoking during pregnancy. CONCLUSIONS: We successfully described differences in miRNA profiles in umbilical cord blood associated with basic characteristics connected with mother. Our data suggest that miRNAs in umbilical cord blood are detectable and associated with a wide range of maternal characteristics. These results indicate that miRNAs could potentially serve, and should be studied, as biomarkers for screening and diagnosis of pregnancy-associated complications and pathologies.

Role of combined prenatal and postnatal paracetamol exposure on asthma development: the Czech ELSPAC study.

BACKGROUND: Prenatal and postnatal paracetamol exposure has been previously associated with asthma development in childhood in Western populations. We explore the association between prenatal and postnatal paracetamol exposure and asthma development in a Central European sample of Czech children, suggesting possible additive effect of the both exposures. Furthermore, since aspirin had been used more widely during study data collection in Central Europe, we also compared asthma development for those exposed to paracetamol and aspirin. METHODS: We used data from 3329 children born in the 1990s as members of the prospective Czech European Longitudinal Study of Pregnancy and Childhood. Data about prenatal and postnatal paracetamol and aspirin exposure, and potential covariates were obtained from questionnaires completed by mothers. Data about incident asthma were obtained from paediatrician health records. RESULTS: 60.9% of children received paracetamol only postnatally, 1.5% only prenatally and 4.9% of children were exposed both during pregnancy and infancy. Prevalence of asthma in following population was 5% at 11 years. Being exposed to paracetamol both in prenatal and postnatal period was associated with asthma development (unadjusted OR 1.98, 95% CI 1.02 to 3.87). Being exposed only in the postnatal period was also significantly associated with increased risk of asthma. No association between prenatal exposure only and outcome was found. A higher but non-significant risk of asthma was observed for those whose mothers used paracetamol during pregnancy compared with those who used aspirin. CONCLUSIONS: The main findings of this prospective birth cohort study add to previous observations linking prenatal and early postnatal paracetamol exposure to asthma development. However, the magnitude of effect is relatively modest, and therefore, we recommend paracetamol to remain the analgesic and antipyretic of choice throughout pregnancy and early childhood.

Systemic inflammatory response syndrome is reduced by preoperative plasma-thrombo-leukocyte aphaeresis in a pig model of cardiopulmonary bypass.

OBJECTIVES: The systemic inflammatory response syndrome (SIRS) after cardiac surgery with cardiopulmonary bypass (CPB) exacerbates organ dysfunction and increases postoperative mortality. The aim of this study was to reduce SIRS after CPB in a pig model by profoundly decreasing all blood defence factors (complement, coagulation and fibrinolytic and contact systems, leukocytes and thrombocytes) using pre­operative aphaeresis. METHODS: Thirty-three pigs underwent 3 h of hypothermic CPB with 2 h of cardioplegic arrest, followed by 4 days of observation. One half of the sample underwent prebypass plasma-thrombo-leukocyte aphaeresis with the adjuvant leukofiltration. RESULTS: In the control group, there were classical signs of SIRS (tachycardia, tachypnea and leukocytosis) postoperatively. There was also myocardial ischaemia and the need for inotropic support in 90% of the control animals. Neutrophils showed an increase in superoxide anion production (P < 0.001), and surface neutral protease activity (P < 0.001) and blood endotoxin levels increased (P < 0.01) compared with preoperative levels. In contrast, in the aphaeretic group, there were no classical signs of SIRS; no myocardial ischaemia; minimum neutrophil production of the superoxide anion and protease activity were recorded (P < 0.001); and endotoxin levels were also decreased (P < 0.05) compared with the controls. In the control group, the haemodynamic problems associated with disconnecting from CPB correlated with the histologic findings in the myocardium (leukocyte endothelial adhesion and leukodiapedesis). CONCLUSIONS: Pre­operative plasma­thrombo-leukocyte aphaeresis significantly reduces the major symptoms of SIRS and organ dysfunction after 3 h of CPB without adverse effects, such as bleeding and infection, during the postoperative course.