Louise Pedersen

Living with cat and dog increases vaginal colonization with E. coli in pregnant women

Background Furred pets in the household are known reservoirs for pathogenic bacteria, but it is not known if transmission of bacteria between pet and owner leads to significantly increased rate of infections. We studied whether cats and dogs living in the household of pregnant women affect the commensal vaginal flora, and furthermore the need for oral antibiotics and rate of urinary tract infections during pregnancy. Methods The novel unselected Copenhagen Prospective Study on Asthma in Childhood (COPSAC2010) pregnancy cohort of 709 women participated in this analysis. Detailed information on pet exposure, oral antibiotic prescriptions filled at pharmacy and urinary tract infection during pregnancy was obtained and verified prospectively during clinic visits. Vaginal cultures were obtained at pregnancy week 36. Results Women, who had cat or dog in the home during pregnancy, had a different vaginal flora, in particular with increased Escherichia coli (E. coli) colonization; odds ratio after adjustment for lifestyle confounders and antibiotics 2.20, 95% CI, [1.27–3.80], p = 0.005. 43% of women living with cat and/or dog in the home used oral antibiotics compared to 33% of women with no cat or dog; adjusted odds ratio 1.51, 95% CI, [1.08–2.12], p = 0.016. Women living with cat had increased frequency of self-reported urinary tract infection; adjusted odds ratio 1.57, 95% CI, [1.02–2.43], p = 0.042. Conclusions The increased vaginal E. coli colonization in women living with cat or dog suggests a clinically important transmission of pathogenic bacteria from pet to owner substantiated by increased rate of antibiotic use and urinary tract infections which, which is of particular concern during pregnancy.

Neonatal Cytokine Profile in the Airway Mucosal Lining Fluid Is Skewed by Maternal Atopy

RATIONALE Heredity from mother or father may impact differently in complex diseases, such as atopy. Maternal atopy is a stronger risk factor than paternal atopy for the development of atopy in the offspring. We hypothesized that mothers and fathers atopy would have a differential imprinting on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. OBJECTIVES To study parental atopic imprinting on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. METHODS Eighteen cytokines and chemokines were quantified in nasal mucosal lining fluid in 309 neonates from the novel unselected Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohort. MEASUREMENTS AND MAIN RESULTS Maternal, but not paternal, atopic status (asthma, hay fever, or eczema with or without sensitization) was associated with general down-regulation of all 18 mediators assessed by principal component analysis (overall P = 0.015). CONCLUSIONS Maternal atopy, but not paternal atopy, showed a strong linkage with a suppressed mucosal cytokine and chemokine signature in asymptomatic neonates, suggesting imprinting by the maternal milieu in utero or perinatal life.

Deep phenotyping of the unselected COPSAC2010 birth cohort study

We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others.

Altered Response to A(H1N1)pnd09 Vaccination in Pregnant Women: A Single Blinded Randomized Controlled Trial

Background Pregnant women were suspected to be at particular risk when H1N1pnd09 influenza became pandemic in 2009. Our primary objective was to compare the immune responses conferred by MF59®-adjuvanted vaccine (Focetria®) in H1N1pnd09-naïve pregnant and non-pregnant women. The secondary aims were to compare influences of dose and adjuvant on the immune response. Methods The study was nested in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) pregnancy cohort in 2009-2010 and conducted as a single-blinded block-randomised [1∶1∶1] controlled clinical trial in pregnant women after gestational week 20: (1) 7.5 µg H1N1pnd09 antigen with MF59-adjuvant (Pa7.5 µg); (2) 3.75 µg antigen half MF59-adjuvanted (Pa3.75 µg); (3) 15 µg antigen unadjuvanted (P15 µg); and in non-pregnant women receiving (4) 7.5 µg antigen full adjuvanted (NPa7.5 µg). Blood samples were collected at baseline, 3 weeks, 3 and 10 months after vaccination, adverse events were recorded prospectively. Results 58 pregnant women were allocated to Pa7.5 µg and 149 non-pregnant women were recruited to NPa7.5 µg. The sero-conversion rate was significantly increased in non-pregnant (NPa7.5 µg) compared with pregnant (Pa7.5 µg) women (OR = 2.48 [1.03–5.95], p = 0.04) and geometric mean titers trended towards being higher, but this difference was not statistically significant (ratio 1.27 [0.85–1.93], p = 0.23). The significant titer increase rate showed no difference between pregnant (Pa7.5 µg) and non-pregnant (NPa7.5 µg) groups (OR = 0.49 [0.13–1.85], p = 0.29). Conclusion Our study suggests the immune response to the 7.5 µg MF59-adjuvanted Focetria® H1N1pnd09 vaccine in pregnant women may be diminished compared with non-pregnant women. Trial Registration ClinicalTrials.gov NCT01012557.

Prevalence and Predictors of Antibiotic Administration during Pregnancy and Birth

Background Antibiotic treatment during pregnancy and birth is very common. In this study, we describe the estimated prevalence of antibiotic administration during pregnancy and birth in the COPSAC2010 pregnancy cohort, and analyze dependence on social and lifestyle-related factors. Methods 706 pregnant women from the novel unselected Copenhagen Prospective Study on Asthma in Childhood (COPSAC2010) pregnancy cohort participated in this analysis. Detailed information on oral antibiotic prescriptions during pregnancy filled at the pharmacy was obtained and verified longitudinally. Information on intrapartum antibiotics, social, and lifestyle-factors was obtained by personal interviews. Results The prevalence of antibiotic use was 37% during pregnancy and 33% intrapartum. Lower maternal age at birth; adjusted odds ratio (aOR) 0.94, 95% CI, [0.90-0.98], p = 0.003 and maternal smoking; aOR 1.97, 95% CI, [1.07-3.63], p = 0.030 were associated with use of antibiotics for urinary tract infection during pregnancy. Maternal educational level (low vs. high), aOR 2.32, 95% CI, [1.24-4.35], p = 0.011, maternal asthma; aOR 1.99, 95% CI, [1.33-2.98], p < 0.001 and previous childbirth; aOR 1.80, 95% CI, [1.21-2.66], p = 0.004 were associated with use of antibiotics for respiratory tract infection during pregnancy. Lower gestational age; aOR 0.72, 95% CI, [0.61-0.85], p < 0.001, maternal smoking; aOR 2.84, 95% CI, [1.33-6.06], p = 0.007, and nulliparity; aOR 1.79, 95% CI, [1.06-3.02], p = 0.030 were associated with administration of intrapartum antibiotics in women giving birth vaginally. Conclusion Antibiotic administration during pregnancy and birth may be influenced by social and lifestyle-factors. Understanding such risk factors may guide preventive strategies in order to avoid unnecessary use of antibiotics.

Association between whole-blood polyunsaturated fatty acids in pregnant women and early fetal weight

Background/objectives:Studies suggest that intake of marine n-3 polyunsaturated fatty acids (n-3 PUFA) in pregnancy have an impact on birth weight, but only few have investigated the effect on early fetal growth. The objective of the study was to investigate the association between levels of PUFA in maternal blood in gestational week 24 and biometric measures and estimated fetal weight in gestational week 20.Subjects/methods:In the COPSAC2010 cohort, whole-blood fatty acid composition (a biomarker of PUFA intake) from 583 women in week 24 was analyzed by gas chromatography. Biometric data (head circumference, abdominal circumference and femur length) were collected by ultra sound in week 20 and fetal weight was estimated. Associations between whole-blood PUFA (docosahexaenoic acid (DHA), total n-3 PUFA, n-6/n-3 PUFA, total n-6 PUFA) and fetal weight and biometrics measures were analyzed by multivariable-adjusted linear regression analyses.Results:There was a wide range in maternal blood DHA, which varied from 1.8 to 6.9% depending on socioeconomic status, smoking and body mass index. After adjusting for these variables, no association was observed between any of the assessed PUFA components and the circumference of head or abdomen or fetal weight. However, an inverse association was established between DHA and total n-3 PUFA and femur length (P<0.02).Conclusion:Maternal whole-blood PUFA composition, specifically her n-3 PUFA status, in gestational week 24 was not associated with overall early fetal weight gain, but this study indicates that it may decrease the length of femur.

Vaccine Targeting of Subdominant CD8+ T Cell Epitopes Increases the Breadth of the T Cell Response upon Viral Challenge, but May Impair Immediate Virus Control.

As a result of the difficulties in making efficient vaccines against genetically unstable viruses such as HIV, it has been suggested that future vaccines should preferentially target subdominant epitopes, the idea being that this should allow a greater breadth of the induced T cell response and, hence, a greater efficiency in controlling escape variants. However, to our knowledge the evidence supporting this concept is limited at best. To improve upon this, we used the murine lymphocytic choriomeningitis virus model and adenoviral vectors to compare a vaccine expressing unmodified Ag to a vaccine expressing the same Ag without its immunodominant epitope. We found that removal of the dominant epitope allowed the induction of CD8+ T cell responses targeting at least two otherwise subdominant epitopes. Importantly, the overall magnitude of the induced T cell responses was similar, allowing us to directly compare the efficiency of these vaccines. Doing this, we observed that mice vaccinated with the vaccine expressing unmodified Ag more efficiently controlled an acute viral challenge. In the course of a more chronic viral infection, mice vaccinated using the vaccine targeting subdominant epitopes caught up with the conventionally vaccinated mice, and analysis of the breadth of the CD8+ T cell response revealed that this was notably greater in the former mice. However, under the conditions of our studies, we never saw any functional advantage of this. This may represent a limitation of our model, but clearly our findings underscore the importance of carefully weighing the pros and cons of changes in epitope targeting before any implementation.

Differences in global DNA methylation of testicular seminoma are not associated with changes in histone modifications, clinical prognosis, BRAF mutations or gene expression

Testicular germ cell tumours of young adults are comprised of a heterogeneous group of non-seminomas and a homogeneous group of seminomas. While the majority of seminomas retain a hypo-methylated genome, a small fraction displays a highly methylated genome, resembling hyper-methylated non-seminomas. It is well established from e.g. melanoma, colorectal and thyroid cancer that a methylated phenotype can be correlated to prognosis and can be related to BRAF mutations. In the present study we investigated the global methylation level in 67 seminomas and classified them as hypo-methylated, intermediate, patchy and hyper-methylated, respectively. A selected subset representing each level of DNA methylation and the TCam2 seminoma cell line were subsequently analysed for a range of other epigenetic marks (6 histone marks and 5-hydroxymethylcytosine), the presence of the BRAF V600E de novo mutation, differences in the transcriptome and finally correlated to the clinical outcome. We did not identify any histone marks or hydroxymethylation levels that correlated with the methylation level of the genome. Some histone marks, however, showed a great variation while others were found at the same level in all the investigated seminomas. We did not identify any tumours with the BRAF V600E mutation and transcriptome analysis revealed no significant differences between hypo- and hyper-methylated seminomas. Similarly, no obvious differences in the clinical manifestation of the patients representing hypo- or hyper-methylated seminomas were identified. The level of DNA methylation in testicular seminomas consequently seems secondary to the manifestation of the tumour phenotype.