Sex-specific incidence of asthma, rhinitis and respiratory multimorbidity before and after puberty onset: individual participant meta-analysis of five birth cohorts collaborating in MeDALL.

Introduction: To understand the puberty-related sex shift in the prevalence of asthma and rhinitis as single entities and as respiratory multimorbidities, we investigated if there is also a sex-specific and puberty-related pattern of their incidences. Methods: We used harmonised questionnaire data from 18 451 participants in five prospective observational European birth cohorts within the collaborative MeDALL (Mechanisms of the Development of Allergy) project. Outcome definitions for IgE-associated and non-IgE-associated asthma, rhinitis and respiratory multimorbidity (first occurrence of coexisting asthma and rhinitis) were based on questionnaires and the presence of specific antibodies (IgE) against common allergens in serum. For each outcome, we used proportional hazard models with sex-puberty interaction terms and conducted a one-stage individual participant data meta-analysis. Results: Girls had a lower risk of incident asthma (adjusted HR 0.67, 95% CI 0.61 to 0.74), rhinitis (0.73, 0.69 to 0.78) and respiratory multimorbidity (0.58, 0.51 to 0.66) before puberty compared with boys. After puberty onset, these incidences became more balanced across the sexes (asthma 0.84, 0.64 to 1.10; rhinitis 0.90, 0.80 to 1.02; respiratory multimorbidity 0.84, 0.63 to 1.13). The incidence sex shift was slightly more distinct for non-IgE-associated respiratory diseases (asthma 0.74, 0.63 to 0.87 before vs 1.23, 0.75 to 2.00 after puberty onset; rhinitis 0.88, 0.79 to 0.98 vs 1.20, 0.98 to 1.47; respiratory multimorbidity 0.66, 0.49 to 0.88 vs 0.96, 0.54 to 1.71) than for IgE-associated respiratory diseases. Discussion: We found an incidence 'sex shift' in chronic respiratory diseases from a male predominance before puberty to a more sex-balanced incidence after puberty onset, which may partly explain the previously reported sex shift in prevalence. These differences need to be considered in public health to enable effective diagnoses and timely treatment in adolescent girls.

How effective is the early support program Babylotse-Plus for psychosocially burdened mothers and their infants? A comparative intervention study.

OBJECTIVES: Our aim was to examine the effects of an early perinatal prevention program offered to mothers and families suffering from significant psychosocial burden. METHODS: All mothers giving birth in a Berlin university hospital during Jan-Aug 2013 were screened with a standardized 27-item questionnaire by trained staff. Mothers with a screening-score ≥ 3, who were not enrolled in other public support programs, were defined as psychosocially burdened. They received a detailed needs assessment and were followed up with counseling. When necessary, affected mothers were voluntarily guided through to specialized 'early support' institutions during the 12-month-intervention period. The historical control group (care-as-usual) consisted of children born at the same hospital the year before.At 12 months postnatally, we interviewed mothers in both groups to assess their stress burden and coping skills by Parenting Stress Index and assessed the current childcare condition. Differences between the groups were compared by multivariable logistic regression analyses adjusting for potential confounders. RESULTS: The intervention group and the control group included 225 and 157 families, respectively. After 12-months, mothers in the 'early support' intervention group had significantly less often depression (adjusted odds ratio 0.25, 95%-confidence interval 0.07-0.94), less often a disturbed relationship with the parenting partner (0.34, 0.10-1.14) and reported reduced stress due to the child's demands (0.40, 0.15-1.10) compared to the control group. Childcare indicators did not differ between the 2 groups. CONCLUSIONS: In mothers at high psychosocial risk, the 'early support' intervention program Babylotse-Plus seemed to reduce the occurrence of depression and several stress indicators in the first postnatal year.

Integrating Clinical and Epidemiologic Data on Allergic Diseases Across Birth Cohorts: A Harmonization Study in the Mechanisms of the Development of Allergy Project.

The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3-20 follow-up periods) carried out in 9 European countries during 1990-1998 or 2003-2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.

Sex-Related Allergic Rhinitis Prevalence Switch from Childhood to Adulthood: A Systematic Review and Meta-Analysis.

BACKGROUND: A sex-related switch in the prevalence of asthma from childhood (male predominance) to adulthood (female predominance) has been described, but for allergic rhinitis this remains unclear. We aimed to examine sex- and age-group-specific differences in allergic rhinitis prevalence by systematically evaluating studies from across the globe. METHODS: A systematic search of MEDLINE and Embase for population-based cross-sectional studies was performed regardless of the language of publication. The search was restricted to the present millennium (2000 to June 2014). Study quality was defined by the sampling method, response rate, sample size, and data collection method. To assess sex differences in the prevalence of self- or parent-reported symptoms of rhinitis, calculated pooled estimates of the male-female ratio (MFR) were obtained using random-effects model meta-analyses due to heterogeneity. A meta-regression analysis was also performed. RESULTS: Out of 6,539 publications identified, 67 cross-sectional population-based studies (291,726 males and 301,781 females) were included in our meta-analysis. In children (<11 years of age) significantly more boys than girls had rhinitis symptoms (MFR 1.21, 95% CI 1.17-1.25), whereas in adolescents (11 to <18 years of age) males were significantly less often affected than females (MFR 0.90, 95% CI 0.85-0.95). No sex-specific prevalence difference was observed in adults (MFR 0.96, 95% CI 0.83-1.17). These findings were consistent in all continents except in Asia, where the male predominance remained beyond childhood. CONCLUSIONS: The male predominance of rhinitis prevalence in childhood changed towards a female predominance in adolescence across the globe, except in Asia. Longitudinal studies are needed to confirm these cross-sectional data and examine possible determinants and underlying mechanisms.

Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes.

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.

Implicit and explicit attitudes towards conventional and complementary and alternative medicine treatments: Introduction of an Implicit Association Test.

This study examined associations between anticipated future health behaviour and participants' attitudes. Three Implicit Association Tests were developed to assess safety, efficacy and overall attitude. They were used to examine preference associations between conventional versus complementary and alternative medicine among 186 participants. A structural equation model suggested only a single implicit association, rather than three separate domains. However, this single implicit association predicted additional variance in anticipated future use of complementary and alternative medicine beyond explicit. Implicit measures should give further insight into motivation for complementary and alternative medicine use.

The development of the MeDALL Core Questionnaires for a harmonized follow-up assessment of eleven European birth cohorts on asthma and allergies.

BACKGROUND: Numerous birth cohorts have been initiated in the world over the past 30 years using heterogeneous methods to assess the incidence, course and risk factors of asthma and allergies. The aim of the present work is to provide the stepwise proceedings of the development and current version of the harmonized MeDALL-Core Questionnaire (MeDALL-CQ) used prospectively in 11 European birth cohorts. METHODS: The harmonization of questions was accomplished in 4 steps: (i) collection of variables from 14 birth cohorts, (ii) consensus on questionnaire items, (iii) translation and back-translation of the harmonized English MeDALL-CQ into 8 other languages and (iv) implementation of the harmonized follow-up. RESULTS: Three harmonized MeDALL-CQs (2 for parents of children aged 4-9 and 14-18, 1 for adolescents aged 14-18) were developed and used for a harmonized follow-up assessment of 11 European birth cohorts on asthma and allergies with over 13,000 children. CONCLUSIONS: The harmonized MeDALL follow-up produced more comparable data across different cohorts and countries in Europe and will offer the possibility to verify results of former cohort analyses. Thus, MeDALL can become the starting point to stringently plan, conduct and support future common asthma and allergy research initiatives in Europe.

Comorbidity of eczema, rhinitis, and asthma in IgE-sensitised and non-IgE-sensitised children in MeDALL: a population-based cohort study.

BACKGROUND: Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in children aged 4-8 years. METHODS: In this prospective cohort study, we assessed children from 12 ongoing European birth cohort studies participating in MeDALL (Mechanisms of the Development of ALLergy). We recorded current eczema, rhinitis, and asthma from questionnaires and serum-specific IgE to six allergens. Comorbidity of eczema, rhinitis, and asthma was defined as coexistence of two or three diseases in the same child. We estimated relative and absolute excess comorbidity by comparing observed and expected occurrence of diseases at 4 years and 8 years. We did a longitudinal analysis using log-linear models of the relation between disease at age 4 years and comorbidity at age 8 years. FINDINGS: We assessed 16 147 children aged 4 years and 11 080 aged 8 years in cross-sectional analyses. The absolute excess of any comorbidity was 1·6% for children aged 4 years and 2·2% for children aged 8 years; 44% of the observed comorbidity at age 4 years and 50·0% at age 8 years was not a result of chance. Children with comorbidities at 4 years had an increased risk of having comorbidity at 8 years. The relative risk of any cormorbidity at age 8 years ranged from 36·2 (95% CI 26·8-48·8) for children with rhinitis and eczema at age 4 years to 63·5 (95% CI 51·7-78·1) for children with asthma, rhinitis, and eczema at age 4 years. We did longitudinal assessment of 10 107 children with data at both ages. Children with comorbidities at 4 years without IgE sensitisation had higher relative risks of comorbidity at 8 years than did children who were sensitised to IgE. For children without comorbidity at age 4 years, 38% of the comorbidity at age 8 years was attributable to the presence of IgE sensitisation at age 4 years. INTERPRETATION: Coexistence of eczema, rhinitis, and asthma in the same child is more common than expected by chance alone-both in the presence and absence of IgE sensitisation-suggesting that these diseases share causal mechanisms. Although IgE sensitisation is independently associated with excess comorbidity of eczema, rhinitis, and asthma, its presence accounted only for 38% of comorbidity, suggesting that IgE sensitisation can no longer be considered the dominant causal mechanism of comorbidity for these diseases.

Impact of chemotherapy and radiotherapy in childhood on fertility in adulthood: the FeCt-survey of childhood cancer survivors in Germany.

PURPOSE: Improved treatment for childhood cancer has led to better survival rates of 83 % today. However, long-term side effects including infertility of pediatric patients receiving oncologic treatment remain unclear. We examined the association of chemotherapy and radiotherapy with infertility in survivors of pediatric cancer. METHODS: A questionnaire on fertility was sent to adult survivors listed in the German Childhood Cancer Registry. Fertility status was defined based on information on attempts to conceive, pregnancies, births, menstrual cycle and previous fertility test results. RESULTS: Therapeutic data were obtained from treatment optimization trials. We included 618 childhood cancer survivors (384 women) who reported information allowing us to classify their current fertility status as 'fertile/probably fertile' or 'probably infertile'. Thirty-one percent of 83 female and 29 % of 117 male survivors reported infertility based on previous fertility tests. 'Probably infertile' adult survivors were more likely to have received pelvic radiotherapy (women: adjusted OR 20.24, 95 % CI 4.69-87.29; men: 12.22; 1.18-126.70) than those who were 'fertile/probably fertile'. Etoposide, particularly ≥5,000 mg/m(2) in women, and carboplatin and/or cisplatin in both sexes seemed to have independent risk potential for infertility. Similarly, cancer treatment during or post-puberty compared to treatment before puberty showed a trend toward increased infertility, particularly in male survivors. CONCLUSIONS: Patients and families need to be informed about fertility-preserving measures prior to and also after chemotherapy and radiotherapy.

Environmental exposure assessment in European birth cohorts: results from the ENRIECO project.

Environmental exposures during pregnancy and early life may have adverse health effects. Single birth cohort studies often lack statistical power to tease out such effects reliably. To improve the use of existing data and to facilitate collaboration among these studies, an inventory of the environmental exposure and health data in these studies was made as part of the ENRIECO (Environmental Health Risks in European Birth Cohorts) project. The focus with regard to exposure was on outdoor air pollution, water contamination, allergens and biological organisms, metals, pesticides, smoking and second hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite exposure assessment. Collaborative analyses with data from several birth cohorts have already been performed successfully for outdoor air pollution, water contamination, allergens, biological contaminants, molds, POPs and SHS. Key success factors for collaborative analyses are common definitions of main exposure and health variables. Our review emphasizes that such common definitions need ideally be arrived at in the study design phase. However, careful comparison of methods used in existing studies also offers excellent opportunities for collaborative analyses. Investigators can use this review to evaluate the potential for future collaborative analyses with respect to data availability and methods used in the different cohorts and to identify potential partners for a specific research question.

Health effects of chronic noise exposure in pregnancy and childhood: a systematic review initiated by ENRIECO.

BACKGROUND: Chronic noise is an environmental pollutant and well-known to cause annoyance and sleep disturbance. Its association with clinical and subclinical adverse health effects has been discussed. OBJECTIVES: This systematic review aimed to examine associations between chronic noise exposure during pregnancy or childhood and health outcomes in early and late childhood. METHODS: Following a systematic electronic literature search (MEDLINE, EMBASE), an additional hand search and a critical evaluation of potential articles by 2 independent reviewers, 29 studies were included: 12 on pregnancy/birth outcomes with samples ranging from 115 to 22,761 and 17 on cardiovascular and immune-mediated health outcomes in childhood with samples ranging from 43 to 1542. Evidence levels (3 to 2++) were rated according to the Scottish Intercollegiate Guidelines Network. RESULTS: Chronic noise exposure during pregnancy was not associated with birth weight, preterm birth, congenital anomalies, perinatal and neonatal death based on 6 cohort, 4 case-control, and 2 cross-sectional studies (highest evidence level 2+). There was some evidence supporting an association of chronic noise exposure with increased systolic blood pressure and stress hormone levels in urine and saliva in children evaluating 2 cohort and 15 cross-sectional studies (highest evidence level 2-). CONCLUSIONS: There seemed to be no associations between chronic noise and pregnancy outcomes based on studies with evidence levels up to 2+. Associations between chronic noise and health in children were based mainly on cross-sectional studies. However, the studies included in this comprehensive systematic review showed a high variation in study design, outcome, exposure and confounder assessments.

Maternal smoking in pregnancy and asthma in preschool children: a pooled analysis of eight birth cohorts.

RATIONALE: Although epidemiological studies suggest that exposure to maternal smoking during fetal and early life increases the risk of childhood wheezing and asthma, previous studies were not able to differentiate the effects of prenatal from postnatal exposure. OBJECTIVES: To assess the effect of exposure to maternal smoking only during pregnancy on wheeze and asthma among preschool-age children. METHODS: A pooled analysis was performed based on individual participant data from eight European birth cohorts. Cohort-specific effects of maternal smoking during pregnancy, but not during the first year, on wheeze and asthma at 4 to 6 years of age were estimated using logistic regression and then combined using a random effects model. Adjustments were made for sex, parental education, parental asthma, birth weight, and siblings. MEASUREMENTS AND MAIN RESULTS: Among the 21,600 children included in the analysis, 735 children (3.4%) were exposed to maternal smoking exclusively during pregnancy but not in the first year after birth. In the pooled analysis, maternal smoking only during pregnancy was associated with wheeze and asthma at 4 to 6 years of age, with adjusted odds ratios of 1.39 (95% confidence interval, 1.08-1.77) and 1.65 (95% confidence interval, 1.18-2.31), respectively. The likelihood to develop wheeze and asthma increased statistically significantly in a linear dose-dependent manner in relation to maternal daily cigarette consumption during the first trimester of pregnancy. CONCLUSIONS: Maternal smoking during pregnancy appears to increase the risk of wheeze and asthma among children who are not exposed to maternal smoking after birth.

Childhood leukemia and its impact on graduation and having children: results from a national survey.

To assess the level of graduation, the wish to have children and the course of pregnancy among former patients with childhood leukemia in comparison to the general German population and depending on gender, a nationwide survey was conducted in 2008. In total 63.6% (1476/2319) of the contacted survivors of childhood leukemia participated (mean age 25.7 years, range 19-43 years). Survivors graduated at higher levels of school compared to the general population, with 48.6% (female) versus 38.0% and 52.6% (male) versus 35.8% (p < 0.001). Also, 93.3% of female and 89.3% of male survivors indicated a similar general wish to have children compared to the general population. Survivors reported parenthood less frequently compared to the general population (p < 0.001). The course of pregnancy in survivors was characterized by fewer abortions (p < 0.001). Having leukemia in childhood and adolescence impairs the likelihood of becoming a parent but reduces neither the wish to have children nor the level of graduation.

Association between self-reported questionnaire data on fertility and results of hormone analyses in women after childhood cancer: a cross-sectional study.

AIM: The aim of this study was to compare self-reported questionnaire-based information on fertility impairment with results from hormone analyses in women who underwent chemoradiotherapy during childhood and adolescence. MATERIAL AND METHODS: In a cross-sectional study, questionnaires and hormone analyses (anti-Müllerian hormone [AMH], follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone) were evaluated in 86 female former pediatric oncology patients in Berlin in 2009. RESULTS: Eighty-six women (median age 23 years, range 19-41) participated in the study with a median follow up of 14 years (range 2-30) after diagnosis. Among women with information on permanent and transient amenorrhea, 9% (5/55) of the women stated that they were permanently amenorrheic. Among women not taking oral contraceptives and giving information on the regularity of their menstrual cycle, 18% (4/22) had an irregular menstrual cycle and 82% (18/22) had a regular menstrual cycle. The median AMH values for women who were categorized as infertile by questionnaire-based information were significantly lower than the AMH values of women who were categorized as fertile by questionnaire (0.05 vs 2.2 ng/mL, P = 0.004). Questionnaire-based categories on the regularity of the menstrual cycle and categories based on AMH values showed a satisfying percentage agreement (66.7%) and were moderately correlated (r = 0.42, P = 0.002). CONCLUSION: Self-reported questionnaire data used to detect fertility impairment has limited correspondence with objectively measured AMH values.

Suspected infertility after treatment for leukemia and solid tumors in childhood and adolescence.

BACKGROUND: With improved cure rates of cancer in children and adolescents, the long-term effects of oncological treatment, including impaired fertility, have become an important clinical issue. METHODS: In 2008, we conducted a nationwide survey in Germany in which we asked 4689 female and male patients who had been treated for cancer in childhood or adolescence for information on menstruation, previous fertility testing (if any), attempts to conceive, and pregnancies. In a complementary study carried out in 2009, 748 former cancer patients in Berlin were offered hormone testing and sperm analysis. The defined criteria for suspected infertility were, in women, anti-muellerian hormone levels below 0.1 ng/mL; in men, FSH levels above 10 IU/L and inhibin B levels below 80 pg/mL, or azoospermia. RESULTS: The respondents to the nationwide survey included 1476 leukemia survivors and 1278 persons who had had a solid tumor. 104 former leukemia patients and 96 former solid tumor patients had already undergone fertility testing, leading to the suspicion of infertility in 26% and 34% of the persons in these respective groups (95% confidence intervals [CI], 18%-34% and 25%-43%). The patients who were tested in the Berlin study included 59 leukemia survivors and 104 persons who had had a solid tumor. The frequency of suspected infertility in these two groups was 25% and 27%, respectively (95% CI, 14%-36% and 18%-36%). CONCLUSION: Up to one-third of adults who undergo fertility testing after having been treated for cancer in childhood or adolescence have suspected infertility. Patients and their parents should be counseled about the possibility of infertility and about fertility-preserving measures.

Age at menarche in childhood cancer survivors: results of a nationwide survey in Germany.

BACKGROUND/AIMS: With rising cure rates of childhood cancer, side effects of treatment are attracting increasing interest. The present analysis evaluates the influence of tumor localization, radiotherapy and chemotherapy on the age of menarche. METHODS: 4,689 former pediatric oncology patients, diagnosed 1980-2004, were contacted in collaboration with the German Childhood Cancer Registry. RESULTS: 1,036 out of 1,461 female participants reported their age at menarche and had an oncological diagnosis before menarche. The median age at menarche was 13 years, compared to 12.8 years in the German general population. A significant delay of menarche was seen in patients with pituitary radiation doses of ≥30 Gy (mean 13.6 years, SD 2.2) compared to <30 Gy (mean 12.5 years, SD 1.4, p = 0.05). Patients with additional spinal radiation were even older at menarche (mean 14.4 years, SD 2.5). Pelvic and pelvic-near radiation significantly delayed onset of menarche (mean 14.0 years, SD 1.9 and mean 14.3, SD 2.6, respectively, p < 0.001). Only some chemotherapeutic agents (carboplatin/cisplatin, etoposide) were associated with a menarcheal delay of <1 year. CONCLUSION: Overall, female childhood cancer survivors showed a normal menarcheal age. Pituitary radiation dosage of ≥30 Gy, spinal and pelvic radiotherapy were associated with a moderate delay in the occurrence of menarche.

Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar.

Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program European Union project, aims to generate novel knowledge on the mechanisms of initiation of allergy. Precise phenotypes of IgE-mediated allergic diseases will be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January 24, 2011, to review current knowledge on the IgE-related phenotypes and to explore how a multidisciplinary effort could result in a new integrative translational approach. This article provides a summary of the meeting. It develops challenges in IgE-related phenotypes and new clinical and epidemiologic approaches to the investigation of allergic phenotypes, including cluster analysis, scale-free models, candidate biomarkers, and IgE microarrays; the particular case of severe asthma was reviewed. Then novel approaches to the IgE-associated phenotypes are reviewed from the individual mechanisms to the systems, including epigenetics, human in vitro immunology, systems biology, and animal models. The last chapter deals with the understanding of the population-based IgE-associated phenotypes in children and adolescents, including age effect in terms of maturation, observed effects of early-life exposures and shift of focus from early life to pregnancy, gene-environment interactions, cohort effects, and time trends in patients with allergic diseases. This review helps to define phenotypes of allergic diseases in MeDALL.

European birth cohorts for environmental health research.

BACKGROUND: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. OBJECTIVES: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. METHODS: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother-child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. RESULTS: Questionnaires were completed by 37 cohort studies of > 350,000 mother-child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12-19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. CONCLUSION: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health.

German translation of the Southampton Needle Sensation Questionnaire: use in an experimental acupuncture study.

OBJECTIVE: To create a German version of the Southampton Needle Sensation Questionnaire (SNSQ) in order to measure deqi (needling sensation) in subjects receiving different forms of acupuncture and to evaluate the translated questionnaire in an acupuncture study. METHODS: A forward and backward translation procedure was applied to create a German version of the SNSQ. Discrepancies between translations were resolved by consensus. Healthy participants from an experimental acupuncture trial were asked to fill in the resulting questionnaire comprising of 17 items (none (0) to intense (3)) and a visual analogue scale (VAS) for pain (0-100 mm) after receiving either sham or real acupuncture with or without stimulation. The questionnaire was validated using factor analysis and correlation analysis. RESULTS: Questionnaires from 63 subjects (mean 27.1 years; 69.8% female) were included in the analysis. Participants tended to score toward the low end of each of the 17 items (mean sum score (± SD): 8.9 ± 7.0). Four factors with eigenvalues > 1 were identified using exploratory factor analysis. Both of the original subscales, aching deqi (AD) and tingling deqi (TD), showed good internal consistency (Cronbach's α: AD: 0.71; TD: 0.78) and medium test-retest reliability (AD: r = 0.538, p = 0.002; TD: r = 0.603, p < 0.001). AD feeling (r = 0.574, p < 0.001) and TD feeling (r = 0.496, p < 0.001) correlated with the VAS for pain. CONCLUSION: Factor structure of the original questionnaire could not be reproduced with the German version of the SNSQ in an experimental setting. The questionnaire could not discriminate between pain and deqi. Further research is needed to create a German tool which is more suitable to measure deqi.

Patient counselling on the risk of infertility and its impact on childhood cancer survivors: results from a national survey.

Fertility can be impaired by radiation and chemotherapy among childhood cancer survivors. Therefore, timely and adequate patient counselling about the risk of infertility and preservation methods is needed. The primary study objective was to assess remembered counselling among childhood cancer survivors. As a second objective, the impact of lacking patient counselling on offspring-related attitudes and behaviour was examined. Counselling regarding the late effects of gonadotoxicity that could be recalled by patients was assessed using a questionnaire sent by the German Childhood Cancer Registry. The questionnaire was answered by 2754 adult childhood cancer survivors (53.1% female, mean = 25.7 years). The proportion of patients who could not remember patient counselling about the late effects of chemo-/radiotherapy on fertility decreased significantly over time. In 1980 to 1984 67%, in 2000 to 2004 50% of the patients reported no memories of counselling (p < .001). Counselled patients feared significantly less that their children may have an increased cancer risk (4.4% vs. 6.7%, p = .03). They were also more likely to undergo fertility testing than patients who could not recall counselling (odds ratio = 2.91, 95% confidence interval [2.12, 3.99]). Patients reported an increased memory of patient counselling over the past 25 years. Still, a 50% rate of recalled counselling shows an ongoing need for adequate and especially sustainable counselling of paediatric cancer patients about infertility and other long-term adverse treatment effects. Those who reported a lack of counselling had offspring-related fears more frequently, which stopped them from having children.