Overview of the study design, participation and field work of the German Environmental Survey on Children 2003–2006 (GerES IV)

International Journal of Hygiene and Environmental Health 215 (2012) 435–448

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Mini-Review

Overview of the study design, participation and field work of the German Environmental Survey on Children 2003–2006 (GerES IV) Christine Schulz ∗ , Margarete Seiwert, Wolfgang Babisch, Kerstin Becker, André Conrad, Regine Szewzyk, Marike Kolossa-Gehring German Federal Environment Agency (Umweltbundesamt, UBA), Dessau-Roßlau, Berlin, Germany

a r t i c l e

i n f o

Article history: Received 8 January 2010 Received in revised form 7 February 2012 Accepted 7 February 2012 Keywords: Children Environment Health Cross sectional study Representativeness Response Human biomonitoring Study design

a b s t r a c t The German Federal Environment Agency carried out its fourth German Environmental Survey (GerES IV), which is the first survey on children only and the environment-related module of the German Health Interview and Examination Survey for Children and Adolescents (German acronym: KiGGS), conducted by the Robert Koch Institute (RKI). The German Environmental Surveys are nationwide population studies conducted to determine the exposure to environmental pollutants, to explore exposure pathways and to identify sub-groups with higher exposure. GerES IV was conducted on randomly selected 1790 children aged 3–14 years from the cross-sectional sample of KiGGS. The participants of GerES IV lived in 150 sampling locations all over Germany. Field work was carried out from May 2003 to May 2006. The response rate in GerES IV was 77.3%. Due to the fact that participation in GerES IV was limited to children that had previously participated in the KiGGS study, the total response rate in GerES IV resulted in 52.6%. Response rates did neither differ significantly between West and East Germany, nor between different community sizes, age groups and gender. The basic study programme included blood samples, morning urine, tap water and house dust as well as comprehensive questionnaire-based interviews. In addition, subgroups were studied with regard to “noise, hearing capacity and stress hormones”, “chemical contamination of indoor air” and “biogenic indoor contamination”. A key element of the field work in GerES IV was a home visit to carry out interviews, conduct measurements and collect samples. An exception was blood sampling which was carried out within KiGGS. The quality of field work, data collection, evaluation, and chemical, biological and physical analyses was successfully evaluated by internal and external quality assurance. This comprehensive overview aims at giving other research groups the opportunity to compare different study designs or to adapt their own design to get comparable results. © 2012 Elsevier GmbH. All rights reserved.

Abbreviations: As, arsenic; BBP, butylbenzylphthalate; BMBF, Federal Ministry of Education (German acronym: Bundesministerium für Bildung und Forschung); BMU, Federal Ministry for the Environment, Nature Conservation and Nuclear Safety and Research (German acronym: Bundesministerium für Umwelt, Naturschutz und Reaktorsicherheit); Cd, cadmium; CAPI, Computer Assisted Personal Interview; COPHES, Consortium to Perform Human Biomonitoring on a European Scale; DBP, dibutylphthalate; DEHP, di(2-ethylhexyl)phthalate; DEMOCOPHES, Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale; EEA, European Environmental Agency; GerES, German Environmental Survey; GM, geometric mean; GSD, geometric standard deviation; GSF, GSF-National Research Centre for Environment and Health, Neuherberg, Germany: re-named to HelmholtzZentrum München – German Research Center for Environmental Health; HBM, human biomonitoring; Hg, mercury; IgE, immunglobulin E; KiGGS, German Health Interview and Examination Survey for Children and Adolescents (German acronym: Kinder- und Jugendgesundheitssurvey); N, sample size; NHANES, National Health and Nutrition Examination Survey; PAH, polycyclic aromatic hydrocarbons; Pb, lead; PCB, polychlorinated biphenyls; PDF, portable document format; QNA, quality-neutral non-respondents (German acronym: qualitätsneutrale Ausfälle: QNA); REACH, Registration, Evaluation and Authorisation of Chemicals; RKI, Robert Koch Institute, Germany; RV95 , reference value; SES, socio-economic status; SPSS, Statistical Package for the Social Sciences; UBA, German Federal Environment Agency; VOC, volatile organic compounds; WHO, World Health Organization. ∗ Corresponding author. Tel.: +49 30 8903 5465; fax: +49 30 8903 1830. E-mail address: [email protected] (C. Schulz). 1438-4639/$ – see front matter © 2012 Elsevier GmbH. All rights reserved. doi:10.1016/j.ijheh.2012.02.002

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Introduction Exposure assessment is one of the key elements of the risk assessment procedure which has been developed to evaluate environmental pollutants. An essential step in exposure assessment is the evaluation of the dose that enters the human body and the analysis of different environmental media that can affect humans. In this sense exposure assessment focuses on the initial portion of the environmental health paradigma: from sources, to environmental concentrations, to exposure, to dose. In studies on human exposure assessment, emphasis is placed on estimating the magnitude, duration, and frequency of exposure, as well as estimating the number of people exposed to various concentrations of the agent in question (WHO IPCS, 2000). Until the mid 1980s knowledge of human exposure to environmental pollutants resulted from occupational studies and small-scale studies conducted on selected population groups in specific areas. The findings of these studies could not be extrapolated to the general population. As a consequence, in Germany epidemiologic studies screening the general population for their exposure to chemicals – especially lead – were launched. Monitoring programmes focus on the determination of the internal exposure by human biomonitoring (HBM), the measurement of concentrations of chemicals or their metabolites in human body fluids on tissues, such as blood or urine. In 1985, Germany started a series of repeated cross-sectional studies: the German Environmental Survey (GerES). GerES is a nationwide population representative study on human exposure to various environmental chemicals and its sources. GerES comprises three main instruments of investigation: HBM, monitoring of the domestic environment, and collecting information on exposure pathways and living conditions via questionnaires. The first three surveys, GerES I in 1985/1986, GerES II in 1990/1992 and GerES III in 1998 comprised only adults – with one exception: 6- to 14-year-old children living in the households of the adult participants were also included in GerES II (Becker et al., 2002, 2003; Hoffmann et al., 2000a,b, 2001; Schulz et al., 2007; Seifert et al., 2000a,b). In the 1980s and early 1990s, the only largescale nation-wide population-based survey with a comprehensive biomonitoring programme comparable to GerES was the National Health and Nutrition Examination Survey (NHANES) in the U.S. conducted by the Centers of Disease Control and Prevention’s (CDC’s) National Center for Health Statistics. NHANES is a series of surveys designed to measure and monitor the health and nutritional status of the U.S. population (CDC, 2009). Among the early studies on human environmental exposure, the “Cadmibel study” is regarded as groundbreaking. From 1985 to 1989 it examined the exposure of the Belgian population to cadmium and its health effects (Buchet et al., 1990; Lauwerys et al., 1993, 1994). In Germany, besides GerES several other projects focusing on human biomonitoring have recently been or are being performed in specific regions on specific age groups. Such projects are the studies in hot spot and control areas of North Rhine-Westphalia (Wilhelm et al., 2007), the sentinal health department project on 10-year-olds in Baden-Württemberg (Link et al., 2007), and the Integrated Exposure Assessment Survey (INES) in Bavaria (Fromme et al., 2007). Important current or recently finished population-based exposure-oriented studies in other countries are e.g. the surveys in Canada (Health Canada, 2010), the Environmental Health ˇ Monitoring System (EHMS) in the Czech Republic (Cerná et al., 2011), the French National Nutrition and Health Program (ENNS): 2001–2006–2010 (Hercberg et al., 2008), the Flemish Environment and Health Study (FLEHS) (Den Hond et al., 2009), the Middle Eastern Regional Cooperation Project, 1996–2000 (Safi et al., 2006), the

investigations in Vietnam (Agusa et al., 2009; Minh et al., 2008). All of these surveys comprise several age groups of participants (among them children) and are/were performed in different regions to explore the exposure of the investigated populations. Children are, for a variety of reasons, particularly vulnerable to the impact of environmental pollutants (EEA/WHO, 2002; Au, 2002; Chaudhuri and Fruchtengarten, 2005). Hence, the protection of children is of particular importance for environmental and health politics. Improving the protection of children from environmentally caused health risks requires the systematic and continuous monitoring of the exposure of children to chemical, biological and physical environmental pollutants. Additionally, the factors influencing their exposure need to be investigated. In 2002, the WHO and EEA issued the joint report “Children’s Health and Environment – A Review of Evidence” (EEA/WHO, 2002) and emphasised a lack of information and research data. Therefore the fourth German Environmental Survey examined only children (GerES IV). Like the preceding GerESs, GerES IV was carried out by the German Federal Environment Agency (UBA) in close cooperation with the “German Health Interview and Examination Survey for Children and Adolescents” (German acronym: KiGGS), conducted by the Robert Koch Institute (RKI) (Kurth et al., 2008). GerES IV consists of the core survey and three additional survey programmes. Fig. 1 outlines the relation of the KiGGS and the GerES IV sample as well as the different additional survey programmes conducted on different subsamples of GerES IV. In this article a comprehensive overview of the study design, participation, and the field work of GerES IV is given for the first time. Detailed method descriptions as well as results on children’s exposure can be found in the specific basic reports and articles covering human biomonitoring, house dust, drinking water, indoor air, and noise (UBA, 2008). Objectives The general objectives of the German Environmental Survey on Children (GerES IV) are the collection, provision, updating and evaluation of representative data for a health oriented environmental monitoring and environmental reporting on a national level. The representative data also serve to: • provide a basis for establishing reference values for the exposure of children to environmental contaminants as a basis for a consistent evaluation throughout Germany, • detect temporal trends and regional differences in exposure, • identify and quantify exposure sources and pathways, • determine connections between certain environmental factors and the health situation of children, • establish concepts for prevention, intervention and reduction strategies in the context of measures of health and environmental policies, • evaluate the success of policy and exposure reduction measures, and • identify emerging chemicals in stored samples with recently developed or future analytical methods, such as phthalates and bisphenol A in urine (Becker et al., 2009). The pilot study of GerES IV The concept of GerES IV was tested in a pilot study with 550 participating children and adolescents aged 0–17 years over one year (from March 2001 to March 2002). The pilot study was carried out in close cooperation with the pilot study of the National Health Interview and Examination Survey for Children and Adolescents of the RKI (Kamtsiuris et al., 2000; Kamtsiuris and Lang, 2000). The

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Fig. 1. The GerES IV sample in relation to the KiGGS sample and the GerES IV subsamples used for the additional survey programmes.

objectives of the pilot study of both surveys were to test the feasibility of different ways to recruit participants, different incentives to increase the motivation for participation, and the suitability of the instruments for different age groups. The results of the pilot study lead to the following important decisions regarding the main phase: • Recruitment of children via inhabitant registries proved to be a viable approach as compared to recruitment via schools/classes (Kamtsiuris and Lang, 2000). • D12.50 was given to each family, as this amount proved most suitable as an incentive for participation compared to other amounts or a gift. • The youngest children included in GerES IV were 3 years old, as from a majority of them blood and urine samples could be taken, whereas only a minority of 2-year-olds or younger children provided these samples in the pilot study. • The oldest children included in the study were 14 years old. The age limit was chosen taking into account the low willingness of older adolescents to participate as observed in the pilot study. The age limit was also set to enable trend evaluations of GerES II data of 1990/1992 (6- to 14-year-old children) and GerES IV data. • The automatic hearing test was performed with children aged 8 years or older, as the pilot study had shown that younger children could not correctly follow the instructions. • The examinations of GerES IV were carried out in the households, as in the pilot study only a very few parents disagreed to a home visit.

• The extensive programme of the pilot study for air pollution levels (outdoor, indoor, and personal sampling over two different timeframes) was too demanding for many participants, who did not return the different samplers correctly after the fixed period. Therefore, only indoor air sampling over one week was conducted in the main phase. • The questionnaires were revised taking account of the experience gained in the pilot study. Study population of GerES IV Sampling procedure for the core survey The participants of GerES IV were randomly selected from the cross-sectional sample of the KiGGS study (Kurth et al., 2008). Due to financial constraints, GerES IV only surveyed a subsample of KiGGS. When limiting the GerES IV sample size, both the experiences made in the pilot study (see above) and statistical aspects were taken into consideration. The following statistical aspects were considered when reducing the sample size: a significance level of 0.1% and a statistical power of 80% were assumed, as well as the variances of the pollutant concentrations observed in previous surveys, in particular during the pilot phase of GerES IV (Becker et al., 2004, 2006; Koch et al., 2007; Schulz et al., 2007; Ullrich et al., 2002; Wittassek et al., 2007). Out of all chemicals analysed in the pilot study, lead in blood had the smallest variation (geometric standard deviation (GSD) of

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1.7; geometric mean (GM) of 23.2 ␮g/l; 362 children aged 3–14 years). Based on this variation, a minimum difference of 8% between the geometric means of two subgroups would be significant with a sample size of N = 1800, and a minimum difference of 14% with N = 600. An extremely high variation was found for toluol in indoor air (GSD = 3.4; GM = 50.7 ␮g/m3 ; 479 samples in GerES I; Krause et al., 1991). For the latter variation, the minimum difference results in 20% and 38% with N = 1800 and N = 600, respectively. The targeted sample size for GerES IV of N = 1800 also facilitated choosing the children from the randomly chosen 150 study locations, since for each of the 12 age groups one child per location was to be surveyed. The sample size was reduced to n = 600 for very costly examinations such as analysis of the chemical (VOC; volatile organic compounds) and biogenic (e.g. mould fungi) indoor contaminants or phthalate metabolites in urine. Sampling for KiGGS and GerES IV was performed at the RKI in cooperation with the Center for Survey Design and Methodology (CSDM; Zentrum für Umfragen, Methoden und Analysen, ZUMA, Mannheim) (Kurth et al., 2008). Children aged between 0 and 17 years who were residents and registered at the registry of residents with their main residence in the Federal Republic of Germany were the target population of the KiGGS study. Children and adolescents living in institutions such as hospitals or nursery homes were excluded. Subjects for KiGGS were identified in two stages, first according to the study location and second according to individuals. Overall, 150 study locations were chosen from the total number of German communities (Fig. 2). For this choice, communities were stratified according to Federal State and type of community (Aschpurwis+Behrens GmbH, 2001). The communities or study locations in each stratum were chosen according to the method described by Kamtsiuris et al. (2007). Disproportionately to the population, 100 study locations in West Germany, 45 in East Germany and 5 in Berlin were randomly selected. This resulted in an oversampling in East Germany to get results with a comparable degree of precision for East and West Germany, respectively (Kurth et al., 2008). During the last year of field work, the sample size for KiGGS was increased in order to attain the planned total number of participants of nearly 18,000. For this, additional 17 communities (including subjects) were included. For GerES IV, no increase in sample size was necessary, since the planned number of participants of about 1800 was already assured by the selection procedure (described below). The KiGGS subjects were chosen, almost simultaneously, at a second sampling stage two months before the scheduled survey period started. From the registry of residents of the chosen communities, exactly 24 personal addresses were drawn within each individual age group. The final random choice took place at the RKI, where 8, 9, or 10 children or adolescents respectively, according to age group and study location, were invited to participate in KiGGS. At a third stage, the subjects for GerES IV were chosen at random from the pool of 3- to 14-year-olds who had agreed to participate in KiGGS and who had also been given an appointment for the KiGGS study. Children whose birthday was within the two weeks of investigation in the respective study location were not included in the GerES IV sample. This restriction was necessary to achieve clear information about the age of the children when linking KiGGS and GerES IV data at a later date. For each study location, the potential GerES IV participants of each age group were arranged in a random sequence (ranking). First, the potential subject on rank 1 was contacted. If he or she was not willing to participate, or was not available for one of the reasons indicated below, the subject on the next higher rank was contacted, and so on. Recruitment for GerES IV began two working days before the start of the survey at the respective study location by the

Table 1 Sample sizes, response rates and reasons for non-response. N Sample (selected for GerES among subjects with consent to participate in KiGGS and appointment for KiGGS interview and examinations) Non-response/undeliverable contacts Failure to appear at an agreed appointment for KiGGS or cancellation of the appointment at short notice or the GerES IV examination could not be carried out due to organisational reasons Communication with the child’s parents impossible due to language problems Household in which the child mainly resides (“separation kids”) is not located at the study location Wrong information on age given by the registry of residents Reduced sample (basis for response calculation) Non-response/undeliverable contacts No time Not interested Unable to reach Because of home visit Withdrawn (child scared to participate) Passive refusal Definitely without giving reasons Too much effort Construction/renovation in/around the house Health problems (child ill) Other reasons Total study participants, response

%

2799

482 447

17.2 92.7

24

5.0

6

1.2

5

1.0

2317 527

100 100 41.6 10.4 10.1 8.0 4.6 4.2 3.4 1.9 1.3 0.6 14.0

1790

77.3

coordination centre in Berlin, the RKI, or at the actual location. Children, who had already participated in the KiGGS prior to the GerES IV, were excluded as blood samples had already been taken. Although determining pollutants present in children’s blood was a fundamental aim of GerES IV, for ethical reasons, an additional puncture to get a second blood sample was not supposed to be justified. This randomly chosen sample of GerES IV comprised 2799 potential subjects aged between 3 and 14 years (Table 1). The reduced sample is described in section “Non-participation”. Sampling procedures for the additional survey programmes Programme “noise, hearing capacity and stress hormones”. The findings from the pilot study showed, that most children aged 8 years or older can perform the automatic screening audiometry successfully. Therefore every 8- to 14-year-old child was supposed to additionally participate in the survey programme “noise, hearing capacity and stress hormones”. Programme “chemical contamination of indoor air”. The subjects for this special survey programme of GerES IV were selected at a fourth stage. For a sub-sample of n = 600 participants, the “chemical contamination of indoor air” was planned to be monitored. Therefore, for each study location one child from each of the following age groups: 3–5 years, 6–8 years, 9–11 years, and 12–14 years (four children per location), was selected from the GerES IV sample. At each study location, the respective first subject from each of the four age groups that was visited at home was asked to participate in this additional investigation. The following two exclusion criteria were applied: (1) the family and the child in question were on holiday during or near the end of the scheduled survey period, i.e. the minimum sampling period of 5 days or the maximum sampling period of 8 days could not be met, or (2) the family could not be burdened with the extensive programme. If one of these criteria was met, or if the family was not willing to participate in this extensive programme, then the next subject of the respective age group that was visited at home was selected for this investigation.

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Fig. 2. Study locations for the German Environmental Survey on Children 2003–2006 according to Kamtsiuris et al. (2007).

During the first two weeks of field work (19 May–8 June 2003), thus in the first three study locations, not all passive samplers for monitoring VOC in indoor air were available. Therefore, the indoor air programme started later and the targeted sample size was reduced to 588. To include 588 participants in the programme, 698 families from 147 study locations were identified for participation. Programme “biogenic indoor contamination”. For the monitoring of “biogenic indoor contamination”, a nested case–control study was conducted. As a precondition for selecting cases and controls, there had to be complete blood examinations regarding specific IgE antibodies for 20 widespread allergens (Schlaud et al., 2007) as well as for 5 indoor-specific mould fungi and Alternaria alternata (test by the company Matritech/ADL, Freiburg). All children showing a positive test result for Aspergillus spec., Penicillium crysogenum (notatum), Aspergillus versicolor, Wallemia sebi or Eurotium spp were defined as being suitable cases. A test result of class 1 or higher (≥0.35 kU/l) was regarded as positive. For each case, 8 subjects without positive test result (controls), were randomly selected and invited to participate in this special study (assuming a participation rate of 50%). The random selection was conducted safeguarding that

the criteria age, gender, and survey period were the same among the controls and the cases (frequency matching). Non-participation Non-participation in the core survey From the total sample N = 2799, all quality-neutral nonrespondents (German acronym: QNA) were eliminated. QNA covered the following reasons for not participating: unknown person/wrong address/non-existing address; deceased; household in which the child mainly resides (“separation kids”) was located somewhere else than the study location; wrong age information given by the registry of residents; communication with the child’s parents impossible due to language problems; failure to appear at an agreed appointment for KiGGS or cancellation of the appointment at short notice or the GerES IV examination could not be carried out due to organisational reasons (Table 1). All in all, 482 cases were defined as QNA, resulting in a reduced sample of 2317 cases for GerES IV. This sample size was the basis for calculating the response rate. Out of this reduced sample, 53 families could not be contacted at any time. 474 families were not willing to participate, reporting

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Table 2 Response based on all KiGGS participants selected for GerES IV stratified by sampling characteristics socio-economic status, and season of investigation. Participating familiesa (n) Total Region East Germany West Germany Berlin Community size <100,000 inhabitants ≥100,000 inhabitants Age group 3–5 years 6–8 years 9–11 years 12–14 years Gender Male Female Socio-economic status Low Medium High Missing Season May–October November–April + May 2006

Refused participationb (n)

Families unable to reachc (n)

Response GerES IVd (% with CI)

1790

474

53

77.3 (±1.7)

536 1194 60

157 302 15

12 35 6

76.0 (±3.2) 78.0 (±2.1) 74.1 (±9.5)

901 889

229 245

17 36

78.6 (±2.4) 76.0 (±2.5)

443 449 449 449

109 97 130 138

12 21 13 7

78.6 (±3.4) 79.2 (±3.3) 75.8 (±3.5) 75.6 (±3.5)

883 907

236 238

23 30

77.3 (±2.4) 77.2 (±2.4)

414 853 504 19

157 219 90 8

18 19 15 1

70.3 (±3.7) 78.2 (±2.5) 82.8 (±3.0)

820 970

194 280

18 35

79.5 (±2.5) 75.5 (±2.4)

Note: n, number of cases; CI, 95% confidence interval. a Participating families: families who underwent an environmental home visit and a health examination. b Refused participation: contacted families who refused to participate in GerES IV, or who later withdrew their participation offer. c Families unable to reach: families to whom no contact could be established. d Response GerES IV: participating families/(families who participated, refused to participate, or could not be contacted). Basis for response calculation: N = 2317 KiGGS participants selected for GerES IV.

diverse reasons for this (Table 1). The most common reason given by the families was “no time”, followed by “not interested, not convinced by the sense and purpose of the survey”. The “home visit” was the third most common reason for refusal. 405 (85.4%) of these 474 families not willing to participate, answered a short questionnaire regarding important environmentally related characteristics (e.g. heating with wood or coal, fish consumption, amalgam fillings in teeth). A comparison of participants and non-participants revealed hardly any difference between the two groups. Additional information on GerES IV non-participants could be retrieved from KiGGS data, which showed that the general health of the children, assessed by their parents, and the proportion of mothers who smoked did not differ significantly between participants and non-participants. These results prove the representativeness of the GerES IV sample with regard to key health- and environment-related characteristics. Non-participation in the additional survey programmes Programme “noise, hearing capacity and stress hormones”. The number of non-participants, the percentage of QNA (quality-neutral non-respondents), and the reasons for not participating in the survey programme “noise, hearing capacity and stress hormones” did not differ significantly from those of the age group of the 3- to 7-year-olds. 9% of the children failed to perform the automatic hearing test. Programme “chemical contamination of indoor air”. Of the 689 subject families selected for participation in the survey programme “chemical contamination of indoor air”, 104 did not participate for the following reasons: 70 of the families selected could not be burdened with the comprehensive and extensive programme. With 20 families, it was to be expected that neither the minimum nor the maximum collection time could be kept. 14 families were not willing to participate in this survey programme. A further 5 families did not send back the passive samplers.

Programme “biogenic indoor contamination”. 508 out of the 1038 subject families who were asked to participate in the nested case–control study on “biogenic indoor contamination”, refused to do so. Data of 7 participants could not be used (e.g. child was no longer living in the apartment). Participation Participation in the core survey 1790 children were enrolled in GerES IV, thereby attaining approximately the desired number of participants for the study. 907 were girls, 883 boys. 232 out of the study population of 1790 children had a migration background. Due to the design strategy, the response rate can be defined in 2 different ways, (1) as the GerES specific and (2) as the total response rate. (1) Out of all children selected for participation in GerES IV (N = 2317), 77.3% actually took part. (2) But as only children could be selected for GerES IV who also took part in KiGGS, the non-response in KiGGS has also to be taken into account when computing a total response rate. Since in the KiGGS study 68.1% of children aged 3–14 years participated, multiplying this number with the GerES IV specific response rate of 77.3%, results in a total response rate of 52.6%. The smaller overall response is plausible and can be explained by the additional time needed for the investigations (2 h for KiGGS and 1.5 h for GerES IV). The response rate is in the range of the response rates of comparable studies conducted in Germany recently (Hoffmann et al., 2004; Latza et al., 2004). Table 2 shows the number of participants and the response rates by age group, gender, community size, region (East/West Germany), socio-economic status (SES), and season, based on all children selected for GerES IV. The response rates vary minimally between age groups and genders as well as East and West Germany, when either the GerES specific response rates or the total response rates were compared. Though in the KiGGS study the participation was lower in large cities (≥100,000 residents) than in smaller communities (Kurth et al., 2008), participation in GerES IV did not differ

C. Schulz et al. / International Journal of Hygiene and Environmental Health 215 (2012) 435–448 Table 3 Number and percentage of completed questionnaires, available samples, and measurements in GerES IV. Instrument/sample/measurement

N

%

Questionnaire on residential environment Documentation questionnaire Parents’ questionnaire Drinking water sample Morning urine sample House dust sample Blood sample Children’s questionnaire (children aged 8–10 and 11–14) Noise level measurement (children aged 8–14) Audiometry (children aged 8–14) Interview-guided questionnaire regarding chemical indoor air pollution (only participants of this programme) Self-administered questionnaire regarding chemical indoor air pollution (only participants of this programme) Indoor air sample

1790 1790 1789 1788 1734 1623 1560 1042

100 100 99.9 99.8 97.1 90.7 87.2 99.4

1039

99.1

959 579

91.5 100

576

99.5

579

100

by community size due to the GerES sampling strategy of recruiting participants in each sampling location until the fixed number of 12 was reached. Data on SES suggest a slight bias, as families with a low status tended to refuse participation more often than families with a higher status. In addition, it could be observed that during the cold season (November–April) participation was lower than during the warm season (May–October). To avoid a seasonal bias, neighbouring areas were visited in different seasons. Participation in the additional survey programmes Programme “noise, hearing capacity and stress hormones”. The final sample considered for all noise related analyses consisted of 1048 children 8–14 years of age. Programme “chemical contamination of indoor air”. 579 children aged 3–14 successfully participated in the programme “chemical contamination of indoor air” (297 girls, 287 boys). In relation to the 689 selected subject families, this meant a participation rate of 84.0%. With regard to the sampling characteristics, there were no significant differences in the participation rate in this subsample, either, so that the composition of this sub-sample was nearly identical to that of the entire sample of GerES IV (data not shown). However, subjects with a low SES participated somewhat less – even though not significantly so – in this comprehensive programme, since it was harder on families with a low SES than on families with a higher SES. Programme “biogenic indoor contamination”. The final sample of this nested case–control study resulted in 523 (50.4%) participating families supporting utilisable data, 66 of which were cases and 457 controls. The completeness of the participants’ data records regarding the individual survey instruments was very good, i.e. between 80% and 100% (Table 3). Representativeness, weighting The target population of the GerES IV sample consisted of 9,785,494 children living in Germany aged between 3 and 14 years (Source: Mikrozensus, validation date 31 December 2004, issued by the German Federal Statistical Office, Statistisches Bundesamt). The comparison between the composition of this target population and the GerES IV sample realised is shown in Table 4.

441

Table 4 Composition of GerES IV sample (N = 1790) and target population of children aged 3–14 years stratified by sampling characteristics. Population N = 9,785,494

GerES IV sample N = 1790

Region East Germany West Germany Berlin Community size <100,000 inhabitants ≥100,000 inhabitants Age group 3–5 years 6–8 years 9–11 years 12–14 years Gender Male Female

N

%

%

536 1194 60

29.9 66.7 3.4

11.7 85.0 3.3

1339 451

74.8 25.2

72.9 27.1

443 449 449 449

24.8 25.1 25.1 25.1

23.5 24.7 24.4 27.4

883 907

49.3 50.7

51.3 48.7

Source of target population data: Microcensus, validation date 31 December 2004, issued by the German Federal Statistical Office, Statistisches Bundesamt).

The KiGGS sampling procedure was carried out disproportionately in favour of East Germany to ensure sufficient sample size for analyses stratifying according to residence in former East and West Germany (Kurth et al., 2008). This “oversampling” of East Germany is also reflected in the GerES IV sample. Compared to the population, children from East Germany are present at a disproportionate rate in the sample realised. As the data presented in Table 4 illustrate, children from communities with less than 100,000 inhabitants are disproportionately overrepresented in GerES IV. However, this is not due to the sampling strategy but to the higher willingness of this group to participate. By weighting the cases, the proportions of the sampling characteristics in the sample were adjusted to those present in the target population. Therefore the representativeness of the GerES IV results remained assured. The calculation of the weighting factors was done by the RKI in cooperation with ZUMA, Mannheim. Criteria for selecting substances for analysis in GerES IV The study parameters in GerES comprise substances known or suspected to cause adverse health effects: neurotoxins (Pb, Hg, phthalates); carcinogenic/cocarcinogenic substances (PAHs, benzene, halogenated volatile organic compounds, As, Cd); substances that cause disorders or irritation of the respiratory tract, allergies and asthma (excrements of dust mites, allergens on pet hairs, fungal spores, volatile organic compounds, formaldehyde and carbonyls); substances that have a possible effect on development with potentially long-term consequences (such as DEHP, PCB). In addition, the selection of the substances was determined by 3 main criteria: • The availability of well-established analytical methods suited to study a large number of subjects including the availability of control standard or reference materials for internal and external quality control as well as certification procedures. • The relevance of the substance for environmental and health policy, such as the assessment of prevention, intervention and reduction measures; sustainability assessment, national and international obligations. • Their frequency of occurrence in the environment. • Tables 6 and 7 give an overview of the substances analysed in the samples in GerES IV.

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Table 5 Questionnaires applied in GerES IV. Questionnaire

Answered by

Main topics

Questionnaire on residential environment Documentation questionnaire (interview-guided)

Interviewers

Type of house, streets and surrounding area as well as type of housing neighbourhood

All parents; interviewers

Parents’ questionnaire (interview-guided)

All parents

Children’s questionnaires (interview-guided) Questionnaire on chemical indoor air contamination (interview-guided) Questionnaire on chemical indoor air contamination (self-administered) Questionnaire on biogenic indoor contamination (interview-guided) Non-responder questionnaire (interview-guided)

Children aged 8–10 (version I); children aged 11–14 (version II) Parents participating in this programme; interviewers Parents participating in this programme All parents participating in the case–control study Parents who refused participation

Documentation and additional questions regarding sampling and measurements: morning urine; first flush and random drinking water; contents of vacuum cleaner bags; noise level measurement in front of child’s room and hearing test Characteristics of the home; surroundings of the home; use of chemical products in the household; time spent at different locations; exposure to second hand smoke; dental health status; nutrition; potentially environmentally caused irritations; body ornaments and clothing; noise annoyance; potential adverse effects of noise on child; specific questions on exposurerelevant, age-dependent behaviour (e.g. playing on the floor), which was only addressed to parents of children aged 3 to 10 Music listening habits; hearing disorders; noise annoyance; potential adverse effects by noise and exposure to second hand smoke Documentation of the sampling; characteristics of the room where the sampling was done Exposure-relevant activities in the room with the passive samplers Documentation of the samplings and additional questions regarding rooms and relevant behaviours Exposure-related living conditions and behaviours: heating, fish consumption, amalgam fillings, breast feeding

Instruments: questionnaires and specimen sampling The GerES IV survey comprised standardised questionnaires, human biomonitoring (blood and morning urine samples taken from the children), an indoor monitoring (house dust and indoor

air), and a drinking water monitoring (drinking water taken from the kitchen tap). For children aged 8 years or older, the programme was extended by physical measurements (noise level measurement and screening audiometry) in the programme “noise, hearing capability and stress hormones” and by an additional interview.

Table 6 Samples and parameters analysed in GerES IV. Group of substances

Elements/heavy metals Persistent organic pollutants – POPs

Phthalates

Flame retardants Bisphenol A Dialkyl phosphates Pyrethroids

Type of sample/parameters Blood

Morning urine

Tap water

Cd, Pb, Hg DDE, HCB, ␣-,␥-, ␤-HCH, PCB 28, 52, 101, 138, 153, 180

Sb, As, Cd, Ni, Hg, Tl, U

Cd, Cu, Pb, Ni, U

ETS marker Stress hormones VOC incl. carbonyls

Indoor air

DDT PCB 28, 52, 101, 138, 153, 180, ␥-HCH DEHP metabolites and othersa

BPA total DMP, DMTP, DMDTP, DEP, DETP, DEDTP Metabolites: cis- and trans-DCCA, DBCA, F-PBA, 3-PBA

Further biocides Chlorophenols PAH metabolites

House dust

PCP and others b 1-Hydroxypyrene and othersc Nicotine, cotinine Cortisol, adrenalin, noradrenalin

DEHP, DMP, DEP, BBP, DiBP, DnBP, DnOP, DEHT (DINCH) TCEP, TBEP, TEHP, TPP, TCP

Cyfluthin, ␭-Cyhalothrin, Cypermethrin, Deltamethrin, Emphethrin, d-Phenothrin, Pemethrin Chlorpyrifos, Eulan, Metoxychlor, Propoxur, (PBA) PCP

From n-Hexane to n-Hexadecan

Phthalates: DEHP, di(2-ethylhexyl)phthalate; DMP, dimethylphthalate; DEP, diethylphthalate; BBP, butylbenzylphthalate; DiBP, diisobutylphthalate; DnBP, di-nbutylphthalate; DnOP, di-n-octylphthalate; DEHT, di(2-ethylhexyl)terephthalate; DINCH, diisononyl 1,2-cyclohexanedicarboxylic acid. Flame retardants: TCEP, tris-(2-chloroethyl)-phosphate; TBEP, tris-(2-bytoxyethylen)-phosphate; TEHP, tris-(2-ethylhexyl)-phosphate; TPP, triphenylphosphate; TCP, triscresylphosphate. Dialkyl phosphates: DMP, dimethyl phosphate; DMTP, dimethyl thiophosphate; DMDTP, dimethyl dithiophosphate; DEP, diethyl phosphate; DETP, diethyl thiophosphate; DEDTP, diethyl dithiophosphate. Metabolites of pyrethroides: cis-DCCA and trans-DCCA, cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1carboxylic acid; DBCA, 3-(2,2-dibromvinyl)-2,2dimethylcyclopropan; F-PBA, 4-fluoro-3-phenoxybenzoic acid; 3 PBA, 3-Phenoxybenzoic acid. a Mono(2-ethylhexyl)phthalate (MEHP), 2-ethyl-5-hydroxy-hexylphthalate (5OH-MEHP), 2-ethyl-5-oxohexylphthalate (5oxo-MEHP), mono(2-ethyl5carboxypentyl)phthalate (5cx-MEPP), mono(2-carboxymethylhexyl)phthalate (2cx-MMHP), mono-n-butylphthalate (MnBP), mono-iso-butylphthalate (MiBP), mono-benzylphthalate (MBzP), mono(4-methyl-7-hydroxyoctyl)phthalate (OH-MiNP), mono(4-methyl-7-oxo-octyl)phthalate (oxo-MiNP), mono(4-methyl-7carbooxyheptyl)phthalate (cx-MiNP). b Monochlorophenol (MCP), dichlorophenol (DCP), trichlorophenol (TCP), tetrachlorophenol (TECP). c 1-, 2,9-, and 3-hydroxyphenanthrene, 1,2-phenanthrendihydrodiol, 9,10-phenenanthrendihydrodiol, phenanthren-1,2,3,4-tetrol.

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Table 7 Samples and parameters analysed for the monitoring of “biogenic indoor contamination” in a nested case-control study of GerES IV. Parameters

Type of sample Serum

Specific IgE antibodies: Penicillium chrysogenum (notatum), Aspergillus fumigates, Cladosporium herbarum, Aspergillus versicolor, Alternaria alternata, Wallemia sebi, Eurotium spp., Felis domestica, Dermatophagoides pteronyssinus, Dermatophagoides farinae Culturable mould spores Total spore count Cat allergen: Felis domestica (Fel d 1) House dust mite allergen: Dermatophagoides pteronyssinus (Der p 1), Dermatophagoides farinae (Der f 1)

Outdoor air

Indoor air

Floor dust

×

× ×

×

Mattress dust

×

Questionnaires/interviews Carrying out GerES IV in conjunction with KiGGS had the enormous advantage that KiGGS already surveyed questions that also played a role in interpreting the GerES IV data. They did not have to be asked again for GerES IV and could nevertheless be used for the GerES IV analysis. These questions referred to, among others, sociodemographic information (e.g. education, employment, income); personal data (parents, child, siblings); health related behaviour and risks (exposure to tobacco smoke (Conrad et al., 2010), nutrition, breast feeding status, physical exercise); social, physical, and emotional health; living conditions, and medical care (Hölling et al., 2007). In GerES IV, several standardised interviewer-guided questionnaires and a self-administered questionnaire were used (Table 5). From May 2003 (beginning of field work) until the end of 2004, the environmental interviewers used paper versions of the respective standardised questionnaires to fill in the information given by parents and children with a pencil. From January 2005 until May 2006 (end of field work), the data were recorded as a CAPI (Computer Assisted Personal Interview) using a laptop computer. The data entry masks were created by the company Statistik-Service Dr. Gladitz, Berlin, using Data Entry 4.0 (SPSS Inc., Chicago, IL). The GerES IV questionnaires can be downloaded as PDF files from the UBA website (UBA, 2008). Human biomonitoring HBM is defined as the measurement of concentrations of chemicals or their metabolites in human biological media such as blood, urine, or breast milk. HBM is considered as the method of choice to determine the internal exposure of the population, population groups or individuals thus supplying a basis for estimating health risks and – if necessary – for risk management (Angerer et al., 2007). In GerES IV blood and morning urine samples were taken – provided parents had given their consent – and analysed for environmental contaminants. When taking the blood sample for the KiGGS study, an additional tube (Vacutainer® diagnostics tube containing the anticoagulant sodium heparin, Becton Dickinson, Heidelberg, Germany) was filled with blood (2 ml for children aged 3–6, 6 ml for children aged 7–14). Thus it was assured that only one puncture had to take place. All children who did no longer wear diapers at night were asked to collect their entire morning urine, i.e. the urine present after a night’s sleep. Cleaned and decontaminated (cleaned in a dishwasher, rinsed with 1.3% nitric acid and double-distilled water) 750 ml toilet seat inserts (Tyco Healthcare Deutschland GmbH, Neustadt/Donau, Germany) for collecting the samples were provided to parents of children aged 3–4 years (for girls optionally up to 6 years after consulting with the parents). Parents of older children were provided with cleaned and decontaminated 1 l wideneck square vessels (Kautex, Bonn-Holzlar, Germany). All parents

× ×

were provided with the respective information sheet on correct sampling. At the examination centres, the urine samples were transferred into 6.5 ml, 13 ml and 15 ml tubes (Sarstedt, Nürmbrecht, Germany), and these tubes were stored deep frozen (−20 ◦ C) until analysis. The parameters analysed in the blood and urine samples are given in Table 6. Indoor monitoring Children spend about 60–80% of the day in their homes, depending on season, day and age (Conrad et al., 2012). Spending so much time indoors makes the importance of the indoor air quality even greater. Additionally, a clean environment at home is very important for the children’s health (WHO, 2010). Therefore, the examination of chemical pollutants and biological agents in house dust and in indoor air was included in GerES IV. House dust For examination of house dust the participant supplied the complete vacuum cleaner bag. The whole bag or its contents subsequently were transferred to vacuum compound plastic bags (MR-Verpackung, Walsrode, Germany) and stored at room temperature as cool as possible until transport to Berlin within one week. As the samples possibly contained chewing insects, they were first stored at −20 ◦ C for at least half a year. Then they were kept at a dry and cool place until preparation of the analysis (sieving, fraction <63 ␮m). The parameters (see section “Criteria for selecting substances for analysis in GerES IV”) analysed in the house dust samples are given in Table 6. Chemical contamination of indoor air In order to determine the chemical pollutants in indoor air, three types of passive samplers (Perkin Elmer Tenax tubes, Sigma Aldrich Supelco, Chemie, Teufkirchen, Germany; 3M OVM-3500, Coenen Neuss GmbH, Neuss, Germany and SKC UMEx-100, Scanntec Lab AB, Sweden) were used for the duration of one week (ISO, 2003; Ullrich and Nagel, 1996; Ullrich et al., 1999, 2002). The samples were taken in the room in which the children usually spent the most time of a day (24 h). At the end of the sampling period, participants sent the passive samplers together with the questionnaire on chemical contamination of indoor air to UBA by mail. The SKC UMEx-100 samplers were stored frozen (−20 ◦ C), whereas the other samplers were stored in an exsiccator until analysis. Biogenic indoor contamination According to the WHO (2009) dampness and mould in indoor environments are associated with health problems like upper respiratory tract symptoms and asthma exacerbation. To examine the relationship between sensitisation against mould spores and the occurrence of mould in household, a case–control study was conducted. In this nested case–control study, dust measurements were performed in the child’s room in order to detect biogenic indoor

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pollutants (mould fungi, dust mite allergens, allergens adhering to cat hair). Dust samples were collected with a special sampler (ALK Scherax, Wedel, Germany) on a floor area of 4 × 0.5 m2 for analysis of culturable fungi in the 63 ␮m fraction. Dust mite and cat allergens were determined from collected mattress dust. Culturable mould fungi present in the indoor air were collected by means of impaction (MAS-100® ) approx. 1.5 m above the floor. Cultivation was performed on dichlorane glycerol agar (DG18 agar) and malt extract agar (MEA) in compliance with VDI 4300-10. The total number of mould spores in air was analysed microscopically after slit impaction on glass slides (PS 30® by the company Umweltanalytik Holbach, Germany). Drinking water Drinking water is one of the most important nutrients (WHO, 2003). In Germany, the quality of drinking water distributing by the water suppliers ranges from good to very good and the microbiological, chemical and physical requirements set out by the German Drinking Water Ordinance 2001 (TrinkwV, 2001) have been largely satisfied. But some deterioration of drinking water quality can be traced to house installation systems (Grummt, 2007; Völker et al., 2010). Therefore, in all households, drinking water samples were taken from the tap normally used by the participants to draw water for cooking and drinking. Water standing in the water pipe for at least 4 h during the night was collected in a standardised procedure by the residents (first draw samples in cleaned and decontaminated 1/2 l square vessels, Kautex, Bonn-Holzlar, Germany). All parents were supplied with the respective information sheet on correct sampling. An additional sample (in cleaned and decontaminated 1 l square vessels, Kautex, Bonn-Holzlar, Germany) was taken randomly from the same tap in accordance with the recommendation on the “Evaluation of drinking water quality with respect to the parameters lead, copper and nickel” (UBA, 2004) by the interviewer. The samples were stored at room temperature (as cool as possible) until analysis. They were analysed (see Table 6) for their contents of the elements cadmium, cooper, lead, and nickel, which may enter and dissolve in water through corrosion of pipe and fitting materials. Additionally uranium was measured. As in the preceding years elevated uranium concentrations in drinking water had been reported in increasing numbers from the German states (Konietzka et al., 2005), it was important to gain a systematic overview of the situation in Germany. Noise, hearing capacity and stress hormones Noise affects children in many ways. Exposure to transport noise can lead to annoyance, stress response, cognitive impairment and possibly cardiovascular problems (Babisch, 2003; Babisch et al., 2009, 2012; Maassen et al., 2001; Zuurbier et al., 2007). Therefore, for children aged 8 years or older, a screening audiometry was performed by means of an automatic pure tone audiometer (AURITECT, Type AT 409, Germany), in combination with circumaural audiometry headphones (Sennheiser, Type HDA 200), which had a high passive ambient noise attenuation. The audiometers and headphones utilised were in compliance with the requirements of IEC 60645-1 (DIN EN 60645-1, 2002). Additionally traffic noise was measured outside the child’s bedroom window. The noise level meter used (NORSONIC, Type 116) was in compliance with the requirements of DIN EN 60804 or the new DIN EN 61672-1 (DIN EN 61672-1, 2003), respectively. The basic conditions of the measurements (among others, time of day at which the noise level was measured and which is taken into account for the analysis) as well as the measured average A-weighted noise

level were recorded in the documentation questionnaire (see section “Instruments: questionnaires and specimen sampling”). The children were asked about ear trouble in connection with loud noise events and about their music listening habits according to the standardised interview-guided children’s questionnaire (see section “Questionnaires/interviews”). Morning urine was analysed for stress hormones (cortisol, adrenaline and noradrenaline) (Babisch, 2003). Analyses All samples were coded before analysis and analysed in a randomised sequence to avoid observer bias. Part the chemical analyses was conducted by external laboratories. Contractors had to meet precision and accuracy standards in their internal quality assurance, and had to take part successfully in round robin tests. In GerES IV the external laboratories were: the Department of Hygiene, Social and Environmental Medicine at Ruhr-University Bochum, the Institute and Out-patient Clinic for Occupational, Social and Environmental Medicine in Erlangen-Nürnberg, the University of Rostock, Biochemical Institute for Environmental Carcinogens in Großhadern, EUKOS Umweltanalytik Nord GmbH in Plön; Eurofins (former ERGO) in Hamburg, ADL Matritech GmbH in Freiburg, Bioanalytisches Forschungslabor von Prof. Schöneshöfer in Berlin, Labor Dr. Rabe HygieneConsult in Essen, and AnBUS e.V. in Fürth. The laboratories of the Federal Environment Agency (UBA) performed heavy metal measurements in blood and tap water, catecholamines in urine as well as VOC and aldehydes in indoor air. The UBA were also part of the quality control system. To ensure quality, control standards and reference materials were run together with the samples on a daily basis in all laboratories. External quality control was achieved by regular participation in intercomparison programmes organised by the German Society for Occupational and Environmental Medicine, e.g. Further information about the analytical methods was given in the basic reports and publications. Field work Field work of KiGGS and GerES IV was conducted from May 2003 to May 2006 (Hölling et al., 2007). For GerES IV, the entire logistic infrastructure of the KiGGS study was used. This included route planning, information dissemination and public relation work as well as recruiting subjects, providing rooms, organising removals from one study centre to the next as well as transporting samples and materials to and from Berlin. During this 3-year field work period, three survey teams comprising one paediatrician, assistant medical technician, child nurse and two interviewers travelled through Germany. They followed a defined route, stayed in each of the selected study locations for two weeks, and examined and interviewed children and parents ready to participate. The sampling locations were visited in an elaborate sequence to balance regional and seasonal effects and avoid bias (Hölling et al., 2007). The majority of the field work for GerES IV was performed by the environmental interviewer of the respective KiGGS team (Hölling et al., 2007). The starting point at each study location was a study centre consisting of 4–6 rooms, usually located on the premises of the local health authority or other communal institutions (Hölling et al., 2007). In this centre, the examinations and interviews for the KiGGS study took place, including blood sampling, as well as handling and storage of samples for both KiGGS and GerES IV. An essential part of GerES IV was a home visit of about 1 1/2 h, during which parents and children aged 8 years or older were interviewed, the samples collected, and the measurements performed.

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In front of the apartment, the environmental interviewer determined the Gauß-Krüger coordinates and documented information about the residential environment such as traffic and housing. All the examinations, measurements, interviews, etc. performed in KiGGS and GerES IV had been documented in detail in an operations manual developed jointly by the RKI and the UBA. This RKI/UBA internal manual furthermore defined the entire project management, the team member tasks, the field work process as well as the quality assurance measures (standard operating procedures). Shortly before the start of field work, team members and replacement personnel underwent a comprehensive training course lasting several weeks and accompanied by an external quality assurance (Hölling et al., 2007). The operations manual was available as training documentation and a reference book during field work. During field work, the environmental interviewers underwent a random evaluation during home visits in 47 homes. This quality control measure was supervised by the external quality assurance GSF (GSF-National Research Centre for Environment and Health, Neuherberg, Germany; re-named to HelmholtzZentrum München – German Research Center for Environmental Health; Filipiak-Pittroff and Wölke, 2007, 29 controlling visits), by the UBA (7 controlling visits) and by the RKI (11 controlling visits). Apart from the conduct of the home visits, the preparation, the final sample handling and data administration/data storing were evaluated. Also, work processes performed by the other field personnel were checked as far as they were relevant to the progress of GerES IV. To assure a consistent approach, all the work processes to be performed in connection with GerES IV were evaluated according to predefined quality assurance criteria. The quality assurance expert informed the environmental interviewers about any findings directly after the controlling visit. The evaluation results were also supplied to all partners concerned with quality assurance in form of informational reports. Experiences or shortcomings relevant to more than one team as well as suggestions for improvement were promptly communicated to the environmental interviewers of the other teams. Quality of data entry into a database of the data written down on paper in the field was checked in a random sample of 10% of the filled-in questionnaires. The total amount of errors amounted to 0.15%, thus fulfilling the maximum tolerable error margin of 0.20% predefined by UBA and RKI. Starting in January 2005, data were entered by the environmental interviewers directly into their notebook PCs using the SPSS application “Data Entry”. For the shift from paper-based questionnaires to CAPI, interviewers underwent intensive training. This training as well as the first round of data entry by CAPI was accompanied by the external quality assurance expert. The advantages of data collection via CAPI were (a) a faster performance of interviews, and (b) immediate detection of implausible or inconsistent entries by automatic test routines. Thus, open questions could be clarified right on the spot.

A scientific advisory board was employed to support UBA and RKI for the duration of both surveys. This board regularly evaluated the current status of field work, made recommendations if necessary, based on the quality control reports, and commented on the concepts for scientific analyses and use of the data.

An appropriate and comprehensive communication to the participating child and their parents is an ethical issue related to studies on children (Pedersen et al., 2007). Therefore, every participant was informed about the concentrations of the analysed substances in her/his blood, urine, drinking water and indoor air sample (Helm et al., 2000). This reporting of individual results did not only meet ethical demands, but was also an important incentive for participation. A letter with results was sent immediately when the analyses of one group of substances were completed, as for ethical reasons elevated concentrations of environmental pollutants had to be communicated as fast as possible. In the case of elevated findings the most common exposure sources were specified in the letter and, if applicable, recommendations for exposure reduction were given. For additional support a hotline to a medical doctor of the GerES team was provided. For medical follow-up the participants were encouraged to turn to an outpatient clinic for environmental medicine (a list of clinics was provided in the letter) or to their family physician. To decide whether a given body burden should be regarded as “elevated” or not, the HBM-values and the reference values derived by the German Human Biomonitoring Commission (Schulz et al., 2009, 2011) were applied. The guideline values of the German Drinking Water Ordinance (TrinkwV, 2001) were taken to assess the drinking water results. Chemical pollutants in indoor air were evaluated employing the guideline values (UBA, 2009) developed by the ad-hoc working group composed of members of the Federal Environment Agency’s Indoor Air Hygiene Commission (IRK) and the Permanent Working Group of the Highest State Health Authorities (AOLG). The result of the screening-audiometry was handed over to the parents directly after measurement had been completed. If the hearing impairment at any of the tested frequencies was equal or greater than 40 dB it was recommended to visit an ENT doctor for more elaborated testing of the hearing. Hearing impairments greater than 20 dB were considered in the analyses of potential associations between leisure activities and hearing ability.

Ethics, data protection, and scientific advisory board

Conclusions

The Ethics Committee of the Charité, university medical centre of the Humboldt University of Berlin, and the Federal and Länder Commissioners for Data Protection approved the joint project of RKI and UBA. GerES IV was also appraised by experts commissioned by the funding institutions, the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) and the Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (Bundesministerium für Umwelt, Naturschutz und Reaktorsicherheit, BMU).

GerES IV is the first nation-wide comprehensive study on the exposure of 3- to 14-year-old children to environmental pollutants. The survey is unique in Europe with regard to the age range of the children and the large variety of pollutants measured not only by HBM, but also by indoor monitoring (indoor air, tap water, house dust, mould) and noise measurement. GerES IV achieved a sufficiently high rate of participation, if one takes into account the decreasing willingness to participate in general population-related studies over the last decades (Latza et al., 2004; Hoffmann et al., 2004). And – what is more important

Reporting results to the participants

Public use file To offer other scientists the opportunity to perform additional evaluations of the GerES IV data, a public use file with pollutant concentrations and questionnaire data of all participants was made available. More information about the public use file can be found on the UBA website (UBA, 2010, in German).

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– the representativeness of the GerES IV sample was confirmed by non-responder analyses. The responders and non-responders did not differ notably with regard to demographic and important exposure-related characteristics. Only a slight underrepresentation of low socio-economic status (SES) children could be observed. The structure of the sample was almost identical to the structure of the population with regard to gender, age and community size. The minimal discrepancies could be adjusted by applying case weights. Hence, GerES IV provides representative information about the environmental exposure of 3- to 14-year-old children in Germany as a whole as well as for different groups defined by age, gender, region and other characteristics. Most aims of GerES IV have meanwhile been reached: the extent and distribution of the analysed pollutants in all media was documented, trends were assessed, and exposure sources were identified. Current reference values (RV95 ) for contaminants present in the blood and urine of children were derived. For further information see Schulz et al. (2011). GerES IV data served to initiate and control exposure and risk reduction measures. The survey showed that e.g. decreasing the exposure of children to environmental tobacco smoke is still a predominant task for environmental and health politics and that in a number of households the guideline values of the Drinking Water Ordinance for domestic drinking water are likely to be exceeded. As a consequence of GerES IV data the limit value for uranium in the German Drinking Water Ordinance has meanwhile been reduced to 10 ␮g/l. GerES IV also showed that children are considerably exposed to three out of six analysed plasticisers, the phthalates DEHP, BBP and DBP, which have to undergo authorisation or otherwise their use will be banned from 2014 on due to new chemicals act REACH (Registration, Evaluation and Authorisation of Chemicals). This paper gives a comprehensive overview of the sampling strategy, investigation programmes and instruments in order to provide a detailed knowledge for scientists working in this field. Scientists who have conducted a similar study can better assess the comparability of their data with GerES IV data. Scientists who are planning a study can better decide which elements they might adopt or adapt to their specific situation. Methods applied in GerES IV are based on the expertise and experience collected in the GerES IV pilot study and the three GerESs conducted before one of which also contained a (smaller) sample of children. Thus the usability and efficiency of most design, examination and interview components had been tested and proved before. The knowledge gained with GerES over the years has enabled UBA to provide helpful input and thus contribute to the following European projects. In 2004, the European Commission recognised in its Environment and Health Action Plan 2004–2010 (COM, 2004) the need for more harmonised approaches to human biomonitoring in Europe to allow for better comparability of results and for the desired extension of knowledge on the exposure of the European population to chemicals. Therefore, the EU funds the project COPHES (Consortium to Perform Human Biomonitoring on a European Scale, 2009; COPHES is funded by the 7th Research Framework Programme of the EU) that has been developing guidelines and recommendations for human biomonitoring programmes across the European Union. 35 organisations from 27 countries participate in this project. UBA is one of the workpackage leaders. Embedded in COPHES is the project DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale; DEMOCOPHES is funded by LIFE+; Joas et al., 2012; DEMOCOPHES, 2011), that conducts a pilot study in 17 countries to test the feasibility of the harmonised approach and to develop preliminary reference values for the analysed pollutants. The experience collected in the pilot study will enable COPHES to finetune their guidelines and recommendations.

The new European chemicals legislation REACH that commenced in 2007 is to improve the regulation and thereby safeguard protection of the population against adverse effects coming from the exposure to chemicals. GerES data have proved valuable in identifying problematic chemicals the regulation of which should be considered. A common European approach and harmonised HBM studies will better allow to follow up efficiency of REACH and to ascertain that the responsibility for a safe use and production of chemicals is shifted successfully from governments to the producers, importers and distributors. Acknowledgements We thank all those involved in this study: the families who took part in this time-consuming survey, the numerous colleagues in local health and environmental authorities, city halls, etc., who supported the survey in their constituencies, as well as the survey teams of the KiGGS and the GerES IV study for their commitment and work in the field. We also thank the BMU and BMBF for their financial support, and the GSF (now Helmholtz Zentrum München) for the external quality assurance of GerES IV. At the RKI, we particularly thank Andreas Bauer, Norbert Birkner, Martin Gorecki, Jan Hegerfeld, Andreas Hünken, Heike Hölling, Panagiotis Kamtsiuris, Bärbel-Maria Kurth, Silke Oberwöhrmann, Angelika Schaffrath Rosario, Heribert Stolzenberg, Wolfgang Thierfelder, Michael Voigt, Dorothe Walter und Ute Wolf for the cooperation with KiGGS, for carrying out the field work and for recording the questionnaire data. References Agusa, T., Kunito, T., Minh, T.B., Kim Trang, P.T., Iwata, H., Viet, P.H., Tanabe, S., 2009. Relationship of urinary arsenic metabolites to intake estimates in residents of the Red River Delta, Vietnam. Environ. Pollut. 157, 396–403. Angerer, J., Ewers, U., Wilhelm, M., 2007. Human biomonitoring: state of the art. Int. J. Hyg. Environ. Health 210, 201–228. Aschpurwis+Behrens GmbH, 2001. BIK Region: Metropolitant Areas, City Regions, Middle and Low Order Centers – Description of Method of the Last Update 2000 (in German) http://www.bik-gmbh.de/produkte/regionen/index.html (accessed 17.01.2012). Au, W.W., 2002. Susceptibility of children to environmental toxic substances. Int. J. Hyg. Environ. Health 205, 501–503. Babisch, W., 2003. Stress hormones in the research on cardiovascular effects of noise. Noise Health 5 (18), 1–11. Babisch, W., Neuhauser, H., Thamm, M., Seiwert, M., 2009. Blood pressure of 8–14 year old children in relation to traffic noise at home – results of the German Environmental Survey for Children (GerES IV). Sci. Total Envir. 407, 5839–5843. Babisch, W., Schulz, C., Seiwert, M., Conrad, A., 2012. Noise annoyance as reported by 8–14 year old children. Environ. Behav. 44 (1), 68–86. Becker, K., Kaus, S., Krause, C., Lepom, P., Schulz, C., Seiwert, M., Seifert, B., 2002. German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population. Int. J. Hyg. Environ. Health 205, 297–308. Becker, K., Schulz, C., Kaus, S., Seiwert, M., Seifert, B., 2003. German Environmental Survey 1998 (GerES III): environmental pollutants in urine of the German population. Int. J. Hyg. Environ. Health 206, 15–24. Becker, K., Seiwert, M., Angerer, J., Heger, W., Koch, H.M., Nagorka, R., Rosskamp, E., Schlüter, C., Seifert, B., Ullrich, D., 2004. DEHP metabolites in urine of children and DEHP in house dust. Int. J. Hyg. Environ. Health 207, 409–417. Becker, K., Seiwert, M., Angerer, J., Kolossa-Gehring, M., Hoppe, H.-W., Ball, M., Schulz, C., Thumulla, J., Seifert, B., 2006. GerES IV pilot study: assessment of the exposure of German children to organophosphorus and pyrethroid pesticides. Int. J. Hyg. Environ. Health 209, 221–233. Becker, K., Göen, Th., Seiwert, M., Conrad, A., Pick-Fuß, H., Müller, J., Wittassek, M., Schulz, C., Kolossa-Gehring, M., 2009. GerES IV: phthalate metabolites and bisphenol A in urine of German children. Int. J. Hyg. Environ. Health 212, 685–692. Buchet, J.P., Lauwerys, R., Roels, H., Bernard, A., Bruaux, P., Claeys, F., Ducoffre, G., de Plaen, P., Staessen, J., Amery, A., Lijnen, P., Thijs, L., Rondia, D., Sartor, F., Saintremy, A., Nick, L., 1990. Renal effects of cadmium body burden of the general population. Lancet 336 (8717), 699–702. CDC (Centers of Disease Control and Prevention), 2009. Fourth National Report on Human Exposure to Environmental Chemicals. http://www.cdc.gov/nchs/nhanes.htm (accessed 17.01.2012). COPHES (Consortium to Perform Human Biomonitoring on a European Scale), 2009. Home: http://www.eu-hbm.info/cophes (accessed 17.01.2012). COM, 2004. Communication from the Commission to the Council, the European Parliament and the European Economic and Social Committee on a European

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