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

Contents lists available at SciVerse ScienceDirect

International Journal of Hygiene andEnvironmental Health

j o ur nal homepage: www.elsev ier .de / i jheh

ini-Review

verview of the study design, participation and field work of the Germannvironmental Survey on Children 2003–2006 (GerES IV)

hristine Schulz ∗, Margarete Seiwert, Wolfgang Babisch, Kerstin Becker, André Conrad,egine Szewzyk, Marike Kolossa-Gehring

erman Federal Environment Agency (Umweltbundesamt, UBA), Dessau-Roßlau, Berlin, Germany

r t i c l e i n f o

rticle history:eceived 8 January 2010eceived in revised form 7 February 2012ccepted 7 February 2012

eywords:hildrennvironmentealthross sectional studyepresentativenessesponseuman biomonitoringtudy design

a b s t r a c t

The German Federal Environment Agency carried out its fourth German Environmental Survey (GerESIV), which is the first survey on children only and the environment-related module of the German HealthInterview and Examination Survey for Children and Adolescents (German acronym: KiGGS), conductedby the Robert Koch Institute (RKI). The German Environmental Surveys are nationwide population stud-ies conducted to determine the exposure to environmental pollutants, to explore exposure pathwaysand to identify sub-groups with higher exposure. GerES IV was conducted on randomly selected 1790children aged 3–14 years from the cross-sectional sample of KiGGS. The participants of GerES IV lived in150 sampling locations all over Germany. Field work was carried out from May 2003 to May 2006. Theresponse rate in GerES IV was 77.3%. Due to the fact that participation in GerES IV was limited to childrenthat 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 differentcommunity sizes, age groups and gender. The basic study programme included blood samples, morningurine, 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 con-

tamination of indoor air” and “biogenic indoor contamination”. A key element of the field work in GerESIV was a home visit to carry out interviews, conduct measurements and collect samples. An exceptionwas blood sampling which was carried out within KiGGS. The quality of field work, data collection, evalu-ation, and chemical, biological and physical analyses was successfully evaluated by internal and externalquality assurance. This comprehensive overview aims at giving other research groups the opportunity tocompare different study designs or to adapt their own design to get comparable results.

Abbreviations: As, arsenic; BBP, butylbenzylphthalate; BMBF, Federal Ministry of Eduederal Ministry for the Environment, Nature Conservation and Nuclear Safety and Reseaicherheit); Cd, cadmium; CAPI, Computer Assisted Personal Interview; COPHES, ConsortiEHP, di(2-ethylhexyl)phthalate; DEMOCOPHES, Demonstration of a study to Coordinateental Agency; GerES, German Environmental Survey; GM, geometric mean; GSD, geomealth, Neuherberg, Germany: re-named to HelmholtzZentrum München – German Rese

gE, immunglobulin E; KiGGS, German Health Interview and Examination Survey for Cey); N, sample size; NHANES, National Health and Nutrition Examination Survey; PAH,

ortable document format; QNA, quality-neutral non-respondents (German acronym: quf Chemicals; RKI, Robert Koch Institute, Germany; RV95, reference value; SES, socio-econnvironment Agency; VOC, volatile organic compounds; WHO, World Health Organizatio∗ Corresponding author. Tel.: +49 30 8903 5465; fax: +49 30 8903 1830.

E-mail address: christine.schulz-ch@uba.de (C. Schulz).

438-4639/$ – see front matter © 2012 Elsevier GmbH. All rights reserved.oi:10.1016/j.ijheh.2012.02.002

© 2012 Elsevier GmbH. All rights reserved.

cation (German acronym: Bundesministerium für Bildung und Forschung); BMU,rch (German acronym: Bundesministerium für Umwelt, Naturschutz und Reaktor-um to Perform Human Biomonitoring on a European Scale; DBP, dibutylphthalate;

and Perform Human Biomonitoring on a European Scale; EEA, European Environ-etric standard deviation; GSF, GSF-National Research Centre for Environment andarch Center for Environmental Health; HBM, human biomonitoring; Hg, mercury;hildren and Adolescents (German acronym: Kinder- und Jugendgesundheitssur-polycyclic aromatic hydrocarbons; Pb, lead; PCB, polychlorinated biphenyls; PDF,alitätsneutrale Ausfälle: QNA); REACH, Registration, Evaluation and Authorisationomic status; SPSS, Statistical Package for the Social Sciences; UBA, German Federaln.

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36 C. Schulz et al. / International Journal of Hygie

ntroduction

Exposure assessment is one of the key elements of the riskssessment procedure which has been developed to evaluate envi-onmental pollutants. An essential step in exposure assessment ishe evaluation of the dose that enters the human body and thenalysis of different environmental media that can affect humans.n this sense exposure assessment focuses on the initial portionf the environmental health paradigma: from sources, to environ-ental concentrations, to exposure, to dose. In studies on human

xposure assessment, emphasis is placed on estimating the magni-ude, duration, and frequency of exposure, as well as estimating theumber of people exposed to various concentrations of the agent

n question (WHO IPCS, 2000).Until the mid 1980s knowledge of human exposure to envi-

onmental pollutants resulted from occupational studies andmall-scale studies conducted on selected population groups inpecific areas. The findings of these studies could not be extrap-lated to the general population.

As a consequence, in Germany epidemiologic studies screeninghe general population for their exposure to chemicals – especiallyead – were launched. Monitoring programmes focus on the deter-

ination of the internal exposure by human biomonitoring (HBM),he measurement of concentrations of chemicals or their metabo-ites in human body fluids on tissues, such as blood or urine.

In 1985, Germany started a series of repeated cross-sectionaltudies: the German Environmental Survey (GerES). GerES is aationwide population representative study on human exposureo various environmental chemicals and its sources. GerES com-rises three main instruments of investigation: HBM, monitoringf the domestic environment, and collecting information on expo-ure pathways and living conditions via questionnaires. The firsthree surveys, GerES I in 1985/1986, GerES II in 1990/1992 anderES III in 1998 comprised only adults – with one exception:- to 14-year-old children living in the households of the adultarticipants were also included in GerES II (Becker et al., 2002,003; Hoffmann et al., 2000a,b, 2001; Schulz et al., 2007; Seifertt al., 2000a,b). In the 1980s and early 1990s, the only large-cale nation-wide population-based survey with a comprehensiveiomonitoring programme comparable to GerES was the Nationalealth and Nutrition Examination Survey (NHANES) in the U.S. con-ucted by the Centers of Disease Control and Prevention’s (CDC’s)ational Center for Health Statistics. NHANES is a series of surveysesigned to measure and monitor the health and nutritional statusf the U.S. population (CDC, 2009).

Among the early studies on human environmental exposure,he “Cadmibel study” is regarded as groundbreaking. From 1985 to989 it examined the exposure of the Belgian population to cad-ium and its health effects (Buchet et al., 1990; Lauwerys et al.,

993, 1994).In Germany, besides GerES several other projects focusing on

uman biomonitoring have recently been or are being performedn specific regions on specific age groups. Such projects are thetudies in hot spot and control areas of North Rhine-WestphaliaWilhelm et al., 2007), the sentinal health department project on0-year-olds in Baden-Württemberg (Link et al., 2007), and thentegrated Exposure Assessment Survey (INES) in Bavaria (Frommet al., 2007).

Important current or recently finished population-basedxposure-oriented studies in other countries are e.g. the sur-eys in Canada (Health Canada, 2010), the Environmental Healthonitoring System (EHMS) in the Czech Republic (Cerná et al.,

011), the French National Nutrition and Health Program (ENNS):001–2006–2010 (Hercberg et al., 2008), the Flemish Environmentnd Health Study (FLEHS) (Den Hond et al., 2009), the Middle East-rn Regional Cooperation Project, 1996–2000 (Safi et al., 2006), the

d Environmental Health 215 (2012) 435– 448

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 regionsto explore the exposure of the investigated populations.

Children are, for a variety of reasons, particularly vulnerableto the impact of environmental pollutants (EEA/WHO, 2002; Au,2002; Chaudhuri and Fruchtengarten, 2005). Hence, the protectionof children is of particular importance for environmental and healthpolitics. Improving the protection of children from environmen-tally caused health risks requires the systematic and continuousmonitoring of the exposure of children to chemical, biological andphysical environmental pollutants. Additionally, the factors influ-encing their exposure need to be investigated.

In 2002, the WHO and EEA issued the joint report “Children’sHealth and Environment – A Review of Evidence” (EEA/WHO, 2002)and emphasised a lack of information and research data.

Therefore the fourth German Environmental Survey examinedonly children (GerES IV). Like the preceding GerESs, GerES IV wascarried out by the German Federal Environment Agency (UBA) inclose cooperation with the “German Health Interview and Exam-ination 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 additionalsurvey programmes. Fig. 1 outlines the relation of the KiGGS andthe GerES IV sample as well as the different additional survey pro-grammes 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 firsttime. Detailed method descriptions as well as results on children’sexposure can be found in the specific basic reports and articles cov-ering human biomonitoring, house dust, drinking water, indoor air,and noise (UBA, 2008).

Objectives

The general objectives of the German Environmental Survey onChildren (GerES IV) are the collection, provision, updating and eval-uation of representative data for a health oriented environmentalmonitoring and environmental reporting on a national level. Therepresentative data also serve to:

• provide a basis for establishing reference values for the expo-sure of children to environmental contaminants as a basis for aconsistent 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 environmentalpolicies,

• evaluate the success of policy and exposure reduction measures,and

• identify emerging chemicals in stored samples with recentlydeveloped or future analytical methods, such as phthalates andbisphenol 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 550participating children and adolescents aged 0–17 years over one

year (from March 2001 to March 2002). The pilot study was carriedout in close cooperation with the pilot study of the National HealthInterview and Examination Survey for Children and Adolescents ofthe RKI (Kamtsiuris et al., 2000; Kamtsiuris and Lang, 2000). The

C. Schulz et al. / International Journal of Hygiene and Environmental Health 215 (2012) 435– 448 437

the G

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Fig. 1. The GerES IV sample in relation to the KiGGS sample and

bjectives of the pilot study of both surveys were to test the feasi-ility of different ways to recruit participants, different incentiveso increase the motivation for participation, and the suitability ofhe instruments for different age groups.

The results of the pilot study lead to the following importantecisions regarding the main phase:

Recruitment of children via inhabitant registries proved to be aviable approach as compared to recruitment via schools/classes(Kamtsiuris and Lang, 2000).D12.50 was given to each family, as this amount proved most suit-able as an incentive for participation compared to other amountsor a gift.The youngest children included in GerES IV were 3 years old,as from a majority of them blood and urine samples could betaken, whereas only a minority of 2-year-olds or younger childrenprovided these samples in the pilot study.The oldest children included in the study were 14 years old. Theage limit was chosen taking into account the low willingness ofolder adolescents to participate as observed in the pilot study.The age limit was also set to enable trend evaluations of GerES IIdata of 1990/1992 (6- to 14-year-old children) and GerES IV data.The automatic hearing test was performed with children aged 8years 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 homevisit.

erES IV subsamples used for the additional survey programmes.

• The extensive programme of the pilot study for air pollution lev-els (outdoor, indoor, and personal sampling over two differenttimeframes) was too demanding for many participants, who didnot return the different samplers correctly after the fixed period.Therefore, only indoor air sampling over one week was conductedin the main phase.

• The questionnaires were revised taking account of the experiencegained in the pilot study.

Study population of GerES IV

Sampling procedure for the core survey

The participants of GerES IV were randomly selected from thecross-sectional sample of the KiGGS study (Kurth et al., 2008). Dueto financial constraints, GerES IV only surveyed a subsample ofKiGGS.

When limiting the GerES IV sample size, both the experiencesmade in the pilot study (see above) and statistical aspects weretaken into consideration.

The following statistical aspects were considered when reduc-ing the sample size: a significance level of 0.1% and a statisticalpower of 80% were assumed, as well as the variances of the pol-lutant concentrations observed in previous surveys, in particular

during the pilot phase of GerES IV (Becker et al., 2004, 2006; Kochet 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 bloodhad the smallest variation (geometric standard deviation (GSD) of

4 ne and Environmental Health 215 (2012) 435– 448

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Table 1Sample sizes, response rates and reasons for non-response.

N %

Sample (selected for GerES among subjects with consentto participate in KiGGS and appointment for KiGGSinterview and examinations)

2799

Non-response/undeliverable contacts 482 17.2Failure to appear at an agreed appointment for KiGGS or

cancellation of the appointment at short notice or theGerES IV examination could not be carried out due toorganisational reasons

447 92.7

Communication with the child’s parents impossible dueto language problems

24 5.0

Household in which the child mainly resides(“separation kids”) is not located at the study location

6 1.2

Wrong information on age given by the registry ofresidents

5 1.0

Reduced sample (basis for response calculation) 2317 100Non-response/undeliverable contacts 527 100

No time 41.6Not interested 10.4Unable to reach 10.1Because of home visit 8.0Withdrawn (child scared to participate) 4.6Passive refusal 4.2Definitely without giving reasons 3.4Too much effort 1.9Construction/renovation in/around the house 1.3Health problems (child ill) 0.6

38 C. Schulz et al. / International Journal of Hygie

.7; geometric mean (GM) of 23.2 �g/l; 362 children aged 3–14ears). Based on this variation, a minimum difference of 8% betweenhe geometric means of two subgroups would be significant with

sample size of N = 1800, and a minimum difference of 14% with = 600. An extremely high variation was found for toluol in indoorir (GSD = 3.4; GM = 50.7 �g/m3; 479 samples in GerES I; Krauset al., 1991). For the latter variation, the minimum difference resultsn 20% and 38% with N = 1800 and N = 600, respectively.

The targeted sample size for GerES IV of N = 1800 also facilitatedhoosing the children from the randomly chosen 150 study loca-ions, since for each of the 12 age groups one child per location waso be surveyed.

The sample size was reduced to n = 600 for very costly exam-nations such as analysis of the chemical (VOC; volatile organicompounds) and biogenic (e.g. mould fungi) indoor contaminantsr phthalate metabolites in urine.

Sampling for KiGGS and GerES IV was performed at the RKI inooperation with the Center for Survey Design and MethodologyCSDM; Zentrum für Umfragen, Methoden und Analysen, ZUMA,

annheim) (Kurth et al., 2008). Children aged between 0 and 17ears who were residents and registered at the registry of resi-ents with their main residence in the Federal Republic of Germanyere the target population of the KiGGS study. Children and adoles-

ents living in institutions such as hospitals or nursery homes werexcluded. Subjects for KiGGS were identified in two stages, firstccording to the study location and second according to individuals.

Overall, 150 study locations were chosen from the total num-er of German communities (Fig. 2). For this choice, communitiesere stratified according to Federal State and type of commu-ity (Aschpurwis+Behrens GmbH, 2001). The communities or study

ocations in each stratum were chosen according to the methodescribed by Kamtsiuris et al. (2007). Disproportionately to theopulation, 100 study locations in West Germany, 45 in Eastermany and 5 in Berlin were randomly selected. This resulted inn oversampling in East Germany to get results with a comparableegree of precision for East and West Germany, respectively (Kurtht al., 2008). During the last year of field work, the sample size foriGGS was increased in order to attain the planned total numberf participants of nearly 18,000. For this, additional 17 communi-ies (including subjects) were included. For GerES IV, no increasen sample size was necessary, since the planned number of partici-ants of about 1800 was already assured by the selection proceduredescribed below).

The KiGGS subjects were chosen, almost simultaneously, at aecond sampling stage two months before the scheduled surveyeriod started. From the registry of residents of the chosen com-unities, exactly 24 personal addresses were drawn within each

ndividual age group. The final random choice took place at the RKI,here 8, 9, or 10 children or adolescents respectively, according to

ge group and study location, were invited to participate in KiGGS.At a third stage, the subjects for GerES IV were chosen at random

rom the pool of 3- to 14-year-olds who had agreed to participate iniGGS and who had also been given an appointment for the KiGGStudy. Children whose birthday was within the two weeks of inves-igation in the respective study location were not included in theerES IV sample. This restriction was necessary to achieve clear

nformation about the age of the children when linking KiGGS anderES IV data at a later date.

For each study location, the potential GerES IV participants ofach age group were arranged in a random sequence (ranking).irst, the potential subject on rank 1 was contacted. If he or sheas not willing to participate, or was not available for one of the

easons indicated below, the subject on the next higher rank wasontacted, and so on.

Recruitment for GerES IV began two working days beforehe start of the survey at the respective study location by the

Other reasons 14.0

Total study participants, response 1790 77.3

coordination centre in Berlin, the RKI, or at the actual location.Children, who had already participated in the KiGGS prior to theGerES IV, were excluded as blood samples had already been taken.Although determining pollutants present in children’s blood wasa fundamental aim of GerES IV, for ethical reasons, an additionalpuncture to get a second blood sample was not supposed to bejustified.

This randomly chosen sample of GerES IV comprised 2799potential subjects aged between 3 and 14 years (Table 1). Thereduced sample is described in section “Non-participation”.

Sampling procedures for the additional survey programmesProgramme “noise, hearing capacity and stress hormones”. The find-ings from the pilot study showed, that most children aged 8 yearsor older can perform the automatic screening audiometry suc-cessfully. Therefore every 8- to 14-year-old child was supposed toadditionally participate in the survey programme “noise, hearingcapacity and stress hormones”.

Programme “chemical contamination of indoor air”. The subjects forthis special survey programme of GerES IV were selected at a fourthstage. For a sub-sample of n = 600 participants, the “chemical con-tamination of indoor air” was planned to be monitored. Therefore,for each study location one child from each of the following agegroups: 3–5 years, 6–8 years, 9–11 years, and 12–14 years (fourchildren per location), was selected from the GerES IV sample. Ateach study location, the respective first subject from each of thefour age groups that was visited at home was asked to participate inthis additional investigation. The following two exclusion criteriawere applied: (1) the family and the child in question were onholiday during or near the end of the scheduled survey period, i.e.the minimum sampling period of 5 days or the maximum samplingperiod of 8 days could not be met, or (2) the family could not be

burdened with the extensive programme. If one of these criteriawas met, or if the family was not willing to participate in thisextensive programme, then the next subject of the respective agegroup that was visited at home was selected for this investigation.

C. Schulz et al. / International Journal of Hygiene and Environmental Health 215 (2012) 435– 448 439

ey on

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Fig. 2. Study locations for the German Environmental Surv

uring the first two weeks of field work (19 May–8 June 2003),hus in the first three study locations, not all passive samplersor monitoring VOC in indoor air were available. Therefore, thendoor air programme started later and the targeted sampleize was reduced to 588. To include 588 participants in the pro-ramme, 698 families from 147 study locations were identified forarticipation.

rogramme “biogenic indoor contamination”. For the monitoring ofbiogenic indoor contamination”, a nested case–control study wasonducted. As a precondition for selecting cases and controls, theread to be complete blood examinations regarding specific IgE anti-odies for 20 widespread allergens (Schlaud et al., 2007) as wells for 5 indoor-specific mould fungi and Alternaria alternata (testy the company Matritech/ADL, Freiburg). All children showing

positive test result for Aspergillus spec., Penicillium crysogenumnotatum), Aspergillus versicolor, Wallemia sebi or Eurotium spp wereefined as being suitable cases. A test result of class 1 or higher

≥0.35 kU/l) was regarded as positive. For each case, 8 subjectsithout positive test result (controls), were randomly selected and

nvited to participate in this special study (assuming a participationate of 50%). The random selection was conducted safeguarding that

Children 2003–2006 according to Kamtsiuris et al. (2007).

the criteria age, gender, and survey period were the same amongthe controls and the cases (frequency matching).

Non-participation

Non-participation in the core surveyFrom the total sample N = 2799, all quality-neutral non-

respondents (German acronym: QNA) were eliminated. QNAcovered the following reasons for not participating: unknown per-son/wrong address/non-existing address; deceased; household inwhich the child mainly resides (“separation kids”) was locatedsomewhere else than the study location; wrong age informationgiven by the registry of residents; communication with the child’sparents impossible due to language problems; failure to appear atan agreed appointment for KiGGS or cancellation of the appoint-ment at short notice or the GerES IV examination could not becarried out due to organisational reasons (Table 1). All in all, 482cases were defined as QNA, resulting in a reduced sample of 2317

cases for GerES IV. This sample size was the basis for calculatingthe response rate.

Out of this reduced sample, 53 families could not be contactedat any time. 474 families were not willing to participate, reporting

440 C. Schulz et al. / International Journal of Hygiene and Environmental Health 215 (2012) 435– 448

Table 2Response based on all KiGGS participants selected for GerES IV stratified by sampling characteristics socio-economic status, and season of investigation.

Participating familiesa (n) Refused participationb (n) Families unable to reachc (n) Response GerES IVd (% with CI)

Total 1790 474 53 77.3 (±1.7)Region

East Germany 536 157 12 76.0 (±3.2)West Germany 1194 302 35 78.0 (±2.1)Berlin 60 15 6 74.1 (±9.5)

Community size<100,000 inhabitants 901 229 17 78.6 (±2.4)≥100,000 inhabitants 889 245 36 76.0 (±2.5)

Age group3–5 years 443 109 12 78.6 (±3.4)6–8 years 449 97 21 79.2 (±3.3)9–11 years 449 130 13 75.8 (±3.5)12–14 years 449 138 7 75.6 (±3.5)

GenderMale 883 236 23 77.3 (±2.4)Female 907 238 30 77.2 (±2.4)

Socio-economic statusLow 414 157 18 70.3 (±3.7)Medium 853 219 19 78.2 (±2.5)High 504 90 15 82.8 (±3.0)Missing 19 8 1

SeasonMay–October 820 194 18 79.5 (±2.5)November–April + May 2006 970 280 35 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.

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c Families unable to reach: families to whom no contact could be established.d Response GerES IV: participating families/(families who participated, refused tarticipants selected for GerES IV.

iverse reasons for this (Table 1). The most common reason giveny the families was “no time”, followed by “not interested, not con-inced by the sense and purpose of the survey”. The “home visit”as the third most common reason for refusal.

405 (85.4%) of these 474 families not willing to participate,nswered a short questionnaire regarding important environ-entally related characteristics (e.g. heating with wood or coal,

sh consumption, amalgam fillings in teeth). A comparison ofarticipants and non-participants revealed hardly any differ-nce between the two groups. Additional information on GerESV non-participants could be retrieved from KiGGS data, whichhowed that the general health of the children, assessed byheir parents, and the proportion of mothers who smoked didot differ significantly between participants and non-participants.hese results prove the representativeness of the GerES IVample with regard to key health- and environment-relatedharacteristics.

on-participation in the additional survey programmesrogramme “noise, hearing capacity and stress hormones”. The num-er of non-participants, the percentage of QNA (quality-neutralon-respondents), and the reasons for not participating in the sur-ey programme “noise, hearing capacity and stress hormones” didot differ significantly from those of the age group of the 3- to-year-olds. 9% of the children failed to perform the automaticearing test.

rogramme “chemical contamination of indoor air”. Of the 689 sub-ect families selected for participation in the survey programmechemical contamination of indoor air”, 104 did not participate forhe following reasons: 70 of the families selected could not be bur-ened with the comprehensive and extensive programme. With 20

amilies, it was to be expected that neither the minimum nor the

aximum collection time could be kept. 14 families were not will-ng to participate in this survey programme. A further 5 familiesid not send back the passive samplers.

icipate, or could not be contacted). Basis for response calculation: N = 2317 KiGGS

Programme “biogenic indoor contamination”. 508 out of the 1038subject families who were asked to participate in the nestedcase–control study on “biogenic indoor contamination”, refused todo so. Data of 7 participants could not be used (e.g. child was nolonger living in the apartment).

Participation

Participation in the core survey1790 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 1790children had a migration background.

Due to the design strategy, the response rate can be definedin 2 different ways, (1) as the GerES specific and (2) as the totalresponse rate. (1) Out of all children selected for participation inGerES IV (N = 2317), 77.3% actually took part. (2) But as only chil-dren could be selected for GerES IV who also took part in KiGGS,the non-response in KiGGS has also to be taken into account whencomputing a total response rate. Since in the KiGGS study 68.1%of children aged 3–14 years participated, multiplying this numberwith the GerES IV specific response rate of 77.3%, results in a totalresponse rate of 52.6%. The smaller overall response is plausibleand can be explained by the additional time needed for the inves-tigations (2 h for KiGGS and 1.5 h for GerES IV). The response rate isin the range of the response rates of comparable studies conductedin Germany recently (Hoffmann et al., 2004; Latza et al., 2004).

Table 2 shows the number of participants and the responserates by age group, gender, community size, region (East/WestGermany), socio-economic status (SES), and season, based on allchildren selected for GerES IV. The response rates vary minimallybetween age groups and genders as well as East and West Germany,

when either the GerES specific response rates or the total responserates were compared. Though in the KiGGS study the participationwas lower in large cities (≥100,000 residents) than in smaller com-munities (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– 448 441

Table 3Number and percentage of completed questionnaires, available samples, and mea-surements in GerES IV.

Instrument/sample/measurement N %

Questionnaire on residential environment 1790 100Documentation questionnaire 1790 100Parents’ questionnaire 1789 99.9Drinking water sample 1788 99.8Morning urine sample 1734 97.1House dust sample 1623 90.7Blood sample 1560 87.2Children’s questionnaire (children aged

8–10 and 11–14)1042 99.4

Noise level measurement (children aged8–14)

1039 99.1

Audiometry (children aged 8–14) 959 91.5Interview-guided questionnaire regarding

chemical indoor air pollution (onlyparticipants of this programme)

579 100

Self-administered questionnaire regardingchemical indoor air pollution (only

576 99.5

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Table 4Composition of GerES IV sample (N = 1790) and target population of children aged3–14 years stratified by sampling characteristics.

GerES IV sampleN = 1790

PopulationN = 9,785,494

N % %

RegionEast Germany 536 29.9 11.7West Germany 1194 66.7 85.0Berlin 60 3.4 3.3

Community size<100,000 inhabitants 1339 74.8 72.9≥100,000 inhabitants 451 25.2 27.1

Age group3–5 years 443 24.8 23.56–8 years 449 25.1 24.79–11 years 449 25.1 24.412–14 years 449 25.1 27.4

GenderMale 883 49.3 51.3Female 907 50.7 48.7

participants of this programme)

Indoor air sample 579 100

y community size due to the GerES sampling strategy of recruit-ng participants in each sampling location until the fixed numberf 12 was reached. Data on SES suggest a slight bias, as familiesith a low status tended to refuse participation more often than

amilies with a higher status. In addition, it could be observed thaturing the cold season (November–April) participation was lowerhan during the warm season (May–October). To avoid a seasonalias, neighbouring areas were visited in different seasons.

articipation in the additional survey programmesrogramme “noise, hearing capacity and stress hormones”. The finalample considered for all noise related analyses consisted of 1048hildren 8–14 years of age.

rogramme “chemical contamination of indoor air”. 579 childrenged 3–14 successfully participated in the programme “chemicalontamination of indoor air” (297 girls, 287 boys). In relation tohe 689 selected subject families, this meant a participation ratef 84.0%. With regard to the sampling characteristics, there wereo significant differences in the participation rate in this subsam-le, either, so that the composition of this sub-sample was nearly

dentical to that of the entire sample of GerES IV (data not shown).owever, subjects with a low SES participated somewhat less –ven though not significantly so – in this comprehensive pro-ramme, since it was harder on families with a low SES than onamilies with a higher SES.

rogramme “biogenic indoor contamination”. The final sample ofhis nested case–control study resulted in 523 (50.4%) participatingamilies supporting utilisable data, 66 of which were cases and 457ontrols.

The completeness of the participants’ data records regarding thendividual survey instruments was very good, i.e. between 80% and00% (Table 3).

epresentativeness, weighting

The target population of the GerES IV sample consisted of,785,494 children living in Germany aged between 3 and 14 years

Source: Mikrozensus, validation date 31 December 2004, issued byhe German Federal Statistical Office, Statistisches Bundesamt). Theomparison between the composition of this target population andhe GerES IV sample realised is shown in Table 4.

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 disproportion-ately in favour of East Germany to ensure sufficient sample size foranalyses stratifying according to residence in former East and WestGermany (Kurth et al., 2008). This “oversampling” of East Germanyis also reflected in the GerES IV sample. Compared to the popula-tion, children from East Germany are present at a disproportionaterate in the sample realised.

As the data presented in Table 4 illustrate, children from com-munities with less than 100,000 inhabitants are disproportionatelyoverrepresented in GerES IV. However, this is not due to thesampling strategy but to the higher willingness of this group toparticipate.

By weighting the cases, the proportions of the sampling char-acteristics in the sample were adjusted to those present in thetarget population. Therefore the representativeness of the GerES IVresults remained assured. The calculation of the weighting factorswas 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 orsuspected to cause adverse health effects: neurotoxins (Pb, Hg,phthalates); carcinogenic/cocarcinogenic substances (PAHs, ben-zene, halogenated volatile organic compounds, As, Cd); substancesthat cause disorders or irritation of the respiratory tract, allergiesand asthma (excrements of dust mites, allergens on pet hairs, fungalspores, volatile organic compounds, formaldehyde and carbonyls);substances that have a possible effect on development with poten-tially long-term consequences (such as DEHP, PCB).

In addition, the selection of the substances was determined by3 main criteria:

• The availability of well-established analytical methods suited tostudy a large number of subjects including the availability ofcontrol standard or reference materials for internal and externalquality control as well as certification procedures.

• The relevance of the substance for environmental and healthpolicy, such as the assessment of prevention, intervention andreduction 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.

442 C. Schulz et al. / International Journal of Hygiene and Environmental Health 215 (2012) 435– 448

Table 5Questionnaires applied in GerES IV.

Questionnaire Answered by Main topics

Questionnaire on residentialenvironment

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

Documentation questionnaire(interview-guided)

All parents; interviewers Documentation and additional questions regarding sampling and measurements:morning urine; first flush and random drinking water; contents of vacuum cleanerbags; noise level measurement in front of child’s room and hearing test

Parents’ questionnaire(interview-guided)

All parents Characteristics of the home; surroundings of the home; use of chemical products inthe household; time spent at different locations; exposure to second hand smoke;dental health status; nutrition; potentially environmentally caused irritations; bodyornaments and clothing; noise annoyance; potential adverse effects of noise on child;specific questions on exposurerelevant, age-dependent behaviour (e.g. playing on thefloor), which was only addressed to parents of children aged 3 to 10

Children’s questionnaires(interview-guided)

Children aged 8–10 (version I);children aged 11–14 (version II)

Music listening habits; hearing disorders; noise annoyance; potential adverse effectsby noise and exposure to second hand smoke

Questionnaire on chemical indoor aircontamination (interview-guided)

Parents participating in thisprogramme; interviewers

Documentation of the sampling; characteristics of the room where the sampling wasdone

Questionnaire on chemical indoor aircontamination (self-administered)

Parents participating in thisprogramme

Exposure-relevant activities in the room with the passive samplers

Questionnaire on biogenic indoor All parents participating in the Documentation of the samplings and additional questions regarding rooms andrelevaExposamalg

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contamination (interview-guided) case–control studyNon-responder questionnaire

(interview-guided)Parents who refusedparticipation

nstruments: questionnaires and specimen sampling

The GerES IV survey comprised standardised questionnaires,uman biomonitoring (blood and morning urine samples taken

rom the children), an indoor monitoring (house dust and indoor

able 6amples and parameters analysed in GerES IV.

Group of substances Type of sample/parameters

Blood Morning urine

Elements/heavy metals Cd, Pb, Hg Sb, As, Cd, Ni, Hg, Tl, U

Persistent organicpollutants – POPs

DDE, HCB,�-,�-, �-HCH,PCB 28, 52, 101, 138, 153,180

Phthalates DEHP metabolites andothersa

Flame retardants

Bisphenol A BPA totalDialkyl phosphates DMP, DMTP, DMDTP, DEP,

DETP, DEDTPPyrethroids Metabolites: cis- and

trans-DCCA, DBCA,F-PBA,3-PBA

Further biocides

Chlorophenols PCP and others b

PAH metabolites 1-Hydroxypyrene andothersc

ETS marker Nicotine, cotinineStress hormones Cortisol, adrenalin,

noradrenalinVOC incl. carbonyls

hthalates: DEHP, di(2-ethylhexyl)phthalate; DMP, dimethylphthalate; DEP, diethylutylphthalate; DnOP, di-n-octylphthalate; DEHT, di(2-ethylhexyl)terephthalate; DINCHlame retardants: TCEP, tris-(2-chloroethyl)-phosphate; TBEP, tris-(2-bytoxyethylen)-priscresylphosphate.ialkyl phosphates: DMP, dimethyl phosphate; DMTP, dimethyl thiophosphate; DMDTP,EDTP, diethyl dithiophosphate.etabolites of pyrethroides: cis-DCCA and trans-DCCA, cis- and trans-3-(2,2-dichlorovi

imethylcyclopropan; F-PBA, 4-fluoro-3-phenoxybenzoic acid; 3 PBA, 3-Phenoxybenzoica Mono(2-ethylhexyl)phthalate (MEHP), 2-ethyl-5-hydroxy-hexylphthalate (

carboxypentyl)phthalate (5cx-MEPP), mono(2-carboxymethylhexyl)phthalate (2cxono-benzylphthalate (MBzP), mono(4-methyl-7-hydroxyoctyl)phthalate (OH-Mi

arbooxyheptyl)phthalate (cx-MiNP).b Monochlorophenol (MCP), dichlorophenol (DCP), trichlorophenol (TCP), tetrachloropc 1-, 2,9-, and 3-hydroxyphenanthrene, 1,2-phenanthrendihydrodiol, 9,10-phenenanth

nt behavioursure-related living conditions and behaviours: heating, fish consumption,am fillings, breast feeding

air), and a drinking water monitoring (drinking water taken from

the kitchen tap). For children aged 8 years or older, the programmewas extended by physical measurements (noise level measurementand screening audiometry) in the programme “noise, hearing capa-bility and stress hormones” and by an additional interview.

Tap water House dust Indoor air

Cd, Cu, Pb, Ni, UDDTPCB 28, 52, 101, 138, 153, 180,�-HCH

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

Cyfluthin, �-Cyhalothrin,Cypermethrin, Deltamethrin,Emphethrin,d-Phenothrin, PemethrinChlorpyrifos, Eulan,Metoxychlor, Propoxur, (PBA)PCP

From n-Hexaneto n-Hexadecan

phthalate; BBP, butylbenzylphthalate; DiBP, diisobutylphthalate; DnBP, di-n-, diisononyl 1,2-cyclohexanedicarboxylic acid.hosphate; TEHP, tris-(2-ethylhexyl)-phosphate; TPP, triphenylphosphate; TCP,

dimethyl dithiophosphate; DEP, diethyl phosphate; DETP, diethyl thiophosphate;

nyl)-2,2-dimethylcyclopropane-1carboxylic acid; DBCA, 3-(2,2-dibromvinyl)-2,2- acid.5OH-MEHP), 2-ethyl-5-oxohexylphthalate (5oxo-MEHP), mono(2-ethyl--MMHP), mono-n-butylphthalate (MnBP), mono-iso-butylphthalate (MiBP),NP), mono(4-methyl-7-oxo-octyl)phthalate (oxo-MiNP), mono(4-methyl-7-

henol (TECP).rendihydrodiol, phenanthren-1,2,3,4-tetrol.

C. Schulz et al. / International Journal of Hygiene and Environmental Health 215 (2012) 435– 448 443

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

Parameters Type of sample

Serum Outdoor air Indoor air Floor dust Mattress dust

Specific IgE antibodies: Penicillium chrysogenum (notatum), Aspergillusfumigates, Cladosporium herbarum, Aspergillus versicolor, Alternariaalternata, Wallemia sebi, Eurotium spp., Felis domestica,Dermatophagoides pteronyssinus, Dermatophagoides farinae

×

Culturable mould spores × × ×Total spore count ×

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House dust mite allergen: Dermatophagoides pteronyssinus (Der p 1),Dermatophagoides farinae (Der f 1)

uestionnaires/interviews

Carrying out GerES IV in conjunction with KiGGS had the enor-ous advantage that KiGGS already surveyed questions that also

layed a role in interpreting the GerES IV data. They did not haveo be asked again for GerES IV and could nevertheless be usedor the GerES IV analysis. These questions referred to, among oth-rs, sociodemographic information (e.g. education, employment,ncome); personal data (parents, child, siblings); health relatedehaviour and risks (exposure to tobacco smoke (Conrad et al.,010), nutrition, breast feeding status, physical exercise); social,hysical, and emotional health; living conditions, and medical careHölling et al., 2007).

In GerES IV, several standardised interviewer-guided question-aires and a self-administered questionnaire were used (Table 5).

From May 2003 (beginning of field work) until the end of 2004,he environmental interviewers used paper versions of the respec-ive standardised questionnaires to fill in the information given byarents and children with a pencil. From January 2005 until May006 (end of field work), the data were recorded as a CAPI (Com-uter Assisted Personal Interview) using a laptop computer. Theata entry masks were created by the company Statistik-Service Dr.laditz, Berlin, using Data Entry 4.0 (SPSS Inc., Chicago, IL).

The GerES IV questionnaires can be downloaded as PDF filesrom the UBA website (UBA, 2008).

uman biomonitoring

HBM is defined as the measurement of concentrations of chem-cals or their metabolites in human biological media such as blood,rine, or breast milk. HBM is considered as the method of choiceo determine the internal exposure of the population, populationroups or individuals thus supplying a basis for estimating healthisks and – if necessary – for risk management (Angerer et al., 2007).

In GerES IV blood and morning urine samples were taken –rovided parents had given their consent – and analysed for envi-onmental contaminants.

When taking the blood sample for the KiGGS study, an additionalube (Vacutainer® diagnostics tube containing the anticoagulantodium heparin, Becton Dickinson, Heidelberg, Germany) was filledith blood (2 ml for children aged 3–6, 6 ml for children aged 7–14).

hus it was assured that only one puncture had to take place.All children who did no longer wear diapers at night were asked

o collect their entire morning urine, i.e. the urine present after night’s sleep. Cleaned and decontaminated (cleaned in a dish-asher, rinsed with 1.3% nitric acid and double-distilled water)

50 ml toilet seat inserts (Tyco Healthcare Deutschland GmbH,eustadt/Donau, Germany) for collecting the samples were pro-

ided to parents of children aged 3–4 years (for girls optionallyp to 6 years after consulting with the parents). Parents of olderhildren were provided with cleaned and decontaminated 1 l wide-eck square vessels (Kautex, Bonn-Holzlar, Germany). All parents

××

were provided with the respective information sheet on correctsampling. At the examination centres, the urine samples weretransferred into 6.5 ml, 13 ml and 15 ml tubes (Sarstedt, Nürm-brecht, Germany), and these tubes were stored deep frozen (−20 ◦C)until analysis. The parameters analysed in the blood and urine sam-ples are given in Table 6.

Indoor monitoring

Children spend about 60–80% of the day in their homes, depend-ing on season, day and age (Conrad et al., 2012). Spending somuch time indoors makes the importance of the indoor air qual-ity even greater. Additionally, a clean environment at home is veryimportant for the children’s health (WHO, 2010). Therefore, theexamination of chemical pollutants and biological agents in housedust and in indoor air was included in GerES IV.

House dustFor examination of house dust the participant supplied the

complete vacuum cleaner bag. The whole bag or its contents sub-sequently were transferred to vacuum compound plastic bags(MR-Verpackung, Walsrode, Germany) and stored at room temper-ature as cool as possible until transport to Berlin within one week.As the samples possibly contained chewing insects, they were firststored at −20 ◦C for at least half a year. Then they were kept at adry and cool place until preparation of the analysis (sieving, frac-tion <63 �m). The parameters (see section “Criteria for selectingsubstances for analysis in GerES IV”) analysed in the house dustsamples are given in Table 6.

Chemical contamination of indoor airIn order to determine the chemical pollutants in indoor air, three

types of passive samplers (Perkin Elmer Tenax tubes, Sigma AldrichSupelco, Chemie, Teufkirchen, Germany; 3M OVM-3500, CoenenNeuss GmbH, Neuss, Germany and SKC UMEx-100, Scanntec Lab AB,Sweden) were used for the duration of one week (ISO, 2003; Ullrichand Nagel, 1996; Ullrich et al., 1999, 2002). The samples were takenin the room in which the children usually spent the most time ofa day (24 h). At the end of the sampling period, participants sentthe passive samplers together with the questionnaire on chemicalcontamination of indoor air to UBA by mail. The SKC UMEx-100samplers were stored frozen (−20 ◦C), whereas the other samplerswere stored in an exsiccator until analysis.

Biogenic indoor contaminationAccording to the WHO (2009) dampness and mould in indoor

environments are associated with health problems like upper res-piratory tract symptoms and asthma exacerbation. To examine the

relationship between sensitisation against mould spores and theoccurrence of mould in household, a case–control study was con-ducted. In this nested case–control study, dust measurements wereperformed in the child’s room in order to detect biogenic indoor

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44 C. Schulz et al. / International Journal of Hygie

ollutants (mould fungi, dust mite allergens, allergens adhering toat hair). Dust samples were collected with a special sampler (ALKcherax, Wedel, Germany) on a floor area of 4 × 0.5 m2 for anal-sis of culturable fungi in the 63 �m fraction. Dust mite and catllergens were determined from collected mattress dust. Cultur-ble mould fungi present in the indoor air were collected by meansf impaction (MAS-100®) approx. 1.5 m above the floor. Cultivationas performed on dichlorane glycerol agar (DG18 agar) and malt

xtract agar (MEA) in compliance with VDI 4300-10. The total num-er of mould spores in air was analysed microscopically after slit

mpaction on glass slides (PS 30® by the company Umweltanalytikolbach, Germany).

rinking water

Drinking water is one of the most important nutrients (WHO,003). In Germany, the quality of drinking water distributing by theater suppliers ranges from good to very good and the microbio-

ogical, chemical and physical requirements set out by the Germanrinking Water Ordinance 2001 (TrinkwV, 2001) have been largely

atisfied. But some deterioration of drinking water quality can beraced to house installation systems (Grummt, 2007; Völker et al.,010).

Therefore, in all households, drinking water samples were takenrom the tap normally used by the participants to draw water forooking and drinking. Water standing in the water pipe for at least

h during the night was collected in a standardised procedure byhe residents (first draw samples in cleaned and decontaminated/2 l square vessels, Kautex, Bonn-Holzlar, Germany). All parentsere supplied with the respective information sheet on correct

ampling. An additional sample (in cleaned and decontaminated l square vessels, Kautex, Bonn-Holzlar, Germany) was taken ran-omly from the same tap in accordance with the recommendationn the “Evaluation of drinking water quality with respect to thearameters lead, copper and nickel” (UBA, 2004) by the interviewer.he samples were stored at room temperature (as cool as possible)ntil analysis. They were analysed (see Table 6) for their contents ofhe elements cadmium, cooper, lead, and nickel, which may enternd dissolve in water through corrosion of pipe and fitting materi-ls.

Additionally uranium was measured. As in the preceding yearslevated uranium concentrations in drinking water had beeneported in increasing numbers from the German states (Konietzkat al., 2005), it was important to gain a systematic overview of theituation in Germany.

oise, hearing capacity and stress hormones

Noise affects children in many ways. Exposure to transport noisean lead to annoyance, stress response, cognitive impairment andossibly cardiovascular problems (Babisch, 2003; Babisch et al.,009, 2012; Maassen et al., 2001; Zuurbier et al., 2007). There-ore, for children aged 8 years or older, a screening audiometryas performed by means of an automatic pure tone audiometer

AURITECT, Type AT 409, Germany), in combination with circum-ural audiometry headphones (Sennheiser, Type HDA 200), whichad a high passive ambient noise attenuation. The audiometers andeadphones utilised were in compliance with the requirements of

EC 60645-1 (DIN EN 60645-1, 2002).Additionally traffic noise was measured outside the child’s bed-

oom window. The noise level meter used (NORSONIC, Type 116)as in compliance with the requirements of DIN EN 60804 or the

ew DIN EN 61672-1 (DIN EN 61672-1, 2003), respectively. Theasic conditions of the measurements (among others, time of day athich the noise level was measured and which is taken into account

or the analysis) as well as the measured average A-weighted noise

d Environmental Health 215 (2012) 435– 448

level were recorded in the documentation questionnaire (see sec-tion “Instruments: questionnaires and specimen sampling”).

The children were asked about ear trouble in connection withloud noise events and about their music listening habits accord-ing to the standardised interview-guided children’s questionnaire(see section “Questionnaires/interviews”). Morning urine was ana-lysed for stress hormones (cortisol, adrenaline and noradrenaline)(Babisch, 2003).

Analyses

All samples were coded before analysis and analysed in arandomised sequence to avoid observer bias. Part the chemicalanalyses was conducted by external laboratories. Contractors hadto meet precision and accuracy standards in their internal qual-ity assurance, and had to take part successfully in round robintests. In GerES IV the external laboratories were: the Departmentof Hygiene, Social and Environmental Medicine at Ruhr-UniversityBochum, the Institute and Out-patient Clinic for Occupational,Social and Environmental Medicine in Erlangen-Nürnberg, theUniversity of Rostock, Biochemical Institute for Environmental Car-cinogens in Großhadern, EUKOS Umweltanalytik Nord GmbH inPlön; Eurofins (former ERGO) in Hamburg, ADL Matritech GmbH inFreiburg, Bioanalytisches Forschungslabor von Prof. Schöneshöferin 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, cat-echolamines 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 materialswere run together with the samples on a daily basis in all laborato-ries. External quality control was achieved by regular participationin intercomparison programmes organised by the German Societyfor Occupational and Environmental Medicine, e.g.

Further information about the analytical methods was given inthe basic reports and publications.

Field work

Field work of KiGGS and GerES IV was conducted from May 2003to May 2006 (Hölling et al., 2007). For GerES IV, the entire logisticinfrastructure of the KiGGS study was used. This included routeplanning, information dissemination and public relation work aswell as recruiting subjects, providing rooms, organising removalsfrom one study centre to the next as well as transporting samplesand materials to and from Berlin.

During this 3-year field work period, three survey teams com-prising one paediatrician, assistant medical technician, child nurseand two interviewers travelled through Germany. They followed adefined route, stayed in each of the selected study locations for twoweeks, and examined and interviewed children and parents readyto participate. The sampling locations were visited in an elaboratesequence to balance regional and seasonal effects and avoid bias(Hölling et al., 2007). The majority of the field work for GerES IVwas performed by the environmental interviewer of the respectiveKiGGS team (Hölling et al., 2007).

The starting point at each study location was a study centreconsisting of 4–6 rooms, usually located on the premises of thelocal health authority or other communal institutions (Hölling et al.,2007). In this centre, the examinations and interviews for the KiGGSstudy 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 inter-viewed, the samples collected, and the measurements performed.

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n front of the apartment, the environmental interviewer deter-ined the Gauß-Krüger coordinates and documented information

bout the residential environment such as traffic and housing.All the examinations, measurements, interviews, etc. performed

n KiGGS and GerES IV had been documented in detail in an oper-tions manual developed jointly by the RKI and the UBA. ThisKI/UBA internal manual furthermore defined the entire projectanagement, the team member tasks, the field work process asell as the quality assurance measures (standard operating proce-ures).

Shortly before the start of field work, team members andeplacement personnel underwent a comprehensive trainingourse lasting several weeks and accompanied by an external qual-ty assurance (Hölling et al., 2007). The operations manual wasvailable as training documentation and a reference book duringeld work.

During field work, the environmental interviewers underwent random evaluation during home visits in 47 homes. This qualityontrol measure was supervised by the external quality assuranceSF (GSF-National Research Centre for Environment and Health,euherberg, Germany; re-named to HelmholtzZentrum München –erman Research Center for Environmental Health; Filipiak-Pittroffnd Wölke, 2007, 29 controlling visits), by the UBA (7 controllingisits) and by the RKI (11 controlling visits). Apart from the con-uct of the home visits, the preparation, the final sample handlingnd data administration/data storing were evaluated. Also, workrocesses performed by the other field personnel were checked asar as they were relevant to the progress of GerES IV. To assure

consistent approach, all the work processes to be performed inonnection with GerES IV were evaluated according to predefineduality assurance criteria. The quality assurance expert informedhe environmental interviewers about any findings directly afterhe controlling visit. The evaluation results were also supplied toll partners concerned with quality assurance in form of informa-ional reports. Experiences or shortcomings relevant to more thanne team as well as suggestions for improvement were promptlyommunicated to the environmental interviewers of the othereams.

Quality of data entry into a database of the data written downn paper in the field was checked in a random sample of 10% ofhe filled-in questionnaires. The total amount of errors amountedo 0.15%, thus fulfilling the maximum tolerable error margin of.20% predefined by UBA and RKI. Starting in January 2005, dataere entered by the environmental interviewers directly into theirotebook PCs using the SPSS application “Data Entry”. For thehift from paper-based questionnaires to CAPI, interviewers under-ent intensive training. This training as well as the first round

f data entry by CAPI was accompanied by the external qual-ty assurance expert. The advantages of data collection via CAPI

ere (a) a faster performance of interviews, and (b) immedi-te detection of implausible or inconsistent entries by automaticest routines. Thus, open questions could be clarified right onhe spot.

thics, data protection, and scientific advisory board

The Ethics Committee of the Charité, university medical centref the Humboldt University of Berlin, and the Federal and Länderommissioners for Data Protection approved the joint project ofKI and UBA.

GerES IV was also appraised by experts commissioned byhe funding institutions, the Federal Ministry of Education and

esearch (Bundesministerium für Bildung und Forschung, BMBF) andhe Federal Ministry for the Environment, Nature Conservationnd Nuclear Safety (Bundesministerium für Umwelt, Naturschutz undeaktorsicherheit, BMU).

d Environmental Health 215 (2012) 435– 448 445

A scientific advisory board was employed to support UBA andRKI for the duration of both surveys. This board regularly evaluatedthe current status of field work, made recommendations if neces-sary, based on the quality control reports, and commented on theconcepts for scientific analyses and use of the data.

Reporting results to the participants

An appropriate and comprehensive communication to the par-ticipating child and their parents is an ethical issue related tostudies on children (Pedersen et al., 2007). Therefore, every par-ticipant was informed about the concentrations of the analysedsubstances in her/his blood, urine, drinking water and indoor airsample (Helm et al., 2000). This reporting of individual results didnot only meet ethical demands, but was also an important incen-tive for participation. A letter with results was sent immediatelywhen the analyses of one group of substances were completed, asfor ethical reasons elevated concentrations of environmental pol-lutants had to be communicated as fast as possible. In the case ofelevated findings the most common exposure sources were speci-fied in the letter and, if applicable, recommendations for exposurereduction were given. For additional support a hotline to a medi-cal doctor of the GerES team was provided. For medical follow-upthe participants were encouraged to turn to an outpatient clinic forenvironmental 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 derivedby the German Human Biomonitoring Commission (Schulz et al.,2009, 2011) were applied. The guideline values of the GermanDrinking Water Ordinance (TrinkwV, 2001) were taken to assessthe drinking water results. Chemical pollutants in indoor air wereevaluated employing the guideline values (UBA, 2009) developedby the ad-hoc working group composed of members of the FederalEnvironment Agency’s Indoor Air Hygiene Commission (IRK) andthe Permanent Working Group of the Highest State Health Author-ities (AOLG).

The result of the screening-audiometry was handed over to theparents directly after measurement had been completed. If thehearing impairment at any of the tested frequencies was equalor greater than 40 dB it was recommended to visit an ENT doctorfor more elaborated testing of the hearing. Hearing impairmentsgreater than 20 dB were considered in the analyses of potentialassociations between leisure activities and hearing ability.

Public use file

To offer other scientists the opportunity to perform additionalevaluations of the GerES IV data, a public use file with pollutantconcentrations and questionnaire data of all participants was madeavailable. More information about the public use file can be foundon the UBA website (UBA, 2010, in German).

Conclusions

GerES IV is the first nation-wide comprehensive study on theexposure of 3- to 14-year-old children to environmental pollutants.The survey is unique in Europe with regard to the age range of thechildren and the large variety of pollutants measured not only byHBM, but also by indoor monitoring (indoor air, tap water, housedust, mould) and noise measurement.

GerES IV achieved a sufficiently high rate of participation, ifone takes into account the decreasing willingness to participatein general population-related studies over the last decades (Latzaet al., 2004; Hoffmann et al., 2004). And – what is more important

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46 C. Schulz et al. / International Journal of Hygie

the representativeness of the GerES IV sample was confirmedy non-responder analyses. The responders and non-respondersid not differ notably with regard to demographic and importantxposure-related characteristics. Only a slight underrepresentationf low socio-economic status (SES) children could be observed. Thetructure of the sample was almost identical to the structure of theopulation with regard to gender, age and community size. Theinimal discrepancies could be adjusted by applying case weights.ence, GerES IV provides representative information about thenvironmental exposure of 3- to 14-year-old children in Germanys a whole as well as for different groups defined by age, gender,egion and other characteristics.

Most aims of GerES IV have meanwhile been reached: thextent and distribution of the analysed pollutants in all mediaas documented, trends were assessed, and exposure sourcesere identified. Current reference values (RV95) for contaminantsresent in the blood and urine of children were derived. For further

nformation see Schulz et al. (2011).GerES IV data served to initiate and control exposure and risk

eduction measures. The survey showed that e.g. decreasing thexposure of children to environmental tobacco smoke is still a pre-ominant task for environmental and health politics and that in aumber of households the guideline values of the Drinking Waterrdinance for domestic drinking water are likely to be exceeded. As

consequence of GerES IV data the limit value for uranium in theerman Drinking Water Ordinance has meanwhile been reduced

o 10 �g/l. GerES IV also showed that children are considerablyxposed to three out of six analysed plasticisers, the phthalatesEHP, BBP and DBP, which have to undergo authorisation or other-ise their use will be banned from 2014 on due to new chemicals

ct REACH (Registration, Evaluation and Authorisation of Chemi-als).

This paper gives a comprehensive overview of the samplingtrategy, investigation programmes and instruments in order torovide a detailed knowledge for scientists working in this field.cientists who have conducted a similar study can better assesshe comparability of their data with GerES IV data. Scientists whore planning a study can better decide which elements they mightdopt or adapt to their specific situation. Methods applied in GerESV are based on the expertise and experience collected in the GerESV pilot study and the three GerESs conducted before one of whichlso contained a (smaller) sample of children. Thus the usability andfficiency of most design, examination and interview componentsad been tested and proved before. The knowledge gained witherES over the years has enabled UBA to provide helpful input and

hus contribute to the following European projects.In 2004, the European Commission recognised in its Environ-

ent and Health Action Plan 2004–2010 (COM, 2004) the need forore harmonised approaches to human biomonitoring in Europe to

llow for better comparability of results and for the desired exten-ion of knowledge on the exposure of the European population tohemicals. Therefore, the EU funds the project COPHES (Consortiumo Perform Human Biomonitoring on a European Scale, 2009;OPHES is funded by the 7th Research Framework Programme ofhe EU) that has been developing guidelines and recommendationsor human biomonitoring programmes across the European Union.5 organisations from 27 countries participate in this project. UBA

s one of the workpackage leaders. Embedded in COPHES is theroject DEMOCOPHES (Demonstration of a study to Coordinatend Perform Human Biomonitoring on a European Scale; DEMO-OPHES is funded by LIFE+; Joas et al., 2012; DEMOCOPHES, 2011),hat conducts a pilot study in 17 countries to test the feasibility

f the harmonised approach and to develop preliminary referencealues for the analysed pollutants. The experience collected in theilot study will enable COPHES to finetune their guidelines andecommendations.

d Environmental Health 215 (2012) 435– 448

The new European chemicals legislation REACH that com-menced in 2007 is to improve the regulation and thereby safeguardprotection of the population against adverse effects coming fromthe exposure to chemicals. GerES data have proved valuable in iden-tifying problematic chemicals the regulation of which should beconsidered. A common European approach and harmonised HBMstudies will better allow to follow up efficiency of REACH and toascertain that the responsibility for a safe use and production ofchemicals is shifted successfully from governments to the produc-ers, importers and distributors.

Acknowledgements

We thank all those involved in this study: the families who tookpart in this time-consuming survey, the numerous colleagues inlocal health and environmental authorities, city halls, etc., whosupported the survey in their constituencies, as well as the surveyteams of the KiGGS and the GerES IV study for their commitmentand work in the field. We also thank the BMU and BMBF for theirfinancial support, and the GSF (now Helmholtz Zentrum München)for the external quality assurance of GerES IV. At the RKI, we par-ticularly thank Andreas Bauer, Norbert Birkner, Martin Gorecki,Jan Hegerfeld, Andreas Hünken, Heike Hölling, Panagiotis Kamtsi-uris, Bärbel-Maria Kurth, Silke Oberwöhrmann, Angelika SchaffrathRosario, Heribert Stolzenberg, Wolfgang Thierfelder, Michael Voigt,Dorothe Walter und Ute Wolf for the cooperation with KiGGS, forcarrying out the field work and for recording the questionnaire data.

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