1. Environmental Risk Factors for Allergy Development in Children 1 Čižnár, P., 2 Reichrtov á, E., 2 Palkovi čová, Ľ., 3 McNabb, S.J.N., 3 Dunlop, A.L., 2 Rausová, K., 2 Adam čá kov á - Dodd, A. 1 Children’s Hospital, Comenius University, Bratislava, Slovakia, 2 Institute of Preventive and Clinical Medicine, Bratislava, Slovakia, 3 Centres for Disease Control and Prevention, Atlanta, USA

2.  Allergic diseases (AD) are increasing worldwide, with substantial differences among regions.  Besides genetics and allergen exposure, environmental factors substantially participate in allergy development in early childhood.  There is a considerable effect of environment in the antenatal and postnatal period on the prevalence of atopy (Warner, J.O., Thorax 54, 1999, Suppl. 2, 46-51).  The most frequent diagnosis from AD among infants (up to 12-months of age) is the diagnosis of atopic dermatitis.  Allergic respiratory symptoms often occur among children in early childhood and may indicate the development of asthma later in their life. BACKGROUND

3. Determinants of allergic diseases Genetic susceptibility Allergic sensitization Airway / Skin hyperresponsiveness Disease A E L X L P E O R S G U E R N E Adjuvant factors: Tobacco smoke, Pollutants Lack of protective factors: Infections? Immunization? Nutrition? Trigger factors: Pollutants, Exercise, Infections

4. The project “ Epidemic Investigation of Allergic Diseases among Children in the Slovak Republic ” was launched in 1996 in 8 environmentally different Slovak regions (polluted by metallurgy, chemical industry, agriculture and 1 rural region). INTRODUCTION

5. AIM OF THE PRESENTATION To examine the relationship between selected prenatal factors (incl. placental and cord blood contamination by selected xenobiotics) and total umbilical IgE (uIgE) positivity among a birthed cohort of neonates. To analyse the frequency of selected risk factors and the development of ADs in the first year of life in infants.

6. METHODS Recruitment of the mothers according to Enrolment Criteria Questionnaires Chemical analyses of Hg, Cd and Pb concentrations in the placentas and cord blood samples by AAS Detection of uIgE by fluoroimunoassay (Pharmacia CAP System RAST® FEIA, Kabi Pharmacia Diagnostics AB, Uppsala, Sweden) Clinical examination of 1-year-old children by regional allergists.

7. COHORT CHARACTERISTICS Questionnaire 1 (at birth) - 1978 mothers (app. 250 per region) Quest. 2 & Examination - 1250 (64.4%) children (1st year) Mother‘s age: mean 25.7 years (range: 16-42) Mother‘s education: primary4.6% secondary 83.6% university11.8% Prevalence of self-reported AD in mothers: 39.1% Child‘s gender: girls 49.4% boys 50.6% Number of living siblings: mean 0.81 (range 0-7)

8. Positivity/negativity of total uIgE in newborns [%][%] 37.2% 62.8% Positive uIgE............. > 0.35 kU/L

9. Relationship of Cord blood IgE Positivity to Region Type, Slovak Republic, 1997-1998. Denotes significantly different from the rural region type at the 0.05 level. Reichrtova, E. et al, ACII, 2002

10. Relationship between Cord blood IgE Positivity and Parental Cigarette Smoking, Slovak Republic, 1997-1998. Reichrtova, E. et al, ACII, 2002

11. Predictors of uIgE positivity Predictor %cOR95%CIaOR95%CI%Regression Living in agricult. region 39,92,9(1,8;,4,7 ) 3.6(2.1;6.4)39 Using electricity 16,50,5(0.3;0.9)0.5(0.3;0.8)12 Birth in Spring 33,12,2(1.1;4.4)2.3(1.1;5)10 Living near heavy traffic 43,60,6(0.4;1.0)0.5(0.3;0.9)9 Father employed in agriculture 7,52,5(0.9;7.6)5.8(1.1;31)7 Maternal AD 44,31,6(1.0;2.4)1.8(1.1;3)5 Birth in Autumn 17,31,5(0.9;2.9)2.4(1.2;5.1)1 Reichrtova, E. et al, ACII, 2002

12. Positivity of uIgE and Concentrations of Cd and Hg in Placenta and Cord Blood Placental c(Cd) [  g.g -1 ] r = - 0.2, p<0.001 Umbilical c(Hg) [  g.g -1 ] r = 0.124; p<0.05 [%]

13. Diagnosed ADs among Slovak Infants at 1-Year of Age Allergic Diseases 184/1326 (13.9%) Atopic Eczema 103/1326 (7.7%) ARS 48/1326 (3.6%) Allergic Rhinitis 5/1326 (0.4%) Food 10/1326 (0.8%) Drug 18/1326 (1.4%) IPCM ARS – asthma respiratory symptoms

14. Frequency of atopic dermatitis in the first year of life according to clinical finding and clinical history. Ciznar, P. et al, Lek Obz. 2000.

15. Relationship between Placental Pb Concentrations (25%ile, Median, 75%ile) and ARS in 1-Year-Old Children ARS = Asthma Respiratory Symptoms Plac. Pb concentrations [  g.g -1 ] 0.039 0.038 0.044 0.016 0.03 0.023 IPCM cOR=2.83, 95% CI: 1.33, 6.08 Placental Pb concentration – higher in smoking mothers (p<0.05) aOR=2.61, 95% CI: 1.19, 5.69

16. CONCLUSIONS (1) oNearly one-third of pregnant women in Slovakia report physician-diagnosed allergic disease. oPrevalence of total umbilical IgE positivity in neonates was greater in agricultural regions if compared to rural and industrial regions. oReported incidence of atopic dermatitis in Slovakia is significantly underestimated, and it is comparable with countries with high incidence rates of atopic dermatitis. oAllergy prevention in children should be targeted at the pregnant women and early postnatal period of life

17. CONCLUSIONS (2 ) Hypothesis on intrauterine programming of allergy/atopy with respect to placental xenobiotic contamination is tested in EU 5 th FP project PLUTOCRACY QLK4-CT-2000-00279: „Placental Uptake and Transfer of Environmental Chemicals Relating to Allergy in Childhood Years“.