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2. Effect of air pollution exposure during pregnancy on the steroid profile of newborns Rüedi S*, Proietti Elena*, Gorlanova O, Dick B, Flück C, Röösli M, Latzin P, M. Frey B, Frey U

3. Prenatal air pollution exposure has adverse effects on the infant’s respiratory system. One pathway involved might be via oxidative stress, possibly leading to a modified pattern of steroid production. Introduction

4. We examined a possible association of air pollution exposure during pregnancy and steroid metabolites in the newborn’s urine. Aim Air Pollution pregnancy Steroids profile at one month

5. Methods – BILD cohort Prenatal recruitment Age 1 month Urin collection

6. Air Pollution pregnancy Steroids profile at one month Methods – exposure and outcome  PM10 from background monitoring station  NO2 background monitoring station and hybrid time-space regression model Spot urine mass spectrometry/ gas chromatography

7. Air Pollution pregnancy Steroids profile at one month Methods - statistic season distance to road urban area smoking exposure socio-economic status Sex, gestational age, weight delivery mode Adjusted for:

8. 5β-reductase α-cortolone β-cortolone THE DHE 5α-DHF 5β-reductase 3αHSD α-cortol β-cortol 20aHSD/20βHSD THF α-THF 3αHSD 6β-OHF CYP3A Cortisone ECortisol F 11- β HSD2 (NAD+) 11- β HSD1 (NADH) 5β-DHF Methods - steroids

9. Results – PM 10 (aRR per 10mg/m 3 PM10 increase) All 1.46 (1.06/2.02) Cortisol/Cortisone 1.04 (0.81/1.34) Branche F 1.42 (0.96/2.1) Branche E 1.45 (1.06/1.99) All metabolites 1.6 (1.14/2.28) Branche F metabolites 1.62 (1.04/2.54) Branche E metabolites 1.60 (1.14/2.23) N=129

10. Results – NO 2 background (aRR per 10mg/m 3 NO 2 increase) All No association Cortisol/Cortisone No association Branche F No association Branche E No association All metabolites No association 6βOH cortisol 4.9 (1.6/14.9)* 4.10 (1.6/10.6) *Pathologic CTG aRR 1.6 (1/2.5) N=120 *distance to road (50m) aRR 0.98 (0.97/0.99)

11. Results – NO 2 model (aRR per 10mg/m 3 NO 2 increase) All No association Cortisol/Cortisone No association Branche F No association Branche E No association All metabolites No association 6βOH cortisol 1.3 (0.9/1.7) 6βOH cortisol/F 1.14 (0.9/1.5) 6βOH cortisol/F 1.14 (0.9/1.5) N=120

12. Conclusions PM 10 exposure during pregnancy is associated with an overall increase of stress steroids production. Air pollution exposure during pregnancy is associated with alterations of the steroid profiles in newborns’ urine.

13. Conclusions If air pollution modelling was purely based on home location of mothers without considering maternal mobility, the risk ratio significantly decreased background NO 2 is associated with increased 6bOH- cortisol 6bOH-F/F ratio, which may suggest induction of the cytochrome enzymes. Even at low environmental doses of air pollution we found steroids response as know trigger such as perinatal stress

14. Thank you Elena.proietti@ukbb.ch

15. OHFRRCI No2 background 4.961.6414.94 sex 1.000.731.37 Gest age 0.890.790.99 sectio 0.990.661.48 smoke 0.890.601.32 education mid 0.750.481.16 education upper 0.720.471.12 studywgt 1.00 Road dist 50m 0.980.971.00 urban 0.900.651.25 season 1.560.922.65 p-value 0.01 1.00 0.04 0.96 0.55 0.19 0.15 0.02 0.01 0.54 0.10

16. Methods - DAG Air pollution Steroids SES Pregnancy behaviour psychological stress Maternal education Season sex Gestational age + weight sectio Smoking Urban/rural home

17. PM 10 effect on overall steroids production – different adjustments

18. Air Pollution exposure of the BILD cohort (region of Bern – Switzerland)

19. European Environment Agency – NO2 annual averages 2005