1. Environmental Influences: Welsh Landfill and Gastroschisis studies Dr. Shantini Paranjothy Walport Clinical Lecturer Public Health

2. Overview 1.Nant-y-Gwyddon and Trecatti 2.Study of 24 landfill sites 3.Gastroschisis Enhanced surveillance Case –control study

3. Trecatti landfill site 44 hectares 235,000 – 368,000 tons annually Industrial filter cakes Industrious and metalliferous waste, Contaminated soils Oily wastes, Sewage screenings

4. Nant-y-Gwyddon

5. Trecatti landfill site ExposedUn-expRR 1983 - 8717.8 p 1,00015.7 p 1,0001.1 (0.8, 1.6) 1989 - 9616.5 p 1,000 8.5 p 1,0001.9 (1.3, 2.9) Excluding minor anomalies1.5 (0.9, 2.4) Reported congenital anomaly rates: Office for National Statistics

6. Nant-y-Gwyddon

7. Con anomalies after opening landfill H0: There is no difference in rates of con mals among residents living close to landfill sites in Wales after the landfills opened compared with before they opened. 24 landfill sites in Wales Calculated expected rates for residents within 2km of landfill based on data for all births in residents living > 4km away

8. Con anomalies after opening landfill (1983 – 1997)O/E (Std. RR) Ratio after/before N=16,948 Before 0.9 (0.8, 1.0) After1.2 (1.1, 1.4) 1.4 (1.1, 1.7) (1998 – 2004) After N=10,023 1.02 (0.9, 1.1)

9. Challenges No data on actual exposures or confounders Single site studies – reporting bias, statistical power Multi site studies – heterogeneity of exposures Concentric circular regions –Spatial patterns not accounted for –Results sensitive to radii chosen –Not sensitive to geography

10. Nant-y-Gwyddon all births James L, Matthews I, Nix B Epidemiology Vol 15 (3) 2004

11. KDCP All births

12. Nant-y-Gwyddon con mals

13. KDCP: expected conmals

14. KDCP: observed conmals

15. RR by radii of exposed area

16. KDCP: RR of conmals

17. Gatroschisis 90% survival Surgery within 24hours Long stay on SCBU Feeding problems / TPN Short gut, NEC, Atresias

18. UK Regional prevalence

19. Age distribution of mothers

20. Gastroschisis aetiology Vascular accident 5-10 weeks Cocaine (PAR 6%- 7%) Tobacco (PAR 11% - 26%) Aspirin, decongestants (PAR 4% - 5%)

21. Gastroschisis aetiology Young maternal age Social disadvantage Poor nutrition / Low BMI / Low Zn Alcohol

22. Gastroschisis aetiology Tends to cluster Environmental exposures Metals and organochlorines

23. Enhanced surveillance Information for action Systematic collection of information To generate hypotheses that can be tested in future case-control studies.

24. Methods 1 st April 2006 - 31 st March 2007 Ethical approval from MREC Wales Diagnosis at 18-20 week USS Recruitment by Antenatal Screening Coordinators

25. Data items Demographics Housing and neighbourhood Obstetric and medical history Lifestyle Diet and nutrition Occupational exposures Hobbies and leisure activities

26. Response rates 1 st April 2006 – 31 st March 2007 No. cases reported to CARIS20 Cases reported to study13 Agreed to participate and interviewed 7

27. Results Age 18-26 years Not linked in time place or person BMI 20-32 6 lived near industry – stone quarries, factory, building / road work 6 smoked at least 10 cigs per day 4 reported binge drinking at 5-10 weeks gestation 4 reported use of marijuana

28. Lifestyle factors alcohol smoking Environmental organochlorines metals Dietary low BMI poor nutrition NO Free radicals Glutathione stress Apoptosis R umbilical vein Current hypothesis Gastroschisis

29. Case control study Research questions What is the effect of maternal exposure to chemicals in the environment on the development of gastroschisis? Does binge drinking and smoking in the first ten weeks of pregnancy increase risk of gastroschisis? How does maternal nutritional status and body fat percentage affect the risk of gastroschisis?

30. Case control study Case: Gastroschisis – antenatal diagnosis at anomaly USS Control: Normal anomaly USS, matched for maternal age, from same booking clinic as case Sample size 100 cases 300 controls

31. Methods Blood test – Environmental chemicals, no toxicology Body fat percentage – callipers Interview administered questionnaire

32. Logistics Case identified at 18-20 weeks anomaly scan Antenatal Screening Midwife Give information Follow up Identify and approach 3 controls Study team Consent Interview Blood samples WALES – 13 NHS Trusts, 20 - 30 cases per year

33. Antenatal Screening Wales British Association of Paediatric Medicine British Association of Paediatric Surgeons BINOCAR CARIS British Maternal and Fetal Medicine Health Protection Agency National Public Health Service for Wales Ethical approval from MREC Wales Funded by Birth Defects Foundation Newlife Collaboration between CU and