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

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

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

Nant-y-Gwyddon

Trecatti landfill site ExposedUn-expRR p 1, p 1, (0.8, 1.6) p 1, p 1, (1.3, 2.9) Excluding minor anomalies1.5 (0.9, 2.4) Reported congenital anomaly rates: Office for National Statistics

Nant-y-Gwyddon

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

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, (0.9, 1.1)

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

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

KDCP All births

Nant-y-Gwyddon con mals

KDCP: expected conmals

KDCP: observed conmals

RR by radii of exposed area

KDCP: RR of conmals

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

UK Regional prevalence

Age distribution of mothers

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

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

Gastroschisis aetiology Tends to cluster Environmental exposures Metals and organochlorines

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

Methods 1 st April st March 2007 Ethical approval from MREC Wales Diagnosis at week USS Recruitment by Antenatal Screening Coordinators

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

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

Results Age years Not linked in time place or person BMI 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

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

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?

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

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

Logistics Case identified at 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, cases per year

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