1 / 15

Drugs, booze and heavy metal in pregnancy: Causes of childhood asthma and allergy?

Drugs, booze and heavy metal in pregnancy: Causes of childhood asthma and allergy? . Seif Shaheen Professor of Respiratory Epidemiology Centre for Primary Care and Public Health Blizard Institute Barts and The London School of Medicine and Dentistry s.shaheen@qmul.ac.uk.

adanna
Télécharger la présentation

Drugs, booze and heavy metal in pregnancy: Causes of childhood asthma and allergy?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Drugs, booze and heavy metal in pregnancy:Causes of childhood asthma and allergy? Seif Shaheen Professor of Respiratory Epidemiology Centre for Primary Care and Public Health Blizard Institute Barts and The London School of Medicine and Dentistry s.shaheen@qmul.ac.uk

  2. Hunting for the causes of asthma Primary prevention Secondary prevention in utero infancy childhood adolescence adulthood

  3. Does asthma begin in utero? Early presentation Prenatal risk factors Maternal smoking in pregnancy Antibiotic use in pregnancy Infections in pregnancy Complications of pregnancy Mode of delivery Gestational age at birth Anthropometry at birth

  4. O C H CH3 N OH Paracetamol Cytochrome P450 O O C C H CH3 N CH3 N Glutathione (GSH) Glutathione Transferase SG O OH N-Acetyl-p-benzoquinoneimine NAPQI Glutathione conjugate

  5. Importance of the prenatal environment “The only clever thing I did was to remember that life begins at conception, not at birth….” Alice Stewart

  6. Avon Longitudinal Study of Parents and Children (ALSPAC)

  7. Paracetamol use in late pregnancy and risk of wheezing at 3.5 years(Thorax 2002; 57: 958-63) Adj OR (95% CI) Paracetamol use Never 1.00 Sometimes 1.12(0.98, 1.28) Most days/daily 2.10 (1.30, 3.41)* *P=0.003

  8. Paracetamol use in late pregnancy and asthma and total IgE (Clin Exp Allergy 2005; 35: 18-25) Asthma@6yrs Total IgE@7yrs Adj OR (95% CI) Adj GMR (95% CI) Frequency of use Never 1.00 1.00 Sometimes 1.22 (1.06, 1.41) 1.14 (1.03, 1.26) Most days/ daily 1.62 (0.86, 3.04) 1.52 (0.98, 2.38) P trend:0.0037 0.0034

  9. Further evidence against confoundingIJE 2010; 39: 790-4 • Effects on Total IgE of prenatal exposure • Maternal prenatal 1.21 (1.09, 1.33) 0.00024 • Maternal postnatal 0.95 (0.85, 1.06) 0.35 • Partner postnatal 1.00 (0.86, 1.16) 0.98 • Confounding by unmeasured behavioural factors linked to paracetamol usage unlikely

  10. Gene by environment interaction Strengthening causal inference Biological plausibility modification of paracetamol effect by gene variants influencing toxicity Glutathione-S-transferase GSTT1, GSTM1, GSTP1 conjugates NAPQI with glutathione Nrf2 Nrf2 knockout mice sensitive to paracetamol toxicity Disruption of Nrf2 leads to increased allergic inflammation in a mouse model of asthma

  11. Paracetamol use in early pregnancy and asthma risk stratified by maternal Nrf2(JACI 2010; 126: 1141-8) Adj OR* 95% CI P C:C (n=3754) 0.99 0.81 to 1.21 0.91 T:C/T:T (n=1137) 1.73 1.22 to 2.45 0.002 Interaction 0.02 *Per category of exposure No interaction with child Nrf2 genotype

  12. Of mice and men • A mouse model of asthma (Clare Lloyd) • Prenatal intervention • Outcome: allergic airway inflammation

  13. Could prenatal alcohol be a risk factor? • Danish studies • Associated with raised cord IgE and infant eczema, but not hospitalisation for asthma • BUT • Intake tends to be under-reported • Confounding a big problem

  14. Mendelian randomisation: increasing rigour ALCOHOL Acetaldehyde Acetic acid Alcohol dehydrogenase ADH1B* Aldehydedehydrogenase ALDH2 *Carriers of A allele metabolise faster and drink less

  15. Acknowledgements • Funding • Asthma UK and British Lung Foundation • Colleagues • Jean Golding, John Henderson, Sue Ring, George Davey Smith (Bristol University) • John Holloway (Southampton University) • Roger Newson (Imperial College)

More Related