Pregnancy complications and conditions and respiratory health

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1 Pregnancy complications and conditions and respiratory health Franca Rusconi Unità di Epidemiologia, AOU Meyer

2 Pregnancy complications/conditions and wheezing and asthma in offspring Focus on: Maternal smoking in pregnancy Exposure to air pollution Pregnancy complications - hypertensive disorders of pregnancy - maternal obesity Maternal antibiotics Caesarean section Exposure to farming

3 Piccolipiù 3

4 Pre-schoolwheezingand asthmaat schoolageare associated to reduced lung function at birth Martinez et al, N Engl J Med 1988 Haland et al, N Engl J Med 2006 Bisgaard et al, Am J Respir Crit Care Med 2012

5 Pregnancy complications/conditions and wheezing and asthma in offspring Maternal smoking in pregnancy Hypertensive disorders of pregnancy Diminished lung function at birth. Stick et al, Lancet 1999 Pregnancy complications - hypertensive disorders of pregnancy - maternal obesity Maternal antibiotics Caesarean Exposure to farming

6 Pooled analysis in 8 European birth cohorts. Associations betweeenmaternalsmoking duringpregnancyonly and asthma at 4-6 yrs: a dose-response relationship A Newman, Am J Crit Care Med 2012; 186: 1037

7 Pregnancy complications/conditions and wheezing and asthma in offspring Maternal smoking in pregnancy Exposure to air pollution Pregnancy complications - hypertensive disorders of pregnancy - maternal obesity Maternal antibiotics Caesarean Exposure to farming

8 ESCAPE: a European cohort study

9

10 Pregnancy complications/conditions and wheezing and asthma in offspring Maternal smoking in pregnancy Pregnancy complications - hypertensive disorders of pregnancy Diminished lung function at birth. Stick et al, Lancet maternal obesity Maternal antibiotics Caesarean Exposure to farming

11 Maternal Complications and Procedures in Pregnancy and at Birth and Wheezing Phenotypes in Children F Rusconi, C Galassi, F Forastiere, M Bellasio, M De Sario, G Ciccone, L Brunetti, E Chellini, G Corbo, S La Grutta, E Lombardi, S Piffer, F Talassi, A Biggeri, N Pearce, and the SIDRIA-2 Collaborative Group Hypertension or pre-eclampsia Early transient wheezing Persistent wheezing Late-onset wheezing Am J Respir Crit Care Med, 2007

12 We confirmed an association between preeclampsia and recurrent wheezing in the first 18 months of offspring s life Maternal complications and conditions in pregnancy and wheezing in early childhood: A combined analysis of 14 European birth cohorts Daniela Zugna, Claudia Galassi, Isabelle Annesi-Maesano, Nour Baiz, Henrique Barros, Sofia Correia, Valentina Di Gregori, Liesbeth Duijts, Francesco Forastiere, Mireia Gascon, Hazel Inskip, Vincent W.V. Jaddoe, Maria Pia Fantini, Pernille Stemann Larsen, Anne-Marie Nybo Andersen, John Penders, Maria Skaalum Petersen, Daniela Porta, Ulrike Steuerwald, Jordi Sunyer, Carel Thijs, Martine Vrijheid, Lorenzo Richiardi and Franca Rusconi ERJ September 1, 2013 vol. 42 no. Suppl 57 P1628

13 Diminished endothelial growth factor activity and lung development

14

15 Gagliardi et al, Pediatrics 2014

16 Pregnancy complications/conditions and wheezing and asthma in offspring Maternal smoking in pregnancy Pregnancy complications - hypertensive disorders of pregnancy - maternal overweight/obesity Maternal antibiotics Caesarean Exposure to farming

17 We confirmed an association between overweight and obesity and recurrent wheezing in the first 18 months of offspring s life Maternal complications and conditions in pregnancy and wheezing in early childhood: A combined analysis of 14 European birth cohorts Daniela Zugna, Claudia Galassi, Isabelle Annesi-Maesano, Nour Baiz, Henrique Barros, Sofia Correia, Valentina Di Gregori, Liesbeth Duijts, Francesco Forastiere, Mireia Gascon, Hazel Inskip, Vincent W.V. Jaddoe, Maria Pia Fantini, Pernille Stemann Larsen, Anne-Marie Nybo Andersen, John Penders, Maria Skaalum Petersen, Daniela Porta, Ulrike Steuerwald, Jordi Sunyer, Carel Thijs, Martine Vrijheid, Lorenzo Richiardi and Franca Rusconi ERJ September 1, 2013 vol. 42 no. Suppl 57 P1628

18 Putative mechanisms Maternal adiposity Childhood wheezing/asthma AJ Lowe et al, Plos One June 2013, modified

19 Pregnancy complications/conditions and wheezing and asthma in offspring Maternal antibiotics Caesarean section Altered bowel and vaginal maternal microbial flora Abnormal microbial flora in offspring airways.and gut Disruption of the mucosal immune tolerance and development of Th (Thelper) type 2-mediated diseases

20 Prenatal exposure to antibiotics and wheezing: An internet-based birth cohort study M. Popovic, D. Zugna, C. Galassi, F. Merletti, E. Migliore, L. Gagliardi, F. Rusconi, L. Richiardi ERS, Munich, Sept 2014 The association between prenatal exposure to antibiotics and infant wheezing is largely explained by confounding factors although an excess risk of wheezing after exposure during the third trimester of pregnancy cannot be excluded. Maternal genitourinary infections in pregnancy seem to be associated with wheezing independently of antibiotic use.

21 Traditional farms living Upregulation of innate immunity receptors Protection against development of IgG1, IgG4, IgE antibodies (modified)

22

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