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SELECTED PRENATAL FACTORS EFFECTING ALLERGY AND ASTHMA OUTCOMES

SELECTED PRENATAL FACTORS EFFECTING ALLERGY AND ASTHMA OUTCOMES. Michael V. Keiley, M.D. Adult and Childhood Allergy and Asthma Boise Valley Asthma and Allergy Clinic BVAAC.com Boise, Meridian, Eagle, Nampa, & Caldwell. SELECTED PRENATAL FACTORS EFFECTING ALLERGY AND ASTHMA OUTCOMES.

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SELECTED PRENATAL FACTORS EFFECTING ALLERGY AND ASTHMA OUTCOMES

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  1. SELECTED PRENATAL FACTORS EFFECTING ALLERGY AND ASTHMA OUTCOMES • Michael V. Keiley, M.D. • Adult and Childhood • Allergy and Asthma • Boise Valley Asthma and Allergy Clinic • BVAAC.com • Boise, Meridian, Eagle, Nampa, & Caldwell

  2. SELECTED PRENATAL FACTORS EFFECTING ALLERGY AND ASTHMA OUTCOMES

  3. SELECTED PRENATAL FACTORS POTENTIALLY EFFECTING POSTNATAL ALLERGY AND ASTHMA OUTCOMES • Maternal Diet • Active smoking • Vitamin D • Prebiotics/probiotics • C-section • Maternal stress • Obesity

  4. OTHER PRENATAL FACTORS POTENTIALLY EFFECTING POSTNATAL ALLERGY AND ASTHMA OUTCOMES (continued) • Acetaminophen (paracetamol) exposure • Traditional farm exposure • Bisphenol A exposure

  5. ALLERGIC CONDITIONS • Asthma/wheezing • Allergic rhinitis • Atopic dermatitis • IgE-mediated food allergy

  6. It can be very difficult to separate out the impact of prenatal vs. postnatal factors on allergy and asthma

  7. Specific postnatal allergy and asthma outcomes may be driven by different factors

  8. Credibility of a Theory • Biological plausibility • Multiple studies over a range of ages • Meta-analyses • Randomized-controlled studies • Clinical vs. statistical significance • Guidelines from societies

  9. Maternal Pregnancy Diet • Prevention of non-food allergic illness • Prevention of food allergy

  10. Maternal dietary prevention of non-food allergic illness • “The available epidemiologic evidence is weak but nonetheless supportive with respect to vitamins A, D and E; zinc, fruit and vegetables; and a Mediterranean diet for the prevention of asthma”1 1. Nurmatov, U. J Allergy Clin Immun 20111;127:724-33.

  11. Should a pregnant woman who had a previous child with peanut allergy eat peanut products during her pregnancy ?

  12. WE GREW UP WITH THE NOTION OF THE PEANUT AS A BENIGN, NUTRITIOUS, CHARMING FELLOW . . . BUT TO THE PEANUT-ALLERGIC PERSON AND HIS/HER FAMILY, HE IS A VICIOUS, UNFORGIVING MONSTER!

  13. ALARMING CHARACTERISTICS OF PEANUT ALLERGY • 1-2% of infants/children in westernized English speaking countries • Associated with life-threatening anaphylaxis (50% of reactions) • Reaction may occur on first known exposure (72%) • Provocative dose for symptoms is lower than for other allergens • Occurs earlier in life than other food allergies (median age 22 months) • Accidental ingestion common (55% over three years) • Rarely outgrown • Associated with a very impaired quality of life! • 25-35% are also tree nut allergic

  14. Recommendations for peanut/tree nut consumption during pregnancy and lactation • AAP 2000: Mothers at risk of atopy should avoid peanuts during pregnancy and lactation • AAP 2008: The AAP rescinded their recommendations and replaced it with a statement that the efficacy of this practice remains unproven • AAAAI/ACAAI Food Allergy Draft Practice Parameters 10/9/13: “Do not recommend maternal allergen avoidance…because these approaches have not been proven to be effective for primary prevention of atopic disease” • There are currently no clear recommendations regarding how to proceed • There are some additional data now available that might impact this decision making process

  15. Peanut and tree nut consumption during pregnancy and allergic disease in children • Methods • Data from Danish national Birth cohort (n=61,908) • Maternal peanut and tree nut intake was assessed using a validated midpregnancy food frequency questionnaire • Allergic and asthma outcomes at 18 months and 17 years of age Msalova, S. et. al. J All Clin Immun 2012;130:724-32.

  16. Peanut and tree nut consumption during pregnancy and allergic disease in children • Results • Maternal intake of peanuts and tree nuts was inversely associated with asthma in children at 18 months of age • Compared with mothers consuming no peanuts, children whose mothers reported eating peanuts 1 or more times per week were 0.66 times more likely to have a registry-based and medication related asthma diagnosis, respectively. Msalova, S. et. al. J All Clin Immun 2012;130:724-32.

  17. Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants • Methods • 503 infants 3-15 months of age with likely milk or egg allergy but no previous diagnosis of peanut allergy • IgE CAP-RAST to peanut obtained • Frequency of maternal consumption of peanut was assessed during pregnancy as well as breast feeding Sicherer, S. et. al. J All Clin Immun 2010;126:1191-97

  18. Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants • Results • Frequency of peanut consumption during pregnancy showed a dose-response association with peanut IgE > 5 kU/L in breast fed and non-breast infants • Peanut consumption during breastfeeding was not associated with a peanut IgE >5 kU/l Sicherer, S. et. al. J All Clin Immun 2010;126:1191-97

  19. Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants Sicherer, S. et. al. J All Clin Immun 2010;126:1191-97

  20. Epicutaneous peanut exposure might play an important role sensitization • Peanut reactions usually occur on the 1st know exposure • In animal models cutaneous exposure induces allergy (IgE and intestinal mast cell proliferation) and oral exposure induces tolerance1 • Early-onset severe atopic dermatitis and the application of Arachis (peanut) oil onto eczematous skin are risk factors for the development of peanut allergy2 • A dose-response relationship has been demonstrated between household peanut consumption and peanut allergy in young children3 • Bartnikas, J All ClinImmun2013:131:417-43. • Lack, G. NewEngland Journal of Medicine 2003;348:977-85. • Fox, A. J All ClinImmun2009:123:417-423. .

  21. Peanut protein in household dust is related to household peanut consumption and is biologically active • Methods • 46 families with infants were recruited from a pediatric allergy clinic • Peanut protein was quantified in wipe and dust samples form multiple sites throughout the home • Peanut consumption was assessed by using a validated peanut food frequency questionnaire • Whole dust samples were used to stimulate basophils in peanut-monoallergic and 3 nonallergic children Brough, A. et. al. J All Clin Immun 2013;1132:623-9

  22. Peanut protein in household dust is related to household peanut consumption and is biologically active • Results • There was a significant positive correlation between peanut protein in the infants bed, crib, rail, and play area and reported household peanut consumption over 1 and 6 months. • Dust samples containing peanut protein induced dose-dependent basophil activation in children with peanut allergy Brough, A. et. al. J All Clin Immun 2013;1132:623-9

  23. Distribution of peanut protein in the home environment Brough, A. et. al. J All Clin Immun 2013;1132:623-9.

  24. THE PEANUT ALLERGEN IN THE HOME ENVIRONMENT MAY BE MORE IMPORTANT THAN THE PEANUT PRODUCTS THAT THE PREGNANT WOMEN EATS!

  25. SMOKING

  26. SMOKING DURING PREGNANCY • Nicotine, carcinogens, and other pathogens pass through the placental barrier • Intrauterine smoke exposure (IUS) decreases blood flow as well as oxygen and nutrient delivery • Multiple studies including at least one meta-analysis show impaired postnatal lung function and more wheezing1 1. Burke, H. Pediatrics 2012;129:735-744.

  27. SMOKING DURING PREGNANCY • IUS reduces age-related improvements in bronchial hyperactivity1 • IUS decreases the effects of inhaled steroids on airway hyperresponsiveness1 • IUS associated with hospitalization/mortality from respiratory infections2 • It is very difficult to separate pre and postnatal smoke exposure • Cohen, R. J All Clin Immun 2010:126:491-7. • Metzger, M. Pediatric Infectious Disease Journal 2013;32:e1-7.

  28. Maternal smoking in pregnancy and asthma in preschool children • Pooled analysis of 8 European birth cohorts • Effect of maternal smoking during pregnancy but not during the 1st year on wheezing and asthma at 4-6 years of age • 21,600 children • 735 exposed prenatally but not during the 1st year Neuman, A. et. al. A. J Respir. Crit Care Med 2012;1861037-43

  29. Maternal smoking in pregnancy and asthma in preschool children • Results • Maternal smoking exclusively during pregnancy was associated with wheeze as well as asthma at 4-6 years of age • Maternal smoking only during the 1st trimester was associated with asthma and wheezing at 4-6 years of age (oR 1.39) Neuman, A. et. al. A. J Respir. Crit Care Med 2012;1861037-43

  30. SMOKING CESSATION SHOULD BEGIN BEFORE CONCEPTION!

  31. VITAMIN D

  32. Muehleisen, B. J All Clin Immun 2013;131:324-9. 2012;185:124-32.

  33. Paul, G. Vitamin D and Asthma. Am J Respir Crit Care Med. 2012;185:124-32.

  34. Vitamin D Guidelines • Institute of Medicine: 20 ng/ml (50 nmol/l)1 • Endocrinology Society: 30 ng/ml (75 nmol/l)2 ( (20-30 ng/ml insufficient, < 20 ng/ml deficient) • Conversion: ng/ml X 2.5 = nmol/l • Rosen, C. J ClinEndocrinolMetab2012;97:1146-52. 2. Hollick, M. J ClinEndocrinolMetab2011;96:1911-30.

  35. Sharief, S. J Allergy Clin Immun 2011;127:1195-1202.

  36. Vitamin D insufficiency is associated with challenge-proven food allergy in infants • Methods • 5276 one-year old infants assessed for food allergy • Food challenges were conducted on most of the children with positive tests • 274 food allergic children • 207 non food allergic children were used as controls • Vitamin D status assessed (vitamin D insufficiency 26-50 nmol/L) Allen, K. et. al. A. J Al Clin immun 2013;131:1109-16

  37. Vitamin D insuffeciency is associated with challenge-proven food allergy in infants • Results • Infants of Australian-born parents with vitamin D insufficiency (<50 mmol/l) were more likely to be peanut (aOR 11.51) and/or egg allergic (aOR 3.79) • Infants of Australian-born parents with vitamin D insufficiency were more likely to have multiple food allergies than a single food allergy (aOR 10.48) • Among infants that were food sensitized, vitamin D insufficiency was associated with increased odds of food allergy Allen, K. et. al. A. J Al Clin immun 2013;131:1109-16

  38. Allen, K. et. al. A. J All Clin Immun 2013;131:1109-16

  39. Allen, K. J All Clin Immun 2013;131:1109-16

  40. Vitamin D and food allergy in patients with severe atopic dermatitis • Methods • 39 patients referred for severe atopic dermatitis and food allergy • Patients with atopic dermatitis and food allergy had their serum vitamin D levels compared to those of patients with atopic dermatitis and no food allergy • Results • For every 1-unit increase in 25-OH vitamin D, the chances that someone had food allergy decreased by 6% (p=0.01) Mohiuddin, M. J Al Clin Immun 2013 (article in press)

  41. Nurmatov, U. J Allergy Clin immun 2011;127:724-33.

  42. Cord serum 25-OH vitamin D and risk of early childhood wheezing and atopic dermatitis. • Methods • Cord blood samples from the EDEN birth cohort were analyzed for 25-OH vitamin D • Follow-up for 5 years with ISSAC questionnaire (asthma , wheeze, allergic rhinitis, atopic dermatitis) Baiz, K. et. al. A. J Al Clin Immun (article in press)

  43. Cord serum 25-OH vitamin D and risk of early childhood wheezing and atopic dermatitis. • Results • Median cord serum 25-OH vitamin D level was 17.8 ng/ml • There was an inverse association between 25-OH vitamin D and transient wheezing as well as atopic dermatitis Baiz, K. et. al. A. J Al Clin Immun (article in press)

  44. Cord serum 25-OH vitamin D and risk of early childhood wheezing and atopic dermatitis. Baiz, K. et. al. A. J All Clin Immun (article in press)

  45. PROBIOTICS

  46. Prebiotics and probiotics • Probiotics: Live microorganisms administered in adequate amounts to that confer a beneficial health effect on the host1 • Prebiotics:nondigestible food components that beneficially effect the health of the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon and thereby improve host health2 • Synbiotic: contains both prebiotics and probiotics3 • Sanders, M. Gut 20013:62:787-796 • Gibson, G. J Nutr 1995;125:1401-1412 • Screzenmeir, J. Am J Clin Nut 2001:73:S361-S364

  47. Probiotics • Several meta-analyses show efficacy of probiotics in the prevention of atopic dermatitis • Other issues: • Strain(s) • Quality control (not FDA approved) • Dose? • Administer to mom, baby, or both? • Probiotics plus or minus prebiotics • Administer to entire population or those at risk? • Safety (rare risk of bacteremia in high risk subjects) • May occasionally contain milk protein

  48. Pfefferle, P. et. al. J All Clin Immun 2013;131:1453-63.

  49. Probiotic milk consumption in pregnancy and infancy and subsequent allergic illness • Methods • Norway mother and child cohort study (MoBa) • 40,164 infants at low risk of allergy • Probiotic milk/yogurt consumption assessed • Biola milk/yogurt, Cultura milk (lactobacillus/bifidobacterium) • Questionaire data regarding atopic dermatitis, allergic rhinitis, and asthma Bertelson, R. et. al. J All Clin Immun 2013 (in press)

  50. Probiotic milk consumption in pregnancy and infancy and subsequent allergic illness Bertelson, R. et. al. J All Clin Immun 2013 (in press)

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