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1SELECTED PRENATAL FACTORS EFFECTING ALLERGY AND ASTHMA OUTCOMES

Michael V. Keiley, M.D.Adult and Childhood Allergy and AsthmaBoise Valley Asthma and Allergy ClinicBVAAC.comBoise, Meridian, Eagle, Nampa, & Caldwell

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SELECTED PRENATAL FACTORS EFFECTING ALLERGY AND ASTHMA OUTCOMES23SELECTED PRENATAL FACTORS POTENTIALLY EFFECTING POSTNATAL ALLERGY AND ASTHMA OUTCOMES

Maternal DietActive smokingVitamin D Prebiotics/probioticsC-sectionMaternal stressObesity

34OTHER PRENATAL FACTORS POTENTIALLY EFFECTING POSTNATAL ALLERGY AND ASTHMA OUTCOMES (continued)

Acetaminophen (paracetamol) exposureTraditional farm exposureBisphenol A exposure

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ALLERGIC CONDITIONSAsthma/wheezingAllergic rhinitisAtopic dermatitis IgE-mediated food allergy

56It can be very difficult to separate out the impact of prenatal vs. postnatal factors on allergy and asthma67Specific postnatal allergy and asthma outcomes may be driven by different factors78Credibility of a TheoryBiological plausibilityMultiple studies over a range of agesMeta-analysesRandomized-controlled studiesClinical vs. statistical significance Guidelines from societies

89Maternal Pregnancy Diet

Prevention of non-food allergic illnessPrevention of food allergy

910Maternal 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 asthma1

1. Nurmatov, U. J Allergy Clin Immun 20111;127:724-33.1011Should a pregnant woman who had a previous child with peanut allergy eat peanut products during her pregnancy ? 1112

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!13ALARMING CHARACTERISTICS OF PEANUT ALLERGY1-2% of infants/children in westernized English speaking countriesAssociated with life-threatening anaphylaxis (50% of reactions)Reaction may occur on first known exposure (72%)Provocative dose for symptoms is lower than for other allergensOccurs earlier in life than other food allergies (median age 22 months)Accidental ingestion common (55% over three years)Rarely outgrownAssociated with a very impaired quality of life!25-35% are also tree nut allergic

14AAP 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 avoidancebecause 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

Recommendations for peanut/tree nut consumption during pregnancy and lactation15Peanut and tree nut consumption during pregnancy and allergic disease in children

MethodsData from Danish national Birth cohort (n=61,908)Maternal peanut and tree nut intake was assessed using a validated midpregnancy food frequency questionnaireAllergic and asthma outcomes at 18 months and 17 years of ageMsalova, S. et. al. J All Clin Immun 2012;130:724-32.

1516Peanut and tree nut consumption during pregnancy and allergic disease in children

ResultsMaternal intake of peanuts and tree nuts was inversely associated with asthma in children at 18 months of ageCompared 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.

1617Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants

Methods503 infants 3-15 months of age with likely milk or egg allergy but no previous diagnosis of peanut allergyIgE CAP-RAST to peanut obtained Frequency of maternal consumption of peanut was assessed during pregnancy as well as breast feedingSicherer, S. et. al. J All Clin Immun 2010;126:1191-97

1718Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants

ResultsFrequency of peanut consumption during pregnancy showed a dose-response association with peanut IgE > 5 kU/L in breast fed and non-breast infantsPeanut 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

1819Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infantsSicherer, S. et. al. J All Clin Immun 2010;126:1191-97

1920Epicutaneous peanut exposure might play an important role sensitization Peanut reactions usually occur on the 1st know exposureIn animal models cutaneous exposure induces allergy (IgE and intestinal mast cell proliferation) and oral exposure induces tolerance1Early-onset severe atopic dermatitis and the application of Arachis (peanut) oil onto eczematous skin are risk factors for the development of peanut allergy2A dose-response relationship has been demonstrated between household peanut consumption and peanut allergy in young children3

Bartnikas, J All Clin Immun 2013:131:417-43.Lack, G. New England Journal of Medicine 2003;348:977-85.Fox, A. J All Clin Immun 2009:123:417-423.. 21Methods46 families with infants were recruited from a pediatric allergy clinicPeanut protein was quantified in wipe and dust samples form multiple sites throughout the homePeanut consumption was assessed by using a validated peanut food frequency questionnaireWhole dust samples were used to stimulate basophils in peanut-monoallergic and 3 nonallergic childrenBrough, A. et. al. J All Clin Immun 2013;1132:623-9Peanut protein in household dust is related to household peanut consumption and is biologically active 2122ResultsThere 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;1132:623-9Peanut protein in household dust is related to household peanut consumption and is biologically active 2223Distribution of peanut protein in the home environmentBrough, A. et. al. J All Clin Immun 2013;1132:623-9.

2324THE PEANUT ALLERGEN IN THE HOME ENVIRONMENT MAY BE MORE IMPORTANT THAN THE PEANUT PRODUCTS THAT THE PREGNANT WOMEN EATS!2425SMOKING2526SMOKING DURING PREGNANCYNicotine, carcinogens, and other pathogens pass through the placental barrierIntrauterine smoke exposure (IUS) decreases blood flow as well as oxygen and nutrient deliveryMultiple studies including at least one meta-analysis show impaired postnatal lung function and more wheezing1

1. Burke, H. Pediatrics 2012;129:735-744.

2627SMOKING DURING PREGNANCYIUS reduces age-related improvements in bronchial hyperactivity1IUS decreases the effects of inhaled steroids on airway hyperresponsiveness1IUS 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.

2728Maternal smoking in pregnancy and asthma in preschool children

Pooled analysis of 8 European birth cohortsEffect of maternal smoking during pregnancy but not during the 1st year on wheezing and asthma at 4-6 years of age21,600 children735 exposed prenatally but not during the 1st year

Neuman, A. et. al. A. J Respir. Crit Care Med 2012;1861037-432829Maternal smoking in pregnancy and asthma in preschool children

ResultsMaternal smoking exclusively during pregnancy was associated with wheeze as well as asthma at 4-6 years of ageMaternal 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;1861037-432930SMOKING CESSATION SHOULD BEGIN BEFORE CONCEPTION!3031VITAMIN D31Muehleisen, B. J All Clin Immun 2013;131:324-9. 2012;185:124-32.

Paul, G. Vitamin D and Asthma. Am J Respir Crit Care Med. 2012;185:124-32.34Vitamin D Guidelines

Institute of Medicine: 20 ng/ml (50 nmol/l)1Endocrinology 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 Clin Endocrinol Metab 2012;97:1146-52.2. Hollick, M. J Clin Endocrinol Metab 2011;96:1911-30.3435

Sharief, S. J Allergy Clin Immun 2011;127:1195-1202.3536Vitamin D insufficiency is associated with challenge-proven food allergy in infants

Methods5276 one-year old infants assessed for food allergyFood challenges were conducted on most of the children with positive tests274 food allergic children207 non food allergic children were used as controlsVitamin D status assessed (vitamin D insufficiency 26-50 nmol/L)

Allen, K. et. al. A. J Al Clin immun 2013;131:1109-163637Vitamin D insuffeciency is associated with challenge-proven food allergy in infants

ResultsInfants of Australian-born parents with vitamin D insufficiency (30 ng/mlKeep peanut products out of the home?Take a probiotic?Avoid unnecessary C-sectionsMinimize stressLower their BMI if obese (> 30 kg/m2)

73More studies are desperately needed!7374

7475QUESTIONS75