1 SELECTED PRENATAL FACTORS EFFECTING ALLERGY AND ASTHMA OUTCOMES - PowerPoint Presentation

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SELECTED 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 OUTCOMES

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SELECTED PRENATAL FACTORS POTENTIALLY EFFECTING POSTNATAL ALLERGY AND ASTHMA OUTCOMES

Maternal DietActive smokingVitamin D Prebiotics/probioticsC-sectionMaternal stressObesity

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

Acetaminophen (paracetamol) exposureTraditional farm exposureBisphenol A exposure

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ALLERGIC CONDITIONS

Asthma/wheezingAllergic rhinitisAtopic dermatitis IgE-mediated food allergy

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

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

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Credibility of a Theory

Biological plausibilityMultiple studies over a range of agesMeta-analysesRandomized-controlled studiesClinical vs. statistical significance Guidelines from societies

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Maternal Pregnancy Diet

Prevention of non-food allergic illnessPrevention of food allergy

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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.

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

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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!

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ALARMING CHARACTERISTICS OF PEANUT ALLERGY

1-2% 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 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

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AAP 2000:

Mothers at risk of atopy should avoid peanuts during pregnancy and lactationAAP 2008: The AAP rescinded their recommendations and replaced it with a statement that the efficacy of this practice remains unprovenAAAAI/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

Recommendations for peanut/tree nut consumption during pregnancy and lactation

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Peanut 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 age

Msalova, S. et. al. J

All Clin Immun

2012;130:724-32.

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Peanut 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.

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Maternal 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 feeding

Sicherer, S. et. al. J

All Clin Immun

2010;126:1191-97

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Maternal 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

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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

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Epicutaneous 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 allergy

2

A dose-response relationship has been demonstrated between household peanut consumption and peanut allergy in young children

3

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.

.

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Methods

46 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;1132:623-9

Peanut protein in household dust is related to household peanut consumption and is biologically active

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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;1132:623-9Peanut protein in household dust is related to household peanut consumption and is biologically active

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Distribution of peanut protein in the home environment

Brough, A. et. al. J All Clin Immun 2013;1132:623-9.

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

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SMOKING

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SMOKING DURING PREGNANCY

Nicotine, 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 wheezing11. Burke, H. Pediatrics

2012;129:735-744.

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SMOKING DURING PREGNANCY

IUS 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.

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Maternal 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;1861037-43

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Maternal 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;1861037-43

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SMOKING CESSATION SHOULD BEGIN BEFORE CONCEPTION!

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VITAMIN D

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Muehleisen, B.

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

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Paul, G. Vitamin D and Asthma.

Am J Respir Crit Care Med

. 2012;185:124-32.

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Vitamin 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.

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Sharief, S.

J Allergy Clin Immun 2011;127:1195-1202.

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Vitamin 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;131:1109-16

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Vitamin D insuffeciency is associated with challenge-proven food allergy in infants

ResultsInfants 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

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Allen, K. et. al. A.

J All Clin Immun

2013;131:1109-16

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Allen, K.

J All Clin Immun

2013;131:1109-16

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Vitamin D and food allergy in patients with severe atopic dermatitis

Methods39 patients referred for severe atopic dermatitis and food allergyPatients with atopic dermatitis and food allergy had their serum vitamin D levels compared to those of patients with atopic dermatitis and no food allergyResultsFor 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)

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Nurmatov, U.

J Allergy Clin immun 2011;127:724-33.

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Cord serum 25-OH vitamin D and risk of early childhood wheezing and atopic dermatitis.

MethodsCord blood samples from the EDEN birth cohort were analyzed for 25-OH vitamin DFollow-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)

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Cord serum 25-OH vitamin D and risk of early childhood wheezing and atopic dermatitis.

ResultsMedian cord serum 25-OH vitamin D level was 17.8 ng/mlThere 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)

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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)

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PROBIOTICS

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Prebiotics and probiotics

Probiotics: Live microorganisms administered in adequate amounts to that confer a beneficial health effect on the host1Prebiotics: 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 probiotics

3

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

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Probiotics

Several meta-analyses show efficacy of probiotics in the prevention of atopic dermatitisOther 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

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Pfefferle, P. et. al. J

All Clin Immun 2013;131:1453-63.

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Probiotic milk consumption in pregnancy and infancy and subsequent allergic illness

MethodsNorway mother and child cohort study (MoBa)40,164 infants at low risk

of allergy

Probiotic milk/yogurt consumption assessed

Biola

milk/yogurt,

C

ultura

milk (lactobacillus/

bifidobacterium

)

Questionaire data regarding atopic dermatitis, allergic rhinitis, and asthma

Bertelson, R. et. al.

J All Clin Immun 2013 (in press)

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Bertelson, R. et. al.

J All Clin Immun 2013 (in press)Probiotic milk consumption in pregnancy and infancy and subsequent allergic illness

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Ratuva, S.

J All Clin Immun 2012;130:1355-60.Maternal probiotic supplementation during pregnancy and breast-feeding reduces the risk of eczema in the infant.

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Recommendations from Scientific Societies

American Academy of Pediatrics 2010: Further confirmatory evidence is necessary before a routine recommendation for routine use can be made. There may be some long term benefit of prebiotics in reducing atopy in otherwise healthy children1World Allergy Organization 2012:

Probiotics do not have an established role in the prevention of allergy

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AAAAI/ACAAAI Draft Practice Parameters for Food Allergy (10/19/13)

: “Do not routinely recommend supplementation of the maternal or

infant diet with probiotics or prebiotics as a means to prevent food allergy because there is insufficient evidence to support a beneficial effect”

Thomas, D. et. al.

Pediatrics 2010:126:1217-31

Fiocchi, A.

World Allergy Organ

J5,148-167 (2012)

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DELIVERY BY C-SECTION

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Delivery by c-section

Fetal intestine is sterileAfter delivery, the intestine is colonizedC-section: more colonization with C. difficile, Clostridium cluster I, less colonization with bifiobacteria, bacteroides, E. coliC-section (skin surface microbiota), vaginal delivery (mother’s vaginal microbiota)This altered intestinal microbiota may interfere with the development of immunologic tolerance

Penders, J. et. al.

J All Clin Immun 2013;132:60107.

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Delivery by c-section

Multiple studies show prevention of asthma, food allergy, and allergic rhinitis 2 meta-analyses show at least moderate preventative impact1,2

Bager, P.

Clinical and Experimental Allergy

2008;38:634-642.

Thavagnanam, S.

Clinical and Experimental Allergy

2008;38:629-633

.

.

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Delivery by c-section increases the risk for food sensitization at 2 years

Methods572 children from Detroit were studied and the mode of delivery was notedBlood was drawn for IgE CAP-RAST tests to milk, egg, and peanut near the child’s 2nd birthdayMom’s atopic status was notedAtopy was defined as having one specific IgE greater than or equal to 0.35kU/L

Yonnus, M. et. al. A.

J All Clin Immun 2013 (Abstract #82, #465 presented at the American Academy of Allergy, Asthma, and Immunology Meeting in San Antonio, Tx.)

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Delivery by c-section increases the risk for food sensitization at 2 years

ResultsC-section rate was 35.3%40.9% of the children were sensitized to at least 1 foodChildren of atopic mothers were more like to be sensitized to at least one food (odds ratio 1.8)infants delivered by C-section tended to be sensitized to the allergen they were exposed to at home (mite, cat, dog)

Yonnus, M. et. al. A.

J All Clin Immun 2013 (Abstract #82 presented at the American Academy of Allergy, Asthma, and Immunology Meeting in San Antonio, Tx.)

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Birth by cesearean section, allergic rhinitis, and allergic sensitization among children with a parental history of atopy

Methods432 children with a parental history of atopy were followed from birth to the age of 9 yearsMajor outcome: asthma, allergic rhinitis, or atopy

at 9 years of age

Prospective birth cohort study

Pistiner, M. et. al. A.

J All Clin Immun 2008;122:274-9.

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Birth by cesearean section, allergic rhinitis, and allergic sensitization among children with a parental history of atopy

ResultsChildren born by C-section had a 2-fold higher odds ratio of atopyBirth by C-section was significantly associated with the odds of allergic rhinitis (odds ratio 2.1), but not asthma

Pistiner, M. et. al. A.

J All Clin Immun 2008;122:274-9.

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MATERNAL PRENATAL STRESS

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Maternal prenatal psychological distress and postnatal allergy and asthma outomes

A handful of studies have linked some measure of prenatal maternal stress to postnatal infant/childhood wheezingAny association between maternal stress during pregnancy might be explained by other mechanisms such as social, behavior, or environmental factorsFrom a causative and preventative perspective, it is important to isolate out intrauterine mechanismsOne way to do this is to compare maternal with paternal psychological stress both before and after deliveryMultiple theories: altered infant HPA axis, altered innate and adaptive immune responses, epigenetic programming.

Guxens, M. et. al. A.

J All Clin Immun 2013 (article in press)

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Parental psychological distress during pregnacy and wheezing in preschool children: The generation R study

MethodsPopulation bases cohort study of 4848 children from Rotterrdam, NetherlandsMaternal and paternal stress was assessed in the 2nd trimester and several months after delivery with validated questionnaireWheezing in the children was annually examined by questionnaires from 1-4 years

Physician diagnosed asthma was reported at 6 years

Guxens, M. et. al. A.

J All Clin Immun 2013 (article in press)

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Parental psychological distress during pregnacy and wheezing in preschool children: The generation R study

ResultsMothers with psychological distress during pregnancy had an increased odds of wheezing in their children from 1-4 years of lifeSimilar positive association were noted with the number of wheezing episodes, wheezing patterns, and physician diagnosed asthma at 6 years

Guxens, M. et. al. A.

J All Clin Immun 2013 (article in press)

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Guxens, M. et. al. A.

J All Clin Immun 2013 (article in press)Parental psychological distress during pregnacy and wheezing in preschool children: The generation R study

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Wright, R. et. al. A.

Am J Resp Crit Care Med 2013: 187:1186-93 Disrupted and prenatal maternal cortisol, maternal obesity, and childhood wheeze

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Wright, R. et. al. A.

Am J Resp Crit Care Med 2013: 187:1186-93 Disrupted and prenatal maternal cortisol, maternal obesity, and childhood wheeze

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MATERNAL OBESITY

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Maternal obesity, gestational weight gain, and risk of asthma and atopic disease in offspring: A study within the Danish National Birth Cohort

MethodsCohort study of 38, 874 mother-child pairs from the Danish National Birth CohortMaternal pre pre-pregnancy body mas index (BMI ) and gestational weight gain (GWG) assessedSurvey assessment of asthma, wheezing, atopic eczema , and hay fever at 18 months and 6 years of age ResultsMaternal BMI and to a lesser extent GWG were associated doctor-diagnosed asthma

The effect was unrelated to child BMI and stronger in

nonatopic

children

Harpsoe, M.

J All Clin Immun 2013;131:1033-40.

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Harpsoe, M.

J All Clin Immun 2013;131:1033-40.Maternal obesity, gestational weight gain, and risk of asthma and atopic disease in offspring: A study within the Danish National Birth Cohort

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What should a pregnant women do if she wants to prevent potential allergies and asthma in her offspring?

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I am not aware of any specific recommendations from any organizations

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Some steps that a pregnant women (or someone contemplating pregnancy) might consider

Smoking cessationIncrease 25-OH vitamin D to >30 ng/mlKeep peanut products out of the home?Take a probiotic?Avoid unnecessary C-sectionsMinimize stressLower their BMI if obese (> 30 kg/m2)

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More studies are desperately needed!

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QUESTIONS