Selected Prenatal Factors Effecting Allergy and Asthma Outcomes

advertisement
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
1
SELECTED PRENATAL FACTORS
EFFECTING ALLERGY AND ASTHMA
OUTCOMES
2
SELECTED PRENATAL FACTORS
POTENTIALLY EFFECTING
POSTNATAL ALLERGY AND ASTHMA
OUTCOMES
•
•
•
•
•
•
•
Maternal Diet
Active smoking
Vitamin D
Prebiotics/probiotics
C-section
Maternal stress
Obesity
3
OTHER PRENATAL FACTORS
POTENTIALLY EFFECTING
POSTNATAL ALLERGY AND ASTHMA
OUTCOMES (continued)
• Acetaminophen (paracetamol)
exposure
• Traditional farm exposure
• Bisphenol A exposure
4
ALLERGIC CONDITIONS
•
•
•
•
Asthma/wheezing
Allergic rhinitis
Atopic dermatitis
IgE-mediated food allergy
5
It can be very difficult
to separate out the
impact of prenatal vs.
postnatal factors on
allergy and asthma
6
Specific postnatal
allergy and asthma
outcomes may be
driven by different
factors
7
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
8
Maternal Pregnancy
Diet
–Prevention of non-food
allergic illness
–Prevention of food
allergy
9
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.
10
Should a pregnant
woman who had a
previous child with
peanut allergy eat
peanut products during
her pregnancy ?
11
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!
12
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
13
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
14
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.
15
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.
16
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
17
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
18
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
19
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
1. Bartnikas, J All Clin Immun 2013:131:417-43.
2. Lack, G. New England Journal of Medicine 2003;348:977-85.
3. Fox, A. J All Clin Immun 2009:123:417-423.
20
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
21
Brough, 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
• 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
22
Distribution of peanut protein in the home
environment
.
Brough, A. et. al. J All Clin Immun 2013;1132:623-9
23
THE PEANUT ALLERGEN
IN THE HOME
ENVIRONMENT MAY BE
MORE IMPORTANT
THAN THE PEANUT
PRODUCTS THAT THE
PREGNANT WOMEN
EATS!
24
SMOKING
25
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
26
1. Burke, H. Pediatrics 2012;129:735-744.
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
1. Cohen, R. J All Clin Immun 2010:126:491-7.
2. Metzger, M. Pediatric Infectious Disease Journal 2013;32:e1-7.
27
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
28
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
29
SMOKING
CESSATION SHOULD
BEGIN BEFORE
CONCEPTION!
30
VITAMIN D
31
Muehleisen, 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.
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
1.
2.
Rosen, C. J Clin Endocrinol Metab 2012;97:1146-52.
Hollick, M. J Clin Endocrinol Metab 2011;96:1911-30.
34
Sharief, S. J Allergy Clin Immun 2011;127:1195-1202.
35
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
36
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
37
Allen, K. et. al. A. J All Clin Immun 2013;131:1109-16
Allen, K. J All Clin Immun 2013;131:1109-16
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)
40
Nurmatov, U. J Allergy Clin immun 2011;127:724-33.
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)
42
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 25OH vitamin D and transient wheezing as well
as 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.
Baiz, K. et. al. A. J All Clin Immun (article in press)
44
PROBIOTICS
45
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
1. Sanders, M. Gut 20013:62:787-796
2. Gibson, G. J Nutr 1995;125:1401-1412
3. Screzenmeir, J. Am J Clin Nut 2001:73:S361-S364
46
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
47
48
Pfefferle, P. et. al. J All Clin Immun 2013;131:1453-63.
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)
49
Probiotic milk consumption in pregnancy and infancy and
subsequent allergic illness
50
Bertelson, R. et. al. J All Clin Immun 2013 (in press)
Maternal probiotic supplementation during pregnancy and
breast-feeding reduces the risk of eczema in the infant.
51
Ratuva, S. J All Clin Immun 2012;130:1355-60.
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 children1
•
World Allergy Organization 2012: Probiotics do not have an established
role in the prevention of allergy2
•
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”
1. Thomas, D. et. al. Pediatrics 2010:126:1217-31
2. Fiocchi, A. World Allergy Organ J5,148-167 (2012)
52
DELIVERY BY
C-SECTION
53
Delivery by c-section
• Fetal intestine is sterile
• After delivery, the intestine is colonized
• C-section: more colonization with C. difficile,
Clostridium cluster I, less colonization with
bifiobacteria, bacteroides, E. coli
• C-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.
54
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
1. Bager, P. Clinical and Experimental Allergy 2008;38:634-642.
2. Thavagnanam, S.Clinical and Experimental Allergy 2008;38:629-633.
55
Delivery by c-section increases
the risk for food sensitization at 2
years
• Methods
– 572 children from Detroit were studied and the
mode of delivery was noted
– Blood was drawn for IgE CAP-RAST tests to
milk, egg, and peanut near the child’s 2nd
birthday
– Mom’s atopic status was noted
– Atopy 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,
56
and Immunology Meeting in San Antonio, Tx.)
Delivery by c-section increases
the risk for food sensitization at 2
years
• Results
– C-section rate was 35.3%
– 40.9% of the children were sensitized to at
least 1 food
– Children 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
57
Immunology Meeting in San Antonio, Tx.)
Birth by cesearean section,
allergic rhinitis, and allergic
sensitization among children with
a parental history of atopy
• Methods
– 432 children with a parental history
of atopy were followed from birth
to the age of 9 years
– Major 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.
58
•
Birth by cesearean section,
allergic rhinitis, and allergic
sensitization among children with
a parental history of atopy
• Results
– Children born by C-section had a
2-fold higher odds ratio of atopy
– Birth 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.
59
MATERNAL
PRENATAL
STRESS
60
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 wheezing
• Any association between maternal stress during pregnancy
might be explained by other mechanisms such as social,
behavior, or environmental factors
• From a causative and preventative perspective, it is
important to isolate out intrauterine mechanisms
• One way to do this is to compare maternal with paternal
psychological stress both before and after delivery
• Multiple 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)
61
Parental psychological distress
during pregnacy and wheezing in
preschool children: The
generation R study
•
• Methods
– Population bases cohort study of 4848
children from Rotterrdam, Netherlands
– Maternal and paternal stress was assessed in
the 2nd trimester and several months after
delivery with validated questionnaire
– Wheezing 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)
62
Parental psychological distress
during pregnacy and wheezing in
preschool children: The
generation R study
•
• Results
– Mothers with psychological distress during
pregnancy had an increased odds of wheezing
in their children from 1-4 years of life
– Similar 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)
63
Parental psychological distress during pregnacy and
wheezing in preschool children: The generation R study
64
Guxens, M. et. al. A. J All Clin Immun 2013 (article in press)
Disrupted and prenatal maternal cortisol, maternal
obesity, and childhood wheeze
65
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
66
Wright, R. et. al. A. Am J Resp Crit Care Med 2013: 187:1186-93
MATERNAL
OBESITY
67
Maternal obesity, gestational weight
gain, and risk of asthma and atopic
disease in offspring: A study within the
Danish National Birth Cohort
• Methods
– Cohort study of 38, 874 mother-child pairs from the Danish National
Birth Cohort
– Maternal pre pre-pregnancy body mas index (BMI ) and gestational
weight gain (GWG) assessed
– Survey assessment of asthma, wheezing, atopic eczema , and hay
fever at 18 months and 6 years of age
• Results
– Maternal BMI and to a lesser extent GWG were associated doctordiagnosed asthma
– The effect was unrelated to child BMI and stronger in nonatopic
children
Harpsoe, M. J All Clin Immun 2013;131:1033-40.
68
Maternal obesity, gestational weight gain, and risk of asthma
and atopic disease in offspring: A study within the Danish
National Birth Cohort
69
Harpsoe, M. J All Clin Immun 2013;131:1033-40.
What should a
pregnant women do if
she wants to prevent
potential allergies and
asthma in her
offspring?
70
I am not aware of any
specific
recommendations
from any
organizations
71
Some steps that a pregnant women (or
someone contemplating pregnancy)
might consider
• Smoking cessation
• Increase 25-OH vitamin D to >30 ng/ml
• Keep peanut products out of the home?
• Take a probiotic?
• Avoid unnecessary C-sections
• Minimize stress
• Lower their BMI if obese (> 30 kg/m2)
72
More studies
are desperately
needed!
73
74
QUESTIONS
75
Download