1. Maternal Diet and Infant Atopic Disease at 1-Year
October 2015 Fellow’s Seminar
Maternal Diet and Infant Atopic Disease at 1-Year
Presenter – Keith Tam | Supervisors: Dr. Russell
de Souza, Dr. Michael Zulyniak, Dr. Sonia Anand

2. Overview of Infant Atopic Disease1
IgE-mediated immune response
What do we mean by “atopic disease”?
Eczema (atopic dermatitis)
Asthma
Food allergy
Atopy
Hay fever (allergic rhinitis)
Childhood Prevalence – 20%↑

3. Prevalence of Asthma Worldwide2

4. Overview of Infant Atopic Disease3,4,5
Factors identified in literature:
Genetics
Breastfeeding
Tobacco smoke exposure
Birth parity
Pet exposure
Maternal diet?
Study conducted within FAMILY cohort showed the link between various prenatal and postnatal exposures and risk of infant atopic disease at 1-year.

5. Maternal Diet and Infant Atopic Disease6,7
Maternal food consumption during pregnancy and asthma, respiratory and atopic symptoms in 5-year-old children, Willers et al. 2007
Effect of maternal dietary intake of individual foods during pregnancy on asthma and eczema outcomes in 5-year old children, n = 1924
Maternal apple consumption protective for asthma
Maternal fish consumption  protective for eczema
Maternal diet during pregnancy in relation to eczema and allergic sensitization in the offspring at 2 y of age, Sausenthaler et al. 2007
Intake of specific nutrients in the maternal diet and their effect on allergic sensitization and eczema outcomes in 2-year old children, n = 2641
n−6 polyunsaturated fatty acids  increase risk of allergic sensitization
n−3 polyunsaturated fatty acids  decrease risk of allergic sensitization

6. What are the prenatal and early life
Objective:
What are the prenatal and early life
determinants of infant atopic disease at
one year within the NutriGen cohort?
Focus on maternal diet during pregnancy
Include other prenatal and early life exposures as potential covariates

7. Overview of NutriGen Consortium of 4 multiethnic cohorts, n=5279
ABC (n=94)
CHILD (n=3412)
FAMILY (n=860)
START (n=913)
Collection of data on many of the same variables, but defined differently across cohorts
Advantages:
Larger sample size to observe associations
Ethnic-specific differences

8. Maternal Dietary Patterns – PCA
Plant-based Western Health-conscious

9. Harmonizing Infant Atopy Outcomes Eczema
Allergic Outcome
ABC
CHILD
FAMILY
START
Eczema
Has your child been diagnosed by a doctor with eczema? (completed by mother of infant)
Does this child meet the criteria for diagnosis of Atopic Dermatitis? (completed by clinical professional)
Has your child ever been diagnosed with eczema?
(completed by mother of infant)
Definition: Does infant meet the criteria for clinical diagnosis of eczema/atopic dermatitis?

10. Harmonizing Infant Atopy Outcomes Asthma
Allergic Outcome
ABC
CHILD
FAMILY
START
Asthma
Has your child been diagnosed by a doctor with asthma? (completed by mother of infant)
Was your child diagnosed with asthma? (completed by mother of infant)
Has your child ever been diagnosed with asthma? (completed by mother of infant)
Definition: Has the infant been diagnosed by a physician with asthma?

11. Harmonizing Infant Atopy Outcomes Food Allergy
Allergic Outcome
ABC
CHILD
FAMILY
START
Food allergy
Has your child developed food allergies to cow’s milk/ egg/soy protein/other foods?
(completed by mother of infant at 1-year visit)
Has baby developed a food allergy from birth to 3 months/3mo to 6mo/6mo to 1yr? (completed by mother of infant at 3-month, 6-month, and 1-year visits)
Definition: Has the infant developed food allergies towards any foods from birth until one year of age?

12. Harmonizing Infant Atopy Outcomes Atopy
Allergic Outcome
ABC
CHILD
FAMILY
START
Atopy
N/A
2 skin prick tests completed for each of the following allergens and wheal width measured: alternaria tenuis, cat hair, dog epithelium, D. Pteronyssisinus, D. Farinae, peanut, cow’s milk, egg white, soybean, German cockroach; positive control of histamine; negative control of glycerin
2 skin prick tests completed for each of the following allergens and wheal width measured: alternaria, cat epidermis, dog epidermis, D. Pteronyssisinus, D. Farinae, peanut, milk, egg white, soy, wheat, nut mix, horse epidermis, feather mix, dictyoptera, hormodendrum, aspergillus fumigatus, tree pollen mix, grass pollen mix, ragweed pollen mix, weed pollen mix; ; positive control of histamine; negative control of glycerin
Definition: Average wheal diameter was more than 2mm greater than the negative glycerin control for any of the following allergens: cat dander, dog dander, D. pteronyssisinus, D. farinae, peanut, milk, egg, soy

13. Infant Atopic Diseases in NutriGen
ABC
(n=94)
CHILD
(n=3412)
FAMILY
(n=860)
START
(n=913)
NutriGen
(n=5279)
Eczema
9.1%
11.8%
16.5%
12.3%
12.7%
Asthma 0%
0.5%
2.4%
1.3%
1.0%
Food allergy*
81.8%
12.5%
8.6%
4.0%
10.5%
Atopy
N/A
34.5%
17.8%
14.4%

14. Harmonizing Covariates (25 total)
Ref
Parental history of allergy
Maternal atopy, paternal atopy, maternal asthma, paternal asthma
Maternal characteristics
Age at delivery, pre-pregnancy BMI, ethnicity (Aboriginal, White European, South Asian, East Asian, other)
Infant characteristics
Birth parity, gender, gestational age, BMI at birth, weight gain in first-year
Environmental exposures
Ownership of furry pets, dogs, cats, number of adults/children in household, infant tobacco smoke exposure, maternal tobacco smoke exposure during pregnancy, breastfeeding at 1-year
Socioeconomic status
Maternal highest level of education, household income, maternal/paternal employment, maternal marital status

15. Creating the models Stage 1: Univariate analysis
Ref
Stage 1: Univariate analysis
Stage 2: Multivariate analysis
Eczema and Birth Parity
Candidate variables: p<0.10
Final model: p<0.05
Covariates with biological significance:
Breastfeeding
Maternal/infant smoke exposure

16. What We Found – Eczema Covariate OR (95% CI) p-value Gender (female)
0.63 (0.52 to 0.77)
<0.001
Furry pet exposure*
0.78 (0.61 to 0.98)
0.038
Infant smoke exposure
0.71 (0.39 to 1.19)
0.218
Maternal smoke exposure
1.15 (0.83 to 1.58)
0.386
Breastfeeding at 1-year
0.83 (0.67 to 1.02)
0.080
Maternal Native American ethnicity†
1.16 (0.41 to 2.84)
0.762
Maternal White European ethnicity†
0.86 (0.61 to 1.23)
0.393
Maternal South Asian ethnicity†
1.05 (0.70 to 1.60)
0.813
Maternal East Asian ethnicity†
1.53 (1.63 to 3.80)
Maternal education (middle category)†
1.50 (1.09 to 2.08)
0.014
Maternal education (highest category)†
1.43 (1.03 to 2.02)
0.037
*High level of collinearity between multiple covariates, †Categorical covariates

17. What We Found – Asthma Covariate OR (95% CI) p-value Maternal asthma
2.36 (1.14 to 4.76)
0.017
Paternal asthma
2.41 (0.98 to 5.42)
0.041
Weight gain (kg)
1.46 (1.16 to 1.84)
<0.001
Number of children in household*
1.48 (1.07 to 1.93)
0.011
Infant smoke exposure
1.63 (0.46 to 4.53)
0.390
Maternal smoke exposure
1.88 (0.79 to 4.10)
0.130
Breastfeeding at 1-year
0.51 (0.21 to 1.12)
0.109
*High level of collinearity between multiple covariates

18. What We Found – Food Allergy
 Covariate
OR (95% CI)
p-value
Gender (female)
0.74 (0.58 to 0.94)
0.017
Infant smoke exposure
0.87 (0.49 to 1.48)
0.632
Maternal smoke exposure
1.57 (1.11 to 2.20)
0.011
Breastfeeding at 1-year
1.35 (1.05 to 1.72)
Maternal Native American ethnicity†
2.56 (1.02 to 6.11)
0.039
Maternal White European ethnicity†
0.80 (0.54 to 1.23)
0.302
Maternal South Asian ethnicity†
0.33 (0.19 to 0.58)
<0.001
Maternal East Asian ethnicity†
1.31 (0.77 to 2.23)
0.322
*High level of collinearity between multiple covariates, †Categorical covariates, ‡Indicator variable for missing data

19. What We Found – Atopy Covariate OR (95% CI) p-value Maternal atopy
0.005
Paternal atopy
1.40 (1.11 to 1.79)
0.006
Number of adults in household
1.16 (1.01 to 1.32)
0.037
Infant smoke exposure
0.54 (0.29 to 0.94)
0.043
Maternal smoke exposure
1.07 (0.76 to 1.46)
0.684
Breastfeeding at 1-year
1.16 (0.93 to 1.45)
0.169
Maternal Native American ethnicity†
0.52 (0.08 to 1.84)
0.388
Maternal White European ethnicity†
0.81 (0.58 to 1.14)
0.208
Maternal South Asian ethnicity†
1.68 (0.88 to 3.13)
0.108
Maternal East Asian ethnicity†
2.05 (1.38 to 3.10)
<0.001
Household income (middle category)†
1.55 (1.08 to 2.25)
0.021
Household income (highest category)†
1.45 (1.00 to 2.12)
0.054
*High level of collinearity between multiple covariates, †Categorical covariates

20. Maternal Dietary Pattern Analysis
1. Dietary patterns were entered as 3 separate variables into adjusted multivariate model for each outcome
2. Dietary patterns entered as quartiles one at a time, keeping other two dietary patterns as raw scores

21. Results: Plant-based diet
Outcome
OR (95% CI)
p-value
Eczema
1.12 (1.01 to 1.25)
0.033
Asthma
0.98 (0.70 to 1.37)
0.901
Food allergy
1.07 (0.94 to 1.21)
0.294
Atopy
1.20 (1.08 to 1.33)
<0.001

22. Results: Western diet Outcome OR (95% CI) p-value Eczema
0.004
Asthma
0.97 (0.66 to 1.46)
0.882
Food allergy
0.98 (0.86 to 1.11)
0.743
Atopy
0.94 (0.84 to 1.06)
0.330

23. Results: Health-conscious diet
Outcome
OR (95% CI)
p-value
Eczema
0.93 (0.83 to 1.04)
0.184
Asthma
0.51 (0.32 to 0.77)
0.002
Food allergy
1.08 (0.95 to 1.23)
0.222
Atopy
0.196

24. Conclusion
Confirmed previous findings of associations between prenatal/early life exposures and infant atopic disease
Breastfeeding at 1-year decreases risk of atopic diseases
Pet exposure decreases eczema risk at 1-year
Smoke exposure increases asthma risk at 1-year
Found significant ethnic differences in prevalence of atopic diseases
More prevalent in infants of East Asian mothers
Demonstrated significant associations between maternal dietary patterns and infant atopic disease
Both plant-based and western diets increase eczema risk
Balanced, health-conscious diet greatly decreases asthma risk

25. References
Alexander, Dominik D et al. 'Partially Hydrolyzed 100% Whey Protein Infant Formula And Atopic Dermatitis Risk Reduction: A Systematic Review Of The Literature'. Nutrition Reviews 68.4 (2010): Web.
Alvesco.com,. 'About Asthma | Alvesco.Com'. N.p., Web.
Odijk, J. et al. 'Breastfeeding And Allergic Disease: A Multidisciplinary Review Of The Literature ( ) On The Mode Of Early Feeding In Infancy And Its Impact On Later Atopic Manifestations'. Allergy58.9 (2003): Web.
Nafstad, P. et al. 'Exposure To Pets And Atopy-Related Diseases In The First 4 Years Of Life'.Allergy 56.4 (2001): Web.
Strachan, D. 'Family Size, Infection And Atopy: The First Decade Of The 'Hygiene Hypothesis''.Thorax 55.Suppl 1 (2000): S2. Web.
Willsie, S.K. 'Maternal Food Consumption During Pregnancy And Asthma, Respiratory And Atopic Symptoms In 5-Year-Old Children'. Yearbook of Pulmonary Disease 2009 (2009): Web.
Nwaru, Bright I. et al. 'Maternal Diet During Pregnancy And Allergic Sensitization In The Offspring By 5 Yrs Of Age: Ï¿½A Prospective Cohort Study'. Pediatric Allergy and Immunology 21.1-Part-I (2010): Web.