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Preliminary evaluation of aluminum content in childhood vaccines and risk of
asthma in a Danish nationwide cohort
Prof. Anders Hviid, Statens Serum Institut, Copenhagen, Denmark
Advisory Committee on Immunization Practices, June 23, 2023
Study cohort
•Born in Denmark 2009 -2016
•Study start 1/1 2011 ; study end 12/31 2018
•Follow -up from 2 to 5 -years -of-age
•Exposure and outcome data from nationwide -
registers
•N=470,477 children
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The Danish schedule
3Danish schedule
3 mo.: DiTePeIPVHib1 + PCV1
5 mo.: DiTePeIPVHib2 + PCV2
12 mo.: DiTePeIPVHib3 + PCV3
15 mo.: MMR1
4 yrs: MMR2
5 yrs: DiTePeIPV booster
12 yrs: HPV1 and HPV2
Cumulative aluminium exposure
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Asthma outcome definitions
•Hospital contacts, ICD-10 J45 (asthma), J46 (status asthmaticus) , in-and
outpatients
•Community anti -asthmatics prescriptions: Inhaled corticosteroids (n=2), short -
acting beta -agonists (n=3), montelukast (n=2), long -acting beta -agonists (n=1)
•Primary outcome: Hospitalization and/or anti -asthma drug use
•Exclusion criteria: Any prescriptions orhospitalizations before the age of 2.
•Date of outcome: First among the above events
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Secondary outcomes -latent class analysis
Inpt. Outpt . SABA ICS LABA MON Cluster 1: ” Montelukast ”
6.5%
Cluster 2: ”SABA”
23.3%
Cluster 3: ” Hospitalization ”
7.9%
Cluster 4: ” Inhaled corticosteroids +/-SABA”
62.3%
6SABA: Short-acting beta agonist; LABA: Long-acting beta agonist; ICS: Inhaled corticosteroid; MON: Montelukast.
Cohort characteristics
7Cumulative aluminum received by 2-yrs- of-age
KOEN: Sex; OPR: Mothers country of origin .
Main Results –Hosp. or anti -asthma medication
Table : Association between cumulative aluminum received through vaccines by age 2 and asthma by
age 5 among 470477 Danish children born 2009 to 2016 and followed 2011 to 2018
Asthma cases1 Person -years of follow -up Hazard ratio (95% CIs)2
0 mg 62 13,082.00 0.90 (0.68 to 1.19)
<2.25mg 327 65,167.16 1.00 ( - to -)
2.25mg 446 78,643.45 1.07 (0.92 to 1.24)
>2.25mg -<3.375mg 1092 206,053.42 1.00 (0.88 to 1.14)
3.375mg 3096 597,727.75 0.98 (0.86 to 1.11)
>3.375mg 838 165,528.63 1.00 (0.84 to 1.18)
1Hospitalization and/or anti -asthma prescription drug use
2Adjusted for sex, year of birth, maternal country of origin, and MMR vaccination by age 2.
8Aluminum
Main Results –Dose -response
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Association between aluminum and asthma clusters
10Hazard Ratio* (95% CI)
* Adjusted for sex, year of birth , maternal country of origin , MMR vaxbefore 2-yrs-of-age Comparing >3.375mg
cumulative aluminum received
through vaccines by 2-yrs- of-age
to <2.25mg
Limitations
11•Limited variability in cumulative aluminum
•Validity of using asthma diagnosis and anti -
asthma drug use before 5 -yrs-of-age
Take -away
•No support for an association between
aluminium in vaccines and asthma by 5 -
yrs-of-age in Denmark
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