TY - JOUR

T1 - Risk factors for granulomas in children following immunization with aluminium-adsorbed vaccines

T2 - A Danish population-based cohort study

AU - Hoffmann, Stine Skovbo

AU - Thiesson, Emilia Myrup

AU - Johansen, Jeanne Duus

AU - Hviid, Anders

N1 - Funding Information: This study received support from Helsefonden, Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis legat and The Lundbeck Foundation for the submitted work. The National Allergy Research Centre is supported by a grant from the Danish Environmental Protection Agency under the Ministry of Environments and Food.

PY - 2022

Y1 - 2022

N2 - Background: Aluminium-adsorbed vaccines may in some children cause severely itching nodules at the injection site, known as vaccination granulomas. Objective: To investigate vaccine-, child- and maternal-level risk factors for the development of vaccination granulomas following immunization with aluminium-adsorbed vaccines. Methods: A Danish population-based cohort study with 553 932 children born in Denmark from 1 January 2009 to 31 December 2018, vaccinated with an aluminium-adsorbed vaccine during the first year of life, followed until 31 December 2020. Poisson regression was used to estimate granuloma rate ratios according to the type of adjuvant, accumulated dose of aluminium, timing of vaccination appointments, sex, gestational age, having siblings with granulomas, maternal age and maternal ethnicity. Results: We identified 1901 vaccination granuloma cases (absolute risk, 0.34%). Among vaccine level factors, revaccination (third vs. first vaccination appointment, adjusted rate ratio [RR] 1.26, 95% confidence interval [CI] 1.03–1.55), the specific adjuvant used (aluminium phosphate vs. hydroxide, RR 0.58, 95% CI 0.48–0.70) and dosage (≥1.0 mg vs. <1.0 mg, RR 1.34, 95% CI 1.19–1.52) were associated with risk of granulomas; the timing of vaccination appointments was not. Among child-level factors, female sex (vs. males, RR 1.12, 95% CI, 1.02–1.22), prematurity (vs. term birth, RR 0.71, 95% CI, 0.54–0.93) and having sibling(s) with granulomas (vs. no siblings with granulomas, RR 46.15, 95% CI, 33.67–63.26) were associated with risk of granulomas. Among maternal-level factors, non-Danish ethnicity (vs. Danish, RR 0.51, 95% CI, 0.42–0.63) and young maternal age (<20 years vs. 20–39 years, RR 0.46, 95% CI 0.25–0.83) were associated with risk of granulomas. Conclusions: Several risk factors for vaccination granulomas at the vaccine, child and maternal levels, were identified. Reducing the dose of aluminium or replacing aluminium hydroxide with aluminium phosphate could reduce the risk of granulomas. However, this must be balanced against the potential for reduced immunogenicity.

AB - Background: Aluminium-adsorbed vaccines may in some children cause severely itching nodules at the injection site, known as vaccination granulomas. Objective: To investigate vaccine-, child- and maternal-level risk factors for the development of vaccination granulomas following immunization with aluminium-adsorbed vaccines. Methods: A Danish population-based cohort study with 553 932 children born in Denmark from 1 January 2009 to 31 December 2018, vaccinated with an aluminium-adsorbed vaccine during the first year of life, followed until 31 December 2020. Poisson regression was used to estimate granuloma rate ratios according to the type of adjuvant, accumulated dose of aluminium, timing of vaccination appointments, sex, gestational age, having siblings with granulomas, maternal age and maternal ethnicity. Results: We identified 1901 vaccination granuloma cases (absolute risk, 0.34%). Among vaccine level factors, revaccination (third vs. first vaccination appointment, adjusted rate ratio [RR] 1.26, 95% confidence interval [CI] 1.03–1.55), the specific adjuvant used (aluminium phosphate vs. hydroxide, RR 0.58, 95% CI 0.48–0.70) and dosage (≥1.0 mg vs. <1.0 mg, RR 1.34, 95% CI 1.19–1.52) were associated with risk of granulomas; the timing of vaccination appointments was not. Among child-level factors, female sex (vs. males, RR 1.12, 95% CI, 1.02–1.22), prematurity (vs. term birth, RR 0.71, 95% CI, 0.54–0.93) and having sibling(s) with granulomas (vs. no siblings with granulomas, RR 46.15, 95% CI, 33.67–63.26) were associated with risk of granulomas. Among maternal-level factors, non-Danish ethnicity (vs. Danish, RR 0.51, 95% CI, 0.42–0.63) and young maternal age (<20 years vs. 20–39 years, RR 0.46, 95% CI 0.25–0.83) were associated with risk of granulomas. Conclusions: Several risk factors for vaccination granulomas at the vaccine, child and maternal levels, were identified. Reducing the dose of aluminium or replacing aluminium hydroxide with aluminium phosphate could reduce the risk of granulomas. However, this must be balanced against the potential for reduced immunogenicity.

KW - adjuvant

KW - aluminium

KW - children

KW - contact allergy

KW - granuloma

KW - hydroxide

KW - phosphate

KW - vaccination

U2 - 10.1111/cod.14180

DO - 10.1111/cod.14180

M3 - Journal article

C2 - 35778959

AN - SCOPUS:85134162899

VL - 87

SP - 430

EP - 438

JO - Contact Dermatitis. Supplement

JF - Contact Dermatitis. Supplement

SN - 1396-6669

IS - 5

ER -