背景：某些儿童的铝吸附疫苗可能会在注射部位引起严重的瘙痒结节，称为疫苗接种肉芽肿。
目的：研究疫苗-，用铝吸附疫苗免疫接种后发生疫苗接种肉芽肿的儿童和孕产妇水平危险因素.
方法：一项基于丹麦人群的队列研究，研究对象为2009年1月1日至2018年12月31日在丹麦出生的553932名儿童，在出生后的第一年接种了铝吸附疫苗，直到2020年12月31日。根据佐剂的类型，使用泊松回归来估计肉芽肿率比率，铝的累积剂量，疫苗接种预约的时间，性别,胎龄,有肉芽肿的兄弟姐妹，母亲年龄和母亲种族。
结果：我们确定了1901例疫苗接种肉芽肿病例（绝对风险，0.34%）。在疫苗水平因素中，再接种（第三vs.第一次接种疫苗预约，调整后的利率比率[RR]1.26，95%置信区间[CI]1.03-1.55)，使用的特定佐剂(磷酸铝vs.氢氧化物,RR0.58，95%CI0.48-0.70）和剂量（≥1.0mgvs.<1.0mg,RR1.34，95％CI1.19-1.52）与肉芽肿的风险相关；疫苗接种预约的时间不是。在儿童层面的因素中，女性性别(vs.男性,RR1.12，95%CI，1.02-1.22），早产(vs.足月出生,RR0.71，95%CI，0.54-0.93），并且有同胞患有肉芽肿（与没有肉芽肿的兄弟姐妹，RR46.15，95%CI，33.67-63.26）与肉芽肿风险相关。在母亲层面的因素中，非丹麦种族(vs.丹麦语,RR0.51，95%CI，0.42-0.63）和年轻产妇年龄（<20岁vs.20-39年,RR0.46，95%CI0.25-0.83）与肉芽肿风险相关。
结论：疫苗接种肉芽肿的几个危险因素，儿童和产妇的水平，已确定。减少铝的剂量或用磷酸铝代替氢氧化铝可以降低肉芽肿的风险。然而,这必须与降低免疫原性的可能性相平衡。
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.
