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英国儿童早期接触抗菌药物与随后发生花粉热的情况:利用全科医学研究数据库和医生独立网络进行的病例对照研究

Early-life exposure to antibacterials and the subsequent development of hayfever in childhood in the UK: case-control studies using the General Practice Research Database and the Doctors' Independent Network.

作者信息

Bremner S A, Carey I M, DeWilde S, Richards N, Maier W C, Hilton S R, Strachan D P, Cook D G

机构信息

Department of Community Health Sciences, St George's Hospital Medical School, London, UK.

出版信息

Clin Exp Allergy. 2003 Nov;33(11):1518-25. doi: 10.1046/j.1365-2222.2003.01794.x.

Abstract

BACKGROUND

Theoretically, antibacterial agents in early life might influence allergic sensitization in two ways: (i) as an indicator of infectious illness, they might be expected to protect against allergy; (ii) alternatively they might increase the risk through effects on the commensal bowel flora. Epidemiological evidence linking the prescription of antibacterial agents in early life to the subsequent development of hayfever is conflicting.

OBJECTIVE

To establish definitively whether an association exists between early-life antibacterial exposure and childhood hayfever diagnosis.

METHODS

Nested case-control studies were based on birth cohorts of children identified within two large UK general practice databases of electronic patient records. One hundred and sixteen thousand and four hundred and ninety-three children from 605 general practices were identified as being continuously registered from birth to at least age 5 years. Seven thousand and ninety-eight cases were diagnosed with hayfever after the age of 2 years. One control per case was matched for practice, birth month, sex and still being registered on case diagnosis date. Odds ratios were derived from conditional logistic regressions within each database followed by pooling using a fixed-effect model.

RESULTS

The pooled odds ratio for hayfever was 1.11, 95% CI (1.03-1.20) if exposed to antibacterials in the first year of life, 1.35 (1.25-1.46) in year 2 and 1.47 (1.37-1.59) in year 3. Adjusting for consultation frequency reduced these odds ratios to 0.92, 1.05 and 1.10, respectively. There was no evidence that broader spectrum antibacterials, exposure in any specific month of year 1 or in the grass pollen season influenced the risk of hayfever.

CONCLUSION

These data exclude any important effect of antibacterial exposure in infancy on subsequent hayfever risk. Associations reported in earlier studies have likely been exaggerated through publication bias and by lack of control for the tendency of some families to consult frequently for a range of conditions.

摘要

背景

从理论上讲,生命早期使用抗菌药物可能通过两种方式影响过敏致敏:(i)作为感染性疾病的一个指标,它们可能有望预防过敏;(ii)或者,它们可能通过对肠道共生菌群的影响增加风险。将生命早期抗菌药物的处方与随后花粉症的发生联系起来的流行病学证据相互矛盾。

目的

明确生命早期接触抗菌药物与儿童花粉症诊断之间是否存在关联。

方法

巢式病例对照研究基于英国两个大型电子病历全科医疗数据库中确定的儿童出生队列。来自605个全科医疗诊所的116493名儿童被确定从出生到至少5岁持续注册。7098例在2岁后被诊断为花粉症。每例病例匹配一名对照,匹配因素包括诊所、出生月份、性别以及在病例诊断日期仍在注册。比值比通过每个数据库内的条件逻辑回归得出,随后使用固定效应模型进行合并。

结果

如果在生命的第一年接触抗菌药物,花粉症的合并比值比为1.11,95%可信区间(1.03 - 1.20);在第二年为1.35(1.25 - 1.46);在第三年为1.47(1.37 - 1.59)。调整就诊频率后,这些比值比分别降至0.92、1.05和1.10。没有证据表明广谱抗菌药物、在第一年的任何特定月份或草花粉季节接触会影响花粉症风险。

结论

这些数据排除了婴儿期接触抗菌药物对随后花粉症风险的任何重要影响。早期研究中报道的关联可能因发表偏倚以及未控制一些家庭因多种情况频繁就诊的倾向而被夸大。

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