Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Department of Pediatrics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
JAMA Pediatr. 2018 Jun 4;172(6):e180315. doi: 10.1001/jamapediatrics.2018.0315.
Allergic diseases are prevalent in childhood. Early exposure to medications that can alter the microbiome, including acid-suppressive medications and antibiotics, may influence the likelihood of allergy.
To determine whether there is an association between the use of acid-suppressive medications or antibiotics in the first 6 months of infancy and development of allergic diseases in early childhood.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted in 792 130 children who were Department of Defense TRICARE beneficiaries with a birth medical record in the Military Health System database between October 1, 2001, and September 30, 2013, with continued enrollment from within 35 days of birth until at least age 1 year. Children who had an initial birth stay of greater than 7 days or were diagnosed with any of the outcome allergic conditions within the first 6 months of life were excluded from the study. Data analysis was performed from April 15, 2015, to January 4, 2018.
Exposures were defined as having any dispensed prescription for a histamine-2 receptor antagonist (H2RA), proton pump inhibitor (PPI), or antibiotic.
The main outcome was allergic disease, defined as the presence of food allergy, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria, contact dermatitis, medication allergy, or other allergy.
Of 792 130 children (395 215 [49.9%] girls) included for analysis, 60 209 (7.6%) were prescribed an H2RA, 13 687 (1.7%) were prescribed a PPI, and 131 708 (16.6%) were prescribed an antibiotic during the first 6 months of life. Data for each child were available for a median of 4.6 years. Adjusted hazard ratios (aHRs) in children prescribed H2RAs and PPIs, respectively, were 2.18 (95% CI, 2.04-2.33) and 2.59 (95% CI, 2.25-3.00) for food allergy, 1.70 (95% CI, 1.60-1.80) and 1.84 (95% CI, 1.56-2.17) for medication allergy, 1.51 (95% CI, 1.38-1.66) and 1.45 (95% CI, 1.22-1.73) for anaphylaxis, 1.50 (95% CI, 1.46-1.54) and 1.44 (95% CI, 1.36-1.52) for allergic rhinitis, and 1.25 (95% CI, 1.21-1.29) and 1.41 (95% CI, 1.31-1.52) for asthma. The aHRs after antibiotic prescription in the first 6 months of life were 2.09 (95% CI, 2.05-2.13) for asthma, 1.75 (95% CI, 1.72-1.78) for allergic rhinitis, 1.51 (95% CI, 1.38-1.66) for anaphylaxis, and 1.42 (95% CI, 1.34-1.50) for allergic conjunctivitis.
This study found associations between the use of acid-suppressive medications and antibiotics during the first 6 months of infancy and subsequent development of allergic disease. Acid-suppressive medications and antibiotics should be used during infancy only in situations of clear clinical benefit.
过敏疾病在儿童中很常见。早期接触可能改变微生物组的药物，包括抑酸药物和抗生素，可能会影响过敏的可能性。
确定婴儿期前 6 个月使用抑酸药物或抗生素与儿童早期过敏疾病的发展之间是否存在关联。
设计、地点和参与者：这是一项回顾性队列研究，在 792130 名国防部 TRICARE 受益人的儿童中进行，这些儿童在军事健康系统数据库中有出生医疗记录，记录时间为 2001 年 10 月 1 日至 2013 年 9 月 30 日，从出生后 35 天内开始持续入组，直至至少 1 岁。研究排除了出生时住院时间超过 7 天或在生命的前 6 个月内被诊断出任何过敏疾病的儿童。数据分析于 2015 年 4 月 15 日至 2018 年 1 月 4 日进行。
暴露定义为有任何开具的组胺 2 受体拮抗剂（H2RA）、质子泵抑制剂（PPI）或抗生素处方。
主要结果是过敏疾病，定义为存在食物过敏、过敏反应、哮喘、特应性皮炎、过敏性鼻炎、过敏性结膜炎、荨麻疹、接触性皮炎、药物过敏或其他过敏。
在 792130 名纳入分析的儿童中（49.9%为女孩），有 60209 名（7.6%）被处方 H2RA，13687 名（1.7%）被处方 PPI，131708 名（16.6%）被处方抗生素。每个孩子的数据中位数可用时间为 4.6 年。分别接受 H2RA 和 PPI 处方的儿童的调整后的危险比（aHR）分别为 2.18（95%CI，2.04-2.33）和 2.59（95%CI，2.25-3.00）用于食物过敏，1.70（95%CI，1.60-1.80）和 1.84（95%CI，1.56-2.17）用于药物过敏，1.51（95%CI，1.38-1.66）和 1.45（95%CI，1.22-1.73）用于过敏反应，1.50（95%CI，1.46-1.54）和 1.44（95%CI，1.36-1.52）用于过敏性鼻炎，以及 1.25（95%CI，1.21-1.29）和 1.41（95%CI，1.31-1.52）用于哮喘。婴儿期前 6 个月使用抗生素的处方后的 aHR 为 2.09（95%CI，2.05-2.13）用于哮喘，1.75（95%CI，1.72-1.78）用于过敏性鼻炎，1.51（95%CI，1.38-1.66）用于过敏反应，以及 1.42（95%CI，1.34-1.50）用于过敏性结膜炎。
这项研究发现，婴儿期前 6 个月使用抑酸药物和抗生素与随后过敏疾病的发展之间存在关联。只有在明确的临床获益情况下，才应在婴儿期使用抑酸药物和抗生素。
