Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial
Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(16)31418-0
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发表时间：
2017-01-21
期刊：
影响因子：
168.9
通讯作者：
Ohya, Yukihiro
中科院分区：
文献类型：
--
作者：
Natsume, Osamu;Kabashima, Shigenori;Ohya, Yukihiro
背景越来越多的证据表明，作为食物过敏一级预防的一种策略，早期消费比推迟推出更有益。然而，及早引入此类固体食品引起的过敏反应一直是一个问题。我们调查了早期向患有湿疹的婴儿逐步注射鸡蛋并结合最佳的湿疹治疗是否可以在1岁时预防鸡蛋过敏。方法在这项随机、双盲、安慰剂对照的试验中，我们从日本的两个中心招募了4-5个月大的患有湿疹的婴儿。排除标准包括：胎龄37周前出生、有食用鸡蛋或鸡蛋制品的经历、对鸡蛋有即刻过敏反应史、对特定类型食物的非即刻过敏反应史、以及任何严重疾病的并发症。婴儿被随机分配(四个区组大小；按机构和性别分层)，早期引入卵子或安慰剂(1：1)。鸡蛋组的参与者从6个月到9个月龄每天口服加热蛋粉50毫克，此后每天口服250毫克，直到12个月龄。我们在入院时积极治疗受试者的湿疹，并在整个干预期间保持控制，没有恶化。参与者和医生被蒙面分配，分配被隐藏。主要结果是，在所有随机分配的接受干预的参与者中，采用标准化方法盲目评估12个月大时通过开放口服食物挑战确认患有母鸡鸡蛋过敏的参与者的比例。这项试验在大学医院医学信息网临床试验登记处注册，编号为UMIN000008673。在2012年9月18日至2015年2月13日期间，我们随机分配了147名参与者(鸡蛋组73[50%]，安慰剂组74[50%])。这项试验的终止是基于对100名参与者进行的预定中期分析的结果，结果显示两组之间存在显著差异(鸡蛋组47名参与者中有4名[9%]对安慰剂组47名参与者有鸡蛋过敏；风险比0.222[95%可信区间0.081-0.607]；p=0.0012)。在初步分析人群中，鸡蛋组60名参与者中有5名(8%)有鸡蛋过敏，而安慰剂组61名参与者中有23名(38%)有鸡蛋过敏(风险比0.221[0.090-0.543]；p=0.0001)。两组之间唯一的不良事件差异是入院(鸡蛋组60人中有6人[10%]，而安慰剂组没有人；p=0.022)。在服用试验粉后，鸡蛋组9名参与者(15%)发生了19起急性事件，而安慰剂组11名参与者(18%)发生了14起事件。在高危婴儿中，逐步引入加热的鸡蛋并进行积极的湿疹治疗是一种安全有效的预防鸡蛋过敏的方法。在这项研究中，我们开发了一种实用的方法来克服由食物过敏引起的第二波过敏流行病。
Background Evidence is accumulating that early consumption is more beneficial than is delayed introduction as a strategy for primary prevention of food allergy. However, allergic reactions caused by early introduction of such solid foods have been a problematic issue. We investigated whether or not early stepwise introduction of eggs to infants with eczema combined with optimal eczema treatment would prevent egg allergy at 1 year of age.Methods In this randomised, double-blind, placebo-controlled trial, we enrolled infants 4-5 months of age with eczema from two centres in Japan. Exclusion criteria were being born before 37 weeks of gestational age, experience of ingestion of hen's eggs or egg products, history of immediate allergic reaction to hen's eggs, history of non-immediate allergic reaction to a particular type of food, and complications of any severe disease. Infants were randomly assigned (block size of four; stratified by institution and sex) to early introduction of egg or placebo (1:1). Participants in the egg group consumed orally 50 mg of heated egg powder per day from 6 months to 9 months of age and 250 mg per day thereafter until 12 months of age. We aggressively treated participants' eczema at entry and maintained control without exacerbations throughout the intervention period. Participants and physicians were masked to assignment, and allocation was concealed. The primary outcome was the proportion of participants with hen's egg allergy confirmed by open oral food challenges at 12 months of age, assessed blindly by standardised methods, in all randomly allocated participants who received the intervention. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000008673.Findings Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0.222 [95% CI 0.081-0.607]; p=0.0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0.221 [0.090-0.543]; p=0.0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0.022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder.Interpretation Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent hen's egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy.