Background

Primary prevention of food allergy by early introduction of allergenic foods seems promising. We aimed to determine whether early food introduction or the application of regular skin emollients in infants from a general population reduced the risk of food allergy.

Methods

This 2 × 2 factorial, cluster-randomised trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway, and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine 18-week ultrasound examination were cluster-randomised at birth to the following groups: (1) no intervention group; (2) the skin intervention group (skin emollients; bath additives and facial cream; from age 2 weeks to <9 months, both at least four times per week); (3) the food intervention group (early complementary feeding of peanut, cow's milk, wheat, and egg from age 3 months); or (4) combined intervention group (skin and food interventions). Participants were randomly assigned (1:1:1:1) using computer-generated randomisation based on clusters of 92 geographical areas and eight 3-month time blocks. Study personnel performing clinical assessments were masked to group allocation. The primary outcome was allergy to any interventional food at 36 months of age. The primary efficacy analysis was done by intention-to-treat analysis, which included all participants who were randomly assigned, apart from three individuals who withdrew their consent. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). This study is registered as ClinicalTrials.gov, NCT02449850.

Findings

We recruited 2697 women with 2701 pregnancies, from whom 2397 newborn infants were enrolled between April 14, 2015, and April 11, 2017. Of these infants, 597 were randomly assigned to the no intervention group, 575 to the skin intervention group, 642 to the food intervention group, and 583 to the combined intervention group. One participant in each of the no intervention, food intervention, and skin intervention groups withdrew consent and were therefore not included in any analyses. Food allergy was diagnosed in 44 children; 14 (2·3%) of 596 infants in the non-intervention group, 17 (3·0%) of 574 infants in the skin intervention group, six (0·9%) of 641 infants in the food intervention group, and seven (1·2%) of 583 infants in the combined intervention group. Peanut allergy was diagnosed in 32 children, egg allergy in 12 children, and milk allergy in four children. None had allergy to wheat. Prevalence of food allergy was reduced in the food intervention group compared with the no food intervention group (risk difference –1·6% [95% CI –2·7 to –0·5]; odds ratio [OR] 0·4 [95% CI 0·2 to 0·8]), but not compared with the skin intervention group (0·4% [95% CI –0·6 to 1· 5%]; OR 1·3 [0·7 to 2·3]), with no significant interaction effect (p=1·0). Preventing food allergy in one child required early exposure to allergenic foods in 63 children. No serious adverse events were observed.

Interpretation

Exposure to allergenic foods from 3 months of age reduced food allergy at 36 months in a general population. Our results support that early introduction of common allergenic foods is a safe and effective strategy to prevent food allergy.

Funding

Full funding sources listed at end of paper (see Acknowledgments).

中文翻译：

---

早期食物干预和润肤剂预防幼儿食物过敏 (PreventADALL)：一项因子、多中心、整群随机试验

背景

通过早期引入过敏性食物来初步预防食物过敏似乎很有希望。我们的目的是确定在普通人群的婴儿中早期引入食物或使用常规皮肤润肤剂是否会降低食物过敏的风险。

方法

这项 2 × 2 因子、整群随机试验在挪威奥斯陆的奥斯陆大学医院和 Østfold 医院信托基金以及瑞典斯德哥尔摩的卡罗林斯卡大学医院进行。在产前常规 18 周超声检查中招募的妇女的婴儿在出生时被整群随机分配到以下组：（1）无干预组；（2）皮肤干预组（润肤剂；沐浴添加剂和面霜；2周至<9个月，每周至少4次）；（3）食物干预组（从3月龄开始早期辅食花生、牛奶、小麦、鸡蛋）；或（4）联合干预组（皮肤和食物干预）。参与者被随机分配（1:1:1:1），使用基于 92 个地理区域和 8 个 3 个月时间块的集群的计算机生成随机化。进行临床评估的研究人员对分组分配不知情。主要结果是在 36 个月大时对任何干预性食物过敏。主要疗效分析是通过意向治疗分析完成的，其中包括所有被随机分配的参与者，除了三个撤回同意的人。这是在 ORAACLE（奥斯陆儿童哮喘和过敏研究小组；肺和环境）内进行的一项研究。本研究注册为 ClinicalTrials.gov，NCT02449850。除了撤回同意的三个人。这是在 ORAACLE（奥斯陆儿童哮喘和过敏研究小组；肺和环境）内进行的一项研究。本研究注册为 ClinicalTrials.gov，NCT02449850。除了撤回同意的三个人。这是在 ORAACLE（奥斯陆儿童哮喘和过敏研究小组；肺和环境）内进行的一项研究。本研究注册为 ClinicalTrials.gov，NCT02449850。

发现

我们招募了 2697 名妇女和 2701 名孕妇，在 2015 年 4 月 14 日至 2017 年 4 月 11 日期间招募了 2397 名新生儿。在这些婴儿中，597 名被随机分配到不干预组，575 名被分配到皮肤干预组，642 名至食物干预组，联合干预组 583 人。无干预组、食物干预组和皮肤干预组各有一名参与者撤回同意，因此不包括在任何分析中。44 名儿童被诊断出食物过敏；非干预组 596 名婴儿中有 14 名（2·3%），皮肤干预组 574 名婴儿中有 17 名（3·0%），食物干预组 641 名婴儿中有 6 名（0·9%），和联合干预组 583 名婴儿中有 7 名 (1·2%)。32名儿童被诊断出花生过敏，12名儿童被诊断出鸡蛋过敏，和四个孩子的牛奶过敏。没有人对小麦过敏。与无食物干预组相比，食物干预组的食物过敏患病率降低（风险差异 –1·6% [95% CI –2·7 至 –0·5]；优势比 [OR] 0·4 [ 95% CI 0·2 至 0·8]），但未与皮肤干预组比较（0·4% [95% CI –0·6 至 1·5%]；或 1·3 [0·7 至2·3]），没有显着的交互作用（p=1·0）。预防 1 名儿童的食物过敏需要 63 名儿童及早接触致敏性食物。没有观察到严重的不良事件。但与皮肤干预组相比（0·4% [95% CI –0·6 到 1·5%]；OR 1·3 [0·7 到 2·3]），没有显着的交互作用（p =1·0)。预防 1 名儿童的食物过敏需要 63 名儿童及早接触致敏性食物。没有观察到严重的不良事件。但与皮肤干预组相比（0·4% [95% CI –0·6 到 1·5%]；OR 1·3 [0·7 到 2·3]），没有显着的交互作用（p =1·0)。预防 1 名儿童的食物过敏需要 63 名儿童及早接触致敏性食物。没有观察到严重的不良事件。

解释

在一般人群中，从 3 个月大开始接触致敏性食物可减少 36 个月大的食物过敏。我们的研究结果支持早期引入常见的过敏食物是预防食物过敏的安全有效的策略。

资金

论文末尾列出的全部资金来源（见致谢）。