Long Term Antibiotic Use and Weight Gain in Children and Adolescents

描述(申请人提供)：肥胖和超重在儿童中迅速流行。造成这一现象的一个因素可能是感染，无论是特定暴露的变化还是定植菌群的变化，抗生素的使用(ABX)也可能起作用。ABX对家畜的促生长作用早在20世纪40年代的S就已为人所知。在人类中长期使用ABX的类似效果似乎越来越可信。1950年S对新兵进行的一项试验表明，服用ABX的新兵比服用安慰剂的新兵增加了更多的体重。最近，接受ABX治疗的心内膜炎患者与没有接受ABX治疗的匹配对照组相比，体重显著增加。研究人员假设，肥胖和肠道微生物区系之间存在联系，ABX也可以通过改变肠道微生物区系来影响体重。在幼儿中，通过在配方奶粉中添加益生菌改变肠道微生物区系，导致体重显著增加。研究ABX对体重的作用是具有挑战性的，因为服用ABX的患者通常会生病，然后在改善健康的过程中体重增加。然而，一些相对健康的受试者确实接受了ABX，这一群体是我们研究的重点。假设：在健康的儿童和青少年中，长期使用ABX会促进体重增加，这比基于ABX之前的增长预期的体重增加更大。目的：1.研究在健康儿童和青少年正常生长的基础上，延长口服ABX是否会导致比预期更大的体重增加。2.评估特定类别的ABX是否比其他类别对体重的影响更大。3.研究ABX效应的持续时间。设计：首先，我们将使用过去10年的数据，从大型初级保健环境中的患者中进行一项回溯性队列研究。约6700名儿童和青少年被处方延长口服ABX e4周(并让药房填写ABX前后的数据和体重)。在我们的初步分析中，我们将重点关注青少年痤疮患者，这是最健康和最同质的群体。其中约500人在ABX前后有体重和身高。我们还将分析儿童，研究ABX对更广泛年龄段的影响。在我们的初步分析中，每个患者都将充当他/她自己的对照。我们将使用标准t检验来衡量ABX前最后一次BMI Z分数和ABX后第一次BMI(主要结果)之间的变化，以及BMI Z分数变化e0.5的比例。在二次分析中，我们还将捕捉每个受试者的数据轨迹，并探索其他变量对所研究的关联的影响。其次，我们将进行嵌套式病例对照研究，比较口服ABX治疗的青少年痤疮患者与仅服用局部药物的匹配对照组的痤疮患者。通过这些分析，我们将消除个体间的变异性，最大限度地减少个体内的变异性，并考虑到与正常生长相关的变化。潜在影响：记录ABX的促生长作用将为肠道微生物区系和感染在儿童肥胖中的作用提供进一步的经验性支持，并为新的预防策略开辟新的视野。我们想要研究在健康的儿童和青少年中长期使用ABX是否具有促进生长的作用，这种作用是否特定于某些抗生素，以及停止使用抗生素后是否会持续体重增加。找到抗生素和体重之间的联系可能会为预防儿童肥胖症的策略开辟新的视野。 公共卫生相关性：我们想要研究在健康的儿童和青少年中长期使用ABX是否具有促进生长的作用，这种作用是否特定于某些抗生素，以及停止使用抗生素后是否会持续体重增加。找到抗生素和体重之间的联系可能会为预防儿童肥胖症的策略开辟新的视野。

DESCRIPTION (provided by applicant): Obesity and overweight in children have rapidly become epidemic. One factor that may contribute to this phenomenon is infection, either changes in specific exposures or in colonizing flora, and use of antibiotics (ABX) may also play a role. The growth promoting effects of ABX in farm animals have been known since the 1940's. A similar effect of prolonged ABX use in humans seems increasingly plausible. A 1950's trial in army recruits showed that those treated with ABX gained more weight than did placebo controls. More recently, endocarditis patients receiving ABX had marked weight gain compared to matched controls without ABX. Investigators hypothesize that there is an association between obesity and gut microbiota and that ABX can affect weight also by altering gut microbiota. In young children, changes in gut microbiota by adding probiotics to formula have resulted in marked weight increase. Studying the role of ABX on weight is challenging because patients who take ABX are usually ill and then gain weight in the course of improving their health. Some relatively healthy subjects however, do receive ABX and this group is the focus of our study. HYPOTHESIS: Prolonged ABX use in healthy children and adolescents promotes weight gain that is greater from what would be expected based on their pre-ABX growth. OBJECTIVES:1. To study whether prolonged oral ABX in healthy children and adolescents results in greater weight gain than expected based on their normal growth. 2. To assess whether specific classes of ABX classes affect weight more than others. 3. To study the duration of such ABX effect. DESIGN: First, we will do a retrospective cohort study using data from the past 10 years, from patients in a large primary care setting. About 6,700 children and adolescents were prescribed prolonged oral ABX for e4 weeks (and had pharmacy fill data AND weights pre/post-ABX). In our primary analysis we will focus on adolescents with acne, the most healthy and homogeneous group. About 500 of those had weights AND heights pre/post- ABX. We will analyze also children, to study the effect of ABX on a broader spectrum of ages. In our primary analysis each patient will serve as his/her own control. We will measure the change between last pre-ABX BMI Z-score and first post-ABX (primary outcome) using standard t-test AND also the proportion that had a BMI Z-score change e0.5. In secondary analyses we will also capture the trajectory of data for each subject and explore the effect of additional variables on the studied association. Second, we will do a nested case-control study to compare adolescents with acne on oral ABX with a matched control group of acne patients only on topicals. With these analyses we will eliminate between-individuals variability, minimize within-individual variability and account for changes associated with normal growth. POTENTIAL IMPACT: Documentation of growth promoting effects of ABX will provide further empiric support for the role of gut microbiota and infection in childhood obesity and open new horizons for novel preventive strategies. We want to study whether prolonged ABX use in healthy children and adolescents has a growth promoting effect, whether this effect is specific to certain antibiotics and whether any weight gain is sustained after antibiotic cessation. Finding a link between antibiotics and weight may open new horizons for strategies to prevent childhood obesity. PUBLIC HEALTH RELEVANCE: We want to study whether prolonged ABX use in healthy children and adolescents has a growth promoting effect, whether this effect is specific to certain antibiotics and whether any weight gain is sustained after antibiotic cessation. Finding a link between antibiotics and weight may open new horizons for strategies to prevent childhood obesity.