抗生素是儿童肥胖的“万恶之源”?JAMA等四大期刊结论不一
2016/03/30
关于抗生素与儿童肥胖,国际顶级期刊已有论文报道。然而近日,刊于《JAMA》及《Gastroenterology》杂志上的两项关于儿童肥胖与抗生素的研究结论却不相一致。


今年2月份,复旦大学的研究人员在国际权威期刊《Environment International》表明儿童时期抗生素暴露可能是儿童肥胖的危险因素之一。那么,抗生素暴露,真的是儿童肥胖的“万恶之源”?近日,刊于《JAMA》及《Gastroenterology》杂志上的两项关于儿童肥胖与抗生素的研究结果却不相一致。

《JAMA》:“暴露于抗生素对年幼儿童有很多影响,但体重增加可能不是其中之一”

在《JAMA》3月22日的论文中,研究人员表示在新生儿出生的前六个月中未发现抗生素与肥胖的关联。该研究由费城儿童医院的医学博士.Jeffrey S. Gerber及其同事完成,研究对象来自美国宾西尼亚州、新泽西及特拉华州不同种族和社会经济背景下不同程度暴露于抗生素的38522名儿童和92名双胞胎(46对)。

在该研究中,5287例(14%)儿童在出生的前6个月暴露在抗生素下,研究发现,在2-5岁之间,抗生素暴露与多余的体重增加没有明显的关联。同样,是否暴露于抗生素对双胞胎的体重差异并没有影响。作者写道,“暴露于抗生素对年幼的孩子有很多影响,但体重增加可能不是其中之一。”

《Gastroenterology》:“抗生素被用于促进牲畜体重已有几十年,我们的研究表明抗生素对人类也有同样的效果”

然而,3月19日发表在《Gastroenterology》上的研究表明接受三种以上抗生素的2岁以下儿童患早期肥胖的风险更高。在该论文中,研究人员回顾性研究了健康促进网络(Health Improvement Network,英国代表人群数据库)中的21714名儿童。合格的受试者为出生前三个月在数据库中登记并接受48个月随访的儿童,随访期间统计了受试者48个月内所接受过的所有处方以及所适应的环境,包括同胞和母亲的肥胖、分娩方式、出生年月、社会经济地位及早期肥胖等。

研究人员发现,1306名儿童在4岁时开始肥胖,且 4岁时抗生素的暴露与肥胖风险的增加有关,暴露量越大,关联比例越大。抗真菌药物与肥胖风险无关。


本文作者在一次新闻发布会上说,“抗生素被用于促进牲畜体重已有几十年,我们的研究表明抗生素对人类也有同样的效果。这支持了抗生素可能逐渐改变肠道微生物的组成和功能的观点,从而诱发儿童肥胖。”然而作者警示,他们的研究结果并不意味着不能使用抗生素,而是强调在成熟前避免使用抗生素的原因。

《International Journal of Obesity》:“抗生素的使用可能影响整个儿童期的体重”

约翰霍普金斯大学彭博公共卫生学院流行病学、环境健康科学教授Brian Schwartz医学博士表示,“尽管两项研究的结论不同,但并不完全矛盾。在我看来,JAMA上的研究关注的是临床上的个体,而不是人群,且没有校准一些重要的变量,因而可能低估了规模效应。”但他表示JAMA的作者做得很好。目前有越来越多的文献显示抗生素与儿童肥胖之间的关联,不过JAMA研究人员评估了6个月至7岁儿童的体重,但目前很多研究评估的指标是身体质量指数而不是体重,更令人惊讶的是,这篇文章的作者没有考虑到分娩方式和产前抗生素暴露,已有研究表明剖腹产影响儿童微生物并与体重有关。

去年,Schwartz医学博士及其同事在《International Journal of Obesity》杂志上表明抗生素的使用可能影响整个儿童期的体重。“我们的研究表明,抗生素导致体重增加,但在儿童早期这种影响效果不是特别强,这也是JAMA上的研究所关注的一部分,但他们没有揭示新生儿前6个月暴露于抗生素对体重的影响。”

然而,《Gastroenterology》上的研究强调了一些重要的变量,包括分娩方式,他们的研究结果发现肥胖风险随抗生素处方量的增加而增大,这与Schwartz医学博士在《International Journal of Obesity》杂志上的研究结果相一致。

《Environment International》:“儿童时期抗生素暴露可能是儿童肥胖的危险因素之一”

复旦大学研究人员于2013年起在对上海地区对586名8到11岁学龄儿童进行随访,测定了尿中21种抗生素,包括5种大环内酯类抗生素、2种β-内酰胺类抗生素、3种四环素类抗生素、4种喹诺酮类抗生素、4种磺胺类抗生素和3种氯霉素类抗生素,同时采用体质指数和腰围判断儿童超重或肥胖。结果发现儿童时期抗生素暴露可能是儿童肥胖的危险因素之一,相关结果于2月22日发表在国际权威杂志《环境国际》(Environment International)杂志上。


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  • Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity

    Background & Aims Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. Methods We performed a retrospective cohort study of 21,714 children in The Health Improvement Network —a population-representative dataset of more than 10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. Results In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR]=1.21; 95% confidence interval [CI], 1.07–1.38). Odds ratios increased with repeated exposures: for 1–2 prescriptions, OR=1.07 (95% CI, 0.91-1.23); for 3–5 prescriptions, OR=1.41 (95% CI, 1.20–1.65); for 6 or more prescriptions, OR=1.47 (95% CI, 1.19–1.82). Antifungal agents were not associated with obesity (OR=0.81; 95% CI, 0.59–1.11). Conclusions Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity.

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  • Antibiotic use and childhood body mass index trajectory

    Background/Objectives: Antibiotics are commonly prescribed for children. Use of antibiotics early in life has been linked to weight gain but there are no large-scale, population-based, longitudinal studies of the full age range among mainly healthy children. Subjects/Methods: We used electronic health record data on 163 820 children aged 3–18 years and mixed effects linear regression to model associations of antibiotic orders with growth curve trajectories of annual body mass index (BMI) controlling for confounders. Models evaluated three kinds of antibiotic associations—reversible (time-varying indicator for an order in year before each BMI), persistent (time-varying cumulative orders up to BMIj) and progressive (cumulative orders up to prior BMI (BMIj-1))—and whether these varied by age. Results: Among 142 824 children under care in the prior year, a reversible association was observed and this short-term BMI gain was modified by age (P<0.001); effect size peaked in mid-teen years. A persistent association was observed and this association was stronger with increasing age (P<0.001). The addition of the progressive association among children with at least three BMIs (n=79 752) revealed that higher cumulative orders were associated with progressive weight gain; this did not vary by age. Among children with an antibiotic order in the prior year and at least seven lifetime orders, antibiotics (all classes combined) were associated with an average weight gain of approximately 1.4 kg at age 15 years. When antibiotic classes were evaluated separately, the largest weight gain at 15 years was associated with macrolide use. Conclusions: We found evidence of reversible, persistent and progressive effects of antibiotic use on BMI trajectories, with different effects by age, among mainly healthy children. The results suggest that antibiotic use may influence weight gain throughout childhood and not just during the earliest years as has been the primary focus of most prior studies.

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  • Antibiotics detected in urines and adipogenesis in school children

    Background Although antibiotic use during early life has been demonstrated to be related to the altered adipogenesis in later life, limited data are available for the effect of antibiotic exposure in school children on adiposity from various sources, including from the use or contaminated food or drinking water. Objective To explore the association between the internal exposure of antibiotics from various sources and adipogenesis in school children using the biomonitoring of urinary antibiotics. Methods After 586 school children aged 8–11 years were selected from Shanghai in 2013, total urinary concentrations (free and conjugated) of 21 common antibiotics from six categories (macrolides, β-lactams, tetracyclines, fluoroquinolones, sulfonamides, and phenicols), including five human antibiotics (HAs), two antibiotics preferred as HA, four veterinary antibiotics (VAs), and ten antibiotics preferred as VA, were measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Creatinine-corrected urinary concentrations of antibiotics were used to assess their exposure. Overweight or obesity was determined by the body mass index or waist circumference-based criteria deriving from national data. Results All 21 antibiotics were found in urines with the overall detection frequency of 79.6%. The multinomial logistic regression analyses showed the significant associations of overweight and obesity with the exposure to VAs and antibiotics preferred as VA, but not with HAs or antibiotics preferred as HA. After adjusted for a number of obesity-relevant variables, the odds ratios (95% confidence interval) of BMI-based obesity risk of tertiles 2 and 3 of urinary concentrations relative to tertile 1 were respectively 2.54 (1.27, 5.07) and 2.92 (1.45, 5.87) for florfenicol, 0.57 (0.12, 2.63) and 3.63 (1.41, 9.32) for trimethoprim, and 3.00 (1.56, 5.76) and 1.99 (0.99, 4.01) for sum of veterinary antibiotics. Similar results were found when the outcome used WC-based obesity risk. The associations were sex related and mainly observed in boys. Conclusions Some types of antibiotic exposure, which were mainly from food or drinking water, were associated with an increased risk of obesity in school children. Due to the cross-sectional design, more longitudinal and experimental studies are warranted to further test these findings.

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