背景:儿童肥胖是一个重要的公共卫生问题,代表了世界上最严峻的挑战。生命早期的抗生素暴露已被确定为可能破坏肠道微生物组发育的潜在因素。这可能对肥胖有影响。
目的:本研究旨在评估早期接触抗生素的儿童患肥胖症的风险。
方法:采用一项意大利回顾性儿科人群队列研究,使用Pedianet数据库对2004年至2018年出生的儿童进行研究。孩子必须在足月出生,体重正常,没有遗传疾病或先天性异常.我们通过在生命的第一年记录的抗生素处方数量评估了从出生到生命的6、12和24个月的第一个抗生素处方的时间以及剂量反应关系(无,1、2和≥3个处方)。肥胖定义为≤5岁儿童的BMIz评分>3,>5岁儿童的BMIz评分>2。使用世界卫生组织的增长参考。使用婴儿性别计算肥胖发生率(IR)×100人年和相对的95%CI,居住区,学龄前和学龄儿童,和面积剥夺指数,它们是感兴趣的协变量。使用混合效应Cox比例风险模型来估计24个月至14岁儿童肥胖与早期抗生素暴露之间的风险比和95%CI。将家庭儿科医生视为随机因素。进行了一些亚组和敏感性分析,以评估我们结果的稳健性。
结果:在确认的121,540名儿童中,在生命的第一年内,至少有54,698人被开了抗生素,在随访期间有26,990人被归类为肥胖,发生率为4.05例(95%CI4.01-4.10)×100人年。在6个月的不同抗生素处方时间中,肥胖的风险保持一致。1年,和2年(完全调整的风险比[aHR]1.07,95%CI1.04-1.10;aHR1.06,95%CI1.03-1.09;和aHR1.07,95%CI1.04-1.10)。增加抗生素暴露的数量会显著增加肥胖的风险(P趋势<.001)。个体特定年龄分析显示,与在生命的第五个月后首次使用抗生素的人中观察到的情况相比,非常早(0至5个月)开始抗生素治疗对儿童肥胖症的影响最大(aHR1.12,95%CI1.08-1.17)。这些结果在亚组和敏感性分析中是一致的。
结论:这项基于人群的大型研究结果支持早期接触抗生素与儿童肥胖风险增加之间的关联。随着抗生素处方数量的增加和第一次处方时年龄的年轻,这种关联逐渐增强。
BACKGROUND: Childhood obesity is a significant public health problem representing the most severe challenge in the world. Antibiotic exposure in early life has been identified as a potential factor that can disrupt the development of the gut microbiome, which may have implications for obesity.
OBJECTIVE: This study aims to evaluate the risk of developing obesity among children exposed to antibiotics early in life.
METHODS: An Italian retrospective pediatric population-based cohort study of children born between 2004 and 2018 was adopted using the Pedianet database. Children were required to be born at term, with normal weight, and without genetic diseases or congenital anomalies. We assessed the timing of the first antibiotic prescription from birth to 6, 12, and 24 months of life and the dose-response relationship via the number of antibiotic prescriptions recorded in the first year of life (none, 1, 2, and ≥3 prescriptions). Obesity was defined as a BMI z score >3 for children aged ≤5 years and >2 for children aged >5 years, using the World Health Organization growth references. The obese incidence rate (IR) × 100 person-years and the relative 95% CI were computed using infant sex, area of residence, preschool and school age, and area deprivation index, which are the covariates of interest. A mixed-effect Cox proportional hazards model was used to estimate the hazard ratio and 95% CI for the association between antibiotic exposure in early life and child obesity between 24 months and 14 years of age, considering the family pediatricians as a random factor. Several subgroup and sensitivity analyses were performed to assess the robustness of our results.
RESULTS: Among 121,540 children identified, 54,698 were prescribed at least an antibiotic within the first year of life and 26,990 were classified as obese during follow-up with an incidence rate of 4.05 cases (95% CI 4.01-4.10) × 100 person-year. The risk of obesity remained consistent across different timings of antibiotic prescriptions at 6 months, 1 year, and 2 years (fully adjusted hazard ratio [aHR] 1.07, 95% CI 1.04-1.10; aHR 1.06, 95% CI 1.03-1.09; and aHR 1.07, 95% CI 1.04-1.10, respectively). Increasing the number of antibiotic exposures increases the risk of obesity significantly (P trend<.001). The individual-specific age analysis showed that starting antibiotic therapy very early (between 0 and 5 months) had the greatest impact (aHR 1.12, 95% CI 1.08-1.17) on childhood obesity with respect to what was observed among those who were first prescribed antibiotics after the fifth month of life. These results were consistent across subgroup and sensitivity analyses.
CONCLUSIONS: The results from this large population-based study support the association between early exposure to antibiotics and an increased risk of childhood obesity. This association becomes progressively stronger with both increasing numbers of antibiotic prescriptions and younger age at the time of the first prescription.