Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milano, Italy.
Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padova, Padova, Italy.
JMIR Public Health Surveill. 2024 May 31;10:e51734. doi: 10.2196/51734.
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.
This study aims to evaluate the risk of developing obesity among children exposed to antibiotics early in life.
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.
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.
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.
儿童肥胖是一个严重的公共卫生问题，是全世界面临的最严峻挑战。早期生活中接触抗生素已被确定为可能破坏肠道微生物组发育的潜在因素，这可能与肥胖有关。
本研究旨在评估儿童早期接触抗生素后肥胖的风险。
采用意大利基于儿科人群的回顾性队列研究，使用 Pedianet 数据库纳入 2004 年至 2018 年出生的儿童。要求儿童足月出生，体重正常，无遗传疾病或先天性异常。我们评估了从出生到 6、12 和 24 个月时首次使用抗生素的时间以及在第一年记录的抗生素处方数量（无、1、2 和≥3 张）的剂量反应关系。肥胖的定义为 5 岁以下儿童的 BMI z 评分>3，5 岁以上儿童的 BMI z 评分>2，使用世界卫生组织生长参考值。使用婴儿性别、居住地区、学前和学龄期以及地区贫困指数作为感兴趣的协变量，计算肥胖发生率（IR）×100 人年和相对 95%置信区间（CI）。使用混合效应 Cox 比例风险模型估计早期生活中接触抗生素与 24 个月至 14 岁儿童肥胖之间的关联的风险比（HR）和 95%CI，考虑到家庭儿科医生为随机因素。进行了多项亚组和敏感性分析，以评估我们结果的稳健性。
在确定的 121540 名儿童中，54698 名儿童在第一年中至少开了一种抗生素，26990 名儿童在随访期间被诊断为肥胖，发病率为 4.05 例（95%CI 4.01-4.10）×100 人年。抗生素处方的不同时间（6 个月、1 年和 2 年）均显示肥胖风险一致（完全调整后的 HR [aHR] 1.07，95%CI 1.04-1.10；aHR 1.06，95%CI 1.03-1.09；aHR 1.07，95%CI 1.04-1.10）。抗生素暴露次数的增加显著增加了肥胖的风险（P 趋势<.001）。个体年龄分析表明，早期（0-5 个月）开始抗生素治疗对儿童肥胖的影响最大（aHR 1.12，95%CI 1.08-1.17），与 5 个月后首次开抗生素的儿童相比。这些结果在亚组和敏感性分析中是一致的。
这项基于人群的大型研究结果支持了早期接触抗生素与儿童肥胖风险增加之间的关联。这种关联随着抗生素处方数量的增加和首次处方时年龄的减小而逐渐增强。
