子宫内暴露于抗生素与 18000 名成年后代结直肠癌风险的前瞻性队列研究。
In-utero exposure to antibiotics and risk of colorectal cancer in a prospective cohort of 18 000 adult offspring.
机构信息
Department of Health Promotion and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth Houston), School of Public Health, Houston, TX, USA.
Child Health and Development Studies, Public Health Institute, Berkeley, CA, USA.
出版信息
Int J Epidemiol. 2023 Oct 5;52(5):1448-1458. doi: 10.1093/ije/dyad004.
BACKGROUND
Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring.
METHODS
The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact.
RESULTS
Of 18 751 liveborn offspring, about 15% (n = 2635) were exposed in utero to antibiotics: 5.4% (n = 1016) to tetracyclines, 4.9% (n = 918) to penicillins, 4.2% (n = 785) to short-acting sulfonamides and 1.5% (n = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides.
CONCLUSION
Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood.
背景
结直肠癌（CRC）的发病率在年轻人和中年人群中呈上升趋势，这表明生命早期的暴露是危险因素。我们研究了胎儿期暴露于抗生素与成年后代 CRC 风险之间的关系。
方法
儿童健康与发展研究是一项前瞻性队列研究，纳入了 1959 年至 1966 年期间在加利福尼亚州奥克兰接受产前护理的女性，并于 1967 年 6 月前分娩。从怀孕前 6 个月至分娩后，从母亲的医疗记录中提取诊断疾病和所有规定的药物。我们确定了在怀孕期间接受抗生素治疗的母亲，包括青霉素类、四环素类、短效磺胺类和长效磺胺类。通过与加利福尼亚癌症登记处的链接，确定成年（年龄≥18 岁）后代的 CRC 诊断。使用 Cox 比例风险模型估计调整后的危险比（aHR），随访时间从出生到癌症诊断、死亡或最后一次联系。
结果
在 18751 名活产后代中，约 15%（n=2635）在子宫内暴露于抗生素：四环素 5.4%（n=1016），青霉素 4.9%（n=918），短效磺胺类 4.2%（n=785）和长效磺胺类 1.5%（n=273）。与未暴露于抗生素的后代相比，在子宫内暴露与成年后代 CRC 之间的关联为：四环素的 aHR 为 1.03（95%CI 0.32，3.31）；青霉素的 aHR 为 1.12（95%CI 0.35，3.58）；短效磺胺类的 aHR 为 0.83（95%CI 0.20，3.42）；长效磺胺类的 aHR 为 4.40（95%CI 1.63，11.88）。
结论
我们的研究结果支持胎儿期暴露于长效磺胺类药物与成年后 CRC 之间存在关联。
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