In-utero exposure to antibiotics and risk of colorectal cancer in a prospective cohort of 18 000 adult offspring.

Abstract

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. 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. 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. Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood.