Experimental evidence suggests that perinatal light imprinting of circadian clocks and systems may affect downstream physiology and cancer risk in later life. For humans, the predominant circadian stimulus is the daily light-dark cycle. Herein, we explore associations between perinatal photoperiod characteristics (photoperiod: duration of daylight as determined by time-of-year and location) and childhood cancer risk. We use pooled data on 182,856 mothers and babies from prospective birth cohorts in six countries (Australia, Denmark, Israel, Norway, UK, USA) within the International Childhood Cancer Cohort Consortium (I4C). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In line with predicted differential dose–responses, restricted cubic splines indicate a potential non-linear, non-monotonic relationship between perinatal mean daily photoperiod (0–24 h) and childhood cancer risk. In a restricted analysis of 154,121 individuals who experienced third trimester photoperiods exclusively within the 8–16-h range, the relative risk of developing childhood cancer decreased by 9% with every hour increase in third trimester mean daily photoperiod [HR: 0.91 (95%CIs: 0.84–0.99)]. In conclusion, in this first study of perinatal photoperiod and childhood cancer, we detected an inverse [“protective”] linear association between third trimester mean daily photoperiod and childhood cancer risk in the 8–16-h set of the total study population. Limited statistical power impeded the investigation of risks with individuals exposed to more extreme photoperiods. Future studies are needed to confirm differential photoperiod-associated risks and further investigations into the hypothesized circadian imprinting mechanism are warranted.

实验证据表明，生物钟和系统的围产期光印记可能会影响晚年的下游生理和癌症风险。对于人类来说，主要的昼夜节律刺激是每天的明暗循环。在这里，我们探讨了围产期光周期特征（光周期：由一年中的时间和地点确定的日光持续时间）与儿童癌症风险之间的关联。我们使用来自国际儿童癌症队列联盟 (I4C) 的六个国家（澳大利亚、丹麦、以色列、挪威、英国、美国）的 182,856 名母亲和婴儿的汇总数据。Cox 比例风险回归用于估计风险比 (HR) 和 95% 置信区间 (CI)。与预测的不同剂量反应一致，受限三次样条表示潜在的非线性，围产期平均日光周期（0-24小时）与儿童癌症风险之间的非单调关系。在对 154,121 名仅在 8-16 小时范围内经历了孕晚期光周期的个体进行的限制性分析中，随着孕晚期平均每日光周期每小时增加一小时，患儿童癌症的相对风险降低了 9% [HR：0.91 (95% CI：0.84–0.99)]。总之，在这项关于围产期光周期和儿童癌症的第一项研究中，我们在总研究人群的 8-16 小时组中检测到妊娠晚期平均每日光周期与儿童癌症风险之间存在反向 [“保护性”] 线性关联。有限的统计能力阻碍了对暴露于更极端光周期的个人的风险调查。