Newman Thomas B, Wickremasinghe Andrea C, Walsh Eileen M, Grimes Barbara A, McCulloch Charles E, Kuzniewicz Michael W
Departments of Epidemiology and Biostatistics, and Pediatrics, University of California, San Francisco, California; Division of Research, Kaiser Permanente Northern California, Oakland, California; and
Departments of Epidemiology and Biostatistics, and Department of Pediatrics, Kaiser Permanente Santa Clara, Santa Clara, California.
Pediatrics. 2016 Jun;137(6). doi: 10.1542/peds.2015-1354.
To investigate the association between neonatal phototherapy use and childhood cancer.
This retrospective cohort study included 499 621 children born at ≥35 weeks' gestation from 1995 to 2011 in Kaiser Permanente Northern California hospitals, who survived to hospital discharge and were followed ≥60 days. We obtained data on home and inpatient phototherapy, covariates, and cancer incidence from electronic records. We used propensity-adjusted Cox and Poisson models to control for confounding and unequal follow-up times.
There were 60 children with a diagnosis of cancer among 39 403 exposed to phototherapy (25 per 100 000 person-years), compared with 651 of 460 218 unexposed children (18 per 100 000 person-years; incidence rate ratio [IRR] 1.4; P = .01). Phototherapy was associated with increased rates of any leukemia (IRR 2.1; P = .0007), nonlymphocytic leukemia (IRR 4.0; P = .0004), and liver cancer (IRR 5.2; P = .04). With adjustment for a propensity score that incorporated bilirubin levels, chromosomal disorders, congenital anomalies, and other covariates, associations were no longer statistically significant: Adjusted hazard ratios (95% confidence intervals) were 1.0 (0.7-1.6) for any cancer, 1.6 (0.8-3.5) for any leukemia, 1.9 (0.6-6.9) for nonlymphocytic leukemia, and 1.4 (0.2-12) for liver cancer. Upper limits of 95% confidence intervals for adjusted 10-year excess risk were generally <0.1% but reached 4.4% for children with Down syndrome.
Although phototherapy use was associated with increased cancer rates (particularly nonlymphocytic leukemia), control for confounding variables eliminated or attenuated the associations. Nonetheless, the possibility of even partial causality suggests that avoiding unnecessary phototherapy may be prudent.
探讨新生儿光疗的使用与儿童癌症之间的关联。
这项回顾性队列研究纳入了1995年至2011年在北加利福尼亚州凯撒医疗中心医院出生、孕周≥35周、存活至出院且随访时间≥60天的499621名儿童。我们从电子记录中获取了家庭和住院光疗、协变量以及癌症发病率的数据。我们使用倾向得分调整的Cox模型和泊松模型来控制混杂因素和随访时间的不均衡。
在39403名接受光疗的儿童中,有60名被诊断患有癌症(每10万人年25例),而在460218名未接受光疗的儿童中有651名(每10万人年为18例;发病率比[IRR]为1.4;P = 0.01)。光疗与任何白血病(IRR 2.1;P = 0.0007)(非淋巴细胞白血病(IRR 4.0;P = 0.0004)以及肝癌(IRR 5.2;P = 0.04)的发病率增加有关。在对纳入胆红素水平、染色体疾病、先天性异常和其他协变量的倾向得分进行调整后,这些关联不再具有统计学意义:任何癌症的调整后风险比(95%置信区间)为1.0(0.7 - 1.6),任何白血病为1.6(0.8 - 3.5),非淋巴细胞白血病为1.9(0.6 - 6.9),肝癌为1.4(0.2 - 12)。调整后的10年超额风险的95%置信区间上限通常<0.1%,但唐氏综合征儿童达到4.4%。
虽然光疗的使用与癌症发病率增加有关(特别是非淋巴细胞白血病),但对混杂变量的控制消除或减弱了这种关联。尽管如此,即使存在部分因果关系的可能性也表明,谨慎避免不必要的光疗可能是明智的。