Importance An increasing number of children worldwide are born after the use of fertility treatment, although it remains unclear whether the treatment affects the risk of childhood cancer and whether any associations observed are due to the use of specific drugs, the use of specific procedures, or the underlying infertility. Objective To examine the association between different types of fertility treatments and cancer risk in children. Design, Setting, and Participants A retrospective cohort study based on Danish population-based registry data and the Danish Infertility Cohort (individual record linkage) that included 1 085 172 children born in Denmark between January 1, 1996, and December 31, 2012, linked with parental information. There were a total of 2217 children diagnosed with cancer (follow-up occurred during 1996-2015). Exposures Maternal fertility treatment during the index pregnancy, including the use of fertility drugs (clomiphene [n = 33 835], gonadotropins [n = 57 136], gonadotropin-releasing hormone analogs [n = 38 653], human chorionic gonadotropin [n = 68 181], progesterone [n = 41 628], and estrogen [n = 16 948]) and assisted reproductive technology (in vitro fertilization [n = 19 448], intracytoplasmic sperm injection [n = 13 417], and frozen embryo transfer [n = 3356]). Each exposure was examined separately and compared with children born to fertile women. Main Outcomes and Measures Hazard ratios and incidence rate differences for childhood cancer. Results After 12.2 million person-years of follow-up (mean, 11.3 years), the incidence rate of childhood cancer was 17.5 per 100 000 for children born to fertile women (n = 910 291) and 44.4 per 100 000 for children born after the use of frozen embryo transfer (n = 3356). Compared with children born to fertile women, the use of frozen embryo transfer was associated with an elevated risk of childhood cancer (14 cancer cases; hazard ratio, 2.43 [95% CI, 1.44 to 4.11]; incidence rate difference, 26.9 [95% CI, 2.8 to 51.0] per 100 000), mainly due to an increased risk of leukemia (5 cancer cases; incidence rate, 14.4 per 100 000; hazard ratio, 2.87 [95% CI, 1.19 to 6.93]; incidence rate difference, 10.1 [95% CI, -4.0 to 24.2] per 100 000) and sympathetic nervous system tumors (<5 cancer cases; hazard ratio, 7.82 [95% CI, 2.47 to 24.70]). There were no statistically significant associations with the use of the other types of fertility treatment examined. Conclusions and Relevance Among children born in Denmark, the use of frozen embryo transfer, compared with children born to fertile women, was associated with a small but statistically significant increased risk of childhood cancer; this association was not found for the use of other types of fertility treatment examined.

中文翻译：

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生育治疗与儿童癌症风险之间的关联

重要性 全世界越来越多的儿童在使用生育治疗后出生，尽管尚不清楚该治疗是否会影响儿童患癌症的风险，以及观察到的任何关联是否是由于使用特定药物、使用特定程序或潜在的不孕症。目的研究不同类型的生育治疗与儿童癌症风险之间的关联。设计、设置和参与者 基于丹麦人口登记数据和丹麦不孕症队列（个体记录关联）的回顾性队列研究包括 1996 年 1 月 1 日至 2012 年 12 月 31 日期间在丹麦出生的 1 085 172 名儿童，链接有家长信息。共有 2217 名儿童被诊断出患有癌症（随访时间为 1996-2015 年）。暴露在指数妊娠期间的母亲生育治疗，包括使用生育药物（克罗米芬 [n = 33 835]、促性腺激素 [n = 57 136]、促性腺激素释放激素类似物 [n = 38 653]、人绒毛膜促性腺激素 [n = 68 181]、孕激素 [n = 41 628] 和雌激素 [n = 16 948]）和辅助生殖技术（体外受精 [n = 19 448]、卵胞浆内单精子注射 [n = 13 417] 和冷冻胚胎移植[n = 3356]）。每次暴露都单独检查，并与生育妇女所生的孩子进行比较。主要结果和措施儿童癌症的危险比和发病率差异。结果 经过 1220 万人年（平均 11.3 年）的随访，育龄妇女所生儿童的儿童癌症发病率为 17.5/100 000（n = 910 291）和 44。使用冷冻胚胎移植后出生的儿童每 100 000 人中有 4 人（n = 3356）。与生育妇女所生的孩子相比，使用冷冻胚胎移植与儿童癌症风险升高相关（14 例癌症病例；风险比，2.43 [95% CI，1.44 至 4.11]；发病率差异，26.9 [95%] CI，2.8 至 51.0]/100000），主要是由于白血病风险增加（5 例癌症；发病率，14.4/100000；风险比，2.87 [95% CI，1.19 至 6.93]；发病率差异， 10.1 [95% CI, -4.0 to 24.2] per 100 000）和交感神经系统肿瘤（<5 个癌症病例；风险比，7.82 [95% CI, 2.47 to 24.70]）。与所检查的其他类型的生育治疗的使用没有统计学上的显着关联。结论和相关性 在丹麦出生的儿童中，与生育妇女所生的孩子相比，冷冻胚胎移植的使用与儿童癌症风险的增加有关，但具有统计学意义；使用其他类型的生育治疗未发现这种关联。