Department of Gynecology and Obstetrics, Rigshospitalet Section 4031, Copenhagen, Denmark.
Danish Cancer Society Research Center, Copenhagen, Denmark.
J Clin Oncol. 2022 Dec 1;40(34):3975-3984. doi: 10.1200/JCO.22.00599. Epub 2022 Jul 7.
In utero exposure to maternal cancer and cancer treatment might influence the child's short- and long-term health and development. The objective of the study was to investigate short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero.
This nationwide cohort study identified all liveborn children in Denmark between January 1978 and December 2018. Exposure was defined as maternal cancer diagnosis during pregnancy, and in a subgroup analysis, exposure to chemotherapy in utero. The main outcomes of interest were overall mortality, somatic diagnoses, and psychiatric diagnoses identified in the National Health Registers. Follow-up started at birth and ended at an event, death, emigration, or end of 2018. Hazard ratios of end points adjusted for potential confounders were estimated using Cox regression analysis.
Of 2,526,163 included liveborn children, 690 (0.03%) were exposed to maternal cancer in utero. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality, adjusted hazard ratio 0.8 (95% CI, 0.4 to 1.5), nor increased risk of congenital malformations, overall somatic or psychiatric disease. During the period 2002-2018, of 378 (0.03%) children exposed to cancer in utero, 42 (12.5%) were exposed to chemotherapy. Among these 42 children, in utero exposure to chemotherapy was not associated with selected somatic diseases nor to congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy.
Overall, findings did not indicate excess risk of mortality or severe morbidity among children exposed to cancer in utero. Fetal exposure to chemotherapy was not associated with adverse health outcomes in childhood.
母体癌症及其治疗在子宫内暴露可能会影响儿童的短期和长期健康和发育。本研究的目的是调查在子宫内暴露于母体癌症的儿童的短期和长期躯体和精神结局。
这项全国性队列研究确定了丹麦在 1978 年 1 月至 2018 年 12 月期间所有的活产儿。暴露定义为母亲在怀孕期间诊断出癌症，在亚组分析中，暴露于子宫内化疗。主要观察指标为国家健康登记册中确定的总死亡率、躯体诊断和精神诊断。随访从出生开始，直至发生事件、死亡、移民或 2018 年年底结束。使用 Cox 回归分析对潜在混杂因素进行调整后，估计终点的风险比。
在纳入的 2526163 名活产儿中，有 690 名（0.03%）在子宫内暴露于母亲的癌症。与未暴露的胎儿相比，子宫内暴露的儿童总体死亡率没有更高，调整后的风险比为 0.8（95%CI，0.4 至 1.5），也没有增加先天性畸形、总体躯体疾病或精神疾病的风险。在 2002-2018 年期间，378 名（0.03%）子宫内暴露于癌症的儿童中，有 42 名（12.5%）暴露于化疗。在这 42 名儿童中，与未接受化疗的子宫内暴露于母亲癌症相比，子宫内暴露于化疗与选定的躯体疾病或先天性畸形无关。
总体而言，研究结果并未表明在子宫内暴露于癌症的儿童死亡率或严重发病率过高。胎儿暴露于化疗与儿童期不良健康结局无关。
