The main data available on the safety of radiation during pregnancy originate from animal studies and from studies of survivors of atomic or nuclear disasters. The effect of radiotherapy to treat maternal cancer on fetal development is uncertain. This report presents a unique cohort and aims to determine the long-term neurocognitive, psychosocial and physical outcomes of offspring of mothers treated with radiotherapy during pregnancy. In this international, multicentre, mixed retrospective–prospective cohort study, we recruited participants between Aug 5, 2006, and Aug 24, 2023, aged between 1·5 and 46 years, at three referral centres in Belgium, the Netherlands, and the USA. Participants were eligible if they were born from mothers treated with radiotherapy during pregnancy. Fetal radiation doses were obtained from medical records and participants were followed up at predefined ages (1·5, 3, 6, 9, 12, 15, and 18 years) and 5-yearly in adulthood, based on age at enrolment, using a neurocognitive test battery (measuring intelligence, attention, and memory), parent-reported executive function and psychosocial questionnaires, and a medical assessment. Results were compared with test-specific normative data. Linear regression models investigated associations between radiotherapy factors (fetal radiation dose, gestational age at the start and end of radiotherapy, and radiotherapy duration) and outcomes. 68 maternal cases of radiotherapy during pregnancy were registered by the three participating centres, of which 61 resulted in a livebirth and were therefore eligible to participate in the child follow-up study. After excluding those who did not give consent, 43 participants born from 42 mothers treated with radiotherapy during pregnancy were included in the study (median age at first assessment 3 years [IQR 2–11]; median age at last assessment 12 years [9–18]; median number of assessments two [1–4]). 18 (42%) of the included participants were female and 25 (58%) male, and 37 (86%) were of White ethnicity. Mean neurocognitive outcomes of the entire cohort were within normal ranges. No associations were found with fetal radiation dose or timing of radiotherapy during pregnancy. Six (16%) of 38 participants with neurocognitive outcomes scored lower than one SD on at least one neurocognitive outcome, three (7%) reported chronic medical conditions (spasmophilia, spastic diplegia, and IgG deficiency), and three (7%) were diagnosed with attention-deficit hyperactivity disorder (of whom two scored lower on attention). Of ten (23%) participants with lower neurocognitive score(s), a chronic medical condition, or attention-deficit hyperactivity disorder, eight were born preterm. The remaining 33 (77%) participants showed no neurocognitive, psychosocial, or chronic physical problems. We show on average normal neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy. Differences in outcomes could not be explained by exposure to radiotherapy during pregnancy. These results suggest that extra-abdomino-pelvic radiotherapy exposure during pregnancy in general does not adversely affect outcomes of liveborn children. Further research with a larger sample is necessary to confirm these findings. Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Research Foundation Flanders.

中文翻译：

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产前接受放射治疗后的长期神经认知、社会心理和身体结果：国际癌症、不孕不育和妊娠网络的多中心队列研究

关于怀孕期间辐射安全性的主要数据来自动物研究和原子或核灾难幸存者的研究。放射治疗治疗母体癌症对胎儿发育的影响尚不确定。本报告提出了一个独特的队列，旨在确定怀孕期间接受放射治疗的母亲的后代的长期神经认知、心理社会和身体结果。在这项国际、多中心、混合回顾性-前瞻性队列研究中，我们在比利时、荷兰和美国的三个转诊中心招募了 2006 年 8 月 5 日至 2023 年 8 月 24 日期间年龄在 1·5 岁至 46 岁之间的参与者。如果参与者是由在怀孕期间接受放射治疗的母亲所生，则他们符合资格。胎儿辐射剂量是从病历中获得的，参与者在预定年龄（1·5、3、6、9、12、15 和 18 岁）进行随访，成年后每 5 年根据入组年龄进行一次随访，使用神经认知测试电池（测量智力、注意力和记忆力）、家长报告的执行功能和心理社会问卷以及医学评估。将结果与特定测试的规范数据进行比较。线性回归模型研究了放疗因素（胎儿辐射剂量、放疗开始和结束时的胎龄以及放疗持续时间）与结果之间的关联。三个参与中心登记了 68 例在怀孕期间接受放射治疗的孕产妇病例，其中 61 例顺利分娩，因此有资格参加儿童随访研究。排除那些未给予同意的人后，42名在怀孕期间接受放射治疗的母亲所生的43名参与者被纳入研究（首次评估时的中位年龄为3岁[IQR 2-11]；最后一次评估时的中位年龄为12岁[9- 18]；评估中位数为 2 [1-4]）。纳入的参与者中有 18 名（42%）为女性，25 名（58%）为男性，37 名（86%）为白人。整个队列的平均神经认知结果均在正常范围内。没有发现与胎儿辐射剂量或怀孕期间放疗时间的关联。 38 名具有神经认知结果的参与者中，有 6 名 (16%) 的至少一项神经认知结果得分低于 1 个标准差，3 名 (7%) 报告有慢性疾病（痉挛症、痉挛性双瘫和 IgG 缺乏），3 名 (7%) 患有慢性疾病。被诊断患有注意力缺陷多动障碍（其中两人注意力得分较低）。在神经认知评分较低、患有慢性疾病或注意力缺陷多动障碍的 10 名 (23%) 参与者中，有 8 名早产。其余 33 名 (77%) 参与者没有表现出神经认知、心理社会或慢性身体问题。我们显示，产前接受放射治疗后，神经认知、社会心理和身体结果平均正常。结果的差异不能用怀孕期间接受放射治疗来解释。这些结果表明，怀孕期间接受腹腔外盆腔放射治疗通常不会对活产儿的结局产生不利影响。有必要进行更大样本的进一步研究来证实这些发现。 Kom Op Tegen Kanker、KWF Kankerbestrijding、Stichting Tegen Kanker、法兰德斯研究基金会。