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

IF 19.9 1区 医学 Q1 PEDIATRICS Lancet Child & Adolescent Health Pub Date : 2024-04-16 DOI:10.1016/S2352-4642(24)00075-0
Indra A Van Assche MSc , Kristel Van Calsteren PhD , Jurgen Lemiere PhD , Jana Hohmann MSc , Jeroen Blommaert PhD , Evangeline A Huis in 't Veld MSc , Elyce Cardonick MD , Charlotte LeJeune MD , Nelleke P B Ottevanger PhD , Prof Els P O Witteveen PhD , Martine van Grotel PhD , Prof Marry M van den Heuvel-Eibrink PhD , Prof Lieven Lagae PhD , Maarten Lambrecht PhD , Prof Frédéric Amant PhD
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引用次数: 0

摘要

关于孕期辐射安全的主要数据来自动物实验和对原子或核灾难幸存者的研究。治疗母体癌症的放射治疗对胎儿发育的影响尚不确定。本报告介绍了一个独特的队列,旨在确定在怀孕期间接受放射治疗的母亲的后代在神经认知、社会心理和身体方面的长期结果。在这项国际性、多中心、回顾性和前瞻性混合队列研究中,我们招募了2006年8月5日至2023年8月24日期间在比利时、荷兰和美国的三个转诊中心接受放疗的1-5岁至46岁的参与者。如果参与者的母亲在怀孕期间接受过放射治疗,那么他们就符合条件。研究人员从医疗记录中获取了胎儿的辐射剂量,并根据入组年龄在预定年龄(1-5岁、3岁、6岁、9岁、12岁、15岁和18岁)和成年后每5年对参与者进行一次随访,随访方法包括神经认知测试(测量智力、注意力和记忆力)、家长报告的执行功能和社会心理问卷以及医疗评估。研究结果与特定测试的常模数据进行了比较。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。三个参与中心共登记了68例孕期接受放射治疗的孕产妇,其中61例为活产,因此有资格参与儿童随访研究。在剔除未表示同意的产妇后,42 名接受过孕期放疗的产妇所生的 43 名婴儿被纳入研究范围(首次评估的中位年龄为 3 岁 [IQR:2-11];最后一次评估的中位年龄为 12 岁 [9-18];评估次数的中位数为 2 次 [1-4])。其中女性 18 人(42%),男性 25 人(58%),白人 37 人(86%)。整个组群的平均神经认知结果均在正常范围内。没有发现胎儿辐射剂量或怀孕期间接受放疗的时间有任何关联。在 38 名有神经认知结果的参与者中,有 6 人(16%)至少有一项神经认知结果的得分低于 1 SD,有 3 人(7%)报告患有慢性疾病(痉挛性肢体瘫痪、痉挛性偏瘫和 IgG 缺乏症),有 3 人(7%)被诊断患有注意力缺陷多动障碍(其中 2 人在注意力方面得分较低)。在 10 名(23%)神经认知评分较低、患有慢性疾病或注意力缺陷多动症的参与者中,有 8 人是早产儿。其余 33 名参与者(77%)没有神经认知、社会心理或慢性身体问题。我们的研究结果表明,产前接受放射治疗后,神经认知、社会心理和身体状况平均正常。孕期接受放疗无法解释结果的差异。这些结果表明,怀孕期间接受腹盆腔外放射治疗一般不会对活产婴儿的预后产生不利影响。有必要对更大样本进行进一步研究,以证实这些发现。Kom Op Tegen Kanker、KWF Kankerbestrijding、Stichting Tegen Kanker、佛兰德斯研究基金会。
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Long-term neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy: a multicentre cohort study of the International Network on Cancer, Infertility, and Pregnancy

Background

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.

Methods

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.

Findings

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.

Interpretation

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.

Funding

Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Research Foundation Flanders.

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来源期刊
Lancet Child & Adolescent Health
Lancet Child & Adolescent Health Psychology-Developmental and Educational Psychology
CiteScore
40.90
自引率
0.80%
发文量
381
期刊介绍: The Lancet Child & Adolescent Health, an independent journal with a global perspective and strong clinical focus, presents influential original research, authoritative reviews, and insightful opinion pieces to promote the health of children from fetal development through young adulthood. This journal invite submissions that will directly impact clinical practice or child health across the disciplines of general paediatrics, adolescent medicine, or child development, and across all paediatric subspecialties including (but not limited to) allergy and immunology, cardiology, critical care, endocrinology, fetal and neonatal medicine, gastroenterology, haematology, hepatology and nutrition, infectious diseases, neurology, oncology, psychiatry, respiratory medicine, and surgery. Content includes articles, reviews, viewpoints, clinical pictures, comments, and correspondence, along with series and commissions aimed at driving positive change in clinical practice and health policy in child and adolescent health.
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