Department of Oncology, KU Leuven, Leuven, Flanders, Belgium.
Department of Human Genetics, University Hospital Leuven, Leuven, Belgium.
BMJ Open. 2024 Mar 28;14(3):e081833. doi: 10.1136/bmjopen-2023-081833.
Around 1 in 1000-2000 pregnancies are affected by a cancer diagnosis. Previous studies have shown that chemotherapy during pregnancy has reassuring cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care. However, although these children perform within normal ranges for their age, subtle differences have been identified. Given that chemotherapeutic compounds can cross the placenta, the possibility that prenatal chemotherapy exposure mutates the offspring's genome and/or epigenome, with potential deleterious effects later in life, urges to be investigated.
This multicentric observational study aims to collect cord blood, meconium and neonatal buccal cells at birth, as well as peripheral blood, buccal cells and urine from infants when 6, 18 and/or 36 months of age. Using bulk and single-cell approaches, we will compare samples from chemotherapy-treated pregnant patients with cancer, pregnant patients with cancer not treated with chemotherapy and healthy pregnant women. Potential chemotherapy-related newborn genomic and/or epigenomic alterations, such as single nucleotide variants, copy number variants and DNA-methylation alterations, will be identified in mononuclear and epithelial cells, isolated from blood, buccal swabs and urine. DNA from maternal peripheral blood and paternal buccal cells will be used to determine de novo somatic mutations in the neonatal blood and epithelial cells. Additionally, the accumulated exposure of the fetus, and biological effective dose of alkylating agents, will be assessed in meconium and cord blood via mass spectrometry approaches.
The Ethics Committee Research of UZ/KU Leuven (EC Research) and the Medical Ethical Review Committee of University Medical Center Amsterdam have approved the study. Results of this study will be disseminated via presentations at (inter)national conferences, through peer-reviewed, open-access publications, via social media platforms aimed to inform patients and healthcare workers, and through the website of the International Network on Cancer, Infertility and Pregnancy (www.cancerinpregnancy.org).
大约每 1000-2000 次妊娠中就有一次受到癌症诊断的影响。先前的研究表明，妊娠期间接受化疗具有令人安心的认知和心脏新生儿结局，因此被提议作为标准治疗方法。然而，尽管这些儿童的表现与其年龄相符，但仍存在细微差异。鉴于化疗化合物可以穿过胎盘，因此有必要研究产前化疗暴露是否会使后代的基因组和/或表观基因组发生突变，从而在以后的生活中产生潜在的有害影响。
这项多中心观察性研究旨在在出生时收集脐带血、胎粪和新生儿口腔细胞，以及婴儿 6、18 和/或 36 个月时的外周血、口腔细胞和尿液。我们将使用批量和单细胞方法，比较患有癌症的接受化疗的孕妇、未接受化疗的患有癌症的孕妇和健康孕妇的样本。将在单核细胞和上皮细胞中鉴定潜在的与化疗相关的新生儿基因组和/或表观基因组改变，如单核苷酸变异、拷贝数变异和 DNA 甲基化改变，这些改变将从血液、口腔拭子和尿液中分离出来。将使用母亲外周血和父亲口腔细胞的 DNA 来确定新生儿血液和上皮细胞中的新生体体细胞突变。此外，将通过质谱方法在胎粪和脐带血中评估胎儿的累积暴露量和烷化剂的生物有效剂量。
UZ/KU 鲁汶大学伦理研究委员会（EC 研究）和阿姆斯特丹大学医学伦理审查委员会已批准该研究。该研究的结果将通过在（国际）会议上的演讲、经过同行评审的开放获取出版物、针对患者和医疗保健工作者的社交媒体平台以及通过癌症、不孕和妊娠国际网络（www.cancerinpregnancy.org）的网站进行传播。
