{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:05:00Z","timestamp":1765818300000,"version":"3.48.0"},"reference-count":33,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"unspecified","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013845","name":"Foundation against Cancer","doi-asserted-by":"crossref","award":["2015-143"],"award-info":[{"award-number":["2015-143"]}],"id":[{"id":"10.13039\/501100013845","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013845","name":"Foundation against Cancer","doi-asserted-by":"crossref","award":["FAF-F\/2018\/1264"],"award-info":[{"award-number":["FAF-F\/2018\/1264"]}],"id":[{"id":"10.13039\/501100013845","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Commission \u2018MSCA-IF\u2019","award":["893131"],"award-info":[{"award-number":["893131"]}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["11K6822N"],"award-info":[{"award-number":["11K6822N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["I001818N"],"award-info":[{"award-number":["I001818N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C14\/21\/113"],"award-info":[{"award-number":["C14\/21\/113"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C14\/22\/125"],"award-info":[{"award-number":["C14\/22\/125"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,3,5]]},"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Around 1 in 1000\u20132000 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\u2019s genome and\/or epigenome, with potential deleterious effects later in life, urges to be investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analyses<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"www.cancerinpregnancy.org\">www.cancerinpregnancy.org<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-081833","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T14:02:47Z","timestamp":1711634567000},"page":"e081833","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7490-7487","authenticated-orcid":false,"given":"Ilana","family":"Struys","sequence":"first","affiliation":[{"name":"Department of Oncology, KU Leuven, Leuven, Flanders, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Oncology, KU Leuven, Leuven, Flanders, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koenraad","family":"Devriendt","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University Hospital Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lode","family":"Godderis","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, KU Leuven, Leuven, Flanders, Belgium"},{"name":"External Service for Prevention and Protection at Work, Heverlee, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Segers","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, University Hospital Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Thienpont","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, KU Leuven, Leuven, Flanders, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"van Boxtel","sequence":"additional","affiliation":[{"name":"Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristel","family":"Van Calsteren","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Voet","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, KU Leuven, Leuven, Flanders, Belgium"},{"name":"Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Flanders, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Wolters","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liesbeth","family":"Lenaerts","sequence":"additional","affiliation":[{"name":"Department of Oncology, KU Leuven, Leuven, Flanders, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic","family":"Amant","sequence":"additional","affiliation":[{"name":"Department of Oncology, KU Leuven, Leuven, Flanders, Belgium"},{"name":"Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven, Belgium"},{"name":"Gynecologic Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"2025121509021176000_14.3.e081833.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30059-7"},{"key":"2025121509021176000_14.3.e081833.2","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2021.13180","article-title":"Association of chemotherapy timing in pregnancy with congenital malformation","volume":"4","author":"van Gerwen","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2025121509021176000_14.3.e081833.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.62.4445"},{"key":"2025121509021176000_14.3.e081833.4","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1001\/jamaoncol.2015.2413","article-title":"Breast cancer diagnosed during pregnancy: adapting recent advances in breast cancer care for pregnant patients","volume":"1","author":"Loibl","year":"2015","journal-title":"JAMA Oncol"},{"key":"2025121509021176000_14.3.e081833.5","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz228"},{"key":"2025121509021176000_14.3.e081833.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1508913"},{"key":"2025121509021176000_14.3.e081833.7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ejca.2020.07.004","article-title":"Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy","volume":"138","author":"Vandenbroucke","year":"2020","journal-title":"Eur J Cancer"},{"key":"2025121509021176000_14.3.e081833.8","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1200\/JCO.22.02005","article-title":"Cognitive and behavioral development of 9-year-old children after maternal cancer during pregnancy: a prospective multicenter cohort study","volume":"41","author":"Van Assche","year":"2023","journal-title":"J Clin Oncol"},{"key":"2025121509021176000_14.3.e081833.9","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2020.100598","article-title":"The impact of cancer and chemotherapy during pregnancy on child Neurodevelopment: a multimodal neuroimaging analysis","volume":"28","author":"Blommaert","year":"2020","journal-title":"EClinicalMedicine"},{"key":"2025121509021176000_14.3.e081833.10","doi-asserted-by":"crossref","first-page":"10314","DOI":"10.1080\/14767058.2022.2128645","article-title":"Impact of chemotherapy during pregnancy on fetal growth","volume":"35","author":"Maggen","year":"2022","journal-title":"J Matern Fetal Neonatal Med"},{"key":"2025121509021176000_14.3.e081833.11","doi-asserted-by":"publisher","DOI":"10.1111\/IGC.0b013e3181fb18c8"},{"key":"2025121509021176000_14.3.e081833.12","doi-asserted-by":"publisher","DOI":"10.1177\/1933719110379650"},{"key":"2025121509021176000_14.3.e081833.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2010.08.019"},{"key":"2025121509021176000_14.3.e081833.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2009.04.009"},{"key":"2025121509021176000_14.3.e081833.15","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.3390\/cancers13061238","article-title":"Cancer during pregnancy: a review of preclinical and clinical transplacental transfer of anticancer agents","volume":"13","author":"Benoit","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2025121509021176000_14.3.e081833.16","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.ajog.2012.10.007","article-title":"Comparative transplacental transfer of taxanes using the human perfused cotyledon placental model","volume":"207","author":"Berveiller","year":"2012","journal-title":"Am J Obstet Gynecol"},{"key":"2025121509021176000_14.3.e081833.17","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ajog.2015.02.022","article-title":"How much platinum passes the placental barrier? Analysis of platinum applications in 21 patients with cervical cancer during pregnancy","volume":"213","author":"K\u00f6hler","year":"2015","journal-title":"Am J Obstet Gynecol"},{"key":"2025121509021176000_14.3.e081833.18","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-022-33663-5","article-title":"Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue","volume":"13","author":"Kuijk","year":"2022","journal-title":"Nat Commun"},{"key":"2025121509021176000_14.3.e081833.19","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-24858-3","article-title":"The evolution of hematopoietic cells under cancer therapy","volume":"12","author":"Pich","year":"2021","journal-title":"Nat Commun"},{"key":"2025121509021176000_14.3.e081833.20","first-page":"1860","article-title":"Elevated mutational age in blood of children treated for cancer contributes to therapyrelated myeloid neoplasms","volume":"12","author":"Bertrums","year":"2022","journal-title":"Cancer Discov"},{"key":"2025121509021176000_14.3.e081833.21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1010634","article-title":"Copy number footprints of platinum-based anticancer therapies","volume":"19","author":"Gonzalez","year":"2023","journal-title":"PLoS Genet"},{"key":"2025121509021176000_14.3.e081833.22","doi-asserted-by":"crossref","DOI":"10.1186\/s13058-022-01537-9","article-title":"DNA methylation changes in response to neoadjuvant chemotherapy are associated with breast cancer survival","volume":"24","author":"Pedersen","year":"2022","journal-title":"Breast Cancer Res"},{"key":"2025121509021176000_14.3.e081833.23","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0170085","article-title":"Differential DNA methylation regions in adult human sperm following adolescent chemotherapy: potential for epigenetic inheritance","volume":"12","author":"Shnorhavorian","year":"2017","journal-title":"PLoS One"},{"key":"2025121509021176000_14.3.e081833.24","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-090413-025514"},{"key":"2025121509021176000_14.3.e081833.25","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.77"},{"key":"2025121509021176000_14.3.e081833.26","doi-asserted-by":"publisher","DOI":"10.1101\/gr.175141.114"},{"key":"2025121509021176000_14.3.e081833.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0525-5"},{"key":"2025121509021176000_14.3.e081833.28","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.138"},{"key":"2025121509021176000_14.3.e081833.29","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3370"},{"key":"2025121509021176000_14.3.e081833.30","doi-asserted-by":"crossref","unstructured":"Huber AR , Manders F , Oka R , et al . Characterizing mutational load and Clonal composition of human blood. J Vis Exp July 11, 2019. doi:10.3791\/59846","DOI":"10.3791\/59846"},{"key":"2025121509021176000_14.3.e081833.31","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/s41436-021-01171-4","article-title":"Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG)","volume":"23","author":"Miller","year":"2021","journal-title":"Genet Med"},{"key":"2025121509021176000_14.3.e081833.32","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit149"},{"key":"2025121509021176000_14.3.e081833.33","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1080\/10937404.2014.898167","article-title":"Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy","volume":"17","author":"Cooke","year":"2014","journal-title":"J Toxicol Environ Health B Crit Rev"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-081833","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:02:24Z","timestamp":1765818144000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-081833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,28]]},"published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1136\/bmjopen-2023-081833"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-081833","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2024,3]]}}}