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
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 dete...
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| Veröffentlicht in: | The lancet child & adolescent health 2024-06, Vol.8 (6), p.433-442 |
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| creator | Van Assche, Indra A Van Calsteren, Kristel Lemiere, Jurgen Hohmann, Jana Blommaert, Jeroen Huis in 't Veld, Evangeline A Cardonick, Elyce LeJeune, Charlotte Ottevanger, Nelleke P B Witteveen, Els P O van Grotel, Martine van den Heuvel-Eibrink, Marry M Lagae, Lieven Lambrecht, Maarten Amant, Frédéric |
| description | 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 |
| doi_str_mv | 10.1016/S2352-4642(24)00075-0 |
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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.</description><identifier>ISSN: 2352-4642</identifier><identifier>EISSN: 2352-4650</identifier><identifier>DOI: 10.1016/S2352-4642(24)00075-0</identifier><identifier>PMID: 38640941</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adolescent ; Adult ; Belgium - epidemiology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Middle Aged ; Neoplasms - psychology ; Neoplasms - radiotherapy ; Netherlands ; Pregnancy ; Prenatal Exposure Delayed Effects ; Prospective Studies ; Radiotherapy - adverse effects ; Retrospective Studies ; United States - epidemiology ; Young Adult</subject><ispartof>The lancet child & adolescent health, 2024-06, Vol.8 (6), p.433-442</ispartof><rights>2024 Elsevier Ltd</rights><rights>Copyright © 2024 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c313t-d6c45b56bdbb32c435d5f6e938436012ddd9ab4985d8e58dace4acec46b9bf743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38640941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van Assche, Indra A</creatorcontrib><creatorcontrib>Van Calsteren, Kristel</creatorcontrib><creatorcontrib>Lemiere, Jurgen</creatorcontrib><creatorcontrib>Hohmann, Jana</creatorcontrib><creatorcontrib>Blommaert, Jeroen</creatorcontrib><creatorcontrib>Huis in 't Veld, Evangeline A</creatorcontrib><creatorcontrib>Cardonick, Elyce</creatorcontrib><creatorcontrib>LeJeune, Charlotte</creatorcontrib><creatorcontrib>Ottevanger, Nelleke P B</creatorcontrib><creatorcontrib>Witteveen, Els P O</creatorcontrib><creatorcontrib>van Grotel, Martine</creatorcontrib><creatorcontrib>van den Heuvel-Eibrink, Marry M</creatorcontrib><creatorcontrib>Lagae, Lieven</creatorcontrib><creatorcontrib>Lambrecht, Maarten</creatorcontrib><creatorcontrib>Amant, Frédéric</creatorcontrib><title>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</title><title>The lancet child & adolescent health</title><addtitle>Lancet Child Adolesc Health</addtitle><description>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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Belgium - epidemiology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasms - psychology</subject><subject>Neoplasms - radiotherapy</subject><subject>Netherlands</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Prospective Studies</subject><subject>Radiotherapy - adverse effects</subject><subject>Retrospective Studies</subject><subject>United States - epidemiology</subject><subject>Young Adult</subject><issn>2352-4642</issn><issn>2352-4650</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd2OFCEQhTtG427WfQQNl2syrdBA_3hjzMSfTSZqol4TGqpn0G6qBXq1388Hk90Z99YLAqn6zingFMVTRl8wyuqXXyouq1LUorqqxHNKaSNL-qA4P5UlfXh_FtVZcRnj9wyxtmUNFY-LM97WgnaCnRd_duj3ZYIwEQ9LQIN775K7gQ2Z42oOGNE4PW6I9pbMhzU6o0eCSzI4QSR6yFIyB_A65Tr8njEuAUhCErR1mA4Q9Ly-IppMy5icAZ9y2-ABQyIxLXYlOJCMkWufrbKNQ5-dPkL6heEHQU-22hsImwwMEJIbXVqP1_kcYO9zc31SPBr0GOHytF8U3969_br9UO4-vb_evtmVhjOeSlsbIXtZ97bveWUEl1YONXS8FbymrLLWdroXXSttC7K12oDIy4i67_qhEfyiuDr6zgF_LhCTmlw0MI7aAy5RcSo4bShnTUblETUBYwwwqDm4SYdVMapuM1R3GarbgFQl1F2Gimbds9OIpZ_A3qv-JZaB10cA8kNvHAQVjYP8Q9YFMElZdP8Z8ReN87F5</recordid><startdate>202406</startdate><enddate>202406</enddate><creator>Van Assche, Indra A</creator><creator>Van Calsteren, Kristel</creator><creator>Lemiere, Jurgen</creator><creator>Hohmann, Jana</creator><creator>Blommaert, Jeroen</creator><creator>Huis in 't Veld, Evangeline A</creator><creator>Cardonick, Elyce</creator><creator>LeJeune, Charlotte</creator><creator>Ottevanger, Nelleke P B</creator><creator>Witteveen, Els P O</creator><creator>van Grotel, Martine</creator><creator>van den Heuvel-Eibrink, Marry M</creator><creator>Lagae, Lieven</creator><creator>Lambrecht, Maarten</creator><creator>Amant, Frédéric</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202406</creationdate><title>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</title><author>Van Assche, Indra A ; Van Calsteren, Kristel ; Lemiere, Jurgen ; Hohmann, Jana ; Blommaert, Jeroen ; Huis in 't Veld, Evangeline A ; Cardonick, Elyce ; LeJeune, Charlotte ; Ottevanger, Nelleke P B ; Witteveen, Els P O ; van Grotel, Martine ; van den Heuvel-Eibrink, Marry M ; Lagae, Lieven ; Lambrecht, Maarten ; Amant, Frédéric</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c313t-d6c45b56bdbb32c435d5f6e938436012ddd9ab4985d8e58dace4acec46b9bf743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Belgium - epidemiology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasms - psychology</topic><topic>Neoplasms - radiotherapy</topic><topic>Netherlands</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Prospective Studies</topic><topic>Radiotherapy - adverse effects</topic><topic>Retrospective Studies</topic><topic>United States - epidemiology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Assche, Indra A</creatorcontrib><creatorcontrib>Van Calsteren, Kristel</creatorcontrib><creatorcontrib>Lemiere, Jurgen</creatorcontrib><creatorcontrib>Hohmann, Jana</creatorcontrib><creatorcontrib>Blommaert, Jeroen</creatorcontrib><creatorcontrib>Huis in 't Veld, Evangeline A</creatorcontrib><creatorcontrib>Cardonick, Elyce</creatorcontrib><creatorcontrib>LeJeune, Charlotte</creatorcontrib><creatorcontrib>Ottevanger, Nelleke P B</creatorcontrib><creatorcontrib>Witteveen, Els P O</creatorcontrib><creatorcontrib>van Grotel, Martine</creatorcontrib><creatorcontrib>van den Heuvel-Eibrink, Marry M</creatorcontrib><creatorcontrib>Lagae, Lieven</creatorcontrib><creatorcontrib>Lambrecht, Maarten</creatorcontrib><creatorcontrib>Amant, Frédéric</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The lancet child & adolescent health</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Assche, Indra A</au><au>Van Calsteren, Kristel</au><au>Lemiere, Jurgen</au><au>Hohmann, Jana</au><au>Blommaert, Jeroen</au><au>Huis in 't Veld, Evangeline A</au><au>Cardonick, Elyce</au><au>LeJeune, Charlotte</au><au>Ottevanger, Nelleke P B</au><au>Witteveen, Els P O</au><au>van Grotel, Martine</au><au>van den Heuvel-Eibrink, Marry M</au><au>Lagae, Lieven</au><au>Lambrecht, Maarten</au><au>Amant, Frédéric</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>The lancet child & adolescent health</jtitle><addtitle>Lancet Child Adolesc Health</addtitle><date>2024-06</date><risdate>2024</risdate><volume>8</volume><issue>6</issue><spage>433</spage><epage>442</epage><pages>433-442</pages><issn>2352-4642</issn><eissn>2352-4650</eissn><abstract>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.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>38640941</pmid><doi>10.1016/S2352-4642(24)00075-0</doi><tpages>10</tpages></addata></record> |
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| ispartof | The lancet child & adolescent health, 2024-06, Vol.8 (6), p.433-442 |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adolescent Adult Belgium - epidemiology Child Child, Preschool Female Humans Infant Male Middle Aged Neoplasms - psychology Neoplasms - radiotherapy Netherlands Pregnancy Prenatal Exposure Delayed Effects Prospective Studies Radiotherapy - adverse effects Retrospective Studies United States - epidemiology Young Adult |
| title | 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 |
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