Child outcomes after prenatal exposure to platinum and taxane-based chemotherapy: an unplanned interim analysis of the international network on cancer, infertility, and pregnancy studyResearch in context
Summary: Background: Platina and taxanes are frequently used chemotherapeutic agents to treat cancer, also when diagnosed during pregnancy. This report presents an interim analysis of the largest series of children prenatally exposed to platinum and/or taxane agents and aims to determine their phys...
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Elsevier
2024-12-01
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| author | Indra A. Van Assche Kristel Van Calsteren Evangeline A. Huis in ’t Veld Mathilde van Gerwen Laura Heylen Charlotte L. LeJeune Elyce Cardonick Michael J. Halaska Robert Fruscio Monica Fumagalli Elisabeth M. van Dijk-Lokkart Jurgen Lemiere Martine van Grotel Lieven Lagae Marry M. van den Heuvel-Eibrink Frédéric Amant |
| author_facet | Indra A. Van Assche Kristel Van Calsteren Evangeline A. Huis in ’t Veld Mathilde van Gerwen Laura Heylen Charlotte L. LeJeune Elyce Cardonick Michael J. Halaska Robert Fruscio Monica Fumagalli Elisabeth M. van Dijk-Lokkart Jurgen Lemiere Martine van Grotel Lieven Lagae Marry M. van den Heuvel-Eibrink Frédéric Amant |
| author_sort | Indra A. Van Assche |
| collection | DOAJ |
| description | Summary: Background: Platina and taxanes are frequently used chemotherapeutic agents to treat cancer, also when diagnosed during pregnancy. This report presents an interim analysis of the largest series of children prenatally exposed to platinum and/or taxane agents and aims to determine their physical health and neurocognitive outcomes. Methods: As part of a multicentre, prospective cohort study (ClinicalTrials.gov: NCT00330447), children born between 2000 and 2022 were assessed between 2005 and 2024 at ages 1.5–18 years (interim analysis; median length of follow-up, 3.2 years (IQR 3.0–6.4)) by a comprehensive neurocognitive test battery, parent-reported questionnaires, and a physical assessment. Mixed-effects regression and Type III Analysis of Variance models were used to investigate associations between these outcomes and platinum/taxane cumulative dose and agent type, with best-fit models corrected for age and covariates (gestational age at birth, chemotherapy timing, other chemotherapy, sex, parental education level, maternal death). Findings: In total, 144 children were included (13% exposed to platinum, 62% to taxanes, 25% to both). Of these, 101 were assessed at age 1.5 years, 96 at age 3, 63 at age 6, 32 at age 9, 18 at age 12, 7 at age 15, and 2 at age 18 years. Neurocognitive outcomes were within normal ranges across all ages, compared with test-specific normative data. Eight children (6%) reported ototoxicity, seven (5%) reported chronic medical conditions, three (2%) had congenital malformations, and two (1%) were diagnosed with Attention-Deficit Hyperactivity Disorder. Thirty-three children (23%) needed extra neurocognitive support, of which 64% were born preterm. Children prenatally exposed to paclitaxel scored lower on visuospatial (β = 0.64 ± 0.21, p = 0.0052) and verbal memory (β = 0.68 ± 0.27, p = 0.015) than those exposed to docetaxel. Interpretation: In this interim analysis, we found normal neurocognitive outcomes and no increase in congenital malformations nor medical conditions after prenatal exposure to platinum/taxane-based chemotherapy. However, owed to the limited number of older children, further investigation regarding their potential neurotoxicity and its long term effects is necessary in follow-up studies with larger samples. Funding: Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Cooperatio program, Research Foundation Flanders. |
| format | Article |
| id | doaj-art-f5c3e461287c4daeb19e9e5593f787dc |
| institution | OA Journals |
| issn | 2589-5370 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
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| series | EClinicalMedicine |
| spelling | doaj-art-f5c3e461287c4daeb19e9e5593f787dc2025-08-20T02:13:59ZengElsevierEClinicalMedicine2589-53702024-12-017810292210.1016/j.eclinm.2024.102922Child outcomes after prenatal exposure to platinum and taxane-based chemotherapy: an unplanned interim analysis of the international network on cancer, infertility, and pregnancy studyResearch in contextIndra A. Van Assche0Kristel Van Calsteren1Evangeline A. Huis in ’t Veld2Mathilde van Gerwen3Laura Heylen4Charlotte L. LeJeune5Elyce Cardonick6Michael J. Halaska7Robert Fruscio8Monica Fumagalli9Elisabeth M. van Dijk-Lokkart10Jurgen Lemiere11Martine van Grotel12Lieven Lagae13Marry M. van den Heuvel-Eibrink14Frédéric Amant15Department of Development and Regeneration, Unit of Woman and Child, KU Leuven, BelgiumDepartment of Development and Regeneration, Unit of Woman and Child, KU Leuven, Belgium; Department of Obstetrics and Gynaecology, Unit of Foetomaternal Medicine, UZ Leuven, BelgiumCenter for Gynecological Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, NetherlandsCenter for Gynecological Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Department of Child & Adolescent Psychiatry and Psychosocial Care, Amsterdam UMC, University of Amsterdam, the NetherlandsFaculty of Psychology and Educational Sciences, Unit of Clinical Psychology, KU Leuven, BelgiumDepartment of Obstetrics and Gynaecology, Unit of Foetomaternal Medicine, UZ Leuven, Belgium; Department of Oncology, Unit of Gynaecological Oncology, KU Leuven, BelgiumDepartment of Obstetrics and Gynecology, Cooper University Health Care, Camden, NJ, USADepartment of Obstetric Gynecology, University Hospital Kralovske Vinohrady and 3rd Medical Faculty, Charles University, Prague, CzechiaDepartment of Medicine and Surgery, Clinic of Obstetrics and Gynecology, University of Milan-Bicocca, Fondazione IRCCS San Gerardo, Monza, ItalyDepartment of Clinical Sciences and Community Health, University of Milan, Milano, Italy; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, NICU, Milano, ItalyDepartment of Child & Adolescent Psychiatry and Psychosocial Care, Amsterdam UMC, University of Amsterdam, the Netherlands; Amsterdam Reproduction and Development, Child Development, Amsterdam, the NetherlandsDepartment of Oncology, Unit of Pediatric Oncology, KU Leuven, Belgium; Department of Pediatrics, Unit of Pediatric Hemato-Oncology, UZ Leuven, BelgiumPrincess Máxima Center for Pediatric Oncology, Utrecht, NetherlandsDepartment of Development and Regeneration, Unit of Woman and Child, KU Leuven, Belgium; Department of Pediatrics, Unit of Pediatric Neurology, UZ Leuven, BelgiumPrincess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; University Medical Center Utrecht-Wilhelmina Children's Hospital, Division of Child Health, Utrecht, NetherlandsCenter for Gynecological Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; Department of Oncology, Unit of Gynaecological Oncology, KU Leuven, Belgium; Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, UZ Leuven, Belgium; Corresponding author. Division of Gynecological Oncology, Department of Obstetrics and Gynaecology, UZ Leuven, Herestraat 49, 3000, Leuven, Belgium.Summary: Background: Platina and taxanes are frequently used chemotherapeutic agents to treat cancer, also when diagnosed during pregnancy. This report presents an interim analysis of the largest series of children prenatally exposed to platinum and/or taxane agents and aims to determine their physical health and neurocognitive outcomes. Methods: As part of a multicentre, prospective cohort study (ClinicalTrials.gov: NCT00330447), children born between 2000 and 2022 were assessed between 2005 and 2024 at ages 1.5–18 years (interim analysis; median length of follow-up, 3.2 years (IQR 3.0–6.4)) by a comprehensive neurocognitive test battery, parent-reported questionnaires, and a physical assessment. Mixed-effects regression and Type III Analysis of Variance models were used to investigate associations between these outcomes and platinum/taxane cumulative dose and agent type, with best-fit models corrected for age and covariates (gestational age at birth, chemotherapy timing, other chemotherapy, sex, parental education level, maternal death). Findings: In total, 144 children were included (13% exposed to platinum, 62% to taxanes, 25% to both). Of these, 101 were assessed at age 1.5 years, 96 at age 3, 63 at age 6, 32 at age 9, 18 at age 12, 7 at age 15, and 2 at age 18 years. Neurocognitive outcomes were within normal ranges across all ages, compared with test-specific normative data. Eight children (6%) reported ototoxicity, seven (5%) reported chronic medical conditions, three (2%) had congenital malformations, and two (1%) were diagnosed with Attention-Deficit Hyperactivity Disorder. Thirty-three children (23%) needed extra neurocognitive support, of which 64% were born preterm. Children prenatally exposed to paclitaxel scored lower on visuospatial (β = 0.64 ± 0.21, p = 0.0052) and verbal memory (β = 0.68 ± 0.27, p = 0.015) than those exposed to docetaxel. Interpretation: In this interim analysis, we found normal neurocognitive outcomes and no increase in congenital malformations nor medical conditions after prenatal exposure to platinum/taxane-based chemotherapy. However, owed to the limited number of older children, further investigation regarding their potential neurotoxicity and its long term effects is necessary in follow-up studies with larger samples. Funding: Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Cooperatio program, Research Foundation Flanders.http://www.sciencedirect.com/science/article/pii/S2589537024005017Cancer during pregnancyPrenatal chemotherapy exposurePlatinum-based chemotherapyTaxane-based chemotherapyChild development |
| spellingShingle | Indra A. Van Assche Kristel Van Calsteren Evangeline A. Huis in ’t Veld Mathilde van Gerwen Laura Heylen Charlotte L. LeJeune Elyce Cardonick Michael J. Halaska Robert Fruscio Monica Fumagalli Elisabeth M. van Dijk-Lokkart Jurgen Lemiere Martine van Grotel Lieven Lagae Marry M. van den Heuvel-Eibrink Frédéric Amant Child outcomes after prenatal exposure to platinum and taxane-based chemotherapy: an unplanned interim analysis of the international network on cancer, infertility, and pregnancy studyResearch in context EClinicalMedicine Cancer during pregnancy Prenatal chemotherapy exposure Platinum-based chemotherapy Taxane-based chemotherapy Child development |
| title | Child outcomes after prenatal exposure to platinum and taxane-based chemotherapy: an unplanned interim analysis of the international network on cancer, infertility, and pregnancy studyResearch in context |
| title_full | Child outcomes after prenatal exposure to platinum and taxane-based chemotherapy: an unplanned interim analysis of the international network on cancer, infertility, and pregnancy studyResearch in context |
| title_fullStr | Child outcomes after prenatal exposure to platinum and taxane-based chemotherapy: an unplanned interim analysis of the international network on cancer, infertility, and pregnancy studyResearch in context |
| title_full_unstemmed | Child outcomes after prenatal exposure to platinum and taxane-based chemotherapy: an unplanned interim analysis of the international network on cancer, infertility, and pregnancy studyResearch in context |
| title_short | Child outcomes after prenatal exposure to platinum and taxane-based chemotherapy: an unplanned interim analysis of the international network on cancer, infertility, and pregnancy studyResearch in context |
| title_sort | child outcomes after prenatal exposure to platinum and taxane based chemotherapy an unplanned interim analysis of the international network on cancer infertility and pregnancy studyresearch in context |
| topic | Cancer during pregnancy Prenatal chemotherapy exposure Platinum-based chemotherapy Taxane-based chemotherapy Child development |
| url | http://www.sciencedirect.com/science/article/pii/S2589537024005017 |
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