Karin Jerhamre Sundh1, Anna-Karina A Henningsen2, Karin Källen3, Christina Bergh4, Liv Bente Romundstad5, Mika Gissler6, Anja Pinborg7, Rolv Skjaerven8, Aila Tiitinen9, Ditte Vassard2, Birgitta Lannering10, Ulla-Britt Wennerholm11. 1. Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital/Östra, SE-416 85 Gothenburg, Sweden. 2. Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 3. Department of Reproduction Epidemiology, Tornblad Institute, Institution of Clinical Sciences, Lund University, Lund, Sweden. 4. Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Sweden Academy, University of Gothenburg, Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. 5. Department of Obstetrics and Gynaecology, Fertility Clinic, St Olavs University Hospital, Trondheim, Norway Department of Public Health, NTNU, Trondheim, Norway. 6. THL, National Institute for Health and Welfare, Helsinki, Finland Nordic School of Public Health, Gothenburg, Sweden. 7. Department of Obstetrics and Gynaecology, Fertility Clinic, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark. 8. Department of Global Public Health, University of Bergen, Bergen, Norway Medical Birth Registry of Norway, National Institute of Public Health, Bergen, Norway. 9. Department of Obstetrics and Gynaecology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland. 10. Department of Clinical Sciences, Paedriatic Oncology, University of Gothenburg, Gothenburg, Sweden. 11. Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital/Östra, SE-416 85 Gothenburg, Sweden ulla-britt.wennerholm@vgregion.se.
Abstract
STUDY QUESTION: Do children and young adults born after assisted reproductive technology (ART) have an increased risk of cancer? SUMMARY ANSWER: Children born after ART showed no overall increase in the rate of cancer when compared with children born as a result of spontaneous conception. WHAT IS KNOWN ALREADY: Children born after ART have more adverse perinatal outcomes, i.e. preterm births, low birthweights and birth defects. Previous studies have shown divergent results regarding the risk of cancer among children born after ART. STUDY DESIGN, SIZE, DURATION: A retrospective Nordic population-based cohort study was performed, comprising all children born after ART in Sweden, Denmark, Finland and Norway between 1982 and 2007. The mean (±standard deviation) follow-up time was 9.5 (4.8) years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Children born after ART (n = 91 796) were compared with a control group of children born after spontaneous conception. This control group was almost 4-fold the size of the ART group (n = 358 419) and matched for parity, year of birth and country. Data on perinatal outcomes and cancer were obtained from the National Medical Birth Registries, the Cancer Registries, the Patient Registries and the Cause of Death Registries. The cancer diagnoses were divided into 12 main groups. Hazard ratios (HRs) and adjusted HR were calculated. Adjustments were carried out for country, maternal age, parity, sex, gestational age and birth defects. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant increase in overall cancer rates among children born after ART when compared with children born after spontaneous conception (adjusted HR 1.08; 95% CI 0.91-1.27). Cancer, of any form, was found among 181 children born after ART (2.0/1000 children, 21.0/100 000 person-years) compared with 638 children born after spontaneous conception (1.8/1000 children, 18.8/100 000 person-years). Leukaemia was the most common type of cancer (n = 278, 0.62/1000 children) but no significantly increased incidence was found among children born after ART. An increased risk was observed for 2 of 12 cancer groups. They were central nervous system tumours (adjusted HR 1.44; 95% CI 1.01-2.05) and malignant epithelial neoplasms (adjusted HR 2.03; 95% CI 1.06-3.89); the absolute risks were 0.46/1000 and 0.15/1000 children, respectively, corresponding to an absolute increased risk of 0.14/1000 and 0.08/1000 children, respectively. LIMITATIONS, REASONS FOR CAUTION: As this is an observational study, the main limitation is the fact that it is not possible to adjust for all potential confounders. We were not able to control for confounders such as socio-economic status and perinatal factors, such as Apgar score, which other studies have suggested affect cancer rates. WIDER IMPLICATIONS OF THE FINDINGS: The results of this large population-based cohort study are in agreement with most previously published studies. The main findings are reassuring for couples undergoing ART, children born after ART and clinicians working with ART. STUDY FUNDING/COMPETING INTERESTS: No conflict of interest was reported. The study was supported by grants from The European Society for Human Reproduction and Embryology (ESHRE), Sahlgrenska University Hospital, Gothenburg, Sweden, the University of Copenhagen, Denmark, the Danish Agency of Science, Technology and Innovation and the Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).
STUDY QUESTION: Do children and young adults born after assisted reproductive technology (ART) have an increased risk of cancer? SUMMARY ANSWER: Children born after ART showed no overall increase in the rate of cancer when compared with children born as a result of spontaneous conception. WHAT IS KNOWN ALREADY: Children born after ART have more adverse perinatal outcomes, i.e. preterm births, low birthweights and birth defects. Previous studies have shown divergent results regarding the risk of cancer among children born after ART. STUDY DESIGN, SIZE, DURATION: A retrospective Nordic population-based cohort study was performed, comprising all children born after ART in Sweden, Denmark, Finland and Norway between 1982 and 2007. The mean (±standard deviation) follow-up time was 9.5 (4.8) years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Children born after ART (n = 91 796) were compared with a control group of children born after spontaneous conception. This control group was almost 4-fold the size of the ART group (n = 358 419) and matched for parity, year of birth and country. Data on perinatal outcomes and cancer were obtained from the National Medical Birth Registries, the Cancer Registries, the Patient Registries and the Cause of Death Registries. The cancer diagnoses were divided into 12 main groups. Hazard ratios (HRs) and adjusted HR were calculated. Adjustments were carried out for country, maternal age, parity, sex, gestational age and birth defects. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant increase in overall cancer rates among children born after ART when compared with children born after spontaneous conception (adjusted HR 1.08; 95% CI 0.91-1.27). Cancer, of any form, was found among 181 children born after ART (2.0/1000 children, 21.0/100 000 person-years) compared with 638 children born after spontaneous conception (1.8/1000 children, 18.8/100 000 person-years). Leukaemia was the most common type of cancer (n = 278, 0.62/1000 children) but no significantly increased incidence was found among children born after ART. An increased risk was observed for 2 of 12 cancer groups. They were central nervous system tumours (adjusted HR 1.44; 95% CI 1.01-2.05) and malignant epithelial neoplasms (adjusted HR 2.03; 95% CI 1.06-3.89); the absolute risks were 0.46/1000 and 0.15/1000 children, respectively, corresponding to an absolute increased risk of 0.14/1000 and 0.08/1000 children, respectively. LIMITATIONS, REASONS FOR CAUTION: As this is an observational study, the main limitation is the fact that it is not possible to adjust for all potential confounders. We were not able to control for confounders such as socio-economic status and perinatal factors, such as Apgar score, which other studies have suggested affect cancer rates. WIDER IMPLICATIONS OF THE FINDINGS: The results of this large population-based cohort study are in agreement with most previously published studies. The main findings are reassuring for couples undergoing ART, children born after ART and clinicians working with ART. STUDY FUNDING/COMPETING INTERESTS: No conflict of interest was reported. The study was supported by grants from The European Society for Human Reproduction and Embryology (ESHRE), Sahlgrenska University Hospital, Gothenburg, Sweden, the University of Copenhagen, Denmark, the Danish Agency of Science, Technology and Innovation and the Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).
Authors: Zuelma A Contreras; Johnni Hansen; Beate Ritz; Jorn Olsen; Fei Yu; Julia E Heck Journal: Cancer Epidemiol Date: 2017-07-14 Impact factor: 2.984
Authors: Michael L Eisenberg; Barbara Luke; Katherine Cameron; Gary M Shaw; Allan A Pacey; Alastair G Sutcliffe; Carrie Williams; Julian Gardiner; Richard A Anderson; Valerie L Baker Journal: J Assist Reprod Genet Date: 2020-09-30 Impact factor: 3.412
Authors: Mandy Spaan; Alexandra W van den Belt-Dusebout; Marry M van den Heuvel-Eibrink; Michael Hauptmann; Cornelis B Lambalk; Curt W Burger; Flora E van Leeuwen Journal: Hum Reprod Date: 2019-04-01 Impact factor: 6.918