TY - JOUR

T1 - Cancer in children and young adults born after assisted reproductive technology

T2 - a Nordic cohort study from the Committee of Nordic ART and Safety (CoNARTaS)

AU - Sundh, Karin Jerhamre

AU - Henningsen, Anna-Karina A

AU - Källen, Karin

AU - Bergh, Christina

AU - Romundstad, Liv Bente

AU - Gissler, Mika

AU - Pinborg, Anja

AU - Skjaerven, Rolv

AU - Tiitinen, Aila

AU - Vassard, Ditte

AU - Lannering, Birgitta

AU - Wennerholm, Ulla-Britt

N1 - © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2014/9

Y1 - 2014/9

N2 - 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).

AB - 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).

KW - Adolescent

KW - Child

KW - Female

KW - Humans

KW - Male

KW - Neoplasms

KW - Proportional Hazards Models

KW - Registries

KW - Reproductive Techniques, Assisted

KW - Retrospective Studies

KW - Scandinavian and Nordic Countries

KW - Young Adult

U2 - 10.1093/humrep/deu143

DO - 10.1093/humrep/deu143

M3 - Journal article

C2 - 24990274

VL - 29

SP - 2050

EP - 2057

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 9

ER -