| Summary: | <p>Study question: Do children born after donor assisted reproductive technology (ART) have an increased risk of developing childhood cancer in comparison to the general population? Summary answer: This study showed no overall increased risk of childhood cancer in individuals born after donor ART.</p><p> What is known already: Most large population based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date. Study design, size, duration: This retrospective cohort study utilized record linkage to determine the outcome status of all 12,186 children born in Great Britain (1992-2008) after donor ART. The cohort included 12,137 members contributed 95,389 person-years of follow-up (average follow-up 7.86 years).</p><p> Participants, setting, methods: Records of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992-2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardised population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type, and fresh/ cryopreserved cycles.</p><p> Main results and the role of chance: In our cohort of 12,137 children born after donor assisted reproductive technology (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardised incidence ratio (SIR) 0.83; 95% confidence interval (CI) 0.43-1.45; P=0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95%CI 1.25-37.14; P<0.05). This increased hepatoblastoma risk was associated 47 with low birthweight.</p><p> Limitations, reasons for caution: Although this study includes a large number of children born after donor ART, the rarity of specific diagnostic sub-groups of childhood cancer results in few cases and therefore wide confidence intervals for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available.</p><p> Wider implications of the findings: This study is the first to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasised that the absolute risks are very small. However, an on-going investigation with a longer follow-up is needed.</p>
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