Dataset Information

Assisted reproductive technology and association with childhood cancer subtypes.

ABSTRACT:

Objectives

To investigate the association between assisted reproductive technology (ART) use and childhood cancer subtype.

Study design

We deployed a cross-sectional survey of 1701 parents of children with cancer about their ART use, demographics, and gestational and perinatal factors. Multivariable logistic regression modeled the association between ART use, birthweight and multiple gestation status with childhood cancer, by subtype.

Results

ART use was highest among children with osteosarcoma relative to children with other cancer types, and this association was statistically significant in multivariable models (OR = 4.4; 95% CI = 1.7-11.3; p = 0.0020). ART use was also elevated among children with hepatoblastoma, but this relationship appeared to be due to the strong associations between ART use and lower birthweight in our sample. No specific ART modality appeared to drive these associations. In univariate models, multiple gestation was associated with a 2.7-fold increased odds of hepatoblastoma (OR = 2.71; 95% CI = 1.14-6.42; p = 0.02) and a 1.6-fold increased odds of neuroblastoma (OR = 1.62; 95% CI = 1.03-2.54; p = 0.03), but these associations were not retained in multivariable models.

Conclusions

Associations between ART use and hepatoblastoma risk may be attributable to birthweight, a known hepatoblastoma risk factor. ART use may also be associated with osteosarcoma, independent of birthweight, an association not previously observed in studies limited to cancers diagnosed before adolescence. Evaluating long-term health outcomes in children conceived by ART, throughout adolescence and potentially into adulthood, appears warranted.

SUBMITTER: Gulrajani NB

PROVIDER: S-EPMC9939138 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Assisted reproductive technology and association with childhood cancer subtypes.

Gulrajani Natalie B NB Montes Samuel S McGough Daniel D Wimberly Courtney E CE Khattab Ameera A Semmes Eleanor C EC Towry Lisa L Cohen Jennifer L JL Hurst Jillian H JH Landi Daniel D Hill Sherika N SN Walsh Kyle M KM

Cancer medicine 20220805 3

<h4>Objectives</h4>To investigate the association between assisted reproductive technology (ART) use and childhood cancer subtype.<h4>Study design</h4>We deployed a cross-sectional survey of 1701 parents of children with cancer about their ART use, demographics, and gestational and perinatal factors. Multivariable logistic regression modeled the association between ART use, birthweight and multiple gestation status with childhood cancer, by subtype.<h4>Results</h4>ART use was highest among child ...[more]

PMID: 35929579

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Project description:ImportanceThe number of children born through the use of assisted reproductive technology (ART) has been increasing. These children may have higher risks for epigenetic alteration and adverse perinatal outcomes, which may be associated with childhood cancers.ObjectiveTo determine the associations between different modes of conception and childhood cancers and potential mediation by preterm birth and low birth weight.Design, setting, and participantsThis nationwide, population-based cohort study included registry data from 2 308 016 eligible parents-child triads in Taiwan from January 1, 2004, to December 31, 2017. A total of 1880 children with incident childhood cancer were identified. Data were analyzed between September 1, 2020, and June 30, 2022.ExposureMode of conception, defined as (1) natural conception, (2) subfertility and non-ART (ie, infertility diagnosis but no ART-facilitated conception), or (3) ART (ie, infertility diagnosis and ART-facilitated conception).Main outcomes and measuresDiagnosis of childhood cancer according to the International Classification of Childhood Cancers, Third Edition.ResultsThe mean (SD) paternal and maternal ages were 33.28 (5.07) and 30.83 (4.56) years, respectively. Of the 2 308 016 children, 52.06% were boys, 8.16% were born preterm, and 7.38% had low birth weight. During 14.9 million person-years of follow-up (median, 6 years [IQR, 3-10 years]), ART conception was associated with an increased risk of any type of childhood cancers compared with natural conception (hazard ratio, 1.58; 95% CI, 1.17-2.12) and subfertility with non-ART conception (hazard ratio, 1.42; 95% CI, 1.04-1.95). The increased cancer risk of children conceived with ART was mainly owing to leukemia and hepatic tumor. The increased cancer risk associated with ART conception was not mediated by preterm birth or low birth weight.Conclusions and relevanceIn this cohort study, children conceived via ART had a higher risk of childhood cancers than those conceived naturally and those born to parents with an infertility diagnosis did not use ART. The increased risk could not be explained by preterm birth or low birth weight.

Project description:Study questionDo women who give birth after assisted reproductive technology (ART) have an increased risk of cancer compared with women who give birth without ART?Summary answerWithout correction, the results indicate an increase in overall cancer risk, as well as a 50% increase in risk of CNS cancer for women giving birth after ART, however the results were not significant after correcting for multiple analyses.What is known alreadyStudies regarding the effects of hormonal treatments involved with ART on subsequent cancer risk have provided inconsistent results, and it has also been suggested that infertility itself could be a contributory factor.Study design, size, durationA population-based cohort consisting of all women registered in the Medical Birth Registry of Norway as having given birth between 1 January 1984 and 31 December 2010 was assembled (n = 812 986). Cancers were identified by linkage to the Cancer Registry of Norway. Study subjects were followed from start of first pregnancy during the observational period until the first cancer, death, emigration, or 31 December 2010.Participants/materials, setting, methodsOf the total study population (n = 806 248), 16 525 gave birth to a child following ART. Cox regression analysis computed hazard ratios (HR) and 95% confidence intervals (CI) comparing cancer risk between ART women and non-ART women; for overall cancer, and for cervical, ovarian, uterine, central nervous system (CNS), colorectal and thyroid cancers, and for malignant melanoma.Main results and the role of chanceA total of 22 282 cohort members were diagnosed with cancer, of which 338 were ART women and 21 944 non-ART women. The results showed an elevated risk in one out of seven sites for ART women. The HR for cancer of the CNS was 1.50 (95% CI 1.03- 2.18), and among those specifically subjected to IVF (without ICSI) the HR was 1.83 (95% CI 1.22-2.73). Analysis of risk of overall cancer gave an HR of 1.16 (95% CI 1.04-1.29). Among those who had delivered only one child by the end of follow-up, the HR for ovarian cancer was 2.00 (95% CI 1.08-3.65), and for those nulliparous at entry the HR was 1.80 (95% CI 1.04-3.11). However, all findings became non-significant after correcting for multiple analyses.Limitations, reasons for cautionThe results of elevated risk of overall cancer and CNS cancer lost significance when adjusting for multiple analyses, implying an important limitation of the study. The follow-up time was relatively short, especially for ART women. In addition, as the cohort was relatively young, there were few incident cancers, especially for some rarer cancer forms, such as uterine cancer. Risk assessments according to different causes of infertility could not be done.Wider implications of the findingsIn light of the findings in the present study, further studies should be made on risk of CNS and ovarian cancer, and continued monitoring of all those treated with ART is encouraged. Our findings may only be generalizable to women who give birth after ART, and the risk for women who remain nulliparous after ART remains to be assessed.Study funding/competing interestThe study was funded by the Norwegian National Advisory Unit on Women's Health. All authors claim no competing interests.

Project description:BackgroundThe relationship between assisted reproductive technology (ART) and childhood cancer risk has been widely debated. Previous meta-analyses did not adequately account for the impact of infertility, and this study addresses this gap.ObjectiveOur primary objective was to assess the relative risk (RR) of childhood cancer in infertile populations using ART versus non-ART offspring, with a secondary focus on comparing frozen embryo transfer (FET) and fresh embryo transfer (fresh-ET).MethodsA literature review was conducted through PubMed, Embase, Cochrane, and Web of Science, with a cutoff date of July 10, 2024. The study was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY 202470119). Inclusion criteria were based on the PICOS (Population, Intervention, Comparison, Outcomes, and Study Design) framework: infertile or subfertile couples (population), ART interventions (in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI], FET, and fresh-ET), non-ART comparison, and childhood cancer risk outcomes. Data abstraction focused on the primary exposures (ART vs non-ART and FET vs fresh-ET) and outcomes (childhood cancer risk). The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale, and the evidence quality was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Pooled estimates and 95% CIs were calculated using random effects models.ResultsA total of 18 studies were included, published between 2000 and 2024, consisting of 14 (78%) cohort studies and 4 (22%) case-control studies, all of which were of moderate to high quality. The cohort studies had follow-up periods ranging from 3 to 18 years. Compared with non-ART conception, ART conception was not significantly associated with an increased risk of childhood overall cancer (RR 0.95, 95% CI 0.71-1.27; GRADE quality: low to moderate). Subgroup analyses of IVF (RR 0.86, 95% CI 0.59-1.25), ICSI (RR 0.76, 95% CI 0.26-2.2), FET (RR 0.98, 95% CI 0.54-1.76), and fresh-ET (RR 0.75, 95% CI 0.49-1.15) showed similar findings. No significant differences were found for specific childhood cancers, including leukemia (RR 0.99, 95% CI 0.79-1.24), lymphoma (RR 1.22, 95% CI 0.64-2.34), brain cancer (RR 1.22, 95% CI 0.73-2.05), embryonal tumors (RR 1, 95% CI 0.63-1.58), retinoblastoma (RR 1.3, 95% CI 0.73-2.31), and neuroblastoma (RR 1.02, 95% CI 0.48-2.16). Additionally, no significant difference was observed in a head-to-head comparison of FET versus fresh-ET (RR 0.99, 95% CI 0.86-1.14; GRADE quality: moderate).ConclusionsIn conclusion, this study found no significant difference in the risk of childhood cancer between offspring conceived through ART and those conceived through non-ART treatments (such as fertility drugs or intrauterine insemination) in infertile populations. While infertility treatments may elevate baseline risks, our findings suggest that whether individuals with infertility conceive using ART or non-ART methods, their offspring do not face a significantly higher risk of childhood cancer. Further research, especially comparing infertile populations who conceive naturally, is needed to better understand potential long-term health outcomes.

Project description:ImportancePeople conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population.ObjectiveTo investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study.Design, setting, and participantsThis cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022.ExposuresConception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction).Main outcomes and measuresThe main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups.ResultsUp to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units).Conclusions and relevanceThese findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

Dataset Information

Assisted reproductive technology and association with childhood cancer subtypes.

Objectives

Study design

Results

Conclusions

Publications

Assisted reproductive technology and association with childhood cancer subtypes.

Similar Datasets

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