Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011.
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ABSTRACT:
SUBMITTER: Spaan M
PROVIDER: S-EPMC10279651 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
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Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011.
Spaan Mandy M Pontesilli Martina M van den Belt-Dusebout Alexandra W AW Burger Curt W CW van den Heuvel-Eibrink Marry M MM Ravelli Anita C J ACJ Goddijn Mariëtte M Lambalk Cornelis B CB Roseboom Tessa J TJ van Leeuwen Flora E FE
Human reproduction open 20230601 3
<h4>Study question</h4>Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen-thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population?<h4>Summary answer</h4>After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI.<h4>Wh ...[more]
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Project description:STUDY QUESTION:Do children conceived by ART have an increased risk of cancer? SUMMARY ANSWER:Overall, ART-conceived children do not appear to have an increased risk of cancer. WHAT IS KNOWN ALREADY:Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce. STUDY DESIGN, SIZE, DURATION:A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS:All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers' questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios [HRs]) and with the general population (standardized incidence ratios [SIRs]). MAIN RESULTS AND THE ROLE OF CHANCE:The median follow-up was 21 years (interquartile range (IQR): 17-25) and was shorter in ART-conceived children (20 years, IQR: 17-23) compared with naturally conceived children (24 years, IQR: 20-30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72-1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90-1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73-2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81-2.85; 1.80, 95% CI: 0.65-4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81-7.37) and melanoma (HR = 1.86, 95% CI: 0.66-5.27) were non-significantly increased for ART-conceived compared with naturally conceived children. LIMITATIONS, REASONS FOR CAUTION:Despite the large size and long follow-up of the cohort, the number of cancers was rather small for subgroup analyses as cancer in children and young adults is rare. WIDER IMPLICATIONS OF THE FINDINGS:Overall, ART-conceived children do not appear to have an increased cancer risk after a median follow-up of 21 years. This large study provides important results, enabling physicians to better inform couples considering ART about the long-term safety of ART for their children. However, larger studies with prolonged follow-up are needed to investigate cancer risk in adults and in children conceived by ICSI and/or from cryopreserved embryos. STUDY FUNDING/COMPETING INTEREST(S):This work was supported by The Dutch Cancer Society (NKI 2006-3631) which funded the OMEGA-women's cohort and Children Cancer Free (KIKA;147) which funded the OMEGA-offspring cohort. We declare no competing interests.
| S-EPMC6443110 | biostudies-literature
Project description:Study questionIs the growth pattern of children conceived by ART different compared to naturally conceived children.Summary answerBoth ART and underlying parental subfertility may contribute to differences in early childhood growth between children conceived with and without the use of ART.What is known alreadyChildren conceived by ART weigh less and are shorter at the time of delivery. The extent to which differences in growth according to mode of conception persist during childhood, and the role of underlying parental subfertility, remains unclear.Study design, size, durationWe conducted a prospective study population-based study. We studied 81 461 children participating in the Norwegian Mother, Father and Child Cohort Study (MoBa) and 544 113 adolescents screened for military conscription.Participants/materials, setting, methodsConception by ART as registered in the Medical Birth Registry. We compared maternally reported length/height and weight among children in MoBa from mid-pregnancy to age 7 according to mode of conception using mixed-effects linear regression. Differences in self-reported height and weight at 17 years of age at screening for military conscription were assessed with linear regression.Main results and the role of chanceAt birth, children conceived by ART were shorter (boys -0.3 cm; 95% CI, -0.5 to -0.1), girls -0.4 cm; 95% CI, -0.5 to -0.3) and lighter (boys -113 grams; 95% CI, -201 to -25, girls -107 grams; 95% CI, -197 to -17). After birth, children conceived by ART grew more rapidly, achieving both greater height and weight at age 3. Children conceived by ART had a greater height up to age 7, but did not have a greater height or weight by age 17. Naturally conceived children of parents taking longer time to conceive had growth patterns similar to ART children. Children born after frozen embryo transfer had larger ultrasound measures and were longer and heavier the first 2 years than those born after fresh embryo transfer.Limitations, reasons for cautionsSelection bias could have been introduced due to the modest participation rate in the MoBa cohort. Our reliance on self-reported measures of length/height and weight could have introduced measurement error.Wider implications of the findings: Our findings provide reassurance that offspring conceived by ART are not different in height, weight or BMI from naturally conceived once they reach adolescence.Study funding/competing interest(s)Research Council of Norway; Medical Research Council; National Institute of Environmental Health Sciences. The authors have no competing interest.Trial registration numberN/A.
| S-EPMC7970724 | biostudies-literature
Project description: Not available
| S-EPMC9308959 | biostudies-literature
Project description:Prior studies on the association between fertility treatment and childhood cancer risk have generated inconsistent results. We performed a systematic review and meta-analysis of observation studies to summarize the evidence regarding the relation of fertility treatment with childhood cancer risk. A systematic literature search of several databases was conducted through April 2018 to identify relevant studies. The outcomes of interest included overall cancer, haematological malignancies, neural tumours, other solid tumours, and eight specific cancers. The overall risk estimates and corresponding 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Sixteen cohort and thirteen case-control studies were included. Results showed that children conceived by fertility treatment had significantly higher risk for developing overall cancer (relative risk [RR]: 1.16, 95% CI: 1.01, 1.32), haematological malignancies (RR: 1.39, 95% CI: 1.21, 1.60) and other solid tumours (RR: 1.57, 95% CI: 1.14, 2.16). For specific cancers, fertility treatment was associated with a significantly increased risk of leukaemia (RR: 1.31, 95% CI: 1.09, 1.57) and hepatic tumours (RR: 2.26, 95% CI: 1.32, 3.85). Sensitivity analysis validated evidence of the robustness of the findings. The results may demonstrate a possible association between fertility treatment and an increased risk of cancer among the offspring. However, the findings cannot say whether this increased risk is due to the subfertility itself or to the fertility treatment. Further research is needed to address the underlying mechanisms.
| S-EPMC6590158 | biostudies-literature
Project description:BackgroundOver 8 million individuals worldwide have been conceived through assisted reproductive technologies (ART). There is conflicting evidence on the cardiovascular health of ART offspring. This study aimed to investigate vascular function in a cohort of children, adolescents and young adults conceived through ART compared to spontaneously conceived peers.MethodsAnthropometric variables, diet quality, level of physical activity and sedentary behavior were assessed. An extensive evaluation of vascular function was conducted. Blood pressure as well as endothelial function were evaluated. Carotid intima-media thickness was recorded sonographically. Blood draws were taken to determine blood lipids as well as HbA1c.ResultsIn total, 66 ART subjects conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection and 86 spontaneously conceived peers were included in this observational cohort study. Both groups were similar in age [11.31 (8.10-18.00) vs. 11.85 (8.72-18.27) years, P=0.373]. ART subjects displayed a significantly higher body fat percentage [19.30% (15.80-26.02%) vs. 15.91% (13.21-21.00%), P=0.007]. Both groups did not differ significantly in diet quality, physical activity, sedentary behavior, and vascular function. Blood lipids and HbA1c were comparable between both groups. ART subjects showed significantly lower levels of triglycerides compared to spontaneously conceived peers. The prevalence of lipoprotein (a) [Lp(a)] ≥50 mg/dL tended to be higher within the ART cohort. Vascular function did not deteriorate more profoundly with age in ART subjects than in spontaneously conceived peers.ConclusionsThe results of the current study do not indicate a significantly lower vascular function in a cohort of children, adolescents and young adults conceived through ART compared to spontaneously conceived peers. Future studies should address the prevalence of elevated Lp(a) levels in infertile individuals who sought ART treatment. In addition, more studies evaluating body fat percentage as well as cardiovascular morbidity in adult ART subjects are required. For a more precise cardiovascular risk stratification, multi-center studies with larger ART sample sizes, preferably at adult age, are required in the future.
| S-EPMC10560362 | biostudies-literature
Project description:Pediatric oncology patients are at risk for poor outcomes with respiratory viral infections. Outcome data for COVID-19 in children and young adults with cancer are needed; data are sparse for obese/overweight and adolescent and young adult subgroups. We conducted a single center cohort study of COVID-19 outcomes in patients younger than 25 years with cancer. Candidate hospitalization risk factors were analyzed via univariable and multivariable analyses. Eighty-seven patients with cancer and COVID-19 were identified. Most were Hispanic/Latinx (n = 63, 72%). Forty-two (48%) were overweight/obese. Anticancer therapy included chemotherapy only (n = 64, 74%), chimeric antigen receptor T-cells (CAR-T, n = 7), hematopoietic stem cell transplantation (HSCT, n = 12), or CAR-T and HSCT (n = 4). There was no COVID-19 related mortality. Twenty-six patients (30%) required COVID-19 related hospitalization; 4 required multiple hospitalizations. Nine (10%) had severe/critical infection; 6 needed intensive care. COVID-19 resulted in anticancer therapy delays in 22 (34%) of 64 patients on active therapy (median delay = 14 days). Factors associated with hospitalization included steroids within 2 weeks prior to infection, lymphopenia, previous significant non-COVID infection, and low COVID-19 PCR cycle threshold value. CAR-T recipients with B-cell aplasia tended to have severe/critical infection (3 of 7 patients). A COVID-19 antibody response was detected in 14 of 32 patients (44%). A substantial proportion of COVID-19 infected children and young adults with cancer require inpatient management; morbidity may be high in B-cell immunodeficiency. However, a majority of patients can be taken through chemotherapy without prolonged therapy delays. Viral load is a potential outcome predictor in COVID-19 in pediatric cancer.
| S-EPMC9350252 | biostudies-literature
Project description:Evidence regarding the psychiatric morbidity of children born after Assisted Reproductive Techniques (ART) is inconsistent and limited. While normal mental well-being for ART children is usually reported, concerns are still being raised. Previous studies examine only some psychiatric disorders, but not all of them, ignore the impact of multiplicity, and limit the follow-up time to childhood. We examined all psychiatric diagnoses for singletons until their young adulthood. The aim was to study whether the risk of psychiatric disorders differs between ART and spontaneously conceived (SC) singletons until young adulthood. This retrospective Finnish population-based register study includes all ART and SC live-born children born in Finland during 1990-2013 and their hospital care in 1990-2014 (n = 1,425,975 of which 1,385,956, 97.2% were singletons). After excluding multiples, the final population included 17,610 ART and 1,368,346 SC singletons in 1990-2013 from the Finnish Medical Birth Registry. These data were linked to the Finnish Hospital Discharge Registry with the child's and mother's encrypted IDs. ART singletons had fewer psychiatric diagnoses (ART 10.2%, n = 1796, SC 12.0%, n = 164,408), but they received their diagnoses earlier (mean 8.3 years old, SD 5.0) than SC singletons (mean 10.5 years old, SD 5.7). After adjusting for confounding factors, ART singletons had an increased likelihood of getting a psychiatric diagnosis until young adulthood and the results were similar for boys (adjusted hazard ratios [aHR] = 1.16, 95% confidence interval (CI) 1.10-1.24) and girls (aHR = 1.25, 95% CI 1.16-1.35). We conclude that ART children receive their psychiatric diagnoses earlier than SC children, in particular during childhood and early adolescence. After adjusting for confounding factors ART children a slightly increased likelihood of any psychiatric diagnosis compared to SC controls.
| S-EPMC7369258 | biostudies-literature
Project description:Background and objectiveAn increasing number of children are born after assisted reproductive technology (ART), and monitoring their long-term health effects is of interest. This study compares cancer risk in children conceived by ART to that in children conceived without.MethodsThe Medical Birth Registry of Norway contains individual information on all children born in Norway (including information of ART conceptions). All children born between 1984 and 2011 constituted the study cohort, and cancer data were obtained from the Cancer Registry of Norway. Follow-up started at date of birth and ended on the date of the first cancer diagnosis, death, emigration, or December 31, 2011. A Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of overall cancer risk between children conceived by ART and those not. Cancer risk was also assessed separately for all childhood cancer types.ResultsThe study cohort comprised 1 628 658 children, of which 25 782 were conceived by ART. Of the total 4554 cancers, 51 occurred in ART-conceived children. Risk of overall cancer was not significantly elevated (HR 1.21; 95% CI 0.90-1.63). However, increased risk of leukemia was observed for children conceived by ART compared with those who were not (HR 1.67; 95% CI 1.02-2.73). Elevated risk of Hodgkin's lymphoma was also found for ART-conceived children (HR 3.63; 95% CI 1.12-11.72), although this was based on small numbers.ConclusionsThis population-based cohort study found elevated risks of leukemia and Hodgkin's lymphoma in children conceived by ART.
| S-EPMC5178823 | biostudies-literature
Project description:ObjectiveThe increasing use of assisted reproductive technologies (ART) has led to a growing interest in the health outcomes of offspring. However, the impact of ART on the immune system of children remains poorly understood. While only two publications were found, their findings contradict each other and did not consider other risk factors in their analysis except for ART use. Therefore, this study aimed to examine the potential impact of ART on the immune system of offspring.MethodsA case-control study was conducted in Kazakhstan to investigate the immune system of ART-conceived children compared to those conceived naturally (NC). The study included participants who met certain criteria, such as having undergone a successful ART program resulting in the birth of either a single or multiple pregnancies. Patients who used donor oocytes/sperm, intrauterine insemination, or surrogacy were excluded. Anamnesis data were collected from children in both groups, and laboratory measurements were performed and analyzed using IBM SPSS Statistic 26.ResultsA total of 120 children conceived by ART and 132 NC children under the age of five were included in our study. We observed that compared with NC group, ART children had lower IgA and IgG levels (p < 0.001), absolute lymphocytosis, high levels of active T-lymphocytes (p = 0.001), and pathological T-helper levels (p = 0.004). Therefore, the clinical presentation of respiratory diseases was lower in ART group. Children born after frozen embryo transfers showed significantly higher levels of T-cytotoxic and active T-lymphocytes compared to children born after fresh embryo transfers (p = 0.007 and p = 0.020, respectively). We utilized ordinal logistic regression to control for confounding variables such as multiple pregnancy, cesarean section, premature birth, and breastfeeding. Despite this, the significant impact of ART on immunogram parameters persisted, indicating the independent and influential nature of ART or other unaccounted factors.
| S-EPMC11620871 | biostudies-literature
Project description:Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1-2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses.
| S-EPMC10719096 | biostudies-literature