Conception With ART Linked to Childhood Cancers

Children conceived via assisted reproductive technology (ART) may have a higher risk of developing childhood cancers, a Taiwanese population-based cohort study suggested.

Over 14.9 million person-years of follow-up, ART conception was associated with an increased risk of any type of childhood cancer compared with natural conception (HR 1.58, 95% CI 1.17-2.12), and subfertility with non-ART conception (HR 1.42, 95% CI 1.04-1.95), reported Li-Yin Chien, ScD, of the National Yang Ming Chiao Tung University in Taipei City, and colleagues.

The increased cancer risk for children conceived with ART was mainly due to leukemias and hepatic tumors, with associated increased risk for leukemias (HR 2.10, 95% CI 1.20-3.70), and hepatic tumors (HR 2.71, 95% CI 1.28-5.73) compared with natural conception after adjusting for confounders. ART was also associated with higher risks for these cancers when compared with subfertility and non-ART (leukemias: HR 1.88, 95% CI 1.03-3.43; hepatic tumors: HR 2.41 95% CI 1.05-5.52), they noted in JAMA Network Open.

“Our findings suggest that couples seeking ART treatment need to be informed of the low but significantly increased risk of childhood cancers,” Chien and team wrote. “Healthcare workers should collect information on the mode of conception and screen children conceived through ART for early detection of childhood cancers.”

In an accompanying commentary, Marie Hargreave, PhD, of the Danish Cancer Society Research Center in Copenhagen, noted that other studies have also reported associations with other cancers, such as neuroblastomas, central nervous system tumors, sarcomas, and retinoblastomas.

“Consistency in the findings for childhood cancer types would strengthen the evidence for an association of ART with the development of cancer in children, because different cancer types likely have different etiologies,” she wrote. “However, investigating different childhood cancer types is made difficult by their rarity, calling for large or collaborative studies.”

Furthermore, given that there is an association between ART and childhood cancers, “what part of ART conveys the risk?” Hargreave continued. “Whether the increased risk is associated with specific ART procedures, certain fertility drugs, or the underlying infertility of the parents remains to be investigated and will be important for furthering the understanding and possible prevention of cancer in children.”

In a stratified analysis, the association between mode of conception and childhood cancer did not differ significantly by source of infertility and child sex. However, while the use of frozen embryos was not associated with cancer risk, the use of fresh embryos was associated with increased cancer risk.

“Sensitivity analyses of unmeasured confounders for those associations indicated that fairly substantial confounding would be required to explain the associations,” Chien and team wrote.

Additionally, “although preterm birth and low birth weight seem to be plausible mechanisms, the findings of this study suggest that these variables did not mediate the association between ART conception and childhood cancers,” they added, though they found that the “other decomposed associations were not significant either, suggesting that the limited number of cases may have influenced the results.”

For this study, Chien and colleagues used registry data on 2,308,016 eligible parents-child triads in Taiwan from January 2004 through December 2017. Mean paternal and maternal ages were 33.3 and 30.8. Of the children, 52.1% were boys, 8.2% were born preterm, and 7.4% had low birth weight.

A total of 1,880 children with incident childhood cancer were identified.

The incidence rates of childhood cancers per million person-years were the highest for the ART group (203.1), followed by subfertility and non-ART (137.6), and lowest for natural conception (121.4). Incidence rates per million person-years for leukemias were 56.2 for ART, 34.4 for non-ART, and 29.8 for natural conception, while these rates for hepatic tumors were 34.6, 9.9, and 8.2, respectively.