ART conception may pose risk of childhood cancers

Children born via assisted reproductive technology (ART) may be at higher risk of developing cancers compared with their counterparts who were conceived naturally or born to parents with an infertility, as shown in a recent study from Taiwan.

In a large cohort, ART conception conferred a 58-percent and 42-percent increase in the risk of any type of childhood cancers compared with natural conception (hazard ratio [HR], 1.58, 95 percent confidence interval [CI], 1.17–2.12) and non-ART conception among parents with infertility diagnoses (HR, 1.42, 95 percent CI, 1.04–1.95), respectively. [JAMA Netw Open 2022;5:e2230157]

The increased cancer risk among children conceived with ART was driven by the occurrence of leukaemia (HR, 1.88, 95 percent CI, 1.03–3.43) and hepatic tumours (HR, 2.41, 95 percent CI, 1.05–5.52).

“This study found significant differences in the risk of childhood cancers when comparing ART conception with subfertility-and-non-ART conception, but no significant differences were found between natural conception and subfertility with no use of ART. [These] suggest that the increased cancer risk may be due to ART treatment rather than subfertility,” the investigators said, who acknowledged, however, that ART conception may be a proxy for more severe infertility.

Furthermore, “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. However, we found that the other decomposed associations were not significant either, suggesting that the limited number of cases may have influenced the results,” they pointed out.

The analysis was based on 2,308,016 father-mother-child triads (mean paternal age, 33.28 years, mean maternal age 30.83 years, 52.06 percent boys). About 97 percent of children were singletons, 8.16 percent were born preterm, and 7.38 percent had low birth weight. ART-conceived children had the highest percentages of multiple gestations (48.95 percent), preterm birth (36.45 percent), and low birth weight (36.35 percent).

A total of 1,880 children developed cancers over a median follow-up of 6 years, with the incidence rates being the highest for the ART group, followed by the subfertility-and-non-ART group, and lowest for natural conception group. This was true for any type of cancer (203.1, 137.6, and 121.4 per million person-years), leukaemia (56.2, 34.4, and 29.8 per million person-years), and hepatic tumours (34.6, 9.9, and 8.2 per million person-years).

The study had several limitations, including the limited number of cases for various types of childhood cancers and consequently a failure to accurately analyse them. Additionally, the lack of information on out-migration might lead to misclassification.

“We were not able to verify sequential ignorability assumptions in the interpretation of mediation analyses, but we have employed covariate adjustment in our analyses to make the assumptions plausible,” the investigators noted.

Despite these limitations, “[o]ur findings suggest that couples seeking ART treatment need to be informed of the low but significantly increased risk of childhood cancers. Healthcare workers should collect information on the mode of conception and screen children conceived through ART for early detection of childhood cancers,” they said.