ART-conceived children may be at increased risk of leukaemia

Children conceived through assisted reproductive technology (ART), particularly fresh or frozen embryo transfer (ET), were more likely to develop leukaemia than those conceived naturally, according to a recent study.

Data from the French National Mother-Child Register was used to evaluate 8,526,306 children (median age 6.4 years, 51.2 percent boys) born between January 1, 2010 and December 31, 2021 in France. Of these, 260,236 children were born after medically assisted reproduction (MAR), including fresh ET (1.6 percent), frozen ET (0.8 percent), and artificial insemination (0.7 percent), while the remaining were conceived naturally. [JAMA Newt Open 2024;doi:10.1001/jamanetworkopen.2024.9429]

Over a median follow-up of 6.7 years, 9,256 children were diagnosed with cancer. Of these, 165 and 57 were born after fresh and frozen ET, respectively, and 70 were born via artificial insemination.

The researchers noted that these children with cancer were more likely to be born preterm, large-for-gestational age, and to be diagnosed with congenital malformations than those without cancer.

The overall risk of cancer did not differ between children conceived naturally and after MAR (hazard ratios [HRs], 1.12 [fresh ET], 1.02 [frozen FET], and 1.09 [artificial insemination]).

However, in terms of specific cancer types, leukaemia was the most common, accounting for 29.4 percent of all cases and 79.1 percent of acute lymphoblastic leukaemia (ALL), which occurred in 39 and 20 children born after fresh and frozen ET, respectively, as well as 16 children born after artificial insemination.

Compared with children conceived naturally, children born after frozen ET had a higher risk of ALL (HR, 1.61; risk difference [RD], 23.2 per million person-years).

With a longer median follow-up duration of 8.8–9.4 years, based on the analysis restricted to children born between 2010 and 2015, children conceived via fresh ET had a higher risk of leukaemia than those conceived naturally (HR, 1.42; adjusted RD, 19.7 per million person-years). “Of note, this is the time when fresh ET was more common than frozen ET,” wrote Dr Marie Hargreave from the Danish Cancer Society Research Center in Copenhagen, Denmark, in an editorial. [JAMA Netw Open 2024;doi:10.1001/jamanetworkopen.2024.9435]

“Our findings do not provide evidence of an increased risk of other types of childhood cancer among children born after MAR,” the researchers noted.

“Overall, the risk of any cancer was not increased among children born after MAR. However, the findings suggest that children born after fresh or frozen ET had a higher risk of leukaemia [compared with children conceived naturally],” they concluded.

“This study is the latest among several high-quality studies to report an increased risk of leukaemia among children born after ART. More large high-quality studies are needed to corroborate the accumulating evidence of increased cancer risk among children after ART and to investigate what aspects of ART may confer higher risk,” Hargreave highlighted.