Can IVF Up Childhood Cancer Risk?

Each year, assisted reproductive technologies (ART), usually in vitro fertilization (IVF), are responsible for more than 1% of the infants born in the United States—this averages to more than 61,000 babies in 2011 alone.¹ Over the years, follow-up of these children has produced conflicting findings surrounding an increased risk for childhood cancers, due either to maternal risk factors or risk factors inherent to ART conception.

A new study from the United Kingdom provides reassuring evidence that ART does not contribute to overall cancer risk. This large cohort study, which included 106,013 children from 83,697 pregnancies, used the UK Human Fertilisation and Embryology Authority (HFEA) database to identify children born between 1992 and 2008 following ART. In the United Kingdom, registration of all births resulting from ART and the ensuing outcomes is required, providing a very complete set of data. Donor-assisted data were not included because of UK privacy laws.²

The study found that 108 children developed cancer. No child had more than one cancer diagnosis, and baseline demographics of the children who developed cancer were similar to those who did not.² Based on these data, the overall standardized incidence ratio (SIR) was 0.98 (95% CI: 0.81-1.19). The results were similar when the cohort was stratified by a number of variables, including sex, age, birth weight, parents’ ages, and others, indicating no overall excess risk for cancer.² When looking at specific cancer types, no excess risk for leukemia, neuroblastoma, retinoblastoma, and most other tumors was identified. However, the number of hepatic tumors, specifically hepatoblastomas, was higher than would be expected (SIR: 3.27; 95% CI: 1.20-7.12; P = 0.03), an increased risk highly associated with low birth weight (P = 0.002 for birth weight < 2,500 g).² Additionally, the study found an excess number of rhabdomyosarcomas (SIR: 2.62; 95% CI: 1.26-4.82; P = 0.02). This increased risk was not related to birth weight or gestational age, but the number of rhabdomyosarcomas among children born to fathers 40 years or older was higher than expected (SIR: 5.93; 95% CI: 2.18-12.90; P = 0.004).² The absolute excess risk per 1 million person-years was calculated to be 8.82 cases of rhabdomyosarcoma and 6.21 cases of hepatoblastoma.²

These results are consistent with those of a 2001 study from the Netherlands, at the time the largest of its kind, which analyzed data from 17,000 children (n = 9,479 born after ART) and found a SIR for all cancers of 1.0 (95% CI: 0.6-1.7).³ A Swedish study published in 2010 followed a cohort of 26,692 children born following IVF from 1982 to 2005. In age-adjusted analysis, the odds ratio for cancer was 1.34 (95% CI: 1.02-1.76), which was not influenced by adjusting for various maternal risk factors. Although this study found a moderate increase in cancer risk among the children, the authors noted this could not definitively be attributed to IVF over other factors.⁴

Reassuringly, no increase in overall cancer incidence emerged in this latest large cohort of children up to age 15 years. Based on this data, children born through ART had no higher rates of common childhood cancers, such as leukemia. Although rates of hepatoblastoma (associated with low birth weight) and rhabdomyosarcoma (perhaps associated with paternal age) were higher than would be expected. In any event, the overall conclusion drawn from this study is that an absolute excess risk for either of these cancers was low, less than nine cases per 1 million person-years.

References

1. Centers for Disease Control and Prevention. What is assisted reproductive technology? Updated September 20, 2013. http://www.cdc.gov/art/. Accessed November 12, 2013.
2. Williams CL, Bunch KJ, Stiller CA, et al. Cancer risk among children born after assisted conception. N Engl J Med. 2013;369(19):1819-1827.
3. Klip H, Burger CW, de Kraker J, et al. Risk of cancer in the offspring of women who underwent ovarian stimulation for IVF. Human Reprod Update. 2001;16(11):2451-2458.
4. Källén B, Finnström O, Lindam A, et al. Cancer risk in children and young adults conceived by in vitro fertilization. Pediatrics. 2010;126(2):270-276.