In vitro fertilization and risk of childhood leukemia in Greece and Sweden

Background: Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets. Methods: The hospital-based case-control study in Greece derived from the National Registry for Childhood Hematological Malignancies (1996-2008, 814 leukemia and 277 lymphoma incident cases with their 1:1 matched controls). The Swedish case-control study was nested in the Swedish Medical Birth Register (MBR) (1995-2007, 520 leukemia and 71 lymphoma cases with their 5,200 and 710 matched controls) with ascertainment of incident cancer cases in the National Cancer Register. Study-specific and combined odds ratios (OR) were estimated using conditional logistic regression, with adjustment for possible risk factors. Results: Nationwide studies pointed to similar size excess risk of leukemia following IVF, but to a null association between IVF and lymphoma. The proportion of leukemia cases conceived through IVF was 3% in Greece and 2.7% in Sweden; prevalence of IVF in matched controls was 1.8% and 1.6%, respectively. In combined multivariable analyses, the increased risk of leukemia was confined to age below 3.8 years (OR=2.21; 95% confidence interval, CI: 1.27-3.85) and to acute lymphoblastic leukemia (ALL) (OR=1.77; 95% CI: 1.06-2.95) with no sufficient evidence of excess risk for other leukemias (OR=1.34; 95% CI: 0.38-4.69). Following IVF, OR for ALL was 2.58 (95% CI: 1.37-4.84) before age 3.8 and 4.29 (95% CI: 1.49-12.37) before age 2 years. Conclusions: IVF seems to be associated with increased risk of early onset ALL in the offspring.