Non-chromosomal congenital anomalies and risk of childhood leukaemia: An Italian population-based case-control study

Introduction: The association between chromosomal conditions such as Down syndrome and increased CL risk of childhood leukemia (CL) is well established, while the association between non-chromosomal birth defects is far less clear. We conducted a population-based case-control study in two provinces of Northern Italy to evaluate CL risk in children born with non-chromosomal anomalies. Methods: We identified all leukemia cases diagnosed in children (<15 years) in the Modena and Reggio Emilia provinces through the Italian National Childhood Cancer Register in the period 1998-2013. For each case, we randomly selected four population controls matched by age, sex, province of residence and calendar year. Through the Emilia-Romagna Region population-based Birth Defects Registry, we retrieved information about occurrence and type of congenital malformations for each study subject. We computed the odds ratio (OR) of CL for children affected by non-chromosomal birth defects using a multivariable conditional logistic regression model. Results: We eventually included 132 cases and 528 controls, 5 of which (2 cases and 3 controls) were affected by a non-chromosomal congenital malformation. We found an increased risk of CL in children born with non-chromosomal anomalies, with an OR of 2.7 (95% confidence interval 0.4–16.0). Conclusions: Despite the limited stability of the risk estimates and the risk of unmeasured and residual confounding, our study appears to suggest an association between non-chromosomal birth defects and risk of childhood leukemia.