Risk of cancer among children with birth defects: a novel approach

Associations between birth defects (BDs) and childhood cancers have been studied previously and have identified several specific birth defect-cancer associations. No studies have examined the risk after exclusion of known associations.

We analyzed data from high-quality population-based registers of BDs and cancers for Western Australian births 1982 to 2007. The cohort comprised 641,036 babies still alive at 90 days. Two experts independently reviewed all 120 births with a BD and a cancer to determine whether the cancer was congenital, caused by the BD, known to be associated with the BD or otherwise. These categories were used in sensitivity analyses. Cox regression was used to estimate hazard ratios (HRs) for any cancer and specific cancers associated with any BD and specific BDs.

The HR for any cancer among children with any BD was 1.96 (95% confidence interval, 1.59-2.43). The HR for any cancer among children with a BD not known to be related to a cancer (n = 57) was 1.19 (95% confidence interval, 0.91-1.56). The HR for the latter association among children diagnosed with cancer before 5 years of age was 1.74 (95% confidence interval, 1.28-2.37).

This novel approach aimed to prevent inflated HRs arising from reverse causation, and allow identification of associations beyond those already well documented. Larger studies using this method are needed to explore currently undocumented associations between BDs and cancers.