Increased risk of cancer in children with spina bifida: a population-based assessment of 14 million births
Introduction
There is emerging evidence that children with non-syndromic structural birth defects are more likely to develop cancer compared to those without birth defects. However, few assessments have focused specifically on cancer risk in children with spina bifida (SB). Therefore, we explored this association in a population-based cohort of >14 million children from five U.S. states: Massachusetts, Michigan, North Carolina, Oklahoma, and Texas.
Methods
Individual level data from birth certificates, birth defects registries, and cancer registries were linked in each state; demographic and diagnostic variables were harmonized; and the data were pooled for the overall analysis. We used Cox proportional hazards models to evaluate the association between SB and cancer overall (cancer risk through 18 years of age) and by the following cancer groups: hematologic malignancies, central nervous system (CNS) tumors, and non-CNS solid tumors. A hazard ratio (HR) and 95% confidence interval (CI) was calculated for each spina bifida-cancer association, adjusted for maternal age, race/ethnicity, infant sex, and state.
Results
Among the 14,826,607 children included in the birth cohort, 5,258 were diagnosed with SB (3.6 per 10,000 live births). The proportion of children with SB who developed cancer was 0.55% (N=29) compared to 0.14% among those without SB. The estimated marginal probability of cancer at five years was 0.2% among those with SB and 0.06% in those without birth defects (Gray’s test p < 0.001). In the multivariable model, children with SB were 3.3-times more likely to develop cancer compared to children without birth defects (95% CI: 2.03, 5.40; p = 1.75 x 10-6). When looking at specific cancer groups, children with SB were 5.0-times more likely to develop a non-CNS solid tumor compared to children without birth defects (95% CI: 2.63, 9.71; p = 1.22 x 10-6). While not statistically significant, the risk of hematologic malignancies (HR=1.90; 95% CI: 0.71, 5.07; p = 0.20) and CNS tumors (HR=3.08; 95% CI: 0.99-9.55; p=0.05) was also higher in children with SB compared to those without birth defects.
Conclusion
In this population-based assessment, we demonstrated that children with SB were more likely to develop cancer compared to children without birth defects. Notably, the risk for non-CNS solid tumors was particularly high. Our findings could point to disrupted pathways that lead both to SB and cancer. Ongoing analyses include evaluating risk based on co-occurring birth defects and selected demographic factors, as well as looking at specific cancers that children with SB develop. Ultimately, this work could lead to new surveillance strategies in children living with SB.