P2-259 Cancer risk in children with birth defects: a longitudinal, population-based assessment among 2.7 million births

Abstract

Assessing cancer risk among children with birth defects has important implications for etiologic research and clinical management. With a few exceptions, the literature to date is inconclusive. To develop this information, we used a population-based approach that combined longitudinal, statewide birth cohorts from Arizona, Iowa, and Utah, among over 2.7 million births born from 1983-2006. Birth defects were identified through statewide birth defect registries, cancer cases through linked cancer registries. A population-based cohort of over 43,000 children with major birth defects (including trisomies 13, 18, and 21) was compared to a three-times larger cohort of nearly 148,000 births without birth defects, randomly sampled from the same underlying birth population and frequency-matched to the birth defects cohort by birth year. We used a Kaplan-Meier time-toevent approach, accounting for censoring by death, to estimate cancer risk up to age 15 years. Compared to the reference cohort, children with birth defects appeared to have a statistically significant, nearly three-fold increase in risk for cancer (Relative Risk [RR], 2.73). Risk was highest among children with chromosomal conditions, specifically Down syndrome (RR, 13.2), and was driven largely by leukemias. Risk for cancer, however, remained moderately increased also among those with a birth defect but without these chromosomal anomalies (RR, 1.82). In this group, cancer risk was driven mainly by brain tumors and some embryonal tumors (neuroblastoma, hepatoblastoma), and occurred mainly in children with brain malformations, cleft palate, rectal malformations, and some heart defects. These population-based findings support and extend previous findings that suggest an increased risk for cancer in children with birth defects, including non-chromosomal birth defects, and suggest selected case groups in which further research could help identify a common genetic susceptibility to cancer and birth defects.