A History of Large for Gestational Age at Birth and Future Risk for Pediatric Neoplasms: A Population-Based Cohort Study

Abstract
Objective: The aim of this study was to evaluate the association between large for gestational age (LGA) at birth and future risk of childhood neoplasm. Study design: a population-based cohort to compare the long-term risk (up to the age of 18 years) of childhood neoplasms (benign and malignant) in children that were born LGA vs. those that were appropriate for gestational age (AGA), between the years 1991–2014. Childhood neoplasms diagnosis were defined according to international classification of disease 9 (ICD-9) codes recorded medical files. Kaplan–Meier survival curves were used in order to compare cumulative incidence of oncological morbidity over the study period. The Cox proportional hazards model was used to control for confounders. Results: 231,344 infants met the inclusion criteria; out of those 10,369 were diagnosed LGA at birth. Children that were LGA at birth had a higher incidence of leukemia (OR 2.25, 95%CI 1.08–4.65, p = 0.025) as well as kidney tumors (OR = 4.7, 95%CI = 1.02–21.9, p = 0.028). In addition, cumulative incidence over time of childhood malignancies, leukemia, and kidney tumors were significantly higher in LGA children (Log Rank = 0.010, 0.021, and 0.028, respectively). In a Cox regression model controlling for other perinatal confounders, LGA at birth remained independently associated with an increased risk for childhood malignancy (adjusted HR 1.51, 95%CI 1.02–2.23, p = 0.039). Conclusion: LGA at birth is associated with increased long-term risk for childhood malignancy and specifically leukemia and kidney tumors. This possible link may help to improve current knowledge regarding potential exposures that are associated with childhood cancer development.