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.
Highlights
The theory of fetal “programing” during pregnancy deals with the possibility that some intrauterine exposures cause changes in fetal development that may have implementations on future risk for specific diseases during childhood [1]
Long-term incidence of childhood neoplasms was compared between children who were born with the diagnosis of Large for gestational age (LGA) [18] and those who were born appropriate for gestational age (AGA) (5th centile < birth weight < 95th centile)
In the current study we found that a diagnosis of LGA at birth is significantly related to increased incidence of total malignant neoplasms during childhood, leukemia and kidney cancer
Summary
The theory of fetal “programing” during pregnancy deals with the possibility that some intrauterine exposures cause changes in fetal development that may have implementations on future risk for specific diseases during childhood [1]. Results from previous studies generally support this association with published data that show an increased risk for childhood cancer and malignancies, such as leukemia and central nervous system tumors in children who were born LGA [9,10,11,12,13,14]. Another study looked on the incidence of acute lymphoblastic leukemia and found similar linear correlation with increased birth weight [10] Despite this trend in literature, other studies have failed to show significant positive association between birth weight and future childhood malignancy incidence [15,16]. The aim of this study was to use two independent databases in order to evaluate the association between a history of LGA at birth and future risk of childhood neoplasms
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