Birth weight and neonatal morbidity as early-life risk factors for childhood cancer: a nationwide cohort study.

BACKGROUND: Childhood cancer is a significant public health issue, and growing evidence suggests that perinatal factors such as birth weight and neonatal complications may influence cancer risk. However, the potential impact of neonatal interventions on subsequent cancer development remains poorly understood. This study aimed to investigate the association between birth weight and childhood cancer risk, and how this relationship may be modulated by neonatal morbidities and interventions. METHODS: We conducted a nationwide population-based cohort study using the National Health Insurance Service database in South Korea. All live births between 2008 and 2014 were included and categorized by birth weight. Cancer incidence was identified through 2018 using ICD-10 codes. Associations between birth weight, neonatal conditions, neonatal interventions, and cancer outcomes were analyzed. RESULTS: Among over 2.9 million children, low birth weight (LBW) infants-particularly those weighing < 1.0 kg-had a significantly increased risk of childhood cancer (adjusted odds ratio [aOR], 4.03). Distinct cancer patterns were observed by birth weight category: hepatoblastoma was most common in infants < 1.5 kg, central nervous system malignancies in those 1.5-2.4 kg, and leukemia in those > 4.0 kg. In LBW infants, bronchopulmonary dysplasia (aOR, 2.21), sepsis (aOR, 1.56), oxygen exposure ≥ 4 days (aOR, 1.32), and ≥ 3 red blood cell transfusions (aOR, 4.03) were significantly associated with increased cancer risk. In contrast, phototherapy and radiography were not found to be associated with cancer development. CONCLUSIONS: These findings demonstrate that both birth weight extremes and neonatal exposures contribute to childhood cancer risk. In particular, conditions such as bronchopulmonary dysplasia and sepsis-and interventions including oxygen therapy and transfusions-may influence oncogenic pathways in LBW infants. Long-term follow-up in high-risk neonatal populations is warranted, along with further research into underlying biological mechanisms.