Role of the perinatal experience on the risk of acute leukemia in childhood or adolescence: Systematic review and meta‐analysis

Acute leukemia is the most common type of cancer in children; however, the etiology is poorly understood. The objective of this review was to summarize the current evidence of the role of perinatal factors in the development of acute leukemia. All epidemiological studies published up to October 2023 that evaluated perinatal risk factors for childhood acute leukemia were identified using a multi-tiered approach in two electronic databases (PubMed and Web of Science), without restriction on publication year or language. A total of 85 studies (13 prospective cohort studies, 62 case-control studies, and 10 pooled analyses) were included. We combined the published risk estimates in a meta-analysis, using the Generic Inverse Variance method. An increased risk of acute leukemia and the lymphoblastic subtype (ALL) was associated with high birth weight (>4000 g) (odds ratio [OR] = 1.35; 95% confidence interval [95% CI] 1.20-1.53 and OR = 1.21; 95% CI 1.08-1.34, respectively), maternal history of abortion (OR = 1.27; 95% CI 1.12-1.43 and OR = 1.24; 95% CI 1.08-1.43, respectively), and maternal diabetes (OR = 1.30; 95% CI 1.14-1.48 and OR = 1.32; 95% CI 1.16-1.50, respectively). In addition, an increased risk for ALL was also associated with maternal hypertension (OR = 1.21; 95% CI 1.06-1.38) and cesarean section (OR = 1.10; 95% CI 1.05-1.16). Our review suggests a potential role for perinatal factors in the development of acute leukemia in children. These findings indicate potential avenues for developing cost-effective prevention strategies applicable at the population level, while the mechanism of action is investigated.