Birth Weight and Subsequent Risk of Total Leukemia and Acute Leukemia: A Systematic Review and Meta-Analysis

Objective: Birth weight, an important indicator of fetal nutrition and degree of development, may affect the risk of subsequent leukemia. At present, little is known about the effect of birth weight on acute myeloid leukemia (AML) and whether there is a dose-dependent relationship of birth weight with acute lymphoid leukemia (ALL) and AML. To address these questions, the present work aimed to systematically investigate the relationship between birth weight and the risk of subsequent leukemia based on the current epidemiological studies Methods: Relevant studies were systematically retrieved from electronic databases PubMed, Embase, and Cochrane Library, from inception to May 15th, 2021. Finally, 28 studies (including 21 case-control studies and 7 cohort studies) were included for the final meta-analysis. Results in cohort studies were performed by risk ratios (RRs), while those in case-control studies by odds ratios (ORs), and all results were assessed by adopting the random-effect model. Besides, a dose-dependent analysis was conducted based on the cohort studies. Results: Compared with the population with normal birth weight (NBW), the population with high birth weight (HBW) might have an increased risk of leukemia (OR 1.33, 95%CI 1.20–1.49; I(2) 0%). Meanwhile, low birth weight (LBW) was associated with a decreased risk of ALL, as evidenced from the pooled analysis of case-control studies (OR 0.83, 95% CI 0.75–0.92; I(2) 23.3%). However, relative to NBW population, the HBW population might have an increased risk of ALL (OR 1.28, 95% CI 1.20–1.35; I(2) 7%). There was no obvious evidence supporting the relationship between LBW and the risk of AML from the pooled analysis of case-control studies (OR, 1.11 95% CI 0.87–1.42; I(2) 31.7%). Conclusions: Overall, in children and young adults, HBW population may be associated with the risks of subsequent leukemia and AML relative to NBW population, but the supporting dose-dependent evidence is lacking. In addition, compared with NBW population, there is stronger evidence supporting a significantly increased risk of subsequent ALL in HBW population, and a decreased risk in LBW population in a dose-dependent manner. More prospective studies with large samples are warranted in the future to validate and complement these findings.