Background: Although numerous epidemiological studies have examined the association between pesticide exposure and acute childhood leukemia (AL), the overall strength of evidence remains inconclusive. Despite major therapeutic advances leading to 5-year survival rates exceeding 90% for childhood acute lymphoblastic leukemia (ALL), survivors often experience long-term adverse outcomes, including reduced quality of life and an increased risk of second primary cancers, underscoring the need to identify preventable risk factors. The aetiology of childhood ALL is thought to involve early-life processes, particularly during prenatal development. While several environmental and biological risk factors have been proposed, existing evidence on prenatal and pre-conception pesticide exposure remains fragmented and has not been systematically synthesized across residential and occupational sources.

Objectives: This study aimed to systematically review the literature and conduct a meta-analysis to evaluate the association between in utero exposure to pesticides and the incidence of acute lymphoblastic leukaemia in offspring, and to explore whether selected study characteristics influenced effect estimates.

Methods: A comprehensive literature search was conducted in PubMed, Embase, and Web of Science without restrictions on language or publication date. Original epidemiological studies reporting risk estimates for maternal pesticide exposure before birth with ALL as the outcome were eligible. Case–control, cohort, and pooled studies were included. Study selection, data extraction, and quality assessment were independently performed by two reviewers. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed-effects and random-effects models. Univariate meta-regressions were conducted to assess the influence of selected study characteristics on effect estimates, using crude effect sizes as outcomes. Between-study variance was estimated using the restricted maximum likelihood (REML) method.

Results: Nineteen studies met the inclusion criteria. In the random-effects meta-analysis of crude estimates based on 17 studies, ever exposure to pesticides during the prenatal period was significantly associated with an increased odds of ALL (OR = 1.63, 95% CI: 1.28–2.06) compared with never exposure, with similar results under the fixed-effects model and moderate heterogeneity (I² = 45.6%). Analyses based on adjusted estimates from 12 studies yielded a lower but still significant association (OR = 1.46, 95% CI: 1.27–1.68). Sensitivity analyses by exposure window showed a significant association for exposure during pregnancy, whereas pre-conception exposure was associated with a higher but less precise estimate, reflecting the limited number of studies. Analyses by exposure pathway indicated a significant association for residential exposure, while associations for occupational exposure were weaker and not statistically significant. Meta-regression analyses showed that no individual study characteristic significantly modified the effect estimate, although factors such as publication year and study design explained part of the between-study heterogeneity.

Conclusions: This systematic review and meta-analysis provide evidence of a positive association between in utero pesticide exposure and childhood acute lymphoblastic leukaemia. However, limited data for pre-conception exposure does not allow us to conclude on an association with ALL. Further well-designed studies with improved exposure assessment are needed to refine these associations and support preventive strategies.