Reproductive
A Target Trial Emulation Assessing the Effects of Prenatal Cannabis Exposure on Menarche Onset in Pre-Adolescents in the Adolescent Brain and Cognitive Development Study Adaeze Anamege* Adaeze Anamege Anamege Anamege University of Florida, Department of Epidemiology
Background: Prenatal cannabis exposure (PCE) has been linked to adverse physiological and behavioral outcomes in children. However, its influence on developmental milestones that mark the onset of reproductive capacity in early adolescence, such as menarche, remains poorly understood. This study estimated the effect of PCE on time to menarche among pre-adolescent girls.
Methods: Using a target trial emulation framework, we analyzed data from the prospective Adolescent Brain and Cognitive Development study. The analytic sample included 4,861 biological mother–child dyads, of whom 296 reported PCE and 4,565 did not report PCE. Stabilized inverse probability of treatment and censoring weights were applied to approximate randomization and account for loss to follow-up. The outcome was time to menarche. A piecewise exponential hazards model was used to estimate the effect of PCE during two time intervals: 0–120 months (early menarche) and >120 months (normal timing). SAS 9.4 was used for all analyses.
Results: In weighted models that did not account for clustering, PCE was associated with a 60% higher hazard of reaching menarche at or before 120 months (HR = 1.60; 95% CI: 1.29–1.99) compared with the no PCE group. After accounting for shared genetic environment among twins and triplets, the hazard ratio remained the same while precision significantly improved (HR = 1.60; 95% CI: 1.54-1.67).
Conclusions: PCE was associated with an increased hazard of early menarche. These findings suggest that prenatal substance exposures may play a meaningful role in shaping reproductive development in offspring and highlight the need to better understand the underlying biological pathways linking early-life cannabis exposure to accelerated pubertal timing. Future studies should explore potential biological mediators and further disentangle prenatal effects from broader familial and developmental factors influencing menarcheal timing.