Abstract Background Prenatal alcohol exposure (PAE) is a risk factor for early‐onset psychopathology. Low birthweight (LBW), one potential consequence of PAE, increases the vulnerability of children for externalizing disorders. This study investigates potential sex‐specific indirect pathways linking PAE to behavioral symptoms in offspring, focusing on LBW as a mediating and moderating factor. Methods Participants were 9–10‐year‐old singleton children whose biological parents reported on pregnancy experiences in the Adolescent Brain Cognitive Development (ABCD) study. PAE was a binary variable, indicating any use during pregnancy. Externalizing behavioral problems were assessed with the Child Behavior Checklist and modeled continuously. LBW (<2500 g) was calculated based on parental reports. We applied a four‐way decomposition analysis with stratification by sex. This causal framework allows to dissect the total effect into controlled direct effect (CDE), reference interaction (INTref), mediated interaction (INTmed), and pure indirect effect (PIE). Results The analytic sample ( N = 7502) was evenly split by sex, and nearly 50% were non‐Hispanic White children. A total of 2083 children were exposed to PAE. The adjusted total effect of PAE on externalizing behavioral problems was identified ( β = 0.91; 95%CI: 0.38, 1.44), with slightly weaker effects observed in males ( β = 0.88; 95%CI: 0.12, 1.64) than in females ( β = 0.98; 95%CI: 0.25, 1.71). Decomposition analysis indicated potential interaction with a major difference in CDE in the presence of LBW and in its absence, specifically for males ( β = 4.30, 95% CI: 1.97, 8.40 and β = 0.70, 95%CI:‐0.17, 1.57, respectively). This indicates higher externalizing behavioral problems in males with a joint exposure to PAE and LBW, also confirmed with the INTref parameter ( β = 0.18, 95%CI: 0.08, 0.4). We found no evidence for mediation (PIE) or mediated interaction (INTmed) via LBW. Conclusion Early identification and intervention for children with PAE have been shown to mitigate the risk of more severe secondary impacts. Our findings highlight the potential importance of birthweight as a factor that may exacerbate behavioral problems among PAE‐exposed offspring, particularly males.
Shchetinina et al. (Sun,) studied this question.