Strengths and Limitations
BPD
This cohort study’s mediation analysis was based on data from a large, rigorously designed, blinded trial with high levels of compliance and standardized measures of BPD and IQ. However, our study has several limitations. The original trial had higher than expected rates of attrition by 5 years’ corrected age owing to the COVID-19 pandemic; however, reassuringly, the magnitude of the indirect effect of DHA supplementation via BPD appeared robust to specific assumptions made about missing data. The accuracy of indirect and direct effect estimates relied on appropriate specification of the underlying causal model linking DHA supplementation, BPD and IQ together. Given the randomized design of the original trial, our concern was restricted to confounders of the BPD-IQ association, and while effort was made to incorporate key confounders, it is not possible to rule out the effects of residual confounding. Additionally, it should be noted that this analysis did not address the trade-off between an increased risk of BPD and improved IQ associated with high-dose DHA supplementation. Although we did not observe adverse health signals, including for respiratory-related hospitalizations, from parent reports at the 5-year assessment, further investigation is needed to fully assess the association of the modest increase in BPD risk from DHA with long-term pulmonary function.