The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; β = 0.68; 95% CI, 0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; β = 0.21; 95% CI, 0.13-0.29; Q <.001) during the first postnatal days. Here, FGF21 is linked to retinopathy of prematurity.