3.3.2. Myelination (Main Outcome)
BRAIN
Brain myelin development (including myelin water fraction, T1, T2, g-tatio, and FA) at the 3-, 6-, 12-, 18-, and 24-month time points are shown in Non-linear (Gompertz) longitudinal modeling of the MWF in the predefined ROIs showed no statistically significant differences between the investigational and the control group but indicated a non-significant earlier increase (beta difference = −2.746, 95% CI −8.895 to +3.402), a steeper slope (gamma difference = +1.866, 95% CI −27.375 to +31.108), and a higher plateau (eta difference = +5.470, 95% CI −11.467 to +22.406) in the investigational group.The limited number of MRI scans in our study led to large confidence intervals on the parameters of the planned non-linear longitudinal modeling. This limitation was addressed with mixed model analyses including visits as a categorical confounder (post hoc). The observed effect size in our study was higher than anticipated (+0.018 versus +0.005), resulting in significantly higher levels of myelin for the investigational versus the control group, despite the smaller than anticipated sample size. Effects were found for the whole-brain MWF at 6 months (+0.007, 95% CI [+0.0012; +0.0126]; Log-linear longitudinal modeling showed a statistically significant T1 slope difference in the CC splenium for the investigational group (CC splenium slope difference: +76 ms/log(year), 95% CI [0.8; 153]; In addition to the a priori defined brain regions, we also assessed MWF differences (age-wise and longitudinally) across 174 anatomically relevant areas. Results of this post hoc analyses are shown in For the reference group, longitudinal analyses adjusted for the described propensity score indicated no statistically significant differences between the investigational and the non-randomized breastfed reference group for the MWF and T1. A significant slope difference between the investigational and the breastfed reference group was seen for the CC body T2 (LSMean: −5 ms/year in breastfed reference, 