Baseline Fatty Acids and Time‐Averaged Executive Function in Ugandan Children With Perinatal HIV

ABSTRACT Fatty acids (FAs) play critical neurodevelopmental roles, yet associations with executive function among children affected by perinatal HIV remain poorly characterized. This prospective cohort study examined associations between serum FAs and caregiver‐reported executive function and evaluated effect modification by perinatal HIV status among 6–10‐year‐old Ugandan children who had perinatal HIV infection (CPHIV; n = 84), were HIV exposed but uninfected (CHEU; n = 78), or were HIV unexposed and uninfected (CHUU; n = 81). Serum FAs were measured at enrollment, and executive dysfunction was assessed at enrollment, 6, and 12 months (Executive Functioning Index (EFI) and Global Executive Composite (GEC)). Multivariable linear mixed models estimated overall and HIV‐specific mean differences (MDs) and 95% confidence intervals (CIs) in executive dysfunction z‐scores by FA tertiles. Moderate versus low arachidonic acid (MD [95% CI] EFI: −0.40 [−0.71, −0.09]; GEC: −0.30 [−0.58, −0.03]) and highly unsaturated FAs (HUFAs; EFI: −0.41 [−0.72, −0.11]) associated with lower executive dysfunction. Among CPHIV, high Mead acid (20:3 (n‐9)) associated with higher executive dysfunction (EFI: 0.56 [0.11, 1.01]). Among CHEU, lower executive function was associated with high docosatetraenoic acid (EFI: −0.93 [−1.71, −0.15]) and docosahexaenoic acid (GEC: −0.78 [−1.26, −0.31]). These results showed that higher HUFAs associated with better executive function, particularly among CHEU, supporting further nutritional intervention research for children affected by perinatal HIV.