**2. Materials and Methods**

Established methods recommended by the Cochrane Collaboration [16] and according to the principles described in the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) [17] approach were used to conduct this systematic review and meta-analysis. Moreover, the systematic review was structured according to Population, Intervention, Comparison, and Outcome (PICO) characterization [18]. Specifically, the PICO question was whether children and adolescents aged 6–18 years with ADHD should be offered PUFA supplementation. The definitions of population, intervention, comparator, outcomes, and study design are specified in Table 1. The research question is best addressed through a randomized study design in order to evaluate the effectiveness of the intervention so that issues regarding both measured and unmeasured confounding are minimized.

**Table 1.** Population, Intervention, Comparison, and Outcome (PICO) criteria for inclusion and exclusion of studies.


Outcome, secondary Behavioral difficulties, parent rated Behavioral difficulties, teacher rated Quality of life Diarrhea Gastrointestinal discomfort Nausea Timing and effect measures Behavioral difficulties both parent and teacher rated was investigated at end of treatment. Quality of life was investigated at the longest follow-up time (minimum 3 months after end of treatment). In our published protocol, we initially planned to assess diarrhea, gastrointestinal discomfort, and nausea at longest follow-up. This was later changed to end of treatment, as the identified studies did not provide any follow-up data on these outcomes. Study design All randomized controlled studies, with interventions matching the defined research question.

**Table 1.** *Cont.*

The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42020158453 (accepted 28 April 2020) and the systematic review was constructed in accordance to the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement [22,23] (PRISMA checklist is provided in the Supplementary Material).
