Systematic Review and Meta-analysis: The Science of Early-Life Precursors and Interventions for Attention-Deficit/Hyperactivity Disorder

Elizabeth Shephard, Pedro Zuccolo, Iman Idrees, Priscilla Godoy, Erica Salomone, Camilla Ferrante, Paola Sorgato, Luis Catao, Amy Goodwin, Patrick Bolton, Charlotte Tye, Madeleine Groom, Guilherme Polanczyk

Research output: Contribution to journalReview articlepeer-review

22 Citations (Scopus)


Objective: To evaluate which early neurocognitive and behavioral precursors are associated with the development of attention-deficit/hyperactivity disorder (ADHD) and whether these are currently targeted in early interventions. Method: We conducted 2 systematic reviews and meta-analyses of empirical studies to examine the following: (1) early-life (0−5 years) neurocognitive and behavioral precursors associated with familial likelihood for ADHD, an early ADHD diagnosis/elevated ADHD symptoms, and/or the presence of later-childhood ADHD; and (2) interventions delivered to children aged 0 to 5 years targeting the identified precursors or measuring these as outcomes. Standardized mean differences (Hedges’ g) and pre-post-treatment change scores (SMD) were computed. Results: A total of 149 studies (165,095 participants) investigating 8 neurocognitive and behavioral domains met inclusion criteria for part 1. Multi-level random-effects meta-analyses on 136 studies revealed significant associations between ADHD and poorer cognitive (g = −0.46 [95% CIs: −0.59, −0.33]), motor (g = −0.35 [CIs: −0.48, −0.21]) and language (g = −0.43 [CIs: −0.66, −0.19]) development, social (g = 0.23 [CIs: 0.03, 0.43]) and emotional (g = 0.46 [CIs: 0.33, 0.58]) difficulties, early regulatory (g = 0.30 [CIs: 0.18, 0.43]) and sleep (g = 0.29 [CIs: 0.14, 0.44]) problems, sensory atypicalities (g = 0.52 [CIs: 0.16, 0.88]), elevated activity levels (g = 0.54 [CIs: 0.37, 0.72]), and executive function difficulties (g = 0.34 [CIs: 0.05, 0.64] to −0.87 [CIs: −1.35, −0.40]). A total of 32 trials (28 randomized, 4 nonrandomized, 3,848 participants) testing early interventions that targeted the identified precursors met inclusion criteria for part 2. Multi-level random-effects meta-analyses on 22 studies revealed significant intervention-related improvements in ADHD symptoms (SMD = 0.43 [CIs: 0.22, 0.64]) and working memory (SMD = 0.37 [CIs: 0.06, 0.69]). Conclusion: Children aged 0 to 5 years with current or later-emerging ADHD are likely to experience difficulties in multiple neurocognitive/behavioral functions. Early interventions show some effectiveness in reducing ADHD symptoms, but their effects on neurocognitive/behavioral difficulties require further study.

Original languageEnglish
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Publication statusAccepted/In press - 2 Apr 2021


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