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10 May 2021

Shephard E et al. J Am Acad Child Adolesc Psychiatry 2021; Epub ahead of print

This study aimed to evaluate which early neurocognitive and behavioural precursors are associated with the onset and development of ADHD and whether early interventions currently target these precursors. The emergence of early developmental period neurocognitive and behavioural atypicalities associated with ADHD were also investigated.

Two systematic reviews and meta-analyses were conducted to examine: (1) empirical studies of early-life (aged 0–5 years) neurocognitive and behavioural precursors associated with the familial likelihood for ADHD, early ADHD diagnosis, or elevated ADHD symptoms and/or the presence and severity of later-childhood ADHD; and (2) empirical studies of interventions delivered to children in early-life that target the identified precursors in the first meta-analysis or measure them as outcomes. Additionally, the authors investigated whether developmental stage (infancy/toddlerhood [aged 0–2 years] vs preschool [aged 3–5 years]) significantly moderated associations between neurocognitive and behavioural atypicalities and ADHD. For the systematic review, eligible studies were identified using four electronic bibliographic databases (EuropePMC, MEDLINE, PsycINFO, Scopus) and reference lists of eligible articles and review articles.

Early-life neurocognitive and behavioural precursors of ADHD

In total, 149 studies (n=165,095) investigating eight neurocognitive and behavioural function domains* met inclusion criteria, with most studies (65.1%) examining more than one of these functions. Approximately half of the studies (50.3%) focused on preschoolers (aged 3–5 years) while 55 (36.9%) focused on infants/toddlers (aged 0–2 years); 19 (12.8%) studies included both (i.e., children aged 0–5 years). Over half of the studies did not report or provide sufficient information on socioeconomic status (55.0%; n=82) or race and ethnicity (61.7%; n=92). Multilevel random-effects meta-analyses on 136 studies revealed significant associations between ADHD and the following:

  • Poorer cognitive (Hedge’s g [g]=-0.46; 95% confidence interval [CI] -0.59 to -0.33), motor (g=-0.35; 95% CI -0.48 to -0.21) and language (g=-0.43; 95% CI -0.66 to -0.19) development
  • Social (g=0.23; 95% CI 0.03–0.43) and emotional (g=0.46; 95% CI 0.33–0.58) difficulties
  • Early regulatory (g=0.30; 95% CI 0.18–0.43) and sleep (g=0.29; 95% CI 0.14–0.44) problems
  • Sensory atypicalities (g=0.52; 95% CI 0.16–0.88)
  • Elevated activity levels (g=0.54; 95% CI 0.37–0.72)
  • Executive function difficulties (g=0.34; 95% CI 0.05–0.64 to g=-0.87; 95% CI -1.35 to -0.40).

Early interventions targeting early-life neurocognitive and behavioural precursors associated with ADHD

Twenty-eight randomised and four non-randomised trials (n=3848) testing early interventions targeting the identified precursors met inclusion criteria for the second objective of the study. Most identified studies (81.3%) included preschoolers (aged 3–5 years) while two (6.25%) focused on infants/toddlers (aged 0–2 years) and four (12.5%) studies included both (children aged 0–5 years). Around half of the studies did not provide sufficient information on socioeconomic status (43.8%) or race and ethnicity (50%). The interventions that most studies tested were diverse and included, for example, parent-training programmes, cognitive training, neurofeedback and yoga. These interventions directly or indirectly targeted self-regulation, and several targeted social and emotional functioning, language ability and executive functions. Outcome measures were assessed immediately post-intervention and included ADHD symptoms, language and motor abilities, social and emotional functioning, early regulatory problems, activity level and executive functions. Multilevel random-effects meta-analyses on 22 studies revealed significant intervention-related improvements in ADHD symptoms (pre–post-treatment change score [SMD]=0.43; 95% CI 0.22–0.64) and working memory (SMD=0.37; 95% CI 0.06–0.69).

A limitation of this study is that findings must be interpreted in the context of significant heterogeneity and publication bias. Furthermore, there is unclear generalisability and representativeness of these results to the global population, due to inadequate reporting of socioeconomic and racial and ethnic backgrounds of participant samples. In addition, effect sizes could not be computed from all publications, so small effect sizes from non-significant findings may be underrepresented in this study and pooled effect sizes may overestimate true associations between early neurocognitive precursors and ADHD and intervention effects. Pooled estimates may also have been affected by the failure to nest effect sizes across studies in the models. Furthermore, effects of individual neurocognitive measures and interventions could not be investigated due to large cross-study variability, and studies published since the final search date of this review have not been included; therefore, this study does not provide the latest findings in this field.

The authors concluded that children aged 0–5 years with current or later-emerging ADHD may experience multiple neurocognitive or behavioural function difficulties, particularly overactivity, executive function difficulties and sensory processing atypicalities. Early interventions, such as behavioural parent-training programmes, may show some effectiveness in reducing ADHD symptoms and may be the most appropriate treatment model for infants and young children with ADHD or elevated likelihood for developing ADHD; however, in the authors’ opinion, they require further investigation.

Read more about the science of early-life precursors and interventions for ADHD here


*The eight domains included: general cognitive, language and motor abilities; social and emotional functioning; sleep; early regulatory problems (e.g., excessive crying); sensory processing; activity level; executive function; and brain structure and resting-state neurophysiological activity.

Shephard E, Zuccolo PF, Idrees I, et al. Systematic review and meta-analysis: the science of early-life precursors and interventions for attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2021; Epub ahead of print.

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