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

doi:10.1016/j.jaac.2021.03.016

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 journal › Review article › peer-review

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Abstract

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 language	English
Journal	Journal of the American Academy of Child and Adolescent Psychiatry
DOIs	https://doi.org/10.1016/j.jaac.2021.03.016
Publication status	Accepted/In press - 2 Apr 2021

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10.1016/j.jaac.2021.03.016

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Shephard, E., Zuccolo, P., Idrees, I., Godoy, P., Salomone, E., Ferrante, C., Sorgato, P., Catao, L., Goodwin, A., Bolton, P., Tye, C., Groom, M., & Polanczyk, G. (Accepted/In press). Systematic Review and Meta-analysis: The Science of Early-Life Precursors and Interventions for Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child and Adolescent Psychiatry. https://doi.org/10.1016/j.jaac.2021.03.016

@article{b415999bd83644049e0e61806727928d,

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

abstract = "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{\textquoteright} 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.",

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

note = "Funding Information: E. Shephard is supported by a postdoctoral fellowship from the S?o Paulo Research Foundation (FAPESP; ref: 18/22396-7). L.F.C. Cat?o is supported by a scientific initiation bursary from FAPESP (ref: 19/24819-5). C. Tye is supported by the Tuberous Sclerosis Association and the National Institute for Health research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Prof. Polanczyk is supported by FAPESP (grant 2016/22455-8) and the National Council for Scientific and Technological Development (CNPq; grant 310582/2017-2). Disclosure: Prof. Polanczyk has been in the past 3 years a member of the advisory boards of Shire/Takeda and Medice and a speaker for Shire/Takeda, Novo Nordisk, and Ach?. He has received travel expenses for continuing education support from Shire/Takeda and royalties from Editora Manole. Drs. Shephard, Zuccolo, Salomone, Goodwin, Prof. Bolton, Drs. Tye and Groom, Mss. Idrees, Godoy, Ferrante, Sorgato, and Mr. Cat?o have reported no biomedical financial interests or potential conflicts of interest. Funding Information: E. Shephard is supported by a postdoctoral fellowship from the S{\~a}o Paulo Research Foundation (FAPESP; ref: 18/22396-7). L.F.C. Cat{\~a}o is supported by a scientific initiation bursary from FAPESP (ref: 19/24819-5). C. Tye is supported by the Tuberous Sclerosis Association and the National Institute for Health research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. G.V. Polanczyk is supported by FAPESP (grant 2016/22455-8) and the National Council for Scientific and Technological Development (CNPq; grant 310582/2017-2). Publisher Copyright: {\textcopyright} 2021 American Academy of Child & Adolescent Psychiatry",

year = "2021",

month = apr,

day = "2",

doi = "10.1016/j.jaac.2021.03.016",

language = "English",

journal = "Journal of the American Academy of Child and Adolescent Psychiatry",

issn = "0890-8567",

publisher = "Elsevier Limited",

}

Shephard, E, Zuccolo, P, Idrees, I, Godoy, P, Salomone, E, Ferrante, C, Sorgato, P, Catao, L, Goodwin, A , Bolton, P , Tye, C, Groom, M & Polanczyk, G 2021, 'Systematic Review and Meta-analysis: The Science of Early-Life Precursors and Interventions for Attention-Deficit/Hyperactivity Disorder', Journal of the American Academy of Child and Adolescent Psychiatry. https://doi.org/10.1016/j.jaac.2021.03.016

TY - JOUR

T1 - Systematic Review and Meta-analysis: The Science of Early-Life Precursors and Interventions for Attention-Deficit/Hyperactivity Disorder

AU - Shephard, Elizabeth

AU - Zuccolo, Pedro

AU - Idrees, Iman

AU - Godoy, Priscilla

AU - Salomone, Erica

AU - Ferrante, Camilla

AU - Sorgato, Paola

AU - Catao, Luis

AU - Goodwin, Amy

AU - Bolton, Patrick

AU - Tye, Charlotte

AU - Groom, Madeleine

AU - Polanczyk, Guilherme

N1 - Funding Information: E. Shephard is supported by a postdoctoral fellowship from the S?o Paulo Research Foundation (FAPESP; ref: 18/22396-7). L.F.C. Cat?o is supported by a scientific initiation bursary from FAPESP (ref: 19/24819-5). C. Tye is supported by the Tuberous Sclerosis Association and the National Institute for Health research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Prof. Polanczyk is supported by FAPESP (grant 2016/22455-8) and the National Council for Scientific and Technological Development (CNPq; grant 310582/2017-2). Disclosure: Prof. Polanczyk has been in the past 3 years a member of the advisory boards of Shire/Takeda and Medice and a speaker for Shire/Takeda, Novo Nordisk, and Ach?. He has received travel expenses for continuing education support from Shire/Takeda and royalties from Editora Manole. Drs. Shephard, Zuccolo, Salomone, Goodwin, Prof. Bolton, Drs. Tye and Groom, Mss. Idrees, Godoy, Ferrante, Sorgato, and Mr. Cat?o have reported no biomedical financial interests or potential conflicts of interest. Funding Information: E. Shephard is supported by a postdoctoral fellowship from the São Paulo Research Foundation (FAPESP; ref: 18/22396-7). L.F.C. Catão is supported by a scientific initiation bursary from FAPESP (ref: 19/24819-5). C. Tye is supported by the Tuberous Sclerosis Association and the National Institute for Health research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. G.V. Polanczyk is supported by FAPESP (grant 2016/22455-8) and the National Council for Scientific and Technological Development (CNPq; grant 310582/2017-2). Publisher Copyright: © 2021 American Academy of Child & Adolescent Psychiatry

PY - 2021/4/2

Y1 - 2021/4/2

N2 - 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.

AB - 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.

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U2 - 10.1016/j.jaac.2021.03.016

DO - 10.1016/j.jaac.2021.03.016

M3 - Review article

SN - 0890-8567

JO - Journal of the American Academy of Child and Adolescent Psychiatry

JF - Journal of the American Academy of Child and Adolescent Psychiatry

ER -

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

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