Table 2 List in chronological order of the 44 studies included here

Bernardi et al. (2010) [26]

Italy

Cross-sectional (January 2004–January 2008)

To compare bipolar disorder (BD) patients with/without ADHD diagnosis in childhood on clinical and temperamental characteristics.

100 patients with BD, 18 of which with ADHD (10 remitted (aADHD-BD) and 8 persistent (cADHD-BD) in adulthood)

Exclusion criteria were: (1) any clinically significant medical conditions, organic brain disorders, (2) current substance/alcohol abuse or dependence (in the last 6 months), since it may precipitate BD episodes and impair ADHD symptoms at present increasing their intensity; and (3) any lifetime comorbid mental disorders (except previous secondary symptoms of anxiety or substance abuse as based on temporal onset and symptoms severity in remission from at least 6 months), unwillingness or inability to comply with study assessments, or inability to provide informed consent.

Inclusion criteria were: (1) an age range of at least 18 and no greater than 30 years to avoid a retrospective ADHD diagnosis time that was potentially too long; (2) remission of BD for at least 3 months, as assessed by Young Mania Rating Scale and Hamilton Depression Scale scores, in order to reduce possible diagnostic confounders of symptom overlap between ADHD and acute mania; and (3) the presence of at least one parent able to describe the patient’s lifetime course of disease symptoms, in order to confi rm. th e age of onset of ADHD. The presence of at least one parent was considered necessary also to report about the onset and the course of BD symptoms and to distinguish them from symptoms of oppositional defi ant disorder or conduct disorder.

DSMIV-TR (Supported by the WURS)

AO (Mean ± SD, years): -Overall: 6.50 ± 1.04; cADHD: 6.75 ± 0.88; aADHD 6.30 ± 1.15.

Kopp et al. (2010) [27]

Sweden

Descriptive

To clinically describe girls referred for problems with social interaction, attention/academic problems, or tics, comparing symptomatology and comorbidity.

60 clinic girls aged 7 to 16 years with a tested FSIQ ≥80 were selected and matched for age with 60 randomly selected schoolgirls.

Girls with previously diagnosed LD (FSIQ ≤70) had been excluded. However, after full assessment, 12 clinic girls were found to meet criteria for LD (9 of whom were less than age 7 at referral). They were retained because they had not been diagnosed or suspected of LD before entering the study. Other exclusion criteria were defined as parental inadequate command of the Swedish language and serious physical disorders (e.g., cerebral palsy and severe epilepsy).

DSM-IV; Griffiths; WPPSIR; WISC-III; WAIS-R; 10-Item Conners’ Scale; CTRS-R:L; FTF; ASSQ; DSRS; GAF; Severity of Psychosocial Stressors Scale, Children and Adolescents; ADI-R; CAPA; VABS-DLS; ADOS-G

AD (Mean ± SD, years): -Among the clinic girls with ADHD diagnosis (n = 46), 13.0 ± 3.4; Among the matched clinic girls with ADHD diagnosis (n = 34):12.7 ± 2.6.

Polanczyk et al. (2010) [28]

UK

Prospective longitudinal (From 1999 to 2000, 7 years follow-up)

To test the implications of extending the ADHD AO criterion from age 7 to 12.

66 met full ADHD criteria; 2 met ADHD criteria, except AO criterion; 1183 without ADHD, symptom onset before age 7 years; 181 without ADHD, symptom onset between ages 7 and 12 years; 547 without ADHD, never had symptoms.

Mother and teacher reports symptoms according to DSM-IV.

At age 12, 66 children (3.3%) met full diagnostic criteria for ADHD, including AO criterion. Among the 181 children with AO between age 7 and 12 years, only 2 met full diagnostic criteria for ADHD (except the AO criterion).

Prihodova et al. (2010) [29]

Czech Republic

Case control (2007)

To evaluate the sleep macrostructure in the ADHD group comparing with controls.

31 patients with ADHD and 26 matched controls (age range 6–12 years).

The enrollment criteria were as follows: (1) ADHD diagnosed on the basis of DSM-IV, (2) no previous pharmacological treatment for ADHD, (3) no history of any chronic physical condition (including obesity), chronic sleep disorder, neurological or other psychiatric disorders (including mental retardation and autism) based on a complete pediatric report and on a neurological and psychiatric examination, (4) no current medication (psychotropic or general) and (5) the patient’s and his/her parents’ willingness to participate in the study and informed consent signed by the parents. All participants were in the prepubertal or early pubertal stages as assessed by Tanner scale. All were of Caucasian origin. They underwent psychological, psychiatric and neurological testing. Information about their sleep habits and sleep disturbances was collected from the parents and children by means of a detailed clinical interview and Pediatric Sleep Questionnaire.

DSM-IV and Children’s Psychiatric Rating Scale; CPRS; CBCL; CMAS; CDI; WISC-III

Parentally reported AO was between 4 and 6 years.

Berek et al. (2011) [30]

Germany

Multicentre, prospective, open-label, single-arm, non-interventional

To compare clinical and health-related quality of life outcomes between children and adolescents treated with Methylphenidate

822 patients with ADHD. Among these, 785 have valid data on age at diagnosis: 565 children (6–12 years) and 220 adolescents (13–18 years).

Children and adolescents aged 6–18 years who had a confirmed diagnosis of ADHD by ICD-10 criteria, and in whom treatment with OROS® MPH was medically indicated and planned by the treating physician, were eligible to participate in the studies.

ICD-10

AD (Mean ± SD/Median/[Range]), years: -Overall: 8.06 ± 2.49/8.0/[1.0–16.0]; −Children: 7.31 ± 1.85/7.0/[2.0–12.0]; −Adolescents: 9.97 ± 2.86/10.0/[1.0–16.0].

Gustafsson and Källén (2011) [31]

Sweden

Population-based (Study initiated in 2005)

To evaluate the impact of pre- and perinatal factors on the risk of developing ADHD.

237 children with ADHD diagnosis and 31,775 typically developing children, born between 1986 and 1996

Individuals for whom no linkage was possible (e.g. children who were born abroad) or children who were born in Sweden but outside Malmo¨ were not included in the final analysis.

DSM-III-R before 1994 and DSM-IV from 1994 onwards

AD varied between 5 and 17 years, with most children diagnosed between 8 and 12 years of age.

Muller et al. (2011) [32]

Belgium, Germany, Ireland, the Netherlands, Spain, Switzerland, UK and Israel

Large multi-centre (recruitment between April 2003 and April 2007)

To analyse the International Multi-centre ADHD Genetics sample with respect to demographic features and psychopathological characteristics.

The sample consisted of 1068 probands with the combined type of ADHD and 1446 ‘unselected’ siblings. Age (Mean ± SD) = 10.8 ± 3.1 years.

Families were excluded from genetic analyses, if either the proband or the participating sibling had an IQ < 70, a diagnosis of schizophrenia or autism, a neurological disorder of the central nervous system or a genetic disorder that might mimic ADHD based on both history and clinical assessment. Children with classical or atypical autism were excluded from the IMAGE project because some genetic regions are known to be associated both with autism and ADHD. There was no rule for assigning proband status to a certain child of a family when several children fulfilled criteria for ADHD-CT.

Recruited families had at least one child with diagnosed or suspected combined type Attention Deficit-Hyperactivity Disorder (ADHD-CT). Further entry criteria for assessment were: white Caucasian ethnicity of all participants, availability of one or more sibling, children between the ages of 5 and 17 years, participation of a minimum of four family members including one parent, and consent of all persons to give blood samples or buccal swabs for DNA extraction.

PACS interview and the DSM-IV items of the CTRS questionnaire

Age at detection of Inattention (I) and Hyperactivity/ Impulsivity (H/I) symptoms (Mean [Range]), years: -Siblings (No diagnosis) I: 6.19 [1–16]; H/I:3.93 [1–15]; −Siblings (Hyperactive/ Impulsive) I: 4.31 [1–11]; H/I: 3.13 [1–6]; −Siblings (Inattentive) I: 4.80 [1–6]; H/I: 3.56 [0–10]; −Siblings (Combined) I: 4.07 [0–10]; H/I: 2.8 [0–7]; −Siblings (All subtypes) I: 4.59 [0–16]; H/I: 3.09 [0–15]; −Probands (Combined) I: 4.22 [0–12]; H/I:2.36 [0–11]. N.B.: The same data available also by gender

Durá-Travé et al. (2012) [33]

Spain

Follow-up (Between January and December, 2009)

To determine the repercussions of drug therapy with osmotic-release oral system methylphenidate during 4 years on the weight and height curve of these patients.

187 ADHD patients under treatment with osmotic-release oral system methylphenidate for at least 48 months since their diagnosis. Among them, 158 combined subtype (84.5%) and 29 inattentive subtype (15.5%). Age at baseline (Mean ± SD) = 8.14 ± 1.60 years

The patients who had stopped treatment during school holidays or summer periods were excluded.

DSM-IV

AD (Mean ± SD), years = 8.14 ± 1.60; 84.5% of patients were diagnosed during school age (6–10 years), 10.5% during preschool age (< 6 years), and 5% of patients during adolescence (> 10 years). There were no significant differences in AD regarding sex and clinical subtype.

Garbe et al. (2012) [34]

Germany

Population-Based Cohort (From a first diagnosis of ADHD in 2005, until discontinuation of insurance, death, or December 31, 2008)

To evaluate drug treatment of ADHD in children and youth in Germany with respect to the time until treatment, the initial treatment choice, switches between drugs, and persistence of drug treatment.

6210 children and adolescents 3–17 years of age, with a first diagnosis of ADHD in 2005.They had either received one inpatient or at least two outpatient ICD-10 GM diagnoses within a time interval of 365 days.

Subjects were required to be continuously ensured for at least 12 months before the date of cohort entry.

ICD-10 GM (German modification)

AD (years)

M F T

3–5 9.0 7.6 8.7

6–8 36.3 34.9 36.0

9–11 31.3 36.4 32.5

12–14 18.1 14.3 17.2

15–17 5.3 6.8 5.6

Total 100,100,100

Kirov et al. (2012) [35]

Germany

To investigate sleep architecture in children with ADHD by targeting the first-night effect as a possible confounder.

20 unmedicated children with ADHD combined type (8–15 years old; mean 11.24, SD 2.31) and 19 healthy controls, matched for age and gender.

Exclusion criteria for both healthy children and children with ADHD were the presence of internal diseases and neurological problems not associated with ADHD. Subjects with total IQ less than 80 also were excluded. Further exclusion criteria applied for the controls were current sleep problems. Also, none of the controls met any DSM-IV criteria for the presence of any psychiatric disorder. Patients who met DSM-IV criteria for the presence of psychiatric disorders different from ADHD were excluded.

DSM-IV; clinical tests for neurological and internal diseases,including routine electroencephalogram and electrocardiogram

Mean [range] AO = 5.9 [4–8] years

Tuithof et al. (2012) [36]

the Netherlands

Survey (Between November 2007 and July 2009)

To investigate the childhood ADHD association with prevalence and onset of 3 stages of alcohol use (alcohol initiation, regular alcohol use, and alcohol use disorder) and the conduct disorder role in this association.

3309 respondents aged 18–49 years (mean age 32). Childhood ADHD was present in 74 of the respondents.

CIDI (version 3.0) was used according to DSM-IV criteria

The mean AO of ADHD was 6.7 (95% CI: 5.4–8.0) years

Andreou and Trott (2013) [37]

Greece

Matched case-control

To examine the performance of adults, diagnosed with ADHD in childhood, on semantic and phonemic verbal fluency tasks.

30 university students diagnosed with ADHD in childhood (26 combined type and 4 hyperactive impulsive type) and 30 controls. Mean years of age 20.5, SD = 1.5

Students of both groups must have met the following criteria: (a) entered the Greek university through the national Greek system of exams, (b) reported Greek as their native language, (c) were free from medications known to affect the central nervous system, and (d) had no history of neurological or psychiatric disease.Students who were included in the ADHD group must have also met the following criteria: (a) had received an ADHD diagnosis in childhood, according to DSM-IV criteria and (b) obtained a high score in the ADHD questionnaire adapted from Conners’ Hyperactivity Index. Students who were included in the control group must have obtained a low score

DSM-IV;ADHD questionnaire adapted from Conners’ Hyperactivity Index

The mean AD was 6.2 years of age, SD = 0.9.

Bahmanyar et al. (2013) [38]

Sweden

Follow-up (From January 1, 2006 until December 31, 2009)

To describe the paediatric population with ADHD and their pharmacological treatment.

7931 individuals who, for the first time, were diagnosed or medically treated for ADHD before 19 years of age during 2006–2007

All patients who, for the first time, received a diagnosis of ADHD or treatment for ADHD before 19 years of age in Sweden between January 1st, 2006 and December 31st, 2007 were identified using the National Patient Register and the Prescribed Drug Register.

ICD-10, DSM-IV

The mean age of incident paediatric patients with a recorded ADHD diagnosis or treatment for ADHD is 12.0 years (SD = 3.7).

Hodgkins et al. (2013) [39]

France, Germany, Italy, the Netherlands, Spain and UK

Retrospective chart-review (ADHD diagnosis between January 2004 and June 2007 followed up until 2009)

To descriptively illustrate variation in physician practice patterns in the management of ADHD in various Western European countries.

340 physicians reviewed and abstracted charts for 779 patients (130 France, 151 Germany, 144 Italy, 74 the Netherlands, 134 Spain, 146 UK). Each physician managed approximately 20 patients aged 6 to 12 years and 15 patients aged 13 to 17 years.

Patient charts were excluded if there was evidence of enrolment in a randomized clinical trial.

Physicians were screened as eligible for inclusion in the study if they were engaged in clinical practice for between 3 and 30 years, managed the treatment of at least five ADHD patients (aged 6–17 years) per month and were responsible for making ADHD treatment decisions. Physicians were required to identify the most recent ADHD patients (up to a maximum of five patients aged 6–17 years) that they had seen at the time of the review. In order for patients to be included in the study, they should have had a documented diagnosis of ADHD between January 2004 and June 2007 and have had at least 2 years of follow-up post-diagnosis. Patients were also required to have received either pharmacological treatment or BT following the ADHD diagnosis.

DSM-IV; ICD-9/ICD-10; ADHD Connors Test

Mean (SD)/Median/Range AD:

-Overall: 8.9 (2.6)/9/ [2–15] years

-France: 9.1 (2.5)/9/ [3–14] years

-Germany: 8.4 (2.1)/8/ [2–15] years

-Italy: 8.7 (2.9)/8/ [4–14] years

-the Netherlands: 8.6 (2.6)/9/ [4–15] years

-Spain: 9.0 (2.3)/9/ [3–15] years

-UK 9.3 (2.8)/9/ [4–15] years

McCarthy et al. (2013) [40]

Ireland

Case control

To explore the resting-state functional connectivity in ADHD and to determine the localization and specificity of ADHD related connectivity differences between adults diagnosed with ADHD in childhood and controls by examining 5 predefined neural networks.

16 adults with combined-type ADHD who underwent careful clinical assessment as children, mean (SD) age at diagnosis: 8.9 (2.1) years; 16 healthy matched controls

Exclusion criteria consisted of previous head injurywith loss of consciousness, comorbid psychiatric disorder or disease, a history of hydrocortisone use, and current alcohol or substance abuse and/or dependency.

Structured Clinical Interview for DSM-IV Axis I Disorders

Mean (SD) AD = 8.9 (2.1) years

Nordström et al. (2013) [41]

Finland

Prospective (From birth, between July 1, 1985 and June 30, 1986, to December 31, 2010)

To complete previous findings about the comorbidity of Disruptive behaviour disorder (DBD) and ADHD and to compare the diagnoses based on a clinical evaluation using K-SADS-PL and the register data.

44 only DBD diagnosis; 91 only ADHD; 72 comorbid DBD and ADHD; 250 no DBD or ADHD. A total of 457 adolescents participated.

Adolescents who were neither ADHD cases nor controls were excluded from analyses.

K-SADS-PL; SWAN scale

The median AO of the psychiatric disorders among adolescents with only DBD was 14.9, IQR (interquartile range) = [6.4–18.9], with only ADHD 7.5, IQR = [4.3–15.1] and with comorbid DBD and ADHD 15.3 (IQR = 8.6–20.3).

Socanski et al. (2013) [42]

Norway

Retrospective chart-review

To investigate the prevalence and characteristics of epilepsy in a large, unselected cohort of children with ADHD.

607 children (82.4% males) aged 6–14 years with ADHD were identified. Of these 14 (2.3%) had a history of epilepsy and 13 of these had active epilepsy

Patients with IQ below50 and those meeting criteria for pervasive developmentaldisorder were excluded

DSM-IV-TRCBCL; CPRS; CTRS; ADHD rating scale IV

Mean (SD) AD of ADHD, years: Total sample 9.4 (2.5); Children with epilepsy 8.2 (2.3); children without epilepsy 9.4 (2.5) (p-value = 0.07).

Caci et al. (2014) [43]

France, Germany, Italy, the Netherlands, Spain and UK

Cross-sectional (From May 2010 to June 2010)

To assess the degree to which ADHD impairs patients’ everyday lives and to identify the areas of life most affected by the condition.

959 children/adolescents aged < 20 were included in the analyses: 535 with ADHD (ADHD group) and 424 without ADHD (control group).

Respondents who provided implausible or impossible answers (e.g. reporting a time to diagnosis that exceeded the age of the child) were excluded, as well as the UK control group (as child age was not collected). Analyses focus on a subgroup of respondents who reported on children/adolescents aged 6 years (respondents with children aged 5 years or younger were excluded).

Caregiver-reported diagnosis

Mean (SD) AD was 7.0 (2.8) years, ranging from 6.3 (2.1) years in Germany to 7.6 (3.1) years in the Netherlands. Diagnosis was obtained following the consultation of 2.7 (2.6) doctors, ranging from 2.3 (1.8) in the Netherlands to 3.2 (4.0) in France, over a mean period of 20.4 (23.9) months, ranging from 12.2 (19.0) in Spain to 31.8 (30.0) in the UK.

Dalsgaard et al. (2014) [44]

Denmark

Prospective population-based (From birth until date of death or December 31, 2010)

To examine whether gender and injuries in early childhood were associated with later being prescribed ADHD medication in 3 groups of patients (with ADHD, ASD, and OPD).

Within the cohort of all persons born in Denmark between 1990 and 2001 (n = 852,711), three mutually exclusive groups of patients was identified: 11553 ADHD, 9698 ASD or 48,468 OPD

ICD-10

Age at first psychiatric diagnosis of:

- ADHD: Mean (SD) =9.81 (3.85)

- ASD: Mean (SD) =8.40 (4.06)

- OPD: Mean (SD) =11.40 (5.26)

Genuneit et al. (2014) [45]

Germany

Population-Based prospective birth cohort (From birth in 2000/2001, with follow-up up to age 11)

To investigate the association between Atopic Eczema and ADHD diagnosis, to further determine the temporal sequence, especially with respect to the ages at diagnosis.

770 children. The cumulative incidence of ADHD was 6.2% up to age 11 years (n = 48).

We excluded women who left the hospital immediately after birth, gave birth at < 32 gestational weeks, had a child of < 2500 g, or whose infant was transferred to pediatric care after delivery. We also excluded women who were not speaking German, Turkish, or Russian, the languages in which study material and questionnaires were available.

Parental-reported diagnosis and medication

Among the 48 children with ADHD, 21 were diagnosed up to age 8 years and 27 were diagnosed between 9 and 11 years.

Steinhausen and Bisgaard (2014) [46]

Denmark

Representative study based on a large nationwide psychiatric sample (ADHD diagnosis in the years between 1994 and 2010)

To investigate the risk of various medications in comparison to a control group of non-medicated patients with ADHD, and furthermore risk factors including various co-morbid disorders, duration of medication, age at onset of medication, and year of birth for developing SUD.

20,742 ADHD patients aged between 3 and 60 years

ICD-10

The mean AD was 15.20 (SD = 10.08) years.

Sucksdorff et al. (2015) [47]

Finland

Nationwide, nested, case-control (Born between January 1, 1991, and December 31, 2005, followed until December 31, 2011)

To examine the association between gestational age and ADHD by each gestational week. To study the association of weight for gestational age and ADHD.

10,321 children with ADHD were included in the study. Each patient was matched with 4 controls.

Children who had received an ADHD diagnosis before the age of 2 years, but not after that, were excluded. Children diagnosed with severe or profound mental retardation also were excluded. Children for whom information on gestational age or birth weight was not available or clearly inaccurate were excluded.

ICD-9 from 1987 to 1995; ICD-10 since 1996. 88% of subjects met DSM-IV criteria

The mean AD was 7.6 years (SD 2.9 years, range: 3–19 years).

van den Ban et al. (2015) [48]

the Netherlands

Cohort of ADHD patients diagnosed between January 1999 and December 2010

To analyse differences in starting and discontinuation of ADHD medication between native Dutch youth and those with a Moroccan, Turkish or Surinam cultural background with ADHD

817 (11.6% of total patients) patients that had a diagnosis of ADHD. All patients were younger than 19 years at the time of diagnosis.

598 patients were Dutch natives, 143 Moroccans, 52 Turks and 24 of Surinam’s.

younger than 19 years at the time of diagnosis. Had at least 6 months of history in the composed database before the ADHD diagnosis and could be followed for at least 6 months afterwards.

Diagnosis of ADHD at Altrecht (a large institute for mental health care) identified from the Psychiatric Casus Register.

Almost 60% of the patients are diagnosed at the age of 6–11 year old.

Mean (SD) age at ADHD diagnosis, years: -Overall: 10.1 (3.5); −Dutch natives: 10.1 (3.5); Moroccans: 9.8 (3.3); Turks: 11.4 (3.8); −Surinam’s: 10.7 (3.7).

Total sample age at ADHD diagnosis: 0–5 yrs. 5.6%; 6–11 yrs. 62.8%; 12–18 yrs. 31.6%.

Dutch natives age at ADHD diagnosis: 0–5 yrs. 6.2%; 6–11 yrs. 63.0%; 12–18 yrs. 30.8%.

Maroccan age at ADHD diagnosis: 0–5 yrs. 4.9%; 6–11 yrs. 67.1%; 12–18 yrs. 28.0%.

Turkish age at ADHD diagnosis: 0–5 yrs. 3.8%; 6–11 yrs. 50.0%; 12–18 yrs. 46.2%.

Surinam age at ADHD diagnosis: 0–5 yrs. 0.0%; 6–11 yrs. 58.3%; 12–18 yrs. 41.7%.

Caci et al. (2016) [49]

France

Multicentric, cross sectional (Between November 4, 2013 and January 31, 2014)

To describe the health care trajectories in a sample of French children with ADHD

All the 473 patients in the series were under age of 18 (median age was 11.0 years); 382 were boys (81%).

no exclusion criterion was defined

under the age of 18 in whom ADHD diagnosis had been confirmed by the clinician

ADHD diagnosis confirmed by physician

AD: Mean (SD) = 8.07 (2.19); Median = 7.5.

AO noticed by caregivers: Mean (SD) = 4.45 (2.25).

Age at the first symptoms noticed outside the family: Mean (SD) = 5.00 (2.30).

Lemcke et al. (2016) [50]

Denmark

Longitudinal (from birth until their first ADHD diagnosis or to the end of follow-up on 8 February 2012)

To investigate if children that are later diagnosed with disorders of attention and activity, already early in life have deviations in early development that can differentiate them from children with typical development.

2034 ADHD (F90.0, F90.1, F98.8) cases were included in the study, which corresponds to 2.7% of the study population.

24 children diagnosed with ADHD before 3 years of age were excluded.

Mean (SD) [Range] age at end of follow-up, years: ADHD cases 11.4 (1.30) [8.7–13.9]; Study cohort 11.3 (8.6) [13.9–1.35].

children diagnosed with ADHD before 3 years of age were excluded. Indication for treatment was narcolepsy were removed from the cohort.

ICD-10

Mean (SD) [Range] AD, years = 8.4 (1.98) [3.0–13.4]

Rheims et al. (2016) [51]

France

Multicentre prospective observational (Enrolment between November 2011 and September 2014, follow-up 12–16 week)

To investigate the association between the presence of ADHD and the type of epilepsy, the duration of epilepsy, the seizure frequency, the antiepileptic treatments, the co-occurrence of other psychiatric comorbidities.

160 patients aged between 6 and 16 years completed the follow-up, including 58 in whom Methylphenidate (MPH) had been initiated at study entry. 68 children (42.5%) had ADHD-I and 92 (57.5%) had ADHD-C.

(1) age ≥ 6 years and < 16 years; (2) patients having epilepsy according to International League Against Epilepsy (ILAE) classification14 regardless of underlying epilepsy syndrome, seizure frequency, or ongoing antiepileptic drug treatment; (3) diagnosis of ADHD of Inattentive subtype (ADHD-I) or combined Inattentive/Hyperactive-

Impulsive subtype (ADHD-C) according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria except for the criterion of onset before age of 715; (4) no ongoing specific ADHD treatment, including methylphenidate and atomoxetine.

DSM-IV

ADHD-RS

Mean ± SD AO of ADHD symptoms, years:

- Overall sample: 5.4 ± 1.9, range= [2–13]

- Patients not treated: 5.3 ± 1.8 years

- Patients treated with MPH: 5.6 ± 2.1

Sollie and Larsson (2016) [52]

Norway

Follow-up 2007–2008

To examine the associations between child symptoms, demographic variables and the following parent and family characteristics.

Parents of 214 children (mean age at follow-up: 12.6 years, SD = 2.1) with Hyperkinetic disorders recruited from five child and adolescent mental health outpatient clinics.

children with Hyperkinetic disorders

ICD-10

DBRS

Mean age at follow-up: 12.6 years, SD = 2.1.

The mean interval from the time of diagnosis to follow-up was 3.7 years (SD = 2.2) and ranged from 1 to 10 years.

van Lieshout et al. (2016) [53]

the Netherlands

Follow-up (Enrolment between 2003 and 2006, follow-up on average 6 years)

To investigate ADHD persistence rates, comorbidity rates, symptom severity, overall functioning and the impact of continued pharmacological treatment.

347 participants with ADHD-combined type aged 5–19 years. Mean age at baseline was 11.4 years (SD = 2.8) and mean age at follow-up was 17.4 (SD = 2.8).

age of 5–19 years, Caucasian descent, IQ ≥70, no diagnosis of autism, epilepsy, general learning difficulties, brain disorders and known genetic disorders. Only participants with a diagnosis of ADHD/C based on the algorithm at baseline were included in the current study.

DSM-IV, DSM-5

CPRS-R:L; CTRS-R:L; CAARS-S:L; SDQ; PACS, symptoms as defined by DSM-IV-TR, K-SADS-PL

Mean AO of the first symptom = 2.25 (SD = 1.52) years.

Abel et al. (2017) [54]

Norway

Large Prospective Cohort of women pregnant in their first trimester from all over Norway during the years 1999 to 2008.

To explore the association between iodine intake from food in pregnancy (as a proxy for long-term iodine intake and status) and (i) risk of specialist-diagnosed ADHD in the child and (ii) maternal report of child ADHD symptoms at eight years of age.

77,164 mother-child pairs were included in this study. ADHD diagnosis was registered in 1725 children (2.2%) by December 2015

ICD-10

The median AD was 8.2 years (IQR: 7.0, 9.5 years).

Bachmann et al. (2017) [55]

Germany

Observational; Nationwide routine data of patients diagnosed between 2009 and 2014

To investigate frequency of diagnosis and treatment for ADHD in children, adolescents, and adults, changing between 2009 and 2014 and transition.

In 2009 there were 214,110 members of the Germany’s largest statutory health insurance company aged between 0 and 69 years (71.4% male, mean age 13.5 [± 31.9] years) with a diagnosis of ADHD; in 2014 there were 274,982 (69.7% male, mean age 14.6 [± 35.1] years).

all insurants with a diagnosis of ADHD who were 15 years old in 2008 and who had been continuously insured until 2014.

ICD-10

Graphical representation of ADHD diagnoses in insureds for 2009 and 2014 by age and sex, based on routine data (administrative prevalence). Modal class: 10–14 years

Balboni et al. (2017) [56]

Italy

A posteriori investigation of information derived from a national database

To investigate which item subsets of the Vineland-II can discriminate children with ADHD or specific learning disorders from peers with typical development.

24 children with ADHD (5–14 years), 61 elementary students with specific learning disorders (6–11 years), and 85 controls with typical development (5–14 years).

Italian native speakers and attended a regular education program. T

DSM-IV-TR

diagnosis of ADHD was based on a testing battery assessing attentional and executive functions and on questionnaires given to parents and teachers to evaluate the presence of psychological problems. WISC-III

Children received the diagnosis of ADHD at a mean age of 9 years (range: 5–15 years).

Chen et al. (2017) [57]

Sweden

Cohort (born between 1985 and 2006, followed from their third birthday to 31 December 2009 for ADHD diagnosis)

To estimate the strength and pattern of the familial aggregation of ADHD with greater precision than previously reported.

During the follow-up, 31,865 out of 1,656,943 individuals received ADHD diagnosis

ICD-9 during 1987–1996 and ICD-10 from 1997 onwards; or DSM-IV

Graphical representation of cumulative incidence of ADHD diagnosis among all siblings and all cousins.

Median class: 10–15 years

Pohlabeln et al. (2017) [58]

Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden

Prospective multi-centre cohort

To investigate whether in addition to established early risk factors other, less studied pre-, peri-, and postnatal influences, like gestational hypertension or neonatal respiratory disorders and infections, may increase a child’s risk of developing ADHD.

A total of 15,577 children from 8 European countries were included in the analyses (age range: 2–11.9 years, mean age: 6.2 years, SD: 1.9 years).

192 (15 Belgium, 28 Cyprus, 22 Estonia, 42 Germany, 35 Hungary, 8 Italy, 33 Spain and 9 Sweden) were classified as affected by ADHD.

Parent-reported ADHD diagnosis by a physician or medical health professional

AD:

≤ 4 n = 13 (6.8%)

(4–6] n = 34 (17.7%)

(6–8] n = 93 (48.4%)

≥ 8 n = 52 (27.1%)

Sayal et al. (2017) [59]

Finland

Nationwide population-based

To investigate whether relative age is associated with ADHD diagnosis in a country where prescribing rates are low and whether any such association has changed over time or relates to comorbid disorders.

6136 children born between Jan 1, 1991, and Dec 31, 2004, who were diagnosed with ADHD from age 7 years onwards.

children with severe or profound intellectual disability

children diagnosed with ADHD from age 7 years onwards.

ICD-10

The mean AD in the sample was 9.4 years (standard deviation: 2.4; range: 7–19 years).

Bonati et al. (2018) [60]

Italy

Clinical multicentre; review of patient medical records between September 2011, and December 2017

To confirm the association between relative age (defined as the child’s age within their school year) and ADHD in a different additional national context.

4070 children from age 6 years onwards.

2856 of 4070 subjects evaluated (70%) met the diagnostic criteria for ADHD.

children with severe or profound intellectual disability were excluded

children diagnosed with ADHD from age 6 years onwards.

DSM-IV-TR

WISC-III; K-SADS, CBCL, CPRS-R, CTRS-R, CGI-S

The mean AD was 9.3 years (SD 2.5, range 6–17).

Cornu et al. (2018) [61]

France

Double-blind placebo-controlled randomised trial between 2009 and 2011

To investigate the effects of omega-3 supplements in children with ADHD.

162 children aged 6–15 years (Treated n = 80; Placebo n = 82)

known intolerance to omega-3 fatty acids, intake of fatty acid/fish oil dietary supplements for more than 1 week during the 3 months preceding inclusion, or MPH or other ADHD drug during the month preceding inclusion. Children who required MPH treatment were also excluded to ensure equipoise.

children and adolescents aged 6–15 years referred for hyperactivity symptoms to five reference centres for learning disabilities in France.

DSM-IV-TR

CGI-S

Mean (SD) AD: DHA–EPA 7.0 (3.0); Placebo 6.9 (2.9)

Prasad et al. (2018) [62]

UK (England)

Population-based cohort study

To provide estimates of the risk of fractures, thermal injuries, and poisonings in young people with/ without ADHD

15,126 young people with and 263,724 without ADHD

CYP aged 3 to 17 years during the study period of 1998–2012, with at least one diagnosis code or at least one drug code for ADHD in the CPRD, were included in the population of CYP with ADHD.

ICD-10

AD:

3–4 years 7.7%

5–9 years 51.2%

10–14 years 35.4%

15–17 years 5.7%

Dalsgaard et al. (2019) [63]

Denmark

Cohort study included all individuals born from January 1995 through December 2016 and followed up from birth until December 2016

To estimate age- and sex-specific incidence rates and risks of being diagnosed with any mental disorder during childhood and adolescence

99,926 individuals were diagnosed with a mental disorder before 18 years of age. Among these, 30,776 had ADHD diagnosis

ICD-10-DCR

Incidence peaked earlier in boys than girls in ADHD (8 vs 17 years of age)

Granström et al. (2019) [64]

Sweden

Nationwide, population-based cohort study with an observational period from January 1964 to December 2013.

To assess if individuals with Hirschsprung disease have an increased risk for ADHD

739 individuals with HSCR and 7390 controls. Twenty-six of the individuals with HSCR and 202 of the 7390 controls had ADHD.

Exclusion criteria were applied only to HSCR to avoid including neonates with suspected HSCR admitted for rectal suction biopsies where the biopsies turned out to be negative or patients admitted only to a hospital not providing pediatric surgery.

Prescription of any drug used in the treatment of ADHD used as a proxy for the diagnosis.

The mean age at diagnosis of ADHD was not different between the groups, 18.1 years (SD = 8.4) vs 16.7 years (SD = 7.8), p = 0.39.

Hoang et al. (2019) [65]

UK

Cross-sectional database study of a national surveillance network of children under 19 years of age between January and December 2016

To describe variations in age of ADHD diagnosis and stimulant prescribing among general practitioner practices in a nationwide network and identify factors that might account for these variations.

3470 children with a coded diagnosis of ADHD

3470 children under 19 years of age with a coded diagnosis of ADHD within the RCGP RSC network were included in the study

Read code

The mean age of first ADHD diagnosis was 10.5 years (95% CI 10.1 to 10.9, median 10, IQR 9.0–11.9)

Root et al. (2019) [66]

UK

Population-based cohort study used electronic record data collected before January 3, 2017, from more than 700 general practices

To estimate the associations with intellectual disability and ADHD and investigate association between relative age and childhood depression.

1,042,106 children aged 4 to 15 years

Children receiving an outcome diagnosis before study entry or with missing sex were excluded.

all children who were registered before January 3, 2017, at a general practice contributing high-quality data to the Clinical Practice Research Datalink (CPRD), and younger than 16 years at the last data collection at that general practice. Children were included from their imputed fourth birthday or from 12 months after registering at a practice contributing research quality data to CPRD, if later.

Read code

Median age at ADHD diagnosis was 8.0 years (IQR, 6.7–9.7)

Sun et al. (2019) [67]

Sweden

Prospective cohort study used national registers to identify individuals born from January 1983, through December 2009

To investigate the all-cause and cause-specific mortality risks in ADHD and to explore the potential role of psychiatric comorbidities

2,675,615 individuals with a mean (SD) age at study entry of 6.4 (5.6) years and a mean (SD) follow-up of 11.1 (3.1) years: 1374790 were male (57,919 with an ADHD diagnosis) and 1,300,825 were female (28,751 with an ADHD diagnosis).

all individuals born in Sweden from January 1, 1983, through December 31, 2009, who were alive and residing in Sweden on their 1-year birthday or January 1, 2001 and followed up until death, emigration from Sweden, or December 31, 2013, with the oldest cohort member censored at 31 years of age.

ICD-10

The mean (SD) AD was 14.3 (5.7) years; 13.5 (5.5) years for male and 16.0 (5.6) for female individuals.

Sourander et al. (2019) [68]

Finland

Population-based case-control study

To investigate the association between maternal cotinine levels during pregnancy and ADHD diagnosis in offspring

1079 patients born between 1998 and 1999 and diagnosed with ADHD and 1079 matched controls

ICD-10

The mean AD was 7.3 years (SD: 1.9; range: 2–13.7 years).

Taylor et al. (2019) [69]

Sweden

Population based twin study focused on all birth cohorts between 1992 and 1999

To investigate the degree to which individuals first receiving community diagnoses of ADHD as adults would display discernible signs of neuropsychiatric impairments as children.

662 individuals with diagnoses of ADHD and 14,474 individuals were the comparison group

All diagnoses were required to have been assigned prior to the age of 18.

All diagnoses were required to have been assigned prior to the age of 18.

ICD-10

74 individuals diagnosed after age 18;

394 diagnosed between the ages of 12–18;

194 diagnosed prior to age 12