Table 1.
Characteristics of studies included in meta-analyses of prenatal, birth, and postnatal risk factors for attention-deficit/hyperactivity disorder
| Study | Risk Factors (Included) | Sample size | Age at Outcome Measurement (Years) | Male (%) | ADHD Measurement (Included) | Sample (country) | Measurement |
|---|---|---|---|---|---|---|---|
| Ben Amor et al. (2005) | Labor Complications; Neonatal Illness | 100 | 8.8–10.1 | 34–90 | Diagnosis (clinical, DSM-IV) | Clinical, outpatient research survey/interview including siblings without ADHD as control (Canada) | Retrospective parent report of perinatal factors |
| Bhatia et al. (1991) | Mode of Delivery; Pregnancy Complications | 224 | 3–12 | 85.7 | Diagnosis (clinical, DSM-III) | Clinical, outpatient research survey/interview of children screened in pediatric hospital (India) | Retrospective parent report of pregnancy-related factors |
| Böhm et al. (2019) | Preeclampsia | 13,192 | 7 | 50.6 | Parent report of physician-diagnosed ADHD; SDQP | Cohort Study (MCS) (United Kingdom) | Maternal report |
| Bos-Veneman et al. (2010) | Labor Complications; Neonatal Illness | 65 | 12.2 | 88 | ADHD symptoms (ADHD Rating Scale-TV)P | Clinical, outpatient research survey/interview of children identified in psychiatric clinic (The NetherlandsNetherlandsNetherlands) | Retrospective parent report of perinatal factors |
| Brionet al. (2011) | Pregnancy Weight | 4,873 | 3–4 (47 months) | n/a | ADHD symptoms (SDQ)P | Birth cohort (ALSPAC; United Kingdom) | Self-report of pre-pregnancy weight at enrollment during pregnancy |
| Pregnancy Weight | 2,483 | 3 | n/a | Inattention (CBCL attention problems)P | Birth cohort (Generation R; The Netherlands) | Self-report of pre-pregnancy weight at enrollment postpartum | |
| Chandola et al. (1992) | Apgar Score; Neonatal Illness; Pregnancy Complications | 24,672–24,785 | 3–6 | 51–68.2 | Hyperactivity (Referral to clinic for hyperactivity) | Birth cohort (CBS; Wales) | Pregnancy-related information recorded on birth records prior to maternity hospital discharge |
| Chen et al. (2019) | Perinatal Asphyxia | 4,750 | 10.8 | 77.5 | Clinical diagnosis (ICD-9) | Taiwan Longitudinal Health Insurance Database (Taiwan) | Health insurance database |
| Claycomb et al. (2004) | Labor Complications; Mode of Delivery | 130 | 8.49–10.65 | n/a | Diagnosis (ADHD prescription medication bottle) | Research survey with recruitment through advertisements (USA) | Retrospective parent report of perinatal factors |
| Clements et al. (2015) | Apgar Score, Mode of Delivery | 7,874 | 2–19 | 71.2–73.5 | Diagnosis (ICD-9, DSM-IV) | Matched case control study using electronic health records (USA) | Electronic health records |
| Curran et al. (2016) | Mode of Delivery | 1,722,548 | <3 | 51.4 | Diagnosis (ICD-10) or medication treatment | Cohort study using linked data from National Patient Register and Multi-generation Register (Sweden) | Medical birth register |
| Dachew et al. (2019) | Preeclampsia | 6,597 | 7 | n/a | Diagnosis (DAWBA, DSM-IV)P | ALSPAC (United Kingdom) | Medical record review |
| de Bruin et al. (2006) | Testosterone | 153 | 9.08 | 100 | Diagnosis (clinical, DSM-IV) | Clinical, outpatient research study of children identified in psychiatric clinic; controls recruited from a school (The Netherlands) | Right hand 2nd:4th digit ratio |
| D’Souza et al. (2019) | No Breastfeeding | 6,246 | 2 | n/a | Inattention/hyperactivity (SDQ)P | Longitudinal prospective birth cohort (Growing Up in New Zealand; New Zealand) | Prospective maternal report |
| Fianu and Joelsson (1979) | Mode of Delivery | 1,921 | n/a | n/a | ADHD symptoms (Impulsivity, Hyperkinetic syndrome. Retrospective report of behavior from birth to study date)P | Case reports of premature and breech delivery collected at birth (Sweden) | Retrospective parent report of behavior and achievement from birth to study date |
| Fink et al. (2007) | Testosterone | 58 | 5–7 | 43.1 | Hyperactivity (SDQ)P | School based research study (United Kingdom) | Right hand 2nd:4th digit ratio |
| Testosterone | 56 | 6–11 | 51.8 | Inattention (CBCL attention problems)P | School based research study (Austria) | Right hand 2nd:4th digit ratio | |
| Froehlich et al. (2009) | Neonatal Illness | 2,528 | 8–15 | 63.5 | Diagnosis (DISC-IV, or parent report of previous diagnosis, and treatment with ADHD medication in past year)P | National survey (NHANES; USA) | Retrospective parent report of care in NICU |
| Getahun et al. (2013) | Apgar Score; Labor Complications; Mode of Delivery; Neonatal Illness; Perinatal Asphyxia; Preeclampsia; Pregnancy Complications |
81,678 | 8 | 50.5–74.3 | Diagnosis (medical record of diagnosis and at least 2 ADHD prescriptions) | Nested case-control study (USA) | Medical records (Kaiser Permanente Southern California) |
| Guhn et al. (2020) | Apgar Score, Mode of Delivery | 134,094 | 5.7 | 51 | ADHD symptoms (EDI)T | Cohort study using linked records (Canada) | Linked population-based vital statistics (birth records), and child survey data |
| Gurevitz (2014) | Mode of Delivery | 116 | 7.77–8.17 | 65.5–69 | Diagnosis (clinical, DSM-IV) | Retrospective study (Israel) | Review of well-baby clinic records |
| Gustafsson and Källen (2011) | Apgar Score; Mode of Delivery; Preeclampsia | 32,012 | 5–17 | 51–87 | Diagnosis (clinical, DSM-m-R or DSM-IV) | Case-control study linking medical records (Sweden) | Medical birth registry |
| Gustavson et al. (2019) | Pregnancy Complications |
99,947 | 7.4–17.3 | 51.2 | ADHD diagnosis (ICD-10); ADHD rating scale (DSM-IV) | Norwegian Mother and Child Cohort Study (Norway) | Prospective maternal report |
| Han et al. (2015) | Labor Complications | 19,940 | Elementary school age (<9—>12) | 49.4 | ADHD symptoms (Korean version of the DuPaul Rating Scale, K-ARS)P | School-based survey of parents (South Korea) | Parent report |
| Hanć et al. (2018) | Apgar Score | 278 | 6–18 | 100 | Diagnosis (ICD-10, DSM-IV; Conners’ Parent Rating Scale, Diagnostic Structured Interview for ADHD and Hyperkinetic Disorder) | Poland | Medical registry |
| Hoffman et al. (2010) | Neonatal Illness | 578 | 12–15 | 47.7–80.4 | Diagnosis (parent report of previous diagnosis)P | National survey (NHANES; USA) | Retrospective parent report of care in NICU |
| Ji et al. (2018) | Mode of Delivery, Pregnancy Complications | 1,479 | 7–12 | 48.1 | Diagnosis (ICD-9, ICD-10 codes in medical records) | Prospective birth cohort study using medical records (BBC; USA) | Medical records |
| Jin et al. (2014) | Mode of Delivery, Perinatal Asphyxia | 5,648 | 5–15 | 39.2 | Clinical ADHD diagnosis (DSM-IV) | School-based sample, Zhabei District, Shanghai (China) | Retrospective parent report |
| Jo et al. (2015) | Pregnancy Weight | 1,311 | 6 | 49.9 | Diagnosis (Parent report) and ADHD symptoms (SDQ)P | Nationally distributed longitudinal study (IFPS II, USA) | Maternal report |
| Joelsson et al. (2016) | Apgar Score | 48,943 | 6–20 | n/a | ADHD diagnosis (ICD-9, ICD-10) | Nationwide register study based on a nested case-control design (Finland) | Linkages of three national registers: FHDR FMBR, Finnish Central Population Register |
| Julvez et al. (2007) | No Breastfeeding | 199 | 4 | 50.2 | ADHD symptoms (ADHD-DSM-IV questionnaire)T | Birth cohort (Spain) | Maternal report of breastfeeding obtained by questionnaire at 1 and 4 years, or at 6 months, 14 months, and 2 years (child age) |
| Kadziela-Olech and Piotrowska-Jastrzebska (2005) | Apgar Score; Labor Complications; Pregnancy Complications | 100 | 7.3–7.8 | 85 | Diagnosis (Behavioral Scale of ICD-10 criteria)P, T | School-based Research study (Poland) | Retrospective parent report of pregnancy-related factors |
| Küllén et al. (2011) | Apgar Score; Pregnancy Weight; Mode of Delivery; Preeclampsia | 78,250–681,292 | n/a | n/a | Diagnosis (prescription of methylphenidate or atomoxetine recorded in drug register) | Data linkage with medical records (Sweden) | Medical birth registry |
| Kimetal. (2009) | No Breastfeeding; Mode of Delivery; Neonatal Illness | 2,419 | n/a | 48.6 | Diagnosis (DISC-IV)P | School-based research study (Seoul Child and Adolescent Mental Health Survey; Korea) | Retrospective parent report of pregnancy-related factors |
| Kosidou et al. (2017) | Apgar Score; Preeclampsia; Pregnancy Weight | 558,910 | 3–17 | 68.8 | ADHD diagnosis or treatment (ICD-10) | Matched case-control study using health and population data registers for all children bom in Sweden from 1984 to 2008 (Sweden) | Medical Birth Register (MBR) |
| Li et al. (2011) | Apgar Score | 7,246,218 | ≥3 | 82 | Diagnosis (ICD-10 diagnosis of hyperkinetic disorder recorded in one of two national registers) | Population-based cohort study (Sweden) | Medical birth registry |
| Lin et al. (2017) | Perinatal Asphyxia, Mode of Delivery | 21,243 | 1.3–5.7 | 54.6 | Hyperactivity (CPRS-48)P | School-based cohort Study (LCCS; China) | Questionnaire |
| Linnet et al. (2006) | Apgar Score | 1,355 | 3.5 | n/a | Hyperactivity (PBQ)P | Birth cohort (Denmark) | Midwife report at delivery |
| Liu et al. (2012) | Testosterone | 219 | 11 | 54.8 | Inattention (CBCL; TRF)P, T | School-based research study (China) | Right hand 2nd:4th digit ratio |
| Maher et al. (2020) | Preeclampsia | 10,692 | 3 | 51.4 | ADHD symptoms (SDQ)P | Nationally representative longitudinal study of children (GUI; Ireland) | Questionnaire, interview (maternal-report) |
| Mann and McDermott (2011) | Preeclampsia | 84,721 | 6.49 | 46.7–71.9 | Diagnosis (ICD-9, Medicaid billing data) | Data linkage with medical records (USA) | Medicaid billing data |
| Martel et al. (2008) | Testosterone | 250 | 14.67 | 56.2–63.7 | Diagnosis (clinical, K-SADS-E) and symptoms (K-SADS-E; ADHD Rating Scale)P,T | Clinical research study (USA) | Right hand 2nd:4th digit ratio |
| Martel (2009) | Testosterone | 312 | 13.31 | 50–63.1 | Diagnosis (clinical, K-SADS-E) and ADHD symptoms (ADHD Rating Scales; BASC,CRS)P,T | School, clinic, and community based research study (USA) | Right hand 2nd:4th digit ratio |
| McFadden et al. (2005) | Testosterone | 31–61 | 7–15 | 60.7 | Diagnosis (inattentive or combined type, DSM-IV-TR) | Clinical research study (USA) | Right hand 2nd:4th digit ratio |
| McIntosh et al. (1995) | Labor Complications | 209 | 9.5–10.4 | 53–85 | Diagnosis (DSM-III-R) | School-based research study (USA) | Retrospective parent report of perinatal factors (The Maternal Perinatal Scale) |
| Melchior et al. (2015) | No Breastfeeding | 1,113 | 5 | 51.4–53.4 | ADHD symptoms (SDQ)P | DEN mother-child cohort study (France) | Maternal report questionnaire |
| Mimouni-Bloch et al. (2013) | No Breastfeeding | 159 | 9.5–10.36 | 50.5–73.2 | Diagnosis (clinical) | Clinic-based research study, with sibling and non-psychiatric clinical control groups (Israel) | Retrospective parent report of breastfeeding |
| Motlagh et al. (2010) | Pregnancy Weight; Perinatal Asphyxia; Preeclampsia; Pregnancy Complications | 117 | 11.8–12.2 | 46–73 | Diagnosis (clinical, SADS-PLV) | Clinic-based research study, with population-based controls (USA) | Retrospective parent report of pregnancy and perinatal factors |
| Murray et al. (2016) | Apgar Score, Mode of Delivery | 6,849 | 7 | n/a | ADHD symptoms (SDQ), Diagnosis (DAWBA)P | ALSPAC Birth cohort (United Kingdom) | Birth records |
| Apgar Score, Mode of Delivery | 3,509 | 7 | n/a | ADHD symptoms (SDQ), Diagnosis (DAWBA)P | Pelotas birth cohort (Brazil) | Maternal interview | |
| Park et al. (2014a) | Neonatal Illness | 900 | 6–15 | 73.8–85.4 | ADHD diagnosis (DSM-IV; K-SADS-PL, DISC-IV)P | Research study with clinical recruitment of ADHD sample from hospital and school-based non-ADHD sample (South Korea) | Parent report |
| Park et al. (2014b) | No Breastfeeding | 874 | 8–11 | 58.2 | ADHD Diagnosis (DSM-IV; DISC-IV)P | School sample across five regions (South Korea) | Maternal report |
| Pineda et al. (2007) | Neonatal Illness; Perinatal Asphyxia; Preeclampsia; Pregnancy Complications | 486 | 7.9–8.3 | 47.2–74.5 | Diagnosis (DSM-IV; DICA-PR, BASC, DSM-IV ADHD Symptom Questionnaire, ADHD Checklist; all were being treated with methylphenidate) | Clinic-based research study; controls recruited from schools (Colombia) | Retrospective parent report of pregnancy-related factors as part of BASC |
| Pires et al. (2013) | Neonatal Illness | 366 | 7.9 | 50.8 | ADHD diagnosis/symptoms (CBCL, TRF)P, T | School-based research study (Brazil) | Retrospective maternal report of neonatal illness |
| Pohlabelnetal. (2017) | Mode of Delivery, Preeclampsia | 15,577 | 2–12 | 50.6 | Parent report of diagnosis | European IDEFICS prospective multicenter cohort study (Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden) | Parent questionnaire |
| Pringsheim et al. (2009) | Mode of Delivery; Perinatal Asphyxia | 353 | 9.9–10 | 76.7–83.4 | Diagnosis (clinical, DSM-IV-TR) | Clinic-based case-control research study. Cases had ADHD+Tourette syndrome (TS); controls had TS only (Canada) | Retrospective report of perinatal factors included as part of demographic form for all new patients |
| Roberts & Martel, 2013 | Testosterone | 109 | 4.82 | 46.7–72.2 | ADHD symptoms (K-DBDS, DSM-IV)P | Community-based research study (USA) | Right hand 2nd:4th digit ratio |
| Rodriguez et al. (2008) | Pregnancy Weight | 12,976 | 7–12 | 50 | ADHD symptoms (SDQ; Rutter)T | Follow-up of pregnancy cohorts (Sweden, Denmark, Finland) | Pre-pregnancy weight collected prospectively |
| Rodriguez (2010) | Pregnancy Weight | 907 | 5 | 53 | ADHD symptoms (DSM-IV, SDQ)P, T | Follow-up of pregnancy cohort (Sweden) | Early pregnancy weight recorded in Swedish Medical Birth Register |
| Russell et al. (2014) | Mode of Delivery | 8,443 | 7.2 | 50.3–82.2 | Diagnosis (parent report of previous diagnosis)P | Birth cohort (MCS; United Kingdom) | UK Birth Registration and Maternity Hospital Episode Data |
| Say et al. (2016) | Mode of Delivery, Preeclampsia, Pregnancy Complications | 180 | 3–18 | 71–78 | Clinical diagnosis (DSM-IV) | Case-control study recruited from pediatric clinics and child/adolescent psychiatry clinics (Turkey) | Maternal report |
| Sciberras et al. (2011) | Neonatal Illness | 3,477 | 6.8 | 51 | Diagnosis (parent report of previous diagnosis)P | Nationally representative population-based birth cohort (LSAC; Australia) | Retrospective parent report of whether the child required intensive care at birth |
| Shih et al. (2020) | Mode of Delivery | 16,376 | 8 | 52.5 | Diagnosis (parent report of previous diagnosis)P | National prospective longitudinal cohort study (Taiwan) | Parent report |
| Silva et al. (2014) | Apgar Score; Labor Complications; Mode of Delivery; Perinatal Asphyxia; Preeclamp- sia |
43,062 | 0–25 | 77 | Diagnosis (use of stimulant medication recorded in MODDS) | Population-based, record linkage case-control study (Australia) | Prospectively ascertained pregnancy and perinatal information obtained from MNS |
| Stadler et al. (2016) | No Breastfeeding | 474 | 7–13 | 63.9 | Diagnosis (DSM-5; KSAD-S-E, Conners, DuPaul ADHD Rating Scale IV)P | Case control cohort (USA) | Maternal report |
| St. Sauver et al. (2004) | Labor Complications | 5,631 | n/a | 50.1–75.4 | Diagnosis (algorithm based on ADHD symptoms, diagnosis, use of stimulants) | Birth cohort (USA) | Birth certificate (perinatal information) records linked to school and medical records |
| Stevenson et al. (2007) | Testosterone | 187 | n/a | 27.8 | ADHD symptoms (DSM-IV)S | School (college)-based research study (USA) | Right hand 2nd:4th digit ratio |
| Sucksdorff et al. (2018) | Preeclampsia, Pregnancy Complications, Mode of Delivery, Neonatal Illness | 49,533 | 6–20 | n/a | ADHD diagnosis (ICD-9, ICD-10) | Nested case-control study based on the Finnish Prenatal study of ADHD (Finland) | Linkages of three national registers: FHDR FMBR, Finnish Central Population Register |
| Wagner et al. (2009) | Labor Complications; Neonatal Illness | 748 | 8.13 | 49.2 | ADHD symptoms (HBQ, CBQ, DISC-IV)P | Wisconsin Twin Panel (USA) | Perinatal risk factors coded from medical records using OCS, NCS |
| Wang et al. (2019) | Mode of Delivery, No Breastfeeding | 401 | 8.6 | 79–84 | Diagnosis, (SNAP and clinical interview; DSM-IV)P | Community based case-control study (China) | Face to face interview |
| Wiggs et al. (2016) | Pregnancy Complications, Neonatal Illness | 464 | 6–17 | 55 | Diagnosis (DSM-IV ADHD Rating Scale, Conners’ Rating Scale - Revised Short Form, K-SADS-E)P,T,S | Research study recruited from community and clinics (USA) | Parent report |
| Zhu et al. (2015) | Mode of Delivery, No Breastfeeding, Pregnancy Complications, Pregnancy Weight |
1,765 | 4 | 54 | ADHD symptoms (Conners’ Hyperactivity IndexP | Research study recruited prenatally from hospital (China) | Parent interview and medical records |
ADHDT The Attention Deficit Hyperactivity Disorder Test, ALSPAC Avon Longitudinal Study of Parents and Children, BASC Behavior Assessment System for Children, BBC Boston Birth Cohort, C-ASQ Conners abbreviated symptom questionnaire, CBCL Child Behavior Checklist, CBQ Children Behavior Questionnaire, CBS Cardiff Birth Survey, CPRS-48 Conners’ Parent Rating Scale-Revised, CRS Conners Rating Scale, DAWBA Development and Wellbeing Assessment, DEN Étude sur les Déterminants pré - et postnatals pré coces du développement psychomoteur et de la santé de l’Enfant, DICA-PR Diagnostic Interview for Children and Adolescents - Parent Revised Version, DSM-IIIR Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, DSM-TV Diagnostic and Statistical Manual of Mental Disorders, 4th edition, DSM-TV-TR Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision, DSM-5 Diagnostic and Statistical Manual of Mental Disorders, 5th edition, EDI Early Development Instrument, FHDR Finnish Hospital Discharge Register, FMBR Finnish Medical Birth Register, GUI Growing Up in Ireland, HBQ MacArthur Health and Behavior Questionnaire, IFPSII The Infant Feeding Practices Study n, IDEFICS study Identification and prevention of dietary- and lifestyle-induced health effects in children and infants, K-DBDS Kiddie-Disruptive Behavior Disorder Schedule, K-SADS-E Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children, Epidemiological Version, LCCS The Longhua Child Cohort Study, LSAC Longitudinal Study of Australian Children, MCS Millennium Cohort Study, MNS Midwives Notification System, MODDS Monitoring of Drugs of Dependence System, n/a not available, NCS Neonatal Complications Scale, NHANES National Health and Nutrition Examination Survey, NICU Neonatal intensive care unit, OCC Odense Child Cohort, OCS Obstetrical Complications Scale, PBQ Preschool Behavior Questionnaire, SADS-PLV Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, SDQ Strengths and Difficulties Questionnaire, TBCS Taiwan Birth Cohort Study, TRF Teacher Report Form
P
Parent report;
T
Teacher report;
S
Self report