Table 2.
Summary of 12 studies reporting neurodevelopmental outcomes in children beyond age 2y
| Study | Quality ratinga | Methadone‐exposed | Unexposed | Ageb | Drug informationc | Assessment tool | Main findingsd (results appear as methadone vs unexposed) |
|---|---|---|---|---|---|---|---|
| Strauss et al.48 | B | 31 | 27 | 5y | No information | MSCA | 86.8 (13.3) vs 86.2 (16.2), ns |
| Lifschitz et al.49 | B | 26 | 41 | 3y 5mo | 95% taking heroin or psychoactive drugs | MSCA | 90.4 (13) vs 89.4 (10.8), ns |
| Rosen and Johnson37 | B | 39 | 21 | 3y | 42 (mean of original cohort) | M‐P | 44.6 (2.1) vs 46.3 (2.3) ns |
| Davis and Templer53 | C | 12 | 28 | 8y 6mo | No information | WISC‐R | 89.58 (10.32) vs 96.32 (8.72) no p‐value |
| Wilson41 | B | 26 | 41 | 3–5y | No information |
MSCA (GCI) Survey and school reports IQ testing |
GCI: 90.4 (13.0) vs 89.4 (10.8) ns IQ 1–2 SD below norm 8% vs 5%, language disability 8% vs 5%, special education needs 16% vs 19%, behavioural problems 75% vs 48%, psychiatric referral 16% vs 5% |
| 12 | 12 | 6–11y | |||||
| Kaltenbach and Finnegan38 | B | 27 | 17 | 3y 6mo–4y 6mo | Mean dose 38.42 | MSCA (GCI) | GCI: 106.5 (12.96) vs 106.05 (13.10), t=0.11 |
| Sandberg et al.54 | B | 30 | 16 | 5–8y |
39.5 (males), 38.7 (females) Original cohort, 68% polydrug use; 15% moderate to heavy alcohol intake |
CGPQe
CBAQe (males only) |
Methadone‐exposed males showed more feminine game play than comparison males (p<0.04) |
| van Baar39 | B | 19 | 34 | 2y 6mo | No information |
BSID (MDI, PDI, NDI) WWPAe |
MDI 86 (15) vs 98 (16) p<0.05 PDI 102 (16) vs 100 (18) ns NDI 93 (16) vs 102 (22) WWPA 1.62 (1.03–2.66) vs 1.64 (1.28–2.52) ns |
| de Cubas and Field50 | B | 20 | 20 | 8y 6mo |
No drug information. ‘Moderate alcohol use’ |
SBIS KABC‐A RATC CBCLe |
SBIS: 97.6 vs 98.1, ns KABC‐A: 98.8 vs 102.4, no p‐value RATC: methadone‐exposed scored higher on anxiety, aggression, rejection, maladaptive outcome, p<0.01 for all CBCL: more behaviour problems p<0.05 |
| van Baar and de Graaff52 | B | 23 | 32 | 3y 6mo | Polydrug use; 16 out of 35 heroin and cocaine, only 2 out of 35 solely methadone |
SON‐IQ at 3y 6mo; RDLSC and RDLSE at 4y; RAKIT at 4y 6mo and 5y 6mo; IBR at 3y 6mo (n=22), 4y 6mo (n=23), 5y 6mo (n=22) |
SON‐IQ: 99 (9) vs 109 (11), p<0.01 RDLSC: 46 (6) vs 52 (6), p<0.01 RDLSE: 46 (9) vs 50 (6), p<0.05 RAKIT 4y 6mo: 85 (11) vs 103 (15), p<0.01 RAKIT 5y 6mo: 90 (12) vs 102 (17), p<0.05 IBR: results median (range): 3y 6mo: free of fear: 9 (4–9) vs 6.5 (2–9), p<0.05; activity level: 6 (3–9) vs 5 (2–9), p<0.05; attention: 5 (1–7) vs 5.5 (1–9) p<0.05; fine motor: 3 (1–5) vs 3 (1–5), p<0.05 4y 6mo: cooperation: 6 (2–9) vs 7 (3–9), p<0.01; endurance: 4 (2–9) vs 6 (1–9), p<0.01; attention: 8 (2–9) vs 5 (2–8), ns 5y 6mo: cooperation: 6 (1–9) vs 8 (4–9), p<0.01; free of fear: 8 (2–9) vs 9 (5–9), ns; attention: 5 (2–8) vs 5 (3–9), ns |
| 26 | 32 | 4y | |||||
| 23 | 31 | 4y | |||||
| 22 | 30 |
6mo 5y 6mo |
|||||
| Hunt et al.51 | B | 67 | 44 | 3y | No information |
SBIS; VSMS; MSCA; RDLSC and RDLSE |
SBIS: 99.9 (15.1) vs 107.5 (13.4), p<0.01 VSMSL: 38.4 (8.1) vs 46.1 (7.7), p<0.05 MSCA: 49.5 (8.7) vs 53.9 (8.3), p<0.05 RDLSC: 42.4 (11.6) vs 49.2 (11.4), p<0.05 RDLSE: 35.5 (7.9) vs 42.8 (12.8), p<0.05 |
| Konijnenberg et al.55 | B | 24 | 0 | 4y |
Mean 85.96f; polydrug use in 40% (illegal drug use), 25% alcohol |
CBCLe | Scores >55 on aggressive behaviour and withdrawn behaviour |
aQuality rating: A, good; B, intermediate; C, poor; based on modified Grading of Recommendations Assessment Development and Evaluation criteria (Table SI, online supporting information). bAge expressed in months (mo) or years (y). cDrug information includes mean daily methadone dose (in milligrams) and information on maternal polydrug use (defined as methadone plus any other drug use during pregnancy, excluding tobacco), where these are reported. Unless otherwise stated, all information in this column refers to methadone‐exposed group only. dScores are presented as mean values (standard deviation) unless otherwise stated. eQuestionnaire completed by parent or caregiver. fMean methadone dose excludes outlier daily dose of 660mg methadone. MSCA, McCarthy Scales of Childhood Abilities; ns, not significant; M‐P, Merril‐Palmer Scale; WISC‐R, Wechsler Intelligence Scale for Children–Revised; GCI, general cognitive index (used in the MSCA); SD, standard deviation; CGPQ, Child Game Participation Questionnaire; CBAQ, Child Behavior Attitude Questionnaire; BSID, Bayley Scales of Infant Development (original version 1969); MDI, mean developmental index (cognitive score); PDI, psychomotor developmental index (motor score); NDI, non‐verbal developmental index; WWPA, Werry‐Weiss Peters Activity Scale; SBIS, Stanford‐Binet Intellectual Scale; KABC‐A, Kaufman Assessment Battery for Children, achievement component (tests the acquired knowledge of fact); RATC, Robert's Apperception Test for Children (tests the child's perception of common interpersonal situations); CBCL, Child Behavior Checklist; SON‐IQ, Snijders‐Oomen Nonverbal Intelligence Test; RDLSC, Reynell Developmental Language Scales (Comprehensive); RDLSE, Reynell Developmental Language Scales (Expressive); RAKIT, Revision of the Amsterdam Children's Intelligence Test; IBR, Infant behaviour record; VSMS, Vineland Social Maturity Scale.