Table 1.
Summary of the eight studies included in the meta‐analysis
| Study | Quality ratinga | Methadone‐exposed | Unexposed | Ageb | Drug informationc | Assessment tool | Main findingsd (results appear as methadone vs unexposed) | Commentse |
|---|---|---|---|---|---|---|---|---|
| Strauss et al.35,f | B | 25 | 26 | 3mo |
No dosing information No drug screening or polydrug information |
BSID (MDI, PDI) at all ages | 6mof: MDI 115.7 (16.8) vs 114.3 (20.9), PDI 109.4 (12.2) vs 111.7 (14.5) |
Original cohort 60 methadone‐exposed infants vs 53 unexposed infants (no information on matching); data reported only for infants who underwent BSID at all three time points. Attrition rate at 6mo was 58.4% vs 51%. One case of SIDS in the methadone‐exposed group. Gestational age at birth not stated. Assessor blinding not stated. No information about NAS or treatment. |
| 25 | 26 | 6mof | ||||||
| 25 | 26 | 1y | ||||||
| Kaltenbach et al.40,g | B | 26 | 27 | 1y |
Mean dose for 1y cohort: 30; mean dose for 2y cohort: 18 No drug screening or polydrug information |
BSID (MDI) at all ages | 2yg: MDI 90.88 (8.26) vs 94.62 (11.93) ns |
Original cohort 43 methadone‐exposed infants vs 51 unexposed (matched for maternal SES, ethnicity and medical conditions). Attrition rate at 2y 60.5% vs 53%. Assessors blinded to group. 62% 1y‐olds and 67% 2y‐olds had been treated for NAS in the neonatal period. No pharmacological agent stated |
| 17 | 24 | 2yg | ||||||
| Chasnoff et al.36,f,g | B | 31 | 34 | 3mo |
Mean dose 14.6±10.2 (5–40) Maternal interview and urine screening; 4 out of 31 used drugs in addition to heroin during pregnancy |
BSID (MDI, PDI) at all ages |
6mof: MDI 105.9 (12.4) vs 111.0 (12.3); PDI 103.9 (9.0) vs 107.6 (15.1) 2yg: MDI 97.5 (16.1) vs 96.2 (15.9); PDI 99.3 (16.9) vs 98.2 (8.9) No p‐values stated |
Original cohort 39 methadone exposed vs 34 unexposed (matched for maternal age, education, gravidity, and smoking). Attrition rate at 6mo was 66.7% vs 14.7%; at 2y attrition rate was 84.6% vs 58.8%. All infants were born at term. Assessor blinding not stated. No information about NAS or treatment. |
| 13 | 29 | 6mof | ||||||
| 11 | 27 | 1y | ||||||
| 6 | 14 | 2yg | ||||||
| Rosen and Johnson37,f,g | B | 41 | 23 | 6moa,f |
42 (mean of original cohort) Maternal urine screening; 56% of original cohort polydrug use (BDZ, opiates, cocaine, barbiturates, TCA) 15% reported ‘mod‐severe’ alcohol intake |
BSID (MDI, PDI) at 6mo, 12mo, 18mo, and 2y; M‐P at 3y |
6mof: MDI 95 (2.5) vs 100.7 (4.2), ns, PDI 101 (2.8) vs 105.1 (2.9), ns 2yg: MDI 90.4 (2.6) vs 96.9 (3.1) ns PDI 99.1 (2.7) vs 108 (2.7), p=0.05 All scores are mean (standard error)h |
Original cohort 61 methadone‐exposed infants vs 32 unexposed infants (matched for maternal ethnicity, SES, infant sex, birthweight, and gestational age). Attrition rate at 6mo was 32.8% vs 28.1%; at 2y was 44.3% vs 31.3%. Both groups included infants born preterm. Assessor blinding not stated. 75% methadone‐exposed had NAS; number treated pharmacologically not stated |
| 41 | 22 | 1y | ||||||
| 38 | 23 | 18mo | ||||||
| 34 | 22 | 2ya,g | ||||||
| 39 | 21 | 3y | ||||||
| Kaltenbach and Finnegan38,f,g | B | 27 | 17 | 6mof |
Mean dose 38.42 No drug screening or polydrug information |
BSID (MDI) at 6mo, 1y, and 2y; MSCA (GCI) at 3y 6mo–4y 6mo |
6mof: MDI 107.9 (12.23) vs 105.6 (7.31), no p‐value 2yg: MDI 100.9 (18.04) vs 103.9 (11.49) no p‐value |
No information about original cohort, therefore attrition rates unknown. Unexposed group were matched for maternal ethnicity and SES. Mean gestational age infants not stated. Blinding of assessors not stated. 92% were treated for NAS; pharmacological agent not stated. |
| 27 | 17 | 1y | ||||||
| 27 | 17 | 2yg | ||||||
| 27 | 17 | 3y 6mo– | ||||||
| 27 | 17 | 4y 6mo | ||||||
| Wilson41,g | B | 33 | 54 | 9mo |
No dosing information Maternal urine screening; 93% used psychoactive drugs |
BSID (MDI) at 9mo, 18mo, and 2yc | 2yg: MDI 88.8 (15.5) vs 90.2 (14.6) ns | Original cohort 39 methadone‐exposed vs 57 unexposed infants (matched for maternal age, ethnicity, SES, and marital status). Attrition rate at 2y was 18% vs 16%. Mean gestational age not stated for either group. Assessor blinding not stated. 87% original cohort treated for NAS, pharmacological agent not stated. |
| 29 | 42 | 18mo | ||||||
| 32 | 48 | 2yg | ||||||
| 26 | 41 | 3–5y | ||||||
| 12 | 12 | 6–11y | ||||||
| van Baar39, f,g | B | 21 | 37 | 6mof |
No dosing or screening information; Original cohort; six IV drug users; 94% used multiple drugs; 60% use cocaine |
BSID (MDI, PDI, NDI) at all ages WWPAf at 18mo (n=14), 2y (n=16), and 2y 6mo (n=15) |
6mof; MDI 103 (12) vs 107 (13), PDI 116 (18) vs 114 (21), NDI 105 (13) vs 109 (14) 2yg: MDI 86 (15) vs 98 (16) p<0.05 PDI 102 (16) vs 100 (18) ns, NDI 93 (16) vs 102 (22) |
Original cohort 35 methadone‐exposed vs 37 unexposed infants (not matched). Attrition rate at 6mo was 19.2% vs 0% and at 2y was 19.3% vs 8.1%. Assessor blinding not stated. 28 out of 35 (80%) were treated for NAS, pharmacological agent not stated. |
| 21 | 34 | 1y | ||||||
| 18 | 34 | 18mo | ||||||
| 21 | 34 | 2yg | ||||||
| 19 | 34 | 2y 6mo | ||||||
| Hans and Jeremy42, g | B | 33 | 45 | 4mo |
Mean <20 (range 3–40) Maternal interview and MUS; 13 out of 33 cocaine, 18 out of 33 cannabis, 11 out of 33 alcohol use |
BSID (MDI, PDI) at all ages | 2yg: MDI 92 (12.7) vs 96 (12.3); PDI 100 (14.2) vs 108 (14.9) |
Original cohort 47 methadone‐exposed vs 45 unexposed infants (matched for maternal age, SES, and IQ). Attrition rate 29.8% vs 0%. Assessors blinded to group. No information about NAS or treatment. |
| 33 | 45 | 8mo | ||||||
| 33 | 45 | 1y | ||||||
| 33 | 45 | 18mo | ||||||
| 33 | 45 | 2yg |
aQuality rating: A, good; B, intermediate; C, poor; based on modified Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria (Table SI, online supporting information). bAge expressed in months (mo) or years (y). cDrug information includes mean daily methadone dose (in milligrams), maternal urine screening, and/or infant urine screening for drug exposure 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. dFull details from these studies is available in Table SII (online supporting information). Scores are presented as mean values (standard deviation) unless otherwise stated. eComments include information on attrition, matching, gestation, blinding, proportion of infants treated for NAS, and pharmacological treatment for NAS, where provided in the original study. fStudies included in meta‐analysis at 6mo. gStudies included in meta‐analysis at 2y. hStandard errors were converted to standard deviations for the meta‐analysis. BSID, Bayley Scales of Infant Development; MDI, Mental Developmental Index; PDI, Psychomotor developmental Index; SIDS, sudden infant death syndrome; NAS, neonatal abstinence syndrome; SES, socio‐economic status; BDZ, benzodiazepine; TCA, tricyclic antidepressant; M‐P, Merrill‐Palmer Scale; MSCA, McCarthy Scales of Childhood Abilities; GCI, General Cognitive Index; ns, not significant; IV, intravenous; NDI, non‐verbal developmental index; WWPA, Werry‐Weiss Peters Activity Scale; MUS, maternal urine screening.