Table 2.
Systematic review of the randomized studies regarding the neonatal abstinence syndrome
| Author, year | Study design | No. of patients (Int. /Cont.) | Type of Opioid exposure in uterus | Intervention | Control | Drop out (%) (Int. /Cont.) | Assessment tool | Primary outcome | Results |
|---|---|---|---|---|---|---|---|---|---|
| Davis, 2018 [6] | Multi centric, randomized, double-blind, clinical trial | 59/59 | Buprenorphine/Methadone/opioids for pain decreasing in pregnancy | methadone | Morphine | 1.7/0 | Finnegan | LOS | methadone was associated with decreased mean number of days for LOS by 14% (P = .046) |
| Kraft, 2017 [7] | single-site, randomized, double-blind, clinical trial | 33/30 | Methadone/ buprenorphine | sublingual buprenorphine | oral morphine | 9/6.7 |
MOTHER NAS scale |
Median length of treatment | shorter duration in Int. group vs. Cont. group [15 d vs. 28 d(p < 0.001)] |
| Nayeri, 2015 [8] | Multi centric randomized, open-label, clinical trial | 30/30 | Opium/heroin/methadone/cocaine/methamphetamine | Phenobarbital | Oral Morphine | 0/0 | Finnegan | Mean length of treatment | Non Sig. difference for the duration of treatment between Int. group (8.5 ± 4 d) vs. Cont. (8.5 ± 5 d) (P = 0.9) |
| Bada, 2015 [1] | randomized, double-blind clinical trial | 15/16 | Methadone, Buprenorphine, Oxycodone, hydrocodone Benzodiazepines | morphine | clonidine | 0/0 | Finnegan | Median length of Treatment | Longer duration of treatment in Int. group (39 d) Vs. Cont. (28 d) (p = 0.02) |
| Brown, 2014 [9] | single-site, randomized, double-blind clinical trial | 15/16 | Methadone/ buprenorphine | methadone | morphine | 0/0 | modified Finnegan | Median length of opioid treatment | shorter duration in Int. group vs. Cont. group [14 d vs. 21 d (p = 0.008)] |
| Surran, 2013 [10] | single site, open-label, randomized clinical trial | 34/34 | Methadone/ Buprenorphine/ Oxycodone | Clonidine+ morphine | Phenobarbital +morphine | 6/0 | Modified Finnegan | Median length of morphine treatment | Longer duration of treatment in clonidine Vs. Phenobarbital group [18.2 d Vs. 13.6 d, p = 0.037)] |
| Kraft, 2011 [11] | single site, open-label, Randomized, clinical trial | 12/12 | Buprenorphine/ Methadone | Sublingual buprenorphine | Morphine | 0/0 | MOTHER NAS score | Mean length of treatment | shorter duration in Int. group vs. Cont. group [23 ± 12 d vs. 38 ± 14 d, (p = 0.01)] |
| Agthe, 2009 [2] | Multi centric, double-blind, randomized, clinical trial | 40/40 |
Methadone/ Heroin/ Cocaine |
oral clonidine/ DTO* | placebo/DTO* | 0/0 | modified Finnegan | median length of treatment | shorter duration in Int. group vs. Cont. group [11 d vs. 15 d (p = 0.02)] |
| Kraft, 2008 [12] | open-label, randomized, clinical trial | 13/13 | opioids | sublingual buprenorphine | Opium solution | 8/0 | modified Finnegan | safety, tolerability, | Length of treatment (22d Vs. 32d), length of stay (27d Vs. 38d) were not significantly different |
| Langenfeld, 2005 [13] | Randomized double-blind clinical trial | 16/17 | Morphine/ Methadone | tincture of opium | Morphine | 0/0 | Finnegan |
1.Length of treatment 2.total dose of tincture of opium needed |
Length of treatment wasn’t different significantly (26.9 d Vs.29.8 d) |
| Coyle, 2005 [14] | partially Randomized, clinical trial | 17/15 | methadone | phenobarbital/ DTO* | placebo/ DTO* | 0/0 | Finnegan |
infant neurobehaviour during the first three weeks of life. LOS |
improved orientation, quality of movement, lower total stress/ abstinence score (p < 0.05) Shorter duration in Int. group Vs. control [39.6 ± 25 d Vs. 69.8 ± 31 d (p < 0.01)] |
| Jackson, 2004 [15] | Double blind, randomized clinical trial | 41/34 | opioids | morphine | phenobarbital | 0/0 | Lipsitz | Median length of treatment | Shorter duration in Int. group Vs. control [8 d vs. 12 d (p = 0.02)] |
| Coyle 2002, [16] | partially randomized, clinical trial | 10/10 | Methadone/ heroin | Phenobarbital/ DTO* | Placebo/ DTO* | 0/0 | Finnegan | duration of hospitalization | Shorter duration in Int. group Vs. control [38 d vs. 79 d (P < 0 .001)] |
LOS length of stay, Int. Intervention, Cont. Control, vs. versus, d day, DTO Diluted tincture of opium
*DTO: 0.4 mg/mL morphine