Table 2

Treatment comparison trials

Reference	Type of drug exposure in utero	No of infants examined	Treatments	Randomisation	Outcome measure	Results
Kron et al³⁴	Methadone	26	Paregoric/phenobarbitone/diazepam	Not stated whether randomised	Sucking	Average sucking rate 31.1 sucks/min in paregoric group, 19.9 sucks/min in phenobarbitone group (p<0.05), and 39.6 sucks/min in control infants. Sucking rate 6.5 sucks/min in diazepam group versus 23.8 sucks/min in the controls
Finnegan et al³²	Methadone	38	Paregoric/phenobarbitone	Not randomised	Sucking	Average sucking rate 29.0 sucks/min in the paregoric treated, 24.1 sucks/min in the phenobarbitone treated infants
Kron et al³³	Diamorphine/methadone	42	Paregoric/phenobarbitone/diazepam	Not stated whether randomised	Sucking	Average sucking rate 30.5 sucks/min in the paregoric group (n=5), 19.4 sucks/min in the phenobarbitone group (n=28), 18.4 sucks/min in the diazepam group (n=6), and 23.2 in the controls (n=8)
Herzlinger et al³⁶	Diamorphine/methadone	65	Paregoric/diazepam	Not randomised	Seizures	Two of 48 paregoric treated infants and 5 of 12 diazepam treated infants had seizures (p<0.01)
Kandall et al⁸	Diamorphine/methadone	132	Tincture of opium/diazepam	Not stated	Seizures	More convulsions seen in infants treated with diazepam (p<0.01)
Kandall et al³⁸	Methadone	111	Paregoric/phenobarbitone	Randomisation method not stated	Seizures	No infant had seizures in the paregoric group, 7 of 62 infants in the phenobarbitone group had seizures (p<0.025)
Pacifico et al³⁷	Diamorphine	25	Morphine/phenobarbitone + diazepam/morphine + phenobarbitone + diazepam	Not stated	Symptom control	Maximum withdrawal score 35 in the morphine treated group, 75 in the phenobarbitone + diazepam group and 100 in the phenobarbitone + diazepam + morphine group
Kahn et al³⁹	Diamorphine	38	Phenobarbitone/chlorpromazine	Randomisation method not stated	Symptom control	There was no significant difference in symptom control, as assessed by clinical observation in the 19 infants treated with chlorpromazine and the 19 treated with phenobarbitone
Finnegan et al⁴⁴	Opiate/polydrug	139	Paregoric/phenobarbitone/diazepam	Randomisation method not stated	Symptom control	Opiate exposed group; treatment success (as assessed by no need for a second therapeutic agent) 13 of 14 paregoric treated, 13 of 26 phenobarbitone treated and 0 of 5 diazepam treated infants.
						Polydrug exposed group, treatment success; 11 of 18 paregoric treated, 54 of 61 phenobarbitone treated and 6 of 9 diazepam treated infants
Finnegan and Ehrlich⁴³	Opiate/polydrug	300	Paregoric/phenobarbitone/diazepam	Randomisation method not stated	Days to symptom control	Opiate exposed infants, mean days to symptom control 4.9 in paregoric treated, 6.7 in phenobarbitone treated and 9.5 in diazepam treated infants.
						Polydrug exposed: 3.5 days in the phenobarbitone treated, 4.7 in the diazepam treated and 7 in the paregoric treated infants
Kaltenbach and Finnegan⁴⁰	Methadone	69	Paregoric/phenobarbitone/diazepam	Randomisation method not stated	Symptom control Developmental outcome at 6 months	2 of 23 paregoric treated, 11 of 20 phenobarbitone treated and 10 of 10 diazepam treated infants required a second agent to control symptoms.
						No significant difference in the developmental outcome at 6 months of the three groups
Madden et al⁴²	Diamorphine/methadone	50	Methadone/phenobarbitone/diazepam	Randomisation method not stated	Duration of treatment	Mean treatment duration: 11.7 days in methadone treated, 14.5 days in phenobarbitone treated and 10.2 days in diazepam treated infants
Carin et al⁴¹	Methadone	31	Paregoric/phenobarbitone	Randomisation method not stated	Duration of treatment	Mean duration of treatment: 22 days in phenobarbitone treated infants, 17 days in paregoric treated infants (p<0.01)