When a sedative is needed to ameliorate symptoms in newborn infants with opiate withdrawal due to maternal opiate use in pregnancy, phenobarbitone is preferred. Use of opiates (commonly prescribed methadone or illicit heroin) by pregnant women may result in a withdrawal syndrome in their newborn infants. This may result in disruption of the mother-infant relationship, sleeping and feeding difficulties, weight loss and seizures. Treatments for newborn infants used to ameliorate these symptoms and reduce complications include opiates, sedatives (phenobarbitone or diazepam) and supportive treatments (swaddling, settling, massage, relaxation baths, pacifiers or waterbeds). Trials of sedatives have generally been of poor quality. Individual studies have reported that use of phenobarbitone compared to supportive care alone reduces the amount time an infant needs supportive care, is better than diazepam at preventing treatment failure and reduces the severity of withdrawal in infants treated with a opiate. In infants treated with an opiate, the addition of a sedative (phenobarbitone or clonidine) may reduce withdrawal severity, although safety and efficacy need confirming. The long term effects of use of phenobarbitone on an infant's development have not been determined.
Infants with NAS due to opiate withdrawal should receive initial treatment with an opiate. Where a sedative is used, phenobarbitone should be used in preference to diazepam. In infants treated with an opiate, the addition of phenobarbitone or clonidine may reduce withdrawal severity. Further studies are needed to determine the role of sedatives in infants with NAS due to opiate withdrawal and the safety and efficacy of adding phenobarbitone or clonidine in infants treated with an opiate for NAS.
Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. Treatments used to ameliorate symptoms and reduce morbidity include opiates, sedatives and non-pharmacological treatments.
To assess the effectiveness and safety of using a sedative compared to a non-opiate control for NAS due to withdrawal from opiates, and to determine which type of sedative is most effective and safe.
This update included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2010), MEDLINE 1966 to April 2010 and abstracts of conference proceedings.
Trials enrolling infants with NAS born to mothers with an opiate dependence with > 80% follow-up and using random or quasi-random allocation to sedative or control. Control could include another sedative or non-pharmacological treatment.
Each author assessed study quality and extracted data independently.
Seven studies enrolling 385 patients were included. There were substantial methodological concerns for most studies including the use of quasi-random allocation methods and sizeable, largely unexplained differences in reported numbers allocated to each group.
One study reported phenobarbitone compared to supportive care alone did not reduce treatment failure or time to regain birthweight, but resulted in a significant reduction in duration of supportive care (MD -162.1 min/day, 95% CI -249.2, -75.1). Comparing phenobarbitone to diazepam, meta-analysis of two studies found phenobarbitone resulted in a significant reduction in treatment failure (typical RR 0.39, 95% CI 0.24, 0.62). Comparing phenobarbitone with chlorpromazine, one study reported no significant difference in treatment failure.
In infants treated with an opiate, one study reported addition of clonidine resulted in no significant difference in treatment failure, seizures or mortality. In infants treated with an opiate, one study reported addition of phenobarbitone significantly reduced the proportion of time infants had a high abstinence severity score, duration of hospitalisation and maximal daily dose of opiate.