Presented at the Neonatal Society 2008 Autumn Meeting.

Twigg S, Smith ZA, Kempley ST

Barts and the London School of Medicine and Dentistry, Queen Mary University of London Neonatal Unit, Barts and the London Children’s Hospital, Whitechapel, London, UK

Background: Infants born to drug abusing mothers may develop neonatal abstinence syndrome (NAS). Historically, a number of agents have been used to manage the condition, including opioids, clonidine, chloral hydrate, chlorpromazine (CPZ), diazepam and phenobarbitone. At present, the limited evidence available supports morphine for infants whose mothers used opioids (1). However, recent data suggests that CPZ may be associated with reduced duration of NAS and reduced length of stay when compared to morphine (2).

Aim: To determine whether withdrawal scores improved with the addition of CPZ or morphine in neonates already receiving one of these agents.

Methods: Retrospective audit of the records of 18 term infants with NAS admitted to the Royal London Hospital neonatal unit between 2000 and 2008. Three groups were studied: Group 1 (n=6): started treatment with morphine but had chlorpromazine added or substituted Group 2 (n=6): started treatment with chlorpromazine but had morphine added or substituted Group 3 (n=6): treated with morphine only, data collection at a comparable postnatal age Information regarding maternal, antenatal and neonatal factors was collected, including withdrawal scores. Analysis of withdrawal scores in each group was performed using two-way ANOVA, to evaluate the effect of treatment change and the day of treatment separately.

Results: Groups were comparable in terms of gestation, birth weight and maternal drug use. When CPZ was added to morphine, this was usually for rising symptom scores. All babies on CPZ requiring addition of morphine did so following a clinical diagnosis of convulsions. Comparing five days before and after a change in drug treatment, addition or substitution of a second drug was associated with a reduction in symptom scores. In Group 3, the reduction in scores over a comparable time period failed to achieve statistical significance (see Table).

In Groups 1 & 2, there was a rising symptom score before the treatment change, reversed on addition of the second drug. In group 3, there was a steady decline in symptom scores.

Conclusion: Morphine and CPZ appear to have additive effects in the treatment of NAS. A clinical diagnosis of seizures was a frequent reason for adding morphine to CPZ treatment. Future trials could consider dual agent therapy (morphine plus CPZ) in this condition.

References
1. Osborn DA, Jeffrey HE and Cole MJ. Sedatives for opiate withdrawal in newborn infants. Cochrane Database Syst Rev. 2005, (3), CD002053
2. Mazurier E, et al. Comparison of chlorpromazine versus morphine hydrochloride for treatment of neonatal abstinence syndrome. Acta Paediatrica 2008 Oct;97(10):1358-61