Treatment Of Neonatal Abstinence Syndrome Research Articles

Methadone‐exposed newborn infants: outcome after alterations to a service for mothers and infants

To evaluate the impact of a shared care approach in clinical management with a drug liaison midwife (DLM) service for mothers and infants established in 1995-1996 in an inner city area and to address the problem of congenital abnormality and microcephaly with fetal drug exposure. Descriptive analysis of data in live births of women enrolled in a methadone maintenance programme in 1991-1994 (n = 78) and 1997-2001 (n = 98), including time spent in hospital, treatment for neonatal abstinence syndrome (NAS), admission to the neonatal medical unit (NMU) and follow-up for child health checks. In 1997-2001 compared with 1991-1994, the mothers used more methadone in the last week of pregnancy (median 40.0 mg/day vs. 21.5 mg/day, P = 0.0006) and there were more preterm deliveries (36% vs. 21%, P = 0.03). The infants spent less time in hospital (median 5 days vs. 28 days, P < 0.0001), a smaller proportion had treatment for NAS (14% vs. 79%, P < 0.0001), and NMU admission was reduced (median 14 days vs. 26 days, P < 0.0003). Neonatal convulsions (P = 0.0001) and jaundice (P < 0.001) occurred less frequently, and more infants were breastfed (P = 0.001). One infant in each study group had a cleft palate and none had microcephaly. Child health checks for 18-24 months showed a favourable outcome in 1997-2001. We altered antenatal care and modified neonatal management, subsequently infants spent less time in hospital and NMU admissions were reduced with less NAS treatment. Congenital abnormalities and microcephaly were not common and as regular child health checks were possible, the impact of the DLM service in shared management merits further investigation, for mother-infant bonding and developmental outcome.

Management of neonatal abstinence syndrome in neonatal intensive care units: a national survey

To determine the monitoring and treatment of neonatal abstinence syndrome (NAS) in neonatal intensive care units (NICUs) following opiate or polydrug exposure in utero. A pretested questionnaire was distributed via email to the chiefs of the neonatology divisions with accredited Fellowship programs in Neonatal-Perinatal Medicine in the United States. Of the 102 individuals contacted, 75 participated in the survey. In all, 41 of the respondents (54.5%) have a written policy regarding the management of neonatal NAS. The method of Finnegan is the most commonly used abstinence scoring system (49 of 75, 65%), while only three respondents use the Lipsitz tool. Opioids (tincture of opium, or morphine sulfate solution) are used most commonly for management of both opioid (63% of respondents) and polydrug (52% of respondents) withdrawal, followed by phenobarbital (32 % of respondents) for polydrug withdrawal and methadone (20% of respondents) for opioid withdrawal. In all, 53 respondents (70%) use phenobarbital, and 19 (25%) use intravenous morphine to control opioid withdrawal seizures, while 61 (81%) use phenobarbital in cases of polydrug withdrawal seizures. Only 53 respondents (70%) always use an abstinence scoring system to determine when to start, titrate, or terminate pharmacologic treatment of neonatal NAS. The management of neonatal psychomotor behavior consistent with withdrawal varies widely, with inconsistent policies to determine its presence or treatment. Only about half of NICUs have written guidelines for the management of NAS, which may preclude effective auditing of this practice. Educational interventions may be necessary to ensure changes in clinical practice.

Can methadone concentrations predict the severity of withdrawal in infants at risk of neonatal abstinence syndrome?

Aim: To assess the usefulness of cord and serum methadone concentrations at 2 days of age in predicting the severity of neonatal abstinence syndrome (NAS) in infants whose mothers received...

A randomised controlled trial of morphine versus phenobarbitone for neonatal abstinence syndrome

Background: The incidence of neonatal abstinence syndrome (NAS) has increased 10-fold over the last decade in Glasgow. In the Princess Royal Maternity Hospital, it now accounts for 17% of special...

Outcomes of infants born to mothers receiving methadone for pain management in pregnancy

Objective: To assess the outcomes of infants born to mothers receiving methadone for the management of pain in pregnancy. Design: A retrospective audit was conducted of neonatal outcomes in 19...

270 Toxicity and seizure caused by injection of lidocaine

The non-medical use of prescription drugs, in general, and opioids, in particular, is a national epidemic, resulting in enormous addiction rates, healthcare expenditures, and overdose deaths. Prescription opioids are overly prescribed, illegally trafficked, and frequently abused, all of which have created a new opioid addiction pathway, adding to the number of opioid-dependent newborns requiring treatment for neonatal abstinence syndrome (NAS), and contributing to challenges in effective care in maternal and fetal/neonatal (M-F/N) medicine. The standard of care for illicit or prescription opioid dependence during pregnancy is opioid agonist (methadone or buprenorphine) substitution therapy, which are also frequently abused. The next generation of pharmacotherapies for the treatment of illicit or prescription opioid addiction in the M-F/N interactional dyad must take into consideration the interplay between genetic, epigenetic, and environmental factors. Addiction to illicit drugs during pregnancy presents unique challenges to effectively treat the mother, and the developing fetus and infant after delivery. New pharmacotherapies should be safe to the developing fetus, effective in treating the physical and psychological consequences of addiction in the mother, and reduce the incidence and severity of NAS in the infant after birth. More pharmacotherapeutic options should be available to the physician such that a more individualized rather than a one-drug/strategy-fits-all approach can be used. A myriad of new and exciting pharmacotherapeutic strategies for the treatment of opioid dependence and addiction are on the horizon. This review focuses on such three strategies: (i) pharmacotherapeutic targeting of the serotonergic system; (ii) mixed opioid immunotherapeutics (vaccines); (iii) pharmacogenomics as a therapeutic strategy to insure personalized care. We review and discuss how these strategies may offer additional treatment modalities for the treatment of M-F/N during pregnancy and the treatment of the infant after birth.

Maternal drug use and length of neonatal unit stay.

Infants with neonatal abstinence syndrome (NAS) may require a prolonged neonatal unit admission, which has implications for both their families and bed occupancy. The aim of this study was to test the hypothesis that the duration of neonatal unit stay would be influenced by the type of maternal drug use and particularly prolonged for the infants whose mothers had taken methadone with other substances. The medical records of infants born at term who were admitted consecutively to a neonatal unit because of NAS were reviewed. Data were collected regarding antenatal and neonatal factors likely to affect neonatal stay. Comparisons were then made between three groups of infants: those whose mothers took methadone alone, methadone plus other drugs or non-methadone opioids. Level three neonatal intensive care unit. Forty-one infants with a median gestational age of 39 (range 37-42) weeks. The 41 infants had a median duration of admission of 30 (range 3-68) days. Thirty-six of the infants required treatment for NAS; their median duration of treatment was 29 (range 6-68) days. The duration of stay and requirement for treatment were greater in the infants exposed to methadone and other drugs compared to those exposed to non-methadone opiods only (P = 0.0212, P = 0.0343, respectively). The duration of stay without requirement for treatment was also longest in the methadone plus other drugs group (P = 0.0117). Prolonged treatment and neonatal unit stay are influenced by the type of maternal drug abused.

A ‘one-stop’ clinic for drug using pregnant women

This study reviews the impact of a multidisciplinary team approach on maternal and fetal outcomes in women who substance-abuse during pregnancy. The multidisciplinary team includes obstetrician, senior midwife, prescribing/addiction unit doctor, health visitor and ultrasonographer. Women were seen in a hospital environment and attended every 2 weeks, or more if required. This was a retrospective study of 218 patients attending the specialised ‘one-stop’ clinics in three large hospitals from January 1999 to December 2001. Overall, the mean gestation at booking was 17.2 weeks with a decreasing trend from over 18 weeks to 16 weeks over the 3 years. The mean gestation at delivery was 38.1 weeks with a mean birth weight of 2.9 kg, demonstrating a good outcome in the majority of women. At the beginning of pregnancy, 60% of the women used heroin regularly. At discharge 6 weeks postnatally only 28% were still substance-using. Of the remaining women, 50% were on a substitution programme of either methadone or dihydrocodeine. Around 25% of the babies required treatment for neonatal abstinence syndrome. Most of the babies went home with their mother.

Opiate treatment for opiate withdrawal in newborn infants.

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 an opiate, compared to a sedative or non-pharmacological treatment, for treatment of NAS due to withdrawal from opiates. The evidence for use of different opiates was assessed in subgroup analyses. The standard search strategy of the Cochrane Neonatal Review Group including searches (up to March 2002) of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002), MEDLINE (1966-March 2002), previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. Trials enrolling infants with NAS born to mothers with an opiate dependence, with > 80% follow up and using random or quasi-random allocation to opiate or control. Control could include an opiate, sedative or non-pharmacological treatment. Each author assessed study quality and extracted data independently. Primary outcomes included control of symptoms, seizure occurrence, mortality and neurodevelopment. Treatment effect was expressed using relative risk (RR), risk difference (RD), mean difference (MD) and weighted mean difference (WMD). Meta-analysis was performed using a fixed effect model. Six studies enrolling a total of 511 infants met inclusion criteria (Carin 1983, Finnegan 1984, Kaltenbach 1986, Kandall 1983, Khoo 1995, Madden 1977); however, two (Finnegan 1984, Kaltenbach 1986) may be sequential reports that include some identical patients. The studies enrolled infants of mothers who had used opiates with or without other drugs during pregnancy. Methodological concerns included the use of quasi-random rather than random patient allocation methods in three studies, and sizeable, largely unexplained differences in reported numbers allocated to each group in four studies. Opiate (morphine) vs supportive care only: One study (Khoo 1995) found no significant effect on treatment failure (RR 1.29, 95% CI 0.41, 4.07), a significant increase in hospital stay (MD 15.0 days, 95% CI 8.9, 21.1) and significant reductions in time to regain birthweight (MD -2.8 days, 95% -5.3, -0.3) and duration of supportive care (MD -197.2 minutes/day, 95% CI -274.2, -120.3). Opiate vs phenobarbital: Meta-analysis of three studies found no significant difference in treatment failure (typical RR 0.78, 95% CI 0.46, 1.32). One of these studies (Finnegan 1984) reported that opiate treatment resulted in a significant reduction in treatment failure among infants of mothers who had used only opiates; however, as this was a post-hoc analysis, this result should be interpreted with caution. One study (Kandall 1983) reported a reduction in seizures, of borderline statistical significance, with the use of opiate. Opiate vs diazepam: Meta-analysis of two studies found a significant reduction in treatment failure (RR 0.43, 95% CI 0.23, 0.80) with the use of opiate. No study reported neurodevelopment by allocated treatment group. Opiates, as compared to supportive care only, appear to reduce the time to regain birth weight and reduce the duration of supportive care, but increase the duration of hospital stay; there is no evidence of effect on treatment failure. When compared to phenobarbital, opiates may reduce the incidence of seizures but, overall, there is no evidence of effect on treatment failure. When compared to diazepam, opiates reduce the incidence of treatment failure. A post-hoc analysis generates the hypothesis that treatment effects may vary according to whether the population includes infants born to all opiate users (i.e. with or without other drug exposure) or is restricted to infants of mothers who used opiates only. In view of the methodologic limitations of the included studies the conclusions of this review should be treated with caution. Further research is needed.

Treatment of neonatal abstinence syndrome with breast milk containing methadone.

This article addresses the management of pregnant women participating in a methadone maintenance program. An approach to management of the labor of a woman on a methadone maintenance program is described along with a summary of what to anticipate at delivery and postpartum, and options for management of the infant who manifests symptoms of the neonatal abstinence syndrome.

381 NEDNATAL ABSTINENCE, PHARMACOTHERAPY, AND DEVELOPMENTAL OUTCOME

The majority of infants born to drug-dependent women undergo neonatal abstinence syndrome (NAS) and often require pharmocotherapy for the treatment of withdrawal symptoms. Phenobarbitol, paregoric, and diazepam have been recommended for the treatment of the syndrome. While some investigators have examined the efficacy of these agents in treating NAS, there are no data regarding the use of specific pharmacologic agents and developmental outcome. This study evaluated 85 infants bom to drug-dependent women who were maintained on methadone during pregnancy. Severity of infant withdrawal was assessed with the Neonatal Abstinence Scoring system (Pediatric Research 7:319, 1973). Infants who required pharmacotherapy were randomly assigned to one of four treatment regimens: paregoric, phenobarbitol (titration), phenobarbitol (loading), and diazepam. When treatment was not successful with the assigned agent, one of the other agent(s) was used. At 6 months of age, the developmental status of infants was assessed with the Bayley Scales of Mental Development. Based on NAS treatment, four groups were delineated: I) paregoric (n=21); II) phenobarbitol (n=17); III) more than one agent (n=31); and IV) no treatment. (Data for the phenobarbitol loading and titration groups were combined since analysis revealed no differences between groups. All infants who initially received diazepam were included in Group III since diazepam as a single agent was not successful). Results of one way analysis of variance revealed no differences in developmental status between groups (p = <.10, f=.25). Scores for all groups were well within the normal range of development. Implications of these findings include, 1) the severity of withdrawal is not related to developmental outcome when appropriately managed with pharmacotherapy, and 2) the use of pharmacotherapy does not adversely effect the developmental outcome and may help ameloriate the consequences of NAS.