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Treatment of neonatal abstinence syndrome.

Neonatal abstinence syndrome (NAS) is suffered by infants withdrawing from substances on which they have become physically dependent after in utero exposure. They may require prolonged treatment and spend weeks or even months in hospital. A wide range of drugs have been used to treat NAS. The efficacy of few, however, have been adequately investigated. Evidence suggests that opioids are the most appropriate, at least in infants exposed to diamorphine or methadone. In all "head to head" trials, diazepam has been shown to be ineffective. Morphine and methadone are currently the most commonly prescribed opioids to treat NAS, but randomised trials have not been undertaken to determine which is the more beneficial. Many infants with NAS have been exposed to multiple substances in utero. Further research is required into whether a single opiate or a multiple drug regimen is the best option for such patients.

Clinical Trials as Topic↗

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

AIMS: To determine the monitoring and treatment of neonatal abstinence syndrome (NAS) in neonatal intensive care units (NICUs) following opiate or polydrug exposure in utero. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Humans↗

Management of neonatal abstinence syndrome in neonates born to opioid maintained women.

Neonates born to opioid-maintained mothers are at risk of developing neonatal abstinence syndrome (NAS), which often requires pharmacological treatment. This study examined the effect of opioid maintenance treatment on the incidence and timing of NAS, and compared two different NAS treatments (phenobarbital versus morphine hydrochloride). Fifty-three neonates born to opioid-maintained mothers were included in this study. The mothers received methadone (n=22), slow-release oral morphine (n=17) or buprenorphine (n=14) throughout pregnancy. Irrespective of maintenance treatment, all neonates showed APGAR scores comparable to infants of non-opioid dependent mothers. No difference was found between the three maintenance groups regarding neonatal weight, length or head circumference. Sixty percent (n=32) of neonates required treatment for NAS [68% in the methadone-maintained group (n=15), 82% in the morphine-maintained group (n=14), and 21% in the buprenorphine-maintained group (n=3)]. The mean duration from birth to requirement of NAS treatment was 33 h for the morphine-maintained group, 34 h for the buprenorphine-maintained group and 58 h for the methadone-maintained group. In neonates requiring NAS treatment, those receiving morphine required a significantly shorter mean duration of treatment (9.9 days) versus those treated with phenobarbital (17.7 days). Results suggest that morphine hydrochloride is preferable for neonates suffering NAS due to opioid withdrawal.

Adult↗

[Neonatal abstinence syndrome and maternal toxicological profile].

Neonatal abstinence syndrome (NAS) is one of the most frequent manifestations in the neonates of drug-addicted mothers. It is caused by the abrupt interruption of the transplacentar passage of drugs from the mother to the fetus. The aim of this study was to evaluate the correlation between drugs taken during pregnancy and NAS. Data were examined relating to 223 neonates born during 1975-1992 to drug-addict mothers. Neonates were subdivided into four groups according to the maternal toxicological profile. It was thus possible to observe that there is a greater prevalence of NAS in cases of polypharmacomania and that it gradually diminishes in the children of heroin addicts and those receiving methadone treatment. Moreover, the intensity of the syndrome is correlated to the high doses of methadone and/or heroin. In the group of neonates whose mothers had complied with the methadone treatment protocol, the severity of NAS was proportional to the dose taken by the mother. In conclusion, the management of pregnant drug addicts following a controlled methadone treatment programme is accompanied by improved obstetric help and is the most suitable way of reducing perinatal complications and the prevalence of NAS.

Dose-Response Relationship, Drug↗

Neonatal abstinence syndrome due to codeine.

The neonatal abstinence syndrome (NAS) is a potentially life threatening illness associated with significant morbidity especially in the neonatal period. A case of NAS due to codeine prescribed for pain relief during pregnancy is reported. Clinicians should be aware that narcotic derivatives prescribed in late pregnancy can give rise to this type of problem.

Acetaminophen↗

Neonatal abstinence syndrome following abrupt cessation of breastfeeding.

Neonatal abstinence syndrome is seen commonly in infants born to women on methadone maintenance. Many of these infants are breast-fed but few data are available on the distribution of methadone in breast milk, particularly for women receiving doses greater than 60 mg daily. We report two infants who appeared to develop neonatal abstinence syndrome, after abrupt discontinuation of breast-feeding by women receiving 70 mg and 130 mg of methadone. Women on methadone maintenance on high doses should be counselled to wean breast-feeding gradually.

Breast Feeding↗

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 care baby unit (SCBU) admissions. OBJECTIVE: To compare opiate replacement therapy (morphine sulphate) with the present standard treatment (phenobarbitone) for management of NAS. The primary study end point was duration of pharmaceutical treatment. Secondary end points were the requirement for additional drugs and the requirement for SCBU admission. DESIGN: Double blind, randomised controlled clinical trial. METHODS: Differential diagnoses were excluded, and two consecutive Lipsitz scores > 4 defined NAS requiring treatment. Infants were randomised to receive morphine sulphate or phenobarbitone. Treatments were identical in appearance, odour, and volume. Increments, decrements, and discontinuation of treatments were protocol driven. RESULTS: Seventy five infants participated. All mothers received opiate replacement therapy (methadone) during pregnancy and most used other drugs (n = 62, 83%). No significant difference in maternal drug use patterns was observed between treatment groups. Median treatment duration was four days shorter with opiate replacement (8 v 12 days, Mann-Whitney U test, p = 0.02). Phenobarbitone treated infants tended to require second line treatment (47% v 35%, chi(2) test, p = 0.11) and SCBU admission (62% v 30%, chi(2) test, p = 0.04) more often. CONCLUSIONS: Opiate replacement therapy appears to be superior for management of symptomatic NAS when maternal opiate use is prevalent. The shorter treatment duration and lower requirement for higher intensity nursing may have significant cost implications. Tailoring NAS treatment to local maternal drug use may result in similar benefits.

Double-Blind Method↗

Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants.

OBJECTIVE: To compare the prevalence and clinical characteristics of neonatal abstinence syndrome in neonates exposed and not exposed to selective serotonin reuptake inhibitors (SSRIs) in utero. DESIGN: Cohort study. SETTING: Tertiary care center. Patients One hundred twenty term infants, of whom 60 had prolonged in utero exposure to SSRIs, including paroxetine hydrochloride, fluoxetine, citalopram hydrobromide, sertraline hydrochloride, and venlafaxine hydrochloride. MAIN OUTCOME MEASURES: Neonatal abstinence syndrome was assessed with the Finnegan score as follows: score of 8 or above, severe; score of 4 to 7, mild; and score of 0 to 3, normal. All infants were followed up with a standardized protocol that included repeated Finnegan score assessments and cardiorespiratory monitoring until normalization of the Finnegan score. RESULTS: Of the 60 neonates exposed to SSRIs in utero, 8 showed severe and 10 showed mild symptoms of a neonatal abstinence syndrome. All nonexposed neonates had a normal Finnegan score. In neonates who developed severe symptoms, the maximum mean daily Finnegan scores were recorded within 2 days after birth, although maximum individual scores were recorded as long as 4 days after birth. CONCLUSIONS: Neonatal abstinence syndrome occurs in 30% of neonates exposed to SSRIs in utero. These neonates should be monitored for at least 48 hours after birth. The long-term effects of prolonged exposure to SSRIs, particularly in neonates who develop severe symptoms, have yet to be determined.

Adult↗

Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome.

This study was designed to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. This randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care. Participants were opioid-dependent pregnant women and their neonates. Treatment involved daily administration of either sublingual buprenorphine or oral methadone using flexible dosing of 4-24 mg or 20-100 mg, respectively. Primary a priori outcome measures were: (1) number of neonates treated for NAS; (2) amount of opioid agonist medication used to treat NAS; (3) length of neonatal hospitalization; and (4) peak NAS score. Two of 10 (20%) buprenorphine-exposed and 5 of 11 (45.5%) methadone-exposed neonates were treated for NAS (p=.23). Total amount of opioid-agonist medication administered to treat NAS in methadone-exposed neonates was three times greater than for buprenorphine-exposed neonates (93.1 versus 23.6; p=.13). Length of hospitalization was shorter for buprenorphine-exposed than for methadone-exposed neonates (p=.021). Peak NAS total scores did not significantly differ between groups (p=.25). Results suggest that buprenorphine is not inferior to methadone on outcome measures assessing NAS and maternal and neonatal safety when administered starting in the second trimester of pregnancy.

Administration, Sublingual↗

Neonatal abstinence syndrome.

A 12 month review of infants admitted with neonatal abstinence syndrome to a neonatal intensive care unit was undertaken. The relationship of maternal drug abuse to symptoms, the effectiveness of pharmacologic agents in controlling symptoms and the length of inpatient stay were investigated. A retrospective review of maternal and infant records was performed. Those infants with a serial Finnegan score greater than 8 were treated. Pharmacologic treatment was oral morphine sulphate (0.2 mg 4-6 hourly), phenobarbitone (3-7 mgs/kg/day), or combination of the above. 43 infants were admitted to the hospital during the year. The average maternal age was 24.6 years, (18-34 years). Drug use volunteered by the mothers was methadone alone in 6 cases, methadone and benzodiazepines in 14, methadone and heroin and benzodiazepines in 7, methadone and heroin in 10, heroin alone in 2, and other multiple drug use including oral morphine sulphate, dothiepin and cannabis in 4. Average gestational age was 40.3 (35-42 weeks). The average birthweight was 2.81 kgs (1.89-3.91 kgs). Time to onset of withdrawal symptoms was 2.8 (1-13) days. The duration of pharmacologic treatment (oral morphine sulphate and/or phenobarbitone) was 21.8 (1-62) days. The total hospital stay for the 43 infants was 1,011 days. This study confirms that polydrug abuse is the commonest type of drug abuse in Dublin. The duration of withdrawal symptoms is loosely related to drug type, but increasing duration of symptoms is noted for infants exposed to benzodiazepines. Our experience would favour the use of morphine sulphate to treat pure opiate withdrawal symptoms. Over the 12-month period, there was an average occupancy of 3 beds per day in the paediatric department.

Adolescent↗

[The clinical and epidemiological aspects of the neonatal abstinence syndrome].

Retrospectively, were tested maternal-neonatal factors of 47 newborn with neonatal abstinence syndrome comparing them with a control group of 100 newborn, during the period from 1985 to 1991. An average incidence of 6/1000 living newborn were affected by abstinence syndrome. The mothers were young (75%), smokers (74%), unemployed (80%), with a high rate of previous abortions (21%) and with a bad pregnancy control. Within our environment, abstinence syndrome increase has been detected among children of young gypsy mothers. Heroin (88%) was the most popular drug. Nevertheless a change has been noted in the last few years in the drug administration going from intravenous to the inhalational route. The duration of syndrome was less in the newborn whose mothers had inhaled heroin and in the premature newborn. It was proved that there was a high rate of HIV (40%), hepatitis B (23%), and syphilis markers (25%).

Adult↗

Neonatal abstinence syndrome: assessment and management.

A scoring system for the neonatal abstinence syndrome has been devised and implemented as both a clinical and investigative tool. The score monitors the passively addicted infant in a more comprehensive and objective fashion, and facilitates a more precise evaluation of the clinical status of the infant undergoing withdrawal. In addition, the scoring system has been applied in research designed to test the comparative usefulness of various pharmacologic agents currently recommended for the neonatal abstinence syndrome, and has been found useful in following the progression and diminution of withdrawal symptomatology before, during, and after therapy. Furthermore, the scoring system provides a basis ofr developing uniform criteria for the assessment and treatment of the neonate born to the addicted mother.

Administration, Oral↗

Effects of breast milk on the severity and outcome of neonatal abstinence syndrome among infants of drug-dependent mothers.

OBJECTIVE: The purpose of this research was to assess the effects of breast milk on the severity and outcome of neonatal abstinence syndrome. METHODS: We conducted a retrospective chart review of 190 drug-dependent mother and infant pairs. Patients were categorized according to the predominant type of milk consumed by the infant on the fifth day of life (breast milk: n = 85 or formula: n = 105). The Finnegan's scoring system was used to monitor withdrawal, and medication was commenced if there were 2 scores of > or = 8. RESULTS: Mean Finnegan scores were significantly lower in the breast milk group during the first 9 days of life even after stratifying for prematurity and exposure to polydrug and methadone. Significantly fewer infants required withdrawal treatment in the breast milk group. The median time to withdrawal occurred considerably later in breast milk group. In a multivariate analysis controlled for exposure to drugs of high risk of neonatal abstinence syndrome, polydrug, and prematurity, breast milk group was associated with lower need for neonatal abstinence syndrome treatment. CONCLUSIONS: Breast milk intake is associated with reduced neonatal abstinence syndrome severity, delayed onset of neonatal abstinence syndrome, and decreased need for pharmacologic treatment, regardless of the gestation and the type of drug exposure.

Breast Feeding↗

Neonatal abstinence syndrome: strategies for care of the drug-exposed infant.

Neonatal abstinence syndrome (NAS), a clinical condition that has been recognized for over 30 years, remains a significant clinical issue, although our knowledge of abstinence, its treatment, and outcome continues to grow. The condition is now complicated by polydrug use (which is becoming more prevalent) as well as concomitant use of tobacco, and psychoactive substances that are frequently prescribed to pregnant women. This article reviews the neonatal effects of a variety of substances, discusses the state of the art for clinical care of drug-exposed infants, including NAS patients, and updates the reader on areas of current research.

Female↗

Neonatal abstinence syndrome at Glasgow Royal maternity hospital.

OBJECTIVE: To get a clearer idea of the magnitude of the problem of Neonatal Abstinence Syndrome and, in particular, the number of cases and the severity and length of any withdrawal symptoms. DESIGN: Retrospective review of casenotes. SETTING: GRMH, Rottenrow Neonatal Unit Jan 1994-Aug. 1996. SUBJECTS: Infants admitted to the Neonatal Unit with the label "Infant of a Drug Abusing Mother" and their mothers. RESULTS: Sixty-four infants qualified for the audit i.e. on average two children per month. Most mothers had a polydrug habit taking both opiates and benzodiazepines. Thirty per cent of infants were premature and, as a group they were lighter and had a smaller OFC than the national average. Fifty-three infants suffered NEONATAL ABSTINENCE SYNDROME, 50 of these being "jittery, restless or irritable". Only four had convulsions. Most infants' withdrawal presented within 72 hours (median 24 hours) and lasted for less than six days. Infants exposed to methadone had symptoms for longer but required less treatment than infants exposed to heroin. Forty infants needed treatment with phenobarbitone for a median of four days. Only six infants needed other drugs. Median age of discharge was 11 days and 49 out of 53 went home with their mothers. CONCLUSIONS: The Glaswegian polydrug pattern would make morphine/methadone unsuitable treatment. If these infants are not showing signs of withdrawal at 72 hours it is, in our opinion, reasonable to discharge them. Infants should not be discharged with outstanding problems, as follow-up is usually unsuccessful.

Hospitals, Maternity↗

Frequency of newborn behaviours associated with neonatal abstinence syndrome: a hospital-based study.

OBJECTIVES: To determine the frequency of neonatal abstinence syndrome (NAS) among unselected term newborns, using newborn behaviour data only. METHODS: This hospital-based prospective exploratory study used clinical observations of newborn behaviours, mothers' observations of their newborns, and newborn chart data to determine the prevalence of suspected and confirmed cases of NAS in a convenience sample of unselected term newborns "rooming in" with their mothers in a large central city acute-care referral hospital. Over a 4-month period, 824 out of 1008 newborns were observed at between 8 and 30 hours of life by specially trained nurse observers. Behaviours recorded and their weighting were adapted from the Neonatal Abstinence Scoring System (NASS) by Finnegan and Kaltenbach. Newborns with scores of 5 or greater and "suspect for NAS" were referred to their physicians for confirmation or refutation of the clinical findings. The prevalence of "suspect for NAS" and confirmed NAS, as well as of individual neonatal behaviours, was calculated. RESULTS: Thirty-one (3.8%) of 824 term "rooming in" newborns were identified with findings suggestive of NAS. Four newborns were positively identified as having NAS and treated. The identification was confirmed by post hoc affirmation of maternal drug use. Individual behaviours occurring in 10% or more of newborns included excessive sneezing, nasal stuffiness, unsustained suck, tremor, and abnormal nipple latch. CONCLUSIONS: Clinical observation of newborn behaviour may identify NAS. Further studies are recommended to correlate this methodology with laboratory findings, as are more in-depth maternal questionnaires concerning use of mood-altering substances. The prevalence of NAS is likely underestimated because of early hospital discharge. A coordinated system of early identification and infant-specific assessment and treatment, both in hospital and following discharge home, is advocated.

Alberta↗

A retrospective study of length of hospital stay in infants treated for neonatal abstinence syndrome with methadone versus oral morphine preparations.

PURPOSE: Length of hospital stay (LOS) of infants treated for neonatal abstinence syndrome (NAS) with methadone was compared to LOS of those treated with an oral morphine preparation (OMP, neonatal morphine solution, or deodorized tincture of opium). METHODS: A retrospective review of medical records of infants treated for NAS due to in utero exposure to methadone and/or illicit drugs such as heroin or morphine was performed for birthweight, neonatal abstinence scores, infant and maternal illicit drug exposure history, maternal methadone dose (if any), and details of treatment. Length of stay was the primary outcome measure. RESULTS: Forty-six infants met the inclusion criteria. The median LOS of infants treated with methadone versus OMP was not significant (P > 0.05). Prolonged LOS was associated with larger pharmacological treatment doses required to control withdrawal symptoms, larger maternal methadone dose, and increased birthweight. After adjusting for these factors, exposure to opioids in utero, maternal nicotine use, hospital of treatment, severity of withdrawal symptoms, and foster care placement were not significantly associated with LOS in univariate or multivariate analyses. CONCLUSIONS: These results suggest that infants treated with OMP or methadone have similar LOS. Longer LOS is associated with both higher maternal methadone doses and higher opioid treatment dose requirements after birth. The potential effect of maternal methadone dose on neonatal LOS should be considered when treating expectant mothers on methadone maintenance therapy.

Administration, Oral↗

[Use of diazepam in the treatment of opioid neonatal abstinence syndrome].

INTRODUCTION: The fetal opiate exposure presents many risks for the newborn. One of the most important is the neonatal abstinence syndrome that associates neurological and digestive signs. In some cases the vital prognosis can be involved. The evaluation of the syndrome's severity is based on certificated scales. The mortality has been reduced by the improved management of these neonates. Diamorphine, phenobarbital, chlorpromazine and diazepam are the most currently used. However, there is no consensus on the treatment. The data concerning the treatment are controversial, especially for the use of diazepam. The aim of our study was to describe the effects of diazepam obtained in three different centers and to compare our results to those of the literature. POPULATION AND METHODS: Twenty-three neonates were included. They were all hospitalized for abstinence syndrome and treated by diazepam. The Finnegan scale was used to evaluate the symptom's severity and the effects of the diazepam. The principal evaluation criteria were the duration of treatment and hospitalization, the timing in recovery of birth weight and the percentage of birth weight loss. RESULTS: The average treatment duration was 7 days, the average hospitalization duration was 18 days, the birth weight was recovered at 10 days of life and the percentage of loss of birth weight was 6.5%. Diazepam treatment failed in only one case. No case of intense dehydration occurred. CONCLUSION: Due to the retrospective design of the study, the diazepam could not be compared to other drugs. Nevertheless, it argues against the "anti-diazepam" attitude. A controlled randomised prospective study is needed to evaluated the optimal therapeutic strategy.

Adult↗