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CORK Bibliography: Neo-natal Abstinence Syndrome

37 citations. January 2009 to present

Prepared: March 2012

Agthe AG; Kim GR; Mathias KB; Hendrix CW; Chavez-Valdez R; Jansson L et al. Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: A randomized, controlled trial. Pediatrics 123(5): e849-e856, 2009. (42 refs.)

OBJECTIVE. To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome. METHODS. Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of >= 9) were enrolled at 2 hospitals during 2002-2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 mu g/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation. RESULTS. The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15 days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age. CONCLUSIONS. In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.

[Anon]. Perinatal risk factors for the neonatal abstinence syndrome in infants born to women on methadone maintenance therapy. (editorial). Obstetrics & Gynecological Survey 65(10): problem ?603-604, 2010. (0 refs.)

Bakstad B; Sarfi M; Welle-Strand GK; Ravndal E. Opioid maintenance treatment during pregnancy: Occurrence and severity of neonatal abstinence syndrome. European Addiction Research 15(3): 128-134, 2009. (38 refs.)

Background: Opioid maintenance treatment (OMT) is widely used to treat pregnant women with a history of opioid dependence. This study investigated whether maternal methadone/buprenorphine dose and nicotine use in pregnancy affects the occurrence and duration of neonatal abstinence syndrome (NAS) in the infant. Methods: Forty-one pregnant women from OMT programmes in Norway who gave birth between January 2005 and January 2007 were enrolled in a national prospective study. Thirty-eight women (81% of the population) were interviewed in the last trimester of pregnancy and 3 months after delivery. Data from the European Addiction Severity Index and a questionnaire measuring enrolled birth information were compared with medical records and urine analyses. Results: Treatment requiring NAS occurred in 58% of the methadone-exposed and in 67% of the buprenorphine-exposed infants. There was no significant relationship between a maternal dose of methadone or buprenorphine in pregnancy and NAS treatment duration for the infant. The mean number of cigarettes consumed correlated significantly with NAS treatment duration for the methadone group. Birth weight for the methadone group was approximately 200 g above international findings despite high doses during pregnancy. Conclusions: Maternal methadone/buprenorphine dose predicted neither the occurrence nor the need for NAS treatment for the infant.

Booth RE; Lehman WEK; Latkin CA; Dvoryak S; Brewster JT; Royer MS et al. Individual and network interventions with injection drug users in 5 Ukraine cities. American Journal of Public Health 101(2): 336-343, 2011. (4 refs.)

Objectives. We evaluated the effects of an individual intervention versus a network intervention on HIV-related injection and sexual risk behaviors among street-recruited opiate injection drug users in 5 Ukraine cities. Methods. Between 2004 and 2006, 722 opiate injection drug users were recruited to participate in interventions that were either individually based or based on a social network model in which peer educators intervened with their network members. Audio computer-assisted self-interview techniques were used to interview participants at baseline and follow-up. Results. Multiple logistic analyses controlling for baseline injection and sexual risks revealed that both peer educators and network members in the network intervention reduced injection-related risk behaviors significantly more than did those in the individually based intervention and that peer educators increased condom use significantly more than did those in the individual intervention. Individual intervention participants, however, showed significantly greater improvements than did network members with respect to reductions in sexual risk behaviors. Conclusions. Social network interventions may be more effective than individually based interventions in changing injection risk behaviors among both peer educators and network members. The effectiveness of network interventions in changing sexual risk behaviors is less clear, probably owing to network composition and inhibitions regarding discussing sexual risk behaviors.

Cleary BJ; Donnelly J; Strawbridge J; Gallagher PJ; Fahey T; Clarke M et al. Methadone dose and neonatal abstinence syndrome-systematic. Review and meta-analysis. (review). Addiction 105(12): 2071-2084, 2010. (105 refs.)

Aim: To determine if there is a relationship between maternal methadone dose in pregnancy and the diagnosis or medical treatment of neonatal abstinence syndrome (NAS). Methods: PubMed, EMBASE, the Cochrane Library and PsychINFO were searched for studies reporting on methadone use in pregnancy and NAS (1966-2009). The relative risk (RR) of NAS was compared for methadone doses above versus below a range of cut-off points. Summary RRs and 95% confidence intervals (CI) were estimated using random effects meta-analysis. Sensitivity analyses explored the impact of limiting meta-analyses to prospective studies or studies using an objective scoring system to diagnose NAS. Results: A total of 67 studies met inclusion criteria for the systematic review; 29 were included in the meta-analysis. Any differences in the incidence of NAS in infants of women on higher compared with lower doses were statistically non-significant in analyses restricted to prospective studies or to those using an objective scoring system to diagnose NAS. Conclusions Severity of the neonatal abstinence syndrome does not appear to differ according to whether mothers are on high- or low-dose methadone maintenance therapy.

Cleary BJ; Donnelly JM; Strawbridge JD; Gallagher PJ; Fahey T; White MJ et al. Methadone and perinatal outcomes: A retrospective cohort study. American Journal of Obstetrics and Gynecology 204(2): e-article 139.e1, 2011. (30 refs.)

OBJECTIVE: The purpose of this study was to examine the relationship among methadone maintenance treatment, perinatal outcomes, and neonatal abstinence syndrome. STUDY DESIGN: This was a retrospective cohort study of 61,030 singleton births at a large maternity hospital from 2000-2007. RESULTS: There were 618 (1%) women on methadone at delivery. Methadone-exposed women were more likely to be younger, to book late for antenatal care, and to be smokers. Methadone exposure was associated with an increased risk of very preterm birth <32 weeks of gestation (adjusted odds ratio [aOR], 2.47; 95% confidence interval [CI], 1.40-4.34), being small for gestational age <10th percentile (aOR, 3.27; 95% CI, 2.49-4.28), admission to the neonatal unit (aOR, 9.14; 95% CI, 7.21-11.57), and diagnosis of a major congenital anomaly (aOR, 1.94; 95% CI, 1.10-3.43). There was a dose-response relationship between methadone and neonatal abstinence syndrome. CONCLUSION: Methadone exposure is associated with an increased risk of adverse perinatal outcomes, even when known adverse sociodemographic factors have been accounted for. Methadone dose at delivery is 1 of the determinants of neonatal abstinence syndrome.

Dryden C; Young D; Hepburn M; Mactier H. Maternal methadone use in pregnancy: Factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources. BJOG: An International Journal of Obstetrics and Gynaecology 116(5): 665-671, 2009. (43 refs.)

The objectives of this study were to investigate factors associated with the development of neonatal abstinence syndrome (NAS) and to assess the implications for healthcare resources of infants born to drug-misusing women. Retrospective cohort study from 1 January 2004 to 31 December 2006. Inner-city maternity hospital providing dedicated multidisciplinary care to drug-misusing women. Four hundred and fifty singleton pregnancies of drug-misusing women prescribed substitute methadone in pregnancy. Case note review. Development of NAS and duration of infant hospital stay. 45.5% of infants developed NAS requiring pharmacological treatment. The odds ratio of the infant developing NAS was independently related to prescribed maternal methadone dose rather than associated polydrug misuse. Breastfeeding was associated with reduced odds of requiring treatment for NAS (OR 0.55, 95% CI 0.34-0.88). Preterm birth did not influence the odds of the infant receiving treatment for NAS. 48.4% infants were admitted to the neonatal unit (NNU) 40% of these primarily for treatment of NAS. The median total hospital stay for all infants was 10 days (interquartile range 7-17 days). Infants born to methadone-prescribed drug-misusing mothers represented 2.9% of hospital births, but used 18.2% of NNU cot days. Higher maternal methadone dose is associated with a higher incidence of NAS. Pregnant drug-misusing women should be encouraged and supported to breastfeed. Their infants are extremely vulnerable and draw heavily on healthcare resources.

Esmaeili A; Keinhorst AK; Schuster T; Beske F; Schlosser R; Bastanier C. Treatment of neonatal abstinence syndrome with clonidine and chloral hydrate. Acta Paediatrica 99(2): 209-214, 2010. (11 refs.)

Aim: The objective of this retrospective study is to compare the medical treatment of neonatal narcotic abstinence syndrome with clonidine and chloral hydrate with the commonly used combination therapy of morphine and phenobarbital. Methods: From 1998 to 2008, a total of 133 newborns suffering from neonatal narcotic abstinence syndrome were treated at our clinic. All of these patients were born to mothers who had received methadone substitution for drug addiction during the course of pregnancy. Results: Twenty-nine patients received clonidine and chloral hydrate, and 64 patients were treated with morphine and phenobarbital for abstinence syndrome. The duration of treatment was significantly shorter in the clonidine/chloral hydrate group (median: 14 days vs. 35 days). Correspondingly, the period of hospitalization was also considerably shorter in the clonidine/chloral hydrate group (median: 32 days vs. 44 days). In addition, patients in the clonidine/chloral hydrate group exhibited markedly reduced withdrawal symptoms. Conclusion: This study suggests that a treatment of neonatal abstinence syndrome with clonidine in omission of opiates is possible without causing short-term adverse cardiovascular effects. Considering the retrospective design of the study, controlled and prospective trials are needed.

Goel N; Beasley D; Rajkumar V; Banerjee S. Perinatal outcome of illicit substance use in pregnancy: Comparative and contemporary socio-clinical profile in the UK. European Journal of Pediatrics 170(2): 199-205, 2011. (23 refs.)

The aim of the study was to determine the contemporary socio-clinical profile and perinatal outcome of illicit substance use in pregnancy in a large UK city and compare with published literature. Cases were identified retrospectively from the 'cause for concern' referrals over 5 years (2003-2007). Data was collected on mother-infant pair from medical notes and laboratory records. Chi-square and Mann-Whitney U tests were used where appropriate for statistical analysis. One hundred sixty-eight women were identified as using illicit substance in pregnancy. Smoking (97.4%), unemployment (85.4%) and single status (42.3%) were frequent. Besides controlled use of methadone, heroin, cannabis and benzodiazepines were the most commonly used drugs. Hepatitis C prevalence was high (29.9%) despite low antenatal screening rates (57.7%). Neonatal morbidity was related to prematurity (22.9%), small for dates (28.6%) and neonatal abstinence syndrome (NAS; 58.9%). By day 5 of life, 95.1% of the babies developing NAS and 96.1% of those requiring pharmacological treatment were symptomatic. Of the infants developing NAS, 31.7% required pharmacological treatment. A total of 82.5% babies went home with their mother, and 21.2% were placed on the Child Protection Register. Only 14.3% were breast feeding at discharge. Illicit substance use in pregnancy continues to be associated with significant maternal and neonatal morbidity, and the socio-clinical profile in this decade appears unchanged in the UK. Hepatitis C prevalence is high, and detection should be improved through targeted antenatal screening. Where facility in the community is unavailable, 5 days of hospital stay is sufficient to safely identify babies at risk of developing NAS. Most babies were discharged home with their mother.

Gray TR; Choo RE; Concheiro M; Williams E; Elko A; Jansson LM et al. Prenatal methadone exposure, meconium biomarker concentrations and neonatal abstinence syndrome. Addiction 105(12): 2151-2159, 2010. (50 refs.)

Aims: Methadone is standard pharmacotherapy for opioid-dependent pregnant women, yet the relationship between maternal methadone dose and neonatal abstinence syndrome (NAS) severity is still unclear. This research evaluated whether quantification of fetal methadone and drug exposure via meconium would reflect maternal dose and predict neonatal outcomes. Design: Prospective clinical study. Setting: An urban drug treatment facility treating pregnant and post-partum women and their children. Participants: Forty-nine opioid-dependent pregnant women received 30-110 mg methadone daily. Measurements: Maternal methadone dose, infant birth parameters and NAS assessments were extracted from medical records. Thrice-weekly urine specimens were screened for opioids and cocaine. Newborn meconium specimens were quantified for methadone, opioid, cocaine and tobacco biomarkers. Findings: There was no relationship between meconium methadone concentrations, presence of opioids, cocaine and/or tobacco in meconium, maternal methadone dose or NAS severity. Opioid and cocaine were also found in 36% and 38% of meconium specimens, respectively, and were associated with positive urine specimens in the third trimester. The presence of opioids other than methadone in meconium correlated with increased rates of preterm birth, longer infant hospital stays and decreased maternal time in drug treatment. Conclusions: Methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) concentrations in meconium did not predict infant birth parameters or NAS severity. Prospective urine testing defined meconium drug detection windows for opiates and cocaine as 3 months, rather than the currently accepted 6 months. The presence of opioids in meconium could be used as a biomarker for infants at elevated risk in the newborn period.

Holbrook A; Kaltenbach K. Gender and NAS: Does sex matter? Drug and Alcohol Dependence 112(1-2): 156-159, 2010. (28 refs.)

Background: Neonatal abstinence syndrome (NAS) is a constellation of symptoms resulting from in utero exposure to opioids that appears in 30-80% of opioid exposed infants. Variability in NAS symtomatology is not well understood, and recently it has been suggested that the sex of the infant may play a role in predicting NAS severity. The current study examines the relationship of sex to need for NAS treatment, length of NAS treatment, and peak dose of medication required to treat NAS symptoms. Methods: Retrospective chart review of 308 infants was conducted to determine whether significant differences exist between male and female neonates in need for NAS treatment, length of treatment and peak dose of medication required. Chi-square, multiple ordinary least squares regression, and analysis of variance (ANOVA) analyses were conducted. Results: No significant differences were found in need for NAS treatment, length of treatment or peak dose of medication required between male and female neonates. Conclusions: Results suggest that no significant differences exist in NAS severity between male and female infants.

Isemann B; Meinzen-Derr J; Akinbi H. Maternal and neonatal factors impacting response to methadone therapy in infants treated for neonatal abstinence syndrome. Journal of Perinatology 31(1): 25-29, 2011. (27 refs.)

Objective: To identify maternal and neonatal factors that impact response to methadone therapy for neonatal abstinence syndrome. Study Design: This is a retrospective review of 128 infants that received pharmacotherapy for opiate withdrawal to identify factors associated with favorable response to methadone therapy. Maternal and neonatal data were analyzed with univariate statistics and multivariate logistic regression. Result: Maternal methadone maintenance dose during pregnancy correlated with length of stay (P=0.009). There was an inverse correlation between the amount of mother's breast milk ingested and length of stay (beta=-0.03, P=0.02). Methadone was initiated later, tapered more rapidly and was more successful as monotherapy in preterm infants. Five percent of infants were admitted to hospital again for rebound withdrawal following reduction of breast milk intake. Conclusion: Severity of neonatal abstinence syndrome may be mitigated by titrating methadone to the lowest effective dose during pregnancy and by encouraging breast milk feeds, which should be weaned gradually.

Jones HE. Commentary on Kraft, et al. (2011): Treatment of neonatal abstinence syndrome - morphine, buprenorphine and beyond. (editorial). Addiction 106(3): 581-582, 2011

Jones HE; Kaltenbach K; Heil SH; Stine SM; Coyle MG; Arria AM et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. New England Journal of Medicine 363(24): 2320-2331, 2010. (44 refs.)

BACKGROUND: Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy. METHODS: We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference. RESULTS: Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events. CONCLUSIONS: These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women.

Jones HE; Kaltenbach K; Heil SH; Stine SM; Coyle MG; Arria AM et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. (review). Obstetrical & Gynecological Survey 66(4): 191-193, 2011. (0 refs.)

The recommended treatment for opioid dependence in pregnant women is methadone, a full mu-opioid agonist. However, in utero exposure to methadone is associated with neonatal abstinence syndrome (NAS) that is characterized by hyperirritability of the central nervous system and a dysfunctional autonomic nervous system. Management of NAS often requires prolonged hospitalization and pharmacologic intervention. A partial mu-opioid agonist, buprenorphine, has been investigated as an alternative treatment for opioid dependence but relatively few studies of this drug have been conducted in pregnant women. Some prospective open-label and controlled studies suggest that NAS occurring in neonates treated prenatally with buprenorphine was less likely to require treatment than NAS in neonates exposed to prenatal methadone. However, the results of these studies have been inconsistent. This double-blind, randomized, controlled study compared the use of buprenorphine and methadone for management of pregnant women with opioid dependency. The study subjects were 175 pregnant opioid-dependent women enrolled at 8 international sites. A total of 131 of these women completed the trial; 58 (44%) were patients receiving buprenorphine and 73 (56%) were women treated with methadone. The 5 primary neonatal outcomes included the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, length of hospital stay, and head circumference. The P values for all group comparisons were calculated according to prespecified thresholds for significance. More women receiving prenatal buprenorphine (28/86, 33%) discontinued treatment as compared with those receiving prenatal methadone (16/89, 18%). In comparison with methadone, neonates of women treated with prenatal buprenorphine required significantly less morphine (mean dose, 1.1 vs. 10.4 mg; P < 0.009), had a 43% decrease in the hospital stay (10.0 vs. 17.5 days, P < 0.009), and spent 58% less time in the hospital receiving medication for NAS (4.1 vs. 9.9 days, P < 0.003). No significant differences were found between groups for other primary or secondary outcomes, including the number of neonates requiring NAS treatment, the peak NAS score, head circumference, or any other adverse neonatal or maternal outcome. These findings suggest that buprenorphine is an acceptable alternative to methadone for treatment for opioid dependency during pregnancy and with further studies, may actually be the preferred therapeutic.

Jones HE; O'Grady KE; Johnson RE; Velez M; Jansson LM. Infant neurobehavior following prenatal exposure to methadone or buprenorphine: Results from the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Substance Use & Misuse 45(13): 2244-2257, 2010. (23 refs.)

This study examined the neurobehavioral functioning of neonates prenatally exposed to methadone (n = 11) or buprenorphine (n = 10), who underwent the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) examinations on days 3, 5, 7, 10, and 14 post-delivery. Linear mixed model analyses revealed that NNNS scores of arousal and excitability showed significant differences between medications over time. Compared to neonates who did not require medication to treat neonatal abstinence syndrome (NAS), neonates receiving pharmacotherapy for NAS showed differences over time in quality of movement, excitability, and lethargy. Results suggest the NNNS may detect subtle differences over time between both neonates prenatally exposed to methadone or buprenorphine and neonates pharmacologically treated or untreated for NAS.

Kraft WK; Dysart K; Greenspan JS; Gibson E; Kaltenbach K; Ehrlich ME. Revised dose schema of sublingual buprenorphine in the treatment of the neonatal opioid abstinence syndrome. Addiction 106(3): 574-580, 2011. (27 refs.)

Aims: More than half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacological therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS. Design: Randomized, Phase 1, open-label, active-control clinical trial comparing sublingual buprenorphine to oral morphine. Setting: Large, urban, tertiary care hospital. Participants: Twenty-four term infants requiring pharmacological treatment for NAS. Measurements: Outcomes were neonatal safety, length of treatment and length of hospitalization. Findings: Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of treatment compared to 38 days for those treated with morphine (P = 0.01), representing a 40% reduction. Length of hospital stay in the buprenorphine group was reduced 24%, from 42 to 32 days (P = 0.05). Conclusions: Sublingual buprenorphine was safe in NAS, with a substantial efficacy advantage over standard of care therapy with oral morphine.

Lacroix I; Berrebi A; Garipuy D; Schmitt L; Hammou Y; Chaumerliac C et al. Buprenorphine versus methadone in pregnant opioid-dependent women: A prospective multicenter study. European Journal of Clinical Pharmacology 67(10): 1053-1059, 2011. (32 refs.)

In order to investigate the effects of exposure to buprenorphine compared with methadone during pregnancy, a prospective multicenter study was conducted in collaboration with maternity hospitals, maintenance therapy centers, and general practitioners involved in addiction care. Ninety pregnant women exposed to buprenorphine and 45 to metadone were selected for the study. During pregnancy, some women were exposed to illicit agents: cannabis (42% in the buprenorphine group vs. 58% in the methadone-treated group), heroin (17% vs. 44%), or cocaine (3% vs. 11%). Pregnancies ended in 85 vs. 40 live births, one vs. two stillbirths, two vs. one spontaneous abortion, two vs. one voluntary termination, and one vs. one medical termination in the buprenorphine and the methadone groups, respectively. Newborns had a birth weight of 2,892 +/- 506 g (buprenorphine) vs. 2,731 +/- 634 g (methadone) and a body length of 47.6 +/- 2.5 cm vs. 47.1 +/- 3 cm. 18.8% vs. 10% of newborns were delivered before 37 weeks of amenorrhea. Neonatal withdrawal syndrome occurred more frequently in the methadone group (62.5% vs. 41.2, p = 0.03). After adjustment for heroin exposure in late pregnancy, rates of neonatal withdrawal were no longer different between the methadone and buprenorphine groups. Twenty-one babies (84%) in the methadone group and 20 (57%) in the buprenorphine group (p = 0.03) required opiate treatment. We did not observe more frequent malformations or cases of withdrawal syndrome in the buprenorphine group than in the methadone-treated group. Buprenorphine appears to be as safe as the currently approved substitute methadone considered to date as the reference treatment for pregnant opioid-dependent women.

Lim S; Prasad MR; Samuels P; Gardner DK; Cordero L. High-dose methadone in pregnant women and its effect on duration of neonatal abstinence syndrome. American Journal of Obstetrics and Gynecology 200(1): Article Number: 70.e1, 2009. (18 refs.)

OBJECTIVE: The purpose of this study was to examine high-dose methadone in pregnant women and its effect on the duration of neonatal abstinence syndrome. STUDY DESIGN: This was a retrospective chart review of 68 neonates and their mothers who received methadone therapy during pregnancy. The last dosage of maternal methadone just before delivery and the length of treatment for neonatal abstinence syndrome were examined with an analysis of variance model. RESULTS: When the data were analyzed for methadone dosages as a continuous variable, each 1-mg increase in the last maternal methadone dosage before delivery was associated with an additional 0.18 days of infant treatment for neonatal abstinence syndrome (P < .001; 95% CI, 0.112-0.255). In other words, every increase of 5.5 mg of methadone in the mother was associated statistically with 1 additional day of neonatal abstinence syndrome treatment for the infant. Gestational age at delivery and birthweight were not statistically significant. CONCLUSION: Higher doses of maternal methadone were associated with an increase in diagnosis and longer duration of neonatal abstinence syndrome.

Liu AJW; Jones MP; Murray H; Cook CM; Nanan R. Perinatal risk factors for the neonatal abstinence syndrome in infants born to women on methadone maintenance therapy. Australian & New Zealand Journal of Obstetrics & Gynaecology 50(3): 253-258, 2010. (31 refs.)

Background: Neonatal abstinence syndrome (NAS) occurs in more than 50% of infants exposed to intrauterine opiates. Maternal opiate dosing has been investigated with conflicting results. Aims: The aims of this study were to correlate maternal methadone dose and other risk factors with the development of NAS requiring pharmacological treatment by using easily accessible clinical parameters. Methods: Retrospective medical record review of data from 228 opioid dependent pregnant women who delivered 232 live-born infants. Logistic regression analysis was performed on maternal, perinatal and neonatal parameters to identify risk factors for NAS requiring treatment. A prediction model was developed and validated on a separate independent cohort of 188 infants. Results: Of the 232 infants, 172 (74%) infants were treated for NAS. The risk of withdrawal increased by 17% per 5 mg increment of the last maternal methadone dose. The risk was lower for younger gestational ages and for those delivered by Caesarean section compared to those delivered by normal vaginal delivery. Through predictive modeling, gestational age, mode of delivery and last methadone dose were established as risk factors for withdrawal. The model was validated by other statistical measures and its diagnostic performance confirmed on the separate independent cohort. Conclusions: Our data suggests that timing and mode of delivery as well as last maternal methadone dose are significant risk factors for the development of NAS requiring treatment. Based on these clinical parameters, risk stratification for perinatal management of pregnancies associated with opioid dependency and risk prediction for the neonate might now be possible.

Mactier H. The management of heroin misuse in pregnancy: Time for a rethink? (review). Archives of Disease in Childhood. Fetal and Neonatal Edition 96(6): F457-F460, 2011. (42 refs.)

Heroin use in pregnancy is a worldwide problem. Methadone maintenance treatment has definite advantages for the mother and is currently recommended in the UK. There is, however, increasing evidence of adverse effects upon developing cortical and visual function in children of treated heroin-addicted mothers. The longer-term implications of this are not yet clear, and are confounded by poly-drug misuse and ongoing social deprivation. There is a paucity of evidence regarding outcome for infants who require pharmacological treatment for neonatal abstinence syndrome compared to those who have only mild symptoms. Well-controlled studies of the treatment of heroin misuse in pregnancy that take account of both neonatal and longer term outcomes for the child are urgently required.

O'Connor A; Alto W; Musgrave K; Gibbons D; Llanto L; Holden S et al. Observational study of buprenorphine treatment of opioid-dependent pregnant women in a family medicine residency: Reports on maternal and infant outcomes. Journal of the American Board of Family Medicine 24(2): 194-201, 2011. (29 refs.)

Purpose: Within a family medicine residency, an outpatient buprenorphine treatment program was provided for pregnant women who were dependent on opioids. The purpose of this study was to investigate the outcomes of infants who were exposed to a range of doses of buprenorphine in utero and to determine how closely observed maternal/fetal outcomes (eg, method of delivery and infants requiring treatment for neonatal abstinence syndrome [NAS]) match those previously reported in the literature. Methods: This study consists of a retrospective case series of 23 infants born to 22 pregnant women who were dependent on opioids and who were treated with buprenorphine during a 31-month period. Results: Thirty-five percent of infants (8 of 23) required treatment for NAS. There was no significant relationship between maternal dose of buprenorphine and birth weight, NAS severity (ie, peak NAS score), or time to first peak NAS score. Infants born to tobacco users had a significantly lower birth weight (P = .0136) than infants born to nonusers. Seventy percent of infants (16 of 23) were breast-feeding at the time of discharge from the hospital. Conclusions: The observations made in this case series are consistent with data previously reported in the literature. Infants in this study were more likely to be breastfed than those previously described by others, but further analysis is necessary to determine whether this finding is significant.

O'Donnell M; Nassar N; Leonard H; Hagan R; Mathews R; Patterson Y et al. Increasing prevalence of neonatal withdrawal syndrome: Population study of maternal factors and child protection involvement. Pediatrics 123(4): E614-E621, 2009. (28 refs.)

OBJECTIVES. Illicit drug use during pregnancy is an important public health issue, with adverse effects on the newborn and implications for subsequent parenting. The aim of this study was to measure the birth prevalence of neonatal withdrawal syndrome over time, associated maternal characteristics and child protection involvement. METHODS. This is a retrospective cohort study that used linked health and child protection databases for all live births in Western Australia from 1980 to 2005. Maternal characteristics and mental health- and assault-related medical history were assessed by using logistic regression models. RESULTS. The birth prevalence of neonatal withdrawal syndrome increased from 0.97 to a high of 42.2 per 10 000 live births, plateauing after 2002. Mothers with a previous mental health admission, low skill level, Aboriginal status or who smoked during pregnancy were significantly more likely to have an infant with neonatal withdrawal syndrome. These infants were at greater risk for having a substantiated child maltreatment allegation and entering foster care. Increased risk for maltreatment was associated with mothers who were aged <30 years, were from socially disadvantaged backgrounds, Aboriginal status, and had a mental health- or assault-related admission. CONCLUSIONS. There has been a marked increase in neonatal withdrawal syndrome in the past 25 years. Specific maternal characteristics identified should facilitate planning for early identification and intervention for these women. Findings demonstrate an important pathway into child maltreatment and highlight the need for well-supported programs for women who use illicit drugs during pregnancy as well as the support after birth. Pediatrics 2009; 123: e614-e621

O'Mara K; Gal P; DaVanzo C. Treatment of neonatal withdrawal with clonidine after long-term, high-dose maternal use of tramadol. Annals of Pharmacotherapy 44(7-8): 1342-1344, 2010. (10 refs.)

OBJECTIVE: To describe a case of tramadol withdrawal in a neonate and treatment with clonidine after exposure to long-term maternal use of high-dose tramadol. CASE SUMMARY: A 34-week gestational age neonate displayed symptoms of tramadol withdrawal within 48 hours of delivery. Due to a confusing initial clinical picture, including presumed congenital Chlamydia, questionable seizures, and an original report of maternal use of ketorolac (Toradol), diagnosis was delayed until day of life 5. Symptoms included jitteriness, myoclonic movements, and irritability. Upon further questioning of the mother, it was revealed that she was actually taking tramadol 600-800 mg daily. The infant was placed on maintenance therapy with oral clonidine (from 1 to 3 mu g/kg orally every 3 hours) until discontinuation on day of life 11. After 3 days off treatment, he began to display symptoms of withdrawal again. Clonidine was restarted at 1 mu g/kg orally every 8 hours and he was discharged home on maintenance clonidine therapy at 18 days postnatal age. A 7-day tapering regimen was initiated 2 weeks after discharge, and no further withdrawal symptoms occurred. DISCUSSION: Few published articles are available to guide clinicians on the clinical course and treatment strategies for tramadol dependence and withdrawal. In neonates, the reports are particularly sparse. Traditional agents used in neonatal opioid withdrawal are narcotics (morphine, tincture of opium, methadone), benzodiazepines (diazepam, lorazepam), and phenobarbital. Clonidine use for neonatal abstinence syndrome from narcotics has been shown to be effective alone or in combination with agents such as other opiates and chloral hydrate. Potential benefits of clonidine therapy include shorter duration of therapy, reduced withdrawal symptoms, and decreased length of hospital stay. CONCLUSIONS: Withdrawal can be prolonged in infants exposed to maternal tramadol use. Clonidine may be a safe and effective option for managing symptoms of neonatal tramadol abstinence.

Osborn DA; Jeffery HE; Cole MJ. Opiate treatment for opiate withdrawal in newborn infants. (review). Cochrane Database of Systematic Reviews 10(CD002059), 2010. (76 refs.)

Background: 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. Objectives: 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. Search strategy: The review was updated in 2010 with additional searches CENTRAL, MEDLINE and EMBASE supplemented by searches of conference abstracts and citation lists of published articles. Selection criteria: Randomized or quasi-randomized controlled trials of opiate treatment in infants with NAS born to mothers with opiate dependence. Data collection and analysis Each author assessed study quality and extracted data independently. Main results: Nine studies enrolling 645 infants met inclusion criteria. There were substantial methodological concerns in all studies comparing an opiate with a sedative. Two small studies comparing different opiates were of good methodology. Opiate (morphine) versus supportive care (one study): A reduction in time to regain birth weight and duration of supportive care and a significant increase in hospital stay was noted. Opiate versus phenobarbitone (four studies): Meta-analysis found no significant difference in treatment failure. One study reported opiate treatment resulted in a significant reduction in treatment failure in infants of mothers using only opiates. One study reported a significant reduction in days treatment and admission to the nursery for infants receiving morphine. One study reported a reduction in seizures, of borderline statistical significance, with the use of opiate. Opiate versus diazepam (two studies): Meta-analysis found a significant reduction in treatment failure with the use of opiate. Different opiates (six studies): there is insufficient data to determine safety or efficacy of any specific opiate compared to another opiate. Authors' conclusions: Opiates compared to supportive care may reduce time to regain birth weight and duration of supportive care but increase duration of hospital stay. When compared to phenobarbitone, opiates may reduce the incidence of seizures but there is no evidence of effect on treatment failure. One study reported a reduction in duration of treatment and nursery admission for infants on morphine. Compared to diazepam, opiates reduce the incidence of treatment failure. A post-hoc analysis generates the hypothesis that initial opiate treatment may be 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.

Osborn DA; Jeffery HE; Cole MJ. Sedatives for opiate withdrawal in newborn infants. (review). Cochrane Database of Systematic Reviews 10: CD002053, 2010. (65 refs.)

Background: 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. Objectives: 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. Search strategy: 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. Selection criteria 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. Data collection and analysis Each author assessed study quality and extracted data independently. Main results: 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 Sedatives for opiate withdrawal in newborn infants (Review) 1 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. Authors' conclusions: 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.

Pizarro D; Habli M; Grier M; Bombrys A; Sibai B; Livingston J. Higher maternal doses of methadone does not increase neonatal abstinence syndrome. Journal of Substance Abuse Treatment 40(3): 295-298, 2011. (14 refs.)

Objective: The purpose of this study is to assess the incidence of clinically significant neonatal abstinence syndrome (NAS) based on maternal antenatal methadone dosing in women with a history of narcotic dependence. Study design: A retrospective review of 174 pregnant women on methadone maintenance was performed. Data were stratified based on maternal methadone dose at delivery: low (0-50 mg/day, n = 59), medium (51-100 mg/day, n = 63), and high (>100 mg/day, a = 52). NAS was defined by Finnegan as score greater than 7 on two occasions. Outcome measures were rate and severity of NAS, birth weight, preterm birth rate, and neonatal morbidities and mortality. Results: The rates of NAS (40.7% vs. 52.4% vs. 40.8%, p > .05), birth weight, and neonatal morbidities were similar regardless of the maternal methadone dose. Although there was a trend toward earlier delivery, the rate of preterm birth among the three groups (low dose, 17%; medium dose, 19%; high dose, 27%; p > .05) was not statistically significant. Conclusion: Higher maintenance dosing of methadone is not associated with increased rate or severity of NAS or other adverse perinatal outcomes. Concerns about NAS should not restrict the methadone dosing during pregnancy. Methadone dosing should not be restricted to lower dosing during pregnancy.

Raith W; Kutschera J; Muller W; Urlesberger B. Active ear acupuncture points in neonates with neonatal abstinence syndrome (NAS). American Journal of Chinese Medicine 39(1): 29-37, 2011. (28 refs.)

The aim of the study was to determine the presence of acupuncture ear points in neonates with Neonatal Abstinence Syndrome (NAS). NAS occurs in the first days of life in neonates whose mothers have a history of drug abuse, and may also occur in neonates whose mothers are currently following substitution therapy. The patients are neonates with NAS admitted over one year to the Division of Neonatology at the University Hospital Graz. The examination took place on the third day after delivery (mean value 70.3 hours) and was performed by a neuronal pen (PS 3 (c) Silberbauer, Vienna, Austria). An integrated sound and optical signal detected the active ear points that were then placed on an ear map. We investigated six neonates (four male, two female). All investigated neonates showed the presence of active ear acupuncture points. The psychovegetative rim was the most common organic area of the children, following by a few organic points. This corresponds with the results found in healthy neonates. In all neonates with NAS, we found the presence of psychic ear points. The identified psychic ear points are the frustration-point, R-point and the psychotropic area nasal from the incisura intertragica. In all neonates with NAS, active organic and psychic ear points were detectable in both ears. In the future, it could be possible to use active ear points for diagnostic and therapeutic purposes.

Sarfi M; Martinsen H; Bakstad B; Roislien J; Waal H. Patterns in sleep-wakefulness in three-month old infants exposed to methadone or buprenorphine. Early Human Development 85(12): 773-778, 2009. (42 refs.)

Background: Infants exposed to opioides in-utero frequently demonstrate withdrawal symptoms in the neonatal period and have difficulties with state regulation. Aim: This study examines sleep-wakefulness-distress patterns as indicators of regulatory mechanisms at 3 months of age. Participants: A national infant cohort (N=35) born to women in high-dose maintenance treatment during pregnancy and a comparison group (N=36) of low-risk infants born in the same period. Outcome measures: Distributions and frequencies of sleep, wakefulness and distress measured in hours and episodes on sleep charts recorded by the mothers in the two groups. Results: Women in maintenance treatment were monitored closely during pregnancy to avoid illicit drug use and to be prepared for motherhood. They were also offered residential treatment before pregnancy and after the child was born. There were no statistical differences between the two groups in any of the 10 measures reflecting diurnal and nocturnal rhythmicity at 3 months despite of neonatal abstinence syndrome in 47% of the exposed infants and significant differences in infant characteristics with respect to birth weight, gestational age and maternal characteristics. Conclusions: Follow-up procedures combining drug monitoring and counseling during pregnancy and in the first months after birth enhance the development of state regulation in terms of sleep-wakefulness patterns.

Seligman NS; Almario CV; Hayes EJ; Dysart KC; Berghella V; Baxter JK. Relationship between maternal methadone dose at delivery and neonatal abstinence syndrome. Journal of Pediatrics (3): 428-U112, 2010. (53 refs.)

Objective: To estimate the relationship between maternal methadone dose and the incidence of neonatal abstinence syndrome (NAS). Study design: We performed a retrospective cohort study of pregnant women treated with methadone for opiate addiction who delivered live-born neonates between 1996 and 2006. Four dose groups, on the basis of total daily methadone dose, were compared (<= 80 mg/d, 81-120 mg/d, 121-160 mg/d, and >160 mg/d). The primary outcome was treatment for NAS. Symptoms of NAS were objectively measured with the Finnegan scoring system, and treatment was initiated for a score >24 during the prior 24 hours. Results: A total of 330 women treated with methadone and their 388 offspring were included. Average methadone dose at delivery was 117 +/- 50 mg/d (range, 20-340 mg/d). Overall, 68% of infants were treated for NAS. Of infants exposed to methadone doses <= 80 mg/d, 81-120 mg/d, 121-160 mg/d, and >160 mg/d, treatment for NAS was initiated for 68%, 63%, 70%, and 73% of neonates, respectively (P = .48). The rate of maternal illicit opiate abuse at delivery was 26%, 28%, 19%, and 11%, respectively (P = .04). Conclusion: No correlation was found between maternal methadone dose and rate of NAS. However, higher doses of methadone were associated with decreased illicit opiate abuse at delivery.

Simmat-Durand L; Lejeune C; Gourarier L. Pregnancy under high-dose buprenorphine. European Journal of Obstetrics & Gynecology and Reproductive Biology 142(2): 119-123, 2009. (21 refs.)

Objective: This study was first conducted to compare the consequences of the use of methadone and high-dose buprenorphine in pregnancy in France and secondly to describe the heterogeneity of women under high-dose buprenorphine. This paper focuses on the second point only. Study design: From October 1998 to September 1999, data on pregnancy, delivery outcomes and neonatal parameters were collected for 251 addicted women on methadone or high-dose buprenorphine (HDB) substitution followed in 35 hospitals and clinics in continental France. Then the data of 159 women who had been taking HDB during pregnancy and had delivered 160 live infants were analyzed. Results: Most of these women were treated as outpatients by general practitioners. 43% of them belong to what we considered a "hidden population" of drug users: most of them were native French citizens, who lived with the future fathers in their own homes, had at least some secondary education, and were usually not followed in specialized centers for drug addicts. Almost all the women smoked every day during their pregnancies; 20% used heroin during the last 4 weeks preceding delivery; 16% admitted having injected HDB at least once. Notably. neither the severity nor the duration of the neonatal abstinence syndrome (NAS) seemed to be related to the daily doses of the substitution agent. Half of the newborns were treated for NAS, mainly with morphine hydrochloride. Conclusion: Although two different populations of women were clearly identified, 64 with no social disadvantage and 95 socially disadvantaged, there was no difference between the groups as for the severity of NAS which was only related to the mothers' compliance with a programme of treatment against addiction.

Stroud LR; Paster RL; Papandonatos GD; Niaura R; Salisbury AL; Battle C et al. Maternal smoking during pregnancy and newborn neurobehavior: Effects at 10 to 27 Days. Journal of Pediatrics 154(1): 10-16, 2009. (36 refs.)

Objective: To examine effects of maternal smoking during pregnancy on newborn neurobehavior at 10 to 27 days. Study design Participants were 56 healthy infants (28 smoking-exposed. 28 unexposed) matched on maternal social class., age, and alcohol use. Maternal smoking during pregnancy was determined by maternal interview and maternal saliva cotinine. Postnatal smoke exposure was quantified by infant saliva cotinine. Infant neurobehavior was assessed through the NICU Network Neurobehavioral Scale. Results: Smoking-exposed infants showed greater need for handling and worse self-regulation (P < .05) and trended toward greater excitability and arousal (P < .10) relative to matched, unexposed infants (all moderate effect sizes). In contrast to prior studies of days 0 to 5, no effects of smoking-exposure on signs of stress/abstinence or muscle tone emerged. In stratified, adjusted analyses, only effects on need for handling remained significant (P < .05, large effect size). Conclusions Effects of maternal smoking during pregnancy at 10 to 27 days lire subtle and consistent with increased need for external intervention and poorer self-regulation. Along with parenting deficits, these effects may represent early precursors for long-term adverse outcomes from maternal smoking during pregnancy. That signs of abstinence shown in prior studies of 0- to 5-day-old newborns did not emerge in older newborns provides further evidence for the possibility of it withdrawal process in exposed infants.

Thajam D; Atkinson DE; Sibley CP; Lavender T. Is neonatal abstinence syndrome related to the amount of opiate used? (review). Journal of Obstetric, Gynecologic and Neonatal Nursing 39(5): 503-509, 2010. (26 refs.)

Objective: To determine if a relationship exists between the dose of heroin and/or substitute medication used in pregnancy and neonatal abstinence syndrome (NAS). Data Sources: Ovid online was used to search the following: EMBASE, Ovid MEDLINE, CINHAL, PscyINFO, Cochrane Database of Systematic Reviews. Study Selection: English language journal articles reporting original research undertaken and published between 1995 and 2009 that examined relationships between NAS and opiate use in pregnancy and with patterns of substance abuse that reflect those of the United Kingdom and other high-resource settings. Data Extraction: The studies were reviewed independently by two authors using predefined quality criteria. Data Synthesis: This was a narrative review; key messages from included studies were discussed in the context of the diversity and commonality of findings in relation to NAS. Conclusions: No correlation between the amount of fetal opioid exposure and expression of NAS was reported in eight of the 10 studies. This observation was consistent across international boundaries, and studies that included both methadone and buprenorphine.

Twomey JE; Caldwell D; Soave R; Fontaine LA; Lester BM. Vulnerable infants program of Rhode Island: Promoting permanency for substance-exposed infants. Child Welfare 89(3): 121-U4, 2010. (40 refs.)

The Vulnerable Infants Program of Rhode Island is a care coordination program to promote permanency for substance-exposed infants by addressing parental needs and increasing collaboration among social service agencies. Over the first four years of the program, there was a decrease in time spent in the newborn nursery beyond medical necessity and identification of permanent placements by 12 months for 84% of infants, with the majority of infants (78%) placed with biological parents or relatives.

Unger A; Jagsch R; Jones H; Arria A; Leitich H; Rohrmeister K et al. Randomized controlled trials in pregnancy: Scientific and ethical aspects. Exposure to different opioid medications during pregnancy in an intra-individual comparison. Addiction 106(7): 1355-1362, 2011. (34 refs.)

Background: Chronic medical conditions such as opioid dependence require evidence-based treatment recommendations. However, pregnant women are under-represented in clinical trials. We describe the first within-subject comparison of maternal and neonatal outcomes for methadone-versus buprenorphine-exposed pregnancies. Although methadone is the established treatment of pregnant opioid-dependent women, recent investigations have shown a trend for a milder neonatal abstinence syndrome (NAS) under buprenorphine. However, it is not only the choice of maintenance medication that determines the occurrence of NAS; other factors such as maternal metabolism, illicit substance abuse and nicotine consumption also influence its severity and duration and represent confounding factors in the assessment of randomized clinical trials. Case series description Three women who were part of the European cohort of a randomized, double-blind multi-center trial with a contingency management tool [the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study], each had two consecutive pregnancies and were maintained on either methadone or buprenorphine for their first and then the respective opposite, still-blinded medication for their second pregnancy. Birth measurements, the total neonatal abstinence score, the total amounts of medication used to treat NAS and the days of NAS treatment duration were assessed. Results: Both medications were effective and safe in reducing illicit opioid relapse and avoiding preterm labor. Methadone maintenance yielded to a significantly higher neonatal birth weight. Data patterns suggest that buprenorphine exposure was associated with lower neonatal abstinence syndrome (NAS) scores. Findings from this unique case series are consistent with earlier reports using between-group analyses. Conclusions: Buprenorphine has the potential to become an established treatment alternative to methadone for pregnant opioid-dependent women. Under special consideration of ethical boundaries, psychopharmacological treatment during pregnancy must be addressed as an integral part of clinical research projects in order to optimize treatment for women and neonates.

Wachman EM; Byun J; Philipp BL. Breastfeeding rates among mothers of infants with neonatal abstinence syndrome. Breastfeeding Medicine 5(4): 159-164, 2010. (36 refs.)

Background: Woman who struggle with drug addiction during pregnancy are perhaps the most vulnerable of new mothers. The opioid substitution medications methadone and buprenorphine are both compatible with breastfeeding. The objective of this study is to determine breastfeeding rates among opioid-dependent women giving birth in a baby-friendly hospital. Methods: We performed a retrospective chart review of all infants born at Boston Medical Center (Boston, MA) between July 2003 and January 2009 with a diagnosis of neonatal abstinence syndrome. Feeding information was obtained, as well as baseline medical information about the mother-infant pairs. Breastfeeding eligibility was determined by a negative urine toxicology screen on admission, no illicit drug use in the third trimester, and a negative human immunodeficiency virus status. Results: Two hundred seventy-six mother-infant pairs were identified. Forty percent of the mothers carried one or more psychiatric diagnoses; 24% were taking two or more psychiatric medications. Sixty-eight percent of the mothers were eligible to breastfeed; of those, 24% breastfed to some extent during their infant's hospitalization. Sixty-percent of those who initiated stopped breastfeeding after an average of 5.88 days (SD 6.51). Conclusions: Breastfeeding rates among opioid-dependent women were low, with three-quarters of those eligible electing not to breastfeed. Of the minority of women who did choose to breastfeed, more than half stopped within 1 week.

Zimmermann-Baer U; Notzli U; Rentsch K; Bucher HU. Finnegan Neonatal Abstinence Scoring System: Normal values for first 3 days and weeks 5-6 in non-addicted infants. Addiction 105(3): 524-528, 2010. (13 refs.)

Objective: The neonatal abstinence scoring system proposed by Finnegan is used widely in neonatal units to initiate and to guide therapy in babies of opiate-dependent mothers. The purpose of this study was to assess the variability of the scores in newborns and infants not exposed to opiates during the first 3 days of life and during 3 consecutive days in weeks 5 or 6. Patients and methods: Healthy neonates born after 34 completed weeks of gestation, whose parents denied opiate consumption and gave informed consent, were included in this observational study. Infants with signs or symptoms of disease or with feeding problems were excluded. A modified scoring system was used every 8 hours during 72 hours by trained nurses; 102 neonates were observed for the first 3 days of life and 26 neonates in weeks 5-6. A meconium sample and a urine sample at weeks 5-6 were stored from all infants to be analysed for drugs when the baby scored high. Given a non-Gaussian distribution the scores were represented as percentiles. Results: During the first 3 days of life median scores remained stable at 2 but the variability increased, with the 95th percentile rising from 5.5 on day 1 to 7 on day 2. At weeks 5-6 median values were higher during daytime (50th percentile = 5, 95th percentile = 8) than night-time (50th percentile = 2, 95th percentile = 6, P = 0.02). Conclusion: Scores increase from days 1-3 to weeks 5-6 and show day-night cycles with 5-6 weeks. Values above 8 can be considered pathological. This data may help to raise suspicion of narcotic withdrawal and to guide therapy.