Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 May 18;5(5):CD002053.
doi: 10.1002/14651858.CD002053.pub4.

Sedatives for opioid withdrawal in newborn infants

Angelika Zankl  1   2 , Jill Martin  1 , Jane G Davey  1 , David A Osborn  1   2
Affiliations
Meta-Analysis

Sedatives for opioid withdrawal in newborn infants

Angelika Zankl et al. Cochrane Database Syst Rev. .

Abstract

Background: Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems.

Objectives: To assess the effectiveness and safety of using a sedative versus control (placebo, usual treatment or non-pharmacological treatment) for NAS due to withdrawal from opioids and determine which type of sedative is most effective and safe for NAS due to withdrawal from opioids.

Search methods: We ran an updated search on 17 September 2020 in CENTRAL via CRS Web and MEDLINE via Ovid. We searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection criteria: We included trials enrolling infants with NAS born to mothers with an opioid dependence with more than 80% follow-up and using randomised, quasi-randomised and cluster-randomised allocation to sedative or control.

Data collection and analysis: Three review authors assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of the evidence.

Main results: We included 10 trials (581 infants) with NAS secondary to maternal opioid use in pregnancy. There were multiple comparisons of different sedatives and regimens. There were limited data available for use in sensitivity analysis of studies at low risk of bias. Phenobarbital versus supportive care: one study reported there may be little or no difference in treatment failure with phenobarbital and supportive care versus supportive care alone (risk ratio (RR) 2.73, 95% confidence interval (CI) 0.94 to 7.94; 62 participants; very low-certainty evidence). No infant had a clinical seizure. The study did not report mortality, neurodevelopmental disability and adverse events. There may be an increase in days' hospitalisation and treatment from use of phenobarbital (hospitalisation: mean difference (MD) 20.80, 95% CI 13.64 to 27.96; treatment: MD 17.90, 95% CI 11.98 to 23.82; both 62 participants; very low-certainty evidence). Phenobarbital versus diazepam: there may be a reduction in treatment failure with phenobarbital versus diazepam (RR 0.39, 95% CI 0.24 to 0.62; 139 participants; 2 studies; low-certainty evidence). The studies did not report mortality, neurodevelopmental disability and adverse events. One study reported there may be little or no difference in days' hospitalisation and treatment (hospitalisation: MD 3.89, 95% CI -1.20 to 8.98; 32 participants; treatment: MD 4.30, 95% CI -0.73 to 9.33; 31 participants; both low-certainty evidence). Phenobarbital versus chlorpromazine: there may be a reduction in treatment failure with phenobarbital versus chlorpromazine (RR 0.55, 95% CI 0.33 to 0.92; 138 participants; 2 studies; very low-certainty evidence), and no infant had a seizure. The studies did not report mortality and neurodevelopmental disability. One study reported there may be little or no difference in days' hospitalisation (MD 7.00, 95% CI -3.51 to 17.51; 87 participants; low-certainty evidence) and 0/100 infants had an adverse event. Phenobarbital and opioid versus opioid alone: one study reported no infants with treatment failure and no clinical seizures in either group (low-certainty evidence). The study did not report mortality, neurodevelopmental disability and adverse events. One study reported there may be a reduction in days' hospitalisation for infants treated with phenobarbital and opioid (MD -43.50, 95% CI -59.18 to -27.82; 20 participants; low-certainty evidence). Clonidine and opioid versus opioid alone: one study reported there may be little or no difference in treatment failure with clonidine and dilute tincture of opium (DTO) versus DTO alone (RR 0.09, 95% CI 0.01 to 1.59; 80 participants; very low-certainty evidence). All five infants with treatment failure were in the DTO group. There may be little or no difference in seizures (RR 0.14, 95% CI 0.01 to 2.68; 80 participants; very low-certainty evidence). All three infants with seizures were in the DTO group. There may be little or no difference in mortality after discharge (RR 7.00, 95% CI 0.37 to 131.28; 80 participants; very low-certainty evidence). All three deaths were in the clonidine and DTO group. The study did not report neurodevelopmental disability. There may be little or no difference in days' treatment (MD -4.00, 95% CI -8.33 to 0.33; 80 participants; very low-certainty evidence). One adverse event occurred in the clonidine and DTO group. There may be little or no difference in rebound NAS after stopping treatment, although all seven cases were in the clonidine and DTO group. Clonidine and opioid versus phenobarbital and opioid: there may be little or no difference in treatment failure (RR 2.27, 95% CI 0.98 to 5.25; 2 studies, 93 participants; very low-certainty evidence). One study reported one infant in the clonidine and morphine group had a seizure, and there were no infant mortalities. The studies did not report neurodevelopmental disability. There may be an increase in days' hospitalisation and days' treatment with clonidine and opioid versus phenobarbital and opioid(hospitalisation: MD 7.13, 95% CI 6.38 to 7.88; treatment: MD 7.57, 95% CI 3.97 to 11.17; both 2 studies, 91 participants; low-certainty evidence). There may be little or no difference in adverse events (RR 1.55, 95% CI 0.44 to 5.40; 2 studies, 93 participants; very low-certainty evidence). However, there was oversedation only in the phenobarbital and morphine group; and hypotension, rebound hypertension and rebound NAS only in the clonidine and morphine group.

Authors' conclusions: There is very low-certainty evidence that phenobarbital increases duration of hospitalisation and treatment, but reduces days to regain birthweight and duration of supportive care each day compared to supportive care alone. There is low-certainty evidence that phenobarbital reduces treatment failure compared to diazepam and very low-certainty evidence that phenobarbital reduces treatment failure compared to chlorpromazine. There is low-certainty evidence of an increase in days' hospitalisation and days' treatment with clonidine and opioid compared to phenobarbital and opioid. There are insufficient data to determine the safety and incidence of adverse events for infants treated with combinations of opioids and sedatives including phenobarbital and clonidine.

PubMed Disclaimer

Conflict of interest statement

AZ: none.

JM: none.

JGD: none.

DO: none.

Figures

1
1
Screen4Me summary diagram. RCT: randomised controlled trial.
2
2
Study flow diagram: review update
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Phenobarbital versus supportive care (all infants), Outcome 1: Treatment failure
1.2
1.2. Analysis
Comparison 1: Phenobarbital versus supportive care (all infants), Outcome 2: Seizures
1.3
1.3. Analysis
Comparison 1: Phenobarbital versus supportive care (all infants), Outcome 3: Days' hospitalisation
1.4
1.4. Analysis
Comparison 1: Phenobarbital versus supportive care (all infants), Outcome 4: Days' pharmacological treatment
1.5
1.5. Analysis
Comparison 1: Phenobarbital versus supportive care (all infants), Outcome 5: Time to regain birth weight (days)
1.6
1.6. Analysis
Comparison 1: Phenobarbital versus supportive care (all infants), Outcome 6: Duration of stay in special care nursery (days)
1.7
1.7. Analysis
Comparison 1: Phenobarbital versus supportive care (all infants), Outcome 7: Duration of supportive care per day (minutes)
2.1
2.1. Analysis
Comparison 2: Phenobarbital versus diazepam (all infants), Outcome 1: Treatment failure
2.2
2.2. Analysis
Comparison 2: Phenobarbital versus diazepam (all infants), Outcome 2: Days' hospitalisation
2.3
2.3. Analysis
Comparison 2: Phenobarbital versus diazepam (all infants), Outcome 3: Days' pharmacological treatment
3.1
3.1. Analysis
Comparison 3: Phenobarbital versus diazepam (infants of mothers using only opioids), Outcome 1: Treatment failure
4.1
4.1. Analysis
Comparison 4: Phenobarbital versus diazepam (infants of mothers using opioids and other drugs), Outcome 1: Treatment failure
5.1
5.1. Analysis
Comparison 5: Phenobarbital versus chlorpromazine (all infants), Outcome 1: Treatment failure
5.2
5.2. Analysis
Comparison 5: Phenobarbital versus chlorpromazine (all infants), Outcome 2: Need for second drug
5.3
5.3. Analysis
Comparison 5: Phenobarbital versus chlorpromazine (all infants), Outcome 3: Seizures
5.4
5.4. Analysis
Comparison 5: Phenobarbital versus chlorpromazine (all infants), Outcome 4: Days' hospitalisation
5.5
5.5. Analysis
Comparison 5: Phenobarbital versus chlorpromazine (all infants), Outcome 5: Adverse events
6.1
6.1. Analysis
Comparison 6: Phenobarbital titration with loading dose versus phenobarbitone titration alone (all infants), Outcome 1: Treatment failure
7.1
7.1. Analysis
Comparison 7: Short versus long course of phenobarbital (all infants), Outcome 1: Treatment failure
8.1
8.1. Analysis
Comparison 8: Short versus long course of chlorpromazine (all infants), Outcome 1: Treatment failure
9.1
9.1. Analysis
Comparison 9: Phenobarbital and opioid versus opioid alone (all infants), Outcome 1: Treatment failure
9.2
9.2. Analysis
Comparison 9: Phenobarbital and opioid versus opioid alone (all infants), Outcome 2: Seizures
9.3
9.3. Analysis
Comparison 9: Phenobarbital and opioid versus opioid alone (all infants), Outcome 3: Percent time Finnegan score ≥ 8
9.4
9.4. Analysis
Comparison 9: Phenobarbital and opioid versus opioid alone (all infants), Outcome 4: Days' hospitalisation
10.1
10.1. Analysis
Comparison 10: Clonidine and opioid versus opioid alone (all infants), Outcome 1: Treatment failure
10.2
10.2. Analysis
Comparison 10: Clonidine and opioid versus opioid alone (all infants), Outcome 2: Seizures
10.3
10.3. Analysis
Comparison 10: Clonidine and opioid versus opioid alone (all infants), Outcome 3: Mortality after discharge
10.4
10.4. Analysis
Comparison 10: Clonidine and opioid versus opioid alone (all infants), Outcome 4: Days' pharmacological treatment
10.5
10.5. Analysis
Comparison 10: Clonidine and opioid versus opioid alone (all infants), Outcome 5: Maximum weight loss (%)
10.6
10.6. Analysis
Comparison 10: Clonidine and opioid versus opioid alone (all infants), Outcome 6: Adverse events (treatment‐related)
10.7
10.7. Analysis
Comparison 10: Clonidine and opioid versus opioid alone (all infants), Outcome 7: Rebound neonatal abstinence syndrome after stopping treatment requiring retreatment
11.1
11.1. Analysis
Comparison 11: Clonidine and opioid versus phenobarbital and opioid (all infants), Outcome 1: Treatment failure
11.2
11.2. Analysis
Comparison 11: Clonidine and opioid versus phenobarbital and opioid (all infants), Outcome 2: Seizures
11.3
11.3. Analysis
Comparison 11: Clonidine and opioid versus phenobarbital and opioid (all infants), Outcome 3: Mortality to discharge
11.4
11.4. Analysis
Comparison 11: Clonidine and opioid versus phenobarbital and opioid (all infants), Outcome 4: Days' hospitalisation
11.5
11.5. Analysis
Comparison 11: Clonidine and opioid versus phenobarbital and opioid (all infants), Outcome 5: Days' pharmacological treatment
11.6
11.6. Analysis
Comparison 11: Clonidine and opioid versus phenobarbital and opioid (all infants), Outcome 6: Adverse events (treatment‐related)
12.1
12.1. Analysis
Comparison 12: Sensitivity analyses, Outcome 1: Treatment failure
12.2
12.2. Analysis
Comparison 12: Sensitivity analyses, Outcome 2: Seizures
12.3
12.3. Analysis
Comparison 12: Sensitivity analyses, Outcome 3: Mortality after discharge
12.4
12.4. Analysis
Comparison 12: Sensitivity analyses, Outcome 4: Days' pharmacological treatment
12.5
12.5. Analysis
Comparison 12: Sensitivity analyses, Outcome 5: Adverse events
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Agthe 2009 {published data only}
    1. 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 2009;123(5):e849-56. [DOI: 10.1542/peds.2008-0978] [PMID: ] - DOI - PMC - PubMed
    1. Agthe AG, Mathias KB, Hendrix CW, Jansson L, Yaster M, Roark TR, et al. A blinded randomized clinical trial of clonidine in combination with diluted tincture of opium (DTO) versus DTO alone for neonatal abstinence syndrome (NAS). European Journal of Pediatrics 2006;165(S1):11.
    1. Agthe AG, Mathias KB, Hendrix CW, Jansson L, Yaster M, Roark TR, et al. Clonidine in combination with diluted tincture of opium (DTO) versus DTO alone for opioid withdrawal in newborn infants: a blinded randomized clinical trial. In: ePAS. 2007:https://www.pas-meeting.org/past-abstracts/.
    1. Liu T, Lewis T, Gauda E, Gobburu J, Ivaturi V. Mechanistic population pharmacokinetics of morphine in neonates with abstinence syndrome after oral administration of diluted tincture of opium. Journal of Clinical Pharmacology 2016;56(8):1009-18. [DOI: 10.1002/jcph.696] [PMID: 26712409] - DOI - PMC - PubMed
    1. NCT00510016. Clonidine as adjunct therapy for the treatment of neonatal abstinence syndrome (NAS). clinicaltrials.gov/ct2/show/NCT00510016 (first received 1 August 2007).
Brusseau 2020 {published data only}
    1. Brusseau C, Burnette T, Heidel RE. Clonidine versus phenobarbital as adjunctive therapy for neonatal abstinence syndrome. Journal of Perinatology 2020;40(7):1050-5. [DOI: 10.1038/s41372-020-0685-2] [PMID: ] - DOI - PubMed
    1. NCT03670160. Clonidine versus phenobarbital as adjunctive therapy for neonatal abstinence syndrome. clinicaltrials.gov/ct2/show/NCT03670160 (first received 13 September 2018).
Coyle 2002 {published data only}
    1. Bier JB, Ferguson AE, Grenon D, Mullane E, Coyle M. The effects of phenobarbital on developmental outcomes in infants with methadone withdrawal: results of a randomized trial. Pediatric Research 2000;47:175A.
    1. Coyle MG, Ferguson A, LaGasse L, Liu J, Lester B. Neurobehavioral effects of treatment for opiate withdrawal. Archives of Disease in Childhood. Fetal and Neonatal Edition 2005;90:F73-4. [DOI: 10.1136/adc.2003.046276] [PMID: ] - DOI - PMC - PubMed
    1. Coyle MG, Ferguson A, Lagasse L, Oh W, Lester B. Diluted tincture of opium (DTO) and phenobarbital versus DTO alone for neonatal opiate withdrawal in term infants. Journal of Pediatrics 2002;140(5):561-4. [DOI: 10.1067/mpd.2002.123099] [PMID: ] - DOI - PubMed
    1. Ferguson AE, Coyle M, LaGasse L, Liu E, Lester B. Neurobehavioural effects of treatment for opiate withdrawal. Pediatric Research 2001;49:18A. - PMC - PubMed
Finnegan 1984a {published and unpublished data}
    1. Finnegan LP, Michael H, Leifer B, Desai S. An evaluation of neonatal abstinence treatment modalities. NIDA Research Monograph 1984;49:282-8. [PMID: ] - PubMed
Kahn 1969 {published data only}
    1. Kahn EJ, Neumann LL, Polk GA. The course of the heroin withdrawal syndrome in newborn infants treated with phenobarbital or chlorpromazine. Journal of Pediatrics 1969;75(3):495-500. [DOI: 10.1016/s0022-3476(69)80281-7] [PMID: 5804200] - DOI - PubMed
Kaltenbach 1986 {published and unpublished data}
    1. Kaltenbach K, Finnegan LP. Neonatal abstinence syndrome, pharmacotherapy and developmental outcome. Neurobehavioral Toxicology and Teratology 1986;8(4):353-5. [PMID: ] - PubMed
Khoo 1995 {unpublished data only}
    1. Khoo KT. The Effectiveness of Three Treatment Regimens Used in the Management of Neonatal Abstinence Syndrome [PhD thesis]. Melbourne (Australia): University of Melbourne, 1995. [hdl.handle.net/11343/38959]
Madden 1977 {published data only}
    1. Madden JD, Chappel JN, Zuspan F, Gumpel J, Mejia A, Davis R. Observation and treatment of neonatal narcotic withdrawal. American Journal of Obstetrics and Gynecology 1977;127:199-201. [DOI: 10.1016/s0002-9378(16)33250-1] [PMID: 831502] - DOI - PubMed
Surran 2013 {published data only}
    1. NCT01175668. Clonidine for neonatal abstinence syndrome study [Comparison of clonidine versus phenobarbital as an adjunct therapy for neonatal abstinence syndrome]. clinicaltrials.gov/ct2/show/NCT01175668 (first received 5 August 2010).
    1. Surran B, Visintainer P, Chamberlain S, Kopcza K, Shah B, Singh R. Comparison of clonidine versus phenobarbital as an adjunct therapy for neonatal abstinence syndrome. A prospective randomized clinical trial. Pediatric Academic Societies Annual Meeting; 2013 May 4-7; Washington, DC. 2013. - PubMed
    1. Surran B, Visintainer P, Chamberlain S, Kopcza K, Shah B, Singh R. Efficacy of clonidine versus phenobarbital in reducing neonatal morphine sulfate therapy days for neonatal abstinence syndrome. A prospective randomized clinical trial. Journal of Perinatology 2013;33(12):954-9. [DOI: 10.1038/jp.2013.95] [PMID: ] - DOI - PubMed
Zimmermann 2020 {published data only}
    1. NCT02810782. How to treat opiate withdrawal in neonates [Pharmacological treatment of narcotic neonatal withdrawal]. clinicaltrials.gov/ct2/show/NCT02810782 (first received 23 June 2016).
    1. Zimmermann U, Rudin C, Duo A, Held L, Bucher HU, Swiss neonatal abstinence syndrome study group. Treatment of opioid withdrawal in neonates with morphine, phenobarbital, or chlorpromazine: a randomized double-blind trial. European Journal of Pediatrics 2020;179(1):141-9. [DOI: 10.1007/s00431-019-03486-6] [PMID: ] - DOI - PMC - PubMed

References to studies excluded from this review

Alroomi 1988 {published data only}
    1. Alroomi LG, Davidson J, Evans TJ, Galea P, Howat R. Maternal narcotic abuse and the newborn. Archives of Disease in Childhood 1988;63(1):81-3. [DOI: 10.1136/adc.63.1.81] [PMID: ] - DOI - PMC - PubMed
Autret 2004 {published data only}
    1. Autret F, Mucignat V, De Montgolfier-Aubron I, Blond MH, Ducrocq S, Lebas F, et al. Use of diazepam in the treatment of opioid neonatal abstinence syndrome. Archives de Pediatrie 2004;11(11):1308-13. [DOI: 10.1016/j.arcped.2004.06.012] [PMID: ] - DOI - PubMed
Bada 2015 {published data only}
    1. Bada HS, Sithisarn T, Gibson J, Garlitz K, Caldwell R, Capilouto G, et al. Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics 2015;135(2):e383-91. [DOI: 10.1542/peds.2014-2377] [PMID: ] - PubMed
Calabrese 1985 {published data only}
    1. Calabrese JR, Gulledge AD. The neonatal narcotic abstinence syndrome: a brief review. Canadian Journal of Psychiatry 1985;30(8):623-6. [DOI: 10.1177/070674378503000814] [PMID: ] - DOI - PubMed
Carin 1983 {published data only}
    1. Carin I, Glass L, Parekh A, Solomon N, Steigman J, Wong S. Neonatal methadone withdrawal. Effect of two treatment regimens. American Journal of Diseases of Children 1983;137:1166-9. [DOI: 10.1001/archpedi.1983.02140380026008] [PMID: ] - DOI - PubMed
Dabek 2013 {published data only}
    1. Dabek MT, Poeschl J, Englert S, Ruef P. Treatment of neonatal abstinence syndrome in preterm and term infants. Klinische Padiatrie 2013;225:252-6. [DOI: 10.1055/s-0033-1349096] [PMID: ] - DOI - PubMed
Daniel 2020 {published data only}
    1. Daniel JM, Davidson LN, Havens JR, Bauer JA, Shook LA. Aromatherapy as an adjunctive therapy for neonatal abstinence syndrome: a pilot study. Journal of Opioid Management 2020;16(2):119-25. [DOI: 10.5055/jom.2020.0558] [PMID: ] - DOI - PubMed
Doberczak 1991 {published data only}
    1. Doberczak TM, Kandall SR, Wilets I. Neonatal opiate abstinence syndrome in term and preterm infants. Journal of Pediatrics 1991;118(6):933-7. [DOI: 10.1016/s0022-3476(05)82214-0] [PMID: ] - DOI - PubMed
Esmaeili 2010 {published data only}
    1. Esmaeili A, Keinhorst AK, Schuster T, Beske F, Schlosser R, Bastanier C. Treatment of neonatal abstinence syndrome with clonidine and chloral hydrate. Acta Paediatrica 2010;99(2):209-14. [DOI: 10.1111/j.1651-2227.2009.01547.x] [PMID: ] - DOI - PubMed
Finnegan 1975a {published data only}
    1. Finnegan LP, Connaughton JF Jr, Kron RE, Emich JP. Neonatal abstinence syndrome: assessment and management. Addictive Diseases 1975;2(1-2):141-58. [PMID: ] - PubMed
Finnegan 1975b {published data only}
    1. Finnegan LP, Kron RE, Connaughton JF, Emich JP. Assessment and treatment of abstinence in the infant of the drug-dependent mother. International Journal of Clinical Pharmacology and Biopharmacy 1975;12(1-2):19-32. [PMID: ] - PubMed
Finnegan 1979 {published data only}
    1. Finnegan LP, Mitros TF, Hopkins LE. Management of neonatal narcotic abstinence utilizing a phenobarbital loading dose method. NIDA Research Monograph 1979;27:247-53. [PMID: ] - PubMed
Finnegan 1984b {published data only}
    1. Finnegan LP, Michael H, Leifer B. The use of phenobarbital in treating abstinence in newborns exposed in utero to psychoactive agents. NIDA Research Monograph 1984;49:329. [PMID: ] - PubMed
Harper 1977 {published data only}
    1. Harper RG, Solish G, Feingold E, Gersten-Woolf NB, Sokal MM. Maternal ingested methadone, body fluid methadone, and the neonatal withdrawal syndrome. American Journal of Obstetrics and Gynecology 1977;129(4):417-24. [DOI: 10.1016/0002-9378(77)90588-9] [PMID: ] - DOI - PubMed
Herzlinger 1977 {published data only}
    1. Herzlinger RA, Kandall SR, Vaughan HG Jr. Neonatal seizures associated with narcotic withdrawal. Journal of Pediatrics 1977;91(4):638-41. [DOI: 10.1016/s0022-3476(77)80523-4] [PMID: ] - DOI - PubMed
Hoder 1981 {published data only}
    1. Hoder EL, Leckman JF, Ehrenkranz R, Kleber H, Cohen DJ, Poulsen JA. Clonidine in neonatal narcotic-abstinence syndrome. New England Journal of Medicine 1981;305(21):1284. [DOI: 10.1056/NEJM198111193052115] [PMID: ] - DOI - PubMed
Hoder 1984 {published data only}
    1. Hoder EL, Leckman JF, Poulsen J, Caruso KA, Ehrenkranz RA, Kleber HD, et al. Clonidine treatment of neonatal narcotic abstinence syndrome. Psychiatry Research 1984;13(3):243-51. [DOI: 10.1016/0165-1781(84)90039-8] [PMID: ] - DOI - PubMed
Kaltenbach 1987 {published data only}
    1. Kaltenbach K, Finnegan LP. Perinatal and developmental outcome of infants exposed to methadone in-utero. Neurotoxicology and Teratology 1987;9(4):311-3. [DOI: 10.1016/0892-0362(87)90021-3] [PMID: ] - DOI - PubMed
Kandall 1983 {published data only}
    1. Kandall SR, Doberczak TM, Mauer KR, Strashun RH, Korts DC. Opiate v CNS depressant therapy in neonatal drug abstinence syndrome. American Journal of Diseases of Children 1983;137(4):378-82. [DOI: 10.1001/archpedi.1983.02140300056015] [PMID: ] - DOI - PubMed
Kron 1975a {published data only}
    1. Kron RE, Kaplan SL, Finnegan LP, Litt M, Phoenix MD. The assessment of behavioural change in infants undergoing narcotic withdrawal: comparative data from clinical and objective methods. Addictive Diseases 1975;2(1-2):257-75. [PMID: ] - PubMed
Kron 1975b {published data only}
    1. Kron RE, Litt M, Finnegan LP. Narcotic addiction in the newborn: differences in behaviour generated by methadone and heroin. International Journal of Clinical Pharmacology and Biopharmacy 1975;12(1-2):63-9. - PubMed
Kron 1976 {published data only}
    1. Kron RE, Litt M, Eng D, Phoenix MD, Finnegan LP. Neonatal narcotic abstinence: effects of pharmacotherapeutic agents and maternal drug usage on nutritive sucking behavior. Journal of Pediatrics 1976;88(4 Pt 1):637-41. [DOI: 10.1016/s0022-3476(76)80026-1] [PMID: ] - DOI - PubMed
Leikin 2009 {published data only}
    1. Leikin JB, Mackendrick WP, Maloney GE, Rhee JW, Farrell E, Wahl M, et al. Use of clonidine in the prevention and management of neonatal abstinence syndrome. Clinical Toxicology 2009;47(6):551-5. [DOI: 10.1080/15563650902980019] [PMID: ] - DOI - PubMed
Mazurier 2008 {published data only}
    1. Mazurier E, Cambonie G, Barbotte E, Grare A, Pinzani V, Picaud JC. Comparison of chlorpromazine versus morphine hydrochloride for treatment of neonatal abstinence syndrome. Acta Paediatrica 2008;97(10):1358-61. [DOI: 10.1111/j.1651-2227.2008.00918.x] [PMID: ] - DOI - PubMed
Nathenson 1971 {published data only}
    1. Nathenson G, Golden GS, Litt IF. Diazepam in the management of the neonatal narcotic withdrawal syndrome. Pediatrics 1971;48(4):523-7. [PMID: ] - PubMed
NCT01360450 {unpublished data only}
    1. NCT01360450. Clonidine to treat Iatrogenic-induced opioid dependence in infants [Efficacy of clonidine in reducing Iatrogenic-induced opioid dependence in infants]. clinicaltrials.gov/ct2/show/NCT01360450 (first received 25 May 2011).
Ostrea 1975 {published data only}
    1. Ostrea EM, Chavez CJ, Strauss ME. A study of factors that influence the severity of neonatal narcotic withdrawal. Addictive Diseases 1975;2(1-2):187-99. [PMID: ] - PubMed
Ostrea 1976 {published data only}
    1. Ostrea EM, Chavez CJ, Strauss ME. A study of factors that influence the severity of neonatal narcotic withdrawal. Journal of Pediatrics 1976;88:642-5. [DOI: 10.1016/s0022-3476(76)80027-3] [PMID: ] - DOI - PubMed
Pacifico 1989 {published data only}
    1. Pacifico P, Nardelli E, Pantarotto MF. Neonatal heroin withdrawal syndrome; evaluation of different pharmacological treatments. Pharmacological Research 1989;21(Suppl 1):63-4. [DOI: 10.1016/s1043-6618(89)80053-2] [PMID: ] - DOI - PubMed
Sutton 1990 {published data only}
    1. Sutton LR, Hinderliter SA. Diazepam abuse in pregnant women on methadone maintenance. Implications for treatment. Clinical Pediatrics 1990;29(2):108-11. [DOI: 10.1177/000992289002900208] [PMID: ] - DOI - PubMed
Tunis 1984 {published data only}
    1. Tunis SL, Webster DM, Izes JK, Finnegan LP. Maternal drug use and the effectiveness of pharmacotherapy for neonatal abstinence. NIDA Research Monograph 1984;55:158. [PMID: ] - PubMed
Wolman 1989 {published data only}
    1. Wolman I, Niv D, Yoval I, Pausner D, Geller E, David MP. Opioid-addicted parturient, labor, and outcome: a reappraisal. Obstetrical & Gynecological Survey 1989;44(8):592-7. [DOI: 10.1097/00006254-198908000-00004] [PMID: ] - DOI - PubMed
Yaster 1996 {published data only}
    1. Yaster M, Kost-Byerly S, Berde C, Billet C. The management of opioid and benzodiazepine dependence in infants, children, and adolescents. Pediatrics 1996;98(1):135-40. [PMID: ] - PubMed
Zelson 1970 {published data only}
    1. Zelson C, Kahn EJ, Neumann L, Polk G. Heroin withdrawal syndrome. Journal of Pediatrics 1970;76(3):483-6. [DOI: 10.1016/s0022-3476(70)80498-x] [PMID: ] - DOI - PubMed

References to ongoing studies

NCT03762317 {published data only}
    1. NCT03762317. Clonidine as adjunct to morphine for neonatal abstinence syndrome [Clonidine as adjunct to morphine in the management of term and near term infants with neonatal abstinence syndrome]. clinicaltrials.gov/ct2/show/NCT03762317 (first received 3 December 2018).

Additional references

AAP 2012
    1. Hudak ML, Tan RC, Committee on Drugs, Committee on Fetus and Newborn, American Academy of Pediatrics. Neonatal drug withdrawal. Pediatrics 2012;129(2):e540-60. [DOI: 10.1542/peds.2011-3212] [PMID: ] - DOI - PubMed
Allegaert 2016
    1. Allegaert K, Anker JN. Neonatal withdrawal syndrome: reaching epidemic proportions across the globe. Archives of Diseases in Childhood. Fetal and Neonatal Edition 2016;10(1):F2-3. [DOI: 10.1136/archdischild-2015-309566] [PMID: ] - DOI - PubMed
Allocco 2016
    1. Allocco E, Melker M, Rojas-Miquez F, Bradley C, Hahn KA, Wachman EM. Comparison of neonatal abstinence syndrome manifestations in preterm versus term opioid-exposed infants. Advances in Neonatal Care 2016;16(5):329-36. [DOI: 10.1097/ANC.0000000000000320] [PMID: ] - PMC - PubMed
Bagley 2014
    1. Bagley SM, Wachman EM, Holland E, Brogly SB. Review of the assessment and management of neonatal abstinence syndrome. Addiction Science & Clinical Practice 2014;9(1):19. [DOI: 10.1186/1940-0640-9-19] [PMID: ] - DOI - PMC - PubMed
Bauchinger 2015
    1. Bauchinger S, Sapetschnig I, Danda M, Sommer C, Resch B, Urlesberger B, et al. Methods in neonatal abstinence syndrome (NAS): results of a nationwide survey in Austria. Zeitschrift für Geburtshilfe und Neonatologie 2015;219(4):185-9. [DOI: 10.1055/s-0035-1545289] [PMID: ] - DOI - PubMed
Bell 1995
    1. Bell GL, Lau K. Perinatal and neonatal issues of substance abuse. Pediatric Clinics of North America 1995;42(2):261-81. [DOI: 10.1016/s0031-3955(16)38946-5] [PMID: ] - DOI - PubMed
Boucher 2017
    1. Boucher AM. Non-opioid management of neonatal abstinence syndrome. Advances in Neonatal Care 2017;17(2):84-90. [DOI: 10.1097/ANC.0000000000000371] [PMID: ] - DOI - PubMed
Brogly 2014
    1. Brogly SB, Saia KA, Walley AY, Du HM, Sebastiani P. Prenatal buprenorphine versus methadone exposure and neonatal outcomes: systematic review and meta-analysis. American Journal of Epidemiology 2014;180(7):673-86. [DOI: 10.1093/aje/kwu190] [PMID: ] - DOI - PubMed
Brogly 2017
    1. Brogly SB, Turner S, Lajkosz K, Davies G, Newman A, Johnson A, et al. Infants born to opioid-dependent women in Ontario, 2002-2014. Journal of Obstetrics and Gynaecology Canada 2017;39(3):157-65. [DOI: 10.1016/j.jogc.2016.11.009] [PMID: ] - DOI - PubMed
Cleary 2010
    1. 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. Addiction 2010;105(12):2017-84. [DOI: 10.1111/j.1360-0443.2010.03120.x] [PMID: ] - DOI - PubMed
Coyle 2012
    1. Coyle MG, Lester BM, Jones HE, Lin H, Graf-Rohrmeister K, Fisher G. Neonatal neurobehaviour effects following buprenorphine versus methadone exposure. Addiction 2012;107(Suppl 1):63-73. [DOI: 10.1111/j.1360-0443.2012.04040.x] [PMID: ] - DOI - PMC - PubMed
Dashe 2002
    1. Dashe JS, Sheffield JS, Olscher DA, Todd SJ, Jackson GL, Wendel GD Jr. Relationship between maternal methadone dosage and neonatal withdrawal. Obstetrics and Gynecology 2002;100(6):1244-9. [DOI: 10.1016/s0029-7844(02)02387-6] [PMID: ] - DOI - PubMed
Davies 2016
    1. Davies H, Gilbert R, Johnson K, Petersen I, Nazareth I, O'Donnell M, et al. Neonatal drug withdrawal syndrome: cross country comparison using hospital administrative data in England, the USA, Western Australia and Ontario, Canada. Archives of Disease in Childhood. Fetal and Neonatal Edition 2016;101(1):F26-30. [DOI: 10.1136/archdischild-2015-308948] [PMID: ] - DOI - PubMed
Disher 2019
    1. Disher T, Gullickson C, Singh B, Cameron C, Boulos L, Beaubien L, et al. Pharmacological treatments for neonatal abstinence syndrome: a systematic review and network meta-analysis. JAMA Pediatrics 2019;173(3):234-43. [DOI: 10.1001/jamapediatrics.2018.5044] [PMID: ] - DOI - PMC - PubMed
Finnegan 2005
    1. Finnegan LP, Kandall SR. Maternal and neonatal effects of alcohol and drugs. In: Lowinson JH, Ruiz P, Millman RB, Langrod JG, editors(s). Substance Abuse: a Comprehensive Textbook. Philadelphia (PA): Lippincott Williams & Wilkins, 2005:805-39.
Fricker 1978
    1. Fricker HS, Segal S. Narcotic addiction, pregnancy, and the newborn. American Journal of Diseases of Children 1978;132(4):360-6. [DOI: 10.1001/archpedi.1978.02120290032004] [PMID: ] - DOI - PubMed
GRADEpro GDT [Computer program]
    1. GRADEpro GDT. Version accessed 20 April 2017. Hamilton (ON): McMaster University (developed by Evidence Prime), 2017. Available at gradepro.org.
Green 1981
    1. Green M, Suffet F. The neonatal narcotic withdrawal index: a device for the improvement of care in the abstinence syndrome. American Journal of Drug and Alcohol Abuse 1981;8(2):203-13. [DOI: 10.3109/00952998108999125] [PMID: ] - DOI - PubMed
Held‐Egli 2009
    1. Held-Egli K, Ruegger C, Das-Kundu S, Schmitt B, Bucher HU. Benign neonatal sleep myoclonus in newborn infants of opioid dependent mothers. Acta Paediatrica 2009;98(1):69-73. [DOI: 10.1111/j.1651-2227.2008.01010.x] [PMID: ] - DOI - PubMed
Higgins 2011
    1. Higgins JP, Altman DG, Sterne JA, on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Higgins 2020
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Cochrane, 2020. Available from training.cochrane.org/handbook/archive/v6.1.
Howard 2017
    1. Howard MB, Schiff DM, Penwill N, Rai A, Wolfgang T, Moses JM, et al. Impact of parental presence at infants' bedside on neonatal abstinence syndrome. Hospital Pediatrics 2017;7(2):63-9. [DOI: 10.1542/hpeds.2016-0147] [PMID: ] - DOI - PubMed
Hulse 1998
    1. Hulse GK, Milne E, English DR, Holman CD. Assessing the relationship between maternal opiate use and neonatal mortality. Addiction 1998;93(7):1033-42. [DOI: 10.1046/j.1360-0443.1998.93710338.x] [PMID: ] - DOI - PubMed
Hunt 2008
    1. Hunt RW, Tzioumi D, Collins E, Jeffery HE. Adverse neurodevelopmental outcome of infants exposed to opiate in-utero. Early Human Development 2008;84(1):29-35. [DOI: 10.1016/j.earlhumdev.2007.01.013] [PMID: ] - DOI - PubMed
Jansson 2016
    1. Jansson LM, Spencer N, McConnell K, Velez M, Tuten M, Harrow CA, et al. Maternal buprenorphine maintenance and lactation. Journal of Human Lactation 2016;32(4):675-81. [DOI: 10.1177/0890334416663198] [PMID: ] - DOI - PubMed
Jones 2010
    1. Jones HE, Kaltenbach K, Heil SH, Stine MD, Coyle MD, Arria AM, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. New England Journal of Medicine 2010;363(24):2320-31. [DOI: 10.1056/NEJMoa1005359] [PMID: ] - PMC - PubMed
Jones 2016
    1. Jones HE, Seashore C, Johnson E, Horton E, O'Grady KE, Andringa K, et al. Psychometric assessment of the neonatal abstinence scoring system and the MOTHER NAS Scale. American Journal of Addiction 2016;25(5):370-3. [DOI: 10.1111/ajad.12388] [PMID: ] - DOI - PubMed
Kaltenbach 2012
    1. Kaltenbach K, Holbrook A, Coyle MG, Heil SH, Salisbury A, Stine S, et al. Predicting treatment for neonatal abstinence syndrome in infants born to women maintained on opioid agonist medication. Addiction 2012;107(Suppl 1):45-52. [DOI: 10.1111/j.1360-0443.2012.04038.x] [23106926] - DOI - PMC - PubMed
Kandall 1976
    1. Kandall SR, Albin S, Lowinson J, Berle B, Eidelman AI, Gartner LM. Differential effects of maternal heroin and methadone use on birthweight. Pediatrics 1976;58(5):681-5. [PMID: ] - PubMed
Kandall 1977
    1. Kandall SR, Albin S, Gartner LM, Lee KS, Eidelman A, Lowinson J. The narcotic-dependent mother: fetal and neonatal consequences. Early Human Development 1977;1(2):159-69. [DOI: 10.1016/0378-3782(77)90017-2] [PMID: ] - DOI - PubMed
Kandall 1993
    1. Kandall SR, Gaines J, Habel L, Davidson G, Jessop D. Relationship of maternal substance abuse to subsequent sudden infant death syndrome in offspring. Journal of Pediatrics 1993;123(1):120-6. [DOI: 10.1016/s0022-3476(05)81554-9] [PMID: ] - DOI - PubMed
Kelly 2015
    1. Kelly LE, Knoppert D, Roukema H, Rieder MJ, Koren G. Oral morphine weaning for neonatal abstinence syndrome at home compared with in-hospital: an observational cohort study. Paediatric Drugs 2015;17(2):151-7. [10.1007/s40272-014-0096-y] [PMID: ] - PubMed
Kennare 2005
    1. Kennare R, Heard A, Chan A. Substance abuse during pregnancy: risk factors and obstetric and perinatal outcomes in South Australia. Australian and New Zealand Journal of Obstetrics and Gynaecology 2005;45(3):220-5. [DOI: 10.1111/j.1479-828X.2005.00379.x] [PMID: ] - DOI - PubMed
Kirchner 2014
    1. Kirchner L, Graf-Rohmeister K, Klebermass-Schrehof K, Weninger M, Jagsch R, Metz V, et al. Neonatal abstinence syndrome in European and North American neonates: differences in clinical characteristics derived from a prospective randomised trial. Klinische Pädiatrie 2014;226(5):274-80. [DOI: 10.1055/s-0034-1372586] [PMID: ] - DOI - PubMed
Kocherlakota 2014
    1. Kocherlakota P. Neonatal abstinence syndrome. Pediatrics 2014;134(2):e547-61. [DOI: 10.1542/peds.2013-3524] [PMID: ] - DOI - PubMed
Kraft 2012
    1. Kraft WK, van den Anker. Pharmacologic management of the opioid neonatal abstinence syndrome. Paediatric Clinics of North America 2012;59(5):1147-65. [DOI: 10.1016/j.pcl.2012.07.006] [PMID: ] - DOI - PMC - PubMed
Kraft 2016
    1. Kraft WK, Stover NW, Davis JM. Neonatal abstinence syndrome: pharmacologic strategies for the mother and infant. Seminars in Perinatology 2016;40(3):203-12. [DOI: 10.1053/j.semperi.2015.12.007] [PMID: ] - DOI - PMC - PubMed
Lam 1992
    1. Lam SK, To WK, Duthie SJ, Ma HK. Narcotic addiction in pregnancy with adverse maternal and perinatal outcome. Australian & New Zealand Journal of Obstetrics & Gynaecology 1992;32(3):216-21. [DOI: 10.1111/j.1479-828x.1992.tb01950.x] [PMID: ] - DOI - PubMed
Lee 2019
    1. Lee JJ, Chen J, Eisler L, Li G, Davis JM, Sun LS. Comparative effectiveness of opioid replacement agents for neonatal opioid withdrawal syndrome: a systematic review and meta-analysis. Journal of Perinatology 2019;39(11):1535-45. [DOI: 10.1038/s41372-019-0437-3] [PMID: ] - DOI - PMC - PubMed
Lipsitz 1975
    1. Lipsitz PJ. A proposed narcotic withdrawal score for use with newborn infants. A pragmatic evaluation of its efficacy. Clinical Pediatrics 1975;14(6):592-4. [DOI: 10.1177/000992287501400613] [PMID: ] - DOI - PubMed
Maas 1990
    1. Maas U, Kattner E, Weingart-Jesse B, Schafer A, Obladen M. Infrequent neonatal opiate withdrawal following maternal methadone detoxification during pregnancy. Journal of Perinatal Medicine 1990;18(2):111-8. [DOI: 10.1515/jpme.1990.18.2.111] [PMID: ] - DOI - PubMed
MacMillan 2018
    1. MacMillan KD, Rendon CP, Verma K, Riblet N, Washer DB, Holmes AV. Association of rooming-in with outcomes for neonatal abstinence syndrome: a systematic review and meta-analysis. JAMA Pediatrics 2018;172(4):345-51. [DOI: 10.1001/jamapediatrics.2017.5195] [PMID: ] - DOI - PMC - PubMed
Marshall 2018
    1. Marshall IJ, Noel-Storr AH, Kuiper J, Thomas J, Wallace BC. Machine learning for identifying randomized controlled trials: an evaluation and practitioner's guide. Research Synthesis Methods 2018;9(4):1-12. [DOI: 10.1002/jrsm.1287] [PMID: ] - DOI - PMC - PubMed
McDonald 2017
    1. McDonald S, Noel-Storr AH, Thomas J. Harnessing the efficiencies of machine learning and Cochrane Crowd to identify randomised trials for individual Cochrane Reviews. Abstracts of the Global Evidence Summit, Cape Town, South Africa. Cochrane Database of Systematic Reviews 2017;9(Suppl 1). [DOI: ]
Middleton 2017
    1. Middleton M, Wright I, Oei JL, Travadi J. Management of infants with neonatal abstinence syndrome in a tertiary care hospital. Journal of Paediatrics and Child Health 2017;53(Suppl 2):106.
Mizrahi 1987
    1. Mizrahi EM, Kellaway P. Characterization and classification of neonatal seizures. Neurology 1987;37(12):1837-44. [DOI: 10.1212/wnl.37.12.1837] [PMID: ] - DOI - PubMed
NDSHS 2013
    1. Australian Institute of Health and Welfare. National Drug Strategy Household Survey detailed report 2013. www.aihw.gov.au/reports/illicit-use-of-drugs/ndshs-2013-detailed/content... (accessed 28 January 2021).
Newman 2015
    1. Newman A, Davies GA, Dow K, Holmes B, Macdonald J, McKnight S, et al. Rooming-in care for infants of opioid-dependent mothers. Canadian Family Physician 2015;61(12):e555-61. [PMID: 27035006] - PMC - PubMed
NHSDA 1999
    1. Office of Applied Statistics, Substance Abuse and Mental Health Administration (SAMHSA). National household survey on drug abuse. 1999. www.datafiles.samhsa.gov/study/national-household-survey-drug-abuse-nhsd... (accessed 28 January 2021).
NHSDA 2013
    1. Substance Abuse and Mental Health Administration (SAMHSA). National household survey on drug abuse. 2013. samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHre... (accessed 28 January 2021).
Noel‐Storr 2018
    1. Noel-Storr AH and the Project Transform team. Cochrane Crowd and Classmate: new ways of working and learning together to produce health evidence. Abstracts of the 26th Cochrane Colloquium, Santiago, Chile. Cochrane Database of Systematic Reviews 2020;1(Suppl 1). [DOI: ]
Oei 2017
    1. Oei JL, Melhuish E, Uebel H, Azzam N, Breen C, Burns L, et al. Neonatal abstinence syndrome and high school performance. Pediatrics 2017;139(2):e20162651. [DOI: 10.1542/peds.2016-2651] [PMID: ] - DOI - PubMed
Olofsson 1983
    1. Olofsson M, Buckley W, Andersen GE, Friis Hansen BS. Investigation of 89 children born by drug-dependent mothers. I. Neonatal course. Acta Paediatrica Scandinavica 1983;72:403-6. [DOI: 10.1111/j.1651-2227.1983.tb09736.x] [PMID: ] - DOI - PubMed
Orlando 2014
    1. Orlando S. An overview of clinical tools used to assess neonatal abstinence syndrome. Journal of Perinatal & Neonatal Nursing 2014;28(3):212-9. [DOI: 10.1097/JPN.0000000000000043] [PMID: ] - DOI - PubMed
Oro 1988
    1. Oro AS, Dixon SD. Waterbed care of narcotic-exposed neonates. A useful adjunct to supportive care. American Journal of Diseases of Children 1988;142:186-8. - PubMed
Pahl 2020
    1. Pahl A, Young L, Buus-Frank ME, Marcellus L, Soll R. Non-pharmacological care for opioid withdrawal in newborns. Cochrane Database of Systematic Reviews 2020, Issue 12. Art. No: CD013217. [DOI: 10.1002/14651858.CD013217.pub2] - DOI - PMC - PubMed
Patel 2013
    1. Patel P, Abdel-Latif ME, Hazelton B, Wodak A, Chen J, Emsley F, et al. Perinatal outcomes of Australian buprenorphine-exposed mothers and their newborn infants. Journal of Paediatric and Child Health 2013;49(9):746-53. [DOI: 10.1111/jpc.12264] [PMID: ] - DOI - PubMed
Patrick 2015
    1. Patrick SW, Dudley J, Martin PR, Harrell FE, Warren MD, Hartmann KE, et al. Prescription opioid epidemic and infant outcomes. Pediatrics 2015;135(5):842-50. [DOI: 10.1542/peds.2014-3299] [PMID: ] - DOI - PMC - PubMed
Peltz 2015
    1. Peltz G, Anand KJ. Long-acting opioids for treating neonatal abstinence syndrome. A high price for a short stay? JAMA 2015;314(19):2023-4. [DOI: 10.1001/jama.2015.13537] [PMID: ] - DOI - PMC - PubMed
Raith 2015
    1. Raith W, Schmölzer BR, Fritz Reiterer A. Laser acupuncture for neonatal abstinence syndrome: a randomised controlled trial. Pediatrics 2015;136(5):876-84. - PubMed
Review Manager 2020 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: The Cochrane Collaboration, 2020.
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editor(s). Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from gdt.guidelinedevelopment.org/app/handbook/handbook.html.
Short 2016
    1. Short VL, Gannon M, Abatemarco DJ. The association between breastfeeding and length of hospital stay among infants diagnosed with neonatal abstinence syndrome: a population-based study on in-hospital births. Breastfeeding Medicine 2016;11:343-9. [DOI: 10.1089/bfm.2016.0084] [PMID: ] - DOI - PubMed
Siu 2014
    1. Siu A, Robinson CA. Neonatal abstinence syndrome: essentials for the practitioner. Journal of Pediatric Pharmacology and Therapeutics 2014;19(3):147-55. [DOI: 10.5863/1551-6776-19.3.147] [PMID: ] - DOI - PMC - PubMed
Spiteri Cornish 2013
    1. Spiteri Cornish K, Hrabovsky M, Scott NW, Myerscough E, Reddy AR. The short and long-term, effects on the visual system of children following exposure to maternal substance misuse in pregnancy. American Journal of Ophthalmology 2013;156(1):190-4. [DOI: 10.1016/j.ajo.2013.02.004] [PMID: ] - DOI - PubMed
Stover 2015
    1. Stover MW, Davis JM. Opioids in pregnancy and neonatal abstinence syndrome. Seminars in Perinatology 2015;39(7):561-5. [DOI: 10.1053/j.semperi.2015.08.013] [PMID: ] - DOI - PMC - PubMed
Strauss 1976
    1. Strauss ME, Andresko M, Stryker JC, Wardell JN. Relationship of neonatal withdrawal to maternal methadone dose. American Journal of Drug and Alcohol Abuse 1976;3(2):339-45. [DOI: 10.3109/00952997609077202] [PMID: ] - DOI - PubMed
Sundelin Wahlsten 2013
    1. Sundelin Wahlsten V, Sarman I. Neurobehavioural development of preschool-age children born to addicted mothers given opiate maintenance treatment with buprenorphine during pregnancy. Acta Paediatrics 2013;102(5):544-9. [DOI: 10.1111/apa.12210] [PMID: ] - DOI - PubMed
Theis 1997
    1. Theis JG, Selby P, Ikizler Y, Koren GS. Current management of the neonatal abstinence syndrome: a critical analysis of the evidence. Biology of the Neonate 1997;71(6):345-56. [DOI: 10.1159/000244435] [PMID: ] - DOI - PubMed
Thomas 2017
    1. Thomas J, Noel-Storr AH, Marshall I, Wallace B, McDonald S, Mavergames C, et al, Living Systematic Review Network. Living systematic reviews: 2. Combining human and machine effort. Journal of Clinical Epidemiology 2017;91:31-7. [DOI: 10.1016/j.jclinepi.2017.08.011] [PMID: ] - DOI - PubMed
Tolia 2015
    1. Tolia VN, Patrick SW, Bennett MM, Murthy K, Sousa J, Smith PB, et al. Increasing incidence of the neonatal abstinence syndrome in the U.S. neonatal ICUs. New England Journal of Medicine 2015;372(22):2118-26. [DOI: 10.1056/NEJMsa1500439] [PMID: ] - DOI - PubMed
Turner 2015
    1. Turner SD, Gomes T, Camacho X, Yao Z, Guittmann A, Mamdani MM, et al. Neonatal opioid withdrawal and antenatal prescribing. CMAJ Open 2015;3(1):E55-61. [DOI: 10.9778/cmajo.20140065] [PMID: ] - DOI - PMC - PubMed
Unger 2012
    1. Unger A, Metz V, Fischer G. Opioid dependent and pregnant: what are the best options for mothers and neonates? Obstetrics and Gynecology International 2012;2012:195954. [DOI: 10.1155/2012/195954] [PMID: ] - DOI - PMC - PubMed
Visconti 2013
    1. Visconti K, Hennessy K, Towers C, Hannessy M, Howard B. Opiate use in pregnancy and newborn head circumference. American Journal of Obstetrics and Gynecology 2013;208:S67-8.
Volpe 2008
    1. Volpe JJ. Neonatal seizures. In: Neurology of the Newborn. Philadelphia (PA): Saunders Elsevier, 2008:203-44. [ISBN: 9781416039952]
Wachman 2018
    1. Wachman EM, Schiff DM, Silverstein M. Neonatal abstinence syndrome: advances in diagnosis and treatment. JAMA 2018;319(13):1362-74. [DOI: 10.1001/jama.2018.2640] [PMID: ] - DOI - PubMed
Walhovd 2007
    1. Walhovd KB, Moe V, Slinning K, Due-Tønnessen P, Bjørnerud A, Dale AM, et al. Volumetric cerebral characteristics of children exposed to opiates and other substances in utero. Neuroimage 2007;36(4):1331-44. [DOI: 10.1016/j.neuroimage.2007.03.070] [PMID: ] - PMC - PubMed
Walhovd 2012
    1. Walhovd KB, Watts R, Amlien I, Woodward LJ. Neural tract development of infants born to methadone-maintained mothers. Pediatric Neurology 2012;47(1):1-6. [DOI: 10.1016/j.pediatrneurol.2012.04.008] [PMID: ] - DOI - PubMed
WHO 2014
    1. World Health Organization. Guidelines for the identification and management of substance use and substance use disorders in pregnancy. who.int/iris/bitstream/10665/107130/1/9789241548731_eng.pdf (accessed April 2017). - PubMed
Wolff 2014
    1. Wolff K, Perez-Montejano R. Opioid neonatal abstinence syndrome: controversies and implications for practice. Current Drug Abuse Reviews 2014;7(1):454-8. [DOI: 10.2174/1874473707666141015215141] [PMID: ] - DOI - PubMed
Zahorodny 1998
    1. Zahorodny W, Rom C, Whitney W, Giddens S, Samuel M, Maichuk G, et al. The neonatal withdrawal inventory: a simplified score of newborn withdrawal. Journal of Developmental and Behavioral Pediatrics 1998;19:89-93. [DOI: 10.097/00004703-199804000-00005] [PMID: ] - DOI - PubMed
Zankl 2021
    1. Zankl A, Martin J, Davey JG, Osborn DA. Opioid treatment for opioid withdrawal in newborn infants. Cochrane Database of Systematic Reviews (in press). - PMC - PubMed

References to other published versions of this review

Osborn 2000
    1. Osborn DA, Cole MJ. Sedatives for opiate withdrawal in newborn infants. Cochrane Database of Systematic Reviews 2000, Issue 2. Art. No: CD002053. [DOI: 10.1002/14651858.CD002053] - DOI - PubMed
Osborn 2002
    1. Osborn DA, Jeffery HE, Cole MJ. Sedatives for opiate withdrawal in newborn infants. Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No: CD002053. [DOI: 10.1002/14651858.CD002053] - DOI - PubMed
Osborn 2005
    1. Osborn DA, Jeffery HE, Cole MJ. Sedatives for opiate withdrawal in newborn infants. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No: CD002053. [DOI: 10.1002/14651858.CD002053.pub2] - DOI - PubMed
Osborn 2010
    1. Osborn DA, Jeffery HE, Cole MJ. Sedatives for opiate withdrawal in newborn infants. Cochrane Database of Systematic Reviews 2010, Issue 10. Art. No: CD002053. [DOI: 10.1002/14651858.CD002053.pub3] - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources