Neonatal Abstinence Syndrome: Twelve Years of Experience at a Regional Referral Center

 

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Abstract

Background:

Infants exposed to opiates antenatally display withdrawal symptoms after birth referred to as neonatal abstinence syndrome (NAS).

Patients:

A total of 366 newborns (166 females, 10 twins) from 361 mothers were diagnosed with NAS from 2000 to 2011 at a single large metropolitan referral center.

Methods:

Retrospective chart review of all newborn infants exposed to opiates in utero.

Results:

20% were premature (gestational age<37 weeks), 32% were small-for-gestational-age (<10^th percentile). 70% of infants (195/278) antenatally exposed to methadone (racemic methadone or levomethadone) required pharmacological treatment for 11 (1–55) days (median; range); however, 45% of infants (28/62) exposed to buprenorphine required pharmacological treatment for a median of only 5 (1–20) days (p=0.014). Pharmacological treatment of infants with phenobarbital (n=189) took a median of 9 (1–53) days, but treatment with morphine (n=39) took 19 (3–55) days (p<0.001). The median duration of hospitalization increased from 11 days in 2000–2004 to 19 days in 2008–2011 (p<0.001). The increased durations of neonatal hospitalization were associated with similar increases in the average dosages of maternal methadone.

Conclusion:

Use of buprenorphine, rather than methadone, for treatment of opiate-addicted pregnant women is associated with fewer and shorter neonatal withdrawal symptoms. The duration of hospitalization and treatment for NAS has increased over time.

Zusammenfassung

Hintergrund:Pränatal opiatexponierte Neugeborene zeigen nach der Geburt Entzugssymptome, die als neonatales Abstinenzsyndrom (NAS) bezeichnet werden.

Patienten:Im Zeitraum von 2000 bis 2011 wurde in einem regionalen Behandlungszentrum bei 366 Neugeborenen (166 weiblich, 10 Zwillinge) NAS diagnostiziert.

Methoden:Retrospektive Datenanalyse aller intrauterin opiatexponierten Neugeborenen.

Ergebnisse:20% der Patienten waren Frühgeborene (<37+0 SSW), 32% waren hypotroph (<10. Perzentile). 70% der Methadon (racemisches Methadon oder Levomethadon)-exponierten Neugeborenen (195/278) wurden für 11 (1–55) Tage (Median, Bereich) medikamentös behandelt, wohingegen nur 45% der Buprenorphin-exponierten Neugeborenen (28/62) nur 5 (1–20) Tage lang behandelt wurden (p=0,014). Die medikamentöse Behandlung mit Phenobarbital (n=189) dauerte 9 (1–53) Tage, die mit Morphin (n=39) 19 (3–55) Tage (p<0,001). Die mediane Behandlungsdauer nahm von 11 Tagen im Zeitraum von 2000–2004 bis auf 19 Tage in den Jahren 2008–2011 zu (p<0,001). Die zunehmende Behandlungsdauer war mit einer zunehmenden durchschnittlichen Tagesdosis der mütterlichen Methadonsubstitution assoziiert.

Schlussfolgerung:Die Substitution schwangerer Frauen mit Buprenorphin statt Methadon ist mit einem kürzeren und weniger schweren neonatalen Entzug assoziiert. Die Krankenhausaufenthalts- und Behandlungsdauer hat über den Beobachtungszeitraum zugenommen.

• References

• 1 Agthe AG, Kim GR, Mathias KB. et al. Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial. Pediatrics 2009; 123: e849-e856
  CrossrefPubMedSearch in Google Scholar
• 2 American Academy of Pediatrics CoD. Neonatal drug withdrawal. American Academy of Pediatrics Committee on Drugs. Pediatrics 1998; 101: 1079-1088
  PubMedSearch in Google Scholar
• 3 Bada HS, Sithisarn T, Gibson J. et al. Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics 2015; 135: e383-e391
  CrossrefPubMedSearch in Google Scholar
• 4 Brown MS, Hayes MJ, Thornton LM. Methadone versus morphine for treatment of neonatal abstinence syndrome: A prospective randomized clinical trial. Journal of perinatology: official journal of the California Perinatal Association 2015; 35: 278-283
  CrossrefPubMedSearch in Google Scholar
• 5 Finnegan LP, Connaughton Jr JF, Kron RE. et al. Neonatal abstinence syndrome: assessment and management. Addictive diseases 1975; 2: 141-158
  PubMedSearch in Google Scholar
• 6 Fokina VM, Patrikeeva SL, Zharikova OL. et al. Transplacental transfer and metabolism of buprenorphine in preterm human placenta. American journal of perinatology 2011; 28: 25-32
  Thieme ConnectPubMedSearch in Google Scholar
• 7 Forcelli PA, Janssen MJ, Vicini S. et al. Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development. Annals of neurology 2012; 72: 363-372
  CrossrefPubMedSearch in Google Scholar
• 8 Hudak ML, Tan RC. Committee On D. et al. Neonatal drug withdrawal. Pediatrics 2012; 129: e540-e560
  CrossrefPubMedSearch in Google Scholar
• 9 Jackson L, Ting A, McKay S. et al. A randomised controlled trial of morphine versus phenobarbitone for neonatal abstinence syndrome. Archives of disease in childhood Fetal and neonatal edition 2004; 89: F300-F304
  CrossrefPubMedSearch in Google Scholar
• 10 Jones HE, Kaltenbach K, Heil SH. et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. The New England journal of medicine 2010; 363: 2320-2331
  CrossrefPubMedSearch in Google Scholar
• 11 Kirchner L, Graf-Rohrmeister K, Klebermass-Schrehof K. et al. Neonatal abstinence syndrome in European and North American neonates: differences in clinical characteristics derived from a prospective randomized trial. Klinische Padiatrie 2014; 226: 274-280
  Thieme ConnectPubMedSearch in Google Scholar
• 12 Kraft WK, Gibson E, Dysart K. et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics 2008; 122: e601-e607
  CrossrefPubMedSearch in Google Scholar
• 13 Lejeune C, Simmat-Durand L, Gourarier L. et al. Prospective multicenter observational study of 260 infants born to 259 opiate-dependent mothers on methadone or high-dose buprenophine substitution. Drug and alcohol dependence 2006; 82: 250-257
  CrossrefPubMedSearch in Google Scholar
• 14 Lintzeris N, Ritter A, Panjari M. et al. Implementing buprenorphine treatment in community settings in Australia: experiences from the Buprenorphine Implementation Trial. The American journal on addictions/American Academy of Psychiatrists in Alcoholism and Addictions 2004; 13 (Suppl. 01) S29-S41
  PubMedSearch in Google Scholar
• 15 McGlone L, Mactier H, Hassan H. et al. In utero drug and alcohol exposure in infants born to mothers prescribed maintenance methadone. Archives of disease in childhood Fetal and neonatal edition 2013; 98: F542-F544
  CrossrefPubMedSearch in Google Scholar
• 16 Muller MJ, Lange M, Paul T. et al. Breast feeding during methadon- and buprenorphin therapy. Klinische Padiatrie 2011; 223: 408-413
  Thieme ConnectPubMedSearch in Google Scholar
• 17 Osborn DA, Jeffery HE, Cole MJ. Opiate treatment for opiate withdrawal in newborn infants. The Cochrane database of systematic reviews 2010; pub3: CD002059
  CrossrefPubMedSearch in Google Scholar
• 18 Siedentopf JNM, Eßer M, Casteleyn S. et al. Erfahrungen mit der Buprenorphineinstellung und anschliessenden Dosisreduktion im Vergleich zu L-Methadon bei schwangeren Opiatabhängigen. Geburtsh Frauenheilk 2004; 64: 711-718
  Thieme ConnectPubMedSearch in Google Scholar
• 19 Tolia VN, Patrick SW, Bennett MM. et al. Increasing incidence of the neonatal abstinence syndrome in US neonatal ICUs. The New England journal of medicine 2015; 372: 2118-2126
  CrossrefPubMedSearch in Google Scholar
• 20 Walsh SL, Preston KL, Bigelow GE. et al. Acute administration of buprenorphine in humans: partial agonist and blockade effects. The Journal of pharmacology and experimental therapeutics 1995; 274: 361-372
  PubMedSearch in Google Scholar
• 21 Women ACoHCfU, American Society of Addiction M. ACOG Committee Opinion No. 524: Opioid abuse, dependence, and addiction in pregnancy. Obstetrics and gynecology 2012; 119: 1070-1076
  CrossrefPubMedSearch in Google Scholar
• 22 Zimmermann-Baer U, Notzli U, Rentsch K. et al. Finnegan neonatal abstinence scoring system: normal values for first 3 days and weeks 5–6 in non-addicted infants. Addiction 2010; 105: 524-528
  CrossrefPubMedSearch in Google Scholar