Neonatales Abstinenzsyndrom bei europäischen und nordamerikani­schen Neugeborenen: Unterschiede im klinischen Verlauf an Hand von Daten einer prospektiven randomisierten Studie

 

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Abstract

Background: Due to the steady increase of substance-dependent pregnant women the neonatal abstinence syndrome has become an increasingly important issue in neonatology. The present study investigates site-specific differences of detailed symptoms and treatment of neonatal abstinence syndrome within the context of an international multicenter clinical trial.

Methods: Site specific neonatal data analyses from a prospective randomized, double-blind, double-dummy clinical trial (MOTHER study) was performed. A standardized NAS rating and treatment protocol was applied, while non-pharmacological care of NAS symptoms differed across the sites.

Results: Urban US neonates exhibited most neurological symptoms (p<0.001) while in Europe autonomous, respiratory and gastrointestinal symptoms were found significantly more often compared to urban and/or rural US (p<0.05). Methadone produced significantly greater scores than buprenorphine in neurological, behavioural and respiratory symptoms regardless of the sites (ps<0.05). NAS treatment rates in all site clusters were similar for methadone-exposed neonates, while in Europe significantly more buprenorphine-exposed neonates were treated (p=0.001) than in US site clusters. Urban US neonates had significantly higher NAS scores (p<0.01) compared to rural US and European neonates, and needed significantly higher morphine doses (p<0.05) with longer treatment duration. Birth weight, length and head circumference did not differ significantly among the site clusters, but APGAR scores were significantly higher in European (p<0.01) neonates.

Conclusion: In addition to intrauterine medication exposure other aspects such as different addiction severity of the mothers, different treatment modalities including rooming-in as well as the frequency of NAS ratings may be influencing the course of NAS.

Zusammenfassung

Hintergrund: Aufgrund der steigenden Zahl drogenabhängiger Schwangerer gewinnt das neonatale Abstinenzsyndrom zunehmend an Bedeutung. Die vorliegende Arbeit untersucht ortsspezifische Unterschiede in Verlauf und Therapie des neonatalen Abstinenzsyndroms im Rahmen einer prospektiven randomisierten klinischen Doppelblindstudie (MOTHER Studie).

Methode: Die neonatalen Daten der MOTHER Studie wurden ortsbezogen analysiert. Sco­ring und Therapieprotokoll waren für alle Zentren standardisiert während die pflegerischen Maßnahmen differierten.

Ergebnisse: Neugeborene in den städtischen Zentren der USA wiesen die höchste Rate an neurologischen Symptomen auf (p<0,001), während in Europa signifikant mehr autonome, respiratorische und gastrointestinale Symptome gefunden wurden (p<0,05). Methadon führte in allen Zentren zu signifikant höheren neurologischen und respiratorischen Symptomen und zu mehr Verhaltensauffälligkeiten als Buprenorphin (ps<0,05). Die Rate an behandlungsbedürftigen Neugeborenen nach Methadonexposition war in allen Zentren gleich, jedoch mussten in Europa signifikant mehr buprenorphinexponierte Neugeborene behandelt werden als in den USA (p=0,001). In den städtischen Zentren der USA fanden sich signifikant höhere NAS Scores als in den ländlichen Gebieten und in Europa (p<0,01), die benötigten Morphindosen waren signifikant höher (p<0,05) und die Behandlungsdauer war länger. Geburtsgewicht, Länge und Kopfumfang wiesen keine signifikanten Unterschiede auf, jedoch waren die APGAR Scores in Europa signifikant höher (p<0,01).

Schlussfolgerung: Züsatzlich zur mütterlichen Medikation während der Schwangerschaft scheinen auch noch andere Faktoren wie ­unterschiedlich schwere Drogenabhängigkeit der Mütter, unterschiedliche Behandlungsmethoden inklusive Rooming-in sowie häufigeres NAS-Rating den Verlauf des neonatalen Entzugssyndroms zu beeinflussen.

• References

• 1 Abdel-Latif ME, Pinner J, Clews S et al. Effects of breast milk on the severity and outcome of neonatal abstinence syndrome among infants of drug-dependent mothers. Pediatrics 2006; 117: e1163-e1169
  CrossrefPubMedGoogle Scholar
• 2 Baewert A, Jagsch R, Winklbaur B et al. Influence of site differences between urban and rural American and Central European opioid-dependent pregnant women and neonatal outcome characteristics. Eur Addict Res 2012; 18: 130-139
  CrossrefPubMedGoogle Scholar
• 3 Belcheva MM, Bohn LM, Ho MT et al. Brain opioid receptor adaptation and expression after prenatal exposure to buprenorphine. Brain Res Dev Brain Res 1998; 111: 35-42
  CrossrefPubMedGoogle Scholar
• 4 Buchi KF, Suarez C, Varner MW. The prevalence of prenatal opioid and other drug use in Utah. Am J Perinatol 2013; 30: 241-244
  Article in Thieme ConnectPubMedGoogle Scholar
• 5 Dabek MT, Poeschl J, Englert S et al. Treatment of neonatal abstinence syndrome in preterm and term infants. Klin Paediatr 2013; 255: 252-256
  Article in Thieme ConnectPubMedGoogle Scholar
• 6 Finnegan LP, Connaughton JF, Kron RE et al. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975; 2: 141-158
  PubMedGoogle Scholar
• 7 Finnegan LP, Kron RE, Connaughton JF et al. Assessment and treatment of abstinence in the infant of the drug-dependent mother. Int J Clin Pharmacol Biopharm 1975; 12: 19-32
  PubMedGoogle Scholar
• 8 Finnegan LP, Kaltenbach K. Neonatal abstinence syndrome. In Hoekelman RA, Friedman SB, Nelson NM. et al. eds. Primary pediatric care. 2^nd ed. St. Louis: Mosby; 1992: 1367-1378
  Google Scholar
• 9 Fischer G, Ortner R, Rohrmeister K et al. Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study. Addiction 2006; 101: 275-281
  Google Scholar
• 10 Gortner L. Neonatal abstinence syndrome – change in therapy options. Klin Padiatr 2013; 225: 243-244
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Hünseler C, Brückle M, Roth B et al. Neonatal opiate withdrawal and rooming-in: a retrospective analysis of a single center experience. Klin Padiatr 2013; 225: 247-251
  Google Scholar
• 12 Jansson LM, Velez M, Harrow C. The opioid-exposed newborn: assessment and pharmacologic management. J Opioid Manag 2009; 5: 47-55
  PubMedGoogle Scholar
• 13 Jones HE, Johnson RE, Jasinski DR et al. Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Drug Alcohol Depend 2005; 79: 1-10
  CrossrefPubMedGoogle Scholar
• 14 Jones HE, O’Grady KE, Malfi D et al. Methadone maintenance vs. methadone taper during pregnancy: maternal and neonatal outcomes. Am J Addict 2008; 17: 372-386
  CrossrefPubMedGoogle Scholar
• 15 Jones HE, Martin PR, Heil SH et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat 2008; 35: 245-259
  CrossrefPubMedGoogle Scholar
• 16 Jones HE, Kaltenbach K, Heil SH et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med 2010; 363: 2320-2331
  CrossrefPubMedGoogle Scholar
• 17 Kakko J, Heilig M, Sarman I. Buprenorphine and methadone treatment of opiate dependence during pregnancy: comparison of fetal growth and neonatal outcomes in two consecutive case series. Drug Alcohol Depend 2008; 96: 69-78
  CrossrefPubMedGoogle Scholar
• 18 Kaltenbach K, Berghella V, Finnegan L. Opioid dependency during pregnancy. Effects and management. Obstet Gynecol Clin North Am 1998; 25: 139-151
  CrossrefPubMedGoogle Scholar
• 19 Lacroix I, Berrebi A, Garipuy D et al. Buprenorphine versus methadone in pregnant opioid-dependent women: a prospective multicenter study. Eur J Clin Pharmacol 2011; 67: 1053-1059
  CrossrefPubMedGoogle Scholar
• 20 Mattick RP, Kimber J, Breen C et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2008; 16 CD002207
  PubMedGoogle Scholar
• 21 Mattick RP, Breen C, Kimber J et al. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev 2009; 8 CD002209
  PubMedGoogle Scholar
• 22 Müller MJ, Lange M, Paul T et al. Breast feeding during methadon- and buprenorphin therapy. Klin Padiatr 2011; 223: 408-413
  Article in Thieme ConnectPubMedGoogle Scholar
• 23 Nanovskaya T, Deshmukh S, Brooks M et al. Transplacental transfer and metabolism of buprenorphine. J Pharmacol Exp Ther 2002; 300: 26-33
  CrossrefPubMedGoogle Scholar
• 24 Osborn DA, Jeffery HE, Cole MJ. Opiate treatment for opiate withdrawal in newborn infants. Cochrane Database Rev 2010; 6 CD002059
  PubMedGoogle Scholar
• 25 Pizarro D, Habli M, Grier M et al. Higher maternal doses of methadone does not increase neonatal abstinence syndrome. J Subst Abuse Treat 2011; 40: 295-298
  Google Scholar
• 26 Poeschl J, Dabek M, Englert S et al. Treatment of neonatal abstinence syndrome in preterm and term neonates. Klin Padiatr 2013; 225: 252-256
  Article in Thieme ConnectPubMedGoogle Scholar
• 27 Schindler SD, Eder H, Ortner R et al. Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy. Addiction 2003; 98: 103-110
  Google Scholar
• 28 Schneck H. Narcotic withdrawal symptoms in the newborn infant resulting from maternal addiction. J Pediatr 1958; 52: 584-587
  CrossrefPubMedGoogle Scholar
• 29 Unger AS, Martin PR, Kaltenbach K et al. Clinical characteristics of central European and North American samples of pregnant women screened for opioid agonist treatment. Eur Addict Res 2010; 16: 99-107
  CrossrefPubMedGoogle Scholar
• 30 Winklbaur B, Kopf N, Ebner N et al. Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: a knowledge synthesis for better treatment for women and neonates. Addiction 2008; 103: 1429-1440
  CrossrefPubMedGoogle Scholar