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

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.

Keywords

intrauterine opioid exposure - neonatal abstinence ­syndrome - methadone - buprenorphine - morphine

Schlüsselwörter

intrauterine Opiatexposition - neonatales Abstinenz­syndrom - Methadon - Buprenorphin - Morphin

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