Outcome reporting in neonates experiencing withdrawal following opioid exposure in pregnancy: a systematic review

Abstract

Background: Neonatal withdrawal secondary to in utero opioid exposure is a growing global concern stressing the psychosocial well-being of affected families and scarce hospital resources. In the ongoing search for the most effective treatment, randomized controlled trials are indispensable. Consistent outcome selection and measurement across randomized controlled trials enables synthesis of results, fostering the translation of research into practice. Currently, there is no core outcome set to standardize outcome selection, definition and reporting. This study identifies the outcomes currently reported in the literature for neonates experiencing withdrawal following opioid exposure during pregnancy.

Methods: A comprehensive literature search of MEDLINE, EMBASE and Cochrane Central was conducted to identify all primary research studies (randomized controlled trials, clinical trials, case-controlled studies, uncontrolled trials, observational cohort studies, clinical practice guidelines and case reports) reporting outcomes for interventions used to manage neonatal abstinence syndrome between July 2007 and July 2017. All "primary" and "secondary" neonatal outcomes were extracted by two independent reviewers and were assigned to one of OMERACT's core areas of "pathophysiological manifestation", "life impact", "resource use", "adverse events", or "death".

Results: Forty-seven primary research articles reporting 107 "primary" and 127 "secondary" outcomes were included. The most frequently reported outcomes were "duration of pharmacotherapy" (68% of studies, N = 32), "duration of hospital stay" (66% of studies, N = 31) and "withdrawal symptoms" (51% of studies, N = 24). The discrepancy between the number of times an outcome was reported and the number of articles was secondary to the use of composite outcomes. Frequently reported outcomes had heterogeneous definitions or were not defined by the study and were measured at different times. Outcomes reported in the literature to date were mainly assigned to the core areas "pathophysiologic manifestations" or "resource use". No articles reported included parent or former patient involvement in outcome selections.

Conclusions: Inconsistent selection and definition of primary and secondary outcomes exists in the present literature of pharmacologic and nonpharmacologic interventions for managing opioid withdrawal in neonates. No studies involved parents in the process of outcome selection. These findings hinder evidence synthesis to generate clinically meaningful practice guidelines. The development of a specific core outcome set is imperative.

Keywords: Core outcome set; Maternal opioid use disorder; Neonatal abstinence syndrome; Neonatal opioid withdrawal syndrome; Neonatal withdrawal syndrome; Opioid exposed newborn baby.

Fig. 1

Prisma article selection flow diagram. NAS neonatal abstinence syndrome

Fig. 2

Outcome matrix of 234 outcome terms (rows) for 47 primary research studies (columns). Red signifies a primary outcome. Blue signifies a secondary outcome. Green signifies a primary and secondary outcome reported in the same article that fit within the same outcome category. NAS neonatal abstinence syndrome, NICU neonatal intensive care unit

Fig. 3

Assignment of outcome terms to OMERACT 2.0 core areas. Parentheses show the number of studies in which the outcome was used as primary outcome/used as secondary outcome. See Table 2 for definitions of adverse events and treatment failure. ER emergency room, NAS neonatal abstinence syndrome, NICU neonatal intensive care unit