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.

Strategies for the Prevention and Treatment of Iatrogenic Withdrawal from Opioids and Benzodiazepines in Critically Ill Neonates, Children and Adults: A Systematic Review of Clinical Studies

“…duration of IWS, relapse, post-ICU physical dependence and healthrelated quality of life). Developing a core outcome set for studies examining IWS, as for conditions such as neonatal abstinence syndrome or delirium [45,46], may address the latter issues. Shared definitions of important and meaningful outcomes would allow combination and comparison of study outcomes and assist in the development of robust conclusions about effectiveness of interventions.…”

Opioid Treatment for Neonatal Opioid Withdrawal Syndrome: Current Challenges and Future Approaches

“…The analysis also concluded that morphine was the least effective treatment used to treat NOWS, whereas methadone, buprenorphine, and clonidine were the most effective. Finally, a systematic review by Shan et al 114 evaluated the consistency in reported outcomes of clinical studies conducted in neonates treated for NOWS among 47 publications published between 2007 and 2017 with 107 primary outcomes and 127 secondary outcomes. The authors concluded that outcomes were similar among studies; however, the definitions of the outcomes varied.…”

“…LOS and DOT are the conventional primary outcomes used to assess the effectiveness of each medication used during NOWS pharmacotherapy. Several studies have compared the pharmacotherapy with morphine, methadone, and buprenorphine in the treatment of NOWS 112–114 . Table 2 includes recent studies (published since 2015), which included assessment tools, compared treatment options (ie, morphine vs methadone, methadone vs buprenorphine, buprenorphine vs morphine), sample size, study type, DOT, LOS, and the number of patients administered adjunctive therapy.…”

“…Several studies have compared the pharmacotherapy with morphine, methadone, and buprenorphine in the treatment of NOWS. [112][113][114] Although most studies suggested that methadone is a better therapy than morphine, 116,117 in the study by Young et al, 115 morphine had a shorter DOT (7.46 vs 38.08 days) and LOS (12.08 vs 44.23 days) compared with methadone. However, the Finnegan scoring system was used to evaluate neonates administered morphine, whereas neonates administered methadone were evaluated using the Neonatal Withdrawal Inventory (NWI) system.…”

A Core Outcome Set for Neonatal Opioid Withdrawal Syndrome

“…12 Authors of a recent review highlighted that a limited number of studies included families in study design, primarily outcome selection. 13 In neonatology, clinical trial populations are small, and studies are often underpowered to answer additional effectiveness questions or conduct meaningful subgroup analysis. 14,15 This compounds the need and relevance for meta-analysis (or data pooling) of multiple studies' results to answer important questions on interventions' safety and effectiveness.…”