2025

Trends of prenatal opioid utilization and neonatal abstinence syndrome in Manitoba, Canada: A 26-year population-based cohort study Paediatrics & Child Health, 05 June 2025

Background: Opioids are prescribed for pain and as opioid agonist therapy for opioid use disorder. This can lead to neonatal abstinence syndrome (NAS) in newborns when used in pregnancy. Few studies have described trends in prenatal opioid prescriptions and NAS by important determinants of health.

Methods: To examine trends in prenatal opioid prescriptions and NAS diagnosis rates we conducted a population-based cohort study of live births in Manitoba, Canada, from January 1995 to March 2021. Live births were considered exposed to opioids prenatally if the pregnant person filled ≥1 opioid prescription during pregnancy. We described trends in NAS diagnosis rates by year, sex, urbanicity, and income quintile.

Results: The cohort included 381,826 live births, of which 26,382 (6.7%) were exposed to prescription opioids prenatally. The proportion of live births exposed to opioid prescriptions during pregnancy increased from 3.7% in 1995 to 7.4% in 2017; however, there was a reduction in recent years. We identified a decrease in codeine prescriptions during pregnancy and an increased number of prescriptions for more potent opioids (oxycodone, hydromorphone, morphine, and opioid agonist therapy). During the study period, there were 1318 newborns diagnosed with NAS. The incidence of NAS in Manitoba more than tripled between 1995 and 2021 (2.0 to 7.6 per 1000 live births).

Interpretation: The incidence of NAS increased over the study period, in line with other jurisdictions. Further research is needed to study the safety of different opioid agonist therapies and multidisciplinary support needed to support parents to care for newborns with NAS in the postpartum period and beyond.

Treatment for substance use disorder in mothers of young children: A systematic review of maternal substance use and child mental health outcomes Addictive Behaviors, 01 April 2025

Substance use disorders (SUD) in mothers of young children can negatively impact the family unit and promote the intergenerational cycle of mental health disorders. This systematic review aims to: 1) provide an overview of substance use treatments for mothers of young children (from birth to 5 years old); 2) synthesize findings on maternal substance use and child/maternal mental health outcomes; and 3) identify key treatment components. Database searches in Medline, PsycINFO, PubMED, and PsycARTICLES were conducted on May 7th, 2024. A total of 14, 916 articles were identified following duplicate removal. Articles were screened following PRISMA guidelines. Eight articles (n = 900) met inclusion criteria. Outcomes of interest included maternal substance use, child/maternal mental health, and treatment components. All studies indicated maternal substance use treatments were at least as, or more, effective in improving maternal substance use and child/maternal mental health outcomes compared to controls. Treatment components included: mother/family mental health, basic needs, parenting skills, occupation/education, operant conditioning, crisis management, and medical education. Operant conditioning was the only treatment component which appeared to positively impact maternal substance use outcomes; no other treatment components were associated with outcomes of interest. This review provides preliminary evidence highlighting the benefits of substance use treatments for mothers of young children on substance use and mental health outcomes. Future randomized controlled trials with harmonized outcome measures and qualitative data that identifies treatment needs of mothers with lived experience are crucial to evaluate maternal substance use treatments and improve treatment development.

2020

Outcome reporting in neonates experiencing withdrawal following opioid exposure in pregnancy: a systematic review Trials, 12 March 2020

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.

A Core Outcome Set for Neonatal Opioid Withdrawal Syndrome, Pediatrics, 01 July 2020

Background: As rates of neonatal opioid withdrawal are increasing, the need for research to evaluate new treatments is growing. Large heterogeneity exists in health outcomes reported in current literature. Our objective is to develop an evidence-informed and consensus-based core outcome set in neonatal opioid withdrawal syndrome (NOWS-COS) for use in studies and clinical practice.

Methods: An international multidisciplinary steering committee was established. A systematic review and a 3-round Delphi was performed with open-ended and score-based assessments of the importance of each outcome to inform clinical management of neonatal opioid withdrawal. Interviews were conducted with parents and/or caregivers on outcome importance. Finally, a consensus meeting with diverse stakeholders was held to review all data from all sources and establish a core set of outcomes with definitions.

Results: The NOWS-COS was informed by 47 published studies, 41 Delphi participants, and 6 parent interviews. There were 63 outcomes evaluated. Final core outcomes include (1) pharmacologic treatment, (2) total dose of opioid treatment, (3) duration of treatment, (4) adjuvant therapy, (5) feeding difficulties, (6) consolability, (7) time to adequate symptom control, (8) parent-infant bonding, (9) duration of time the neonate spent in the hospital, (10) breastfeeding, (11) weight gain at hospital discharge, (12) readmission to hospital for withdrawal, and (13) neurodevelopment.

Conclusions: We developed an evidence-informed and consensus-based core outcome set. Implementation of this core outcome set will reduce heterogeneity between studies and facilitate evidence-based decision-making. Future research will disseminate all the findings and pilot test the validity of the NOWS-COS in additional countries and populations to increase generalizability and impact.

2016

A core outcome set for neonatal abstinence syndrome: study protocol for a systematic review, parent interviews and a Delphi survey Trials, 08 November 2016

Background: The prevalence of neonatal abstinence syndrome (NAS) is increasing globally resulting in an increased incidence of adverse neonatal outcomes and health system costs. Evidence regarding the effectiveness of NAS prevention and management strategies is very weak and further research initiatives are critically needed to support meta-analysis and clinical practice guidelines. In NAS research, the choice of outcomes and the use of valid, responsive and feasible measurement instruments are crucial. There is currently no consensus and evidence-based core outcome set (COS) for NAS.

Methods/design: The development of the NAS-COS will include five stages led by an international Multidisciplinary Steering Committee: (1) qualitative interviews with parents/families and a systematic review (SR) to identify items for inclusion in a COS. The SR will also identify participants for the Delphi survey, (2) a three-round Delphi survey to gain expert opinion on the importance of health outcomes influencing NAS management decisions, (3), a consensus meeting to finalize the items and definitions with experts and COS users, (4) feasibility and pilot testing, development of the COS and explanatory document and (5) implementation planning.

Discussion: Since standardized outcome measurement and reporting will improve NAS clinical research consistency, efficacy and impact, this COS will reflect the minimum set of health outcomes which should be measured in trials evaluating interventions for preventing or treating NAS.