IMPORTANCEOpioids are frequently prescribed to children and adolescents after surgery. Prescription opioid misuse is associated with high-risk behavior in youth. Evidence-based guidelines for opioid prescribing practices in children are lacking.OBJECTIVE To assemble a multidisciplinary team of health care experts and leaders in opioid stewardship, review current literature regarding opioid use and risks unique to pediatric populations, and develop a broad framework for evidence-based opioid prescribing guidelines for children who require surgery.EVIDENCE REVIEW Reviews of relevant literature were performed including all English-language articles published from January 1, 1988, to February 28, 2019, found via searches of the PubMed (MEDLINE), CINAHL, Embase, and Cochrane databases. Pediatric was defined as children younger than 18 years. Animal and experimental studies, case reports, review articles, and editorials were excluded. Selected articles were graded using tools from the Oxford Centre for Evidence-based Medicine 2011 levels of evidence. The Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument was applied throughout guideline creation. Consensus was determined using a modified Delphi technique.FINDINGS Overall, 14 574 articles were screened for inclusion, with 217 unique articles included for qualitative synthesis. Twenty guideline statements were generated from a 2-day in-person meeting and subsequently reviewed, edited, and endorsed externally by pediatric surgical specialists, the American Pediatric Surgery Association Board of Governors, the American Academy of Pediatrics Section on Surgery Executive Committee, and the American College of Surgeons Board of Regents. Review of the literature and guideline statements underscored 3 primary themes: (1) health care professionals caring for children who require surgery must recognize the risks of opioid misuse associated with prescription opioids, (2) nonopioid analgesic use should be optimized in the perioperative period, and (3) patient and family education regarding perioperative pain management and safe opioid use practices must occur both before and after surgery.CONCLUSIONS AND RELEVANCE These are the first opioid-prescribing guidelines to address the unique needs of children who require surgery. Health care professionals caring for children and adolescents in the perioperative period should optimize pain management and minimize risks associated with opioid use by engaging patients and families in opioid stewardship efforts.

Purpose: Pain in the neonate is often challenging to assess but important to control. Physicians often must balance the need for optimal pain control with the need to minimize oversedation and prolonged opioid use. Both inadequate pain control and overuse of opioids can have long-term consequences, including poor developmental outcomes. The aim of this review is to introduce a comprehensive approach to pain management for physicians, nurses, and surgeons caring for critically ill neonates, focusing on nonopioid alternatives to manage procedural pain. Findings: After review, categories of opioid-sparing interventions identified included (1) nonopioid pharmacologic agents, (2) local and regional anesthesia, and (3) nonpharmacologic alternatives. Nonopioid pharmacologic agents identified for neonatal use included acetaminophen, NSAIDs, dexmedetomidine, and gabapentin. Local and regional anesthesia included neuraxial blockade (spinals and epidurals), subcutaneous injections, and topical anesthesia. Nonpharmacologic agents uniquely available in the neonatal setting included skin-to-skin care, facilitated tucking, sucrose, breastfeeding, and nonnutritive sucking. Implications: The use of various pharmacologic and interventional treatments for neonatal pain management allows for the incorporation of opioidsparing techniques in neonates who are already at risk for poor neurodevelopmental outcomes. A multifactorial approach to pain control is paramount to optimize periprocedural comfort and to minimize the negative sequelae of uncontrolled pain in the neonate.

In patients with biliary atresia (BA), the extent of intrahepatic biliary fibrosis negatively correlates with successful surgical bypass of the congenital cholangiopathy as well as subsequent transplant‐free survival. We recently linked the expansion of a population of prominin‐1 (Prom1)‐expressing hepatic progenitor cells to biliary fibrogenesis. Herein, we hypothesized that Prom1‐expressing progenitor cells play a role in BA‐associated fibrosis. Rhesus rotavirus (RRV)‐mediated experimental BA was induced in newborn mice homozygous for the transgene Prom1cre‐ert2‐nlacz, which was knocked in to the Prom1 gene locus, thus creating functional Prom1 knockout (KO) mice, and their wildtype (WT) littermates. Clinical data and tissue samples from BA infants from the Childhood Liver Disease Research Consortium were analyzed. Extrahepatic biliary obliteration was present in both WT and KO mice; there was no difference in serum total bilirubin (TBili) levels. The intrahepatic periportal expansion of the PROM1pos cell population, typically observed in RRV‐induced BA, was absent in KO mice. RRV‐treated KO mice demonstrated significantly fewer cytokeratin‐19 (CK19)‐positive ductular reactions (P = 0.0004) and significantly less periportal collagen deposition (P = 0.0001) compared with WT. RRV‐treated KO mice expressed significantly less integrin‐β6, which encodes a key biliary‐specific subunit of a transforming growth factor (TGF) β activator (P = 0.0004). Infants with successful biliary drainage (Tbili ≤1.5 mg/dL within 3 months postoperatively), which is highly predictive of increased transplant‐free survival, expressed significantly less hepatic PROM1, CK19, and COLLAGEN‐1α compared with those with TBili >1.5 (P < 0.05). Conclusion: Prom1 plays an important role in biliary fibrogenesis, in part through integrin‐mediated TGF pathway activation.