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Introduction: Prophylactic paracetamol for extremely low gestation age neonates (ELGAN, <27 weeks' gestation) with symptomatic patent ductus arteriosus (sPDA) in high-income countries (HIC) reduces medical and surgical interventions. Its effectiveness in low-to-middle-income countries (LMIC) remains uncertain. This study assesses prophylactic paracetamol's impact on sPDA interventions in ELGANs in an LMIC., Methods: This is a retrospective cohort study that compared a historical cohort of ELGANs that were treated with oral ibuprofen or intravenous paracetamol after diagnosis of sPDA ( n = 104) with infants ( n = 76) treated with prophylactic paracetamol (20 mg/kg loading, 7.5 mg/kg qid for 4 days), in a tertiary neonatal intensive care unit (NICU) in Vietnam. Oral ibuprofen or intravenous therapeutic paracetamol were administered if prophylactic paracetamol failed to close sPDA. Surgical ligation was conducted if targeted medical intervention failed, or the infant deteriorated from conditions attributable to sPDA., Results: In the historical cohort, 57 (55%) infants died within 7 days of life compared to 18 (24%) from the prophylactic cohort ( p < 0.01). Of the survivors, 21 (45%) of the historical and 23 (39.7%) of the prophylactic cohort required surgical ligation ( p = 0.6). Duration of hospitalization for survivors was lower in the prophylactic cohort (mean 74 vs. 97 days, p = 0.01). In the prophylactic cohort, 24 (41%) infants did not need further treatment while 34 (59%) required further treatment including ibuprofen and/or paracetamol 28 (48%) and surgical ligation 22 (38%)., Conclusions: Prophylactic paracetamol for ELGAN in LMIC does not reduce the need for surgical ligation, sPDA rates, and other PDA-related morbidities in infants who survive beyond 7 days of age. It may reduce the risk of death and the duration of hospitalization but further study into the reasons behind this need to be determined with larger studies.

Background: The prevalence of neonatal abstinence syndrome is increasing, but the number and quality of clinical practice guidelines available are unknown. This systematic review aimed to identify, appraise and evaluate clinical practice guidelines for neonatal abstinence syndrome., Methods: A systematic search of databases and the grey literature was conducted between 1 June and 1 July 2022. Full-text guidelines published by national or state-wide institutions were included. The recommendations from each guideline were extracted. The AGREE-II instrument was used to assess guideline quality. Sufficient-quality scores were defined as >60 and good-quality scores were >80 for each domain of AGREE-II., Results: A total of 1703 records were identified, and 22 guidelines from the United States, Australia, Canada and the United Kingdom, published between 2012 to 2021, were included. The quality scores were low, with median scores of 37/100 for stakeholder involvement, 33/100 for methodology, 34/100 for applicability and 0 for editorial independence. Scope and purpose scored 72/100, and presentation scored 85/100. Sixteen (73%) guidelines did not meet the cut-offs for clinical use., Conclusion: Many guidelines were of insufficient quality to guide clinical practice for neonatal abstinence syndrome. This emphasises the need for high-quality studies to inform clinical practice guidelines, improve care and reduce the risk of poor outcomes in these high-risk infants.

This study assessed the economic evidence on the pharmacological and non-pharmacological management of infants with neonatal opioid withdrawal syndrome (NOWS). Six databases were searched up to October 2020 for peer-reviewed studies. After titles and abstracts were screened, 79 studies remained for full-text review, and finally, 8 studies were eligible for inclusion in the review. The methodological quality of included studies was assessed using the Drummond checklist. The review showed significant limitations in these studies, with one study being rated as good and the remaining seven studies as of poor quality. There are methodological issues that require addressing, including a lack of detail on cost categories, a robust investigation of uncertainty, and extending the time horizon to consider longer-term outcomes beyond the initial birth hospitalization. Despite these limitations, existing evidence suggests non-pharmacological strategies such as rooming-in were associated with a shorter hospital stay and a decreased need for pharmacological treatment, thereby lowering hospitalization costs. The review highlights the paucity of high-quality studies assessing the cost-effectiveness of intervention strategies for NOWS. There is also a lack of evidence on long-term outcomes associated with NOWS and the treatment of NOWS. The inclusion of economic analyses in future studies will provide evidence to inform policymakers on resource allocation decisions for this patient population.

Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used, but might be ineffective and has side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective was to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: "infant", "premature", "pain", "acupuncture", "skin-to-skin contact", "sucrose", "massage", "musical therapy" and 'breastfeeding'. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but was more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin-to-skin care and musical therapy. Most non-pharmacological methods of analgesia provide a modicum of relief for preterm infants, but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.