iPAPP: study protocol for a multicentre randomised controlled trial comparing safety and efficacy of intravenous paracetamol and indomethacin for the treatment of patent ductus arteriosus in preterm infants.

INTRODUCTION: Patent ductus arteriosus (PDA) causes severe morbidity in premature infants. Although the use of indomethacin is the standard therapy for PDA, it is sometimes not applicable because of its adverse effects, such as renal and platelet dysfunctions. Paracetamol has emerged as an alternative to indomethacin owing to its excellent safety profile in infants. Of the recently reported case series and clinical trials on the use of paracetamol for PDA, there are few reports in Japan on paracetamol use in preterm infants. Furthermore, indications for the use of paracetamol for PDA have not been approved for use in PDA. While the safety of intravenous paracetamol therapy in case series of preterm infants treated for haemodynamically significant PDA (hsPDA) has been reported, studies which were conducted to compare paracetamol to indomethacin are limited. We, therefore, intend to investigate the hypothesis that intravenous administration of paracetamol has superior safety over indomethacin. METHODS AND ANALYSIS: Multicentre open-label randomised controlled trial for intravenous administration of paracetamol for PDA in preterm infants. The inclusion criteria are (1) hsPDA, (2) gestational age from 24 to 34 weeks and birth weight (BW) from 500 to 2000 g, (3) enrolment between 24 hours and 7 days from birth and (4) obtaining parental consent. The primary outcome is renal dysfunction within 48 hours from the last dose of the study drug. Enrolled patients fulfilling all the inclusion criteria are randomly allocated to either intravenous paracetamol or intravenous indomethacin. This trial requires 110 patients. ETHICS AND DISSEMINATION: The clinical trial would follow Japan's Clinical Trials Act. The trial protocol was approved by the Clinical Research Review Board of Saitama Medical University (approval number: 222001). A written informed consent would be obtained from one of the parents. The results are expected to be published in a scientific journal. TRIAL REGISTRATION NUMBER: jRCTs031220386. PROTOCOL VERSION: 31 March 2022, version 1.0.

Interventions for expectant and new parents who are at increased risk for perpetrating child abuse and neglect: protocol for a systematic review and meta-analysis.

INTRODUCTION: The prevention of child abuse and neglect is an urgent matter given the serious effects persisting into adulthood, and the increased risk of the offspring of abused children being abusive themselves. Intervening as early as possible may prevent abuse that can begin in infancy. Although several systematic reviews have investigated the effects of interventions on populations who are at increased risk for perpetrating child abuse and neglect, few studies have focused on women or interventions that start during perinatal periods. This study aims to describe a systematic review to examine the effects of interventions to prevent child abuse and neglect that begin during pregnancy and immediately after childbirth (less than 1 year). The study will involve performing a systematic review and meta-analysis based on the latest research articles and a broader literature search. METHODS AND ANALYSIS: The protocol was prepared using the 2015 statement of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. The review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature search will be performed using the MEDLINE, PsycINFO, Embase and Cochrane Central Register of Controlled Trials databases from inception onward. Randomised controlled trials of interventions that begin during pregnancy or the first year postpartum, designed to prevent child abuse and neglect in families who are at increased risk for these issues, will be included. Data collection, quality assessment and statistical syntheses will be conducted by following the methods in the protocol that are predefined. Any index of child maltreatment will be included as a primary outcome. A meta-analysis and sub-group analyses will be considered based on the characteristics of interventions. ETHICS AND DISSEMINATION: This study does not require ethical approval. The findings will be presented at conferences and will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021266462.