世界卫生组织PROPS试验（早产儿和小于胎龄儿的PRObiotics）

Date Dr. Ameena Goga, Dr. Sachiyo Yoshida, World Health Organization. Contact details:gogaa@who.int,yoshidas@who.int. Contact The WHO PROPS Trial (PRObiotics in Preterm and Small for gestational age infants) Title Aims and objectives of the trial: The overall aim of this trial is to assess the effect of probiotic supplementationon mortality,morbidity, and growth in preterm or termsmall for gestational age (SGA)infants in the first sixmonths of life in South Asia and Sub-Saharan Africa. For preterm infants, the primary objective is to assess theeffectiveness of probiotic supplementation on mortality from enrolment to six months of age. For term SGAinfants theprimary objective is to assess the effectiveness of probiotic supplementation on underweight-freesurvival from enrolment to six months of age. Secondary objectives are: to assess effect on morbidities(sepsis, necrotising enterocolitis, severe diarrhoea and growth [wasting and underweight]) from enrolment tosix months of age; to determine safety outcomes (serious adverse events [SAEs] and probiotic sepsis fromenrolment to six monthsof age; and to understand faecal colonisation of probiotic organisms from enrolmentto six months of age. Details Design. Double-blind, individually-randomised, placebo-controlled, parallel-group clinical trial. Intervention and placebo administration: The intervention will be the strainsBifidobacterium longum subsp.InfantisDSM33361 (B. Infantis) andLactobacillus rhamnosusGG DSM33156 (L. rhamnosus GG). The doseswill be 0.35 billion colony forming units (CFU)B. infantisand 1 billion CFUL. rhamnosusGG once daily for 28days. The strains will be mixed with maltodextrin powder. The placebo will be maltodextrin powder alonewithout the probiotic organisms. The supplements will be given daily by the family to the baby, directlyobserved by research staff during home visits. Study setting and recruitment: The study is being conducted in five sites in five countries; Bangladesh,Ethiopia, Kenya, Nigeria and Pakistan,which were selected after an open call for expressions of interest. Studyrecruitment will be at hospitals in the study sites. Infants will be enrolled at within two days of birth, andsupplementation will commence at that time. Infants will be followed up monthly at home during home visitsfrom research staff. A total of 14,000 infants will be enrolled across the five participating sites. Numerous small trials conducted in the last ten years have reported that probiotics can improve short-andlong-term mortality, necrotising enterocolitis, sepsis, growth and neurodevelopment in preterm and term SGAinfants. In 2022, a World Health Organization (WHO) guideline development group (GDG) reviewed theevidence for the impact of probiotics in preterm and term SGA infants and their final guidelines included aconditional recommendation for the use of probiotics for human milk fed infants < 32 weeksgestation or <1.5kg at birth. However, the evidence of effect on all critical outcomes (mortality, necrotising enterocolitis,sepsis and growth) was graded as low quality due to heterogeneity, risk of bias, indirectness and imprecision.In addition theGDG was not able to make a recommendation on type (i.e. genera, species or strain),formulation (e.g. powder or drops), dose, timing or duration of probiotic administration as there wasinsufficient evidence. Programmaticimplications WHO and other organisations have recommended thatfurther large high-quality trials are implemented toprovide evidence of sufficient quality and applicability to inform policy and practice.The WHO GDGrecommended thatrigorous new research was needed to improve certainty of evidence on critical outcomesand also to understand optimal strains, dosing and duration of probopic supplementation and related impact. Infants will be enrolled over a period of 18 months and followed up until they reach six months of age. Timeline Bangladesh, Ethiopia, Kenya, Nigeria, Pakistan Geographiclocation Ethiopia-MahletAbayneh Gizaw, St Paul’s Hospital Millennium Medical College, Addis Ababa, EthiopiaNigeria-Adejumoke Idowu Ayede, College of Medicine, University of Ibadan and University College Hospital,Ibadan, NigeriaBangladesh-Mohammod Shahidullah, Projahnmo Research Foundation, Dhaka, BangladeshKenya-Benson Singa, Kenya Medical Research Institute, Nairobi, KenyaPakistan-Fyezah Jehan, Aga Khan University, Karachi, Pakistan Principalinvestigators Main externalfundersGates Foundation The trial is sponsored by the World Health Organization (WHO)Department of Sexual, Reproductive, Maternal,Child, Adolescent and Older Persons health (LHR) Coordinator /sponsor Clinical trial registry.ISRCTN12028895.https://www.isrctn.com/ISRCTN12028895Also available on request.Trial protocol. WHO Ethical Review Committee. Also available on request.Statistical analysis plan.ISRCTN12028895.https://www.isrctn.com/ISRCTN12028895Also available onrequest Additionaldocuments