Jon Dorling1, Jane Abbott1, Janet Berrington1, Beth Bosiak1, Ursula Bowler1, Elaine Boyle1, Nicholas Embleton1, Oliver Hewer1, Samantha Johnson1, Edmund Juszczak1, Alison Leaf1, Louise Linsell1, Kenny McCormick1, William McGuire1, Omar Omar1, Christopher Partlett1, Mehali Patel1, Tracy Roberts1, Ben Stenson1, John Townend1. 1. From the Division of Neonatal-Perinatal Medicine, Dalhousie University, Halifax, NS, Canada (J.D.); and Bliss, London (J.A., M.P.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford (B.B., U.B., O.H., E.J., L.L., O.O., C.P., J.T.), and John Radcliffe Hospital (K.M.), Oxford, the Newcastle Neonatal Service, Royal Victoria Infirmary, Newcastle upon Tyne (J.B., N.E.), the Department of Health Sciences, University of Leicester, Leicester (E.B., S.J.), the National Institute for Health Research Southampton Biomedical Research Centre, Department of Child Health, Southampton (A.L.), the Centre for Reviews and Dissemination, University of York, York (W.M.), the School of Health and Population Sciences, University of Birmingham, Birmingham (T.R.), and the Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh (B.S.) - all in the United Kingdom.
Abstract
BACKGROUND: Observational data have shown that slow advancement of enteral feeding volumes in preterm infants is associated with a reduced risk of necrotizing enterocolitis but an increased risk of late-onset sepsis. However, data from randomized trials are limited. METHODS: We randomly assigned very preterm or very-low-birth-weight infants to daily milk increments of 30 ml per kilogram of body weight (faster increment) or 18 ml per kilogram (slower increment) until reaching full feeding volumes. The primary outcome was survival without moderate or severe neurodevelopmental disability at 24 months. Secondary outcomes included components of the primary outcome, confirmed or suspected late-onset sepsis, necrotizing enterocolitis, and cerebral palsy. RESULTS: Among 2804 infants who underwent randomization, the primary outcome could be assessed in 1224 (87.4%) assigned to the faster increment and 1246 (88.7%) assigned to the slower increment. Survival without moderate or severe neurodevelopmental disability at 24 months occurred in 802 of 1224 infants (65.5%) assigned to the faster increment and 848 of 1246 (68.1%) assigned to the slower increment (adjusted risk ratio, 0.96; 95% confidence interval [CI], 0.92 to 1.01; P = 0.16). Late-onset sepsis occurred in 414 of 1389 infants (29.8%) in the faster-increment group and 434 of 1397 (31.1%) in the slower-increment group (adjusted risk ratio, 0.96; 95% CI, 0.86 to 1.07). Necrotizing enterocolitis occurred in 70 of 1394 infants (5.0%) in the faster-increment group and 78 of 1399 (5.6%) in the slower-increment group (adjusted risk ratio, 0.88; 95% CI, 0.68 to 1.16). CONCLUSIONS: There was no significant difference in survival without moderate or severe neurodevelopmental disability at 24 months in very preterm or very-low-birth-weight infants with a strategy of advancing milk feeding volumes in daily increments of 30 ml per kilogram as compared with 18 ml per kilogram. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; SIFT Current Controlled Trials number, ISRCTN76463425.).
RCT Entities:
BACKGROUND: Observational data have shown that slow advancement of enteral feeding volumes in preterm infants is associated with a reduced risk of necrotizing enterocolitis but an increased risk of late-onset sepsis. However, data from randomized trials are limited. METHODS: We randomly assigned very preterm or very-low-birth-weight infants to daily milk increments of 30 ml per kilogram of body weight (faster increment) or 18 ml per kilogram (slower increment) until reaching full feeding volumes. The primary outcome was survival without moderate or severe neurodevelopmental disability at 24 months. Secondary outcomes included components of the primary outcome, confirmed or suspected late-onset sepsis, necrotizing enterocolitis, and cerebral palsy. RESULTS: Among 2804 infants who underwent randomization, the primary outcome could be assessed in 1224 (87.4%) assigned to the faster increment and 1246 (88.7%) assigned to the slower increment. Survival without moderate or severe neurodevelopmental disability at 24 months occurred in 802 of 1224 infants (65.5%) assigned to the faster increment and 848 of 1246 (68.1%) assigned to the slower increment (adjusted risk ratio, 0.96; 95% confidence interval [CI], 0.92 to 1.01; P = 0.16). Late-onset sepsis occurred in 414 of 1389 infants (29.8%) in the faster-increment group and 434 of 1397 (31.1%) in the slower-increment group (adjusted risk ratio, 0.96; 95% CI, 0.86 to 1.07). Necrotizing enterocolitis occurred in 70 of 1394 infants (5.0%) in the faster-increment group and 78 of 1399 (5.6%) in the slower-increment group (adjusted risk ratio, 0.88; 95% CI, 0.68 to 1.16). CONCLUSIONS: There was no significant difference in survival without moderate or severe neurodevelopmental disability at 24 months in very preterm or very-low-birth-weight infants with a strategy of advancing milk feeding volumes in daily increments of 30 ml per kilogram as compared with 18 ml per kilogram. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; SIFT Current Controlled Trials number, ISRCTN76463425.).
Authors: Lyvonne N Tume; Kerry Woolfall; Barbara Arch; Louise Roper; Elizabeth Deja; Ashley P Jones; Lynne Latten; Nazima Pathan; Helen Eccleson; Helen Hickey; Roger Parslow; Jennifer Preston; Anne Beissel; Izabela Andrzejewska; Chris Gale; Frederic V Valla; Jon Dorling Journal: Health Technol Assess Date: 2020-05 Impact factor: 4.014
Authors: Jon Dorling; Oliver Hewer; Madeleine Hurd; Vasha Bari; Beth Bosiak; Ursula Bowler; Andrew King; Louise Linsell; David Murray; Omar Omar; Christopher Partlett; Catherine Rounding; John Townend; Jane Abbott; Janet Berrington; Elaine Boyle; Nicholas Embleton; Samantha Johnson; Alison Leaf; Kenny McCormick; William McGuire; Mehali Patel; Tracy Roberts; Ben Stenson; Warda Tahir; Mark Monahan; Judy Richards; Judith Rankin; Edmund Juszczak Journal: Health Technol Assess Date: 2020-04 Impact factor: 4.014