Effects of delayed versus immediate umbilical cord clamping in reducing death or major disability at 2 years corrected age among very preterm infants (APTS): a multicentre, randomised clinical trial

Background Very preterm infants are at increased risk of adverse outcomes in early childhood. We assessed whether delayed clamping of the umbilical cord reduces mortality or major disability at 2 years in the APTS Childhood Follow Up Study. Methods In this long-term follow-up analysis of the multicentre, randomised APTS trial in 25 centres in seven countries, infants (<30 weeks gestation) were randomly assigned before birth (1:1) to have clinicians aim to delay clamping for 60 s or more or clamp within 10 s of birth, both without cord milking. The primary outcome was death or major disability (cerebral palsy, severe visual loss, deafness requiring a hearing aid or cochlear implants, major language or speech problems, or cognitive delay) at 2 years corrected age, analysed in the intention-to-treat population. This trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12610000633088). Findings Between Oct 21, 2009, and Jan 6, 2017, consent was obtained for follow-up for 1531 infants, of whom 767 were randomly assigned to delayed clamping and 764 to immediate clamping. 384 (25%) of 1531 infants were multiple births, 862 (56%) infants were male, and 505 (33%) were born before 27 weeks gestation. 564 (74%) of 767 infants assigned to delayed clamping and 726 (96%) of 764 infants assigned to immediate clamping received treatment that fully adhered to the protocol. Death or major disability was determined in 1419 (93%) infants and occurred in 204 (29%) of 709 infants who were assigned to delayed clamping versus 240 (34%) of 710 assigned to immediate clamping, (relative risk [RR]) 0.83, 95% CI 0.72-0.95; p=0.010). 60 (8%) of 725 infants in the delayed clamping group and 81 (11%) of 720 infants in the immediate clamping group died by 2 years of age (RR 0.70, 95% CI 0.52-0.95); among those who survived, major disability at 2 years occurred in 23% (144/627) versus 26% (159/603) of infants, respectively (RR 0.88, 0.74-1.04). Interpretation Clamping the umbilical cord at least 60 s after birth reduced the risk of death or major disability at 2 years by 17%, reflecting a 30% reduction in relative mortality with no difference in major disability. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The study indicates that delaying cord clamping for at least 60 seconds can reduce the risk of mortality or major disability in very preterm infants at 2 years of age. The results show that infants in the delayed clamping group had lower rates of mortality and major disability compared to the immediate clamping group.