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

Robledo, K. P.; Tarnow-Mordi, W. O.; Rieger, I.; Suresh, P.; Martin, A.; Yeung, C.; Ghadge, A.; Liley, H. G.; Osborn, D.; Morris, J.; Hague, W.; Kluckow, M.; Lui, K.; Soll, R.; Cruz, M.; Keech, A.; Kirby, A.; Simes, J.; Popat, H.; Reid, S.; Gordon, A.; De Waal, K.; Wright, I. M.; Wright, A.; Buchan, J.; Stubbs, M.; Newnham, J.; Simmer, K.; Young, C.; Loh, D.; Kok, Y.; Gill, A.; Strunk, T.; Jeffery, M.; Chen, Y.; Morris, S.; Sinhal, S.; Cornthwaite, K.; Walker, S. P.; Watkins, A. M.; Collins, C. L.; Holberton, J. R.; Noble, E. J.; Sehgal, A.; Yeomans, E.; Elsayed, K.; Mohamed, A. -L.; Broom, M.; Koh, G.; Lawrence, A.; Gardener, G.; Fox, J.; Cartwright, D. W.; Koorts, P.; Pritchard, M. A.; Mckeown, L.; Lainchbury, A.; Shand, A. W.; Michalowski, J.; Smyth, J. P.; Bolisetty, S.; Adno, A.; Lee, G.; Seidler, A. L.; Askie, L. M.; Groom, K. M.; Eaglen, D. A.; Baker, E. C.; Patel, H.; Wilkes, N.; Gullam, J. E.; Austin, N.; Leishman, D. E.; Weston, P.; White, N.; Cooper, N. A.; Broadbent, R.; Stitely, M.; Dawson, P.; El-Naggar, W.; Furlong, M.; Hatfield, T.; de Luca, D.; Benachi, A.; Letamendia-Richard, E.; Escourrou, G.; Dell'Orto, V.; Sweet, D.; Millar, M.; Shah, S.; Sheikh, L.; Ariff, S.; Morris, E. A.; Young, L.; Evans, S. K.; Belfort, M.; Aagaard, K.; Pammi, M.; Mandy, G.; Gandhi, M.; Davey, J.; Shenton, E.; Middleton, J.; Black, R.; Cheng, A.; Murdoch, J.; Jacobs, C.; Meyer, L.; Medlin, K.; Woods, H.; O'Connor, K. -A.; Bice, C.; Scott, K.; Hayes, M.; Cruickshank, D.; Sam, M.; Ireland, S.; Dickinson, C.; Poulsen, L.; Fucek, A.; Hegarty, J.; Rogers, J.; Sanchez, D.; Zupan Simunek, V.; Hanif, B.; Pahl, A.; Metayer, J.; Duley, L.; Marlow, N.; Schofield, D.; Bowen, J.

doi:10.1016/S2352-4642(21)00373-4

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. Funding: Australian National Health and Medical Research Council.

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 / Robledo, K. P.; Tarnow-Mordi, W. O.; Rieger, I.; Suresh, P.; Martin, A.; Yeung, C.; Ghadge, A.; Liley, H. G.; Osborn, D.; Morris, J.; Hague, W.; Kluckow, M.; Lui, K.; Soll, R.; Cruz, M.; Keech, A.; Kirby, A.; Simes, J.; Popat, H.; Reid, S.; Gordon, A.; De Waal, K.; Wright, I. M.; Wright, A.; Buchan, J.; Stubbs, M.; Newnham, J.; Simmer, K.; Young, C.; Loh, D.; Kok, Y.; Gill, A.; Strunk, T.; Jeffery, M.; Chen, Y.; Morris, S.; Sinhal, S.; Cornthwaite, K.; Walker, S. P.; Watkins, A. M.; Collins, C. L.; Holberton, J. R.; Noble, E. J.; Sehgal, A.; Yeomans, E.; Elsayed, K.; Mohamed, A. -L.; Broom, M.; Koh, G.; Lawrence, A.; Gardener, G.; Fox, J.; Cartwright, D. W.; Koorts, P.; Pritchard, M. A.; Mckeown, L.; Lainchbury, A.; Shand, A. W.; Michalowski, J.; Smyth, J. P.; Bolisetty, S.; Adno, A.; Lee, G.; Seidler, A. L.; Askie, L. M.; Groom, K. M.; Eaglen, D. A.; Baker, E. C.; Patel, H.; Wilkes, N.; Gullam, J. E.; Austin, N.; Leishman, D. E.; Weston, P.; White, N.; Cooper, N. A.; Broadbent, R.; Stitely, M.; Dawson, P.; El-Naggar, W.; Furlong, M.; Hatfield, T.; de Luca, D.; Benachi, A.; Letamendia-Richard, E.; Escourrou, G.; Dell'Orto, V.; Sweet, D.; Millar, M.; Shah, S.; Sheikh, L.; Ariff, S.; Morris, E. A.; Young, L.; Evans, S. K.; Belfort, M.; Aagaard, K.; Pammi, M.; Mandy, G.; Gandhi, M.; Davey, J.; Shenton, E.; Middleton, J.; Black, R.; Cheng, A.; Murdoch, J.; Jacobs, C.; Meyer, L.; Medlin, K.; Woods, H.; O'Connor, K. -A.; Bice, C.; Scott, K.; Hayes, M.; Cruickshank, D.; Sam, M.; Ireland, S.; Dickinson, C.; Poulsen, L.; Fucek, A.; Hegarty, J.; Rogers, J.; Sanchez, D.; Zupan Simunek, V.; Hanif, B.; Pahl, A.; Metayer, J.; Duley, L.; Marlow, N.; Schofield, D.; Bowen, J.. - In: THE LANCET CHILD & ADOLESCENT HEALTH. - ISSN 2352-4642. - 6:3(2022), pp. 150-157. [10.1016/S2352-4642(21)00373-4]