To guide future practice, perinatal trials should be much larger, simpler and less fragile with close to 100% ascertainment of mortality and other key outcomes

Tarnow-Mordi, W. O.; Robledo, K.; Marschner, I.; Seidler, L.; Simes, J.; Rieger, I.; Osborn, D.; Popat, H.; Reid, S.; de Waal, K.; Wright, I.; Wright, A.; Buchan, J.; Stubbs, M.; Newnham, J.; Simmer, K.; Young, C.; Loh, D.; Kok, Y.; Gill, A.; Kluckow, M.; Morris, J.; Jeffery, M.; Chen, Y.; Morris, S.; Sinhal, S.; Cornthwaite, K.; Walker, S.; Watkins, A.; Collins, C.; Holberton, J.; Noble, E.; Sehgal, A.; Yeomans, E.; Elsayed, K.; Mohamed, A. L.; Broom, M.; Koh, G.; Lawrence, A.; Liley, H.; Gardener, G.; Fox, J.; Cartwright, D.; Koorts, P.; Pritchard, M.; Mckeown, L.; Lui, K.; Lainchbury, A.; Shand, A.; Michalowski, J.; Smyth, J.; Bolisetty, S.; Adno, A.; Lee, G.; Seidler, A. L.; Askie, L.; Groom, K.; Eaglen, D.; Baker, E.; Patel, H.; Wilkes, N.; Gullam, J.; Austin, N.; Leishman, D.; Weston, P.; White, N.; Cooper, N.; Broadbent, R.; Stitely, M.; Dawson, P.; El-Naggar, W.; Furlong, M.; de Luca, D.; Benachi, A.; Letamendia, E.; Escourrou, G.; Dell'Orto, V.; Sweet, D.; Millar, M.; Eltayeb, M.; Sheikh, L.; Ariff, S.; Soll, R.; Morris, E.; Young, L.; Evans, S.; Belfort, M.; Aagaard, K.; Pammi, M.; Mandy, G.; Gandhi, M.

doi:10.1016/j.semperi.2023.151789

The Australian Placental Transfusion Study (APTS) randomised 1,634 fetuses to delayed (& GE;60 s) versus immediate (<10 s) clamping of the umbilical cord. Systematic reviews with meta -analy-ses, including this and similar trials, show that delaying clamping in preterm infants reduces mortality and need for blood transfusions. Amongst 1,531 infants in APTS followed up at two years, aiming to delay clamping for 60 s or more reduced the relative risk of the primary compos-ite outcome of death or disability by 17% (p = 0.01). However, this result is fragile because nomi-nal statistical significance (p < 0.05) would be abolished by only 2 patients switching from a non-event to an event, and the primary composite outcome was missing in 112 patients (7%). To achieve more robust evidence, any future trials should emulate the large, simple trials co-ordi-nated from Oxford which reliably identified moderate, incremental improvements in mortality intens of thousands of participants, with <1% missing data. Those who fund, regulate, and con-duct trials that aim to change practice should repay the trust of those who consent to participate by doing everything possible to minimise missing data for key outcomes. & COPY; 2023 Elsevier Inc. All rights reserved.

To guide future practice, perinatal trials should be much larger, simpler and less fragile with close to 100% ascertainment of mortality and other key outcomes / Tarnow-Mordi, W. O.; Robledo, K.; Marschner, I.; Seidler, L.; Simes, J.; Rieger, I.; Osborn, D.; Popat, H.; Reid, S.; de Waal, K.; Wright, I.; Wright, A.; Buchan, J.; Stubbs, M.; Newnham, J.; Simmer, K.; Young, C.; Loh, D.; Kok, Y.; Gill, A.; Kluckow, M.; Morris, J.; Jeffery, M.; Chen, Y.; Morris, S.; Sinhal, S.; Cornthwaite, K.; Walker, S.; Watkins, A.; Collins, C.; Holberton, J.; Noble, E.; Sehgal, A.; Yeomans, E.; Elsayed, K.; Mohamed, A. L.; Broom, M.; Koh, G.; Lawrence, A.; Liley, H.; Gardener, G.; Fox, J.; Cartwright, D.; Koorts, P.; Pritchard, M.; Mckeown, L.; Lui, K.; Lainchbury, A.; Shand, A.; Michalowski, J.; Smyth, J.; Bolisetty, S.; Adno, A.; Lee, G.; Seidler, A. L.; Askie, L.; Groom, K.; Eaglen, D.; Baker, E.; Patel, H.; Wilkes, N.; Gullam, J.; Austin, N.; Leishman, D.; Weston, P.; White, N.; Cooper, N.; Broadbent, R.; Stitely, M.; Dawson, P.; El-Naggar, W.; Furlong, M.; de Luca, D.; Benachi, A.; Letamendia, E.; Escourrou, G.; Dell'Orto, V.; Sweet, D.; Millar, M.; Eltayeb, M.; Sheikh, L.; Ariff, S.; Soll, R.; Morris, E.; Young, L.; Evans, S.; Belfort, M.; Aagaard, K.; Pammi, M.; Mandy, G.; Gandhi, M.. - In: SEMINARS IN PERINATOLOGY. - ISSN 0146-0005. - 47:5(2023). [10.1016/j.semperi.2023.151789]