Clamping the umbilical cord at least 60 seconds 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., found a two-year follow up of the Australian Placental Transfusion Study, the largest-ever clinical trial of delayed cord-clamping of babies born before 30 weeks. It was conducted in 25 hospitals across seven countries.
The study compared outcomes for more than 1,500 babies from the initial study: 767 with caregivers aiming for a 60-second delay in clamping, and 764 with caregivers aiming for cord-clamping before 10 seconds after delivery.
The researchers found that delaying clamping reduces a child's relative risk of death or major disability in early childhood by 17%. This included a 30% reduction in mortality before the age of two.
In addition, 15% fewer infants in the delayed-clamping group needed blood transfusions after birth.
The study, which was published in The Lancet Child and Adolescent Health, was coordinated by the University of Sydney’s NHMRC Clinical Trials Centre in collaboration with the IMPACT Clinical Trials Network of the Perinatal Society of Australia and New Zealand, and the Australian and New Zealand Neonatal Network.
Study lead Prof William Tarnow-Mordi, head of Neonatal and Perinatal Trials at the Clinical Trials Centre and professor of neonatal medicine in the Faculty of Medicine and Health, said just waiting a minute before clamping would have a significant impact worldwide.
“It’s very rare to find an intervention with this sort of impact that is free and requires nothing more sophisticated than a clock,” he said. “This could significantly contribute to the UN’s Sustainable Development Goal to end preventable deaths in newborns and children under five, a goal that has really suffered during the pandemic.”
University of Sydney biostatistician Dr Kristy Robledo, who led the two-year follow-up analysis, said: “Applied consistently worldwide, aiming to wait a minute before cord-clamping in very preterm babies who do not require immediate resuscitation could ensure that an extra 50,000 survive without major disability in the next decade.
“In other words, for every 20 very preterm babies who get delayed instead of immediate clamping, one more will survive without major disability.”
Why wait?
Delayed umbilical cord-clamping is routine in full-term babies to allow the newborn time to adapt to life outside the womb. However, until recently, clinicians generally cut the cord of preterm babies immediately so urgent medical care could be given.
“Ten years ago, umbilical cords were routinely clamped quickly after a very preterm birth and the baby was passed to a paediatrician in case the child needed urgent help with breathing,” said Tarnow-Mordi.
“But we now know that almost all very preterm babies will start breathing by themselves in the first minute, if they are given that time. We think that after delaying cord-clamping, babies get extra red and white blood cells and stem cells from the placenta, helping to achieve healthy oxygen levels, control infection and repair injured tissue.”
What does this mean for babies born today?
The childhood follow-up to the Australian Placental Transfusion Study is the largest world-wide two-year follow-up of preterm cord-clamping, providing the best evidence to date on positive outcomes at two years of age.
Co-author and founder of Miracle Babies Foundation Melinda Cruz, who is a parent of three preterm babies, said she hoped the results would give parents confidence to discuss their options with their birthing professionals.
“I hope that prospective parents around the world will read about this trial and discuss it with their midwives and obstetricians," she said.
From research to practice
The first evidence, published in the American Journal of Obstetrics and Gynecology, indicating that delayed umbilical cord-clamping might have benefits for preterm infants and their mothers, came in 2017 from a systematic review of randomised trials in nearly 3,000 preterm babies.
The Australian Placental Transfusion Study, led by Tarnow-Mordi, was the largest of these trials and named as ‘Trial of the Year’ by Federal Health Minister Greg Hunt and the Australian Clinical Trials Alliance in 2018.
While the World Health Organization recommends that newborns, including preterm babies who do not require positive pressure ventilation, should not have their cord clamped earlier than one minute after birth, this has not always been consistently applied.
Next steps
“Midwives welcome this research: delaying cord-clamping ensures that the physiological changes taking place at the time of birth can happen, and there are clearly very good outcomes, especially for premature babies. We can all do this and now we know we should,” said Prof Caroline Homer, president of the Perinatal Society of Australia and New Zealand and past president of the Australian College of Midwives.
“It’s vital that perinatal professionals record, to the second, the time of first breath and cord-clamping during births to allow for robust, large-scale data to further our work in this area,” said co-author Prof Jonathan Morris, professor of Obstetrics and Gynaecology at the University of Sydney and director of Women and Babies Research at The Kolling Institute.
“Intensive staff training in the new protocols will also be vital as it can be daunting to delay treatment in very early and sick babies, but the evidence suggests this results in the best outcomes for these children.”
The ALPHA Collaboration (Advancing Large collectively Prioritised trials for Health outcomes Assessment) will be vital to taking this research forward. This is an international collaboration of perinatal researchers, professionals, parents and policymakers working with organisations and individuals worldwide to ensure that trials like this can, in the future, run at least 10 times larger and faster, in a new era of increased international collaboration.
Study details
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
Kristy Robledo, William Tarnow-Mordi, Ingrid Rieger, Preeti Suresh, Andrew Martin, Carbo Yeung, Alpana Ghadge, Helen Liley, David Osborn, Jonathan Morris, Wendy Hague, Martin Kluckow, Kei Lui, Roger Soll, Melinda Cruz, Anthony Keech, Adrienne Kirby, John Simes.
Published in The Lancet Child & Adolescent Health on 8 December 2021
Summary
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.
Findings
Between 21 October 2009, and 6 January 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 seconds 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.
See more from MedicalBrief archives:
Complications in first pregnancy linked with increased risk of subsequent preterm birth
Blood test successfully predicts premature birth
Earlier survival of prem babies raises quesions
Stress in pregnancy may affect baby's sex, risk of preterm birth