Associate Professor Joshua Vogel is a Principal Research Fellow at the Burnet Institute in Melbourne, where he co-heads the Global Women’s and Newborn’s Health Group. His research focuses on addressing maternal and perinatal health issues affecting women and families in limited-resource settings. Associate Professor Vogel was the winner of the 2020 Peter Doherty Investigator Grant Award, and the Commonwealth Health Minister’s Award for Excellence in Health and Medical Research.
In 1972, an obstetrician from New Zealand named Mont Liggins and his neonatologist colleague Ross Howie authored a trial that is regarded as one of the most significant in modern obstetrics. They showed that when betamethasone injections are administered to pregnant women at risk of having a preterm baby, maturation of fetal lung tissue could be accelerated and neonatal respiratory distress syndrome could be reduced. Over the subsequent decades, trials and meta-analyses have identified other significant benefits, including reductions in newborn death, necrotizing enterocolitis, and intraventricular haemorrhage.
Considering that preterm birth is the leading cause of newborn and child mortality worldwide and affects nearly 15 million babies every year, the importance of this intervention for families, communities and public health cannot be overstated. Even the iconic Cochrane logo is composed of an early meta-analysis of preterm steroid efficacy, reflective of its special significance.
While steroids have long been a part of preterm birth care in Australia, the same cannot be said of many countries around the world where pregnant women are not guaranteed access to good-quality healthcare. Many in the maternal and newborn health community had strongly advocated for improving access to steroids worldwide, though how steroids could most effectively be scaled up in low-resource settings remained an open question.
Alyce Wilson, Pele Melepia, Sister Melki and Josh Vogel, Rabaul town clinic, East New Britain, Papua New Guinea.
In 2015, the findings of the Antenatal Corticosteroid Trial (ACT) were released - an enormous implementation trial involving nearly 100,00 women and their babies across Guatemala, Argentina, India, Kenya, Pakistan, and Zambia. ACT set out to demonstrate if a package of interventions could scale up steroids in these countries and save lives. On the question of scale up, ACT was undoubtedly effective with steroid use increased fourfold. What was utterly unexpected was that the intervention had no effect on reducing preterm newborn mortality. Worse still, at a population level the intervention appeared to increase neonatal mortality, stillbirth and maternal infections. Needless to say, precisely the opposite of what had been anticipated.
The findings from ACT prompted a much more sceptical re-examination of the available evidence on preterm steroids. By this point, thirty efficacy trials were available in the literature, whose pooled effects clearly pointed to significant reductions in mortality and morbidity. What had not been sufficiently appreciated was that nearly all trials had been conducted in tertiary hospitals in wealthy countries – quite different from the lower-level facilities in lower-income countries where ACT had been conducted. There was a grain of truth in the wry title of a BMJ column by Sir Iain Chalmers at the time – “should the Cochrane logo be accompanied by a health warning?”.
How to make sense of all this, and what can we do about it? It was in late 2015, during my time as a maternal health researcher at the Department of Sexual and Reproductive Health and Research at WHO in Geneva, that this question first emerged. I estimate spending some part of every single workday since then trying to figure it out.
Since 2016, I have been collaborating with an extraordinary group of individuals - researchers, obstetricians and neonatologists across Bangladesh, India, Kenya, Nigeria, Pakistan and Switzerland - that forms the WHO ACTION Collaborators (Antenatal Corticosteroids for Improving Outcomes in Preterm Newborns).
Members of the WHO ACTION Trial research team in Sylhet, Bangladesh, 2018.
Our ACTION-I Trial recruited 2,852 women and their 3,070 babies across 29 hospitals in these five countries. To our collective relief, ACTION-I confirmed that steroids are indeed safe and effective when used in hospital prior to 34 weeks’ gestation, provided that they are accompanied by measures to ensure good-quality care for pregnant women and newborns. I relocated to Melbourne and joined the Burnet Institute in late 2018, and remain a proud member of this collaboration that is running further trials on whether and how preterm steroids can be safely used.
Many lessons can be drawn from the steroids story. For me, the most significant lessons relate to the importance of international collaboration in solving complex scientific challenges.
I was delighted to be recognised in the NHMRC Research Excellence Awards and I am deeply grateful to Professor Kelso, NHMRC Council members, Minister Hunt and the countless others who bring needed resources and due recognition to public health research. However, I remain ill at ease with individual accolades that do not reflect the teamwork that makes them possible. My hope is that this award brings attention to the value of working beyond our own borders for a better world.