Premature babies benefit from repeat steroids

20 January 2015

Repeat doses of steroids given to premature babies before birth will not affect the long-term development of these babies.

This conclusion from a recent University of Auckland study will be good news for parents whose babies were given steroids before birth to prevent serious complications of premature delivery.

Researchers from the University of Auckland, in collaboration with Australian colleagues, had previously shown that repeat antenatal steroids, given to pregnant mothers at risk of delivering before 32 weeks, had important benefits.

Many doctors were reluctant to use this promising treatment because of concern that exposing babies to steroids would increase the risk of long-term complications like diabetes and heart disease.

The latest New Zealand study, (published today in a highly ranked American paediatric journal), is the first to show that repeat doses of antenatal steroids do not adversely impact the later cardiovascular and metabolic health of these premature babies.

“With few treatments available for mothers at risk of preterm birth, this is an important finding”, says Dr Chris McKinlay, a neonatologist and researcher from the Liggins Institute at the University of Auckland. “Forty percent of pregnant women at risk of having a premature birth and given a dose of antenatal steroids do not deliver immediately. We wanted to know if giving repeat doses to these women improved outcomes for their babies without causing harm.”

The study assessed in detail the cardiovascular and metabolic function of 258 premature New Zealand children, at six to eight years of age, who were exposed to repeat steroids or a control placebo treatment before birth. Researchers concluded that repeat does of antenatal steroids did not increase risk factors for cardiovascular and metabolic diseases at early school age.

“The study shows that the treatment is safe,” says Dr McKinlay. “Clinicians wishing to use repeat antenatal steroids can be reassured that the risk of future cardiovascular and metabolic disease from this therapy is low.”

This is the first study to investigate the long term effect of repeat antenatal steroid treatment on cardiovascular and metabolic diseases.

Antenatal steroids are given to a pregnant woman at risk of premature delivery, to mature her baby’s organ systems, especially the lungs, gut and cardiovascular and immune systems, which remain very immature until around 32 weeks and don’t mature fully until after 36 weeks.

Antenatal steroids reduce the risk of preterm lung disease in premature babies, and the need for a ventilator, infection, serious gut complications, and bleeding into the brain.

“All these factors combine to improve survival and prevent serious illness in preterm babies. Steroids such as betamethasone and dexamethasone cross the placenta into the babies’ blood stream to act directly on fetal organs and cells,” says Dr McKinlay. “These synthetic steroids work by mimicking what normal happens in late pregnancy when the baby’s natural steroid levels rise. This sends a signal to the fetal organs that it’s time to start getting ready for life outside the womb.”

“Steroids remain the most important treatment for premature babies and have had a big impact on the reducing complications in preterm births,” says Dr McKinlay. “New Zealand researchers were the first to discover this treatment in the 1960s and since then have tried to improve outcomes from using these steroids.”

The first study that pioneered on the use of steroids for babies at risk of a premature birth, was a clinical trial carried out in Auckland by Professor Sir Graham (Mont) Liggins and Associate Professor Ross Howie, and published in 1972 on the effect of antenatal steroids on fetal lung maturation.

“Since those early days new questions have arisen and we now have to consider how treatments those babies received will affect them throughout life,” says Dr McKinlay. “In the 1990s there was a shift in medical thinking about chronic disease when it was recognised that lifetime disease risk is linked to the conditions before and shortly after birth, especially poor growth.”

“This early environment has a big impact on the risk of diseases later on and scientists have cautioned against exposing premature babies to steroids on the belief that may play a key role in changing how organs function into adulthood,” he says.

Since the pioneering work led by Sir Graham Liggins, researchers at the University of Auckland have published many world-leading studies into the use of these steroids for babies at risk of premature birth. These include major New Zealand and Australian collaborations by leading New Zealand paediatrician, Distinguished Professor Jane Harding and obstetrician, Professor Caroline Crowther, both from the Liggins Institute.

“New Zealand research has made a major contribution to improving the health of preterm babies,” says Dr McKinlay. “The steroid treatments developed here are now used throughout the world and continue to help save the lives of thousands of babies each year.”

“There were concerns about the long-term risks of using repeat doses, but no one had studied this in detail,” he says. “This is partly due to the difficulty of getting children to undergo the tests required to fully assess metabolic and vascular function.”

The study involved following up all the six to eight year old New Zealand children in the original Australasian repeat doses trial (ACTORDS). An impressive 98 percent of them were traced with 81 percent agreeing to take part in the study.

“That was a good response given the challenging testing that they would undergo,” says Dr McKinlay. “It reflects New Zealanders’ willingness and generosity to participate in this type of research, and contribute to this country’s reputation in this field. These families’ contribution makes a real difference.”

Half of the study participants were from the Auckland region and the other half from outside Auckland - from North Cape to Bluff.

The group of six to eight year olds who were willing to participate had to undergo up to seven hours of testing plus additional testing at home. The day started with fasting and frequent blood tests over two hours, followed by body composition scanning, assessment of motor function, and cognitive testing. At home children wore a blood pressure monitor for 24 hours and collected saliva for hormone measurements.

The field work gathering data from these children around New Zealand took two and a half years and was done by Dr McKinlay as part of his four year doctoral studies. His paper from this study won him the Paediatric Academic Society’s best PhD student research award in 2011 and the University of Auckland’s top Doctoral Thesis Award in 2014.

Further information:

  • Premature births account for seven to eight percent of all births in New Zealand (and up to 12 percent in the United States).
  • The Liggins Institute at the University of Auckland is one of the world’s leading centres for research on fetal and child health, nutrition, development, epigenetics and evolutionary medicine.
  • This report was published in the journal Paediatrics, the highest ranked international paediatric journal. It is the first study to report that repeat steroids before birth are safe up to school-age.
  • This study followed up participants in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids, Crowther et al, 2006.
  • Study Title: McKinlay CJD, Cutfield WS, Battin MR, Dalziel SR, Crowther CA, Harding JE. Cardiovascular risk factors in children after repeat antenatal glucocorticoids: an RCT. Pediatrics. 2014. DOI: 10.1542/peds.2014-2408.
  • Study team/authors: Dr Chris McKinlay (Liggins/UOA), Professor Wayne Cutfield (Liggins/UOA), Dr Malcolm Battin (ADHB), Dr Stuart Dalziel (ADHB), Professor Caroline Crowther (Liggins/UOA), Distinguished Professor Jane Harding (Liggins/UOA).
  • Reference for ACTORDS study referred to above: Crowther CA, HaslamRR, Hiller JE, Doyle LW, Robinson JS; Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) Study Group. Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial. Lancet 2006; 367 (9526):1913 – 1919

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