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From evidence to implementation
Deputy Editor-in-Chief Dr Aris T Papageorghiou discusses the latest thinking in
women’s health and highlights articles from this issue in an audio podcast available
at: https://soundcloud.com/bjog/sept-editorial-2020
We all care deeply about our patients
and want to provide evidence-based
care. So why does it take so long for
new practices and treatments to be
adopted despite systematic evidence
demonstrating benefit? An example of
this is the time it took to adopt adminis-
tration of antenatal corticosteroids to
promote fetal lung maturation, now
embedded in our daily practice. The pos-
sible beneficial effects were discovered
serendipitously by Graham ‘Mont’
Liggins, then at the University of Auck-
land in his native New Zealand, and
reported in 1969. While undertaking
studies on the causes of premature birth
in sheep, Liggins observed ‘Partial aera-
tion of the lungs...in lambs...after
receiving dexamethasone’ and suggested
that ‘this may be the result of acceler-
ated appearance of surfactant activity’
(Liggins J Endocrinol 1969;45:515–23).
Excited by his discovery, Liggins
teamed up with Ross Howie, a paediatri-
cian, to undertake a seminal double-
blind randomised controlled trial
between 1969 and 1972. They included
women with premature labour between
24 and 36 weeks, and women for whom
delivery before 37 weeks was planned
because of obstetric complications. In
the trial, betamethasone, when com-
pared with placebo, dramatically
reduced the rates of both respiratory
distress syndrome and mortality. Their
paper, entitled ‘A Controlled Trial of
Antepartum Glucocorticoid Treatment
for Prevention of the Respiratory Dis-
tress Syndrome in Premature Infants’,
was published in 1972 in Pediatrics (Lig-
gins and Howie Pediatrics 1972;50:515–
25), having been rejected by Nature and
The Lancet. This simple treatment now
saves the lives of many thousands of
premature babies, but the path from
this first trial to routine implementation
was long: more evidence was needed,
and a number of studies were under-
taken in subsequent years. Crowley
et al. collected all the evidence available
at the time in another seminal piece
describing a meta-analysis of 12 studies
including 3000 women, in our very own
journal (Br J Obstet Gynaecol 1990;97:
11–25). This formed the basis of the
Royal College of Obstetricians and
Gynaecologists (RCOG) guidelines
2 years later, and a consensus statement
by the National Institutes of Health in
the USA 2 years after that; it is very
likely that it took longer still to reach
implementation in every hospital.
This guidance on the use of prophy-
lactic steroids came more than 20 years
after the initial findings, and over
10 years after Archie Cochrane awarded
our specialty the wooden spoon for the
‘worst use of randomised trials in all of
medicine’. The forest plot on the
Cochrane logo is a reminder of this –it
depicts the meta-analysis of the first
seven studies of antenatal corticos-
teroids, highlighting the importance of
translating evidence into clinical practice
and how lives can be lost due to delay
of implementing evidence.
Surely we are doing better now? In
this issue of BJOG, we have the usual
excellent collection of papers, all of
which lie on the pathway from science
to implementation (Figure 1). I wanted
to highlight two papers that are of
direct relevance to an historical perspec-
tive, both from Wolf and colleagues
(pages 1180–88 and 1217–25). Studies in
the 1990s noted that preterm newborns
of mothers who received magnesium
sulphate for pre-eclampsia or tocolysis
had much lower rates of cerebral palsy,
with an odds ratio of 0.14 and 95% con-
fidence intervals (CIs) comfortably
favouring treatment (0.05–0.51; Lancet
1998;351:292). Further randomised con-
trolled trials followed, and a Cochrane
review (Doyle et al. Cochrane Database
Syst Rev 2009;1:CD004661) showed that
antenatal magnesium sulphate therapy
for women at risk of preterm birth
reduced the risk of infant cerebral palsy
Basic research
Human research
Clinical research Guideline Pracce
Figure 1. The journey of health research to benefit. Source: Morris et al. J R Soc Med 2011;104:510–20.
ª2020 Royal College of Obstetricians and Gynaecologists 1173
DOI: 10.1111/1471-0528.16408
www.bjog.org
Editorial
