Oral
misoprostol alone compared to oral misoprostol followed by oxytocin in
India: a multicentre randomised trial in women induced for hypertension
of pregnancy.
Authors
Prof Shuchita Mundle, MD, Department of Obstetrics and Gynecology, All
India Institute of Medical Sciences, Nagpur, Maharshatra, India.
Kate Lightly, MRCOG, Department of Women’s and Children’s Health,
University of Liverpool, Liverpool, Merseyside, UK
Jill Durocher, BA, Gynuity Health Projects, New York, USA
Hillary Bracken, PhD, The Patient-Centered Outcomes Research Institute,
Washington DC, USA
Moushmi Tadas, DNB, Department of Obstetrics and Gynecology, Government
Medical College, Nagpur, India.
Seema Parvekar, MD, Department of Obstetrics and Gynaecology, Daga
Memorial Women’s Government Hospital, Nagpur, India.
Poonam Varma Shivkumar, MD, Department of Obstetrics and Gynecology,
Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra,
India
Prof Brian Faragher, PhD, Medical Statistics Unit, Department of
Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
Prof Thomas Easterling, PhD, Department of Obstetrics and Gynecology,
University of Washington, Seattle, WA, USA
Simon Leigh, PhD, Nexus Clinical Analytics, Charnock Richard,
Lancashire, UK
Prof Mark Turner, PhD, Department of Women’s and Children’s Health,
University of Liverpool, Liverpool, Merseyside, UK
Prof Zarko Alfirevic, FRCOG, Department of Women’s and Children’s
Health, University of Liverpool, Liverpool, Merseyside, UK
Prof Beverly Winikoff, MD, MPH, Gynuity Health Projects, New York, USA
Prof Andrew D Weeks,* FRCOG, Department of Women’s and Children’s
Health, University of Liverpool, Liverpool, Merseyside, UK
* Corresponding author. Address: Sanyu Research Unit, Department of
Women’s and Children’s Health, Liverpool Women’s Hospital, Crown Street,
Liverpool L8 7SS, UK email aweeks@liverpool.ac.uk
ABSTRACT
Objective : To assess whether, in those requiring ongoing
uterine stimulation after cervical ripening with oral misoprostol and
membrane rupture, augmentation with low dose oral misoprostol is
superior to intravenous oxytocin.
Design: Open-label, superiority randomised trial
Setting: Government hospitals in India
Population: Women induced with oral misoprostol for
hypertensive disease in pregnancy and requiring ongoing induction after
membrane rupture
Methods : Participants received misoprostol (25mcg orally two
hourly) or titrated oxytocin through an infusion pump.
Main Outcome Measure: Caesarean birth
Results : 520 women were randomised and the baseline
characteristics were comparable between the groups. The caesarean
section rate was not reduced by the use of misoprostol (misoprostol
32.3% vs oxytocin 27.3%; adjusted odds ratio 1.226 (95% CI 0.81-1.85,
p=0.33)). There were no differences in rates of hyperstimulation, fetal
heart rate abnormalities, or maternal side effects, although the
geometric mean time from randomisation to birth was 31 minutes longer
with misoprostol. Fewer babies in the misoprostol arm were admitted to
the special care unit (10 vs 21 in the oxytocin group) and there were no
neonatal deaths in the misoprostol group, compared to 3 in the oxytocin
arm. Women’s acceptability ratings were high in both study groups.
Conclusion : Following cervical preparation with oral
misoprostol and membrane rupture, the use of ongoing oral misoprostol
for augmentation did not significantly reduce caesarean rates compared
to oxytocin. The method, however, was safe for both mother and baby.
Funding : MRC, Foreign, Commonwealth and Development Office
(FCDO), National Institute for Health Research (NIHR) and Wellcome Trust
(MR/R006/180/1).
INTRODUCTION
Hypertensive disease in pregnancy is a major cause of maternal
deaths.1 Many of the deaths could be prevented by
timely and effective delivery, but labour induction itself carries
risks. Identifying a safe and effective method suitable for low- and
middle-income settings is a critical public health intervention.
Low dose oral misoprostol (LDOM) is a highly effective method of
induction. Oral administration of 25 micrograms every 2 hours has
received a strong recommendation by both WHO and NICE for cervical
preparation.2,3 Cochrane reviews of LDOM found that it
is more effective than the commonly used vaginal dinoprostone
gel,4,5 and it has the added advantages of being heat
stable and low cost in many settings.
Standard practice for induction is to use a prostaglandin (e.g.
misoprostol or dinoprostone) for cervical preparation. Once active
labour commences and the amniotic membranes rupture, the prostaglandin
is replaced with an intravenous infusion of oxytocin if
required.6 The infusion is titrated every 30 minutes
to stimulate uterine contractions sufficient to progress labour, but not
so much as to cause hyperstimulation. In many countries, electronic
infusion pumps are not available, and oxytocin is administered through a
gravity drip infusion. These poorly regulated infusions require constant
supervision as inadvertent overdosing can lead to hyperstimulation, with
associated maternal and fetal risks.7,8 There is a
need, therefore, to identify cost-effective means of induction in which
the uterotonic can be administered in a safe and standardised way.
In the Cochrane review of LDOM for labour induction, the LDOM was
continued into active labour in 2 studies, whilst in the remaining 57
the stimulation was changed to oxytocin after artificial membrane
rupture.4,9 The main outcomes following continued use
of LDOM into active labour were equivalent or better than in the
comparator arms.
Use of ongoing LDOM allows women to be free to mobilise in labour,
unrestricted by an intravenous infusion, and it could empower women to
be more involved in their care. There could also be significant health
system savings with less use of equipment and staff time.
Despite its promise, an induction protocol continuing LDOM into labour
has never been directly compared to the standard oxytocin regimen in a
randomised trial.
The
study objective was to assess whether, in those requiring ongoing
uterine stimulation after cervical ripening with oral misoprostol and
membrane rupture, augmentation with LDOM is superior to intravenous
oxytocin.
Funding
Funding was provided by the MRC, Foreign, Commonwealth and Development
Office (FCDO), National Institute for Health Research (NIHR) and
Wellcome Trust (MR/R006/180/1) and included external peer review. The
funder attended Trial Steering Committee meetings, but otherwise played
no part in the conduct of the research or writing the paper.
Methods