Transcript EFM in high risk pregnancy

Challenges to Evidence Based
Medicine – the need for more and
better research
S Arulkumaran
Professor Emeritus in O&G
St George’s University of London
“A Fresh Look at”
Interpreting Evidence
RCTs & Meta Analysis
Case control studies
Prospective descriptive studies
Retrospective data analysis/ case
controlled
Confidential enquiries
Different search mechanisms; selection bias; different ways of
analysis > different results with meta analysis
Evidence Based Medicine
The mention of the words often invites
mixed reactions from medical fraternity
There is no return from this
Exclusion and Inclusion criteria should be
spelt out
We need to refine the studies (e.g.
adequacy of numbers) and conclusions
drawn
Background
Some specialists believe that they have
already been doing their best for their patients
at all times and there is nothing in their
practice which needs a change.
It is also argued that there is very little
evidence for majority of what we do in
medicine and so EBM may not be necessary.
IS THIS TRUE?
Challenging that notion
Is general inpatient obstetrics and
gynaecology evidence-based?
A survey of practice with critical review
of methodological issues.
Aamir T Khan1, M Nauman Mehr1, Anne-Marie
Gaynor2, Malcolm Bowcock3 and Khalid S
Khan1 BMC Women's Health 2006, 6:5
Evidence
The study examined the rates of evidencesupported care provided in an obstetricsgynaecology unit. (sample of 325 consecutive
inpatient admissions)
Conclusion
A significant majority (90%) of obstetric
and gynaecological care was found to be
supported by substantial research
evidence.
Then what are the problems/challenges
of EMB in Obstetrics?
Obstetricians in less resourced countries are
worried that they will not know how to search
for, critically appraise, analyse and
implement the available evidence for the
benefit of their patients.
Majority of good quality evidence from NICE,
RCOG, FIGO, GLOWM is now available free
through internet
Challenges need to be appropriate
Some argue that EBM is a cookbook approach to
medicine, and so it may not take cognizance of
individual patient’s needs and circumstances.
Caesarean delivery at maternal request for a 42 year
old woman with 3 miscarriages and 1 failed previous
IVF cycle who is at 41+3 weeks now – would you
offer it?
Evidence is to guide Mrs Average’s treatment and not
the exception as the trials are on Mrs Average
Challenges
In some situations, gold standard evidence
may not be available.
The amount of resources needed to conduct
large randomised trials to obtain sufficient
evidence is often significant
Thus funding sources may ultimately
determine which therapies are subjected to
review and which are not.
Challenges
The quality of individual studies performed to
obtain evidence may vary, which therefore
makes it difficult to compare them and apply
the results to general population
All the evidences produced may not be made
accessible, and this may bias the
results/effectiveness of any particular
approach or intervention.
Breech delivery
A number of questions were raised
following publication of the Term Breech
Trial, largely about selection criteria and
the conduct of labour.
How many offer assisted VD as a routine?
How many offer assisted VD on request?
Planned caesarean section for term breech delivery
G Justus Hofmeyr1,*, Mary Hannah2, Theresa A Lawrie3
Editorial Group: Cochrane Pregnancy and Childbirth Group
Published Online: 22 APR 2003Assessed as up-to-date: 2 AUG 2011
New Questions posed?
It has been suggested that the Term
Breech trial, by reflecting conventional
‘expert’ views, sanctioned the
conventional dorsal lithotomy position for
delivery and thereby missed an
opportunity to evaluate labour and delivery
in upright positions.
RCOG Greentop Guideline 20b
Which results to consider?
More recently, an observational prospective study with an intent-to-treat
analysis conclude that, in units where planned vaginal delivery is a
common practice and when strict criteria are met before and during
labour, planned vaginal delivery of singleton fetuses in breech
presentation at term remains a safe option that can be offered to women.
2526 women with planned vaginal deliveries, 1796 delivered vaginally
(71%). The rate of neonatal morbidity or death was considerably lower
than the 5% in the Term Breech Trial (1.60%; 95% CI 1.14–2.17), and not
significantly different from the planned caesarean section group).
Goffinet F, et al. PREMODA Study Group. Am J Obstet Gynecol 2006;194:1002–11.
Another study from Gerry Visser’s group supports elective CS based on
their large population based study
Preterm labour
Use of a tocolytic drug is associated with a prolongation
of pregnancy for up to 7 days but with no significant
effect on preterm birth and no clear effect on perinatal or
neonatal morbidity.
There is no clear evidence that tocolytic drugs improve
outcome and therefore it is reasonable not to use them.
However, tocolysis should be considered if the few days
gained would be put to good use, such as completing a
course of corticosteroids or in utero transfer.
RCOG Greentop guideline 1b
Preterm labour
There is insufficient evidence for reaching any
firm conclusions about whether or not
maintenance tocolytic therapy following
threatened-preterm labour is worthwhile.
Should we prescribe tocolytic therapy until more
research data is available for those who stop
and restart preterm labour and are too early to
deliver and has no evidence of infection?
Is it lack of evidence or no evidence?
Are there sufficient studies?
Prolonged pregnancy
In the trial by Hannah ME et al, 3407 women with low-risk
singleton pregnancies at 41 weeks were randomly assigned
to IOL within 4 days (with and without cervical ripening) or
expectant management until 44 weeks.
Women in the induction group underwent CS significantly
less frequently than the women who were expectantly
managed (21.2 vs. 24.5%, respectively; P=0.003) due
primarily to a lower rate of CS for non reassuring fetal heart
rate tracings in the induction group.
Hannah ME et al. Canadian Multicenter Postterm Pregnancy Trial
Group. N Engl J Med 1992; 326:1587–92.
Prolonged pregnancy
A subsequent cost–benefit analysis of
these data showed that routine IOL at 41
weeks resulted in significantly lower costs
than expectant management ($2939 vs.
$3132 Canadian, respectively; P<0.05).
Goeree R, Hannah M, Hewson S. Cost-effectiveness of induction of
labour versus serial antenatal monitoring in the Canadian
Multicentre Postterm Pregnancy Trial. CMAJ 1995; 152:1445–50.
Prolonged pregnancy – when to
induce labour?
Despite these data, routine induction at 41 weeks has not been
universally accepted.
Criticism has been made regarding biases in the study by
Hannah ME et a (which forms bulk of the evidence in
systematic reviews) and it has been suggested that analysis by
actual treatment received rather than intention to treat indicated
a higher risk of caesarean sections.
Menticoglou SM, Hall PF. Routine induction of labour at 41
weeks gestation: nonsensus consensus. BJOG 2002; 109:485–
91.
Method of induction may have influenced the CS rates; PG was
used in the active group and oxytocin /ARM in the conservative
group
Other Concerns
It must be remembered that with a given CTG trace, the
clinical actions and decisions vary depending on the overall
clinical picture.
A pathological CTG showing fetal tachycardia with atypical
variable or late decelerations and reduced variability at 3–4
cm cervical dilatation in a primigravida might warrant a CS,
whereas at 7–8 cm it might indicate the need for FBS and an
instrumental delivery in the second stage, if this can be
carried out safely.
CANNOT BE RIGID WITH EBM
Other situations – Delivery of Twins
Twins – Need for well-designed RCTs of
interventions to reduce preterm birth in women
with twin and triplet pregnancy and short
cervix.
Conflicting data about circlage for multiple
pregnancies.
Need for evidence regarding optimal
management when there is EFW discordance
of 25% or more, including optimal timing of
delivery.
Other situations – Episiotomy for previous
3’rd/ 4’th degree tears
Episiotomy and ¾ degree perineal tear
prevention.
Evidence says no role but experienced
obstetricians feel episiotomy helps.
How many would do elective episiotomy or
would you base your decision on patient’s
views/ request.
Maternal request CS
CS at maternal request – Debate continues
especially regarding neonatal benefits
versus maternal safety issues
+ Long term effects.
Are we taking into account individual
circumstances such as high risk maternal
conditions, assisted conception
treatments, small family size, increasing
maternal age etc?
HYPERTENSIVE DISEASE IN PREGNANCY
AND THE USE OF LABETALOL
There is one small head-to-head RCT comparison of oral
labetalol vs parenteral hydralazine (Walker JJ et al. Postgrad
Med 1983) - underpowered to draw any conclusions.
On the basis of this trial, however, considerable experience
has been gained in Yorkshire as part of their successful
guideline (Tuffnell DJ. BJOG 2005)
Upon that success - recommendation was made in the 2011
NICE guidelines that oral labetalol be the drug of choice.
It was listed as the agent of first choice. The onset of action
of oral labetalol is 20-120 minutes, which about the same as
methyldopa and intermediate-acting nifedipine
Peter von Dadelszen
Other than the published pharmacodynamics (e.g., drug
monographs), the most supportive methyldopa data come
from Hamilton M & Kopelman H. BMJ 1963, which show that
the time to effect in patients receiving methyldopa and
diuretic together i.e. similar to women with pre-eclampsia
who are volume constricted.
Currently, in PRE-EMPT Trial - Nifedipine, labetalol and
methyldopa are tested in a RCT of women with severe
pregnancy hypertension.
The trial is led by Hillary Bracken from Gynuity and recruiting
in Nagpur, India.
Bacterial vaginosis as a risk factor for preterm
delivery: a meta-analysis.
Leitich et al. Am. J. Obstet. Gynecol. 2003; 189:139-147.
 18 trials
 20,232 patients
The earlier the diagnosis of BV the greater
the risk of adverse outcome
OR
for PTD
95%CI
< 16 weeks
7.55
1.80 – 31.65
< 20 weeks
4.20
2.11 – 8.39
> 20 weeks
1.82
1.06 – 2.21
Antibiotic treatment of BV in pregnancy: a meta – analysis
Leitich et al. Am J Obstet Gynecol 2003;188:752 - 758
Treatment initiated early made significant difference,
treatments initiated >20wks made no difference.
Study
Number
Mean GA
at random
Category
Outcome
Antibiotic
group
Control
group
OR 95%CI
Carey et al 2000*
1919
19.7
All
Low risk
High risk
< 37
< 35
< 32
< 37
< 37
116 / 953
48 / 953
22 / 953
86 / 852
30 / 101
121 / 966
49 / 966
26 / 966
95 / 857
26 / 109
0.97 (0.74 - 1.27)
0.99 (0.66 – 1.49)
0.85 (0.48 – 1.52)
0.90 (0.66 – 1.23)
1.35 (0.73 – 2.49)
Hauth et al 1995*
258
22.9
High risk
< 37
54 / 172
42 / 86
0.48 (0.28 – 0.82)
Joesoef et al 1995
681
20.3
All
All
< 37
< 32
51 / 340
16 / 340
46 / 341
9 / 341
1.13 (0.74 – 1.74)
1.82 (0.79 – 4.18)
Kekki et al 2001
375
13.5
Low risk
< 37
9 / 187
7 / 188
1.31 (0.48 – 3.59)
Kurkinen et al 2000 
101
12.4
Low risk
< 34
1 / 51
1 / 50
McDonald et al 1997*
480
24.1
All
Low risk
High risk
< 37
< 37
< 37
11 / 242
10 / 225
1 / 17
15 / 238
2 / 221
6 / 17
0.71 (0.32 – 1.57)
1.10 (0.44 – 2.75)
0.11 (0.01 – 1.09)
McGregor et al 
25
30.7
All
< 37
9 / 60
5 / 69
2.26 (0.71 – 7.16)
Morales et al 1994*
80
16.5
High risk
High risk
< 37
< 34
8 / 44
2 /44
16 / 36
4 / 36
0.28 (0.10 – 0.76)
0.38 (0.38 – 2.21)
Systematic review of antibiotic for the treatment of bacterial vaginosis in pregnancy comparing preterm
delivery rates (< 37 weeks) with any antibiotic versus placebo or no treatment.
Adapted from McDonald et al 2005
Cochrane review of all
trials showing lack of
evidence to support
treatment
Effect of antibiotics therapy vs placebo for intermediate
flora or bacterial vaginosis on the risk of preterm birth:
Adapted from McDonald et al
 Clindamycin
 Early treatment
 Route?
Early Rx using oral clindamycin - significant reduction
Effect of antibiotics therapy vs placebo for intermediate
flora or bacterial vaginosis on the risk of preterm birth:
Unpublished meta-analysis of all RCTs using
early oral clindamycin showing benefit
Ugwumadu et al 2006 (unpublished)
Conclusions
The gestation at diagnosis and
Treatment influences the outcome
 Symptomatic pregnant women should be treated
 Women with history of PTB or late miscarriage benefit from Rx
 Treatment when indicated should be initiated early
 Clindamycin appear to be more efficacious than metronidazole
 Both oral & topical clindamycin probably OK if Rx given early
 More trials required to clarify screening the general population
Electronic Fetal Monitoring
Is there evidence to do EFM in high risk labour?
Is there evidence to do EFM in low risk labour?
Does CTG reduce intrapartum mortality?
Retrospective studies
Historical Controls – 1970s
EFM decreased SB rate by 2-3/1000 &
NN death rate by 6-7/1000 (Several
studies)
1) Lee & Baggish – Obstet & Gynecol 1976; 2) Shenkar
et.al. Obstet & Gynecol 1975; 3) Edington et.al. BMJ
1975; 4) Weinraub et.al. Isr J Med Sci 1978;5) Koh et.al.
Can Med Assoc J 1975; 6) Johnstone et.al. Lancet 1978;
7) Hochuli Schweiz Med Wochenschr 1976;8) Lehmann
et al. Geburtshilfe Frauenheilkd 1976
Intrapartum Fetal Heart Rate monitoring
Vs Intermittent Auscultation
N =18,561 – 9 published studies
Higher CS rate - OR – 1.53 (1.17-2.01)
Higher CS rate for ‘FD’ - OR 2.55 (1.81-3.53)
Increased IVD - OR – 1.23 (1.02-1.49)
Increased IVD for ‘FD’ – 2.50 (1.97-3.18)
Decreased PNM due to fetal hypoxia – OR 0.41
(0.17-0.98)
Vintzelios et.al. Obstet Gynecol 1995
Haverkamp et.al. Am JO&G 1976 & 1979; Renou et.al. Am J O&G 1976; Kelso et.al. Am J
Obstet Gynecol 1978; Wood et.al. Am J Obstet Gynecol 1981; Mac Donald et.al. Am J
O&G 1985; Neldam et.al. Eur J Obstet Gynecol1986; Luthy et.al. Obstet Gynecol. 1987;
Vintzileos et.al. Obstet Gynecol. 1993
Comparing continuous electronic fetal monitoring in labour (cardiotocography,
CTG) with intermittent listening (intermittent auscultation, IA)
Alfirevic Z, Devane D, Gyte GML; Published Online: November 8, 2013
Review included 13 trials involving over 37,000 women that compared continuous CTG
monitoring with intermittent auscultation (listening). Most studies were not of high quality
and the review is dominated by one large, well-conducted trial of almost 13,000 women
who received one-to-one care throughout labour. In this trial, the membranes were
ruptured artificially (amniotomy) as early as possible and oxytocin stimulation of
contractions was used in about a quarter of the women.
Overall, there was no difference in the number of babies who died during or shortly after
labour (about one in 300).
Fits (neonatal seizures) in babies were rare (about one in 500 births), but they occurred
significantly less often when continuous CTG was used to monitor the fetal heart rate.
There was no difference in the incidence of cerebral palsy, however, other possible longterm effects have not been fully assessed and need further study.
Continuous monitoring was associated with a significant increase in CS & IVD. Both
procedures are known to carry the risks for mothers although the specific adverse
outcomes were not assessed in the included studies.
-
NEONATAL SEIZURES
PERINATAL MORTALITY
Incidence of IP still births & NN deaths
To study impact of EFM on reduction of IP related
deaths large numbers need to be studied 80 to
100,000.
A review of IP fetal deaths 1982-2002. Mattatall et.al. 2005;
IJOG; IP deaths - 82/121,659 births -0.67/1000; 82 = 51
previable + 20 major anomaly;
Viable = 11 (0.09/1000 or 0.9/10,000)
Conclusion; EFM & rapid operative delivery may reduce
already low rate of IP deaths
Incidence of HIE in the UK 2/ 1000 – Grades 2&3 =1/1000;
50% of grades II & III Die or develop CP
IP – Hypoxia > Asphyxia > IP still births > HIE > NN deaths
Obstetric intervention and benefit in conditions
of very low prevalence
This figure shows the number of cases
required in each arm of a study to
detect changes in interventions and
outcomes, using a 0.8 power and a
type 1 error of 0.05.
To detect a doubling or halving of the CS
rate from 10% requires 220 and 475
cases in each arm, respectively.
A similar doubling or halving in the
incidence of low Apgar scores from
around 0.9% would require 2799
and 5634 cases, and for
encephalopathy 85,012 and 42,488
cases.
Mongelli suggests that the flaws in
much of the evidence have given special
prominence to the negative aspects of
EFM, whereas the possible benefits
have been obscured by studies with
insufficient numbers.
Mongelli et al, BJOG 1997
The intervention-benefit ratio and research models
The positive predictive value (i.e. the proportion of those tested
positive with the predicted outcome) can be derived from test
sensitivity, specificity and disease prevalence.
If intervention occurs whenever a test is positive, the intervention
rate is equivalent to the test positive rate. However, such an
intervention would only be beneficial if the test result is a true
positive.
The intervention-benefit ratio (IBR) can therefore be defined as the
inverse of the positive predictive value.
In the context of EFM the IBR represents the number of interventions
that would be necessary to prevent a case of adverse neonatal
outcome:
Mongelli et al, BJOG 1997
What % of women were electronically monitored in the EFM group?
What % CTG were not interpretable in the first stage? In the second stage?
Did it increase CS or IVD rate?
Did the women in the IA group have FBS in labour?
What was the commonest indication for FBS?
i) I) Abn CTG of FHR?
ii) Ii) Meconium?
iii) Labour> 8 hrs?
FETAL SCALP BLOOD SAMPLING
OPERATIVE DELIVERIES
EFM is equivalent to EFM if FBS is performed for women in
labour > 8 hrs ???
Entry Criteria – at ARM must have clear amniotic fluid
What was the mean cervical dilatation at ARM?
Did it increase CS or IVD?
AT is of little value if ARM at < 1.5 cm shows clear fluid
How many use a partogram?
Is there evidence that partogram is useful to
reduce CS? or infection? or operative
delivery?
Effect of partogram use on outcomes for women in spontaneous labour at term
Lavender T, Hart A, Smyth RMD; Published Online: July 10, 2013
It has been unclear whether a partogram should be used and, if so, which design of
partogram is better for women and babies.
Review authors identified six randomised controlled trials involving 7706 women in
spontaneous labour at term. Two studies, with 1590 women, assessed introducing the
use of a partogram versus routine care without a partogram. Four studies, involving
6116 women, compared different types of partograms.
Overall, there was no evidence from this review that using a partogram reduced or
increased CS rates or had any effect on other aspects of care in labour.
Where different types of partogram were compared, no design appeared better
than others.
A single centre study, conducted in India, however, comparing a partogram with a latent
phase (composite) and one without, demonstrated more favourable outcomes for the
mother and baby when the modified chart was used. It is possible that partograms may
be useful in settings with poorer access to healthcare resources, as studies in Mexico
and Africa also showed some reduction in caesarean section rates with partogram use
and early intervention for delayed progress in labour.
-
World Health Organization partograph in
management of labour – WHO maternal health
and safe motherhood programme*
Summary
As part of the Safe Motherhood Initiative, launched in 1987,
theWorld Health Organization have produced and promoted
a partograph with a view to improving labour management
and reducing maternal and fetal morbidity and mortality. This
partograph has been tested in a multicentre trial in south
east Asia involving 35 484 women.
Introduction of the partograph with an agreed labour
management protocol reduced both prolonged labour (from
6.4% to 3.4% of labours) and the proportion of labours
requiring augmentation (from 20.7% to 9.1%)
Lancet 1994; 343: 1399-404
Four pairs of hospitals in south east Asia were invited to participate (2 pairs in
Indonesia, 1 each in Thailand and Malaysia).
All the centres functioned as district general hospitals in urban environments with
adequate medical and midwifery staffing and suitable facilities for operative obstetric
Figure 1: The WHO partograph
care.
All were already practising
labour
management
including
oxytocin
augmentation.
of labour
on the graph
is recorded
of cervical
dilation
Progress active
against
time (4 hourly observations), with space to record all fetal and maternal
The study ran for 15
months from
January, 1990.
observations.
The1 illustration
shows a woman admitted at 2 cm dilation
(latent phase), who progressed to 4 cm at the next vaginal examination.
During the first Five
months,
all centres
data
on their deliveries
a line (1
This
observation
in the collected
active phase
is transferred
onto the on
Alert
limit ofheld
standardised form cm
for per
entry
onto thelower
database
on computer
at WHO
headquarters
hour-the
normal
the time
scale for all
progress) and
in Geneva.
subsequent maternal and fetal observations is shifted to the right
Full dilationwas
at the next in
After Five months,accordingly.
the WHO partograph
introduced
one of each
cm) occurred
(10 randomly
vaginal
hospital pair.
examination, with delivery 10 minutes later.
Ten months into the study, the partograph was introduced into the remaining hospitals
and thus used in all 8 for the last 5months. No discussions were held concerning labour
management or partography until the partograph was introduced, at which point a
protocol was agreed for commencing women on the
partograph and for labour management. This protocol was adopted
in all 8 hospitals but did not introduce any new form of
management which was not already being carried out.
common
Emergency CS fell from 9.9% to 8.3%, and intrapartum
stillbirths from 0.5% to 0.3%.
Among singleton pregnancies with no complicating factors,
the improved outcome was even more marked, with CS
falling from 6.2% to 4.5%.The improvements took place
among both nulliparous and multiparous women.
The World Health Organisation partograph clearly
differentiates normal from abnormal progress in labour
and identifies those women likely to require intervention.
Its use in all labour wards is recommended.
Lancet 1994; 343: 1399-404
Challenges to Evidence Based Medicine
There is a need for more and better research
Inadequacy of numbers
Inclusion & Exclusion criteria need to be well defined
Details of the study need to be explored (sub group meta
analysis. E.g fruits - mix of apples and pears Vs bananas cf- BV
in early Vs late gestation)
Conclusions drawn must spell out the points to make note if one
is to follow their conclusions (e.g. ARM at Cx <2 cm with AT)
Exclusion of studies based on reviewer’s bias? (Use of WHO
partogram)
Should reviewers of Cochrane are the same as those
conducted the major studies
THANK YOU