Cytotec Induction in the US: An Example of Vigilante
Obstetrics
-by Marsden Wagner MD, MSPH
1. Around 1990 obstetricians stumbled onto the
fact that cytotec, a drug for stomach ulcers,
causes severe uterine contractions and, without
any evidence to back it up, began trying it out
on women to jump start or induce labor. They found
it worked and so, without any idea of what the
risks might be, used it more and more, playing
around with the dosage and with how and when it
is given. It can be reliably estimated that between
1995 and 2000, over a half million women had cytotec
induction. (see below) This use of cytotec was
(and is) not approved:
- by the FDA,
- by the drug regulatory agency of any other
country
- by Searle the pharmaceutical company making
cytotec (the package insert warns physicians
in bold letters to never use cytotec on pregnant
women),
- by the most reliable, valid scientific evidence
(Cochrane library).
Therefore, giving cytotec for induction to millions
of women was experimental but women were not told
this, not told they were unwitting guinea pigs.
Women were not given that basic right of health
care---fully informed choice---were not told it
was not approved by the FDA, by the drug company,
by the best scientific opinion.
Example: In January 2001 Dr Sanchos-Ramos, an
obstetrician in Florida, bragged on a national
radio program that he had done over 5000 cytotec
inductions. When asked, he admitted he had not
told these women this was not FDA approved. He
said he had not had any trouble with all these
cytotec inductions but since he apparently has
not done systematic long term follow-up studies
of the infants or women, he cannot know what the
real outcome of this aggressive intervention has
been. Not waiting for the judge is vigilante obstetrics.
2. Then after years of giving cytotec induction
to millions of women, in 1998 a paper was published
(Wing et al, Obstetrics and Gynecology 91, 2,
828-830) describing an experimental trial of cytotec
induction on women with previous cesarean section
(VBAC) which had to be stopped before the research
was completed because too many women had ruptured
their uterus (a catastrophic obstetric emergency
with high mortality for woman and baby). This
paper had no apparent effect on the continuing
practice of cytotec induction.
But then one year later, in 1999, two papers
appeared in the same issue of an obstetric journal
(Plaut et al and Blanchette et al, American Journal
of Obstetrics and Gynecology, June 1999) reporting
alarming rates of uterine rupture with cytotec
induction for women with previous cesarean section.
In one paper 5.6% of women had a ruptured uterus
and in the other paper the rate of rupture was
3.7%. This is a 28 fold increase in rupture. And
one quarter of the women with a ruptured uterus
had a dead baby. Several months after these papers
were published, the American College of Obstetricians
and Gynecologists (ACOG) finally came out recommending
not to use cytotec induction if the woman had
a previous cesarean section.
Because obstetricians did not wait for the scientific
evidence before using this powerful and dangerous
drug for induction of labor, it can be reliably
estimated (see below) that during the five years
before ACOG finally made this recommendation,
over 25,000 women with previous cesarean section
had been given a cytotec induction, over 1000
of these women ended up with a ruptured uterus,
and over 50 of these women ended up with a dead
baby.
So using cytotec all those years for labor induction
with previous cesarean section, before adequate
scientific evaluation was done is a tragic example
of shutting the barn door after thousands of horses
are out and illustrates why vigilante obstetrics
should never happen.
3. In addition to the dead babies from cytotec
induction, there is good scientific evidence that
cytotec frequently causes uterine hyperstimulation
and considerable anecdotal evidence that such
hyperstimulation during labor leads to severe,
permanent brain damage to the baby. As yet we
have no idea how many brain damaged babies are
out there as a result of cytotec induction but
we know for certain there are such babies.
4. In addition to the increased morbidity and
mortality directly resulting from cytotec induction,
there are other highly undesirable spin offs.
Induction, whether with cytotec or other drugs,
leads to more forceps, vacuum extraction and cesarean
section births. All such "surgical"
births have increased risks for both woman and
baby. The increasing induction rates in the US
partly explain the rising cesarean section rate
which, in turn, is partly responsible for the
rising rate of maternal mortality (women dying
during pregnancy and around the time of birth)
in the US. Yes, women have died from cytotec induction
and other women have died from the cesarean section
which the cytotec induction led to.
Cesarean section also means lower fertility for
the woman in the future so the increasing induction
rate may partly explain the widespread infertility
found in the US.
Because of the increasing rate of uterine rupture
during the 1990s in women with a previous cesarean
section--- which is related to the spread in popularity
of cytotec induction--- ACOG recently recommended
that a woman should not be permitted to attempt
a vaginal birth after previous cesarean section
(VBAC) unless in a hospital with a full time obstetrician
and anesthesiologist. This effectively eliminates
birth in small hospitals, removing the possibility
for a birth near home for large numbers of families.
5. The nature of cytotec tablets present two
special difficulties if used for labor induction.
First, cytotec induction is replacing pitocin
(oxytocin) induction. Pitocin has been very adequately
studied scientifically and we know just how to
use it and what its risks are. Pitocin is given
IV so if a woman develops hyperstimulation or
other problems, all you have to do is pull the
IV and that is the end of the effect of pitocin.
But cytotec is given either orally or in the vagina
where it is absorbed and stays in the body for
hours and cannot be removed even if hyperstimulation
or other problems develop.
Secondly, cytotec is made for stomach ulcers
in 100 microgram tablets. But after a decade of
experimenting on women, 25 micrograms is now the
usual dose for labor induction. Have you ever
tried to take a tablet which does not have a line
down the middle and, using a razor blade, cut
it in half and then into quarters so that each
quarter is exact? This is what hospital pharmacies
all over the country are trying to do. Some hospitals
do not have cytotec induction because their pharmacy
refuses to do what they know is a most inaccurate
dosage.
6. When obstetricians discuss cytotec induction
of labor, listen carefully. Sad to say, but it
is difficult or impossible to detect remorse for
this decade of scientifically unjustified practice
nor compassion for the women who suffered uterine
rupture and dead babies. Rather it is common to
hear only attempts to justify their practice (we
use lots of drugs not approved by the FDA. etc,
etc) and try to defend themselves. The tragedy
of using cytotec induction all those years for
women with previous cesarean section before adequate
scientific evidence on risk could be an opportunity
for learning from mistakes. Here is a prime example
of why we need the FDA and the scientists and
the best evidence before rushing to try a "hot"
new drug or technology but this will not be a
lesson unless the obstetricians can admit they
made a mistake.
7. One way obstetricians try to justify cytotec
induction is by quoting scientific data---data
which good scientists know to be inadequate. But
the obstetricians torture the data until it confesses
to what they want it to say. All the studies they
quote have fatal flaws in their methodology and
their single greatest weakness is that not a single
study is large enough to have sufficient statistical
power for the less common but catastrophic risks
such as uterine rupture and death. This is why
the universally agreed best scientific obstetric
opinion, the Cochrane Library, has maintained
throughout the 1990s and still maintains today
that we do not know enough about the risks of
cytotec induction to recommend its use.
In January 2001 a paper published in a prominent
medical journal reviewed cytotec induction. (Goldberg
et al, New England Journal of Medicine, 344, 1)
It would be easy for the casual reader of this
article to think it is scientific justification
for cytotec induction but careful scientific scrutiny
of the paper suggests otherwise. A brief analysis
of the paper illustrates how author bias invalidates
results. For starters, Goldberg et al greatly
confuse the reader by lumping together all uses
of cytotec during pregnancy---medical abortion,
induction of labor, postpartum hemorrhage, etc..
Each of these indications has very different data
and should never be lumped ----"200 studies
involving a total of more than 16,000 women"
is falsely inflating the data and is most misleading.
The number of studies on cytotec induction is
far fewer, most of them are not randomized experimental
trials and all of them, trials included, are too
small.
In the same paper: "Prescribing a medication
for an off-label indication is common in the treatment
of pregnant women"---this argument has no
justification. Doing something does not prove
it is a good idea. Experience in medical practice
can often mean gaining more and more confidence
in a mistake.
The authors try to justify ignoring the FDA:
off label use (i.e. not FDA approved use) "is
not considered experimental if based on sound
scientific evidence". The whole purpose of
the FDA and on label use is to guarantee the consumer
that there is sound scientific evidence. No one
can disagree that for a number of years in the
early 1990’s cytotec was in widespread use
before there was any sound scientific evidence.
Is there sound scientific evidence today?
The paper goes on at great length documenting
the efficacy of cytotec induction---no one is
debating how effective this drug is. The debate
is with the risks and here the authors admit "
the relative risk of rare adverse outcomes with
the use of misoprostol (cytotec) for labor induction
remains unknown". So these authors never
say this drug is safe for induction and admit
that with regard to risks, we do not know enough
! This is a very weak evidence base and can in
no way be considered "sound scientific evidence".
And yet the authors recommend cytotec induction.
The group disagreeing with Goldberg et al includes
the FDA, Searle (who makes the drug), the Cochrane
Library, the drug regulatory agencies in the UK,
France, Germany, Netherlands, Denmark, Sweden,
Norway. When there is disagreement on the evidence
among the experts, the most conservative and safest
course for the doctor to follow is the fundamental
principle of medical practice: first do no harm.
8. Recently the American College of Obstetricians
and Gynecologists (ACOG) has recommended cytotec
induction if the woman has not had previous cesarean
section. To understand this recommendation it
is necessary to understand ACOG. ACOG is not a
college, it is a trade union and, like every trade
union, its first purpose is to protect the interests
of its members. While a second purpose is to promote
the well being of women, if there is conflict
between these two purposes, the well being of
obstetricians always comes first. Proof? Recently
ACOG made the recommendation that doctors and
hospitals refuse permission for women and families
to make a videotape of their babies’ hospital
birth. Doctors’ fear of litigation comes
before the need of the family to record one of
the most important events in their lives. This
is why ACOG recommendations cannot always be considered
the gospel. Should the United Auto Workers have
the final say on standards of auto safety?
9. Why do obstetricians want cytotec induction?
In a word, convenience. Recently on Good Morning
America I was debating with the President of ACOG
and when I suggested obstetricians sometimes do
things for their own convenience, the President
indignantly replied that obstetricians never do
things for their own convenience. But there is
proof. In a report of the Federal Government,
an analysis of birth certificates shows that vaginal
birth (ie excluding cesarean section) is much
more common Monday through Friday---"While
births were more common on weekdays than on week-ends
in 1989, they have become even more concentrated
on weekdays since 1989. " How can this be?
By scheduling labor induction during those days
most convenient to doctors and hospitals.
Inducing labor sometimes may be medically justified,
but it is never medically indicated in more than
10% of cases and there is no data showing better
outcomes if the rate of induction is over 10%.
But since cytotec induction began to spread in
the US, the national rate of induction has gone
from 10% in 1990 to 18% in 1998. The same Government
report shows that If in addition to this 18% drug
induced kick-start of labor is added the16% of
cases in which the same drugs are used to speed
up ("stimulate") labor which is already
started, then the total of labors in which these
powerful and dangerous drugs are used is 34 %
or over one-third of all births.
Being able to schedule a labor and birth is so
essential to obstetricians because of the nature
of their practice. They are trying to do too much---assist
at the close to 4 million normal pregnancies and
births every year, assist at the _ million complicated
pregnancies and births every year, do preventive
gynecology for all women including cancer screening
and family planning, perform minor and major gynecological
surgical procedures. No other medical specialty
tries to do this much.
Obstetricians need desperately to get some control
into their practice, most especially with the
births which go on for 12 or more hours on a 24
/ 7 basis. So being able to tell Ms Jones to come
to the hospital next Monday at 9 am for a cytotec
jump start of her birth means that by 6 pm that
day, she will likely have given birth and the
doctor can be home for dinner. This is called
"daylight obstetrics" and is every doctor’s
dream.
Of course during the day on Monday the doctor
can still do routine prenatal visits in his/her
office since most American women do not realize
when they sign on with an obstetrician for their
birth that he/she, in fact, will not be there
during her labor but trying to monitor from afar
using the labor and delivery nurse and the telephone.
And research finds that in cases brought to litigation
because a baby died at birth, 70% of the time
the most important reason for the death was absence
of the doctor and failure of communication between
the nurse and absent doctor.
In every other country outside of North America,
this is not the situation since midwives attend
over 80% of births and doctors are never in the
room at any time. And fifteen of these countries
lose fewer women and babies at birth than the
US. So cytotec induction is a reflection of the
maternity system in the US with obstetricians
trying to do too much resulting in women and babies
paying a big price in unnecessary and dangerous
interventions which sometimes lead to disability
and death.
10. Why discuss cytotec induction in the media?
Because of vigilante obstetric practices which
go into widespread use before adequate evaluation,
the usual methods of quality control in health
care---the FDA, the pharmaceutical industry, scientific
opinion, peer review---have all failed to slow
down much less stop the use of cytotec induction.
This leaves only two other methods of quality
control---information to the public and litigation.
There has to date been little or no information
to the public, in large part because of "tribal
loyalties" among doctors who know the problem
but will not speak out in public and blow the
whistle. There are already a number of cases of
litigation for infant death and infant brain damage
after cytotec induction but they are often settled
out of court with a gag rule so no one ever hears
of them. So investigative reporting by the media
becomes most important in protecting women and
babies from dangerous, out-of-control obstetric
practices.
11. Public information on cytotec must always
make a careful distinction between cytotec for
medical abortion early in pregnancy which is safe
and cytotec for induction of labor at the end
of pregnancy which is not approved because of
serious risks.
12. Because the marked rise in pharmacological
induction and augmentation during the past decade
has resulted in so many cases of uterine rupture,
a support group, formed by women who have suffered
from uterine rupture already has over 100 members.
For more information, contact Melissa
Emerine.
Risks of uterine rupture
Normal (unscarred) uterus 1 in 33,000 births
Vaginal birth after cesarean section (VBAC)—*no
induction*—1 in 200 births
VBAC---Oxytocin augmentation 1 in 100 births
VBAC---Oxytocin induction 1 in 43 births
VBAC---cytotec induction 1 in 20 births
Normal (unscarred) uterus---Cytotec induction
UNKNOWN
(Best scientific opinion---all present evidence
shows significantly increased risk of rupture
but level of risk unknown due to inadequate sample
size of studies.)
Neurological injury or death of baby after uterine
rupture 30 %
Death of woman after uterine rupture 1 –
2 %
Cytotec induction in the USA 1994 –
1999
Estimates are all conservative and based on data
from Centers for Disease Control and Prevention
(CDC), American College of Obstetricians and Gynecologists
(ACOG) and papers by Plaut et al * and Blanchette
et al ** (P & B)
All cytotec induction in US 1994 – 1999
births a year (CDC)
4 million on average
15% are induced (CDC) 600,00
25% of inductions use cytotec (ACOG) 150,000
cytotec inductions in 5 years 750,000
Cytotec inductions with previous cesarean section
in US 1994 – 1999
(note---ACOG recommendation against cytotec with
VBAC came at end of 1999)
One Year
Births a year (CDC) 4 million
15% have previous C section (CDC) 600,000
25% try vaginal birth---VBAC (ACOG) 150,000
on average 7% VBACs are induced (CDC) 10,500
(assume _ as many inductions with VBAC)
25% of VBAC inductions use cytotec (ACOG) 2625
4% of VBAC cytotec inductions rupture (P&B)
105
25% of uterine ruptures have dead baby (P&B)
26
Five Years (1994 - 1999)
VBAC cytotec inductions 13,125
VBAC cytotec inductions with rupture 525
VBAC cytotec inductions with dead baby 130
Summary
In the 5 years 1994 to 1999 :
Over _ million women had cytotec induction.
Over 10,000 women had VBAC cytotec induction
Over 500 women with VBAC cytotec induction ruptured
uterus
Over 100 women with VBAC cytotec induction and
rupture of the uterus had a dead baby.
Unknown but significant number of cytotec inductions
had hyperstimulation of the uterus or rupture
leading to a brain damaged baby (anecdotal evidence)
* Plaut M, Schwartz M, Lubarsky S "Uterine
rupture associated with the use of misoprostol
in the gravid patient with a previous cesarean
section" Am J Obstet Gynecol 180: 6, 1535-40,
1999
** Blanchette H, Nayak S, Erasmus S "Comparison
of the safety and efficacy of intravaginal misoprostol
with those of dinoprostone for cervical ripening
and induction of labor in a community hospital"
Am J Obstet Gynecol 180: 6, 1543-50, 1999
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