Open Journal of Obstetrics and Gynecology, 2011, 1, 64-69
doi:10.4236/ojog.2011.12013 Published Online June 2011 ( OJOG
Published Online June 2011 in SciRes.
The effect of introduction of misoprostol for induction of
labour on pregnancy in gravidas with pre-eclampsia
Horace Fletcher, Marvin Reid, Nadine Johnson
Department Obstetrics and Gynaecology, University of the West Indies, Mona Kingston, Jamaica.
Received 25 April 2011; revised 27 May 2011; accepted 5 June 2011.
Misoprostol has revolutionized labour induction since
the early 1990’s, because it is inexpensive and very
effective. Eclampsia is common unless the pregnancy
can be terminated by induction or by caesarean sec-
tion. This study was done to determine the impact of
Misoprostol used for induction of labour, on the out-
come in patients with pre-eclampsia (PE) at the Uni-
versity of the West Indies Kingston Jamaica. This
was a retrospective analysis of pre-eclamptic women
who were managed before and after the introduction
of misoprostol into routine usage for induction of
labour. We compared 793 women (controls) in the pre
misoprostol era (1986-1991) with 709 in the miso-
prostol era (1993-1998). Outcome variables were the
frequency of mild and severe PE, eclampsia, miso-
prostol and syntocinon inductions, foetal complica-
tions and use of caesarean section (CS). Analysis of
frequency of eclampsia, neonatal admissions and CS,
during the misoprostol years, was also done to elimi-
nate other confounding variables because of the in-
fluence of each era. Logistic regression was used to
determine the impact of all variables. In comparison
to controls, patients induced in the misoprostol years
had a greater incidence of severe PE (p < 0.05), neo-
natal admissions (p = 0.007), foetal distress (p < 0.05);
a higher CS rate (p < 0.05); but fewer oxytocin in-
ductions (p < 0.05). However, sub group analysis of
the misoprostol years alone, showed a reduction in
the incidence of CS, eclampsia, and neonatal admis-
sions in women who were induced with misoprostol
(p < 0.05). Logistic regression revealed a lower odds
of CS delivery (OR 0.867, 95% confidence inter-
val .02, .37) using misoprostol. These findings suggest
that in patients with PE, induction of labor with Mi-
soprostol had a beneficial effect on pregnancy out-
come with a decreased incidence of CS, eclampsia
and neonatal admissions, but it has not had a signifi-
cant impact on the main problems in these patients
between the two eras as other factors may be impor-
tant in the management of these patients independent
of misoprostol induction.
Keywords: Misoprostol; Eclampsia; Labour Induction
Pre-eclampsia is defined as the occurrence of hyperten-
sion in combination with proteinuria, developing after 20
weeks gestation in a previously normotensive non-pro-
teinuric patient. It occurs in approximately 3 to 14 % of
all pregnancies worldwide and is the leading cause of
maternal mortality in Jamaica [1,2]. Outcome of preg-
nancies complicated by pre-eclampsia is often good, but
this disease is unpredictable, sometimes progressing
without warning, from its mild to severe form with dev-
astating maternal and foetal complications. The defini-
tive treatment is delivery of the foetus. If untreated;
pre-eclampsia is associated with increased risk to the
foetus of; intrauterine growth restriction, stillbirth, and
neonatal death [3] and to the mother an increased risk of;
eclampsia, severe hypertension, HELLP syndrome
(Haemolysis, Elevated liver enzymes, Low Platelets),
abruption, cerebral haemorrhage, pulmonary oedema,
liver haemorrhage, renal failure. The presence of any of
these findings in the mother usually requires immediate
delivery of the foetus as conservative management in
such cases can result in serious maternal and/or foetal
complications [4].
Misoprostol is a prostaglandin E1 analogue originally
developed for the prevention of non-steroidal drug in-
duced gastritis. However, with the accumulation of evi-
dence that intra-vaginal administration is an effective
alternative to endocervically or vaginally administered
prostaglandin E2 preparations for cervical ripening and
labour induction, at a much reduced cost, it has since
been used extensively worldwide for labour induction
[5-7]. Local work done by Fletcher et al in 1993 and
1994 concurred with these findings [8,9]. A meta-analy-
H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 64-69 65
sis of trials done has shown that vaginal misoprostol
appears to be more effective in inducing labour than
conventional methods of cervical ripening and labour
induction [10].
Misoprostol was first used at the University hospital
in 1992 and has been the principal induction agent used
in patients with an unfavourable cervix, since its intro-
duction [11]. Prior to this time patients with pre-eclamp-
sia requiring delivery, were either delivered by caesarean
section or had induction of labour with oxytocin if the
cervix was favourable or with dinoprostone, which be-
cause of cost was not always available. With the intro-
duction of misoprostol, vaginal delivery could be
planned, attempted and achieved in patients with mild or
severe pre-eclampsia, regardless of gestational age or
cervical Bishop Score as cervical ripening and induction
of labour could now be achieved. In theory, we were no
longer hampered by the presence of an unfavourable
cervix and its associated complication of failed induction.
This factor is particularly relevant in preterm patients
with severe pre-eclampsia, in whom expeditious delivery
is sometimes necessary. Ten percent of pre-eclampsia
occurs in pregnancies less than 34 weeks of g estation bu t
it has been shown that fewer than 1/3rd of women with
severe pre-eclampsia/eclampsia remote from term; i.e.
less than 28 to 32 weeks of gestation- with an unfav our-
able cervix will successfully deliver vaginally [12].
Failed induction is an undesirable complication as it not
only increases caesarean section rates but also increases
foetal and maternal morbidity and mortality.
The purpose of our study was to primarily determine
if the introductio n of Misoprostol for induction of labou r
at UHWI has made a significant difference in the out-
come of the patients with pre-eclampsia requiring deliv-
ery. Our secondary aim was to see if the use of miso-
prostol in pre-eclamptic patients, had any influence on
pregnancy outcome, such as, a decreased incidence of
severe pre-eclampsia, eclampsia or other maternal com-
plications; an improved perinatal outcome; or a decrease
in the caesarean section rate.
This retrospective cohort study was conducted at the
University Hospital of the West Indies. The pregnancy
outcome of all women with pre-eclampsia delivered in
this institution in the five years preceding misoprostol’s
introduction (1986-1991) (Group 1) was compared with
the outcome of those delivered during the five years af-
ter it came into standard usage (1993-1998) (Group 2).
The study was approved by the ethical committee at our
Data was obtained from the labour ward Logbook in
which is recorded information about all the patients de-
livered on the Labour Ward at the University Hospital.
All the patients with pre-eclampsia delivered during the
two 5 year periods were identified. Initials, registration
number, age, parity, gestational age at delivery, labour
inductions and method i.e. Misoprostol versus Oxytocin,
Caesarean Sections done, maternal and foetal complica-
tions, neonatal deaths, birth weight, Apgar score and
Special Care Nursery (SCN) admissions were all re-
The primary outcome variables were the number of
patients with a diagnosis of mild and severe pre-eclamp-
sia; misoprostol and oxytocin inductions; eclampsia and
other maternal complications such as HELLP syndrome,
maternal deaths, ICU admissions and abruption; foetal
complications as measured by the amount SCN admis-
sions, APGAR Score, neonatal deaths and intrauterine
growth retardation (IUGR); Caesarean Sections and in-
dications such as foetal distress, failure to progress,
failed induction and previous C-section. Secondary out-
come variables were the amount of cases of eclampsia,
SCN admissions and C-Sections in those patients in-
duced with misoprostol.
Values were expressed as means with standard devia-
tions, medians with ranges, or frequencies (per cent) as
appropriate. For continuous outcome variables, inde-
pendent t-tests were used to compare differences in
means between periods. Differences in frequencies and
proportions for qualitative outcome variables between
periods were tested with chi-square statistics. Logistic
regression models were constructed to determine the
relationship between period adjusting for possible con-
founding clinical factors and dichotomous outcome
variables. The data were analyzed using Stata version
7.0 for Windows (Stata Corporation, College Station TX
Between 1986 and 1991 (Group 1) there were a total
number of 709 women (47%) with pre-eclampsia deliv-
ered on the labour ward at the university hospital, while
between 1993 and 1989 (Group 2) there were 793
women (53%). Demographic data are shown in Table 1.
Misoprostol was only used for induction in Group 2.
The mean age of the women in was significantly
greater in year group 2 than year group 1 but the birth
weight and gestational age of preterm deliveries in group
1 was significantly greater than group 2. (Table 1).
There was a significant association between the sever-
ity of pre-eclampsia (PE) and year group with the greater
proportion in group 2 but the proportion of women with
severe PE who developed eclampsia was not different
according to year group (Table 1).
As expected there was significantly less use of Oxyto-
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H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 64-69
Copyright © 2011 SciRes.
cin in the latter period (63% vs 34% p < 0.05). Miso-
prostol was used to induce 287 women 42 of whom re-
ceived both oxytocin and misoprostol whilst a total of
364 received oxytocin (Table 1).
Table 4 shows the frequency and proportions of
eclampsia and other maternal complications. There was
no significant difference between the groups and the
frequency of eclampsia, maternal death, abruption,
HELLP syndrome, or ICU admissions.
Foetal Complications are as shown in Ta b l e 2 . There
was a significant association between foetal admissions
to the SCN and year group with more admissions in
group 2 (24% vs 30% p = 0.007) but there was no dif-
ference in the proportions of neonatal deaths or IUGR
between the two groups. There was also no difference in
median Apgar score between the grou ps.
Table 3 shows the frequency of C-Sections and major
indications for C-Section associated with Misoprostol
use for induction of labour. There was a significant asso-
ciation between C-Section and year group with more
C-Sections being done in Group 2 (p = 0.000). There
was also a significant association between foetal distress
and year group with more cases of foetal distress in
Group 2 but no difference in the proportion of failure to
progress, failed induction and previous C-Sections be-
tween the two groups
However sub analysis of year group 2 showed a sig-
nificant association between C-Section incidence,
eclampsia, and SCN admissions with misoprostol use in
the latter 5 years with significantly more C-Sections,
eclampsia and SCN admissions in those who were not
induced with misoprostol (Table 4).
Table 1. Maternal char acteristics.
variables Group 1 Pre-misoprostol
(n = 793) Group 2 After-misoprostol
(n = 709) P value
Age (y)* 26.5 ± 5.3 27.2 ± 6.0 0.02
Parity (median) 0 + 1 0 + 1
Mild PE 531 (74) 455 (57) 0.000
Severe PE 178 (26) 338 (43) 0.000
Misoprostol 0 287 (37)
Oxytocin 264 (34%) 100 (13%) 0.000
Eclampsia 31 (4.3) 45 (5.6) 0.250
Abruption 7 (0.9) 17 (2.1) 0.074
HELLP syndrome 3 (0.4) 3 (0.3) 0.891
ICU admission 4 (0.5) 2 (0.2) 0.339
Maternal death 4 (0.5) 3 (0.3) 0.598
*Values are expressed as mean ± standard deviation. Ot her Values expressed as n (%) of patients u nless otherwise st ated.
Table 2. Fetal and neonatal parameters.
Variables Group1
Pre-misoprostol Group2
After-misoprostol P value
IUGR 25 (3.5) 24 (3.0) 0.586
Gestational age of preterm deliverie s* 32.7 ± 2.9 31.1 ± 3.2 0.003
Birth weight (kg)* 2.8 ± 0.8 2.5 ± 0.8 0.00
SCN Admission 172 (24) 238 (30) 0.007
Neonatal Death 2 (0.2) 4 (0.3) 0.495
*Values are expressed as mean ± standard deviation. Other values expressed as n (%) of patients.
H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 64-69 67
Table 3. C-Section rates and Indications.
Variable Group 1
Pre-misoprostol Group 2
After-misoprostol P value
Caesarean section 218 ( 30) 328 (41) 0.000
Foetal distress 18 (2.5) 55 (6.9) 0.000
Failure to progress 18 (2.5) 23 (2.9) 0.668
Failed induction 12 (1.7) 15 (1.9) 0.772
Previous c-section 30 (4.2) 33 (4.1) 0.946
Values expre ssed as n (%) of patient s.
Table 4. Outcome in patients seen in the misoprostol years.
Variable Misoprostol
N = 287 No Misoprostol
N = 506 P value
Eclampsia 8 (2.7) 37 (7.3) 0.008
C-Section 40 (14) 286 (56) 0.000
SCN admission 58 (21) 180 (35) 0.000
Values expre ssed as n (%) of patient s.
The possible confounding variable of maternal age,
gestational age of preterm deliveries and parity were
eliminated by a logistic regression which showed that
the use of misoprostol lowered the odds of C-Section
delivery OR –0.867 [9 5% conf idence in terval 0 .02, 0.37].
Eliminating these variables, also showed the use of mi-
soprostol was not associated with becoming eclamptic
OR 1.52 [95% confidence interval 0.31, 7.28].
Intra-vaginal misoprostol used in patients with severe
pre-eclampsia remote from term has been previously
confirmed to be effective for labour induction in cases
where expeditious vaginal delivery is necessary [13].
However; this is the first study, to our knowledge ad-
dressing the impact of labour induction with misoprostol
on pregnancy outcome in pre-eclamptic patients. Miso-
prostol is in fact inexpensive, readily available and very
effective in inducing labour even with an unripe cervix.
Its use also avoids the performance of caesarean sections
in patients who are very ill.
It was thought that fewer patients would develop se-
vere PE since they would have been diagnosed and in-
duced before this developed, however a greater propor-
tion of women had severe pre-eclampsia in the latter 5
years than in the earlier period. This is hard to explain
since we do not believe the misopro stol is cau sing sev ere
pre-eclampsia. However despite this finding, the propor-
tion that went on to develop eclampsia was not different,
so in fact fewer women with severe pre-eclampsia, de-
veloped eclampsia. This could possibly have been a
beneficial effect of misoprostol induction. It is however
important to point out that only 37% of the patients in
the misoprostol years were induced with misopro stol and
in these patients caesarean section, eclampsia and ad-
mission to the special care nursery rates were lower than
in the 63% not induced with misoprostol. This is an im-
portant finding because while it is possible that these
patients were not as ill as those not induced with miso-
prostol, it may be an indication that misoprostol use is
beneficial in these patients.
Oxytocin was used with less frequency in the latter 5
years (34 vs. 13%). This concurs with a previous
Meta-analysis which shows that the use of misoprostol
was associated with a 50 % reduction in the use of oxy-
tocin [14].
Although a decrease in the incidence of caesarean
section was expected in the latter years there was a sur-
prising increase, with more caesarean sections being
done during the period in which misoprostol was used.
This is probably not unexpected as the caesarean section
rates in general worldwide have increased over the years.
This was however corrected by elimination of the con-
founding variables which yielded the expected decreased
odds of caesarean section delivery in the latter five years,
as has been previously noted by others [10]. A high cae-
sarean section rate (80%) has been described in eclamp-
tic patients in other centres in the Caribbean and this has
been said to be the best mode of delivery for such pa-
tients [15]. However this present study seems to suggest
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H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 64-69
that misoprostol indu ction may be a useful alternative to
emergency caesarean section in these very ill patients.
The frequency of failure to progress and failed induc-
tion was the same in both groups, so the introduction of
misoprostol did not have a significant impact as ex-
pected and thus show a beneficial effect over the era
with oxytocin induction only. There were also signifi-
cantly more cases of fetal distress in the latter group. An
earlier study had found an association between the inci-
dence of fetal distress and Misoprostol when used in
doses greater than 25ug [7] and this has been a constant
finding of most large studies [10].
The fact that the gestational age at delivery and mean
neonatal birth weight were bo th lower after th e introd uc-
tion of misoprostol is also an important finding. What
this implies is that we now have the ability to intervene
earlier with induction of labour when severe pre-
eclampsia occurs. This could also be a reason for the
greater number of special care nursery admissions.
The overall frequency of eclampsia and other mater-
nal complicatio ns in the two groups were similar and no
improvement was seen in perinatal outcome. The fact
that more special care nursery admissions occurred in
the latter 5 years even though the mean Apgar scores
were similar may be an indication of differences in care
in the two eras. However misoprostol indu ction has been
shown to be associated with foetal distress (hyperstimu-
lation syndrome) and increased passage of meconium
especially at the high doses used at UWI [7,16] .
Pregnancy induced hypertension is the leading cause
of maternal mortality in Jamaica and timely delivery is
the only way to stop the progress of the cond ition. It was
therefore hoped that the introduction of misoprostol to
the obstetric armamentarium would have shown a dra-
matic difference in this outcome in these patients. This
however has not been the case as shown in this study
and also as has been demonstrated by the fact that de-
spite the introduction of misoprostol hypertensive disor-
ders still remain the leading cause of maternal mortality
[12,17] with no decrease in maternal mortality rates.
The main drawback to studies of this type is the im-
pact of differences in management which could have
occurred in the two different time periods which have
not been taken in to account. These may explain some of
the differences seen.
Using the data from one period alone has shown some
differences indicating that the introduction of misopros-
tol may have been beneficial in these patients although
the overall impact appears disappointing.
Thus, it can be concluded that the introduction of mi-
soprostol is beneficial to pregnancy out come in patients
with pre-eclampsia but has not shown significant im-
provements between the two eras, as there are other fac-
tors which may possibly be involved which need to be
identified and corrected. We therefore believe that the
introduction of misoprostol to decrease maternal com-
plication rates in these patients must be associated with
careful patient selection and close monitoring in labour.
[1] Walker, G., McCaw-Binns, A., Ashley, D. and Bernard,
W. (1990) Identifying Maternal deaths in developing
countries: Experience in Jamaica. International Journal
of Epidemiology, 19, 599-605.
[2] Keeling, J., McCaw-Binns, A., Ashley, D. and Golding, J.
(1991) Maternal mortality in Jamaica; Health care provi-
sions and causes of death. International Journal of Gy-
necology & Obstetrics, 35, 19-27.
[3] Xiong, X., Mayes, D., Demianczuk, N., Olson, D.M.,
Davidge, S.T., Newburn-Cook, C., and Saunders, L.D.
(1999) Impact of pregnancy-induced hypertension on fe-
tal growth. American Journal of Obstetrics & Gyneco-
logy, 180, 207-213. doi:10.1016/S0002-9378(99)70176-6
[4] Cunningham, F.G. and Lindheimer, M.D. (1992) Hyper-
tension in pregnancy. The New England Journal of Medi-
cine, 326, 927-932.
[5] Campos, G.A., Guzman, S., Rodriguez, J.G., Voto, L.S.
and Margulies, M. (1994) Misoprostol--a PGE1 analog
for induction of labor at term: comparative and random-
ized study with oxytocin. Revista chilena de obstetricia y
ginecologia, 59, 190-195 (in Spanish).
[6] Chuck, F.J. and Huffaker, B.J. (1995) Labor induction
with intravaginal misoprostol versus intracervical pros-
taglandins E2 gel. randomised comparison. American
Journal of Obstetrics & Gynecology, 173, 1137-1142.
[7] Wing, D.A., Ortiz-Omphroy, G. and Paul, R.H. (1997) A
comparison of intermittent vaginal administration of mi-
soprostol with continuous dinoprostone for cervical rip-
ening and labor induction. American Journal of Obstet-
rics & Gynecology, 177, 612-618.
[8] Fletcher, H., Mitchell, S., Simeon, D., Brown, D. (1993)
Intravaginal misoprostol as a cervical ripening agent.
British Journal of Obstetrics & Gynecology, 100, 641-
644. d oi:10.1111/j.1471-0528.1993.tb14230.x
[9] Fletcher, H., Mitchell, S., Simeon, D. and Brown, D.
(1994) Intra-vaginal misoprostol versus dinoprostone as
cervical ripening and labor-inducing agents. Obstetrics &
Gynecology, 83, 244-247.
[10] Del Valle, G.O., Sanchez-Ramos, L., Jordan, C.W.,
Gaudier, F.L. and Delke, I. (1996) Use of misoprostol
(prostaglandin E1 methyl analogue) to expedite delivery
in severe pre-eclampsia remote from term. Journal of
maternal-fetal medicine, 5, 39-40.
[11] Fletcher, H. and Hutchinson, S. (2001) A retrospective
review of pregnancy outcome after misoprostol (pros-
taglandin E1) induction of labour. West Indian Medical
opyright © 2011 SciRes. OJOG
H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 64-69
Copyright © 2011 SciRes.
Journal, 50, 47-49.
[12] Walker, G., Ashley, D., McCaw, A. and Bernard, G. (1986)
Maternal Mortality in Jamaica. Lancet, I, 486-488.
[13] Alexander, J.M., Bloom, S.L., McIntire, D.D. and
Leveno, K.J. (1999) Severe pre-eclampsia and the very
low birth weight infant: Is induction of labor harmful?
Obstetrics & Gynecology, 9, 485-488.
[14] Hofmeyr, G.J. and Gulmezoglu, A.M. (2001) Vaginal
misoprostol for cervical ripening and induction of labour
(Cochrane Review). Cochrane Database System Review,
1, CD000941.
[15] Bassaw, B., Roopnarinesingh, S., Mohammed, A. and
Kuruvilla, A. (1994) An audit of eclampsia. West Indian
Medical Journal, 43, 18-19.
[16] Rockhead, C., Fletcher, H., Reid M. and Morgan O.
(2003) Induction of labour with Vaginal misoprostol: A
comparison of 50 ug twice daily (50bd) with 100ug used
once daily (100 od). International Journal of Gynecology
& Obstetrics, 80, 271-277.
[17] McCaw-Binns, A., Standard-Goldson, A., Ashley, D.,
Walker, G. and MacGillivray, I. (2001) Access to care
and maternal mortality in Jamaican Hospitals 1993-1995.
International Journal of Epidemiology, 30, 796-801.