doi:10.1111/jog.12697 J. Obstet. Gynaecol. Res.

2015

Should magnesium sulfate be administered to women with

mild pre-eclampsia? A systematic review of published reports
on eclampsia

Yifru Berhan and Asres Berhan

Hawassa University College of Medicine and Health Sciences, Hawassa, Ethiopia

Abstract
Aim: Magnesium sulfate is an evidence-based anticonvulsant drug used to prevent and control eclampsia. Con-
troversy persists on routine administration of magnesium sulfate in cases of pre-eclampsia without severe fea-
tures. Our objective was to assess the pattern of blood pressure and maternal symptoms preceding eclamptic
seizure based on the current published work.
Material and Methods: A comprehensive computer-based publication search was conducted in the African
Journals Online, Google scholar, HINARI, PubMed, and MEDLINE databases and the Cochrane library to iden-
tify descriptive study reports for blood pressure, severity symptoms or stage of pregnancy during convulsion in
women with eclampsia.
Results: A total of 59 publications were eligible for this review. Overall, 21149 eclamptic women from 26
countries were included for the interest of one or more of the selected variables. Out of 18 488 eclamptic
women, the proportion of antepartum, intrapartum and post-partum eclampsia was 59%, 20% and 21%, re-
spectively. Out of 3443 eclamptic women, 25% were normotensive; 20% had mild-to-moderate hypertension;
32% had severe hypertension; and 21% were hypertensive but unclassified. Out of 2163 eclamptic women,
66% and 27% had a headache and visual disturbance, respectively, preceding the occurrence of convulsion.
Out of 2053 eclamptic women, 25% had epigastric area pain, and out of 1092 women with eclampsia, 25%
were asymptomatic.
Conclusion: Although eclampsia is known to result from severe pre-eclampsia with or without organ function
derangement, this review has revealed that a significant number of eclamptic women had either normal blood
pressure or mild-to-moderate hypertension immediately before seizure. The findings are apparently in support
of initiating magnesium sulfate prophylaxis to all women with mild pre-eclampsia.
Key words: descriptive studies, eclampsia, magnesium sulfate, mild pre-eclampsia, systematic publication
review.

Introduction unfolding of the 19th century3 and different treatment

Eclampsia is diagnosed in pregnant or post-partum
women with the onset of generalized tonic–clonic sei-
zure in light of pre-eclampsia, not attributable to other
causes.1,2 Although eclampsia was recognized as a dis-
tinct disease entity (separate from epilepsy) during the
modalities were attempted,4 it is still not possible to
completely prevent its occurrence, even in the best set-
ting.5 As a result, eclampsia remains one of the leading
causes of maternal and perinatal mortality worldwide,
with the majority of the disease burden in the developing
world.6 The incidence of eclampsia in developed nations

Received: August 26 2014.

Accepted: January 13 2015.
Reprint request to: Professor Yifru Berhan, Hawassa University College of Medicine and Health Sciences, PO Box 1560, Hawassa, Ethiopia.
Email: yifrub@yahoo.com

© 2015 The Authors 1

Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology
Y. Berhan and A. Berhan
has declined over the past half century due to improved
antenatal care and early initiation of prevention and
treatment.7 The incidence of eclampsia in high-income
countries is now significantly lower than that in low-
and middle-income countries (Fig. 1).
In the last 2 decades, magnesium sulfate has become
a very popular anticonvulsant drug across the world
to prevent and control eclampsia, particularly in
women with severe pre-eclampsia.1,7 However, the rec-
ommendation of magnesium sulfate to women with
mild pre-eclampsia is remains controversial. According
to the American College of Obstetricians and Gynecol-
ogists (ACOG) 2013 task force recommendation, mag-
nesium sulfate should not be given universally for
the prevention of eclampsia in women with mild pre-
eclampsia evidenced by systolic blood pressure (BP)
of 140–160 mmHg, a diastolic BP of <110 mmHg and
no maternal symptoms.8 The WHO also recommends
the administration of magnesium sulfate for severe
pre-eclampsia, but reserves comment on mild pre-
eclampsia.1
A randomized controlled trial of magnesium sulfate in
women with mild pre-eclampsia showed statistically in-
significant increased risk of severe pre-eclampsia in the
placebo group but no eclampsia in either the treatment
or placebo group.8 In contrast, Alexander et al. showed
that giving magnesium sulfate prophylaxis selectively
to women with severe gestational hypertension was as-
sociated with a significant increase of eclampsia in the
women with mild hypertension.9 In another study, by
Foong and Pollard, 53% of eclamptic episodes could
2 © 2015 The Authors
Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology
have been prevented if seizure prophylaxis was univer-
sally administered for gestational hypertension from
the time of diagnosis through 24 h post-partum.10
As acknowledged by the ACOG 2013 task force, there
is a paucity of data on the importance of magnesium
sulfate prophylaxis for women with mild-to-moderate
hypertension in the absence of severe features. Sibaialso
notes that evidence for the use of magnesium sulfate pro-
phylaxis in mild pre-eclampsia remains uncertain.11
Based on data from two randomized trials,12,13 200
women with mild pre-eclampsia would need to be given
magnesium sulfate to prevent one case of eclampsia.14
According to some authors, if magnesium sulfate is rou-
tinely administered to all, the adverse effects may out-
weigh the risk of seizure.14
Due to lack of adequate data,8,11,15 controversy re-
mains regarding routine administration of magnesium
sulfate to women with mild pre-eclampsia.16–19 This con-
troversy may be settled in the future through meta-
analysis of high-quality randomized double-blind
clinical trials. To date, however, there are no adequate
randomized clinical trials with which to perform such a
meta-analysis on mild pre-eclampsia. This review was
planned to provide an answer to: how many eclamptic
women have mild-to-moderate hypertension and severe
symptoms? Therefore, the purpose of this study was to
assess the blood pressure and pattern of symptoms of
women with eclampsia from different parts of the world
as indirect evidence of the importance of magnesium sul-
fate prophylaxis for women with mild pre-eclampsia or
mild-to-moderate hypertension.
Figure 1 Incidence of eclampsia per
1000 deliveries in some countries
across the globe. Decimal numbers
are rounded to the nearest tenth.

Methods
Study design and area of interest
A systematic review of descriptive publications on
eclampsia was conducted using online available articles
from any part of the world. The incidence of eclampsia
between 1998 and 2013 in select countries was analyzed
for trends. Blood pressure pattern of eclamptic women
before the occurrence of seizure was the main interest
of this review. Symptoms of pre-eclampsia (headache,
visual disturbance, epigastric area pain and vomiting)
and type of eclampsia were also reviewed.
Publication search strategy
A comprehensive computer-based search of the pub-
lished work was conducted by two investigators (Y.B.
and A.B.) independently in the African Journals Online,
Google scholar, HINARI, PubMed and MEDLINE data-
bases and the Cochrane library to identify reports of
blood pressure and symptoms in women who devel-
oped eclampsia during the antepartum, intrapartum
and post-partum periods. The search was further
strengthened by searching the reference lists of re-
trieved articles that reported types of blood pressure
(mild range, moderate range, severe range), or relevant
symptoms during the study period. The search terms
were: ‘eclampsia’, ‘pre-eclampsia’, ‘eclampsia hyperten-
sion’, ‘eclampsia pre-eclampsia’, ‘eclampsia gestational
hypertension’, ‘eclampsia pre-eclampsia magnesium
sulfate’, ‘magnesium sulfate’, ‘eclampsia pre-eclampsia
severity symptoms-headache, visual disturbance, epi-
gastric pain, vomiting’, ‘type of eclampsia-antepartum,
intrapartum, post-partum, late post-partum’ and ‘preg-
nancy induced hypertension’. The selected search terms
were combined alternatively with the Boolean logic
(AND, OR and NOT).
Inclusion criteria and study selection
The predetermined inclusion criteria were: (i) studies on
eclampsia that assessed the blood pressure or severity
symptoms or type of eclampsia; and (ii) studies that
were published in English and conducted between
1930 and 2013. Study selection was conducted in two
stages. First the abstracts of all the retrieved reports were
reviewed and then grouped as ‘eligible for full document
review’ or ‘ineligible for full document review’. Second,
all the reports grouped as ‘eligible for full document re-
view’ were reviewed in detail and grouped as ‘eligible
for this review’ or ‘ineligible for this review’.
From the included studies, the following information
was abstracted: name of the first author, country study
© 2015 The Authors
Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology
Systematic review of reports on eclampsia
conducted, study period, total eclampsia cases included
in the study, mean maternal age, type of eclampsia, dia-
stolic and systolic blood pressure, and selected severity
symptoms of hypertension disorders (headache, blurred
vision, epigastric area pain, vomiting).
Operational definitions
Mild-to-moderate hypertension during pregnancy or
during puerperium was defined as a systolic blood pres-
sure of 140–160 mmHg and/or diastolic blood pressure
of 90–110 mmHg immediately before seizure. Severe
hypertension was considered when the systolic blood
pressure was ≥160 mmHg and/or diastolic blood pres-
sure was ≥110 mmHg.20 Presence of hypertension with
proteinuria after 20 weeks of gestation defines pre-
eclampsia. Severe pre-eclampsia was defined as severe
hypertension or mild-to-moderate hypertension with se-
vere symptoms and significant proteinuria (proteinuria
>300 mg in 24 h urine or +2 and above in the dipstick
test). Mild pre-eclampsia was defined as mild-to-
moderate hypertension without severe symptoms and
without significant proteinuria. In this article, mild-to-
moderate hypertension and mild pre-eclampsia are used
interchangeably.
Data presentation
Data are presented in tables and summarized in figures.
The actual values of each study were added and propor-
tions were determined for the type of eclampsia, distri-
bution of blood pressure and presence of severe
symptoms. Similarly, when two or more studies were
found from the same country during 1998–2013, the de-
nominators (total deliveries) and numerators (total cases
of eclampsia) were added before the incidence of
eclampsia was estimated for that specific country.
Results
The database search retrieved 3424 reports for the
search term ‘pre-eclampsia, eclampsia and blood pres-
sure’. After screening the titles in each database, 389 ar-
ticles were retrieved for abstract review. One hundred
thirteen articles were excluded after reviewing the ab-
stracts. Two hundred seventeen articles were excluded
after full document review; the majority of the excluded
articles were unrelated to the objective of this review
and assessed the treatment outcome of different anti-
convulsant and antihypertensive drugs. Finally, 59 arti-
cles (20 from high-income, 30 from middle-income and
3
Y. Berhan and A. Berhan
nine from low-income countries) were eligible for this
review (Fig. 2).7,9,16,21–76
Overall, 21155 women with eclampsia from 26 coun-
tries were included. The majority of the included stud-
ies were hospital-based and case series. Four studies
reported antepartum and intrapartum eclampsia to-
gether.16,44,52,67 Three studies reported only post-
partum eclampsia24,37,72 and nine studies with no data
on type of eclampsia were included for the interest of
other variables (blood pressure and severity symp-
toms).9,29,33,34,54,60,65,68,71 With the exception of four
studies,24,40,63,72 the majority of studies reported that
eclampsia occurred during the antepartum period
(range: 39–94%). Specifically, intrapartum eclampsia
was dominant in the reports by Ekele (67%) and Knonje
(46%)24,72 and post-partum eclampsia was dominant in
reports by Douglas (44%) and Obiechina (46%)
(Table 1).40,63
Figure 3 shows the summary of all the studies that re-
ported type of eclampsia at three levels (antepartum,
intrapartum and post-partum).7,21–24,26–28,30–32,35–43,45–
51,53,55–59,61–64,66,69,70,72–75
Out of 18 488 eclampsia cases,
the proportion of antepartum, intrapartum and post-
partum eclampsia was 59%, 20% and 21%, respectively.
Two of the included studies reported 15% and 16% late
post-partum eclampsia.44,73
Table 2 shows the 26 studies that reported the blood
pressure (BP) pattern of eclamptic women. In seven
studies,9,27,37,45,56,72 including one unpublished, BP was
classified as normotensive (BP of < 140/90 mmHg),
mild-to-moderate hypertension (systolic BP of
140–160 mmHg and/or diastolic BP of 90–110 mmHg),
and severe hypertension (systolic BP of >160 mmHg
and/or diastolic BP of >110 mmHg) with the exception
of one study7 (systolic BP ≥ 170 mmHg). In nine studies
4 © 2015 The Authors
Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology
(category A), the BP of eclamptic mothers was classified
as mild-to-moderate hypertension and severe hyperten-
sion.7,16,23,29,36,51,54,59,67 The other 10 studies classified
the BP of eclamptics as normotensive and hyperten-
sive.25,31,33,38–40,60,68,70,73 Of the 1989 eclamptic women
(category A), 7% had normal blood pressure; 35% had
mild-to-moderate hypertension, and 56% had severe hy-
pertension. In category B, out of 1454 eclamptic
mothers, 48% and 50% were normotensive and hyper-
tensive, respectively. With the exception of one study,36
most severe hypertension cases of eclampsia were re-
ported from low-income and low–middle-income
countries.16,23,27,29,45,51,56,72
As shown in Figure 4,8–11,13,37,40,70,77–81 of 3443 eclamp-
tic mothers, 25% were normotensive, 20% had mild-to-
moderate hypertension, 32% had severe hypertension,
and 21% were hypertensive but not otherwise classified.
In total, about 45% of eclamptic women reviewed had ei-
ther normal BP or mild-to-moderate hypertension.
Sixteen studies reported some symptoms of pre-
eclampsia (Table 3,7,23,28,32,34,35,37–40,59,65,73,75,76 including
the proportion of patients with headache and visual dis-
turbance. Fourteen studies reported presence of epigas-
tric area pain, and five studies reported vomiting. In
another five studies, symptom-free cases were reported.
Because some symptoms overlap and there were differ-
ences in the denominators used across studies (some
studies did not include the presence or absence of some
of the severity symptoms in their report), the percentage
is not proportionally distributed.
Headache was the commonest symptom in all in-
cluded studies (range: 45–80%). The second most com-
monly reported symptom was visual disturbance. Of
2163 eclamptic mothers, 66% and 27% had headache
and visual disturbance, respectively, preceding the
Figure 2 Flow diagram showing se-
lection of studies.
 Systematic review of reports on eclampsia

Table 1 General characteristics of the included studies. Total eclampsia cases = 21 155
Author Country Study year Total Total Antepartum Intrapartum Post-
deliveries eclampsia % % % partum %
Zwart et al.7 Netherlands†† 2004–2006 358 874 222 (0.06) 39.0 33.0 28.0
Alexander et al.9 USA†† 2000–2004 72 004 87 (0.1) ND ND ND
Noor et al.16 Pakistan¶ 2000 3342 53 (1.6) 75.5† NA 24.5
Abd El Aal21 Egypt¶ 1990–2010 ND 1998 79.8 4.6 15.7
Conde-Agudelo et al.22 Colombia¶ 1993–1995 ND 125 57.6 21.6 20.8
Cooray et al.23 Tanzania§ 2007–2008 3267 46 (1.4) 52.0 15.0 33.0
Ekele et al.24 Nigeria¶ 1995–2004 15 318 657 (4.3) 26.3 67.3 6.4
Al-Safi et al.§§25 USA†† 2003–2009 48 498 22 (0.05) NA NA 100.0
Arora et al.26 India¶ 1984–1992 30 942 271 (0.9) 47.2 31.4 21.4
Obed et al.27 Ghana¶ 1991 10 301 134 (1.3) 41.8 44.0 14.2
Onuh et al.28 Nigeria¶ 1995–2002 7865 103 (1.3) 65.0 21.4 13.6
Yaliwal et al.29 India¶ 2001–2010 5387 98 (1.8) ND ND ND
Adenkale et al.30 Nigeria¶ 2005–2010 3952 83 (2.1) 54.2 22.9 22.9
Rugarn et al.31 Sweden†† 1973–1999 53 782 39 (0.07) 41.0 33.0 27.0
Sibai et al.32 USA†† 1977–1980 20 777 67 (0.3) 46.3 16.4 37.3
Urassa et al.33 Tanzania§ 1999–2000 156 030 1077 (0.7) ND ND ND
Ekholm et al.34 Finland†† 1990–1994 324 658 77 (0.02) ND ND ND
Okogbenin et al.35 Nigeria¶ 1999–2004 3095 74 (2.4) 41.8 31.1 27.0
Andersgaaed et al.36 Scandinavia†† 1998–2000 420 309 210 (0.05) 40.0 29.0 31.0
Katze et al.37 USA†† 2000 50 000 53 (0.1) 53.0 36.0 11.0
Kayem et al.§§38 UK†† 2005–2006 779 437 75 (0.01) NA NA 100.0
Knight et al.39 UK†† 2005–2006 ND 214 45.0 19.0 36.0
Douglas et al.40 UK†† 1992 774 436 383 (0.05) 38.0 18.0 44.0
Bhalerao et al.41 India¶ 2008–2010 6100 55 (0.9) 70.9 18.2 10.9
Pal et al.42 India¶ 1999–2008 140 701 5991(4.3) 64.0 13.0 23.0
Liu et al.43 Canada†† 2003–2010 1 910 729 1530 (0.08) 69.6 16.2 14.2
Lubarsky et al.44 USA†† 1977–1992 112 500 334 (0.3) 71.0† NA 29.0
Thapa et al.45 Nepal§ 2006–2007 5240 68 (1.3) 67.7 22.1 10.3
Yakasai et al.46 Nigeria¶ 2008–2009 13 943 688 (4.9) 44.9 35.0 20.1
Abdullah et al.47 Pakistan¶ 2009 2170 45 (2.0) 47.0 20.0 33.0
Ndaboine et al.48 Tanzania§ 2009–2010 5562 76 (1.4) 67.1 22.4 10.5
Adam et al.49 Sudan¶ 2007–2009 8894 45 (0.5)‡‡ 62.0 15.5 11.1
Efetie et al.50 Nigeria¶ 2000–2005 5868 46 (0.8) 58.7 15.2 26.1
Ade-Ojo et al.51 Nigeria¶ 1994–2003 13 682 124 (0.9) 56.5 25.0 18.5
Buowari et al.52 Nigeria¶ 2004–2006 ND 58 81.0† NA 19.0
Berhan et al.‡ Ethiopia§ 2006–2013 12 432 342 (2.8) 45.0 26.0 29.0
Tukur et al.53 Nigeria¶ 2002–2005 2197 207 (9.4) 54.1 32.9 13.0
Adam-Hondegla et al.54 Togo§ 2007–2009 ND 170 ND ND ND
Muganyizi et al.55 Tanzania§ 2008 ND 366 73.8 6.8 19.4
Agida et al.56 Nigeria¶ 2005–2008 4471 59 (1.3)‡‡ 73.9 19.6 2.2
Olatunji et al.57 Nigeria¶ 1988–1997 5423 93 (1.7) 93.5 4.3 2.2
Eke et al.58 Nigeria¶ 2004–2009 13 536 212 (1.6) 75.5 15.1 9.4
Noraihan et al.59 Malaysia¶ 1999 24 000 50 (0.2) 64.0 20.0 16.0
Morikawa et al.60 Japan†† 2005–2009 301 735 225 (0.07) ND ND ND
Adetoro et al.61 Nigeria¶ 1968–1987 183 365 788 (0.4) 41.4 32.7 25.9
Acquaah-Arhin et al.62 Ghana¶ 1998–2000 34 685 543 (1.6) 59.9 24.5 15.6
Obiechina et al.63 Nigeria§ 1991–2000 15 692 102 (0.7) 38.0 14.7 46.0
Okafor et al.64 Nigeria¶ 2001–2005 4857 40 (0.8) 52.6 15.8 31.6
Chames et al.65 USA†† 1996–2001 ND 89 ND ND ND
Matter et al.66 USA†† 1977–1998 141 254 399 (0.3) 53.0 19.0 28.0
Boudaya et al.67 Tunisia¶ ND ND 28 78.7† NA 21.4
Ducarme et al.68 France†† 1996–2006 19 655 16 (0.08) ND ND ND
Lee et al.69 Canada†† 1981–2000 248 013 70 (0.03) 61.0 13.0 26.0
Turck et al.70 French Guiana†† 1996–2008 21 525 69 (0.3) 59.0 6.0 35.0
Ahmad et al.71 Pakistan¶ 2000–2001 3090 96 (3.1) ND ND ND
(Continues)

© 2015 The Authors 5

Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology
Y. Berhan and A. Berhan

Table 1 (Continued)
Author Country Study year Total Total Antepartum Intrapartum Post-
deliveries eclampsia % % % partum %
Konje et al.72 Nigeria¶ 1975–1986 37 313 347 (0.9) 30.6 46.2 23.2
Chhabra et al.§§73 India¶ 1998–2009 39 050 101 (1.0) NA NA 100.0
Leitch et al.74 Scotland†† 1931–1990 320 645 1259 (0.4) 44.0 33.0 23.0
Abate et al.75 Ethiopia§ 1994–1999 35 741 257 (0.7) 61.6 22.7 15.7
Echendu76 Nigeria 2009 6262 57 (0.9) ND ND ND
†Including intrapartum. ‡Unpublished data. §Low-income country. ¶Middle-income country. ††High-income country (WHO 2013). ‡‡Some cases
were reported as unknown. §§Included only post-partum eclampsia cases. NA, not applicable; ND, no data or not defined.

reports of low rate of eclampsia among women with

Figure 3 Distribution of eclampsia by type. n = 18 488.
Studies that reported antepartum and intrapartum
eclampsia together or only post-partum eclampsia were
excluded from this graph.
occurrence of convulsion. Out of 2053 eclamptic
mothers, 25% had epigastric area pain. Out of 759
mothers with eclampsia, 17% had vomiting. Out of
1092 mothers with eclampsia, 25% were asymptomatic
preceding the occurrence of convulsion (Fig. 4).
Discussion
Hypertension has long been recognized as a manifesta-
tion of pre-eclampsia and a warning sign for occurrence
of eclampsia.3 However, because of the marked variation
in blood pressure among eclamptic mothers, the degree
of hypertension may not always predict risk of eclamp-
sia, as this review has demonstrated. Almost half of the
eclamptic women included in this multi-country review
were not in a state of severe hypertension immediately
before seizure. This finding is in line with some previous
investigators’ findings9,10 but contradictory to other
mild pre-eclampsia.13,77
Because of the variable degree of hypertension among
eclamptic women and varying opinions of previous
authors,8–13,82 the question remains: should magnesium
sulfate be administered to all women with pre-
eclampsia?
This controversy persists in the absence of large ran-
domized clinical trials of magnesium sulfate prophylaxis
for women with mild-to-moderate hypertension without
severe symptoms8,14 and because the cause of eclampsia
continues to be poorly understood.68,83 Based on our cur-
rent review, nearly half of the cases of eclampsia oc-
curred in the absence of severe hypertension and
without any warning symptom or sign.37,68,70 In this re-
view, 25% of 1092 eclamptic women were symptom-free
and 25% of 3443 eclamptic women had normal blood
pressure when the seizure occurred. Out of 18 488
eclamptic mothers, 21% experienced post-partum
eclampsia, including a significant number of cases of late
post-partum eclampsia, highlighting the unpredictable
nature of this disorder.
Previous authors have also noted the challenges in
predicting eclampsia.16,37,67 Katz et al. concluded that
eclampsia was not a progression from severe pre-
eclampsia and recommended reevaluation of the US
practice,37 where seizure prophylaxis is recommended
only for severe pre-eclampsia cases.8,78 Furthermore, a
large-scale study in the UK identified that most eclamp-
tic convulsions occurred in hospitals, presumably unher-
alded by warning signs or symptoms that would have
warranted seizure prophylaxis.40
This high number of women experiencing eclampsia
without prodromal symptoms and signs implies that
the traditionally thought natural course of eclampsia
(gestational hypertension to mild pre-eclampsia to se-
vere pre-eclampsia to eclampsia) may not be the reality,
as Katz et al.37 and Douglas et al.40 previously recog-
nized. Turk et al. reported that only 10% of eclampsia

6 © 2015 The Authors

Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology
 Systematic review of reports on eclampsia

Table 2 Pattern of hypertension among women with eclampsia

A.
Author Sample size Normotensive n (%) †Mild-to-moderate ‡Severe Study
hypertension n (%) hypertension % reported from
Agida et al.45 46¶ 1 (2.2) 11 (23.9) 32 (69.6) LMIC
Konje et al.56 347 37 (10.7) 105 (30.3) 205 (59.0) LMIC
Obed et al.72 134 3 (2.2) 48 (35.8) 83 (62.0) LMIC
Thapa et al.27 68 3 (4.4) 34 (50.0) 31 (45.6) LIC
Katze et al.37 53 45(85.0) 1 (2.0) 7 (13.0) HIC
Berhan†† 342 27 (7.9) 151 (44.1) 164(48.0) LIC
Alexander et al.9 87¶ 32 (36.8) 27 (31.0) 11 (12.6) HIC
Cooray et al.23 46 16 (35.0) 30 (65.0) LIC
Zwart et al.7 139 90 (64.8) 49 (35.2)§ HIC
Noor et al.16 53 18 (34.0) 35 (66.0) LMIC
Adama-Hondegla 170 50 (29.4) 120 (70.6) LIC
et al.54
Andersgaaed 210¶ 42 (20.0) 158 (75.0) HIC
et al.36
Noraihan et al.59 50¶ 25 (50.0) 19 (38.0) UMIC
Boudaya et al.67 28 14 (50.0) 14 (50.0) UMIC
Ade-Ojo et al.51 124 31 (25.0) 93 (75.0) LMIC
Yaliwal et al.29 98 41 (41.8) 57 (58.2) LMIC
Total 1995¶ 148 (7.4) 704 (35.3) 1108 (55.5)

B.
Author Sample size Normotensive n (%) Hypertensive (mild to severe)‡‡ n (%)
40
Douglas et al. 294 112 (38.0) 182 (62.0) HIC
Turck et al.70 69 43 (62.0) 26 (37.8) HIC
Urassa et al.33 399 288 (72.2) 111 (27.8) LIC
Al-Safi et al.25 22 17 (77.3) 5 (22.7) HIC
Rugarn et al.31 39 16 (41.0) 23 (59.0) HIC
Chhabra et al.73 101¶ 5 (4.9) 85 (84.2) LMIC
Kayem et al.38 75¶ 28 (37.3) 37 (49.3) HIC
Knight et al.39 214 113 (53.0) 101 (47.0) HIC
Morikawa et al.60 225 75 (33.3) 150 (66.7) HIC
Ducarme et al.68 16 4 (25.0) 12 (75.0) HIC
Total 1454¶ 701 (48.2) 732 (50.3)
†Includes patients with systolic blood pressure of 140–160 mmHg and/or diastolic blood pressure of 90–110 mmHg. ‡Includes patients with sys-
tolic blood pressure of >160 mmHg and/or diastolic blood pressure of >110 mmHg. §Systolic Bp > =170 mmHg. ¶Some cases are not reported
(total = 56). ††Unpublished data. ‡‡The primary studies reported it as hypertensive. LIC, low-income country; LMIC, low–middle-income coun-
try; UMIC, upper middle income country; HIC, high-income country (Source: WHO world health statistics 2013).

cases were preceded by severe pre-eclampsia; and they
also cited other investigators’ finding that 40–60% of
eclampsia manifested without pre-eclamptic pro-
drome.70 This review lends further evidence to that argu-
ment. In the current review, there was a significant
number of eclamptic seizures that appeared to be in di-
rect progression from a state of normotensive and mild
or moderate hypertension.
The argument is, till future investigators develop a
sensitive and specific biomarker, we cannot do much
to prevent the occurrence of eclampsia among asymp-
tomatic and normotensive pregnant women in the
antepartum and post-partum periods. This was also
well noted by Sibai et al. as there are non-preventable
eclampsia cases.84 However, taking into account the
huge number of women with mild-to-moderate hyper-
tension who were found to have eclampsia, should we
continue observing these women without administer-
ing magnesium sulfate prophylaxis?
As the limited knowledge about the pathogenesis is
a major problem for preventing and treating eclamp-
sia,85 lack of consistent clinical symptoms and signs
also seems to continue being the major challenge to
prevent eclampsia. The argument is: unless the avail-
able sign (mild-to-moderate hypertension for the inter-
est of this review) is taken as a warning for eclampsia

© 2015 The Authors 7

Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology
Y. Berhan and A. Berhan
and serious consideration is given for administering
magnesium sulfate, several mothers may be at risk of
eclampsia. Thus, till a multicenter double-blind ran-
domized clinical trial disproves it otherwise, adminis-
tering magnesium sulfate prophylaxis for all women
with evidences of pre-eclampsia seems imperative
and reasonable.
Similar recommendations were issued by several pre-
vious authors.9,37,79–81 For instance, with the restrictive
administration of magnesium sulfate, the study by
Alexander et al. has demonstrated a potential doubling
in the incidence of eclampsia and increased adverse
maternal and neonatal outcomes directly related to ex-
cess seizures among women with mild gestational hy-
pertension who were observed without magnesium
sulfate.9
8 © 2015 The Authors
Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology
Figure 4 Distribution of hypertension
and selected severe symptoms pre-
ceding the onset of convulsion
among women diagnosed with
eclampsia.
Some authors have recommended restrictive use of
magnesium sulfate due to low incidence of eclampsia
in women with mild pre-eclampsia, and due to concerns
that adverse effects of magnesium sulfate could out-
weigh the risk of eclampsia.11,14,18 However, other evi-
dence may not support this conclusion.
First, as several studies9,10,40,70 and this multi-country
article review have shown, the incidence of eclampsia
is not lower among women with mild pre-eclampsia.
Second, the two clinical trials12,13 that have been cited
as evidence to withhold magnesium sulfate prophylaxis
for women with mild pre-eclampsia were done by en-
rolling a small number of patients, which makes the
power too low for a valid conclusion.18 Third, serious
magnesium sulfate toxicity is not as common as antici-
pated by some authors.9,11,14,16,18,45,86–88 However, it
 Systematic review of reports on eclampsia

Table 3 Distribution of selected severity symptoms in women with eclampsia

Author Eclampsia Headache Visual disturbance Epigastric pain Vomiting Symptom free
cases % % % % %
Katze et al.37 53 64.0 30.0 ND NR NA
Cooray et al.23 46 80.0 46.0 20.0 NR NA
Chames et al.65 89 70.0 30.0 12.0 NA NA
Ekholm et al.34 77 66.0 19.0 23.0 8.0 NA
Sibai et al.32 67 82.5 44.4 19.0 NA NA
Okogbenin et al.35 74 74.3 21.6 14.9 10.8 NA
Knight et al.39 214 56.0 23.0 17.0 NA NA
Chhabra et al.73 101 57.4 6.9 3.9 NA 20.6
Kayem et al.38 75 45.3 17.0 16.0 NA NA
Noraihan et al.59 50 66.0 24.0 36.0 28.0 14.0
Douglas et al.40 383 50.0 19.0 19.0 NA 41.0
Zwart et al.7 222 69.0 41.0 45.0 28.0 10.8
Onuh et al.28 103 82.4 10.6 7.0 NA NA
Abate et al.75 216 83.8 41.6 38.4 NA NA
Echendu76 57 74.0 65.0 NA NA NA
Berhan† 342 74.9 42.1 34.9 11.3 19.0
†Unpublished data. NA, Not applicable; ND, No data; NR, Not reported.

should be noted that a significant reduction in fetal um-
bilical artery and middle cerebral artery pulsatility index
was seen in 24 women with mild pre-eclampsia treated
with magnesium sulfate.89
Fourth, the complications due to eclampsia may be
more catastrophic to the mother and the baby than com-
plications that may be attributed to magnesium sulfate
toxicity. Eclampsia accounts for about 63 000 maternal
deaths worldwide; 99% of these deaths occurred in de-
veloping countries, mainly because of late reporting
and late initiation of seizure prophylaxis.90 Two large
randomized trials have shown very few life-threatening
side-effects of magnesium sulfate, which were manage-
able by discontinuing the drug or by administering cal-
cium gluconate.86,87
While serious magnesium sulfate toxicity does rarely
occur, such toxicity can be prevented and treated and
carries less long-term morbidity and mortality risk than
eclampsia. Adamu et al. noted that maternal outcome
was poor even after introduction of magnesium sulfate
for eclamptic women.91 As a concluding remark, they
said, ‘Interventions for reduction of maternal and perina-
tal mortality must emphasize strategies that prevent the
occurrence of eclampsia’, a view which is shared by the
authors of this review.
From the perspective of cost-effectiveness, the analysis
from the Magpie Trial concluded that magnesium sulfate
for pre-eclampsia costs less and prevents more eclamp-
sia in low gross national income (GNI) countries than
in high GNI countries.92
This review has multiple limitations. Almost all the in-
cluded studies were based in one or a few hospitals,
which may not be representative of the general popula-
tion in the study area or the cited country. The descrip-
tive and case series nature of all the included studies
limited the possibility of conducting further analysis.
The inconsistent classification of hypertension by some
authors has probably underestimated the proportion of
eclamptic women with mild-to-moderate hypertension
or severe hypertension. Because of the retrospective na-
ture of the included studies, some of the eclamptic
women might have been misclassified due to inaccessi-
bility immediately preceding the onset of seizure. As
eclampsia is characterized by generalized tonic–clonic
seizure or coma, the severe symptoms are liable to be for-
gotten by the patients themselves or might not be re-
ported by relatives or accompaniers.
In conclusion, in this rigorous review, antepartum
eclampsia accounted for nearly three-fifths of all eclamp-
sia cases, and women with intrapartum and post-
partum eclampsia were proportional. One-fourth of the
eclamptic women were normotensive; one-fifth had
mild-to-moderate hypertension; and nearly one-third
had severe hypertension. Headache was the most com-
mon symptom in all eclamptic women. Because of little
clinical trial evidence that objects to universal magne-
sium sulfate prophylaxis, the high number of women
with mild pre-eclampsia or without warning symptoms
who developed eclampsia, and the relatively low and
manageable severe magnesium sulfate toxicity, it is im-
perative to continue administering magnesium sulfate
prophylaxis to women with mild pre-eclampsia till a
convincing randomized trial result contradicts or con-
firms this strategy.

© 2015 The Authors 9

Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology
Y. Berhan and A. Berhan
Disclosure
The authors would like to declare that there is no conflict
of interest. There was no financial support for this work.
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