Jurnal CGH

7/26/2019 Jurnal CGH

1/12

Should magnesium sulfate be administered to women withmild pre-eclampsia? A systematic review of published reportson 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 eclampticseizure based on the current published work.

Material and Methods: A comprehensive computer-based publication search was conducted in the AfricanJournals 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 inwomen with eclampsia.

Results: A total of 59 publications were eligible for this review. Overall, 21149 eclamptic women from 26countries were included for the interest of one or more of the selected variables. Out of 18488 eclampticwomen, 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 unclassied. 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 functionderangement, this review has revealed that a signicant number of eclamptic women had either normal bloodpressure or mild-to-moderate hypertension immediately before seizure. The ndings are apparently in supportof initiating magnesium sulfate prophylaxis to all women with mild pre-eclampsia.

Key words: descriptive studies, eclampsia, magnesium sulfate, mild pre-eclampsia, systematic publicationreview.

Introduction

Eclampsia is diagnosed in pregnant or post-partumwomen with the onset of generalized tonicclonic 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

unfolding of the 19th century3 and different treatmentmodalities were attempted,4 it is still not possible tocompletely prevent its occurrence, even in the best set-ting.5 As a result, eclampsia remains one of the leadingcauses of maternal and perinatal mortality worldwide,

with the majorityof thedisease burden in the developingworld.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: [email protected]

2015 The AuthorsJournal of Obstetrics and Gynaecology Research 2015 Japan Society of Obstetrics and Gynecology

831

doi:10.1111/jog.12697 J. Obstet. Gynaecol. Res. Vol. 41, No. 6: 831842, June 2015


2/12

has declined over the past half century due to improvedantenatal care and early initiation of prevention andtreatment.7 The incidence of eclampsia in high-incomecountries is now signicantly 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 worldto prevent and control eclampsia, particularly inwomen with severe pre-eclampsia.1,7 However, the rec-ommendation of magnesium sulfate to women withmild pre-eclampsia is remains controversial. Accordingto the American College of Obstetricians and Gynecol-ogists (ACOG) 2013 task force recommendation, mag-nesium sulfate should not be given universally forthe prevention of eclampsia in women with mild pre-eclampsia evidenced by systolic blood pressure (BP)of 140160mmHg, a diastolic BP of


3/12

Methods

Study design and area of interest

A systematic review of descriptive publications oneclampsia was conducted using online available articlesfrom any part of the world. The incidence of eclampsia

between 1998 and 2013 in select countries was analyzedfor trends. Blood pressure pattern of eclamptic women

before the occurrence of seizure was the main interestof 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, intrapartumand post-partum periods. The search was furtherstrengthened by searching the reference lists of re-trieved articles that reported types of blood pressure(mild range, moderate range, severe range), or relevantsymptoms during the study period. The search termswere:eclampsia,pre-eclampsia,eclampsia hyperten-sion, eclampsia pre-eclampsia, eclampsia gestationalhypertension, eclampsia pre-eclampsia magnesiumsulfate, magnesium sulfate, eclampsia pre-eclampsiaseverity 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 termswere combined alternatively with the Boolean logic(AND, OR and NOT).

Inclusion criteria and study selection

The predetermined inclusion criteria were: (i) studies oneclampsia that assessed the blood pressure or severitysymptoms or type of eclampsia; and (ii) studies thatwere published in English and conducted between1930 and 2013. Study selection was conducted in two

stages. First the abstracts of all the retrieved reports werereviewed and then groupedas eligible for full documentreviewor ineligible for full document review. Second,all the reports grouped as eligible for full document re-view were reviewed in detail and grouped as eligiblefor this revieworineligible for this review.

From the included studies, the following informationwas abstracted: name of the rst author, country study

conducted, study period, total eclampsia cases includedin the study, mean maternal age, type of eclampsia, dia-stolic and systolic blood pressure, and selected severitysymptoms of hypertension disorders (headache, blurredvision, epigastric area pain, vomiting).

Operational denitionsMild-to-moderate hypertension during pregnancy orduring puerperium was dened as a systolic blood pres-sure of 140160 mmHg and/or diastolic blood pressureof 90110 mmHg immediately before seizure. Severehypertension was considered when the systolic bloodpressure was 160 mmHg and/or diastolic blood pres-sure was 110mmHg.20 Presence of hypertension withproteinuria after 20 weeks of gestation denes pre-

eclampsia. Severe pre-eclampsia was dened as severehypertension or mild-to-moderate hypertension with se-vere symptoms and signicant proteinuria (proteinuria

>300 mg in 24 h urine or +2 and above in the dipsticktest). Mild pre-eclampsia was dened as mild-to-moderate hypertension without severe symptoms andwithout signicant proteinuria. In this article, mild-to-moderate hypertension and mild pre-eclampsia are usedinterchangeably.

Data presentation

Data are presented in tables and summarized in gures.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 werefound from the same country during 19982013, the de-nominators (total deliveries) and numerators (total casesof eclampsia) were added before the incidence ofeclampsia was estimated for that specic country.

Results

The database search retrieved 3424 reports for thesearch term pre-eclampsia, eclampsia and blood pres-sure. After screening the titles in each database, 389 ar-

ticles were retrieved for abstract review. One hundredthirteen articles were excluded after reviewing the ab-stracts. Two hundred seventeen articles were excludedafter full document review; the majority of the excludedarticles were unrelated to the objective of this reviewand assessed the treatment outcome of different anti-convulsant and antihypertensive drugs. Finally, 59 arti-cles (20 from high-income, 30 from middle-income and

Systematic review of reports on eclampsia


833


4/12

nine from low-income countries) were eligible for thisreview (Fig. 2).7,9,16,2176

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 studiesreported antepartum and intrapartum eclampsia to-

gether.16,44,52,67

Three studies reported only post-partum eclampsia24,37,72 and nine studies with no dataon type of eclampsia were included for the interest ofother variables (blood pressure and severity symp-toms).9,29,33,34,54,60,65,68,71 With the exception of fourstudies,24,40,63,72 the majority of studies reported thateclampsia occurred during the antepartum period(range: 3994%). Specically, intrapartum eclampsiawas dominant in the reports by Ekele (67%) and Knonje(46%)24,72 and post-partum eclampsia was dominant inreports 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).7,2124,2628,3032,3543,45

51,53,5559,6164,66,69,70,7275 Out of 18488 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% latepost-partum eclampsia.44,73

Table 2 shows the 26 studies that reported the bloodpressure (BP) pattern of eclamptic women. In sevenstudies,9,27,37,45,56,72 including one unpublished, BP wasclassied as normotensive (BP of< 140/90mmHg),mild-to-moderate hypertension (systolic BP of

140160 mmHg and/or diastolic BP of 90110mmHg),and severe hypertension (systolic BP of >160 mmHgand/or diastolic BP of>110mmHg) with the exceptionof one study7 (systolic BP 170 mmHg). In nine studies

(category A), the BP of eclamptic mothers was classiedas mild-to-moderate hypertension and severe hyperten-sion.7,16,23,29,36,51,54,59,67 The other 10 studies classiedthe BP of eclamptics as normotensive and hyperten-sive.25,31,33,3840,60,68,70,73 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 eclampticmothers, 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 lowmiddle-incomecountries.16,23,27,29,45,51,56,72

As shown in Figure4,811,13,37,40,70,7781 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 classied.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 3,7,23,28,32,34,35,3740,59,65,73,75,76 includingthe proportion of patients with headache and visual dis-turbance. Fourteen studies reported presence of epigas-tric area pain, and ve studies reported vomiting. Inanotherve studies, symptom-free cases were reported.Because some symptoms overlap and there were differ-ences in the denominators used across studies (somestudies did not include the presence or absence of someof the severity symptoms in their report), the percentageis not proportionally distributed.

Headache was the commonest symptom in all in-

cluded studies (range: 4580%). The second most com-monly reported symptom was visual disturbance. Of2163 eclamptic mothers, 66% and 27% had headacheand visual disturbance, respectively, preceding the

Figure 2 Flow diagram showing se-lection of studies.

Y. Berhan and A. Berhan


834


5/12

Table 1 General characteristics of the included studies. Total eclampsia cases = 21155

Author Country Study year Totaldeliveries

Totaleclampsia %

Antepartum%

Intrapartum%

Post-partum %

Zwartet al.7 Netherlands 20042006 358 874 222 (0.06) 39.0 33.0 28.0Alexanderet al.9 USA 20002004 72 004 87 (0.1) ND ND NDNooret al.16 Pakistan 2000 3342 53 (1.6) 75.5 NA 24.5

Abd El Aal21

Egypt 19902010 ND 1998 79.8 4.6 15.7Conde-Agudeloet al.22 Colombia 19931995 ND 125 57.6 21.6 20.8Coorayet al.23 Tanzania 20072008 3267 46 (1.4) 52.0 15.0 33.0Ekeleet al.24 Nigeria 19952004 15 318 657 (4.3) 26.3 67.3 6.4Al-Saet al.25 USA 20032009 48 498 22 (0.05) NA NA 100.0Aroraet al.26 India 19841992 30 942 271 (0.9) 47.2 31.4 21.4Obedet al.27 Ghana 1991 10 301 134 (1.3) 41.8 44.0 14.2Onuhet al.28 Nigeria 19952002 7865 103 (1.3) 65.0 21.4 13.6Yaliwalet al.29 India 20012010 5387 98 (1.8) ND ND NDAdenkaleet al.30 Nigeria 20052010 3952 83 (2.1) 54.2 22.9 22.9Rugarnet al.31 Sweden 19731999 53 782 39 (0.07) 41.0 33.0 27.0Sibaiet al.32 USA 19771980 20 777 67 (0.3) 46.3 16.4 37.3Urassaet al.33 Tanzania 19992000 156 030 1077 (0.7) ND ND NDEkholmet al.34 Finland 19901994 324 658 77 (0.02) ND ND NDOkogbeninet al.35 Nigeria 19992004 3095 74 (2.4) 41.8 31.1 27.0

Andersgaaedet al.36

Scandinavia 19982000 420 309 210 (0.05) 40.0 29.0 31.0Katzeet al.37 USA 2000 50 000 53 (0.1) 53.0 36.0 11.0Kayemet al.38 UK 20052006 779 437 75 (0.01) NA NA 100.0Knightet al.39 UK 20052006 ND 214 45.0 19.0 36.0Douglaset al.40 UK 1992 774 436 383 (0.05) 38.0 18.0 44.0Bhaleraoet al.41 India 20082010 6100 55 (0.9) 70.9 18.2 10.9Palet al.42 India 19992008 140 701 5991(4.3) 64.0 13.0 23.0Liuet al.43 Canada 20032010 1 910 729 1530 (0.08) 69.6 16.2 14.2Lubarskyet al.44 USA 19771992 112 500 334 (0.3) 71.0 NA 29.0Thapaet al.45 Nepal 20062007 5240 68 (1.3) 67.7 22.1 10.3Yakasaiet al.46 Nigeria 20082009 13 943 688 (4.9) 44.9 35.0 20.1Abdullahet al.47 Pakistan 2009 2170 45 (2.0) 47.0 20.0 33.0Ndaboineet al.48 Tanzania 20092010 5562 76 (1.4) 67.1 22.4 10.5Adamet al.49 Sudan 20072009 8894 45 (0.5) 62.0 15.5 11.1Efetieet al.50 Nigeria 20002005 5868 46 (0.8) 58.7 15.2 26.1

Ade-Ojoet al.51 Nigeria 19942003 13 682 124 (0.9) 56.5 25.0 18.5Buowariet al.52 Nigeria 20042006 ND 58 81.0 NA 19.0Berhanet al. Ethiopia 20062013 12 432 342 (2.8) 45.0 26.0 29.0Tukuret al.53 Nigeria 20022005 2197 207 (9.4) 54.1 32.9 13.0Adam-Hondeglaet al.54 Togo 20072009 ND 170 ND ND NDMuganyiziet al.55 Tanzania 2008 ND 366 73.8 6.8 19.4Agidaet al.56 Nigeria 20052008 4471 59 (1.3) 73.9 19.6 2.2Olatunjiet al.57 Nigeria 19881997 5423 93 (1.7) 93.5 4.3 2.2Ekeet al.58 Nigeria 20042009 13 536 212 (1.6) 75.5 15.1 9.4Noraihanet al.59 Malaysia 1999 24 000 50 (0.2) 64.0 20.0 16.0Morikawaet al.60 Japan 20052009 301 735 225 (0.07) ND ND NDAdetoroet al.61 Nigeria 19681987 183 365 788 (0.4) 41.4 32.7 25.9Acquaah-Arhinet al.62 Ghana 19982000 34 685 543 (1.6) 59.9 24.5 15.6Obiechinaet al.63 Nigeria 19912000 15 692 102 (0.7) 38.0 14.7 46.0Okaforet al.64 Nigeria 20012005 4857 40 (0.8) 52.6 15.8 31.6

Chameset al.65 USA 19962001 ND 89 ND ND NDMatteret al.66 USA 19771998 141 254 399 (0.3) 53.0 19.0 28.0Boudayaet al.67 Tunisia ND ND 28 78.7 NA 21.4Ducarmeet al.68 France 19962006 19 655 16 (0.08) ND ND NDLeeet al.69 Canada 19812000 248 013 70 (0.03) 61.0 13.0 26.0Turcket al.70 French Guiana 19962008 21 525 69 (0.3) 59.0 6.0 35.0Ahmadet al.71 Pakistan 20002001 3090 96 (3.1) ND ND ND

(Continues)



835


6/12

occurrence of convulsion. Out of 2053 eclampticmothers, 25% had epigastric area pain. Out of 759mothers with eclampsia, 17% had vomiting. Out of1092 mothers with eclampsia, 25% were asymptomaticpreceding 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 variationin blood pressure among eclamptic mothers, the degreeof hypertension may not always predict risk of eclamp-sia, as this review has demonstrated. Almost half of theeclamptic women included in this multi-country reviewwere not in a state of severe hypertension immediately

before seizure. This nding is in line with some previousinvestigators ndings9,10 but contradictory to other

reports of low rate of eclampsia among women withmild pre-eclampsia.13,77

Because of the variable degree of hypertension among

eclamptic women and varying opinions of previousauthors,813,82 the question remains: should magnesiumsulfate be administered to all women with pre-eclampsia?

This controversy persists in the absence of large ran-domized clinical trials of magnesium sulfate prophylaxisfor women with mild-to-moderate hypertension withoutsevere symptoms8,14 and because the cause of eclampsiacontinues 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 andwithout any warning symptom or sign.37,68,70 In this re-

view, 25% of 1092 eclamptic women were symptom-freeand 25% of 3443 eclamptic women had normal bloodpressure when the seizure occurred. Out of 18 488eclamptic mothers, 21% experienced post-partum

eclampsia, including a signicant number of cases of latepost-partum eclampsia, highlighting the unpredictablenature of this disorder.

Previous authors have also noted the challenges inpredicting eclampsia.16,37,67 Katz et al. concluded thateclampsia was not a progression from severe pre-eclampsia and recommended reevaluation of the USpractice,37 where seizure prophylaxis is recommended

only for severe pre-eclampsia cases.8,78 Furthermore, alarge-scale study in the UK identied that most eclamp-tic convulsions occurred in hospitals, presumably unher-alded by warning signs or symptoms that would havewarranted seizure prophylaxis.40

This high number of women experiencing eclampsiawithout prodromal symptoms and signs implies thatthe 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 etal. reported that only 10% of eclampsia

Table 1 (Continued)

Author Country Study year Totaldeliveries

Totaleclampsia %

Antepartum%

Intrapartum%

Post-partum %

Konjeet al.72 Nigeria 19751986 37 313 347 (0.9) 30.6 46.2 23.2Chhabra etal.73 India 19982009 39 050 101 (1.0) NA NA 100.0Leitchet al.74 Scotland 19311990 320 645 1259 (0.4) 44.0 33.0 23.0Abateet al.75 Ethiopia 19941999 35 741 257 (0.7) 61.6 22.7 15.7Echendu76 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 caseswere reported as unknown. Included only post-partum eclampsia cases. NA, not applicable; ND, no data or not dened.

Figure 3 Distribution of eclampsia by type. n =18488.Studies that reported antepartum and intrapartumeclampsia together or only post-partum eclampsia wereexcluded from this graph.



836


7/12

cases were preceded by severe pre-eclampsia; and theyalso cited other investigators nding that 4060% ofeclampsia manifested without pre-eclamptic pro-drome.70 This review lends further evidence to that argu-ment. In the current review, there was a signicant

number of eclamptic seizures that appeared to be in di-rect progression from a state of normotensive and mildor moderate hypertension.

The argument is, till future investigators develop asensitive and specic biomarker, we cannot do muchto prevent the occurrence of eclampsia among asymp-tomatic and normotensive pregnant women in theantepartum and post-partum periods. This was also

well noted by Sibai et al. as there are non-preventableeclampsia cases.84 However, taking into account thehuge number of women with mild-to-moderate hyper-tension who were found to have eclampsia, should wecontinue observing these women without administer-

ing magnesium sulfate prophylaxis?As the limited knowledge about the pathogenesis isa major problem for preventing and treating eclamp-sia,85 lack of consistent clinical symptoms and signsalso seems to continue being the major challenge toprevent 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

Table 2 Pattern of hypertension among women with eclampsia

A.

Author Sample size Normotensiven(%) Mild-to-moderatehypertensionn (%)

Severehypertension %

Studyreported from

Agidaet al.45 46 1 (2.2) 11 (23.9) 32 (69.6) LMICKonjeet al.56 347 37 (10.7) 105 (30.3) 205 (59.0) LMIC

Obedet al.72

134 3 (2.2) 48 (35.8) 83 (62.0) LMICThapaet al.27 68 3 (4.4) 34 (50.0) 31 (45.6) LICKatzeet al.37 53 45(85.0) 1 (2.0) 7 (13.0) HICBerhan 342 27 (7.9) 151 (44.1) 164(48.0) LICAlexanderet al.9 87 32 (36.8) 27 (31.0) 11 (12.6) HICCoorayet al.23 46 16 (35.0) 30 (65.0) LICZwartet al.7 139 90 (64.8) 49 (35.2) HICNooret al.16 53 18 (34.0) 35 (66.0) LMICAdama-Hondeglaet al.54

170 50 (29.4) 120 (70.6) LIC

Andersgaaedet al.36

210 42 (20.0) 158 (75.0) HIC

Noraihanet al.59 50 25 (50.0) 19 (38.0) UMICBoudayaet al.67 28 14 (50.0) 14 (50.0) UMICAde-Ojoet al.51 124 31 (25.0) 93 (75.0) LMIC

Yaliwalet al.29 98 41 (41.8) 57 (58.2) LMICTotal 1995 148 (7.4) 704 (35.3) 1108 (55.5)

B.

Author Sample size Normotensiven(%) Hypertensive (mild to severe)n(%)

Douglaset al.40 294 112 (38.0) 182 (62.0) HICTurcket al.70 69 43 (62.0) 26 (37.8) HICUrassaet al.33 399 288 (72.2) 111 (27.8) LICAl-Saet al.25 22 17 (77.3) 5 (22.7) HICRugarnet al.31 39 16 (41.0) 23 (59.0) HICChhabraet al.73 101 5 (4.9) 85 (84.2) LMICKayemet al.38 75 28 (37.3) 37 (49.3) HICKnightet al.39 214 113 (53.0) 101 (47.0) HICMorikawaet al.60 225 75 (33.3) 150 (66.7) HICDucarmeet al.68 16 4 (25.0) 12 (75.0) HICTotal 1454 701 (48.2) 732 (50.3)

Includes patients with systolic blood pressure of 140160 mmHg and/or diastolic blood pressure of 90110mmHg.Includes patients with sys-tolic blood pressure of>160 mmHg and/or diastolic blood pressure of>110mmHg. 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, lowmiddle-income coun-try; UMIC, upper middle income country; HIC, high-income country (Source: WHO world health statistics 2013).



837


8/12

and serious consideration is given for administeringmagnesium sulfate, several mothers may be at risk ofeclampsia. Thus, till a multicenter double-blind ran-domized clinical trial disproves it otherwise, adminis-tering magnesium sulfate prophylaxis for all womenwith evidences of pre-eclampsia seems imperativeand reasonable.

Similar recommendations were issued by several pre-vious authors.9,37,7981 For instance, with the restrictiveadministration of magnesium sulfate, the study byAlexander et al.has demonstrated a potential doublingin the incidence of eclampsia and increased adversematernal and neonatal outcomes directly related to ex-cess seizures among women with mild gestational hy-pertension who were observed without magnesiumsulfate.9

Some authors have recommended restrictive use ofmagnesium sulfate due to low incidence of eclampsiain women with mild pre-eclampsia, and due to concernsthat 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-countryarticle review have shown, the incidence of eclampsiais not lower among women with mild pre-eclampsia.Second, the two clinical trials12,13 that have been citedas evidence to withhold magnesium sulfate prophylaxisfor women with mild pre-eclampsia were done by en-rolling a small number of patients, which makes thepower too low for a valid conclusion.18 Third, seriousmagnesium sulfate toxicity is not as common as antici-pated by some authors.9,11,14,16,18,45,8688 However, it

Figure 4 Distribution of hypertensionand selected severe symptoms pre-ceding the onset of convulsionamong women diagnosed witheclampsia.



838


9/12

should be noted that a signicant reduction in fetal um-bilical artery and middle cerebral artery pulsatility indexwas seen in 24 women with mild pre-eclampsia treatedwith magnesium sulfate.89

Fourth, the complications due to eclampsia may bemore catastrophic to the mother and the baby than com-plications that may be attributed to magnesium sulfatetoxicity. Eclampsia accounts for about 63 000 maternaldeaths worldwide; 99% of these deaths occurred in de-veloping countries, mainly because of late reportingand late initiation of seizure prophylaxis.90 Two largerandomized 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 rarelyoccur, such toxicity can be prevented and treated andcarries less long-term morbidity and mortality risk thaneclampsia. Adamu et al. noted that maternal outcomewas poor even after introduction of magnesium sulfatefor eclamptic women.91 As a concluding remark, theysaid, Interventions for reduction of maternal and perina-tal mortality must emphasize strategies that prevent theoccurrence of eclampsia, a view which is shared by the

authors of this review.From the perspective of cost-effectiveness, the analysisfromthe Magpie Trial concluded that magnesium sulfatefor pre-eclampsia costs less and prevents more eclamp-sia in low gross national income (GNI) countries thanin 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 studieslimited the possibility of conducting further analysis.The inconsistent classication of hypertension by someauthors has probably underestimated the proportion ofeclamptic women with mild-to-moderate hypertensionor severe hypertension. Because of the retrospective na-ture of the included studies, some of the eclampticwomen might have been misclassied due to inaccessi-

bility immediately preceding the onset of seizure. Aseclampsia is characterized by generalized tonicclonic

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, antepartumeclampsia accounted for nearly three-fths of all eclamp-sia cases, and women with intrapartum and post-partum eclampsia were proportional. One-fourth of theeclamptic women were normotensive; one-fth hadmild-to-moderate hypertension; and nearly one-thirdhad severe hypertension. Headache was the most com-mon symptom in all eclamptic women. Because of littleclinical trial evidence that objects to universal magne-

sium sulfate prophylaxis, the high number of womenwith mild pre-eclampsia or without warning symptoms

who developed eclampsia, and the relatively low andmanageable severe magnesium sulfate toxicity, it is im-perative to continue administering magnesium sulfateprophylaxis to women with mild pre-eclampsia till aconvincing randomized trial result contradicts or con-rms this strategy.

Table 3 Distribution of selected severity symptoms in women with eclampsia

Author Eclampsiacases

Headache%

Visual disturbance%

Epigastric pain%

Vomiting%

Symptom free%

Katzeet al.37 53 64.0 30.0 ND NR NACoorayet al.23 46 80.0 46.0 20.0 NR NAChameset al.65 89 70.0 30.0 12.0 NA NAEkholmet al.34 77 66.0 19.0 23.0 8.0 NASibaiet al.32 67 82.5 44.4 19.0 NA NAOkogbeninet al.35 74 74.3 21.6 14.9 10.8 NAKnightet al.39 214 56.0 23.0 17.0 NA NAChhabraet al.73 101 57.4 6.9 3.9 NA 20.6Kayemet al.38 75 45.3 17.0 16.0 NA NANoraihanet al.59 50 66.0 24.0 36.0 28.0 14.0Douglaset al.40 383 50.0 19.0 19.0 NA 41.0Zwartet al.7 222 69.0 41.0 45.0 28.0 10.8Onuhet al.28 103 82.4 10.6 7.0 NA NAAbateet al.75 216 83.8 41.6 38.4 NA NAEchendu76 57 74.0 65.0 NA NA NABerhan 342 74.9 42.1 34.9 11.3 19.0

Unpublished data. NA, Not applicable; ND, No data; NR, Not reported.



839


10/12

Disclosure

The authors would like to declare that there is no conictof interest. There was no nancial support for this work.

References

1. World Health Organization (WHO). WHO recommendationfor prevention of preeclampsia and eclampsia. 2011. Geneva.[Cited July 2014.] Available from URL: www.who.int/reproductivehealth/publications/maternal_perinatal_health/

2. Stoppler MC, Davis CP. Eclampsia. [Cited July 2014.] Availablefrom URL:http://www.emedicinehealth.com/eclampsia/

3. Bell MJ. A historical overview of preeclampsia-eclampsia.A JObstet Gynecol Neonatal Nurs2010;39: 510518.

4. Duley L, Henderson-Smart D. Magnesium sulphate versus di-azepam for eclampsia. Cochrane Database Syst Rev 2003; 4:CD000127.

5. Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and re-gional estimates of preeclampsia and eclampsia: A systematicreview.Eur J Obstet Gynecol Reprod Biol2013;170: 17.

6. Duley L. The global impact of pre-eclampsia and eclampsia.Semin Perinatol2009;33: 130137.

7. Zwart JJ, Richters A, Ory F, de Vries JI, Bloemenkamp KW, vanRoosmalen J. Eclampsia in the Netherlands. Obstet Gynecol2008;112: 820827.

8. The American College of Obstetricians and Gynecologists(ACOG). Hypertension in pregnancy 2013. [Cited July 2014.]Available from URL:http://www.acog.org/Resources_And_Publications/

9. Alexander JM, McIntire DD, Leveno KJ, Cunningham FG. Se-lective magnesium sulfate prophylaxis for the prevention ofeclampsia in women with gestational hypertension. ObstetGynecol2006;108: 826832.

10. Foong SC, Pollard JK. Eclampsia in Southern Alberta: Is there arole for seizure prophylaxis in all women with gestational hy-pertension?J Obstet Gynaecol Can2003;25: 385389.

11. Rozenberg P. Magnesium sulfate for the management of pre-eclampsia.Gynecol Obstet Fertil2006;34: 5459.

12. Livingston JC, Livingston LW, Ramsey R, Mabie BC, SibaiBM. Magnesium sulfate in women with mild preeclampsia:A randomized controlled trial. Obstet Gynecol 2003; 101:217220.

13. Witlin AG, Friedman SA, Sibai BM. The effect of magnesiumsulfate therapy on the duration of labor in women with mildpreeclampsia at term: A randomized, double blind, placebo-controlled trial.Am J Obstet Gynecol1997;176: 623627.

14. Sibai BM. Magnesium sulfate prophylaxis in preeclampsia:Evidence from randomized trials. Clin Obstet Gynecol 2005;

48: 478488.15. Scott JR. Magnesium sulfate for mild preeclampsia. ObstetGynecol2003;101: 213.

16. Noor S, Halimi M, Faiz NR, Gull F, Akbar N. Magnesium sul-fate in the prophylaxis and treatment of eclampsia. J AyubMed Coll Abbottabad2004;16: 5054.

17. Lim K-H, Steinberg G, Ramus RM. Preeclampsia. Updated 24February 2014. [Cited July 2014.] Available from URL:http://emedicine.medscape.com/

18. Sibai BM. Magnesium sulfate prophylaxis in preeclampsia:Lessons learned from recent trials. Am J Obstet Gynecol2004; 190: 15201526.

19. RoyalCollege of Obstetricians andGynecologists.Guideline No.10 (A). The management of severe preeclampsia/eclampsia,2006. [Cited July 2014.] Available from URL: http://www.neonatalformulary.com/pdfs/uk_guidelines/

20. Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy

for mild to moderate hypertension during pregnancy. CochraneDatabase Syst Rev 2014; CD002252. doi: 10.1002/14651858.CD002252.pub3.

21. Abd El Aal DE, Shahin AY. Management of eclampsia atAssiut University Hospital, Egypt. Int J Gynaecol Obstet2012; 116: 232236.

22. Conde-Agudelo A, Kafury-Goeta AC. Case-control study ofrisk factors for complicated eclampsia. Obstet Gynecol 1997;90: 172175.

23. Cooray SD, Edmonds SM, Tong S, Samarasekera SP,Whitehead CL. Characterization of symptoms immediatelypreceding eclampsia.Obstet Gynecol2011;118: 995999.

24. Ekele BA, Bello SO, Adamu AN. Clusters of eclampsia in a Ni-gerian teaching hospital.Int J Gynaecol Obstet2007;96: 6266.

25. Al-Sa Z, Imudia AN, Filetti LC, Hobson DT, Bahado-SinghRO, Awonuga AO. Delayed postpartum preeclampsia andeclampsia: Demographics, clinical course, and complications.Obstet Gynecol2011;118: 11021107.

26. Arora R, Ganguli RP, Swain S, Oumachigui A, Rajaram P. De-terminants of maternal mortality in eclampsia in India. AustNZ 3 Obstet Gynaecol1994;34: 537539.

27. Obed SA, Wilson JB, Elkins TE. Eclampsia: 134 consecutivecases.Int J Gynaecol Obstet1994;45: 97103.

28. Onuh SO, Aisien AO. Maternal and fetal outcome ineclamptic patients in Benin City, Nigeria. J Obstet Gynaecol2004; 24: 765768.

29. Yaliwal RG, Jaju PB, Vanishree M. Eclampsia and perinatal out-come: A retrospective study in a teaching hospital.J Clin DiagnRes2011;5: 10561059.

30. Adekanle DA, Akinbile TO.Eclampsiaand pregnancy outcomeat Lautech Teaching Hospital, Osogbo, South West, Nigeria.Clin Mother Child Health2012;9. doi: 10.4303/cmch/C120301.

31. Rugarn O, Carling Moen S, Berg G. Eclampsia at a tertiary hos-pital 1973-99.Acta Obstet Gynecol Scand2004;83: 240245.

32. Sibai BM, McCubbin JH, Anderson GD, Lipshitz J, Dilts PV Jr..Eclampsia I. Observations from 67 recent cases. Obstet Gynecol1981;58: 609613.

33. Urassa DP, Carlstedt A, Nystrm L, Massawe SN, LindmarkG. Eclampsia in Dar es Salaam, Tanzania: Incidence, out-come, and the role of antenatal care. Acta Obstet GynecolScand 2006; 85: 571578.

34. Ekholm E, Salmi MM, Erkkola R. Eclampsia in Finland in1990-1994.Acta Obstet Gynecol Scand1999;78: 877882.

35. Okogbenin SA, Eigbefoh JO, Omorogbe F, Okogbo F, Okonta

PI, Ohihoin AG. Eclampsia in Irrua Specialist Teaching Hospi-tal: A ve-year review.Niger J Clin Pract2010;13: 149153.36. Andersgaard AB, Herbst A, Johansen M et al. Eclampsia in

Scandinavia: Incidence, substandard care, and potentially pre-ventable cases.Acta Obstet Gynecol Scand2006;85: 929936.

37. Katz VL, Farmer R, Kuller JA. Preeclampsia into eclampsia: To-ward a newparadigm.Am J Obstet Gynecol 2000; 182: 13891396.

38. Kayem G, Kurinczuk JJ, Spark P, Brocklehurst P, Knight M,UK Obstetric Surveillance System (UKOSS). Maternal and



840
http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://www.neonatalformulary.com/pdfs/uk_guidelines/http://www.neonatalformulary.com/pdfs/uk_guidelines/http://www.neonatalformulary.com/pdfs/uk_guidelines/http://www.neonatalformulary.com/pdfs/uk_guidelines/http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-


11/12

obstetric factors associated with delayed postpartum eclamp-sia: A national study population. Acta Obstet Gynecol Scand2011; 90: 10171023.

39. Knight M , UKOSS. Eclampsia in the United Kingdom 2005.BJOG2007;114: 10721078.

40. Douglas KA, Redman CWG. Eclampsia in the United King-dom.BMJ1994;309: 13951400.

41. Bhalerao A, Kulkarni S, Ghike S, Kawthalkar A, Joshi S,

Somalwar S. Eclampsia: Maternal and Fetal Outcome. J SouthAsian Feder Obst Gynae2013;5: 1921.

42. Pal A, Bhattacharyya R, Adhikari Set al. Eclampsia-scenario ina hospital: a ten years study. Bangladesh Med Res Counc Bull2011;37: 6670.

43. Liu S, Joseph KS, Liston RMet al. Incidence, risk factors, andassociated complications of eclampsia. Obstet Gynecol 2011;118: 987994.

44. Lubarsky SL, Barton JR, Friedman SA, Nasreddine S, RamadanMK, Sibai BM. Late postpartum eclampsia revisited. ObstetGynecol1994;83: 502505.

45. Thapa K, Jha R. Magnesium sulfate: A lifesaving drug.JNMA JNepal Med Assoc2008;47: 104108.

46. Yakasai IA, Gaya SA. Maternal and fetal outcome in patientswith eclampsia at Murtala Muhammad Specialist HospitalKano, Nigeria.Ann Afr Med2011;10: 305309.

47. Abdullah A, Shaikh AA, Jamro B. Maternal and perinatal out-come associated with eclampsia in a teaching hospital, Sukkur.Rawal Med J2010;35: 2326.

48. Ndaboine EM, Kihunrwa A, Rumanyika R, Im HB, MassindeAN. Maternal and perinatal outcomes among eclampticpatients admitted to Bugando Medical Centre, Mwanza,Tanzania.Afr J Reprod Health2012;16: 3541.

49. Adam GK, Bakheit KH, Adam I. Maternal and perinataloutcomes of eclampsia in Gadarif Hospital, Sudan. J ObstetGynaecol2009;29: 619620.

50. Efetie ER, Okafor UV. Maternal outcome in eclamptic pa-tients in Abuja, Nigeria: A 5 year review. Niger J Clin Pract2007; 10: 309313.

51. Ade-Ojo IP, Loto OM. Outcome of eclampsia at the ObafemiAwolowo University Teaching Hospital Complex, Ile-Ife.NigerJ Clin Pract2008;11: 279284.

52. Buowari YD. Pattern and outcome of eclampsia managed at ageneral hospital in North-West, Nigeria. Niger Health J2012;12: 8689.

53. Tukur J, Umar BA, Rabiu A. Pattern of eclampsia in a tertiaryhealth facility situated in a semi-rural town in NorthernNigeria.Ann Afr Med2007;6: 164167.

54. Adama-Hondegla AB, Lawson-Evi K, Bassowa A, Modji S,Egbla K-F, Akbadza K. Perinatal mortality risk factors of infantsborn from eclamptic mothers at Tokoin teaching hospital ofLome.J Med Sci2013;13: 391395.

55. Muganyizi PS, Shagdara MS. Predictors of extra care amongmagnesium sulfate treated eclamptic patients at Muhimbili

National Hospital, Tanzania. BMC Pregnancy Childbirth 2011;11: 41.56. Agida ET, Adeka BI, Jibril KA. Pregnancy outcome in

eclamptics at the University of Abuja Teaching Hospital,Gwagwalada, Abuja: A 3 year review. Niger J Clin Pract2010; 13: 394398.

57. Olatunji AO, Sule-Odu AO. Presentation and outcome ofeclampsia at a Nigerian university hospital. Niger J Clin Pract2007;10: 14.

58. Eke AC, Ezebialu IU, Okafor C. Presentation and outcome ofeclampsia at a tertiary center in South East Nigeria: A 6-year re-view.Hypertens Pregnancy2011;30: 125132.

59. Noraihan MN, Sharda P, Jammal AB. Report of 50 cases ofeclampsia.J Obstet Gynaecol Res2005;31: 302309.

60. Morikawa M, Cho K, Yamada T, Yamada T, Sato S, MinakamiH. Risk factors for eclampsia in Japan between 2005 and 2009.Int J Gynaecol Obstet2012;117: 6668.

61. Adetoro OO. The pattern of eclampsia at the University ofIlorin Teaching Hospital (U.I.T.H.) Ilorin, Nigeria.Int J GynaecolObstet1990;31: 221226.

62. Acquaah-Arhin R, Kwawukume EY. Trends in eclampsia atKorle Bu teaching hospital, Accra Ghana. Niger J Clin Pract2003;6: 14.

63. Obiechina NJ, Udigwe GO. Pattern of eclampsia in Onitsha,Nigeria.Orient J Med2004;16: 1620.

64. Okafor UV, Efetie RE. Critical care management of eclamptics:Challenges in an African setting.Trop Doct2008;38: 1113.

65. Chames MC, Livingston JC, Ivester TS, Barton JR, Sibai BM.Late postpartum eclampsia: A preventable disease?Am J ObstetGynecol2002;186: 11741177.

66. Mattar F, Sibai BM. Eclampsia. VIII. Risk factors for maternalmorbidity.Am J Obstet Gynecol 2000;182: 307312.

67. Boudaya F, Zouaoui B, Ghodhbene Iet al. Eclampsia: Epidemi-ological aspects and management of 28 patients. Tunis Med2008;86: 685688.

68. Ducarme G, Herrnberger S, Pharisien I, Carbillon L, Uzan M.Eclampsia: Retrospective study about 16 cases. Gynecol ObstetFertil2009;37: 1117.

69. Lee W, OConnell CM, Baskett TF. Maternal and perinatal out-comes of eclampsia: Nova Scotia, 1981-2000. J Obstet GynaecolCan2004;26: 119123.

70. Turck M, Carles G, El Guindi W, Helou G, Alassas N, DreyfusM. Sixty-nine consecutive cases of eclampsia: Prodromesand circumstances. J Gynecol Obstet Biol Reprod (Paris) 2011;40: 340347.

71. Ahmad S, Nazli R, Lutfullah G. Frequency of eclampsia and

maternal complications in a tertiary care facility of Peshawar.Pak J Med Res2008; 47. [Cited July 2014.] Available from URL:http://www.pmrc.org.pk/eclampsia-peshawar.htm

72. Konje JC, Obisesan KA, Odukoya OA, Ladipo OA. Presenta-tion and management of eclampsia.Int J Gynecol Obstet 1992;38: 3135.

73. Chhabra S, Tyagi S, Bhavani M, Gosawi M. Late postpartumeclampsia.J Obstet Gynaecol2012;32: 264266.

74. Leitch CR, Cameron AD, Walker JJ. The changing pattern ofeclampsia over a 60-year period. Br J Obstet Gynaecol 1997;104: 917922.

75. Abate M, Lakew Z. Eclampsia a 5 years retrospective review of216 cases managed in two teaching hospitals in Addis Ababa.Ethiop Med J2006;44: 2731.

76. Echendu DA. Pattern of clinical presentation of eclampsia at

Nnamdi Azikiwe University Teaching Hospital, Nnewi, South-eastern Nigeria.Niger J Med2012;21: 313316.77. Hall DR, Odendaal HJ, Smith M. Is the prophylactic adminis-

tration of magnesium sulfate in women with pre-eclampsia in-dicated prior to labour?BJOG2000;107: 903908.

78. The American College of Obstetricians and Gynecologists(ACOG). Clinical management guidelines for obstetrician-Gynecologists number 33, 2002. Diagnosis and managementof preeclampsia and eclampsia. ACOG practice bulletin 2002;



841
http://www.pmrc.org.pk/eclampsia-peshawar.htmhttp://www.pmrc.org.pk/eclampsia-peshawar.htm


12/12

99. [Cited July 2014.] Available from URL: http://www.acog.org/Resources_And_Publications/

79. Wolfe DS, Williams SF, Ross MG, Beall MH, Apuzzio JJ. Doespreeclampsia predict the risk of late postpartum eclampsia?AJP Rep2013;3: 1316.

80. Scott JR. Preventing eclampsia: Magnesium sulfate regimensrevisited.Obst Gynecol2006;108: 824825.

81. Barclay L, NghiemHT. Magnesium sulfatemay benet patients

with mild gestational hypertension.Medscape2006; [Cited July2014.] Available from URL: http://www.medscape.org/viewarticle/545483.

82. Appleton MP, Kuchl TJ, Rebel MA, Adams HR, Knight AB,Gold WR. Magnesiumsulfate versus phenytoin for seizure pro-phylaxis in pregnancy induced hypertension.Am J Obst Gynecol1991;165: 907913.

83. Mathew R, Raj RS, Sudha P. Late postpartum eclampsia with-out prodroma.Neurol India2003;51: 539540.

84. Sibai BM, Abdella TN, Spinnato JA, Anderson GD. Eclampsia.V. The incidence of nonpreventable eclampsia. Am J ObstetGynecol1986;154: 581586.

85. Aagaard-TilleryKM, Belfort MA. Eclampsia:Morbidity, mortal-ity, and management.Clin Obstet Gynecol2005;48: 1223.

86. The Eclampsia Trial Collaborative Group. Which anticonvul-sant for women with eclampsia? Evidence from the Collabora-tive Eclampsia Trial.Lancet1995;345: 14551463.

87. Altman D, Carroli G, Duley Let al. Magpie Trial CollaborationGroup. Do women with pre-eclampsia, andtheirbabies, benetfrom magnesium sulfate? The Magpie Trial: A randomizedplacebo-controlled trial.Lancet2002;359: 18771890.

88. Umezurike CC, Feyi-Waboso PA, Whittaker RC. Treatment ofeclampsia with magnesium sulfate in Aba, South-EasternNigeria.Trop J Obstet Gynaecol2006;25: 2022.

89. Dasgupta S, Ghosh D, Seal SL, Kamilya G, Karmakar M,

Saha D. Randomized controlled study comparing effect ofmagnesium sulfate with placebo on fetal umbilical arteryand middle cerebral artery blood ow in mild preeclampsiaat 34 weeks gestational age. J Obstet Gynaecol Res 2012; 38:763771.

90. Langer A, Villar J, Tell K, Kim T, Kennedy S. Reducingeclampsia-related deaths: A call to action. Lancet 2008;371: 705706.

91. Adamu AN, Ekele BA, Ahmed Y, Mohammed BA, IsezuoSA, Abdullahpi AA. Pregnancy outcome in women witheclampsia at a tertiary centre in northern Nigeria. Afr J MedSci2012; 41: 211219.

92. Simon J, Gray A, Duley L. Magpie Trial CollaborativeGroup. Cost-effectiveness of prophylactic magnesiumsulphate for 9996 women with pre-eclampsia from 33countries: Economic evaluation of the Magpie Trial. BJOG2006; 113: 144151.



842
http://www.acog.org/Resources_And_Publications/http://www.acog.org/Resources_And_Publications/http://www.medscape.org/viewarticle/545483http://www.medscape.org/viewarticle/545483http://www.medscape.org/viewarticle/545483http://www.medscape.org/viewarticle/545483http://www.acog.org/Resources_And_Publications/http://www.acog.org/Resources_And_Publications/

Jurnal CGH

Documents

Transcript of Jurnal CGH