Expectan Mx Mx

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OBSTETRICS

Expectant management of severe preeclampsia remote fromterm: patient selection, treatment, and delivery indicationsBaha M. Sibai, MD; John R. Barton, MD

T he incidence of severe preecla mpsiais 0.9% in the United States. 1 Theclinical course of severe preeclampsiacan result in progressive deterioration inboth maternal and fetal conditions. Tra-ditional management of severe pre-eclampsia has focused on maternalsafety with expedited delivery. Because thesepregnancies are associated with highrates of maternal morbidity and mortal-ity and with potential risks for the fetus,there is general agreement that such pa-tients should be delivered if the di seasedevelops at 34 weeks of gestation. 2,3 Inpatientswith severedisease at 34 weeksof gestation, several authors have sug-gested some form of expectant manage-ment in an attempt to prolong ges tationand improve peri natal outcome. 2-6 In1994, Schiff et al7 summarized thesestudies and published guidelines for theexpectant management of severe pre-eclampsia remote from term. Expectantmanagement was recommended for se-vere disease at 34 weeks of gestationwith stable maternal and fetal condi-tions. For patients with severe fetalgrowth restriction (FGR) with or with-out severe oligohydramnios andpatientswith immature fetal lung maturity stud-ies at 33 0/7-34 0/7 weeks of gestationor evidence of maternal organ dysfunc-

tion (eclampsia, imminent eclampsia,HELLP [hemolysis, elevated liver en-zymes, and low platelet count] syn-drome, severe persistent thrombocyto-penia, abnormal liver enzymes withmaternal symptoms, or pulmonary edema), the authors recommended ste-roids for fetal lung maturity enhance-

ment with delivery 48 hours after the ini-tiation of steroids. The lower gestationalage limit for expectant management wasnot specied in these recommenda-tions. 7 Since that report, practitionersand investigators have expanded theseguidelines to include severe FGR,throm-bocytopenia, eclampsia, HELLP syn-drome, and severe preecla mpsia at 24or 33 weeks of gestation.8-17 The pur-pose of this report as to dene the opti-mal candidates for expectant treatment

of severe preeclampsiaandmaternal andfetal indications for delivery on the basis

of our clinical experience and review of the recent literature (since 1990). Ourobjectives were to review the maternaland perinatal risks of the treatment of severe preeclampsia remote from termincluding patients who are consideredideal candidates for this treatment andcontraindications to this therapy. Rec-

ommendations will then be made basedon this review.

Randomized trialsWhen onereviewsthepublished trialsontheexpectantmanagement of severe pre-eclampsia, there are only 2 randomizedtrials, which included only 133 women,that compare thebenets and risksof ag-gressive and conservative manage-ment. 2,3 In 1990, Odendaal et al 2 studied

38 patients with severe preeclampsia at28-34 weeks of gestation: 20 of the pa-

From the Department of Obstetrics andGynecology, University of CincinnatiCollege of Medicine, Cincinnati, OH (DrSibai), and the Department of Maternal-Fetal Medicine, Central Baptist Hospital,Lexington, KY (Dr Barton).Received Oct. 16, 2006; accepted Feb. 21,2007.Reprints: Baha M. Sibai, MD, Department of Obstetrics & Gynecology, 231 Albert SabinWay, Cincinnati, OH 45267-0526;[email protected]/$32.00 2007 Mosby, Inc. All rights reserved.

doi: 10.1016/j.ajog.2007.02.021

Severe preeclampsia that develops at 34 weeks of gestation is associated with highperinatal mortality and morbidity rates. Management with immediate delivery leads to highneonatal mortality and morbidity rates and prolonged hospitalization in the neonatalintensive care unit because of prematurity. Conversely, attempts to prolong pregnancy withexpectant management may result in fetal death or asphyxial damage in utero and increasedmaternal morbidity. Since 1990, 2 randomized trials and several observational studies haveevaluated the benets vs risks of expectant management of severe preeclampsia at34weeks of gestation. These studies included 1677 women with gestational age between 24and 34 weeks and 115 women with gestational age of 25 weeks (overlap in somestudies). The results of these studies suggest that expectant treatment in a select group ofwomen with severe preeclampsia between 24 0/7 and 32 6/7 weeks of gestation in asuitable hospital is safe and improves neonatal outcome. For gestational age of24 0/7weeks, expectant treatment was associated with high maternal morbidity with limitedperinatal benet. Based on the review of these studies and our own experience, recom-mendations are made for the selection of the appropriate candidates for expectant treatment,criteria for maternal-fetal monitoring, and targets for delivery. Finally, we provide infor-mation regarding maternal counseling based on maternal condition and fetal gestationalage at time of diagnosis.

Key words: expectant management, severe preeclampsia at 34 weeks ofgestation

Cite this article as: Sibai BM, Barton JR. Expectant management of severe preeclampsia remote

from term: patient selection, treatment, and delivery indications. Am J Obstet Gynecol2007;196:514.e1-514.e9.

Clinical Opinion www.AJOG.org

514.e1 American Journal of Obstetrics & Gynecology JUNE 2007


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tients were treated aggressively (glu-cocorticoid therapy followed by delivery in 48 hours), and 18 of the patients weretreated expectantly (glucocorticoidther-apy followed by delivery only for specicmaternal or fetal indications). In thegroup that was treated conservatively,the authors reported no increase in ma-ternal complications but reported a sta-tistically signicant prolongation of pregnancy (mean, 7.1 days), a reduction

in neonates that required ventilation(11% vs 35%), and a reduction in tot alneonatal co mplications (33% vs 75%). 2

Sibai et al3 studied 95 patients with se-vere preeclampsia at 28-32 weeks of gestation: 46 patients were assigned ran-domly to aggressive treatment (glu-cocorticoid therapy followed by delivery in 48 hours), and 49 were assigned ran-domly to expectant treatment(glucocor-ticoid therapy followed by delivery forspecic maternal or fetal indications).

Patients with medical complications,rupture of membranes, preterm labor,

multifetal gestation, fetal compromise,severe FGR, or platelet count 100,000/

L were excluded. In women who weretreated conservatively, there was no in-crease in maternal complications, butthere was a statistically signicant pro-longation of pregnancy (mean, 15.4 vs2.6 days), less time in the neonatal inten-sive care unit (20.2 vs 36.6 days), and areduced incidence of respiratory distresssyndrome (22.4% vs 50.5%). Althoughtheaverage birthweight in this groupwassignicantly higher (1622 g vs 1233 g),there was also a signicantly higher inci-dence of small-for-gestational-age infants(SGA; 30% vs 11%).3 These 2 trials (Table1) demonstrated improved perinatal ben-et with reasonable maternal safety whenexpectant treatment was conducted in acontrolled manner in a select group of pa-tients with severe preeclampsia at 28-34weeks ofgestation (stablematernal and fe-

tal conditions plus a well-dened indica-tion for delivery). 2,3

Observational studiesRecently, the results of several retrospec-tive and observational studies that de-scribed expectant management of severepreeclampsia at 24-34 weeks of gestationhave suggested that such managementimproves perinatal outcome without in-creasing maternal morbidity. 4, 6,8,10,12-17

The results of these studies are summa-rized in Table 1. The reviewed studies in-cluded patients with preeclampsia andpatients with chronic hypertension withsuperimposed preeclampsia. In addi-tion, the authors of these studies did notmention whether the patients who wereincluded had de novo severe preeclamp-siaor hadprogressed from mild to severepreeclampsia at the initiation of expect-ant treatment. The average days of preg-nancy prolongation and the ranges arehighly variable among these studies,which reect theheterogeneity of thepa-

tients who were studied (different crite-ria for severe preeclampsia, varying ges-

TABLE 1Management of severe preeclampsia remote from term

StudyGestationalage (wk) Women (n)

Average days ofprolongation(range)

Relevant aspects of eachtrial

Randomized trials......................... ..... .........................................................................................................................................................................................................................................................................................................................................Sibai et al3 (1994, USA) 28-32 46 15 (3-32) MgSO4 steroids..................................... .... ..............................................................................................................................................................................................................................................................................................................................Odendaal et al2 (1990, South Africa) 26-34 18 7.1 MgSO4 steroids................................................................................................................................................................................................................................................................................................................................................................................

Observational trials......................... ..... .........................................................................................................................................................................................................................................................................................................................................

Sibai et al4 (1990, USA) 24-27 54 13 (2-26) MgSO4 steroids.............................................. ...... ...................................................................................................................................................................................................................................................................................................................Chua and Redman 5 (1992, UK) 24-34 42 ? (1-28) No MgSO4 or steroids........................ ..... ..........................................................................................................................................................................................................................................................................................................................................Olah et al6 (1993, UK) 24-32 28 9.5 (2-26) No MgSO4........................................................ ..... ..........................................................................................................................................................................................................................................................................................................

Visser and Wallenburg8 (1995, The Netherlands)* 26-31 229 14 (0-16) No MgSO4 or steroids...................... ........ .........................................................................................................................................................................................................................................................................................................................................Hall et al12 (2000, South Africa) 26-34 340 10-30 (1-47) MgSO4 steroids...................................... ........ .........................................................................................................................................................................................................................................................................................................................Chammas et al 10 (2000, USA) 24-33 47 6 (1.5-28) MgSO4 steroids................................... ........ ............................................................................................................................................................................................................................................................................................................................

Vigil-DeGarcia13

(2003, Panama) 24-34 129 8.5 (3-30) MgSO 4 steroids................................ ........ ...............................................................................................................................................................................................................................................................................................................................Haddad et al14 (2004, France) 24-34 239 5 (2-35) No MgSO4 or steroids........................... ........ ....................................................................................................................................................................................................................................................................................................................................Oettle et al16 (2004, France) 24-34 131 11.6 (1-89) MgSO 4 steroids........................... ........ ....................................................................................................................................................................................................................................................................................................................................Shear et al 15 (2005, Canada) 24-34 155 5.3 (1-27) MgSO4 steroids......................................... ........ ......................................................................................................................................................................................................................................................................................................................Ganzevoort et al17 (2006, The Netherlands)* 24-34 216 11 (0.2-44) MgSO4 steroids, plasma

volume expansion................................................................................................................................................................................................................................................................................................................................................................................MgSO 4 , magnesium sulfate.

* Included patients with HELLP syndrome, eclampsia, and severe FGR. Included 8 patients with FGR and oligohydramnios. Included patients with severe FGR.

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JUNE 2007 American Journal of Obstetrics & Gynecology 514.e2


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tational ages, presence or absence of severe FGR, presence of maternal organdysfunction).

P ERINATAL C OMPLICATIONSD URING EXPECTANTT REATMENT

The main aim of expectant treatment isto improve perinatal outcome by pro-longing gestation and reducing neonatalmorbidities (acute and long-term).There are potential perinatal complica-tionsduring expectant treatment; conse-quently, all reported studies recom-mended intensive fetal surveillance forearly detection of fetal compromise. Themost common indication for delivery inmost studies was deterioration in fetal sta-tus. Table 2 summarizes the perinatal com-

plications during e xpectant treat ment inthe reported studies. 2,3,5,6,8,10,12-16

During expectant treatment of pa-tients with severe preeclampsia at 24-34weeks of gestation, the rate of perinataldeath in the rep orted studies rangedfrom 0 to 16.6%. 2,3 This variation inperinatal death reects differences ingestational age at inclusion, the presenceor absence of FGR, HELLP syndrome oreclampsia, and quality of neonatal care(year of reporting and county). In-

deed, in recent studies from the UnitedStates, Canada, andFrance, the perinatal

death rat es were 0% at 30 weeks of gestation. 3,14,15

The rate of placental abruption in thereport ed studies ranged from 4.1% to22.9%.3,16 Our particular concern wasnot just abruption but also the risk forfatal abruptio placentae for the fetus.

Specically, 3 of the 4 cases of stillbirthsin the most recent series by Oettle et al 16

were associated with abruptio placentae.In addition, delivery for nonreassuringfetal status ranged from 26% to 75%.From a sample size sta ndpoint, the 2largest studies by Hall et al 12 and Haddadet al14 encompass 579 patients with acombined average of need for delivery that was basedon a worsening fetal statusof 44%. The high incidence of nonreas-suring fetal status during expectant

treatment underscores the need thatthese pregnancies should be managed incenters that are capable of rapid inter-vention for fetal reasons.

M ATERNAL C OMPLICATIONSD URING EXPECTANTT REATMENTThe main aim of the expectant manage-ment of severe preeclampsia remotefrom term is prolonging gestation with-out jeopardizing maternal safety. Be-

cause the clinical course of severe pre-eclampsia can result in progressive

deterioration in maternal condition,there is potential for maternal complica-tions during any protocol for manage-ment of severepreeclampsia. Since 1990,there was 1 maternal death 16 reportedamong 1677 women who underwent ex-pectant treatmentof severepreeclampsia

at 24 weeks of gestation.2-6,8,10,12-16

Table 3 presents the maternal complica-tions during expectant management inreported studies. Therate of HELLPsyn-drome/thrombocytopenia ranged from4.1%-27.1%, whereas the rate of pulmo-nary edema ranged from 0-8.5%. Therates of eclampsia andacute renal failurein recent studies from the United Statesand Europe were at 1%.3,8,14

Expectant treatment of patients withsevere disease therefore must provide

heightened surveillance to ensure ade-quate maternal oxygenation (monitor-ing for pulmonary edema or adult respi-ratory distress syndrome), provideprompt intervention for symptoms of hepatic dysfunction that could lead to aHELLP syndrome or subcapsular hema-toma of the liver, and particularly pro-vide evaluation of the fetal status andmaternal presentation given the risks of placental abruption.

A concern regarding expectant man-

agement is thedevelopment of FGR. TheSGA rate in these published studies

TABLE 2Perinatal complications during expectant management of severe preeclampsia

Study* Abruption (%)Small for gestationalage (%)

Nonreassuring fetaltesting (%) Perinatal death (%)

Randomized trials....................... .... ............................................................................................................................................................................................................................................................................................................................................

Odendaal2

(n 18) 22 Not reported 38.9 16.6......................... ..... .........................................................................................................................................................................................................................................................................................................................................Sibai et al3 (n 49) 4.1 30.1 26.5 0

................................................................................................................................................................................................................................................................................................................................................................................

Observational studies........................ ..... ..........................................................................................................................................................................................................................................................................................................................................

Olah et al6 (n 28) 7.1 Not reported 35.7 7.1........................................................ ..... ..........................................................................................................................................................................................................................................................................................................

Visser and Wallenberg8 (n 229) 5.1 58.1 74.0 13.6...................... ........ .........................................................................................................................................................................................................................................................................................................................................

Hall et al12 (n 340) 20 36 44.4 9.0................................... ........ ............................................................................................................................................................................................................................................................................................................................

Vigil-DeGracia13 (n 129) 8.5 21.7 Not reported 7.0...................................... ........ .........................................................................................................................................................................................................................................................................................................................

Chammas et al 10 (n 47) 12.7 51.1 44.7 6.4................................ ........ ...............................................................................................................................................................................................................................................................................................................................

Haddad et al14 (n 239) 8.7 24.3 42.8 5.4........................... ........ ....................................................................................................................................................................................................................................................................................................................................

Oettle et al16 (n 131) 22.9 Not reported 55.2 13.3........................... ........ ....................................................................................................................................................................................................................................................................................................................................

Shear et al 15 (n 155) 5.8 61.9 Not reported 3.9................................. ...... .........................................................................................................................................................................................................................................................................................................................................* Ganzevoort et al17 was not included in this Table because 55% of patients began with FGR.

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ranged from 21.7% to 61.9% ( Table 2).The rate of development of SGA infantsduring expectant treatment is unknownbecause most reported studies have in-cluded some patients with evidence of FGR. In addition, because these studieshave reported only short-term perinatal

outcome, the effects of poor intrauterinegrowth on long-term development andoutcome remainu nclear. Because of thisconcern, Sibai et al 3 and Schiff et al 7 sug-gested that FGR and oligohydramniosare contraindications to the expectantmanagement of severe preeclampsia. Infact, the ndings by Chammas et al 10

would support this recommendationbe-causepatientswith FGRor FGR with oli-gohydramnios had minimal prolonga-tion of pregnancy past their steroid

window, comparedwith a group with noevidence of either FGR or oligohydram-nios. In add ition, the ndings by Gan-zevoort et al 17 reveal that patients withsevereFGR at the beginningof expectanttreatment had higher perinatal deathand more adverse perinatal outcom es,compared with patients without FGR. 15

In addressing the issue of expectanttreatment of patients with severe pr e-term preeclampsia and FGR, Shear et al 15

concluded that Expectant management

is recommended strongly in fetuses at30 weeks of gestation, irrespective of

fetal growth restriction. This was a ret-rospective study in which perinatal out-comes of both mother and fetus werestratied according to gestational ageandseverity of FGR that was determinedafter delivery. Their conclusions, how-ever, were not supported by the reported

data because all cases of eclampsia, ab-ruption, and pulmonary edema oc-curred in those pregnancies that resultedin a birthweight at 10th percentile.Further, the rates of fetal indications fordelivery were signicantly higher inpregnancies that resulted in FGR.

S EVERE P REECLAMPSIA < 25W EEKSSevere preeclampsia that develops in themid trimester is associated with highperinatal mortality and morbidity rates.4,8,9,17-23 Aggressive treatment withimmediate delivery will result in a highneonatal mortality rate. 4,20,22 In addi-tion, most surviving neonates will expe-rience signicant neonatal complica-tions and will require prolongedhospitalization in neonatal intensivecare units. 4,9,17-24 On the other hand, at-tempts to prolong pregnancy may result

in fetal death or asphyxial damage inutero. 8,9,17-19,21,23 Moreover, this treat-

ment may expose the mo ther to sever emorbidity and even death. 4,8,9,18,19,21,23

There are limited data regarding ma-ternal andperinataloutcomesduring ex-pectant treatment of patients with severepreeclamps ia at 25 weeks of gestation(Table 4).4,8,9,18,19,21,23 Overall, the

number of study patients that were re-ported was 115, and the perinatal deathrate ranged from 71% to 100%, with few newborn infants surviving withouthandicap. 4,21,23,24 Among the 116 births(1 set of twins) that were reported inthesestudies, theperinataldeathrate was83%. Overall, there were 20 surviving in-fants; detailed long-termneurologic out-come wasprovided fora limited numberof these infants. In addition, there was 1maternal death (0.9%) in a patient who

had eclampsia and HELLP syndromewho underwent expect ant treatment at23 weeks of gestation.23 Furthermore,maternal morbidities was very high(Table 4).

P REECLAMPSIA WITH HELLPS YNDROMEThe clinical course of women withHELLP syndrome usually is character-ized by progressive and sometimes sud-

den deterioration in the maternal condi-tion. 25 Because the presence of this

TABLE 3Maternal complications during expectant management of severe preeclampsiaStudy HELLP syndrome (%) Pulmonary edema (%) Renal failure (%) Eclampsia (%)

Randomized trials..................................... .... ..............................................................................................................................................................................................................................................................................................................................

Odendaal et al2 (n 18) Not reported 0 5.5 0......................... ..... .........................................................................................................................................................................................................................................................................................................................................

Sibai et al3 (n 49) 4.1 0 0................................................................................................................................................................................................................................................................................................................................................................................

Observational studies......................... ..... .........................................................................................................................................................................................................................................................................................................................................

Sibai et al4 (n 54) 13.0 0 0 5.6........................ ..... ..........................................................................................................................................................................................................................................................................................................................................

Olah et al6 (n 28) 14.3 0 3.6 0...................... ........ .........................................................................................................................................................................................................................................................................................................................................

Hall et al12 (n 340) 5.2 2.1 1.7 1.2................................................. ......................................................................................................................................................................................................................................................................................................................

Vigil-DeGracia et al13 (n 129) 8.5 2.3 1.6 0...................................... ........ .........................................................................................................................................................................................................................................................................................................................

Chammas et al 10 (n 47) 17.0* 8.5 17.0* 0................................ ........ ...............................................................................................................................................................................................................................................................................................................................

Haddad et al14 (n 239) 14.2 3.8 0 0........................... ........ ....................................................................................................................................................................................................................................................................................................................................

Oettle et al16 (n 131) 4.6 0.8 2.3 2.3........................... ........ ....................................................................................................................................................................................................................................................................................................................................

Shear et al 15 (n 155) 27.1 3.9 Not reported 1.9................................................................................................................................................................................................................................................................................................................................................................................* Reported as HELLP syndrome or deteriorating renal function. Reported as low platelet count.




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syndrome is associated with increased

rates of maternal morbidity and mortal-ity, some authors consider its presencean indicationfor immediatedelivery,ex-cept for the benet of steroids for fetallung maturity in gestations at 24-34weeks. As a result, in most studies withwomen with expectant treatment of se-verepreeclampsia at 34 weeks of gesta-tion, patients with HELLP syndromewere excluded from participation be-cause they were jud ged to be unsuitablefor such treatment. 1-7,10-15 On the other

hand, investigators in The Netherlanddidinclude womenwith HELLP (with orwithout hemolysis) syndrome in suchtreatment regimens.

Visser and Wallenburg 26 reported ex-pectant treatment in 128 women withHELLP syndrome at 34 weeks of ges-tationwhowere treated with plasmavol-ume expansion with the use of invasivehemodynamic monitoring and vasodila-tors. Twenty-two of the 128 patientswere delivered within 48 hours; the re-

maining 106 patients had pregnancy prolongation for a median of 15 days(range, 3-62 days). Fifty-ve of the 106women had antepartum resolution of HELLP syndrome with a median preg-nancy prolongation of 21 days (range,7-62 days). There were no maternaldeaths; 2 patients had eclampsia, and 11patients had hemorrhagic complica-tions. The overall perinatal mortality rate was 14%. They also found that ma-ternal and perinatal outcome in these

pregnancies was similar to the respectiveoutcome in 128 patients with severe pre-

eclampsia without HELLP syndrome

whowere matched formaternaland ges-tational age. They concluded that theirdata do not support the recommenda-tion against expectant treat ment of women with HELL P s yndrome. 26

Van Pampus et al 27 reported the use of bed rest, antihypertensive medications,and salt restriction in 41 women withHELLP syndrome at 35 weeks of ges-tation. Fourteen women (34%) were de-livered within24 hours; in theremaining27 women, pregnancy was prolonged a

median of 3 days (range, 0-59 days). Fif-teen of these 27 women demonstratedcomplete normalization of the labora-tory abnormalities. There were no seri-ous maternal morbidities; however,there were 10 fetal deaths at 27-36 weeksof gestation and no neonatal deaths. Thepregnancy outcomes in these 41 womenwere also compared with the outcomesof 41 women without HELLP syndromewhowere treated in a similar fashion andwhowere found to have similar maternal

and perinatal outcomes.Recently, van Runnard Heimel et al 28

performed a randomized, double-blindtrial in 31women with HELLPsyndromeat 30 weeks of gestation: 15 women re-ceived 50 mg prednisolone intrave-nously twice a day, and 16 women re-ceived a matching placebo. The primary outcome measures werethe entry-to-de-livery interval andthenumberof recur-rent HELLP exacerbations in theantepartum period. The mean entry-to-

delivery interval was similar between the2 groups (6.9 days in prednisolone and

8.0 days in the placebo [9 episodes vs 18

episodes]). Therewere 3 casesof liverhe-matoma or rupture, with 1 maternaldeath in the placebo group. The perina-tal mortality rate was 20% in the pred-nisolone group and 25% in the placebo.

The results of the aforementionedstudies suggest that expectant treatmentis possible in a select group of womenwith alleged HELLP syndrome at 34weeks of gestation. However, despitepregnancyprolongationin some of thesecases, the overall perinatal outcome was

not improved, compared with cases atsimilar gestational age who were deliv-ered within 48 hours af ter the diagnosisof HELLP syndrome. 29 In addition, thenumber of women who were studied inthese reports is inadequate to evaluatematernal safety. Therefore, such treat-ment is currently experimental.

O PTIMAL C ANDIDATES ,T REATMENT , AN D I NDICATIONSFO R

DELIVERY

The main objective of the managementof severe preeclampsia must always bethe safety of the mother and the fetus.Although delivery is always appropriatefor the mother, it might not be best for avery premature fetus. The decision be-tween delivery and expectant treatmentdepends onfetal gestationalage, fetal sta-tus, andseverityof maternalconditionatthe time of assessment. This objectivecan be achieved by the formulation of a

management plan that considers 1 of the following factors: fetal gestational

TABLE 4Expectant management of severe preeclampsia at < 25 weeks of gestationStudy Patients (n) Perinatal death (%) Maternal complications (%)

Sibai et al4 (1990, USA) 15 93 27.................................. ....... .......................................................................................................................................................................................................................................................................................................................................

Moodley et al19 (1993, South Africa) 10 100 50........................................................ ..... ....................................................................................................... ..... .......................................................................................................................................................................................................

Visser and Wallenberg8 (1995, The Netherlands), Withagen et al9(2001, The Netherlands)

25 84 Not reported

.................................................. ........ ......................................................................................................................................................................................................................................................................................................................

Gauler-Senden et al 21 (2006, The Netherlands) 26 22/27 (82)* 65...................... ........ ..................................................................................................................................................................................................................................................................................................................................................

Hall et al18 (2001, South Africa) 8 88 36................................ ........ ........................................................................................................................................................................................................................................................................................................................................

Bunden et al23 (2006, New Zealand) 31 71 71................................................................................................................................................................................................................................................................................................................................................................................* Five surviving infants had no handicap at 9-72 months. One maternal death in a patient with eclampsiaHELLP syndrome. Four surviving infants had no handicap at 18 months.




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age, maternal and fetal status at time of the initial assessment, the presence of la-bor, or rupture of fetal membranes ( Fig-ure). The proposed management algo-rithm and the recommendations that we

discuss are based on small randomizedstudies and several observational studiesand expert opinion. Individual compo-nents have not been subjected to appro-priate large, prospective, randomizedcontrolled clinical trials.

Thepresence of severepreeclampsia at34 0/7 weeks of gestation mandates

immediate hospitalization in the laborand delivery unit. Our policy is to startmagnesium sulfate intravenously to pre-vent convulsions and antihypertensive

medications to lower severe levels of hy-pertension (systolic pressure 160 mm

Hg and/or diastolic pressure 110 mmHg). 30 The aim of antihypertensive ther-apy is to keep systolic blood pressure be-tween 140 and 155 mm Hg and diastolicblood pressure between 90 and 105 mm

Hg. In addition, corticosteroids are ad-ministered for fetal lung maturation.During the observation period, maternaland fetal conditions are assessed, and adecision is made regarding the need fordelivery (Figure 1).

After initial clinical and laboratory evaluation, a decision must be made forimmediate delivery vs expectant treat-ment. Patients with eclampsia, neuro-logic decit (blindness, confusion,motor decit), pulmonary edema, dis-

seminated intravascular coagulation,suspected abruptio placentae, or nonre-

assuring fetal heart rate testing aredeliveredregardless of the benet of cor-ticosteroid s after maternal stabiliza-tion. 2,3,7,14 Patients with a gestational ageof 23 0/7 week should be offered ter-mination of pregnancy because no ba-

bies have survived in reported studiesduring the expectant treatment of severepreeclampsia at this gestationalage.4,8,12,18,19,21,23 In addition, expectanttreatment in patients with gestationalage between 23 0/7 and 23 6/7 results inextremely high maternal and perinatalmorbidity and mortality rates. There-fore, expectant treatment in these pa-tients should be considered only as anoption after extensive counseling. 4,21,23

Maternal evaluation includes moni-

toring of blood pressure, urine output,cerebral status, and the presence of epi-gastric pain, tenderness, labor, or vaginalbleeding. Laboratory evaluation in-cludes a platelet count, liver enzyme andserum creatinine testing, and a type andscreen. Fetal evaluation includes contin-uous fetal heart rate monitoring, a bio-physical prole, and ultrasonographicassessment of fetal growth, amnioticuid status, and umbilical artery Dopp-ler velocimetry. Patients with resistant

severe hypertension despite maximumdoses of intravenous labetalol (220 mg)plus either intravenous hydralazine (25mg), oral nifedipine (50 mg), or persis-tent cerebral symptoms while on magne-sium sulfate deliver within 2 4-48 hours,irrespective of gestational age. 4,7 In addi-tion, patients with thrombocytopenia(platelet count 100,000) or elevatedliver enzymes with epigastric pain andtenderness(HELLP syndro me) or serumcreatinine of 1.5 mg/dL 4,7,14 also are

delivered within 48 hours. Moreover,patients with gestational ageof 33 0/7-346/7 with labor and/or rupture of mem-branes, severe FGR ( 5th percentile forgestational age), 3,4,7,10,14 persistent se-vere oligohydramnios (amniotic uidindex of 5 cm on at least 2 occasionsthat were 24 hours apart), 3,10,13,14 orumbilical artery Doppler st udies withpersistent reverse blood ow 7,12,16 alsoare delivered within 48 hours.

Patients at 24 0/7 to 32 6/7 weeks of

gestation receive individualized treat-ment that is based on their clinical re-

FIGURERecommended treatment for patients with severe preeclampsia at< 34 weeks of gestation

Severe Preeclampsia at < 34 weeks

Admit to Labor & Delivery areaMaternal & Fetal Evaluation x 24 hours

IV Magnesium SulfateAntihypertensives if systolic 160 mm Hg,

diastolic 110 or mean arterial pressure > 125 mm HgCorticosteroids for lung maturity

EclampsiaPulmonary edemaAcute renal failure

Disseminated Coagulopathy Yes Delivery before

< 23 weeks gestation completion of steroidsGestational age 33 0/7-34 0/7 weeks

Non-reassuring fetal status

No

HELLP syndromeSevere FGR oligohydramnios

UAD with reverse diastolic flowPersistent symptoms Steroids

Thrombocytopenia Yes 48 hr delay if possibleGestational age 33 0/7-34 0/7 weeks

Labor or rupture or membranes

No

3 0/7-23 6/7 week 24 0/7-32 6/7 week

CounselingAntihypertensives if needed

Termination of Daily evaluations of maternal-fetal conditionsPregnancy Delivery at 33 6/7 weeks




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tion, fetal presentation, presence of la-bor, and cervical Bishop score. The ce-sarean section rate among reportedstudies ranged from 66%-96%, with thehigher rates for patients with severe pre-eclampsia at 28 weeks of gestation. 2-26

Onthe basis of the available data, werec-ommend that a plan for vaginal delivery be attempted in all patients with a gesta-tional age of 32 0/7 weeks with vertex presentation. In addition, vaginal deliv-ery may be attempted in those womenbetween 27 0/7 and 31 6/7 weeks of ges-tation in the absence of severe FGR and/or reverse UAD ndings. Laborinduction should be carried out ag-gressively once the decision for deliv-ery has been made. 32 This should in-

clude deliver y within 24 hours of theinduction. 32 Serial induction of laboris not appropriate in these cases. Elec-tive cesarean section is recommendedfor all patients with gestational age be-low 27 weeks of and for all those withsevere FGR and/or reverse umbilicalartery Do ppler (U AD) at 32 weeks of gestation. 4,14,15,17

Once the decision is made for deliv-ery, the patients should receive intra-venous magnesium sulfate in labor and

for at least 24 hours after delivery.Some authors recommended a shorterduration of magnesium sul fate therapy in the postpartum period 34,35 ; how-ever, these recommendations do notapply to expectant treatment becauseall protocols have used at least 24 hoursof magnesium sulfat e therapy in suchwomen. 2-4,6,7,10-13,16

During the immediatepostpartum pe-riod, women with severe preeclampsiashouldreceive close monitoring of blood

pressure and symptoms and accuratemeasurements of uid intake and uri-nary output. These women usually re-ceivelarge amounts of intravenous uidsduring labor, as a result of prehydrationbefore epidural analgesia, and intrave-nous uids during the administration of oxytocin andmagnesium sulfate in laborand after delivery. In addition, duringthe postpartum period, there is mobili-zation of extracellular uid that leads toincreased intravascular volume. As a re-

sult, such women areat increasedrisk forpulmonary edema and exacerbation of

severe hypertension after delivery. Afterthe delivery, there is no longer a concernfor reduced uteroplacental blood ow from lower maternal blood pressure;therefore, we recommend using antihy-pertensive drugs if the systolic blood

pressure isat least 155 mmHg and/orthediastolic blood pressure is at least 105mm Hg. 31 Our policy is to use either oralnifedipine (10 mg every 4-6 hr) and/orlabetalol (200-400 mg every 8 hr). In ad-dition, some authors recommenda shortcourse of oral furosemide (20 mg dail y)with oral potassium supplementation. 36

C OMMENTWehave describedthe rationale, thecan-

didates, the recommendations, and theguidelines for treatment of patients withsevere preeclampsia at 34 weeks ofges-tation. These recommendations andguidelines are not absolute rules fortreatment and are based on a review of recent literature and on our experiencewith hundredsof patientswhom wehavetreated during the past decade. It is im-portant to emphasize that the describedprotocol is not a cookbook. We believethat clinical judgment must still play a

considerable role in the treatment of these patients. Nevertheless, the treatingphysician should have full appreciationof the protean manifestations of the syn-drome of preeclampsia andof thepoten-tial for the rapid progression of the dis-easeprocess during expectant treatment.Therefore, expectant treatment shouldbe performed only in a select group of patients after maternal counseling re-garding t he benets and risks of suchtreatment. 2-4,7 It should be performed

only in select hospitals (with adequatematernal and neonatal intensive care fa-cilities) and should include close mater-nal and fetal surveillance and a targetgestational age for delivery and indica-tions for delivery before the target.

Patient selection should include con-sideration of underlying maternal dis-ease and specically those women with agestational age remote from fetal viabil-ity or a gestational age at which the fetuswould have acceptable extrauterine sur-

vival andlong-termintact survival. Indi-viduals who follow this process should

have a well-dened target of gestationalage for delivery based on their facility practices and, particularly, on their out-come at various weekly gestational ageintervals. Treatment should also consistof well-dened indications for delivery

before that target. For example, certainwomen with serious maternal complica-tions should be delivered irrespective of gestationalageand without thebenetof steroids, whereas women with HELLPsyndrome, persistent symptoms, and se-vere FGR can be delivered after steroidbenet.

The care of women with pregnancy complications that are considered nearthe border of viability or periviablegestation involves a complex set of med-

ical, emotional, and social challenges forhealth care professionals and the pa-tients family. 37 Limits of fetal viability,in general, have been pushed back, butthis certainly varies between countriesand even across institutions within thesame country. Fetal viability is a relativeterm because it depends on the neonatalintensive care unit facilities, adequately trained personnel, and nancial re-sources to support these facilities. It isclear, however, if the gestational age iswell lower than that of the limits of via-bility for the center (usually 24 weeksof gestation), then the maternal safety should supersede the fetal benet andthe patient should be treated withdelivery.4,8,9,18-21,23

Finally, those physicians who elect touse this treatment must anticipate thepotential for rapid deterioration in thematernal or fetal status. Therefore, 24-houravailability of anesthesia, neonatol-ogy, operating room staff, and the obste-trician are necessary.

In summary, expectant treatment im-proves perinatal outcome in a selectgroup of women with severe preeclamp-sia at 32 6/7 weeks of gestation. Never-theless, we must emphasize that theserecommendations are based on only 2randomized trials(a total of133women)and several observational studies on thesubject. Therefore, largerandomized tri-als are needed to conrm whether the

benets for theneonate that is associatedwith expectanttreatment donotincrease




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the risk of death or long-term morbidity for the mother. f

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