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OBSTETRICS
514.e1
Randomized trials
When one reviews the published trials on
the expectant management of severe preeclampsia, there are only 2 randomized
trials, which included only 133 women,
that compare the benefits and risks of aggressive and conservative management.2,3 In 1990, Odendaal et al2 studied
38 patients with severe preeclampsia at
28-34 weeks of gestation: 20 of the pa-
Obstetrics
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Clinical Opinion
TABLE 1
Study
Women (n)
Average days of
prolongation
(range)
Randomized trials
.......................................................................................................................................................................................................................................................................................................................................................................
3
4
.......................................................................................................................................................................................................................................................................................................................................................................
2
4
................................................................................................................................................................................................................................................................................................................................................................................
28-32
46
26-34
18
15 (3-32)
7.1
MgSO steroids
MgSO steroids
Observational trials
.......................................................................................................................................................................................................................................................................................................................................................................
4
4
.......................................................................................................................................................................................................................................................................................................................................................................
5
4
.......................................................................................................................................................................................................................................................................................................................................................................
6
4
.......................................................................................................................................................................................................................................................................................................................................................................
8
4
.......................................................................................................................................................................................................................................................................................................................................................................
12
4
.......................................................................................................................................................................................................................................................................................................................................................................
10
4
.......................................................................................................................................................................................................................................................................................................................................................................
13
4
.......................................................................................................................................................................................................................................................................................................................................................................
14
4
.......................................................................................................................................................................................................................................................................................................................................................................
16
4
.......................................................................................................................................................................................................................................................................................................................................................................
15
4
.......................................................................................................................................................................................................................................................................................................................................................................
17
4
MgSO steroids
24-27
54
13 (2-26)
24-34
42
? (1-28)
No MgSO or steroids
24-32
28
9.5 (2-26)
No MgSO
26-31
229
14 (0-16)
Hall et al
26-34
340
10-30 (1-47)
No MgSO or steroids
MgSO steroids
Chammas et al
(2000, USA)
24-33
47
6 (1.5-28)
MgSO steroids
Vigil-DeGarcia
(2003, Panama)
24-34
129
8.5 (3-30)
MgSO steroids
No MgSO or steroids
Haddad et al
24-34
239
5 (2-35)
Oettle et al
(2004, France)
24-34
131
11.6 (1-89)
MgSO steroids
Shear et al
(2005, Canada)
24-34
155
5.3 (1-27)
MgSO steroids
24-34
216
11 (0.2-44)
(2004, France)
Ganzevoort et al
................................................................................................................................................................................................................................................................................................................................................................................
Observational studies
Recently, the results of several retrospective and observational studies that described expectant management of severe
preeclampsia at 24-34 weeks of gestation
have suggested that such management
improves perinatal outcome without increasing maternal morbidity.4, 6,8,10,12-17
The results of these studies are summarized in Table 1. The reviewed studies included patients with preeclampsia and
patients with chronic hypertension with
superimposed preeclampsia. In addition, the authors of these studies did not
mention whether the patients who were
included had de novo severe preeclampsia or had progressed from mild to severe
preeclampsia at the initiation of expectant treatment. The average days of pregnancy prolongation and the ranges are
highly variable among these studies,
which reflect the heterogeneity of the patients who were studied (different criteria for severe preeclampsia, varying ges-
514.e2
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TABLE 2
Abruption (%)
Nonreassuring fetal
testing (%)
Randomized trials
.......................................................................................................................................................................................................................................................................................................................................................................
2
Odendaal (n 18)
22
Not reported
38.9
16.6
30.1
26.5
.......................................................................................................................................................................................................................................................................................................................................................................
3
Sibai et al (n 49)
4.1
................................................................................................................................................................................................................................................................................................................................................................................
Observational studies
.......................................................................................................................................................................................................................................................................................................................................................................
6
Olah et al (n 28)
7.1
Not reported
35.7
7.1
5.1
58.1
74.0
13.6
36
44.4
9.0
.......................................................................................................................................................................................................................................................................................................................................................................
8
.......................................................................................................................................................................................................................................................................................................................................................................
12
(n 340)
Hall et al
20
.......................................................................................................................................................................................................................................................................................................................................................................
13
Vigil-DeGracia
(n 129)
8.5
21.7
Not reported
7.0
Chammas et al
(n 47)
12.7
51.1
44.7
6.4
8.7
24.3
42.8
5.4
Not reported
55.2
13.3
61.9
Not reported
.......................................................................................................................................................................................................................................................................................................................................................................
10
.......................................................................................................................................................................................................................................................................................................................................................................
14
Haddad et al
(n 239)
.......................................................................................................................................................................................................................................................................................................................................................................
16
Oettle et al
(n 131)
22.9
Shear et al
(n 155)
5.8
.......................................................................................................................................................................................................................................................................................................................................................................
15
3.9
................................................................................................................................................................................................................................................................................................................................................................................
* Ganzevoort et al
17
was not included in this Table because 55% of patients began with FGR.
P ERINATAL C OMPLICATIONS
D URING E XPECTANT
T REATMENT
The main aim of expectant treatment is
to improve perinatal outcome by prolonging gestation and reducing neonatal
morbidities (acute and long-term).
There are potential perinatal complications during expectant treatment; consequently, all reported studies recommended intensive fetal surveillance for
early detection of fetal compromise. The
most common indication for delivery in
most studies was deterioration in fetal status. Table 2 summarizes the perinatal complications during expectant treatment in
the reported studies.2,3,5,6,8,10,12-16
During expectant treatment of patients with severe preeclampsia at 24-34
weeks of gestation, the rate of perinatal
death in the reported studies ranged
from 0 to 16.6%.2,3 This variation in
perinatal death reflects differences in
gestational age at inclusion, the presence
or absence of FGR, HELLP syndrome or
eclampsia, and quality of neonatal care
(year of reporting and county). Indeed, in recent studies from the United
States, Canada, and France, the perinatal
514.e3
M ATERNAL C OMPLICATIONS
D URING E XPECTANT
T REATMENT
The main aim of the expectant management of severe preeclampsia remote
from term is prolonging gestation without jeopardizing maternal safety. Because the clinical course of severe preeclampsia can result in progressive
Clinical Opinion
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TABLE 3
Eclampsia (%)
Randomized trials
.......................................................................................................................................................................................................................................................................................................................................................................
2
Odendaal et al (n 18)
Not reported
5.5
.......................................................................................................................................................................................................................................................................................................................................................................
3
Sibai et al (n 49)
4.1
................................................................................................................................................................................................................................................................................................................................................................................
Observational studies
.......................................................................................................................................................................................................................................................................................................................................................................
4
Sibai et al (n 54)
13.0
5.6
Olah et al (n 28)
14.3
3.6
5.2
2.1
1.7
1.2
.......................................................................................................................................................................................................................................................................................................................................................................
6
.......................................................................................................................................................................................................................................................................................................................................................................
12
Hall et al
(n 340)
.......................................................................................................................................................................................................................................................................................................................................................................
13
Vigil-DeGracia et al
(n 129)
8.5
2.3
1.6
17.0*
8.5
17.0*
14.2
3.8
2.3
2.3
.......................................................................................................................................................................................................................................................................................................................................................................
10
Chammas et al
(n 47)
.......................................................................................................................................................................................................................................................................................................................................................................
14
Haddad et al
(n 239)
.......................................................................................................................................................................................................................................................................................................................................................................
16
Oettle et al
(n 131)
4.6
0.8
Shear et al
(n 155)
27.1
3.9
.......................................................................................................................................................................................................................................................................................................................................................................
15
Not reported
1.9
................................................................................................................................................................................................................................................................................................................................................................................
fetal growth restriction. This was a retrospective study in which perinatal outcomes of both mother and fetus were
stratified according to gestational age
and severity of FGR that was determined
after delivery. Their conclusions, however, were not supported by the reported
data because all cases of eclampsia, abruption, and pulmonary edema occurred in those pregnancies that resulted
in a birthweight at 10th percentile.
Further, the rates of fetal indications for
delivery were significantly higher in
pregnancies that resulted in FGR.
514.e4
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TABLE 4
Patients (n)
15
27
Moodley et al
10
100
50
25
84
Gauler-Senden et al
26
................................................................................................................................................................................................................................................................................................................................................................................
19
................................................................................................................................................................................................................................................................................................................................................................................
8
9
Not reported
................................................................................................................................................................................................................................................................................................................................................................................
21
22/27 (82)*
65
................................................................................................................................................................................................................................................................................................................................................................................
18
Hall et al
88
36
31
71
71
................................................................................................................................................................................................................................................................................................................................................................................
23
Bunden et al
................................................................................................................................................................................................................................................................................................................................................................................
O PTIMAL C ANDIDATES ,
T REATMENT , AND I NDICATIONS
FOR D ELIVERY
The main objective of the management
of severe preeclampsia must always be
the safety of the mother and the fetus.
Although delivery is always appropriate
for the mother, it might not be best for a
very premature fetus. The decision between delivery and expectant treatment
depends on fetal gestational age, fetal status, and severity of maternal condition at
the time of assessment. This objective
can be achieved by the formulation of a
management plan that considers 1 of
the following factors: fetal gestational
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FIGURE
Eclampsia
Pulmonary edema
Acute renal failure
Disseminated Coagulopathy
< 23 weeks gestation
Gestational age 33 0/7-34 0/7 weeks
Non-reassuring fetal status
Yes
Delivery before
completion of steroids
No
HELLP syndrome
Severe FGR oligohydramnios
UAD with reverse diastolic flow
Persistent symptoms
Thrombocytopenia
Gestational age 33 0/7-34 0/7 weeks
Labor or rupture or membranes
Yes
Steroids
48 hr delay if possible
No
3 0/7-23 6/7 week
Counseling
Termination of
Pregnancy
Antihypertensives if needed
Daily evaluations of maternal-fetal conditions
Delivery at 33 6/7 weeks
Clinical Opinion
514.e6
Clinical Opinion
Obstetrics
TABLE 5
Indication
Maternal
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
Epigastric/right upper quadrant pain with AST or ALT 2 times the upper
limits of normal
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
3
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
Fetal
Severe FGR (estimated fetal weight, 5th percentile for gestational age)
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
Fetal death
..............................................................................................................................................................................................................................................
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active and twice weekly amniotic fluid
assessment.2-4,7,10,12-15,33 Severe oligohydramnios is defined as an amniotic fluid
index of 5 cm on at least 2 occasions
that are at least 24 hours apart. Severe
oligohydramnios is considered an indication for delivery in all patients with a
gestational age of 30 weeks, irrespective of other fetal testing results. In those
30 weeks of gestation, pregnancy may
be continued with reassuring nonstress
test and umbilical artery Doppler findings. Umbilical artery Doppler studies
are performed weekly, or more often if
FGR is suspected and/or testing reveals
abnormal diastolic flow.13,15,16 Umbilical artery Doppler studies with reverse
diastolic blood flow after initial maternal/fetal stabilization is considered an
indication for delivery. Ultrasonographic assessment of fetal growth is performed every 2 weeks.2-4,7,10-16
If a patient experiences headache that
does not resolve with oral analgesics
within 6 hours and the headache continues to be severe, they should be transferred to the labor and delivery unit and
receive intravenous magnesium sulfate
and antihypertensives as needed. If the
headache persists, preparations should
be made for delivery. Patients with new
onset epigastric or right upper abdominal pain, retrosternal pain or pressure,
and recurrent heart burn, particularly in
association with nausea and vomiting,
are also transferred to the labor and delivery unit for further assessment. If the
symptoms persist and/or the liver enzymes are abnormal, preparations are
made for delivery. In addition, the onset
of uterine contractions and/or vaginal
bleeding requires immediate transfer to
the labor and delivery unit because it
could signify the development of abruptio placentae.
At any time during expectant treatment, the development of any of the
findings that are detailed in Table 5 necessitates delivery. There are no randomized trials that compare the optimal
method of delivery in women with severe
preeclampsia at 34 weeks of gestation.31,32 In general, the decision to perform cesarean delivery in such women
should be based on 1 of the following
factors: fetal gestational age and condi-
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tion, fetal presentation, presence of labor, and cervical Bishop score. The cesarean section rate among reported
studies ranged from 66%-96%, with the
higher rates for patients with severe preeclampsia at 28 weeks of gestation.2-26
On the basis of the available data, we recommend that a plan for vaginal delivery
be attempted in all patients with a gestational age of 32 0/7 weeks with vertex
presentation. In addition, vaginal delivery may be attempted in those women
between 27 0/7 and 31 6/7 weeks of gestation in the absence of severe FGR
and/or reverse UAD findings. Labor
induction should be carried out aggressively once the decision for delivery has been made.32 This should include delivery within 24 hours of the
induction.32 Serial induction of labor
is not appropriate in these cases. Elective cesarean section is recommended
for all patients with gestational age below 27 weeks of and for all those with
severe FGR and/or reverse umbilical
artery Doppler (UAD) at 32 weeks of
gestation.4,14,15,17
Once the decision is made for delivery, the patients should receive intravenous magnesium sulfate in labor and
for at least 24 hours after delivery.
Some authors recommended a shorter
duration of magnesium sulfate therapy
in the postpartum period34,35; however, these recommendations do not
apply to expectant treatment because
all protocols have used at least 24 hours
of magnesium sulfate therapy in such
women.2-4,6,7,10-13,16
During the immediate postpartum period, women with severe preeclampsia
should receive close monitoring of blood
pressure and symptoms and accurate
measurements of fluid intake and urinary output. These women usually receive large amounts of intravenous fluids
during labor, as a result of prehydration
before epidural analgesia, and intravenous fluids during the administration of
oxytocin and magnesium sulfate in labor
and after delivery. In addition, during
the postpartum period, there is mobilization of extracellular fluid that leads to
increased intravascular volume. As a result, such women are at increased risk for
pulmonary edema and exacerbation of
C OMMENT
We have described the rationale, the candidates, the recommendations, and the
guidelines for treatment of patients with
severe preeclampsia at 34 weeks of gestation. These recommendations and
guidelines are not absolute rules for
treatment and are based on a review of
recent literature and on our experience
with hundreds of patients whom we have
treated during the past decade. It is important to emphasize that the described
protocol is not a cookbook. We believe
that clinical judgment must still play a
considerable role in the treatment of
these patients. Nevertheless, the treating
physician should have full appreciation
of the protean manifestations of the syndrome of preeclampsia and of the potential for the rapid progression of the disease process during expectant treatment.
Therefore, expectant treatment should
be performed only in a select group of
patients after maternal counseling regarding the benefits and risks of such
treatment.2-4,7 It should be performed
only in select hospitals (with adequate
maternal and neonatal intensive care facilities) and should include close maternal and fetal surveillance and a target
gestational age for delivery and indications for delivery before the target.
Patient selection should include consideration of underlying maternal disease and specifically those women with a
gestational age remote from fetal viability or a gestational age at which the fetus
would have acceptable extrauterine survival and long-term intact survival. Individuals who follow this process should
Clinical Opinion
514.e8
Clinical Opinion
Obstetrics
514.e9
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evated liver enzymes, and low platelet count.
Obstet Gynecol 2004;103:981-91.
26. Visser W, Wallenburg HCS. Temporising
management of severe preeclampsia with and
without HELLP syndrome. BJOG 1995;102:
111-7.
27. van Pampus MG, Wolf H, Westenberg SM,
der Post V, Bonsel GJ, Treffers PE. Maternal
and perinatal outcome after expectant management of HELLP syndrome compared with preeclampsia without HELLP syndrome. Eur J Obstet Gynecol Reprod Biol 1998;76:31-6.
28. van Runnard Heimel PJ, Huisjes AJM, Fraux
A, Koopman C, Bots ML, Bruinse HW. A randomized placebo-controlled trial of prolonged
prednisolone administration to patients with
HELLP syndrome remote from term. Eur J Obstet Gynecol Reprod Biol 2006;128:187-93.
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Audibert F, Kao L. Sibai BM. Neonatal outcome
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enzymes, and low platelet count) syndrome
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focusing on systolic blood pressure. Obstet Gynecol 2005;105:246-54.
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33. Chari RS, Friedman SA, OBrien JM, Sibai
BM. Daily antenatal testing in women with severe preeclampsia. Am J Obstet Gynecol
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34. Isler CM, Barrilleaux PS, Rinehart BK, Magann EF, Martin JN Jr. Postpartum seizure prophylaxis: Using maternal clinical parameters to
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35. Fontenot MT, Lewis DF, Frederick B, et al. A
prospective randomized trial of magnesium sulfate in severe preeclampsia: use of diuresis as a
clinical parameter to determine the duration of
postpartum therapy. Am J Obstet Gynecol
2005;192:1788-94.
36. Ascarelli MH, Johnson V, McCreary H,
Cushman J, May WL, Martin JN Jr. Postpartum
preeclampsia management with furosemide: a
randomized clinical trial. Obstet Gynecol
2005;105:29-33.
37. Higgins RD, Delivoria-Papadopoulos M,
Raju TNK. Executive summary of the workshop
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