Editorials [Link].

org

What to expect from expectant management in severe

preeclampsia at <34 weeks gestation: pregnancy outcomes
in developed vs developing countries
Baha M. Sibai, MD

P regnancies that are complicated by severe preeclampsia

at <34 weeks’ gestation are associated with high rates of
maternal and perinatal mortality and morbidities worldwide.1
women with severe preeclampsia from 24-33 weeks of
gestation in a suitable hospital is relatively safe and improves
neonatal outcome.1-3
The rates of these complications are substantially higher in The MEXPRE Latin Study is the first multicenter trial that
developing countries with limited health resources.2,3 In was designed to compare the benefits and risks of delivery
Western countries, the rate of severe preeclampsia at <34 after the completion of corticosteroids vs expectant treatment
weeks’ gestation is 0.3%.1 These rates are higher in women in 267 women with severe preeclampsia from 28-33 weeks’
with a history of preterm preeclampsia and multifetal gesta- gestation.4 The trial was conducted at 8 tertiary hospitals in
tion and in those with preexisting medical disorders such as Latin America: 133 women were assigned randomly to de-
hypertension, renal disease, pregestational diabetes mellitus, livery, and 134 women were assigned randomly to expectant
or connective tissue disease. Historically, women with severe treatment. The primary outcome was perinatal death. Sec-
preeclampsia at <34 weeks’ gestation have had delivery ondary outcomes were a composite of adverse maternal and
initiated on diagnosis or after completion of a course of neonatal outcomes. The sample size was calculated with the
corticosteroids for fetal lung maturity because the clinical assumption of a 30% reduction in the rate of the primary
course of such pregnancies is often characterized by pro- outcome from 15% in the delivery group to 10.5% in the
gressive deterioration if delivery if not accomplished.1,2 expectant treatment group. Women in the delivery group
The main objective of expectant management of severe received corticosteroid therapy followed by delivery 24-72
preeclampsia must always be the safety of the mother and hours later. Women in the expectant treatment group received
fetus.2 Although delivery is always appropriate for the corticosteroid therapy followed by delivery only for specific
mother, it might not be best for a premature fetus. Man- maternal/fetal indications or until 34 weeks’ gestation. Three
agement with delivery after corticosteroid administration women were excluded after randomization in the expectant
leads to high neonatal mortality and morbidity rates, whereas treatment group, which left 264 women for analysis. The
attempts to prolong pregnancy with expectant management average pregnancy prolongation in the expectant group was
may result in fetal death, increased rates of fetal growth re- 10.3þ to 8 days, which was significantly higher than the
striction, and increased maternal morbidities.1-3 Since 1990, 2 average of 2.2þ to 0.8 days in the delivery group (P < .0001).
randomized trials that included only 133 women and several Despite this difference in pregnancy prolongation, there were
observational studies that included approximately 1900 no significant differences between groups in either perinatal
women evaluated the benefits and risks of expectant man- deaths (9.4% in delivery group vs 8.7% in expectant group),
agement of severe preeclampsia at <34 weeks’ gestation. The composite neonatal morbidities (56.4% vs 55.5%, respec-
results of these studies were the subject of 3 recent reviews tively), or composite maternal morbidities (20.3% vs 25.3%
that suggested that expectant treatment in a select group of respectively). In addition, women who were assigned
randomly to the expectant group had higher rates of small-
for-gestational-age infants (21.7% vs 9.4%; P ¼ .005) and
higher rates of abruptio placentae (7.6% vs 1.5%; P ¼ .01).
From the Department of Obstetrics and Gynecology and Reproductive
Science, The University of Texas Medical School at Houston,
On the basis of the results of this trial, the authors suggest that
Houston, TX. severe preeclampsia at 28-33 weeks’ gestation should be
The author reports no conflict of interest. managed with delivery after corticosteroid administration.
Reprints: Baha M. Sibai, Professor and Director of Maternal Fetal
The results of the trial are not surprising because pregnancy
Medicine Fellowship, Department of Obstetrics and Gynecology outcome during expectant management depends on gesta-
and Reproductive Science, The University of Texas Medical School tional age at onset and the experience of the clinical center in
at Houston, 6431 Fannin St., MSB 3.286, Houston, TX 77030. treating such patients. This trial was conducted at several
[Link]@[Link]. hospitals in 6 countries in Latin American with different
0002-9378/free expertise in treating such patients. There was no standardized
ª 2013 Mosby, Inc. All rights reserved.
[Link]
protocol for what is considered an “uncontrollable blood
pressure” with the use of oral antihypertensive medications. As
See related article, page 425 a result, this indication was the reason for delivery in 40% of
women in the expectant treatment group. One would expect

400 American Journal of Obstetrics & Gynecology NOVEMBER 2013

[Link] Editorials
this rate to be approximately 6% if maximum doses of com- Finally, current guidelines for expectant management of
bined antihypertensive medications are used.5 In addition, severe preeclampsia at <34 weeks’ gestation are based on the
42% of the patients were enrolled at 32-33 6/7 weeks’ gestation; results from 1 randomized trial in the United States with only
an estimated fetal weight of <10th percentile was considered 95 patients, 1 randomized trial from South Africa with only
an indication for delivery. This will explain the shorter dura- 58 patients, and several observational studies. Several retro-
tion of pregnancy prolongation in this trial (average, 10 days) spective and observational studies have reported increased
compared with the average of 15 days reported by Sibai et al.5 rates of maternal morbidities with such management.1-3
The results of the trial warrant other comments. First, the Therefore, there is an urgent need for randomized trials
trial did not have adequate sample size to answer the question with adequate sample size to address the safety of this man-
of whether expectant management is associated with lower agement in developed countries. Alternatively, there is a need
rate of perinatal mortality (the primary outcome) because the to develop a biomarker to identify those women who will not
rate of this outcome in the delivery group was substantially benefit from such treatment or to develop a targeted novel
lower than assumed in the sample size calculations. This is therapy to treat the underlying pathophysiologic condition
not surprising considering that 42% were enrolled at 32-33 in an attempt to prevent adverse maternal outcomes and
weeks’ gestation, but the perinatal mortality rate was only 2%. prolong gestation beyond what is expected with current
In addition, in a previous retrospective study of expectant management. -
management in similar patients that was reported from
Panama by Vigil-De Gracia et al,6 the reported perinatal
mortality rate in 89 women with gestational age of 29-33 REFERENCES
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