Vous êtes sur la page 1sur 8

Research

ajog.org

OBSTETRICS

Expectant management of mild preeclampsia


versus superimposed preeclampsia up to
37 weeks
Amy M. Valent, DO; Emily A. DeFranco, DO, MS; Allessa Allison, MD; Ahmed Salem, MD;
Lori Klarquist, DO; Kyle Gonzales, DO; Mounira Habli, MD; C. David Adair, MD;
Casey Armistead, RN; Yuping Wang, MD, PhD; David Lewis, MD, MBA; Baha Sibai, MD
OBJECTIVE: We sought to compare maternal and neonatal outcomes

RESULTS: We found no significant differences in rates of neonatal

of expectantly managed pregnancies complicated by chronic hypertension with superimposed preeclampsia vs mild preeclampsia up to
37 weeks of gestation.

composite morbidity or latency periods between women with superimposed preeclampsia and mild preeclampsia. Adverse neonatal
outcomes were significantly higher at <34 compared to 34-366/7
weeks of gestation (97-98% vs 48-50%) in both cohorts. Maternal
adverse composite outcome occurred more frequently in women with
superimposed preeclampsia compared to mild preeclampsia (15% vs
5%; P .003; relative risk, 3.0; 95% confidence interval, 1.45e6.29).

STUDY DESIGN: This was a multicenter retrospective cohort study


of all pregnancies complicated by chronic hypertension with
superimposed preeclampsia or mild preeclampsia expectantly
managed in the hospital from January 2008 through December
2011. The primary outcomes, adverse maternal and neonatal
composite morbidities, were compared between these 2 groups.
Frequency differences of maternal adverse outcomes were stratified by gestational age at delivery of <34 and 34-366/7 weeks of
gestation.

CONCLUSION: Women with superimposed preeclampsia have similar


neonatal outcomes but more maternal complications than women
with preeclampsia without severe features who are expectantly
managed <37 weeks.

Key words: expectant management, hypertension, preeclampsia

Cite this article as: Valent AM, DeFranco EA, Allison A, et al. Expectant management of mild preeclampsia versus superimposed preeclampsia up to 37 weeks. Am J
Obstet Gynecol 2015;212:515.e1-8.

ypertensive disorders are among


the most common pregnancy
complications. Preeclampsia complicates 3-7% of all pregnancies with a 4-5
times higher incidence in the presence of
chronic hypertension.1-4 These conditions markedly increase the risk of both
maternal and neonatal morbidity and
mortality.1,5
Expectant management with close
maternal and fetal surveillance and

planned delivery at 37 weeks of gestation


is recommended for patients with mild
preeclampsia in the absence of other
delivery indications.6-8 The recent
American Congress of Obstetricians
and Gynecologists (ACOG) Task Force
on Hypertension in Pregnancy states
that preterm preeclampsia without severe features may be followed expectantly with inpatient or outpatient
management.7 However, many expert

authorities recommend hospitalization


with a diagnosis of preeclampsia as signicant morbidity and mortality are
increased even without progression to
severe disease.
The broad disease spectrum, especially in the setting of concomitant organ
insult, and the challenge of diagnosing
preeclampsia in the presence of chronic
hypertension has led to a paucity of
quality studies regarding optimal

From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Cincinnati School of Medicine (Drs Valent and
DeFranco); Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Childrens Hospital Medical Center (Drs DeFranco and Habli); and Division
of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Good Samaritan Hospital (Drs Salem, Klarquist, and Habli), Cincinnati, OH;
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of South Alabama Childrens and Womens Hospital, Mobile,
AL (Drs Allison and Lewis and Ms Armistead); Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee
College of Medicine, Chattanooga, TN (Drs Gonzales and Adair); Department of Obstetrics and Gynecology, Louisiana State University Health Sciences
Center, Shreveport, LA (Dr Wang); and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Health,
University of Texas, Houston, TX (Dr Sibai).
Received June 3, 2014; revised Sept. 13, 2014; accepted Oct. 28, 2014.
The authors report no conict of interest.
Presented in poster format at the 79th annual meeting of the Central Association of Obstetricians and Gynecologists, Chicago, IL, Oct. 17-20, 2012.
Corresponding author: Amy M. Valent, DO. miyoshay@ucmail.uc.edu
0002-9378/$36.00  2015 Elsevier Inc. All rights reserved.  http://dx.doi.org/10.1016/j.ajog.2014.10.1090

APRIL 2015 American Journal of Obstetrics & Gynecology

515.e1

Research

Obstetrics

management. The ACOG Practice


Bulletin, addressing chronic hypertension in pregnancy, recommends delivery
at 34 weeks of gestation for patients with
superimposed preeclampsia.9 Management and delivery timing in this patient
population is based on indirect conclusions from severe preeclampsia
studies.10-12 Patient surveillance and
expectant management of severe preeclampsia and chronic hypertension
with superimposed preeclampsia at
tertiary care institutions are similarly
associated with prolonged pregnancy,
decreased neonatal intensive care unit
stays, and respiratory distress syndrome
(RDS) without signicant maternal
compromise <34 weeks.10,11,13 Evidence
supporting that delivery at 34 weeks of
gestation is superior to expectant management until 37 weeks of gestation
for superimposed preeclampsia without
severe disease is lacking.7
Despite the inconsistent recommendations regarding the optimal delivery
timing for superimposed preeclampsia
diagnosed in the preterm period
compared to mild preeclampsia, surprisingly few studies have compared the
maternal and fetal outcomes of these 2
conditions.13,14 Women with chronic
hypertension even without subsequent
superimposed preeclampsia have increased adverse perinatal outcomes
including but not limited to gestational
diabetes, fetal growth restriction, cesarean delivery, and worsening hypertension.1,3,15 Preeclampsia is a risk factor for
long-term cardiovascular conditions and
it is biologically plausible that superimposed preeclampsia represents further
cardiovascular disease and endothelial
dysfunction progression, which places
women at higher risk of adverse outcomes.16 Although there are promising
studies using imaging and biomarkers to
predict preeclampsia and potential disease progression, we still do not fully
understand the natural disease process
or etiology of preeclampsia, especially
superimposed preeclampsia.17,18
The purpose of this study is to
compare the rates of adverse maternal
and neonatal outcomes in patients
with mild preeclampsia and superimposed preeclampsia who are managed

ajog.org
expectantly in the hospital <37 weeks of
gestation. Secondary goal of this study is
to analyze outcomes of pregnancies that
are stratied between 34-366/7 vs <34
weeks of gestation to gain a better
understanding of the natural history of
these 2 disease processes. We hypothesize that in the hospital setting with close
monitoring, patients with superimposed
preeclampsia can be managed safely with
similar perinatal risks as patients with
mild preeclampsia without a hypertensive history.

M ATERIALS

AND

M ETHODS

This was a multicenter retrospective


cohort study including 4 tertiary care
teaching hospitals. All patients admitted
to the University of Cincinnati Medical
Center; University of South Alabama
Childrens and Womens Hospital; Good
Samaritan Hospital, Cincinnati; and
University of Tennessee College of
Medicine, Chattanooga, from January
2008 through December 2011 with a
diagnosis of mild preeclampsia or
chronic hypertension with superimposed preeclampsia were evaluated
for inclusion in this study. The study
period was prior to the ACOG Task
Force on Hypertension in Pregnancy
recommendations for the change in
terminology from mild preeclampsia
to preeclampsia and to distinguish
superimposed preeclampsia with and
without severe features.7
This study was approved by the institutional review board at the University
of Cincinnati, Cincinnati, OH (#1203-02-01) and individual institutional
review board approval was obtained at
all participating centers. International
Classication of Diseases, Ninth Revision
codes and/or antepartum and unit
recording systems were used to identify
all maternal and associated neonatal
charts with the diagnosis of preeclampsia, chronic hypertension, superimposed
preeclampsia, and/or preterm birth.
Coinvestigators at the individual institutions reviewed all potentially eligible
charts, and collected data regarding
maternal demographic characteristics,
gestational age at diagnosis and delivery,
latency period, mode of delivery, indications for delivery, and maternal and

515.e2 American Journal of Obstetrics & Gynecology APRIL 2015

neonatal outcomes. Inclusion criteria


comprised all singleton pregnancies between 240/7 and 366/7 weeks of gestation
with the diagnosis of mild preeclampsia
and chronic hypertension with superimposed preeclampsia that were
managed expectantly in the hospital.
Exclusion criteria were the diagnosis of
severe preeclampsia >340/7 weeks of
gestation at the time of admission, preeclampsia requiring delivery immediately after corticosteroids or maternal
stabilization, preterm labor or prelabor
rupture of membranes on admission,
major medical comorbidities not including chronic hypertension, multifetal
gestation, congenital anomalies, or other
maternal or fetal contraindications to
expectant management.
The primary outcomes of the study
were composites of maternal and
neonatal adverse morbidities. The
maternal composite was dened as 1 of
the following: pulmonary edema,
placental abruption, oliguria, and
eclampsia. The composite of neonatal
morbidities included 1 of the
following: RDS, intraventricular hemorrhage,
necrotizing
enterocolitis,
bronchopulmonary dysplasia, 5-minute
Apgar score of <7, and neonatal death.
Secondary outcome was the latency
duration from day of admission to
delivery. Other maternal morbidities of
interest included progression to severe
preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet
count) syndrome, abnormal liver enzymes, thrombocytopenia, and maternal
death. Additional neonatal complications studied comprised admission to
the neonatal intensive care unit and
suspected neonatal sepsis. Suspected
neonatal sepsis was dened as a neonate
receiving antibiotics during a sepsis
evaluation regardless of the culture
result. All neonatal complications were
diagnosed by a board-certied neonatologist. The collected cohort consisted
of minimal missing information for
primary outcomes of interest, exposure
variables, and covariates (<5%).
Patients included in this study were
categorized into 2 groups based on the
presence or absence of chronic hypertension. Hypertension was dened as

Obstetrics

ajog.org
systolic blood pressure 140 mm Hg or
diastolic blood pressure 90 mm Hg on
2 different occasions >4-6 hours apart
or persistent, elevated pressures requiring
antihypertensive
therapy.
Chronic hypertension was dened as the
use of antihypertensive medications
prior to conception, diagnosis of hypertension <20 weeks gestation, or the
presence of hypertension for >12 weeks
postpartum in a previous pregnancy.
Superimposed preeclampsia was dened
as women with chronic hypertension
who subsequently developed preeclampsia with an acute exacerbation of
preexisting hypertension in addition
to either new-onset proteinuria dened
by 0.3 g of total urinary protein
excretion over a 24-hour period or a
substantial increase in baseline proteinuria if present early in pregnancy. Mild
preeclampsia was dened as hypertension >20 weeks gestation with the
presence of proteinuria.
Upon admission, the patient was
evaluated to ensure she did not meet
criteria for severe preeclampsia. Fetal
viability was conrmed, baseline laboratory values (including but not limited
to liver enzyme tests, renal panel, urinalysis for protein evaluation, and
complete blood cell count) and a 24hour urine collection for total protein
excretion were subsequently completed
in the hospital. Serial ultrasound biometry every 3-4 weeks was performed to
assess fetal growth. Antenatal surveillance with nonstress test, biophysical
prole, Doppler studies, fetal kick
counts, or a combination of these modalities was used to determine fetal wellbeing. Laboratory assessments and
careful maternal clinical evaluations of
vital signs, urine output, symptoms, or
signs of disease progression were
routinely performed. Patients admitted
at <34 weeks of gestation received
antenatal corticosteroids for fetal lung
maturity. Women without evidence of
advancing, severe disease received oral
antihypertensive medications for management of severe range blood pressures
(systolic 160 mm Hg and/or diastolic
110 mm Hg).
For women with mild preeclampsia or
superimposed preeclampsia, expectant

management was continued unless fetal


or maternal indications required immediate intervention. Isolated fetal growth
restriction and isolated proteinuria >5
g/d without the presence of other severe
signs or symptoms were not indications
for delivery at the study institutions. The
progression of severe disease 34 weeks
of gestation was an indication for
delivery for all patients. Fetal reasons for
delivery included nonreassuring fetal
heart tracing or abnormal fetal testing,
which involved fetal growth restriction
with persistent oligohydramnios, umbilical artery Doppler velocimetry with
reversed end-diastolic ow, or nonreassuring biophysical prole score.
Maternal indications for delivery
included the development of renal
insufciency, eclampsia, placental abruption, pulmonary edema, persistent
gastrointestinal or neurologic symptoms, uncontrollable hypertension with
intravenous and/or orally titrated antihypertensive therapy, or laboratory
values suggesting thrombocytopenia
(<100,000/mL) or HELLP syndrome
(hemolysis, elevated liver enzymes [2
times the normal transaminase concentrations], and low platelet).
The criteria for severe preeclampsia
included the presence of 1 of the
following: 2 systolic blood pressures
160 mm Hg or diastolic blood pressures 110 mm Hg >4-6 hours apart
after administration of intravenous
antihypertensive therapy, oliguria (<500
mL or <0.5 mL/kg/h over 24 hours),
cyanosis, thrombocytopenia, elevated
liver enzymes, pulmonary edema,
eclampsia, or worsening/persistent gastrointestinal or neurologic symptoms
(ie, headache, epigastric pain, visual
disturbances, altered mental status). The
development of HELLP syndrome was
dened by evidence of hemolysis on a
peripheral blood smear, elevated lactate
dehydrogenase per institutional laboratory standards, decreased platelets, and
elevated liver enzyme tests.
The frequency of maternal and
neonatal adverse composite outcomes
were compared between pregnancies
complicated by mild preeclampsia and
superimposed preeclampsia. Both composite outcomes and integrated variables

Research

were compared after stratication by


gestational age into pregnancies that
delivered <34 and between 34-366/7
weeks of gestation. Estimated gestational
age was determined with a combination
of last menstrual period, ultrasound
imaging, and clinical assessment, which
is commonly accepted in general practice. Gestational weeks >366/7 were not
included in the data analysis because
expectant management of preeclampsia
is not the advocated approach due to the
progressive risk for adverse perinatal
outcomes.7,8
Statistical analysis was performed using StatView (SAS Institute Inc, Cary,
NC) and GraphPad Prism, version 5.00
for Windows (GraphPad Software, San
Diego, CA). Demographic characteristics were compared using Student t test
for continuous variables and c2 or Fisher
exact test for categorical variables.
Comparisons with a P value < .05 or
95% condence interval (CI) without
inclusion of the null were considered
statistically signicant.

R ESULTS
Over the 3-year study period, 357 patients met inclusion criteria for this
study; 171 pregnancies complicated by
chronic hypertension with superimposed preeclampsia and 186 women
with mild preeclampsia. University of
South Alabama Childrens and Womens
Hospital contributed 109 mother-infant
pairs; the University of Cincinnati
Medical Center contributed 100 pairs;
Good Samaritan Hospital contributed
95 pairs; and University of Tennessee
College of Medicine, Chattanooga, provided 53 mother-infant outcome data.
The demographic characteristics of the
2 groups are presented in Table 1. Patients with chronic hypertension with
superimposed preeclampsia were older,
more commonly multiparous, and
black. Higher rates of oral antihypertensive therapy during pregnancy and
postpartum period were observed
among women with superimposed preeclampsia compared to women without
a history of chronic hypertension.
Although patients with superimposed
preeclampsia were diagnosed and delivered at an earlier gestational age than

APRIL 2015 American Journal of Obstetrics & Gynecology

515.e3

Research

Obstetrics

ajog.org

TABLE 1

Maternal characteristics
Characteristic

Superimpose
preeclampsia, n [ 171

Preeclampsia,
n [ 186

P value

30  6

26  6

< .001

Caucasian

83 (49)

114 (61)

.02

Black

85 (50)

68 (39)

.01

Other

3 (2)

4 (2)

1.0

64 (32)

115 (62)

< .001

Vaginal

35 (21)

72 (38)

< .001

Repeat cesarean

51 (30)

26 (14)

< .001

Primary cesarean

85 (50)

88 (47)

.73

Oral antenatal antihypertensive


medications

128 (75)

15 (1)

< .001

Regimen with 1 medication

43 (25)

0 (0)

< .001

Age, y
Race and ethnicity

Primigravida
Mode of delivery

Continuous variable are presented as mean  SD. Dichotomous variables are presented as number (percent).
Valent. Expectant management of preeclampsia. Am J Obstet Gynecol 2015.

women diagnosed with mild preeclampsia, primary cesarean delivery


rates were not signicantly different
between the 2 groups.
The Figure demonstrates the most
common indications for delivery among
this cohort. Women with superimposed
preeclampsia were more likely to be
delivered for uncontrollable, elevated
blood pressures (57% vs 39%; P <.001),
and pregnancies complicated by mild
preeclampsia were delivered more commonly for the development of persistent
neurologic or gastrointestinal symptoms
(20% vs 6%; P < .001).
Although patients with mild preeclampsia had signicantly shorter hospitalization stays compared to women
with superimposed preeclampsia, no
difference in the latency periods between
diagnosis and delivery among the 2
groups were appreciated, even after
stratication at <34 or 34-366/7 weeks of
gestation (Tables 1 and 2). Pulmonary
edema was more frequently observed in
pregnancies with superimposed preeclampsia, particularly deliveries <34
weeks of gestation. Maternal adverse
composite outcome occurred more
frequently in women with superimposed
preeclampsia (15%) compared to those

with preeclampsia (5%) (relative risk


[RR], 3.0; 95% CI, 1.45e6.29). The rate
of adverse maternal outcome was
signicantly higher in women with
superimposed preeclampsia delivered at
later preterm gestational ages between
34-366/7 weeks (RR, 4.0; 95% CI,
1.13e14.39), as compared to <34 weeks
of gestation (RR, 2.3; 95% CI,
0.95e5.64; Table 3).
Prior to stratication into 2 preterm
gestational age categories, small for
gestational age (26% vs 16%; P .02)
and low birthweight (1941  790 vs 2161
 834 g; P < .001) were more frequent
among neonates born to mothers with
superimposed preeclampsia, but no
signicant difference in the frequency
of critical neonatal complications such
as necrotizing enterocolitis, RDS,
neonatal mortality, or intraventricular
hemorrhage was appreciated between
the 2 groups. Table 4 presents differences
in neonatal outcomes between the 2
groups stratied by gestational age at
delivery. Aside from a 5-minute Apgar
score <7, no signicant differences in
estimated gestational age at delivery
or neonatal outcomes were detected
between women with preeclampsia
and superimposed preeclampsia when

515.e4 American Journal of Obstetrics & Gynecology APRIL 2015

stratied between <34 or 34-366/7 weeks


of gestation. However, compared to
34-366/7 weeks, both cohorts delivering
<34 weeks of gestation had higher rates
of adverse neonatal composite morbidity
and mortality.
A total of 8 perinatal losses occurred in
the study cohort with all deliveries <34
weeks of gestation. There were 2 cases of
stillbirth in the 24th week of pregnancy,
both complicated by intrauterine growth
restriction with estimated fetal weights
of <300 g in the superimposed preeclampsia cohort. Five neonatal deaths
were among extremely preterm births at
<26 weeks of gestation in both study
groups.

C OMMENT
This study is one of the rst and largest
to compare the maternal and neonatal
outcomes following expectant management of pregnancies with mild
preeclampsia and superimposed preeclampsia up to 37 weeks of gestation.
Our multicenter, observational study
demonstrates that expectant, inpatient
management of these 2 diseases result in
similar neonatal outcomes. Without the
presence of severe disease at the time of
admission, they have comparable mean
latency periods from diagnosis to delivery irrespective of the gestational age
at diagnosis.
We found that women with superimposed preeclampsia were more
commonly black, older, multiparous,
and required oral antihypertensive
therapy, which is consistent with previous studies.19 This higher frequency of
antihypertensive treatment may be
indicative of ongoing chronic treatment
of their underlying disorder rather than
a marker of progressive, severe disease
during pregnancy. Antihypertensive
therapy has not been shown to improve
rates of preterm birth or progression to
superimposed preeclampsia but is recommended to reduce the risk of severe
hypertension, worsening end-organ
damage, and maternal complications
including cerebral hemorrhage and
infarction.12,20,21 Physicians are aware of
the increased perinatal risks among
chronic hypertensive women, likely
resulting in a lower threshold for

Obstetrics

ajog.org

FIGURE

Indications for delivery

Bar graph representing common indications for delivery in pregnancies complicated by superimposed preeclampsia (blue) and preeclampsia (green) expectantly managed in hospital setting. The
frequencies do not add up to 100% due to missing or other indications for delivery.
LFT, liver function testing; HELLP, hemolysis, elevated liver enzymes, and low platelet count; NR-ANFS, nonreassuring antenatal fetal
surveillance.
*Persistent neurological or gastrointestinal symptoms.
Valent. Expectant management of preeclampsia. Am J Obstet Gynecol 2015.

conservative inpatient supervision,


aggressive blood pressure management,
and longer hospitalizations. Hypertensive exacerbations and undiagnosed

microvascular disease can complicate the


clinical picture, diagnosis, and management strategies. However, our study
shows that with careful inpatient

TABLE 2

Maternal outcomes
Superimposed
preeclampsia, n [ 171

Outcome variable
EGA at diagnosis, wk

314/7  33/7

Latency, d
Days in hospital
Severe preeclampsia

Preeclampsia,
n [ 186

P value

324/7  31/7

.004

10  13
5 [2e11]

88
5 [3e10]

.12

13  12
9 [6e16]

10  7
8 [6e11]

< .001

149 (87)

157 (84)

.56

Pulmonary edema

7 (4)

0 (0)

.01

Placental abruption

11 (6)

5 (3)

.18

Thrombocytopenia

8 (5)

12 (6)

.62

24 (14)

29 (16)

.79

Oliguria

7 (4)

5 (3)

.66

HELLP

2 (1)

7 (4)

.22

1 (1)

1 (1)

25 (15)

9 (5)

Elevated liver enzymes

Eclampsia
Maternal composite

1.0
.003

Continuous variable are presented as mean  SD or median [interquartile range]. Dichotomous variables are presented as
number (percent).
EGA, estimated gestational age; HELLP, hemolysis, elevated liver enzymes, and low platelet count.
a

Morbidity defined as 1 of the following: pulmonary edema, placental abruption, eclampsia, oliguria.

Valent. Expectant management of preeclampsia. Am J Obstet Gynecol 2015.

Research

management, women with superimposed preeclampsia can continue


pregnancy >34 weeks of gestation with
titrating doses of antihypertensives as
long as the blood pressure responds to
these increases.
Women in both groups were found
to have high rates of neonatal mortality and respiratory morbidities,
especially deliveries <34 weeks of
gestation. Hypertensive disorders may
contribute to impaired fetal growth
and increase the risk for birth of
small-for-gestational-age infants.22,23
Consistent with previously published
studies, we found that women with
superimposed preeclampsia had higher
rates of small for gestational age and
overall lower average birthweights than
patients with mild preeclampsia, but
no difference was observed when
stratied by gestational age at delivery.3,9,24 This could be explained in
part by the increased use of oral antihypertensive maintenance therapy in
superimposed preeclamptic patients,
which is known to reduce mean arterial pressure and is associated with
small for gestational age independent
of duration of therapy.25
Given the minimal observed difference in frequency of these adverse
neonatal outcomes with a probability
value >5%, we conclude that no significant difference in neonatal outcomes
occurs following births to superimposed
preeclampsia and mild preeclampsia
pregnancies managed expectantly in the
late preterm period. Similarly, the likelihood of an adverse neonatal outcome
for births <34 weeks of gestation did not
differ between the 2 cohorts but the
frequency of adverse neonatal morbidity
was signicantly higher (94-97%) than
those managed and delivered between
34-366/7 weeks of gestation. We did
observe a higher frequency of RDS in
late preterm infants than is commonly
reported in prospectively performed
studies.26 This may be related to
misclassication of some cases of oxygen
requirement or respiratory complications as RDS that may not have not have
met strict criteria for RDS if dened as
such prospectively. Despite this, it is
unlikely that RDS cases were

APRIL 2015 American Journal of Obstetrics & Gynecology

515.e5

Research

Obstetrics

ajog.org

TABLE 3

Maternal outcomes stratified by preterm gestational age groups


<340/7 wks of gestation
Superimposed
preeclampsia, n [ 92

Outcome variable
EGA at diagnosis, wk

29

2/7

2

5/7

8.6  11.1

Latency, d
Days in hospital

12.2  9.1

Severe preeclampsia

34-366/7 wks of gestation


Preeclampsia,
n [ 80
30

1/7

2

5/7

P value

Superimposed
preeclampsia, n [ 79
6/7

2

4/7

Preeclampsia,
n [ 106

P value

1

.22

34

4/7

6/7

.08

33

6.2  4.1

.06

11.7  15.6

8.5  9.6

.09

9.6  3.7

.02

14.6  14.2

9.1  7.7

< .001

80 (87)

67 (77)

.70

69 (87)

90 (85)

.80

Pulmonary edema

6 (7)

0 (0)

.02

1 (1)

0 (0)

.85

Placental abruption

6 (7)

4 (5)

.93

5 (6)

1 (1)

.10

Thrombocytopenia

6 (7)

6 (7)

1.0

2(3)

6 (6)

.51

1.0

Elevated liver enzymes

12 (13)

10 (12)

12 (15)

19 (18)

Oliguria

4 (4)

2 (2)

.82

3 (4)

3 (3)

1.0

HELLP

1 (1)

5 (6)

.15

1 (1)

2 (2)

1.0

1 (1)

1 (1)

0 (0)

0 (0)

1.0

16 (17)

6 (8)

9 (11)

3 (2)

Eclampsia
Maternal composite

1.0
.08

.77

.04

Continuous variable are presented as mean  SD. Dichotomous variables are presented as number (percent).
EGA, estimated gestational age; HELLP, hemolysis, elevated liver enzymes, and low platelet count.
a

Morbidity defined as 1 of the following: pulmonary edema, placental abruption, eclampsia, oliguria.

Valent. Expectant management of preeclampsia. Am J Obstet Gynecol 2015.

differentially misclassied between the


superimposed preeclampsia and mild
preeclampsia groups.
The majority of pregnancies in this
study complicated by superimposed
preeclampsia and mild preeclampsia
developed severe preeclampsia. Compared to previous severe preeclampsia
studies and acknowledging variance
in sample sizes, similar rates of HELLP
and placental abruption were observed
in this study.11,13 Tuuli et al19 retrospectively studied the same pregnancy populations but observed lower rates of
placental abruption. However, their
study included patients over an 18 year
period and disease management has
changed progressively during this time.
Although a higher frequency of overall
composite maternal morbidity was
observed in women with superimposed
preeclampsia, the statistical differences
in the overall composite morbidity between 34-366/7 weeks of gestation were
driven by increased rates of placental
abruption without a signicant difference in neonatal outcome compared to
pregnancies with mild preeclampsia.
Expectant management >34 weeks of

gestation did not increase the risk of


serious maternal complications such as
HELLP, eclampsia, or pulmonary
edema.
Higher rates of pulmonary edema
were observed among women with
superimposed preeclampsia but all of
the events occurred <34 weeks and not
in later gestational ages. Severe hypertension was a more frequent delivery
indication for women with superimposed preeclampsia compared to
worsening neurologic or gastrointestinal symptoms in those women with
mild preeclampsia. An acute hypertensive crisis commonly precipitates pulmonary edema causing signicant
vasoconstriction, increased afterload,
and redistribution of uid centrally into
pulmonary circulation, placing all
women with preeclampsia at increased
risk.27,28 Alternatively, these women
may represent advanced endothelial
dysfunction predisposing them to
disease progression or insufcient
maternal immunologic response or
tolerance at an early gestation.
The latency duration found in this
study is consistent with previously

515.e6 American Journal of Obstetrics & Gynecology APRIL 2015

published studies reporting an average


duration between 8.4-9.7 days in
pregnancies complicated by superimposed preeclampsia.13,14 However,
prior studies followed management
recommendations suggested for severe
preeclampsia in women diagnosed with
superimposed preeclampsia, delivering
at 34 weeks of gestation even in the
absence of signs or symptoms of severe
disease. The practice of planned early
delivery at 34 weeks for women with
superimposed preeclampsia in the previously reported studies may have
inuenced the reported outcomes,
possibly demonstrating shorter latency
periods and more adverse neonatal outcomes related to prematurity.
Expectant management in the preterm period and delivery at 37 weeks,
unless earlier delivery was indicated due
to the development of signs or symptoms of severe disease, is consistent with
the most recent recommendations from
the ACOG Task Force on Hypertension
in Pregnancy.7 This study was performed
prior to the institution of the task force
guidelines for management. However,
removal of 5 g of proteinuria and fetal

Obstetrics

ajog.org

Research

TABLE 4

Neonatal outcomes
<340/7 wks of gestation
Superimposed
preeclampsia, n [ 92

Outcome variable

4/7

2

4/7

34-366/7 wks of gestation


Preeclampsia,
n [ 80
0/7

2

Superimposed
preeclampsia, n [ 79

P value

4/7

.18

35

5/7

1

0/7

EGA at delivery

30

Days in hospital

34.4  28.2

39.8  32.3

.25

6.0  4.6

NICU admission

86 (93)

71 (89)

.41

35 (44)

5-min Apgar 7

31

Preeclampsia,
n [ 106
35

6/7

1

0/7

7.3  9.0

P value
.17
.24

49 (46)

.91

15 (16)

16 (20)

.67

16 (20)

7 (7)

.01

1450  628

1446  628

.96

2576  579

2621  596

.61

SGA

28 (30)

15 (19)

.11

17 (22)

14 (13)

.20

RDS

33 (36)

21 (26)

.23

14 (18)

19 (18)

1.0

BPD

7 (8)

6 (8)

1 (1)

2 (2)

1.0

NEC

7 (8)

4 (5)

.71

0 (0)

1 (1)

1.0

13 (14)

13 (16)

.86

14 (18)

20 (19)

1.0

9 (10)

7 (9)

1 (1)

3 (3)

6 (7)

2 (3)

.38

0 (0)

0 (0)

89 (97)

75 (94)

.57

38 (48)

53 (50)

Birthweight, g

Suspected sepsis
IVH
Death

Neonatal composite

1.0

1.0

.87
1.0
.92

Continuous variable are presented as mean  SD. Dichotomous variables are presented as number (percent).
BPD, bronchopulmonary dysplasia; EGA, estimated gestational age; IVH, intraventricular hemorrhage of any grade; NEC, necrotizing enterocolitis; NICU, neonatal intensive care unit; RDS, respiratory
distress syndrome; SGA, small for gestational age.
a

Neonate received antibiotics; b Morbidity defined as 1 of the following: NICU admission, Apgar score 7 at 5 min, RDS, BPD, NEC, IVH, and death (fetal or neonatal).

Valent. Expectant management of preeclampsia. Am J Obstet Gynecol 2015.

growth restriction as indications for delivery in the new recommendations


would not have changed the outcomes of
this study as they were not direct indications for delivery at any participating
center. Although the old criteria had
oliguria as a sign of severe disease, the
frequencies of oliguria were not statistically signicant between the 2 groups
and would not have changed the rate of
adverse maternal outcome in our study.
A major strength of this study is the
large number of patients managed at 4
tertiary level centers, representing wide
national demographic regions and populations; therefore, we believe our ndings are widely generalizable. This study
addresses an issue that is not well studied
and important in perinatal management.
We specically excluded patients from
this study with other serious disease
comorbidities such as renal disease, systemic lupus erythematosus, and other
end-organ dysfunction. Likely through
different disease processes, women
with these disease states have risks for

worse perinatal outcomes regardless of


inclusion in either group and would not
represent the risks and outcomes specically of these hypertensive diseases
focused in this study.
This study faces the inherent weaknesses of any observational study.
Relying on International Classication of
Diseases, Ninth Revision codes for hypertensive diseases and preterm birth,
not all patients who meet inclusion
criteria may have been identied at all
participating centers. The maternal-fetal
medicine specialists at each institution
may have variations in management and
practicing styles despite all centers
consistently managing both patient cohorts expectantly until 37 weeks of
gestation during the study period.
Exclusion of other comorbidities, especially pregestational diabetes, may
somewhat limit the generalizability of
our ndings to all patient populations
presenting with chronic hypertension
and preeclampsia; however, we believe
these patients represent a unique

high-risk population who warrant individualized management regardless of


additional pregnancy complications.
Selection bias could inuence the study
ndings as physicians may have chosen
to deliver women with superimposed
preeclampsia who were perceived to be
at higher risk immediately, leaving a
lower risk study population that may not
represent the risks and outcomes of this
entire cohort. When the 2 groups were
further stratied by gestational age at
delivery (<34 and 34-366/7 weeks), our
study groups were further restricted in
numbers and limited the sample size to
detect a true difference for more rare
adverse outcomes. However, the statistically signicant ndings represent true
risk differences.
We found considerable perinatal
morbidity and mortality risks associated
with preeclampsia and chronic hypertension with superimposed preeclampsia. However, compared to each other,
neonatal complication rates do not differ
irrespective of gestational age. Although

APRIL 2015 American Journal of Obstetrics & Gynecology

515.e7

Research

Obstetrics

at later gestational ages maternal adverse outcomes are increased predominantly in women with superimposed
preeclampsia, overall adverse neonatal
morbidity is much lower without an increase in serious maternal morbidities.
This study further supports both cohorts
and especially superimposed preeclampsia should be managed at centers
where appropriate maternal and neonatal resources are available. As
currently practiced among women with
mild preeclampsia, it is reasonable and
safe to manage superimposed preeclampsia similarly with close inpatient
observation and delivery at 37 weeks of
gestation, unless an earlier indication
arises based on worsening disease, to
decrease neonatal morbidity. This retrospective study creates the basic platform
to study both populations prospectively
with larger cohorts to clearly determine if
these are 2 different disease processes and
truly require different delivery management and timing.
ACKNOWLEDGMENT
The authors thank Suneet Chauhan, MD, for his
contribution to the study design and support for
the development of this study.

REFERENCES
1. Sibai BM, Lindheimer M, Hauth J, et al. Risk
factors for preeclampsia, abruptio placentae,
and adverse neonatal outcomes among women
with chronic hypertension; National Institute of
Child Health and Human Development Network
of Maternal-Fetal Medicine Units. N Engl J Med
1998;339:667-71.
2. Sibai BM, Caritis SN, Thom E, et al. Prevention of preeclampsia with low-dose aspirin in
healthy, nulliparous pregnant women; the National Institute of Child Health and Human
Development Network of Maternal-Fetal Medicine Units. N Engl J Med 1993;329:1213-8.
3. Vanek M, Sheiner E, Levy A, Mazor M.
Chronic hypertension and the risk for adverse
pregnancy outcome after superimposed preeclampsia. Int J Gynaecol Obstet 2004;86:7-11.
4. Ananth CV, Keyes KM, Wapner RJ. Preeclampsia rates in the United States, 19802010: age-period-cohort analysis. BMJ
2013;347:f6564.

ajog.org
5. Kuklina EV, Ayala C, Callaghan WM. Hypertensive disorders and severe obstetric morbidity
in the United States. Obstet Gynecol 2009;113:
1299-306.
6. Sibai BM. Management of late preterm and
early-term pregnancies complicated by mild
gestational hypertension/pre-eclampsia. Semin
Perinatol 2011;35:292-6.
7. American College of Obstetricians and
Gynecologists; Task Force on Hypertension
in Pregnancy. Hypertension in pregnancy:
report of the American College of Obstetricians
and Gynecologists Task Force on Hypertension
in Pregnancy. Obstet Gynecol 2013;122:
1122-31.
8. Koopmans CM, Bijlenga D, Groen H, et al.
Induction of labor versus expectant monitoring
for gestational hypertension or mild preeclampsia after 36 weeks gestation (HYPITAT): a multicenter, open-label randomized
controlled trial. Lancet 2009;374:979-88.
9. American College of Obstetricians and
Gynecologists. Chronic hypertension in pregnancy. ACOG Practice bulletin no. 125. Obstet
Gynecol 2012;119:396-407.
10. Odendaal HJ, Pattinson RC, Bam R,
Grove D, Kotze TJ. Aggressive or expectant
management for patients with severe preeclampsia between 28-34 weeks gestation: a
randomized controlled trial. Obstet Gynecol
1990;76:1070-5.
11. Sibai BM, Mercer BM, Schiff E,
Friedman SA. Aggressive versus expectant
management of severe preeclampsia at 28 to 32
weeks gestation: a randomized controlled trial.
Am J Obstet Gynecol 1994;171:818-22.
12. Sibai BM, Koch MA, Freire S, et al. The
impact of prior preeclampsia on the risk of
superimposed preeclampsia and other adverse
pregnancy outcomes in patients with chronic
hypertension. Am J Obstet Gynecol 2011;204:
345.e1-6.
13. Vigil-De Gracia P, Montufar-Rueda C,
Ruiz J. Expectant management of severe preeclampsia and preeclampsia superimposed on
chronic hypertension between 24 and 34
weeks gestation. Eur J Obstet Gynecol Reprod
Biol 2003;107:24-7.
14. Samuel A, Lin C, Parviainen K, Jeyabalan A.
Expectant management of preeclampsia
superimposed on chronic hypertension.
J Matern Fetal Neonatal Med 2011;24:907-11.
15. Ferrer RL, Sibai BM, Mulrow CD,
Chiquette E, Stevens KR, Cornell J. Management of mild chronic hypertension during pregnancy: a review. Obstet Gynecol 2000;96:
849-60.
16. Mosca L, Aggarwal B, MochariGreenberger H, et al. Association between
having a caregiver and clinical outcomes 1 year

515.e8 American Journal of Obstetrics & Gynecology APRIL 2015

after hospitalization for cardiovascular disease.


Am J Cardiol 2012;109:135-9.
17. Cnossen JS, Morris RK, ter Riet G, et al.
Use of uterine artery Doppler ultrasonography
to predict pre-eclampsia and intrauterine growth
restriction: a systematic review and bivariable
meta-analysis. CMAJ 2008;178:701-11.
18. Powers RW, Jeyabalan A, Clifton RG, et al.
Soluble fms-like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies. PLoS
One 2010;5:e13263.
19. Tuuli MG, Rampersad R, Stamilio D,
Macones G, Odibo AO. Perinatal outcomes in
women with preeclampsia and superimposed
preeclampsia: do they differ? Am J Obstet
Gynecol 2011;204:508.e1-7.
20. Committee on Obstetric Practice. Emergent
therapy for acute-onset, severe hypertension
with preeclampsia or eclampsia. Committee
opinion no. 514. Obstet Gynecol 2011;118:
1465-8.
21. Martin JN Jr, Thigpen BD, Moore RC,
Rose CH, Cushman J, May W. Stroke and severe preeclampsia and eclampsia: a paradigm
shift focusing on systolic blood pressure. Obstet
Gynecol 2005;105:246-54.
22. Allen VM, Joseph K, Murphy KE, Magee LA,
Ohlsson A. The effect of hypertensive disorders
in pregnancy on small for gestational age and
stillbirth: a population based study. BMC Pregnancy Childbirth 2004;4:17.
23. Zetterstrom K, Lindeberg SN, Haglund B,
Hanson U. Chronic hypertension as a risk
factor for offspring to be born small for gestational age. Acta Obstet Gynecol Scand 2006;85:
1046-50.
24. Chappell LC, Enye S, Seed P, Briley AL,
Poston L, Shennan AH. Adverse perinatal
outcomes and risk factors for preeclampsia
in women with chronic hypertension: a
prospective study. Hypertension 2008;51:
1002-9.
25. von Dadelszen P, Ornstein MP, Bull SB,
Logan AG, Koren G, Magee LA. Fall in mean
arterial pressure and fetal growth restriction in
pregnancy hypertension: a meta-analysis. Lancet 2000;355:87-92.
26. Lubow JM, How HY, Habli M, Maxwell R,
Sibai BM. Indications for delivery and short-term
neonatal outcomes in late preterm as compared
with term births. Am J Obstet Gynecol
2009;200:e30-3.
27. Dennis AT, Solnordal CB. Acute pulmonary
edema in pregnant women. Anaesthesia
2012;67:646-59.
28. Schobel HP, Fischer T, Heuszer K,
Geiger H, Schmieder RE. Preeclampsiaea state
of sympathetic overactivity. N Engl J Med
1996;335:1480-5.

Vous aimerez peut-être aussi