Académique Documents
Professionnel Documents
Culture Documents
ajog.org
OBSTETRICS
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).
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.
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
515.e1
Research
Obstetrics
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
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
Research
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
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
128 (75)
15 (1)
< .001
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.
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
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.
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)
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.
Research
515.e5
Research
Obstetrics
ajog.org
TABLE 3
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
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
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.
Obstetrics
ajog.org
Research
TABLE 4
Neonatal outcomes
<340/7 wks of gestation
Superimposed
preeclampsia, n [ 92
Outcome variable
4/7
2
4/7
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).
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