Expectant management of severe preeclampsia at less than 27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management

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Expectant management of severe preeclampsia at less than 27 weeks’ gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management Annette E. Bombrys, DO; John R. Barton, MD; Elizabeth A. Nowacki, DO; Mounira Habli, MD; Leeya Pinder, MD; Helen How, MD; Baha M. Sibai, MD OBJECTIVE: The objective of the study was to determine perinatal outcome and maternal morbidities based on gestational age (GA) at the onset of expectant management in severe preeclampsia at less than 27 weeks. STUDY DESIGN: This was a retrospective analysis of outcome in pa-

tients with severe preeclampsia. Forty-six patients (51 fetuses) with severe preeclampsia at less than 27 weeks were studied. Corticosteroids were administered beyond 23 weeks. Perinatal and maternal complications (a composite maternal morbidities including HELLP (hemolysis, elevated liver enzymes, and low platelet count ) syndrome, pulmonary edema, eclampsia, and renal insufficiency were analyzed.

vivors in those with a GA less than 23 weeks, at 23 to 23 6/7 weeks, 2 of 10 (20%) survived, and both reached 26 weeks at delivery. For those at 24 to 24 6/7, 25 to 25 6/7, and 26 to26 6/7 weeks, the perinatal survival rates were 5 of 7 (71%), 13 of 17 (76%), and 9 of 10 (90%), respectively; but rates of respiratory complications were high. There were no maternal deaths, but overall maternal morbidity was 21 of 46 (46%), but was 9 of 14 (64%) in those at less than 24 weeks.

RESULTS: Four patients had multifetal gestations (1 triplet, 3 twins).

CONCLUSION: Perinatal outcome in severe preeclampsia in the midtrimester is dependent on GA at onset of expectant management and GA at delivery. Given the high maternal morbidity and extremely low perinatal survival in expectant management at less than 24 weeks, termination of pregnancies should be offered after extensive counseling.

Median days of prolongation was 6 (range 2-46). Overall perinatal survival was 29 of 51 (57%). Birthweights of 27 (53%) were less than 10%, and 18 (35%) were less than 5%. There were no perinatal sur-

Key words: expectant management, outcome, second trimester, severe preeclampsia

Cite this article as: Bombrys AE, Barton JR, Nowacki EA, et al. Expectant management of severe preeclampsia at less than 27 weeks’ gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management. Am J Obstet Gynecol 2008;199:247.e1-247.e6.

T

here are limited data regarding pregnancy outcome in expectant management of severe preeclampsia in the second trimester.1-8 Recommended management has been largely based on expert opinion with few prospective and retrospective

studies that have addressed expectant management remote from term. Recently Sibai and Barton1 reviewed all the available studies in the literature

From the Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine Division of Maternal-Fetal Medicine, Cincinnati, OH (Drs Bombrys, Habli, Pinder, How, and Sibai); Central Baptist Hospital, Lexington, KY (Dr Barton); and Southview Hospital, Dayton, OH (Dr Nowacki). Presented at the 28th Annual Meeting of the Society for Maternal-Fetal Medicine, Dallas, TX, Jan. 28-Feb. 2, 2008. Received March 1, 2008; revised May 7, 2008; accepted June 25, 2008. Reprints: Baha M. Sibai, MD, Univeristy of Cincinnati, ML 0526, 234 Goodman Ave, Cincinnati, OH 45221. [email protected]. 0002-9378/$34.00 • © 2008 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2008.06.086

For Editors’ Commentary, see Table of Contents See related editorial, page 209

regarding expectant management remote from term. In that review, the authors found only 115 patients with severe preeclampsia at less than 25 weeks who were managed expectantly. The overall perinatal mortality rate was extremely high (83%) and maternal complications were substantial (57%).1 Based on this review, they suggested that patients at 23 weeks or less should be offered termination of pregnancy; whereas those at 24 weeks or longer can be offered expectant management following extensive counseling.1 However, this review did not provide information about counseling that apply to women at a specific week of gestation (less than 23, 23-24, 24-25, 2526, 26 to 26 6/7 weeks). The purpose of this study was to evaluate maternal and perinatal outcomes with expectant management of severe preeclampsia at less than 27 weeks of gestation with data stratified according to

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FIGURE

Flow chart for Patient Selection

≥

Bombrys. Severe preeclampsia at less than 27 weeks. Am J Obstet Gynecol 2008.

specific week of gestation at time of onset of expectant management.

M ATERIALS AND M ETHODS We retrospectively reviewed the medical records of 336 gravid women with severe or severe superimposed preeclampsia, who delivered prior to 34 0/7 weeks, at the University of Cincinnati in Cincinnati, OH, and Central Baptist Hospital in Lexington, KY, between January 2000 and June 2007. This study was approved by the institutional review boards at both centers. A diagnosis of severe or superimposed preeclampsia was based on the criteria of the American College of Obstetricians and Gynecologists.9 The diagnosis of severe preeclampsia in those receiving expectant management was based on the presence of preeclampsia in association with 1 or more of the following: severe hypertension (systolic blood pressure of 160 mm Hg or greater and/or diastolic blood pressure of 110 mm Hg or greater on at least 2 occasions) and/or proteinuria of 5 g or greater per 24 hours and/or cerebral manifestations. All patients had to have documentation of the disease for 48 hours or longer to be considered expectantly managed. 247.e2

Patients with maternal or fetal indications requiring delivery within the first 48 hours of admission or gestational age of a gestation of 27 0/7 weeks or longer at the time of diagnosis were not included in this analysis (Figure). Exclusion criteria were the presence of thrombocytopenia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, eclampsia, renal failure, or pulmonary edema. In addition, the presence of severe oligohydramnios or severe fetal growth restriction (FGR) and reverse umbilical artery Doppler were exclusion criteria. Fetal viability was confirmed in all patients at admission. Patients were monitored carefully on the labor and delivery unit for a minimum of 24 hours. All patients were extensively counseled regarding the maternal and perinatal risks of expectant management.1 Initial drug therapy consisted primarily of intravenous magnesium sulfate to prevent convulsions and bolus injections of hydralazine or labetalol to maintain a systolic blood pressure below 160 mm Hg and a diastolic blood pressure below 105 mm Hg. Intravenous fluids and urinary output were documented during the observation period. Corticosteroids

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for fetal lung maturity were given to all patients at 23 5/7 weeks or greater (betamethasone 12 mg/d for 2 days). During the observation period, a baseline ultrasound for dating, amniotic fluid index, fetal weight, and Doppler (measurements of fetal vessels), when possible, were performed. Gestational age was determined by last menstrual period and/or first-trimester ultrasound evaluation. In case of absent first-trimester ultrasound, dating was confirmed by the second-trimester ultrasound. Fetal weight was estimated by ultrasound using the Hadlock formula and fetal growth percentile was recorded. Oligohydramnios was defined as an amniotic fluid index 5cm or less for singleton pregnancy and the largest vertical pocket of 2 cm or less for twins.7 Baseline laboratory evaluation (minimum of urinalysis for protein, complete blood count, renal profile, and liver function tests) along with a 24 hour urine for protein was obtained. After the initial observation period, patients were transferred to the high-risk antepartum floor. Oral antihypertensive medications were used only in those with severe hypertension to maintain systolic blood pressure below 160 mm Hg and diastolic blood pressure less than 105 mm Hg. The antihypertensive drugs used were labetalol and/or nifedipine. Fetal well-being was assessed daily by maternal kick counts and nonstress testing, biophysical profile, umbilical artery Doppler, or a combination of these tests and those with gestational age of 23 weeks or greater. Serial ultrasound was performed to evaluate fetal growth and amniotic fluid status. Maternal evaluation included frequent blood pressure measurements along with weight and questioning for symptoms of worsening preeclampsia (headache, nausea and/or vomiting, right upper quadrant pain, abdominal pain, or visual disturbances). In addition, complete blood count and liver enzymes were obtained daily. Maternal indications for delivery included laboratory data suggestive of worsening disease (thrombocytopenia or HELLP syndrome), abruptio placentae, pulmonary edema, acute renal failure,

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TABLE 1

Neonatal and pregnancy outcomes stratified by gestational age at onset of expectant managementa Admission GA (wks) 21 to 22 6/7

Number Days of gained fetuses (range)

Delivery Neonatal GA Fetal death, death, (wks) n (%) n (%)

Perinatal Survivors, n (%)

Severe RDS, CLD, n (%) n (%)

IVH, n (%)

NEC, n (%)

NA

NA

NA

NA

0 (0)

0 (0)

0 (0)

0 (0)

1 of 6 (17)

7

3 (2-10)

22.86

7 (100)

0 (0)

0 (0)

23 to 23 6/7 10

4 (3-46)

24.36

2 (20)

6 (60)

2 (20)

1 of 2 (50)

24 to 24 6/7

7

9.5 (3-33) 26.36

1 (17)

1 (17)

5 (71)

6 of 6 (100) 3 of 6 (50)

25 to 25 6/7 17

6.5 (3-43) 26.57

4 (24)

0 (0)

13 (76)

26 to 26 6/7 10

7 (3-41)

27.71

0 (0)

1 (10)

9 (90)

Total

6 (2-46)

26.29

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

11 of 13 (85) 5 of 13 (38) 1 of 13 (8) 1 of 13 (8)

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

6 of 9 (67)

1 of 10 (10) 0 (0)

1 of 10 (10)

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

51

14 of 51 (27) 8 of 51 (16) 29 of 51 (57) 24 of 37 (65) 9 of 37 (24) 1 of 37 (3) 3 of 37 (8)

................................................................................................................................................................................................................................................................................................................................................................................ a

All neonatal complications are based on babies who were born alive after greater than 23 weeks.

Bombrys. Severe preeclampsia at less than 27 weeks. Am J Obstet Gynecol 2008.

neurologic symptoms, and uncontrolled hypertension. Fetal indications for delivery included nonreassuring fetal heart rate tracing (NRFHTs), abnormal fetal testing (umbilical artery Doppler, biophysical profile, and an estimated fetal weight below the fifth percentile for gestational age with oligohydramnios). Outcome data included maternal demographics and maternal and neonatal outcomes. Demographic data included maternal age, ethnicity, past medical and obstetrical history (chronic hypertension and previous history of preeclampsia), gestational age at diagnosis, days of expectant management, gestational age at delivery, indication for delivery, and mode of delivery. Maternal morbidities included placental abruption, pulmonary edema, HELLP syndrome, renal insufficiency, eclampsia, disseminated intravascular coagulation (DIC), and death. Pulmonary edema was diagnosed based on physical exam and characteristic chest radiograph findings. Diagnosis of HELLP syndrome was based on diagnosis of preeclampsia or superimposed preeclampsia with the following: hemolysis diagnosed by characteristic blood smear, derangements in serum lactate dehydrogenase of 600 U/L or greater, total bilirubin (1.2 mg/dL or greater), decreased hemoglobin and hematocrit, elevated liver enzymes to greater than 2 times the upper limit of normal, and low platelet count (100,000 cells/␮L or less). DIC was defined as low platelet count (less than 100,000, low fibrinogen) less than 300 mg/dL), and

prolonged prothrombin time (14 seconds or longer). Renal insufficiency was defined as serum creatinine greater than 1.2 mg/dL. Neonatal data included birthweight, Apgar scores, neonatal intensive care unit (NICU) admissions, and length of stay. Neonatal morbidities includes respiratory distress syndrome (RDS), chronic lung disease (CLD), grades III and IV intraventricular hemorrhage (IVH), grades II and III periventricular leukomalacia, and fetal and neonatal death. All neonates with a birthweight less than 10%, adjusted for sex, were considered small for gestational age.10 Those with birthweight below the fifth percentile were considered to have severe FGR. RDS was defined with characteristic findings on radiographic examination and oxygen requirement at 24 hours of life. Bronchopulmonary dysplasia was defined as oxygen requirements at 28 days of life. Grade III IVH was defined as hemorrhage with ventricular dilatation and grade IV IVH as hemorrhage with parenchymal spread.6 Necrotizing enterocolitis (NEC) was defined by characteristic clinical signs and symptoms with radiographic findings of pneumatosis cystoides intestinalis or pneumoperitoneum or portal air.6 Data analysis of pregnancy prolongation and adverse maternal and perinatal outcomes were analyzed based on gestational age on admission and divided by weeks as follows: less than 23 0/7 weeks,

23 0/7 to 23 6/7 weeks, 24 0/7 to 24 6/7 weeks, 25 0/7 to 25 6/7 weeks, and 26 0/7 to 26 6/7 weeks. Data are presented as median with SD or percentage with range, as applicable. P ⬍ .05 was considered significant.

R ESULTS Forty-six pregnancies with 51 fetuses (3 sets of twins and 1 set of triplets) met inclusion criteria for expectant management: 6 with 7 fetuses (twins) at 21 0/7 to 22 6/7, 8 with 10 fetuses (triplets) at 23 0/7 to 23 6/7, 6 with 7 fetuses (twins) at 24 0/7 to 24 6/7, 16 with 17 fetuses (twins) at 25 0/7 to 25 6/7, and 10 with 10 fetuses at 26 0/7 to 26 6/7. Mean maternal age was 27.8 ⫾ 6.0 years (range 16-40). Median systolic blood pressure at onset of expectant management was 180 mm Hg (range 152-216). Median diastolic blood pressure was 103 mm Hg (range 85-131). Sixty-five percent were Caucasian. 20% had chronic hypertension, and 15% had a history of previous severe preeclampsia. Indications for delivery were maternal in 21 patients, fetal in 22 patients, or both in 3 patients. Fetal indications for delivery were for fetal demise (n ⫽ 14) and/or severe FGR with abnormal testing. Mode of delivery was cesarean section in 39 patients (85%) and vaginal in 7 patients (15%). Indication for cesarean section included NRFHTs (28%), previous cesarean section (26%), malpresentation (21%), an unfavorable cervix (21%), and maternal indications (5%). Table 1 summarizes days of pregnancy

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TABLE 2

Maternal outcome stratified by gestational age at onset of expectant management Admission GA (wks)

Number of patients

HELLP, n (%)

Abruptio placentae, n (%)

Pulmonary edema, n (%)

Renal insufficiency, n (%)

Eclampsia, n (%)

Composite outcome, n (%)

21 to 22 6/7

6

3 (50)

0 (0)

1 (17)

0 (0)

0 (0)

4 (67)

23 to 23 6/7

8

3 (38)

1 (13)

1 (13)

1 (13)

0 (0)

5 (63)

24 to 24 6/7

6

2 (33)

0 (0)

0 (0)

0 (0)

0 (0)

2 (33)

25 to 25 6/7

16

2 (13)

2 (13)

0 (0)

0 (0)

1 (6)

5 (63)

26 to 26 6/7

10

1 (10)

3 (30)

0 (0)

1 (10)

0 (0)

5 (50)

Total

46

11 (24)

6 (13)

2 (4)

2 (4)

1 (2)

21 (46)

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

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These complications developed during expectant management and were the maternal indications for delivery. GA, gestational age. Bombrys. Severe preeclampsia at less than 27 weeks. Am J Obstet Gynecol 2008.

prolongation and perinatal outcomes stratified by gestational age at time of expectant management. The overall perinatal survival was 57%, but there were no perinatal survivors among those with expectant management at less than 23 weeks. In those with gestational age 24 weeks or greater at the time of expectant management, the perinatal survival was 74% (27 of 34). The overall mean birthweight was 650 ⫾ 238 g (range 256-1653): Twenty-seven (53%) were below the 10th percentile and 18 (35%) were below the fifth percentile for gestational age at birth. Eight of the 18 (44%) with a birthweight less than the fifth percentile died. Two of the 8 were delivered because of maternal complications and a gestational age at 23 weeks or less and 6 for severe FGR: 5 of the 6 had abnormal fetal testing. There were only 2 survivors among those who had expectant management at 23 to 23 6/7 weeks: 1 was delivered at 25 5/7 weeks’ gestation and the other at 30 2/7 weeks’ gestation. Among those who had expectant management at 24 weeks, the 5 survivors were delivered at 26 weeks or greater, whereas the 2 that died had severe FGR. Among those with expectant management at 25 to 25 6/7 weeks, all 4 fetal deaths had severe FGR. The overall mean neonatal hospital stay was 47 days (range 1-202). Table 2 summarizes maternal complications according to gestational at time of expectant management. Maternal 247.e4

complications were significantly higher in those who had expectant management at less than 24 weeks as compared with those who had management at 24 weeks or greater (64% vs 38%, P ⬍ .05). There were no deaths or cases of DIC.

C OMMENT Severe preeclampsia in the second trimester is becoming an increasing problem because of increased percentage of pregnancies by assisted reproductive technologies, advanced maternal age at first pregnancy, increasing rates of preexisting medical conditions such as chronic hypertension and renal disease, and increasing rates of higher-order multiple gestations. Most obstetricians have limited, if any, experience in managing these types of pregnancies. Optimal management of severe preeclampsia in the midtrimester usually depends on balancing the risks to the mother and the fetus from pregnancy prolongation vs the risk of extreme prematurity from immediate delivery (high neonatal mortality, prolonged hospital stay in the NICU, and long-term disability in surviving infants). In general, pregnancy outcome in women with severe preeclampsia at less than 27 weeks will depend on gestational age at onset of disease as well as maternal and fetal status at time of presentation to a perinatal center.1-8 Our findings reveal that 9% of women who develop severe preeclampsia in the second trimester

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have a multifetal gestation. In addition, we found that the overall perinatal survival was 57% (29 of 51) with survival dependent on gestational age at onset of expectant management, gestational age at delivery, and the presence or absence of severe FGR at birth. These findings expand on and support the results of previous studies.2,5-7 We had no perinatal survivors in those who had expectant management below 23 weeks, and the survival rate was only 20% at 23 to 23 6/7 weeks. Combined with results of previous studies, there were a total of 27 reported pregnancies (28 fetuses) in women who had expectant management at less than 23 weeks with no reported perinatal survivors and a maternal complication rate of 30-67% (Table 3).2,8 There were a total of 60 patients with expectant management at less than 24 weeks, with a perinatal survival of 10%. There were a total of 20 reported pregnancies (22 fetuses) with expectant management between 23 0/7 and 23 6/7 weeks gestation, with only 4 of the 22 (18%) surviving. The reported maternal complications in these pregnancies ranged from 25% to 63%. For patients with gestational age between 24 0/7 and 24 6/7 weeks, the perinatal survival was 15 of 26 (58%), and for those who had expectant management at 25 to 25 6/7 weeks, the perinatal survival was 19 of 27 (70%). Considering the high maternal complications reported in these women (37-

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www.AJOG.org 67%),2,8 we recommend that patients who develop severe preeclampsia at less than 23 weeks be encouraged to have a termination of pregnancy and counseled accordingly. In addition, for those having expectant management at 23 to 23 6/7 weeks, the reported perinatal survival was 4 of 22 (18%) with a maternal morbidity of 25-63% (Table 3). Moreover, there are no data on long-term neonatal morbidities among surviving infants in this group. This information should be made available to parents considering expectant management to help them in their decision. The findings of our study and those reported recently from Western countries suggest that expectant management is justified in those with gestational age between 24 0/7 and 26 6/7 weeks’ gestation because perinatal survival exceeds 60% overall and reaches as high as 100% for those at 26 to 26 6/7 weeks.6,8 However, it must be emphasized that neonatal complications remain very high in these patients despite the administration of corticosteroids. In addition, maternal morbidities also remain very high, although all were reversible. Therefore, the previously mentioned findings underscore the importance of intensive maternal and fetal evaluations during expectant management of these women. Moreover, these results are based on careful patient selection and intensive management by a maternal fetal medicine specialist in a tertiary care center. There is continued debate about expectant management of severe preeclampsia in patients with FGR.1 This debate concerns the days of pregnancy prolongation as well as the increased risk of fetal demise during expectant management of such women. In 1 previous study, Shear et al11 recommended expectant management in all patients with gestational age below 30 weeks irrespective of severe FGR. However, this study evaluated outcome based on fetal growth at delivery and not at the time of expectant management. In addition, serious maternal morbidities were common in this group. Our findings reveal that the presence of severe FGR at birth is associated with a poor perinatal outcome. These findings

TABLE 3

Perinatal survival and maternal complications in expectant management of severe preeclampsia at less than 27 week’s of gestation Admission GA (wk) Authors (year) Less than 23 0/7

Sibai et al2 (1990)

Perinatal Maternal Cases, n survival, complications (fetus) n (%) (%) 7

0

30

14

0

57

0

67

.............................................................................................................................................................................................................................................. 8

Budden et al (2006)

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

Current study (2008)

6 (7)

.............................................................................................................................................................................................................................................. 3

Less than 24 0/7

Pattison et al (1988)

11

0

NR

Sibai et al (1990)

15

7

27

8

0

50

18

65

.............................................................................................................................................................................................................................................. 2 .............................................................................................................................................................................................................................................. 4

Moodley et al (1993)

.............................................................................................................................................................................................................................................. 7

Gaugler Senden et al (2006) 26 (28)

.............................................................................................................................................................................................................................................. 2

23 0/7 to 23 6/7

Sibai et al (1990)

8

12.5

25

Budden et al (2006)

4

25

25

Current study (2008)

8 (10)

20

63

Haddad et al (2004)

6

33

50

Budden et al (2006)

13

61

31

71

33

.............................................................................................................................................................................................................................................. 8 .............................................................................................................................................................................................................................................. .............................................................................................................................................................................................................................................. 6

24 0/7 to 24 6/7

.............................................................................................................................................................................................................................................. 8 ..............................................................................................................................................................................................................................................

Current study (2008)

6 (7)

.............................................................................................................................................................................................................................................. 6

25 0/7 to 25 6/7

Haddad et al (2004)

10

60

40

Current study (2008)

17

76

38

.............................................................................................................................................................................................................................................. .............................................................................................................................................................................................................................................. 5

26 0/7 to 26 6/7

7

57

NR

Haddad et al (2004)

Hall et al (2001)

26

100

30

Current study (2008)

10

90

50

.............................................................................................................................................................................................................................................. 6 .............................................................................................................................................................................................................................................. ..............................................................................................................................................................................................................................................

Adjusted for changes in current study. NR, not reported. Bombrys. Severe preeclampsia at less than 27 weeks. Am J Obstet Gynecol 2008.

expand on and support the findings of previous studies.12-14 Consequently, we recommend that patients with evidence of severe FGR at time of onset of disease be delivered following completion of a course of corticosteroids. Our study has some limitations. It is a retrospective study with limited number of patients who had expectant management at less than 24 weeks. In addition, our recommendations for severe FGR are based on a small sample size. Moreover, we do not have long-term follow-up data on surviving infants. In summary, our findings and those obtained from the review of the literature should be used by physicians who care for patients with severe preeclampsia at less than 27 weeks gestation to counsel the patient and her family about the potential risk and benefits to them and their unborn infants. f

REFERENCES 1. Sibai BM, Barton JR. Expectant management of severe preeclampsia remote from term: Patient selection, treatment, and delivery indications. Am J Obstet Gynecol 2007;196:514.e1-9. 2. Sibai BM, Akl S, Fairlie F, Moretti M. A protocol for managing severe preeclampsia in the second trimester. Am J Obstet Gynecol 1990; 163:733-8. 3. Pattinson RC, Odendaal HJ, du Toit R. Conservative management of severe proteinuric hypertension before 28 week’s gestation. S Afr Med J 1988;73:516-8. 4. Moodley J, Koranteng SA, Rout C. Expectant management of early onset of severe pre-eclampsia in Durban. S Afr Med J 1993;83:584-7. 5. Hall DR, Odendaal HJ, Steyn DW. Expectant management of severe pre-eclampsia in the mid-trimester. Eur J Obstet Gynecol Reprod Biol 2001;96:168-72. 6. Haddad B, Deis S, Goffinet F, et al. Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks’ gestation. Am J Obstet Gynecol 2004;190:1590-7.

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SMFM Papers 7. Gaugler-Senden IP, Huijssoon AG, Visser W, Steegers EA, de Groot CJ. Maternal and perinatal outcome of preeclampsia with an onset before 24 weeks’ gestation. Audit in a tertiary referral center. Eur J Obstet Gynecol Reprod Biol 2006;128:216-21. 8. Budden A, Wilkinson L, Buksh MJ, McCowan L. Pregnancy outcome in women presenting with pre-eclampsia at less than 25 weeks gestation. Aust N Z J Obstet Gynaecol 2006;46:407-12. 9. ACOG Committee on Practice Bulletins— Obstetrics. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclamp-

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www.AJOG.org sia. Number 33, January 2002. Obstet Gynecol 2002;99:159-67. 10. Alexander GR, Himes JH, Kaufman RB, et al. A United States National Reference for Fetal Growth. Obstet Gynecol 1996;87: 163-8. 11. Shear RM, Rinfert D, Leduc L. Should we offer expectant management in cases of severe preterm preeclampsia with fetal growth restriction? Am J Obstet Gynecol 2005;192:1119-25. 12. Haddad B, Kayem G, Deis S, Sibai BM. Are perinatal and maternal outcomes different during expectant management of severe preeclampsia in the presence of intrauterine

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growth restriction? Am J Obstet Gynecol 2007;196:237.e1-237.e5. 13. Ganzevoort W, Rep A, Bonsel GJ, et al. A randomised controlled trial comparing two temporising management strategies, one with and one without plasma volume expansion, for severe and early onset pre-eclampsia. BJOG 2005;112:135868. 14. Witlin AG, Saade GR, Mattar F, Sibai BM. Predictors of neonatal outcome in women with severe preeclampsia or eclampsia between 24 and 33 weeks’ gestation. Am J Obstet Gynecol 2000;182:607-11.