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Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation
American Journal of Obstetrics and Gynecology (2004) 190, 1590e7
www.elsevier.com/locate/ajog
Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks’ gestation Bassam Haddad, MD,a,* Ste´phanie Deis, MD,a Francxois Goffinet, MD, PhD,b Bernard J Paniel, MD,a Dominique Cabrol, MD, PhD,b Baha M Sibaı¨, MDc CHI Cre´teil, Cre´teil, Francea; AP-HP Cochin Port Royal, Paris, Franceb; University of Cincinnati, Cincinnati, Ohioc
–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– KEY WORDS Early severe preeclampsia Expectant management Perinatal outcome Maternal morbidity
Objective: This study was undertaken to determine maternal and perinatal outcomes after expectant management of severe preeclampsia between 24 and 33 weeks’ gestation. Study design: A prospective observational study of 239 women with severe preeclamptic and undelivered after antenatal steroid prophylaxis was performed. Pregnancy prolongation and maternal and perinatal morbidities were analyzed according to the gestational age at time of expectant management: 24 to 28, 29 to 31, and 32 to 33 weeks. Statistical analysis was performed by Student t test and c2 test. Results: The days of pregnancy prolongation were significantly higher among those managed at less than 29 weeks (6) compared with the other groups (4). There were 13 perinatal deaths: 12 in those managed at less than 29 weeks and 1 in those managed at 29 to 31 weeks. Neonatal morbidities were significantly higher among those managed at less than 29 weeks compared with the other groups. There were no instances of maternal death or eclampsia. Maternal morbidities were similar among the groups. Conclusion: Expectant management of severe preeclampsia at 24 to 33 weeks in a tertiary care center is associated with good perinatal outcome with a minimal risk for the mother. Ó 2004 Elsevier Inc. All rights reserved.
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The course of early severe preeclampsia is associated with a progressive deterioration of the maternal condition. Delivery remains the only definite treatment. There
Presented at the Seventieth Annual Meeting of the Central Association of Obstetricians and Gynecologists, October 1-4, 2003, LaJolla, Calif. * Reprint requests: Bassam Haddad, MD, Department of Obstetrics and Gynecology, CHI Creteil, 40 avenue de verdun, 94010 Creteil, France. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.03.050
is a broad agreement to terminate the pregnancy when maternal or fetal conditions are altered, or once 34 weeks’ gestation is reached. Delivery at earlier gestational age, however, is associated with increased risk of adverse neonatal outcome.1 In addition, fetal lung maturity is not accelerated by preeclampsia,2 and neonatal outcome remains closely dependent on the use of corticosteroid for fetal lung maturity enhancement.3 The results of these findings have led to a policy of expectant management to improve neonatal outcome. Expectant management, however, may worsen maternal condition.4
Haddad et al Two randomized trials have shown an improvement of perinatal outcome without deterioration of maternal condition.5,6 These 2 studies, however, had limited sample size (total of 133 patients studied). This study was undertaken to determine maternal and perinatal outcomes after expectant management of singleton pregnancies with severe preeclampsia between 24 and 33 weeks’ gestation.
Material and methods Over a 6-year period (January 1, 1996, and December 31, 2001), all women with singleton pregnancies and with severe preeclampsia admitted at 2 perinatal centers (CHI Creteil and AP-HP Cochin Port-Royal) and who remained undelivered after receiving a full course of corticosteroid therapy (betamethasone or dexamethasone intramuscular, 12 mg/d for 2 days), had expectant management to prolong pregnancy. Expectant management was performed in labor or in high-risk pregnancy unit, depending on severity of clinical or biologic parameters. A resident, a midwife, a nurse, and a senior obstetrician were dedicated to these patients. The diagnosis of severe preeclampsia was made according American College of Obstetricians and Gynecologist (ACOG) criteria.7 Pregnancies with unstable conditions for either the mother or the fetus during the first 48 hours after admission were excluded from the study. Particularly, women with eclampsia, HELLP syndrome, severe uncontrolled hypertension (defined as difficulties to stabilize systolic blood pressure !160 mm Hg and systolic blood pressure !110 mm Hg), abruptio placentae, abnormal fetal heart rate monitoring, severe oligohydramnios (defined as amniotic fluid biggest pocket !2 cm or amniotic fluid index !5 cm) or reversed end diastolic flow in umbilical artery were excluded. Prophylactic magnesium sulfate was not used at any time during expectant management, in labor or the postpartum period. Maternal monitoring included 4 hourly blood pressure measurements, clinical evaluation of symptoms twice daily at least, and analysis of 24-hour urine excretion. Antihypertensive drugs were used to keep systolic blood pressure at 150 mm Hg or lower and diastolic blood pressure 100 mm Hg or lower. Intravenous nicardipine or intravenous labetalol were used as first line treatment in women with severe hypertension (defined as systolic blood pressure R160 mm Hg or diastolic blood pressure R110 mm Hg). When necessary these 2 drugs were used together. Blood tests included hemoglobin, platelet count, liver enzymes, creatinine, lactate dehydrogenase, fibrinogen, D-dimers, prothrombin, and partial thromboplastin times. These tests were performed daily or every other day, depending on clinical symptoms and laboratory findings. Fetal evaluation included ultrasound evaluation of fetal growth and estimation of amniotic
1591 fluid volume at entry, fetal heart rate monitoring, and clinical evaluation of fetal movements twice daily. Fetal indications for delivery during expectant management were abnormal fetal heart rate monitoring (repeated late decelerations, or decreased long-term variability), severe intrauterine growth retardation (IUGR), and oligohydramnios. Maternal indications for delivery during expectant management were major maternal complications (defined below), except for maternal death, severe uncontrolled hypertension, despite maximum doses of combined antihypertensive therapy (nicardipine and labetalol), persistent headaches or visual disturbance, persistent epigastic pain, low platelet count (!100,000 cells/mL), and oligoanuria. The main outcome of the study was days pregnancy prolongation defined as full days gained since the admission. Secondary outcomes were perinatal mortality and morbidity, days hospitalized in neonatal intensive care unit (NICU), and life-threatening maternal morbidity. Major perinatal complications included: fetal and neonatal death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) grade 3 and 4, and necrotizing enterocolitis (NEC). RDS was defined by the presence of characteristic radiographic findings and an oxygen requirement at 24 hours. BPD was defined as an oxygen requirement at 28 days after birth. IVH grade 3 was defined as hemorrhage with ventricular dilation, and grade 4 as hemorrhage with parenchymal spread. NEC was defined by characteristic clinical symptoms with radiographic findings of pneumatosis cystoides intestinalis or pneumoperitoneum or portal air. Major maternal complications included: maternal death, eclampsia, HELLP syndrome, abruptio placentae, disseminated intravascular coagulopathy (DIC), pulmonary edema, and acute renal failure. HELLP syndrome was defined by the presence of all 3 of the following criteria: hemolysis (characteristic peripheral blood smear and serum lactate dehydrogenase [LDH] R600 U/L or serum total bilirubin R1.2 mg/dL), elevated liver enzymes (serum aspartate aminotransferase [AST] R70 U/L), and low platelet counts (!100,000 cells/ mL).8 DIC was defined as the presence of 3 or more of the following criteria: low platelets (!100,000 cells/ mL), low fibrinogen (!300 mg/dL), positive D-dimers (R50 mg/dL), or prolonged prothrombin (R14 seconds) and partial thromboplastin (R40 seconds) times. Pulmonary edema was diagnosed on the basis of clinical findings and chest radiograph. Acute renal failure was diagnosed in the presence of oligoanuria in association with elevated serum creatinine greater than 120 mmol/L (>1.4 mg/dL). The need for dialysis was considered as severe acute renal failure. Gestational age was determined by last menstrual period and/or first trimester ultrasound examination.
1592 Table I
Haddad et al Clinical characteristics of study population
Age (y)* White (%) African (%) Nullipara (%) Previous preeclampsia (%) Chronic hypertension (%) Gestational age at admission (wks)*
31 (19 - 45) 63 32 55 13 17 29 (24-33.3)
* Values are expressed as median and range.
Severe IUGR was defined as birth weight less than fifth percentile.9 Pregnancy prolongation, and adverse perinatal and maternal outcomes were analyzed according to gestational age at time of admission which was divided into 3 groups: 24 weeks 0/7 days to 28 weeks 6/7 days, 29 weeks 0/7 days to 31 weeks 6/7 days, 32 weeks 0/7 days to 33 weeks 2/7 days of gestation. Data are presented as median and range, or percentage, as appropriate. Categorical variables were compared by c2 test. Continuous variables were analyzed by Student t test. A P value !.05 was considered significant. The evaluation of our conservative management did not need approval of our ethical committee because it was a prospective collection of data in women who received standard management at both hospitals. Therefore, our ethical committee has waved requirement for approval.
Results During the study period, there were 31,466 singleton deliveries. 381 (1.2%) singleton pregnancies were admitted for severe preeclampsia between 24 weeks 0/7 days and 33 weeks 2/7 days. Among these, 239 women were expectantly managed. Demographic and clinical characteristics are presented in Table I. Two hundred thirty-three (97.5%) infants were born alive. Median gestational age was 30.4 (25-34) weeks. Median birth weight of these infants was 1115 g (4803110 g). Six fetal deaths occurred before delivery at a median gestational age of 27.3 weeks (24.8-30 weeks), median birth weight of these infants was 590 g (360930 g). Five of these 6 deaths occurred in those expectantly managed at less than 29 weeks. Three of the 6 stillbirths had severe IUGR and birth weight below 500 g (360-480 g). One of the stillbirths died from abruption at 30 weeks (930 g). The median number of days in pregnancy prolongation days was 5 (2-35). The days gained were significantly higher among those who had expectant management at less than 29 weeks compared with the other 2 groups (6, 4, 4, respectively, Table II). Neonatal
outcomes are shown in Table II. Seven infants died during NICU hospitalization. All 7 were in the group at less than 29 weeks’ gestation and were delivered at a median gestational age of 26.3 weeks (25-30.6 weeks). Median birth weight of these 7 infants was 600 g (520-960 g). Overall, there were 13 perinatal deaths for a total perinatal mortality of 5.4%. Of these 13 deaths, 12 occurred in those expectantly managed at ! 29 weeks (median gestational age at delivery: 26.2 weeks [24.8-30.6 weeks], median birth weight: 650 g (360-960 g]) (Table III). The rates of IUGR were not statistically different among the 3 groups. The rates of RDS, BPD, IVH grade 3 to 4 were significantly higher among those who had expectant management at less than 29 weeks compared with 29 to 32 weeks, and 32 weeks or more, respectively. Median days of artificial ventilation were significantly higher among those who had expectant management at less than 29 weeks compared with 29 to 32 weeks, and 32 weeks or more, respectively. In addition, half of the infants delivered of women expectantly managed at 29 weeks or more needed mechanical ventilation less than 1 day. Overall, neonatal complications were rare (only 1 case of RDS) among those who had expectant management at 32 weeks or more. The length of days in NICU was significantly higher among those who had expectant management at less than 29 weeks when compared with the other 2 groups, respectively (Table II). There were no instances of maternal death or eclampsia or severe acute renal failure necessitating dialysis among the 239 women. Only 1 woman had serum creatinine 221 mmol/L or greater (R2.5 mg/dL). In addition, there were no differences among the 3 groups regarding development of antepartum HELLP syndrome, abruptio placentae, and pulmonary edema. Two of the 3 women who had DIC had abruptio placentae. Maternal outcomes are summarized by gestational age at admission in Table IV. Delivery was obtained by cesarean section in 95.8%. Common indications for delivery were maternal reasons for 48.5%, followed by fetal distress for 42.8%. In 8.7% indication for delivery were both maternal and fetal reasons. One hundred forty-two patients were excluded from the study during the first 48 hours after admission for maternal or fetal reasons. Maternal outcomes are summarized in Table V. Overall in our population, 37% of women were not considered eligible for expectant management.
Comment Recent studies have suggested that fetal lung maturity,2 as well as fetal neurologic and physical development,10 were not accelerated in pregnancies complicated by preeclampsia. In addition, neonatal mortality is closely
1593
Haddad et al Table II
Perinatal outcomes according to gestational age at onset of expectant management
Admission GA (wks) Delivery GA (wks) Birth weight (g) Prolongation (d) IUGR Neonatal mortality* Artificial ventilation (d) RDSz BPDz IVHy NEC NICU (d)
!29 wks (n = 110)
%29-!32 wks (n = 97)
R32 wks (n = 32)
27.4 28.4 885 6 28 7 3 69 34 6 6 22.5
30.3 31.1 1250 4 27
32.3 33 1617 4 3 0 10 1 0 0 0 5
(24-28.8) (24.8-32.7) (360-2560) (2-35)*y (25) (7) (0-60)yz (66) (33) (6) (6) (0-100)z
10 36 6 1 8
(29-31.8) (29.3-33.8) (480-2560) (2-32)* (27) 0 (0-17)*z (37) (6) 0 (1) (0-57)yz
(32-33.3) (32.3-34) (1190-3110) (2-12)y (9) (0-4)*y (3)
(0-18)yz
Data are shown as number (%), or median (range), as appropriate. GA, gestational age. * P ! .05, y P ! .01, z P ! .0001.
Table III Perinatal death, pregnancy prolongation and perinatal outcome according to gestational age at onset of expectant management Admission GA (wks)
Delivery GA (wks)
Days gained
Fetal death (n)
RDS* n (%)
BPDy n (%)
IVH* n (%)
NEC* n (%)
Neonatal death (n)
Perinatal mortality n (%)
24 (n = 6) 25 (n = 10) 26 (n = 23) 27 (n = 28) 28 (n = 43) 29 (n = 35) 30 (n = 34) 31 (n = 28) 32-33 (n = 32)
25.1 26.9 27.3 28.4 29.3 30 31 32.1 33
7 11 5 6 6 5 4 5 4.5
3 0 0 0 2 1 0 0 0
3 9 19 19 19 19 10 7 1
2 4 13 9 6 5 0 1 0
0 1 1 1 3 0 0 0 0
0 2 3 1 0 0 0 1 0
1 4 0 1 1 0 0 0 0
4 4 0 1 3 1 0 0 0
(100) (90) (83) (68) (46) (56) (29) (25) (3)
(100) (67) (57) (33) (15) (15) (4)
(10) (4) (4) (7)
(20) (13) (4)
(4)
(67) (40) (3.6) (7) (2.9)
Percentage calculated after exclusion of fetal death (*) or perinatal death (y).
Table IV
Maternal complications according to gestational age at onset of expectant management
Admission GA (wks)
Antepartum HELLP n (%)
Abruptio placentae n (%)
Pulmonary edema n (%)
DIC n (%)
Renal insufficiency n (%)
24 (n = 6) 25 (n = 10) 26 (n = 23) 27 (n = 28) 28 (n = 43) 29 (n = 35) 30 (n = 34) 31 (n = 28) 32-33 (n = 32)
2 4 4 2 5 4 7 2 4
0 1 2 2 2 1 1 3 2
1 0 2 2 1 0 1 1 1
0 2 (20) 0 1 (4) 0 0 0 0 0
0 0 3 2 1 1 2 2 2
(33) (40) (17) (7) (12) (11) (21) (7) (13)
(10) (9) (7) (5) (3) (3) (11) (6)
dependent on gestational age at delivery,11 and on the use of corticosteroid treatment to enhance fetal lung maturity.12 These studies have highlighted the need of expectant management to improve perinatal outcome in women with early-onset severe preeclampsia. The goal
(17) (9) (7) (2) (3) (4) (3)
(13) (7) (2) (3) (6) (7) (6)
of delivery of a live mature newborn infant in optimal condition, however, must not be achieved at the expense of maternal safety. This study was undertaken to determine pregnancy prolongation, and perinatal and maternal outcomes after
1594
Haddad et al
Table V Maternal complications in women excluded from the study (n = 142) compared with those included in the study (n = 239)
Eclampsia Antepartum HELLP Abruptio placentae Pulmonary edema DIC
Women excluded (n = 142) No. (%)
Study population (n = 239) No. (%)
P
11 (8) 48 (34)
0 34 (14)
!.001 !.001
19 (13)
14 (6)
!.05
3 (2)
9 (4)
ns
5 (3)
3 (1)
ns
expectant management of singleton pregnancies with severe preeclampsia between 24 and 33 weeks’ gestation. In this study, pregnancies were prolonged by a median number of 5 days, with a significantly greater period gained at earlier gestations. Days of pregnancy prolongation observed in this study are in agreement with results of recent trials.13,14 Two prospective randomized controlled trials comparing expectant management with early intervention have been published.5,6 The first study that included 38 patients found a mean pregnancy prolongation of 7.1 days in the group of women expectantly managed (n = 18).5 In a larger randomized controlled trial in which 95 patients where included, the mean pregnancy prolongation was 15 days.6 Regarding perinatal and neonatal mortality rates, our results are encouraging, as our observed rates were 5.4% and 3%, respectively. These results are in agreement with those published some years ago by Hall et al,13 with an important difference in that 46% of our population had gestational age at expectant management less than 29 weeks’ gestation compared with 26% in Hall et al study.15 Interestingly, there were no instances of perinatal death in women expectantly managed at 30 or more weeks’ gestation in our study. Neonatal morbidity was clearly related to gestational age at onset of expectant management and this is in agreement with previous studies.11,16,17 Increasing gestational age correlates with a reduction of respiratory distress syndrome.11,16 In addition, neonatal outcome was excellent during expectant management at 32 to 33 weeks. The sample size, however, is too low for valid conclusions. A much larger number of patients at 32 to 33 weeks needs to be studied before the benefits or safety of expectant management can be stated with certainty. Regarding maternal complications, expectant management was associated with a high incidence of antepartum HELLP syndrome (14.2%). This rate is higher than that previously reported,6,13 and this may be related to our population in which a majority of women
are white. The rate of abruptio placentae (5.9%) is similar to those reported in previous studies.1,6 There were, however, no instances of maternal death, eclampsia, or severe acute renal failure necessitating dialysis in our study, which is a reassuring finding. We did not use magnesium sulfate in the prevention of eclampsia in our management of women with early onset of severe preeclampsia. Some studies have suggested the usefulness of such therapy in women with severe preeclampsia.18,19 It is important to note, however, that in the MAGPIE trial, magnesium sulfate was not associated with a significantly decreased rate of eclampsia in the subgroup of women included from countries with low perinatal mortaliy.19 This absence of seizures in our patients may be related to the close maternal observation, to the use of aggressive blood pressure control, or to the sample size. The excellent perinatal outcome obtained in women expectantly managed at 30 weeks or more is certainly related to improvements in neonatal care, to corticosteroid treatment to enhance fetal lung maturity, and also to pregnancy prolongation. Some physicians would regard the delivery at 30 weeks or more after corticosteroid treatment to be in the best interests for both the mother and the fetus. Our study does not answer this question. In addition, Sibai et al6 have shown that expectant management, after corticosteroid treatment in women with severe preeclampsia after 30 weeks’ gestation, improved perinatal outcome with a minimal risk to the mother, even if their study had limited sample size. In summary, close and frequent observation of maternal and fetal status during expectant management of severe preeclampsia at 24 to 33 weeks in a tertiary care facility is associated with good perinatal mortality and neonatal outcome with a minimal risk for the mother.
References 1. Sibai BM, Spinnato JA, Watson DL, Hill GA, Anderson GD. Pregnancy outcome in 303 cases with severe preeclampsia. Obstet Gynecol 1984;64:319-25. 2. Schiff E, Friedman SA, Mercer BM, Sibai BM. Fetal lung maturity is not accelerated in preeclamptic pregnancies. Am J Obstet Gynecol 1993;169:1096-101. 3. Crowley P. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol 1995; 173:322-35. 4. Sibai BM, Taslimi M, Abdella TN, Brooks TF, Spinnato JA, Anderson GD. Maternal and perinatal outcome of conservative management of severe preeclampsia in mid-trimester. Am J Obstet Gynecol 1985;152:32-7. 5. Odendaal HJ, Pattinson RC, Bam R, Grove D, Kotz TJW. Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks’ gestation: a randomized controlled trial. Obstet Gynecol 1990;76:1070-5. 6. Sibai BM, Mercer BM, Schiff E, Friedman SA. Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks’
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gestation: a randomized controlled trial. Am J Obstet Gynecol 1994;171:818-22. The American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Washington, DC: The College; 1996 ACOG Technical Bulletin No: 219. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol 1993;169:1000-6. Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol 1996;87:163-8. Chari RS, Friedman SA, Schiff E, Frangieh AT, Sibai BM. Is fetal neurologic and physical development accelerated in preeclampsia? Am J Obstet Gynecol 1996;174:829-32. 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. Amorin MMR, Santos LC, Faundes A. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. Am J Obstet Gynecol 1999;180:1283-8. Hall DR, Odendaal HJ, Steyn DW, Grove D. Expectant management of early onset, severe pre-eclampsia: maternal outcome. BJOG 2000;107:1252-7. Chammas MF, Nguyen TM, Li MA, Nuwayhid BS, Castra LC. Expectant management of severe pre-eclampsia: is intrauterine growth restriction an indication for immediate delivery? Am J Obstet Gynecol 2000;183:853-8. Hall DR, Odendaal HJ, Kirsten GF, Smith J, Grove D. Expectant management of early onset, severe pre-eclampsia: perinatal outcome. BJOG 2000;107:1258-64. Abramovici D, Friedman SA, Mercer BM, Audibert F, Kao L, Sibai BM. Neonatal outcome in severe preeclampsia at 24 to 36 weeks’ gestation: Does the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome matter? Am J Obstet Gynecol 1999;180:221-5. Bernstein I, Horbar JD, Badger GJ, Ohlsson A, Golan A, for the Vermont Oxford Network. Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. Am J Obstet Gynecol 2000;182:198-206. Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995;333:201-5. Magpie Trial Collaboration Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002; 359:1877-90.
Discussion DR JAMES N. MARTIN, JR, Jackson, Miss. Dr James J. Walker, Professor of OBGYN at St James University Hospital hi Leeds, UK, wrote recently that ‘‘the mainstay of the management of severe preeclampsia is early referral, stabilization of the mother with antihypertensive therapy and anticonvulsants if required, full assessment of the mother and the baby, and delivery on the best day in the best way.’’1 Beyond the unspoken critical concept of correct diagnosis, we might summarize the core words (ie, the core concepts of Dr Walker) as referral, stabilization, assessment, and timely delivery.
1595 At issue is how best to manage the pregnancy complicated by severe preeclampsia before term, specifically between 24 and 34 weeks’ gestation, surely one of the most vexing obstetric issues currently plaguing the provider. There have been a number of trials undertaken in the last 15 years, either as randomized trials of aggressive versus expectant management, or more frequently as case series of patients with attempted expectant management. Professor Haddad’s article today is the latest of the latter type, and is second in size only to that of the series of 340 patients of Hall et al2 reported 3 years ago. Unfortunately, more questions than answers are raised by the authors’ information, and there is no comparison group upon which to validate the claim, as the authors do, that ‘‘expectant management of severe preeclampsia at 24 to 33 weeks in a tertiary care center improves perinatal outcome with a minimal risk for the mother.’’ Four years ago in 1999 Many et al3 reviewed the available data on this issue concluded that there were 4 unresolved problems in managing severe preeclampsia remote from term: 1. The lack of uniform criteria delineating severity of preeclampsiadwhich ones are or are not candidates for expectancy; 2. The lack of uniform criteria for ceasing conservative management and delivering; 3. The lack of consistency between institutions for providing high-risk maternal and newborn care (and expertise); and 4. Small patient numbers so far are insufficient to detect a small increased risk of maternal mortality with expectant, conservative management. What new information does Professor Haddad and his colleagues bring to the table today to expand our knowledge and clarify any of these 4 unresolved problems? Let’s consider them in order: 1. What about criteria for severity of preeclampsia? Other than the use of ‘‘ACOG criteria,’’ we are not told which specific criteria were used for diagnosis or whether the criteria/expression of the disease relates to the eventual maternal-fetal-neonatal outcome, or even whether the type of severe preeclampsia relates to survival of the initial 48- to 72-hour evaluation/ stabilization period and candidacy for expectant, conservative management. Can the authors help with this vital information (question 1)? 2. What about criteria for ceasing conservative management and changing expectancy to action? There are no specific summaries of endpoints used to indicate need for delivery whether urgent or emergent and how these relate to eventual maternal and neonatal outcome. Can the authors help with this vital information (question 2)? For instance, what failed to indicate the subsequent development
www.elsevier.com/locate/ajog
Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks’ gestation Bassam Haddad, MD,a,* Ste´phanie Deis, MD,a Francxois Goffinet, MD, PhD,b Bernard J Paniel, MD,a Dominique Cabrol, MD, PhD,b Baha M Sibaı¨, MDc CHI Cre´teil, Cre´teil, Francea; AP-HP Cochin Port Royal, Paris, Franceb; University of Cincinnati, Cincinnati, Ohioc
–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– KEY WORDS Early severe preeclampsia Expectant management Perinatal outcome Maternal morbidity
Objective: This study was undertaken to determine maternal and perinatal outcomes after expectant management of severe preeclampsia between 24 and 33 weeks’ gestation. Study design: A prospective observational study of 239 women with severe preeclamptic and undelivered after antenatal steroid prophylaxis was performed. Pregnancy prolongation and maternal and perinatal morbidities were analyzed according to the gestational age at time of expectant management: 24 to 28, 29 to 31, and 32 to 33 weeks. Statistical analysis was performed by Student t test and c2 test. Results: The days of pregnancy prolongation were significantly higher among those managed at less than 29 weeks (6) compared with the other groups (4). There were 13 perinatal deaths: 12 in those managed at less than 29 weeks and 1 in those managed at 29 to 31 weeks. Neonatal morbidities were significantly higher among those managed at less than 29 weeks compared with the other groups. There were no instances of maternal death or eclampsia. Maternal morbidities were similar among the groups. Conclusion: Expectant management of severe preeclampsia at 24 to 33 weeks in a tertiary care center is associated with good perinatal outcome with a minimal risk for the mother. Ó 2004 Elsevier Inc. All rights reserved.
–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
The course of early severe preeclampsia is associated with a progressive deterioration of the maternal condition. Delivery remains the only definite treatment. There
Presented at the Seventieth Annual Meeting of the Central Association of Obstetricians and Gynecologists, October 1-4, 2003, LaJolla, Calif. * Reprint requests: Bassam Haddad, MD, Department of Obstetrics and Gynecology, CHI Creteil, 40 avenue de verdun, 94010 Creteil, France. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.03.050
is a broad agreement to terminate the pregnancy when maternal or fetal conditions are altered, or once 34 weeks’ gestation is reached. Delivery at earlier gestational age, however, is associated with increased risk of adverse neonatal outcome.1 In addition, fetal lung maturity is not accelerated by preeclampsia,2 and neonatal outcome remains closely dependent on the use of corticosteroid for fetal lung maturity enhancement.3 The results of these findings have led to a policy of expectant management to improve neonatal outcome. Expectant management, however, may worsen maternal condition.4
Haddad et al Two randomized trials have shown an improvement of perinatal outcome without deterioration of maternal condition.5,6 These 2 studies, however, had limited sample size (total of 133 patients studied). This study was undertaken to determine maternal and perinatal outcomes after expectant management of singleton pregnancies with severe preeclampsia between 24 and 33 weeks’ gestation.
Material and methods Over a 6-year period (January 1, 1996, and December 31, 2001), all women with singleton pregnancies and with severe preeclampsia admitted at 2 perinatal centers (CHI Creteil and AP-HP Cochin Port-Royal) and who remained undelivered after receiving a full course of corticosteroid therapy (betamethasone or dexamethasone intramuscular, 12 mg/d for 2 days), had expectant management to prolong pregnancy. Expectant management was performed in labor or in high-risk pregnancy unit, depending on severity of clinical or biologic parameters. A resident, a midwife, a nurse, and a senior obstetrician were dedicated to these patients. The diagnosis of severe preeclampsia was made according American College of Obstetricians and Gynecologist (ACOG) criteria.7 Pregnancies with unstable conditions for either the mother or the fetus during the first 48 hours after admission were excluded from the study. Particularly, women with eclampsia, HELLP syndrome, severe uncontrolled hypertension (defined as difficulties to stabilize systolic blood pressure !160 mm Hg and systolic blood pressure !110 mm Hg), abruptio placentae, abnormal fetal heart rate monitoring, severe oligohydramnios (defined as amniotic fluid biggest pocket !2 cm or amniotic fluid index !5 cm) or reversed end diastolic flow in umbilical artery were excluded. Prophylactic magnesium sulfate was not used at any time during expectant management, in labor or the postpartum period. Maternal monitoring included 4 hourly blood pressure measurements, clinical evaluation of symptoms twice daily at least, and analysis of 24-hour urine excretion. Antihypertensive drugs were used to keep systolic blood pressure at 150 mm Hg or lower and diastolic blood pressure 100 mm Hg or lower. Intravenous nicardipine or intravenous labetalol were used as first line treatment in women with severe hypertension (defined as systolic blood pressure R160 mm Hg or diastolic blood pressure R110 mm Hg). When necessary these 2 drugs were used together. Blood tests included hemoglobin, platelet count, liver enzymes, creatinine, lactate dehydrogenase, fibrinogen, D-dimers, prothrombin, and partial thromboplastin times. These tests were performed daily or every other day, depending on clinical symptoms and laboratory findings. Fetal evaluation included ultrasound evaluation of fetal growth and estimation of amniotic
1591 fluid volume at entry, fetal heart rate monitoring, and clinical evaluation of fetal movements twice daily. Fetal indications for delivery during expectant management were abnormal fetal heart rate monitoring (repeated late decelerations, or decreased long-term variability), severe intrauterine growth retardation (IUGR), and oligohydramnios. Maternal indications for delivery during expectant management were major maternal complications (defined below), except for maternal death, severe uncontrolled hypertension, despite maximum doses of combined antihypertensive therapy (nicardipine and labetalol), persistent headaches or visual disturbance, persistent epigastic pain, low platelet count (!100,000 cells/mL), and oligoanuria. The main outcome of the study was days pregnancy prolongation defined as full days gained since the admission. Secondary outcomes were perinatal mortality and morbidity, days hospitalized in neonatal intensive care unit (NICU), and life-threatening maternal morbidity. Major perinatal complications included: fetal and neonatal death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) grade 3 and 4, and necrotizing enterocolitis (NEC). RDS was defined by the presence of characteristic radiographic findings and an oxygen requirement at 24 hours. BPD was defined as an oxygen requirement at 28 days after birth. IVH grade 3 was defined as hemorrhage with ventricular dilation, and grade 4 as hemorrhage with parenchymal spread. NEC was defined by characteristic clinical symptoms with radiographic findings of pneumatosis cystoides intestinalis or pneumoperitoneum or portal air. Major maternal complications included: maternal death, eclampsia, HELLP syndrome, abruptio placentae, disseminated intravascular coagulopathy (DIC), pulmonary edema, and acute renal failure. HELLP syndrome was defined by the presence of all 3 of the following criteria: hemolysis (characteristic peripheral blood smear and serum lactate dehydrogenase [LDH] R600 U/L or serum total bilirubin R1.2 mg/dL), elevated liver enzymes (serum aspartate aminotransferase [AST] R70 U/L), and low platelet counts (!100,000 cells/ mL).8 DIC was defined as the presence of 3 or more of the following criteria: low platelets (!100,000 cells/ mL), low fibrinogen (!300 mg/dL), positive D-dimers (R50 mg/dL), or prolonged prothrombin (R14 seconds) and partial thromboplastin (R40 seconds) times. Pulmonary edema was diagnosed on the basis of clinical findings and chest radiograph. Acute renal failure was diagnosed in the presence of oligoanuria in association with elevated serum creatinine greater than 120 mmol/L (>1.4 mg/dL). The need for dialysis was considered as severe acute renal failure. Gestational age was determined by last menstrual period and/or first trimester ultrasound examination.
1592 Table I
Haddad et al Clinical characteristics of study population
Age (y)* White (%) African (%) Nullipara (%) Previous preeclampsia (%) Chronic hypertension (%) Gestational age at admission (wks)*
31 (19 - 45) 63 32 55 13 17 29 (24-33.3)
* Values are expressed as median and range.
Severe IUGR was defined as birth weight less than fifth percentile.9 Pregnancy prolongation, and adverse perinatal and maternal outcomes were analyzed according to gestational age at time of admission which was divided into 3 groups: 24 weeks 0/7 days to 28 weeks 6/7 days, 29 weeks 0/7 days to 31 weeks 6/7 days, 32 weeks 0/7 days to 33 weeks 2/7 days of gestation. Data are presented as median and range, or percentage, as appropriate. Categorical variables were compared by c2 test. Continuous variables were analyzed by Student t test. A P value !.05 was considered significant. The evaluation of our conservative management did not need approval of our ethical committee because it was a prospective collection of data in women who received standard management at both hospitals. Therefore, our ethical committee has waved requirement for approval.
Results During the study period, there were 31,466 singleton deliveries. 381 (1.2%) singleton pregnancies were admitted for severe preeclampsia between 24 weeks 0/7 days and 33 weeks 2/7 days. Among these, 239 women were expectantly managed. Demographic and clinical characteristics are presented in Table I. Two hundred thirty-three (97.5%) infants were born alive. Median gestational age was 30.4 (25-34) weeks. Median birth weight of these infants was 1115 g (4803110 g). Six fetal deaths occurred before delivery at a median gestational age of 27.3 weeks (24.8-30 weeks), median birth weight of these infants was 590 g (360930 g). Five of these 6 deaths occurred in those expectantly managed at less than 29 weeks. Three of the 6 stillbirths had severe IUGR and birth weight below 500 g (360-480 g). One of the stillbirths died from abruption at 30 weeks (930 g). The median number of days in pregnancy prolongation days was 5 (2-35). The days gained were significantly higher among those who had expectant management at less than 29 weeks compared with the other 2 groups (6, 4, 4, respectively, Table II). Neonatal
outcomes are shown in Table II. Seven infants died during NICU hospitalization. All 7 were in the group at less than 29 weeks’ gestation and were delivered at a median gestational age of 26.3 weeks (25-30.6 weeks). Median birth weight of these 7 infants was 600 g (520-960 g). Overall, there were 13 perinatal deaths for a total perinatal mortality of 5.4%. Of these 13 deaths, 12 occurred in those expectantly managed at ! 29 weeks (median gestational age at delivery: 26.2 weeks [24.8-30.6 weeks], median birth weight: 650 g (360-960 g]) (Table III). The rates of IUGR were not statistically different among the 3 groups. The rates of RDS, BPD, IVH grade 3 to 4 were significantly higher among those who had expectant management at less than 29 weeks compared with 29 to 32 weeks, and 32 weeks or more, respectively. Median days of artificial ventilation were significantly higher among those who had expectant management at less than 29 weeks compared with 29 to 32 weeks, and 32 weeks or more, respectively. In addition, half of the infants delivered of women expectantly managed at 29 weeks or more needed mechanical ventilation less than 1 day. Overall, neonatal complications were rare (only 1 case of RDS) among those who had expectant management at 32 weeks or more. The length of days in NICU was significantly higher among those who had expectant management at less than 29 weeks when compared with the other 2 groups, respectively (Table II). There were no instances of maternal death or eclampsia or severe acute renal failure necessitating dialysis among the 239 women. Only 1 woman had serum creatinine 221 mmol/L or greater (R2.5 mg/dL). In addition, there were no differences among the 3 groups regarding development of antepartum HELLP syndrome, abruptio placentae, and pulmonary edema. Two of the 3 women who had DIC had abruptio placentae. Maternal outcomes are summarized by gestational age at admission in Table IV. Delivery was obtained by cesarean section in 95.8%. Common indications for delivery were maternal reasons for 48.5%, followed by fetal distress for 42.8%. In 8.7% indication for delivery were both maternal and fetal reasons. One hundred forty-two patients were excluded from the study during the first 48 hours after admission for maternal or fetal reasons. Maternal outcomes are summarized in Table V. Overall in our population, 37% of women were not considered eligible for expectant management.
Comment Recent studies have suggested that fetal lung maturity,2 as well as fetal neurologic and physical development,10 were not accelerated in pregnancies complicated by preeclampsia. In addition, neonatal mortality is closely
1593
Haddad et al Table II
Perinatal outcomes according to gestational age at onset of expectant management
Admission GA (wks) Delivery GA (wks) Birth weight (g) Prolongation (d) IUGR Neonatal mortality* Artificial ventilation (d) RDSz BPDz IVHy NEC NICU (d)
!29 wks (n = 110)
%29-!32 wks (n = 97)
R32 wks (n = 32)
27.4 28.4 885 6 28 7 3 69 34 6 6 22.5
30.3 31.1 1250 4 27
32.3 33 1617 4 3 0 10 1 0 0 0 5
(24-28.8) (24.8-32.7) (360-2560) (2-35)*y (25) (7) (0-60)yz (66) (33) (6) (6) (0-100)z
10 36 6 1 8
(29-31.8) (29.3-33.8) (480-2560) (2-32)* (27) 0 (0-17)*z (37) (6) 0 (1) (0-57)yz
(32-33.3) (32.3-34) (1190-3110) (2-12)y (9) (0-4)*y (3)
(0-18)yz
Data are shown as number (%), or median (range), as appropriate. GA, gestational age. * P ! .05, y P ! .01, z P ! .0001.
Table III Perinatal death, pregnancy prolongation and perinatal outcome according to gestational age at onset of expectant management Admission GA (wks)
Delivery GA (wks)
Days gained
Fetal death (n)
RDS* n (%)
BPDy n (%)
IVH* n (%)
NEC* n (%)
Neonatal death (n)
Perinatal mortality n (%)
24 (n = 6) 25 (n = 10) 26 (n = 23) 27 (n = 28) 28 (n = 43) 29 (n = 35) 30 (n = 34) 31 (n = 28) 32-33 (n = 32)
25.1 26.9 27.3 28.4 29.3 30 31 32.1 33
7 11 5 6 6 5 4 5 4.5
3 0 0 0 2 1 0 0 0
3 9 19 19 19 19 10 7 1
2 4 13 9 6 5 0 1 0
0 1 1 1 3 0 0 0 0
0 2 3 1 0 0 0 1 0
1 4 0 1 1 0 0 0 0
4 4 0 1 3 1 0 0 0
(100) (90) (83) (68) (46) (56) (29) (25) (3)
(100) (67) (57) (33) (15) (15) (4)
(10) (4) (4) (7)
(20) (13) (4)
(4)
(67) (40) (3.6) (7) (2.9)
Percentage calculated after exclusion of fetal death (*) or perinatal death (y).
Table IV
Maternal complications according to gestational age at onset of expectant management
Admission GA (wks)
Antepartum HELLP n (%)
Abruptio placentae n (%)
Pulmonary edema n (%)
DIC n (%)
Renal insufficiency n (%)
24 (n = 6) 25 (n = 10) 26 (n = 23) 27 (n = 28) 28 (n = 43) 29 (n = 35) 30 (n = 34) 31 (n = 28) 32-33 (n = 32)
2 4 4 2 5 4 7 2 4
0 1 2 2 2 1 1 3 2
1 0 2 2 1 0 1 1 1
0 2 (20) 0 1 (4) 0 0 0 0 0
0 0 3 2 1 1 2 2 2
(33) (40) (17) (7) (12) (11) (21) (7) (13)
(10) (9) (7) (5) (3) (3) (11) (6)
dependent on gestational age at delivery,11 and on the use of corticosteroid treatment to enhance fetal lung maturity.12 These studies have highlighted the need of expectant management to improve perinatal outcome in women with early-onset severe preeclampsia. The goal
(17) (9) (7) (2) (3) (4) (3)
(13) (7) (2) (3) (6) (7) (6)
of delivery of a live mature newborn infant in optimal condition, however, must not be achieved at the expense of maternal safety. This study was undertaken to determine pregnancy prolongation, and perinatal and maternal outcomes after
1594
Haddad et al
Table V Maternal complications in women excluded from the study (n = 142) compared with those included in the study (n = 239)
Eclampsia Antepartum HELLP Abruptio placentae Pulmonary edema DIC
Women excluded (n = 142) No. (%)
Study population (n = 239) No. (%)
P
11 (8) 48 (34)
0 34 (14)
!.001 !.001
19 (13)
14 (6)
!.05
3 (2)
9 (4)
ns
5 (3)
3 (1)
ns
expectant management of singleton pregnancies with severe preeclampsia between 24 and 33 weeks’ gestation. In this study, pregnancies were prolonged by a median number of 5 days, with a significantly greater period gained at earlier gestations. Days of pregnancy prolongation observed in this study are in agreement with results of recent trials.13,14 Two prospective randomized controlled trials comparing expectant management with early intervention have been published.5,6 The first study that included 38 patients found a mean pregnancy prolongation of 7.1 days in the group of women expectantly managed (n = 18).5 In a larger randomized controlled trial in which 95 patients where included, the mean pregnancy prolongation was 15 days.6 Regarding perinatal and neonatal mortality rates, our results are encouraging, as our observed rates were 5.4% and 3%, respectively. These results are in agreement with those published some years ago by Hall et al,13 with an important difference in that 46% of our population had gestational age at expectant management less than 29 weeks’ gestation compared with 26% in Hall et al study.15 Interestingly, there were no instances of perinatal death in women expectantly managed at 30 or more weeks’ gestation in our study. Neonatal morbidity was clearly related to gestational age at onset of expectant management and this is in agreement with previous studies.11,16,17 Increasing gestational age correlates with a reduction of respiratory distress syndrome.11,16 In addition, neonatal outcome was excellent during expectant management at 32 to 33 weeks. The sample size, however, is too low for valid conclusions. A much larger number of patients at 32 to 33 weeks needs to be studied before the benefits or safety of expectant management can be stated with certainty. Regarding maternal complications, expectant management was associated with a high incidence of antepartum HELLP syndrome (14.2%). This rate is higher than that previously reported,6,13 and this may be related to our population in which a majority of women
are white. The rate of abruptio placentae (5.9%) is similar to those reported in previous studies.1,6 There were, however, no instances of maternal death, eclampsia, or severe acute renal failure necessitating dialysis in our study, which is a reassuring finding. We did not use magnesium sulfate in the prevention of eclampsia in our management of women with early onset of severe preeclampsia. Some studies have suggested the usefulness of such therapy in women with severe preeclampsia.18,19 It is important to note, however, that in the MAGPIE trial, magnesium sulfate was not associated with a significantly decreased rate of eclampsia in the subgroup of women included from countries with low perinatal mortaliy.19 This absence of seizures in our patients may be related to the close maternal observation, to the use of aggressive blood pressure control, or to the sample size. The excellent perinatal outcome obtained in women expectantly managed at 30 weeks or more is certainly related to improvements in neonatal care, to corticosteroid treatment to enhance fetal lung maturity, and also to pregnancy prolongation. Some physicians would regard the delivery at 30 weeks or more after corticosteroid treatment to be in the best interests for both the mother and the fetus. Our study does not answer this question. In addition, Sibai et al6 have shown that expectant management, after corticosteroid treatment in women with severe preeclampsia after 30 weeks’ gestation, improved perinatal outcome with a minimal risk to the mother, even if their study had limited sample size. In summary, close and frequent observation of maternal and fetal status during expectant management of severe preeclampsia at 24 to 33 weeks in a tertiary care facility is associated with good perinatal mortality and neonatal outcome with a minimal risk for the mother.
References 1. Sibai BM, Spinnato JA, Watson DL, Hill GA, Anderson GD. Pregnancy outcome in 303 cases with severe preeclampsia. Obstet Gynecol 1984;64:319-25. 2. Schiff E, Friedman SA, Mercer BM, Sibai BM. Fetal lung maturity is not accelerated in preeclamptic pregnancies. Am J Obstet Gynecol 1993;169:1096-101. 3. Crowley P. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol 1995; 173:322-35. 4. Sibai BM, Taslimi M, Abdella TN, Brooks TF, Spinnato JA, Anderson GD. Maternal and perinatal outcome of conservative management of severe preeclampsia in mid-trimester. Am J Obstet Gynecol 1985;152:32-7. 5. Odendaal HJ, Pattinson RC, Bam R, Grove D, Kotz TJW. Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks’ gestation: a randomized controlled trial. Obstet Gynecol 1990;76:1070-5. 6. Sibai BM, Mercer BM, Schiff E, Friedman SA. Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks’
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gestation: a randomized controlled trial. Am J Obstet Gynecol 1994;171:818-22. The American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Washington, DC: The College; 1996 ACOG Technical Bulletin No: 219. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol 1993;169:1000-6. Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol 1996;87:163-8. Chari RS, Friedman SA, Schiff E, Frangieh AT, Sibai BM. Is fetal neurologic and physical development accelerated in preeclampsia? Am J Obstet Gynecol 1996;174:829-32. 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. Amorin MMR, Santos LC, Faundes A. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. Am J Obstet Gynecol 1999;180:1283-8. Hall DR, Odendaal HJ, Steyn DW, Grove D. Expectant management of early onset, severe pre-eclampsia: maternal outcome. BJOG 2000;107:1252-7. Chammas MF, Nguyen TM, Li MA, Nuwayhid BS, Castra LC. Expectant management of severe pre-eclampsia: is intrauterine growth restriction an indication for immediate delivery? Am J Obstet Gynecol 2000;183:853-8. Hall DR, Odendaal HJ, Kirsten GF, Smith J, Grove D. Expectant management of early onset, severe pre-eclampsia: perinatal outcome. BJOG 2000;107:1258-64. Abramovici D, Friedman SA, Mercer BM, Audibert F, Kao L, Sibai BM. Neonatal outcome in severe preeclampsia at 24 to 36 weeks’ gestation: Does the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome matter? Am J Obstet Gynecol 1999;180:221-5. Bernstein I, Horbar JD, Badger GJ, Ohlsson A, Golan A, for the Vermont Oxford Network. Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. Am J Obstet Gynecol 2000;182:198-206. Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995;333:201-5. Magpie Trial Collaboration Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002; 359:1877-90.
Discussion DR JAMES N. MARTIN, JR, Jackson, Miss. Dr James J. Walker, Professor of OBGYN at St James University Hospital hi Leeds, UK, wrote recently that ‘‘the mainstay of the management of severe preeclampsia is early referral, stabilization of the mother with antihypertensive therapy and anticonvulsants if required, full assessment of the mother and the baby, and delivery on the best day in the best way.’’1 Beyond the unspoken critical concept of correct diagnosis, we might summarize the core words (ie, the core concepts of Dr Walker) as referral, stabilization, assessment, and timely delivery.
1595 At issue is how best to manage the pregnancy complicated by severe preeclampsia before term, specifically between 24 and 34 weeks’ gestation, surely one of the most vexing obstetric issues currently plaguing the provider. There have been a number of trials undertaken in the last 15 years, either as randomized trials of aggressive versus expectant management, or more frequently as case series of patients with attempted expectant management. Professor Haddad’s article today is the latest of the latter type, and is second in size only to that of the series of 340 patients of Hall et al2 reported 3 years ago. Unfortunately, more questions than answers are raised by the authors’ information, and there is no comparison group upon which to validate the claim, as the authors do, that ‘‘expectant management of severe preeclampsia at 24 to 33 weeks in a tertiary care center improves perinatal outcome with a minimal risk for the mother.’’ Four years ago in 1999 Many et al3 reviewed the available data on this issue concluded that there were 4 unresolved problems in managing severe preeclampsia remote from term: 1. The lack of uniform criteria delineating severity of preeclampsiadwhich ones are or are not candidates for expectancy; 2. The lack of uniform criteria for ceasing conservative management and delivering; 3. The lack of consistency between institutions for providing high-risk maternal and newborn care (and expertise); and 4. Small patient numbers so far are insufficient to detect a small increased risk of maternal mortality with expectant, conservative management. What new information does Professor Haddad and his colleagues bring to the table today to expand our knowledge and clarify any of these 4 unresolved problems? Let’s consider them in order: 1. What about criteria for severity of preeclampsia? Other than the use of ‘‘ACOG criteria,’’ we are not told which specific criteria were used for diagnosis or whether the criteria/expression of the disease relates to the eventual maternal-fetal-neonatal outcome, or even whether the type of severe preeclampsia relates to survival of the initial 48- to 72-hour evaluation/ stabilization period and candidacy for expectant, conservative management. Can the authors help with this vital information (question 1)? 2. What about criteria for ceasing conservative management and changing expectancy to action? There are no specific summaries of endpoints used to indicate need for delivery whether urgent or emergent and how these relate to eventual maternal and neonatal outcome. Can the authors help with this vital information (question 2)? For instance, what failed to indicate the subsequent development