[Medscape Women's Health 7(1), 2002. © 2002 Medscape, Inc.]
Objective: To observe whether the pregnancy can be
safely continued for a reasonable period to gain fetal maturity in cases of
eclampsia and severe pre-eclampsia.
Methods: Fifty-one patients were
followed up in a specialized care (eclampsia) unit in Dhaka Medical College and
Hospital between January 1998 and October 2000. Twenty-one patients with
complaints of headache and blurred vision, and 30 patients with history of
convulsion, all at gestational age < 36 weeks, were enrolled for this study.
Magnesium sulfate was used to prevent convulsion in severe pre-eclampsia and to
control convulsion in eclampsia. After conducting a baseline assessment,
pregnancy was continued to gain fetal maturity. Patients were monitored
closely. Diastolic blood pressure, 24-hour urinary total protein (UTP), and
serum uric acid were chosen as the main parameters to detect the deterioration
of a patient's condition. Pregnancy was terminated when deterioration occurred,
as determined clinically or by 1 or more of the above parameters. Dexamethasone
was used during the waiting period for fetal lung maturity. Patient outcomes
were analyzed.
Results: At admission, the
patients' mean gestational age (± SD) was 30.65 ± 2.38 weeks, and the range was
24-34 weeks. Mean diastolic blood pressure was 109.06 ± 11.61 mm Hg, 24-hour
UTP was 2.25 ± 1.73 g/24 h , and serum uric acid level was 5.5 ± 1.12 mg/dL.
Pregnancy was continued for a mean of 13.27 ± 8.26 days (range, 3-35 days).
Thirty-two babies (62.75%) with birth weight 1.0-2.5 kg (2.02 ± 0.45) were born
alive. Six of them (18.75%) weighing between 1.0 and 1.5 kg at birth were
referred to the intensive care unit, and 1 (3.13%) weighing 1 kg at birth died
within 5 minutes after birth. Among live-born babies, 93.75% were in good
condition at the time of discharge from the hospital. Intrauterine death
occurred in 19 (37.25%).cases. Twelve of them delivered spontaneously within 7
days of death and 7 required induction. In all cases, maternal condition was
satisfactory.
Conclusion: In carefully selected
cases and with close supervision, pregnancy may be continued in women with
eclampsia and severe pre-eclampsia to increase fetal maturity without
increasing the risk to the mother.
Eclampsia and severe pre-eclampsia that
develop long before term are associated with increased rates of perinatal
mortality and morbidity.
The progression from severe pre-eclampsia to eclampsia is a
continuous process; patients with severe pre-eclampsia who remain untreated may
develop eclampsia. Occurrence of a seizure that is not attributable to other
causes in a pre-eclamptic patient is known as eclampsia. It is conventionally
considered to be the end stage of the disorder, but this is an
oversimplification. Some patients have only systemic disturbances and the
problem can be controlled easily with rapid recovery after delivery. Other
patients may become desperately ill with progressive renal failure,
disseminated intravascular coagulation (DIC), microangiopathic hemolysis, and
liver dysfunction. Thus, convulsions are a marker for severe illness but not
always a reliable one. Some patients with pre-eclampsia are more dangerously
ill than others with eclampsia.[1] If convulsion can be controlled and all other parameters
remain indicative of a state of severe pre-eclampsia, women with eclampsia can
be treated as if they had severe pre-eclampsia.
The clinical course of these conditions may lead to progressive
deterioration of both mother and fetus . Because the only cure for these
conditions is delivery, there is universal agreement that patients should be
delivered if severe pre-eclampsia develops after 34 weeks of gestation or if
development of convulsion occurs anytime during the gestational period.[2,3]
Aggressive management with immediate delivery leads to high
neonatal mortality and morbidity resulting from prematurity. Thus, prolonged
hospitalization in a neonatal intensive care unit (ICU) is necessary for the
majority of surviving newborn infants.[4-7] Moreover, a significant proportion of
surviving infants have long-term disability.[8] Conversely, attempts to prolong
pregnancy with expectant management may result in fetal death or asphyxial
damage in utero as well as increased maternal morbidity.[5,7,9]
It is recognized that termination of pregnancy is the only
definitive cure of the pathophysiologic events of pre-eclampsia and eclampsia.
So, an arbitrary time period for delivery of all patients with these
complications has not been thought to be in the best interest of either the
mother or the fetus. But there is considerable disagreement about management of
patients with severe pre-eclampsia before 34 weeks' gestation. Some
institutions consider delivery to be the definitive therapy for all cases,
regardless of gestational age, whereas others recommend prolonging pregnancy in
all severely premature pre-eclamptic gestations until 1 of the following
occurs: development of fetal lung maturity, development of fetal or maternal
distress, or achievement of gestational age of 34 to 36 weeks.[4,9-11]
Eclampsia is a grave condition, and as there is a constant threat
of eclampsia in cases of severe pre-eclampsia, maternal well-being should
always receive priority. However, if convulsive fits can be controlled and the
features promptly stabilized with treatment before fetal maturity has been
attained , continuation of the pregnancy for a few weeks may be considered.[12] Continuation of pregnancy for a few more
weeks with the hope of delivering a more mature baby should be weighed against
the potential risk conferred by such a procedure. Not only may the underlying
disease process flare up at any moment, but there is a considerable risk that
the baby will die in utero or become undernourished and that spontaneous
premature labor will occur. Thus, only in selected cases is one justified to
continue the pregnancy; this requires keeping the patient in the hospital with
close monitoring of maternal and fetal condition and strictly following the
management protocol recommended for severe pre-eclampsia.[13]
We observed, after controlling convulsion, that some patients were
unwilling to immediately terminate their pregnancy; this resulted in a 3- to
4-day delay in termination. Although the perinatal death rate was very high,
patients were discharged in good condition. On the basis of this experience, we
sought to determine whether pregnancy can be continued in cases of eclampsia
and severe pre-eclampsia in order to improve neonatal outcome -- without
causing any harm to the mother.
This descriptive study was conducted at
Dhaka Medical College and Hospital between January 1998 and October 2000 and
included 21 patients with severe pre-eclampsia (with premonitory signs and
symptoms of eclampsia, ie, headache, blurred vision, and restlessness) and 30
patients with eclampsia, all of whom were at < 36 weeks' gestation. We
selected a 36-week cutoff point for gestational age because of the high
neonatal morbidity and mortality among babies born before this cutoff point in
our country. Poor neonatal care facilities are the primary reason for this. At
our institution, 9352 babies were born in 1999. Of these, 4478 were high-risk
pregnancies (unpublished Dhaka Medical College Hospital statistics). The
neonatal care unit has only 8 beds with 1 incubator and 2 phototherapy
machines. The unit does not admit a baby if a bed is not available. Outside the
hospital, there are a few private well-equipped institutions with ICUs. But the
cost for care in these units is about 4000Taka (BSD), or about $70 USD, per
day; this cost exceeds most patients' monthly
income!
All patients had a live fetus at the time of inclusion and all had
documented evidence of the disease -- ie, proteinuria, edema. high blood
pressure, convulsion -- before management started. Patients with maternal and
fetal indications necessitating immediate delivery on admission were not
included. Exclusion criteria were as follows: Glasgow Coma Scale < 15, heart
failure, severe oliguria, anuria, pulmonary edema, renal failure, HELLP
(hemolysis, elevated liver enzymes, and low platelet count) syndrome, DIC, hepatic
failure, recurrent convulsion after magnesium sulfate, gross intrauterine
growth retardation, fetal distress (nonreassuring fetal status), and patient
unwillingness to stay in the hospital.
All patients were admitted into the Eclampsia Unit of the Obstetrics
and Gynecology Department. They came from in and around Dhaka; some of them
were referred from other hospitals and health centers, and some came directly
to this institution. Those who were referred from other hospitals or health
centers had received at least 1 injection of diazepam. Initial management at
this institution included the following: intravenous injection of magnesium
sulfate, 4 g, administered slowly; magnesium sulfate, 3 g intramuscularly (IM),
in each buttock as a loading dose, followed by 2.5 g IM in each alternate
buttock every 4 hours for 24 hours; bed rest; oral phenobarbitone, and an
antihypertensive (eg, methyldopa, hydralazine, nifedipine) as required. Oral
methyldopa, with or without nifedipine, was administered to maintain diastolic
blood pressure at a level between 90 and 100 mm Hg. If diastolic blood pressure
increased to above 110 mm Hg after magnesium sulfate therapy or despite
adequate oral antihypertensive medications, intravenous bolus doses of
hydralazine, 5-7 mg, or a continuous intravenous infusion of hydralazine was
administered.
All patients underwent 24-hour urine collection for measurement of
urinary total protein (UTP). Serum urea, creatinine, uric acid, SGOT, SGPT, and
platelet count were determined in all cases. Ultrasonography was performed for
estimation of gestational age of the fetus; for this, the last menstrual period
and height of the uterus were correlated. During the initial 24-hour
observation, all patients received dexamethasone, 12 mg IM, every 12 hours for
48 hours.
Before starting conservative management, patients and their
relatives were informed about the management plan and risks and benefits of
conservative management. If the patient agreed to continue conservative
management of eclampsia, she signed a consent form. After the initial 24-hour
observation period, patients were again counseled regarding maternal and
perinatal risks and benefits of conservative management.
The goal of the conservative management was to prolong pregnancy
until 36 completed weeks or until the onset of either maternal or fetal
complications (fetal death, fetal distress, or static growth). Patients were
monitored by staff specially trained in eclampsia management. Monitoring included
inquiry about any complaints, blood pressure measurement 4 times daily, fetal
heart sound auscultation 2 times daily, fetal growth monitoring by
ultrasonography every 2 weeks, and repetition of other tests whenever
necessary. Patients were instructed to report the development of features such
as persistent headaches, insomnia, visual disturbances, epigastric pain, and
such other features as uterine contractions, cramps, vaginal bleeding, ruptured
membrane, or decreased fetal movement.
Blood pressure was controlled by administering methyldopa and oral
nifedipine. The initial dose of methyldopa was 250 mg every 8 hours up to a
maximum dose of 500 mg every 6 hours. Nifedipine, 10 mg, was administered every
8 hours up to a maximum dose of 10 mg every 6 hours. The aim of therapy was to
keep systolic blood pressure at a level between 140 and 150 mm Hg and diastolic
blood pressure at a level between 90 and 100 mm Hg. If diastolic blood pressure
rose to 110 mm Hg or above, hydralazine was administered in 1 of 2 ways: 20 mg
diluted in 10 cc distilled water, administered by IV directly in 5-mg boluses
or 20 mg in 200 cc normal saline, administered by IV drip at the rate of 10
drops per minute and increased as necessary. Dexamethasone therapy was repeated
weekly until delivery.
Laboratory evaluations of UTP, urea, uric acid, platelet count,
SGOT, and SGPT were repeated weekly whenever initial parameters were higher
than normal levels. Otherwise, tests were not repeated because of limited
facilities. Fetal evaluation included kick count, auscultation of fetal heart
sound, measurement of fundal height, and ultrasonography performed every 2
weeks.
Termination of pregnancy was based on both maternal and fetal
indications. Maternal indications for delivery were the following: uncontrolled
severe hypertension in spite of the adequate antihypertensive therapy, onset of
persistent headache, epigastric pain, vaginal bleeding (abruptio placentae),
and ruptured membranes. Fetal indications for delivery included fetal distress
(or, nonreassuring fetal status, [as determined by auscultating fetal heart
sound and, in some cases, by biophysical profile) fetal death, static growth,
and attainment of 36 weeks pregnancy. All patients were discharged with stable
blood pressure levels and 1+ or absent urinary albumin.
Analysis of data included assessment of maternal complications,
laboratory findings, days gained during management, and perinatal outcome.
Perinatal outcome parameters included mortality, gestational age at delivery,
birth weight, birth condition, neonatal complications, and number of days spent
in neonatal intensive care. Results were expressed as mean ± SD and relative
risk.
Of 51 patients, 21 were diagnosed with
severe pre-eclampsia, and 30 were diagnosed with eclampsia. The average age of
the patients was 25.21 ± 4.64 years (range, 17-35 years). Most of the patients
were primigravid (68.63%), and no patients had antenatal check-up before
admission to the hospital. Average gestational age was 30.65 ±2.38 weeks (range,
24-34 weeks) (Table 1).
Table 2 shows the patients' conditions at admission. Patients had
diastolic blood pressure levels ranging from 90-140 mm Hg with a mean value of
109.05 ± 11.61 mm Hg. Most of the patients (90.2%) had 2+ to 4+ proteinuria, and
74.51% had moderate leg edema. All patients were fully conscious at admission.
Laboratory investigations are shown in Table 3. Urea, SGOT, SGPT,
and platelet count were within normal limits. The mean UTP was 2.25g/24 hours
(range, 0.12-6.53 g/24 h; serum uric acid was 5.5 mg/dL (range, 3.6-8.7 mg/dL;
and serum creatinine was 1.31 mg/dL (range, 0.7-3.6 mg/dL).
Table 4 summarizes pregnancy outcomes. The average pregnancy
prolongation was 13.27 ± 8.26 days, with a range of 3-35 days.
Twelve patients reached 36 weeks of gestation. Of these, 5 were at
32 weeks, 3 were at 33 weeks, and 4 were at 34 weeks at the time of
recruitment. One of the babies weighed 2.3 kg at birth, 7 weighed 2.4 kg, and 4
weighed 2.5 kg at birth. Prognosis was unsatisfactory for those patients whose
gestational age was < 30 weeks (see Discussion, below). Of the 16 patients
with gestational age < 30 weeks, only 1 baby survived. The patient came into
the study at a gestational age of 28 weeks and pregnancy was continued for
another 2 weeks. The baby's birth weight was 1 kg. Lower segment cesarean
section was performed because the mother's 24-hour UTP rose from 1.5 g to 3 g
and blood pressure could not be controlled satisfactorily.
Intrauterine death occurred in 19 (37.25%) cases. Only 1 patient
(1.96%) developed a maternal complication (abruptio placentae) 3 weeks after
development of convulsion. Table 5 shows the indication for termination of
pregnancy. Eighteen patients, including 12 with intrauterine death, went into
spontaneous labor at different ages of gestation. Other pregnancies were
terminated for the following reasons (1) no improvement after treatment (n = 7
[13.73%]; although none of these patients had recurrent or persistent seizure,
they all had uncontrolled blood pressure and increasing uric acid and total
protein values), (2) patient's desire (n = 2 [3.92%]); (3) fetal compromise (n
= 15 [29.41%]); (4) attainment of 36 weeks (n = 7 [13.72%]; 12 patients
attained 36 weeks gestation, but 5 went into spontaneous labor); (5) premature
rupture of membrane (n = 1 [1.96%]); and (6) abruptio placentae (n = 1
[1.96%]).
For the 32 live-born babies, the average birth weight was 2.02 kg
± 0.45 (range, 1.0-2.5 kg). Six babies weighing 1.0-1.5 kg at birth were referred
to the ICU; 1 of them died 2 days after birth, 1 died 3 days after birth, and 4
were discharged from hospital after 3 weeks.
Table 6 shows the perinatal outcomes before and after 30 weeks of
gestation. Live birth occurred in only 12.5% of those whose gestational age was
24-29 weeks and in 85.71% of those whose gestational age was >= 30 weeks at
recruitment. Relative risk of intrauterine death was 6.13 times higher for
infants of gestational age < 30 weeks than for those of gestational age
>= 30 weeks (95% CI, 2.66-14.08).
The first goal of management of severe
pre-eclampsia and eclampsia is prevention or control of convulsions and
stabilization of the patient's basic cardiovascular status. Administration of
magnesium sulfate by an established protocol[14] is considered to be the most rapid,
efficient, and safe pharmacologic approach for accomplishing this goal.
Hospitalization is an essential part of this management because it
is necessary to evaluate the full extent of the effects of the disease process
on the mother and fetus. Only in this way can the patient experience minimal
physiologic stress while undergoing the laboratory procedures needed to assess
maternal conditions, especially renal and hepatic function.
Finally, the aim should be to designate the time of delivery in
such a fashion that both the mother and fetus are best able to tolerate
delivery while providing the fetus with the maximum chance of extrauterine
survival.
Most clinical centers have limited experience in managing such
patients. As a result, there are no recommended protocols for conservative
management of patients with severe pre-eclampsia and eclampsia. Thus,
management has been based on retrospective observations and empiric clinical
experience, with an aim to secure safety of the mother first and a secondary
goal of safe delivery and survival of the newborn.
We wish to emphasize that the group of patients included in this
study were carefully selected. First, they were judged suitable for expectant
management if they had no other medical obstetric complications or
complications of eclampsia and if they remained stable during the initial
24-hour observation period.
We found that it was possible to prolong pregnancy by an average
of 13.27 ± 8.26 days (range, 3-35 days) in our study population. Platelet
count, SGOT, SGPT, and serum urea of all patients were within normal limits.
Only 24-hour UTP, uric acid, and creatinine values were higher than normal in
most of the patients.
Schiff and colleagues[15] concluded that the level of proteinuria and the rate of
increase in proteinuria during conservative management are not important
predictors of maternal or perinatal outcome. In their study, patients whose
protein excretion reached 10-20 g/24 h had outcomes and admission-to-delivery
intervals similar to those seen in women who had mild proteinuria (< 5 g/24
h).
In our study, the maximum protein excretion was 6.53 g/24 h in a
patient whose pregnancy could be continued for only 3 days, and she gave birth
to a stillborn baby. The uric acid level of that patient was within the normal
limit (4.30 mg/dL). On the other hand, for a patient whose protein excretion
was 0.37 g/24 h, pregnancy could be continued for 15 days longer, and she gave
birth to a baby weighing 2.5 kg. The uric acid level of this patient was 7.8
mg/dL.
The maximum uric acid level, 8.7 mg/dL, was observed in a patient
whose pregnancy could be continued for only 3 days (spontaneous delivery
occurred); . the birth weight of her baby, who died 24 hours after birth, was
only 1 kg. Surprisingly, the 24-hour protein excretion of this patient was only
0.70 g. Thus, it is difficult to say whether uric acid or protein excretion has
a more predictive value of pregnancy outcome. Lim and associates[16] found only a weak correlation between
serum uric acid levels and the severity of disease. They showed a weak
correlation between serum uric acid levels and maternal blood pressure and
birth weight of the baby.
It is important to note that delivery was delayed until 36 weeks'
gestation in 12 patients, and none of those infants required admission to the
neonatal ICU. The patients whose gestational age was far away from term (<
30 weeks) during enrollment showed poor prognosis. Sixteen patients had a
gestational age between 24 and 29 weeks. Of these, intrauterine death occurred
in 14 cases; 2 patients did not respond to treatment, and cesarean section was
performed 2 weeks after admission at 30 and 31 weeks, respectively. Both of
these babies were transferred to the ICU; their birth weights were 1 kg and 1.2
kg, respectively. One survived and the other died 2 days after birth.
Lin and coworkers[17] reported the outcome of perinatal death in 95
pre-eclamptic pregnancies at < 30 weeks' gestation. Their study was
conducted at the Chicago Lying-In-Hospital between 1958 and 1976; the patients
were diagnosed with hypertensive disorder of pregnancy.
Martin and Tupper[9] reported on 55 patients with severe pre-eclampsia who were
treated conservatively; 9 were between 24 and 30 weeks' gestation. Two of the 9
pregnancies resulted in stillbirths, and 1 ended in neonatal death. Goodlin and
colleagues[18] reported on 11 patients with severe pre-eclampsia who were
treated conservatively; 4 were at 24-27 weeks' gestation. Two of these 4 gave
birth to stillborn babies, and 1 died during the neonatal period; 2 survived.
Moore and Redman[19] reported on 24 patients with severe pre-eclampsia before
34 weeks' gestation who were treated conservatively. Of these, 4 patients had
onset of symptoms during midtrimester that resulted in 2 stillbirths and 2
neonatal deaths. On the basis of these data, it is clear that if severe
pre-eclampsia develops before 30 weeks of gestation, the result of conservative
management is not satisfactory, which is consistent with the findings of the
current study.
Maternal morbidity was not high in our study. Only 1 patient
developed abruptio placentae 3 weeks after her admission; her convulsions had
occurred at 28 weeks of gestation. Sibai and colleagues[20] found high maternal morbidity in
patients with severe pre-eclampsia who were conservatively managed, which is
not consistent with the results of our study. Conservative management did not
significantly improve perinatal outcome in this series, as intrauterine death
occurred in almost all cases of midtrimester pregnancy. However, the maternal
condition was quite stable in the majority of cases during continuation of
pregnancy.
No death or major complication developed in this series. During
discharge, all patients had stable blood pressure and 1+ or absent urinary
albumin. The mean time interval between delivery and discharge was similar to
that of other patients who were not enrolled in this series. Because of
cultural and socioeconomic conditions, almost all patients were lost to
follow-up after discharge. Even though counseling was offered, no patient came
for follow-up. The limitation of this study, then, is that we are not able to
follow up on the long-term effects of conservative treatment of these patients.
We conclude that in selected cases, with
close monitoring and supervision, conservative management can be attempted in
cases of severe pre-eclampsia and eclampsia after 30 weeks of gestation. This
is especially important in developing countries, where neonatal intensive care
is either nonexistent or beyond the reach of many patients. Further controlled
trials involving a larger number of patients are needed to establish the safety
of the protocol.
|
|
Range |
Mean ± SD |
|
Age (Yrs) |
17-35 |
25.21
± 4.69 |
|
Gestational age at admission (weeks) |
24-34 |
30.27
± 2.59 |
|
Parity |
Number |
Percentage |
|
Nil |
35 |
68.63 |
|
1-2 |
11 |
21.57 |
|
3-4 |
5 |
9.80 |
|
Severe pre-eclampsia |
21 |
41.18 |
|
Eclampsia |
30 |
58.82 |
|
Diastolic BP (mm Hg) |
Range |
Mean ± SD |
|
Number |
Percentage |
|
|
Proteinuria |
||
|
+ |
5 |
9.80 |
|
++ |
10 |
19.61 |
|
+++ |
33 |
64.70 |
|
++++ |
3 |
5.88 |
|
Edema |
||
|
Nil |
5 |
9.80 |
|
+ |
8 |
15.69 |
|
++ |
27 |
52.94 |
|
+++ |
11 |
21.57 |
|
Glasgow Coma Scale |
||
|
15 |
51 |
100 |
|
Specimen |
Range |
Mean ± SD |
|
24-hour UTP (g/24 h) |
0.12
- 6.53 |
2.25
± 1.73 |
|
Urea (mg/dL) |
22
- 65 |
41.25
± 7.32 |
|
Creatinine (mg/dL) |
0.7
- 3.6 |
1.31
± .56 |
|
Uric acid (mg/dL) |
3.0
- 8.7 |
5.5
± 1.12 |
|
SGOT (IU/L) |
7
- 42 |
17.85
± 8.06 |
|
SGPT (IU/L) |
10
- 42 |
20.0
± 11.57 |
|
Platelet count (n/mm3) |
100
- 300 |
202.81
± 49.82 |
UTP = urinary total protein
|
Outcome |
Range |
Mean ± SD |
|
Pregnancy continued (days) |
3
- 35 |
13.27
± 8.26 |
|
Birth weight (kg) |
1.0
- 2.5 |
2.02
± 0.45 |
|
|
Number |
Percentage |
|
Complications |
||
|
Abruptio placentae |
1 |
1.96 |
|
Intrauterine death |
19 |
37.25 |
|
Mode of delivery |
||
|
Vaginal |
25 |
49.02 |
|
Spontaneous labor |
14 |
56 |
|
Induction |
11 |
44 |
|
Cesarean section |
26 |
50.98 |
|
Elective |
22 |
84.62 |
|
Emergency |
4 |
15.38 |
|
Indications |
Number |
Percentage |
|
Resistant to treatment |
7 |
13.73 |
|
Unstable blood pressure |
5 |
71.43 |
|
Increasing UTP |
1 |
14.28 |
|
Increasing uric acid |
1 |
14.28 |
|
Patient desire |
2 |
3.92 |
|
Fetal compromise |
15 |
29.41 |
|
Attainment of 36 weeks |
7 |
13.73 |
|
Premature rupture membrane |
1 |
1.96 |
|
Abruptio placentae |
1 |
1.96 |
|
Spontaneous labor |
18 |
35.29 |
UTP = urinary total protein
|
Gestational age at
recruitment |
Still born |
Live born |
RR (95% CI) |
|
24-29 weeks' gestation |
14
(87.5%) |
2
(12.5%) |
6.13
(2.66-14.08) |
|
30-34 weeks' gestation |
5
(14.28%) |
30
(85.71%) |
|
|
Total |
19
(37.25%) |
32
(62.75%) |
Mosammat Rashida Begum,
MBBS, FCPS, has
no significant financial interests to disclose.
Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.