Incidence, risk factors, and associated complications of eclampsia.

Abstract

To estimate trends in incidence and identify risk factors and maternal and neonatal consequences of eclampsia in Canada.
We conducted a population-based cohort study of all women and their newborns (N=1,910,729) delivered in the hospital in Canada (excluding Quebec) from 2003 to 2009. The data were obtained from the Canadian Institute for Health Information. Logistic models were used to examine the association with potential determinants and consequences of eclampsia.
The incidence of eclampsia declined dramatically from 12.4 per 10,000 deliveries in 2003 to 5.9 in 2009. Among singleton deliveries, nulliparity (adjusted odds ratio [OR] 2.3; 95% confidence interval [CI] 2.0-2.6), anemia (adjusted OR 2.4; 95% CI 2.0-3.0), and existing heart disease (adjusted OR 4.8; 95% CI 2.9-7.3) increased the risk of eclampsia. The declining trend in eclampsia remained unchanged after accounting for changes in potential determinants and risk factors during the study period. Eclampsia was associated with increased risks of maternal death (adjusted OR 26.8; 95% CI 9.7-73.8), assisted ventilation (adjusted OR 102.3; 95% CI 78.2-133.8), respiratory distress syndrome (adjusted OR 36.2; 95% CI 15.3-85.3), acute renal failure (adjusted OR 20.9; 95% CI 11.4-38.3), obstetric embolism (adjusted OR 9.1; 95% CI 4.1-19.9), and other complications. Adverse neonatal outcomes associated with eclampsia included neonatal death (adjusted OR 2.9; 95% CI 1.6-5.5), respiratory distress syndrome (adjusted OR 5.1; 95% CI 4.1-6.3), and small-for-gestational age birth (adjusted OR 2.6; 95% CI 2.3-3.0).
Despite declining incidence and improved care of women with eclampsia, the condition remains strongly associated with serious adverse consequences.

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Incidence, Risk Factors, and Associated
Complications of Eclampsia
Shiliang Liu, MD, PhD, K. S. Joseph, MD, PhD, Robert M. Liston, MD, Sharon Bartholomew, MHSc,
Mark Walker, MD, MSc, Juan Andre ´s Leo ´n, MD, MSc, Russell S. Kirby, PhD, MSc, Reg Sauve, MD, MPH,
and Michael S. Kramer, MD, for the Maternal Health Study Group of the Canadian Perinatal
Surveillance System (Public Health Agency of Canada)
OBJECTIVE: To estimate trends in incidence and identify
risk factors and maternal and neonatal consequences of
eclampsia in Canada.
METHODS: We conducted a population-based cohort
study of all women and their newborns (N?1,910,729)
delivered in the hospital in Canada (excluding Quebec)
from 2003 to 2009. The data were obtained from the
Canadian Institute for Health Information. Logistic mod-
els were used to examine the association with potential
determinants and consequences of eclampsia.
RESULTS: The incidence of eclampsia declined dramati-
cally from 12.4 per 10,000 deliveries in 2003 to 5.9 in 2009.
Among singleton deliveries, nulliparity (adjusted odds
ratio [OR] 2.3; 95% confidence interval [CI] 2.0–2.6),
anemia (adjusted OR 2.4; 95% CI 2.0–3.0), and existing
heart disease (adjusted OR 4.8; 95% CI 2.9–7.3) increased
the risk of eclampsia. The declining trend in eclampsia
remained unchanged after accounting for changes in
potential determinants and risk factors during the study
period. Eclampsia was associated with increased risks of
maternal death (adjusted OR 26.8; 95% CI 9.7–73.8),
assisted ventilation (adjusted OR 102.3; 95% CI 78.2–
133.8), respiratory distress syndrome (adjusted OR 36.2;
95% CI 15.3–85.3), acute renal failure (adjusted OR
20.9; 95% CI 11.4–38.3), obstetric embolism (adjusted OR
9.1; 95% CI 4.1–19.9), and other complications. Adverse
neonatal outcomes associated with eclampsia included
neonatal death (adjusted OR 2.9; 95% CI 1.6–5.5), respi-
ratory distress syndrome (adjusted OR 5.1; 95% CI 4.1–
6.3), and small-for-gestational age birth (adjusted OR 2.6;
95% CI 2.3–3.0).
CONCLUSION: Despite declining incidence and im-
proved care of women with eclampsia, the condition
remains strongly associated with serious adverse conse-
quences.
(Obstet Gynecol 2011;118:987–94)
DOI: 10.1097/AOG.0b013e31823311c1
LEVEL OF EVIDENCE: II
E
maternal and perinatal mortality and morbidity
worldwide.1–5Variable rates and temporal trends
have been observed in countries such as Canada
and the United States and in European countries
over recent decades; the magnitude of eclampsia
clampsia, the occurrence of a seizure in association
with preeclampsia, remains an important cause of
See related editorial on page 976 and related article on page 995.
From the Health Surveillance and Epidemiology Division, Centre for Chronic
DiseasePreventionandControl,PublicHealthAgencyofCanada,Ottawa,Ontario,
Canada; the Department of Obstetrics and Gynaecology, University of British
Columbia and the Children’s and Women’s Hospital of British Columbia, Van-
couver, British Columbia, Canada; the School of Population and Public Health,
University of British Columbia, Vancouver, British Columbia, Canada; the
Department of Obstetrics and Gynaecology, University of Ottawa and Ottawa
Health Research Institute, Ottawa, Ontario, Canada; the Department of Commu-
nity and Family Health, University of South Florida, Tampa, Florida; the
Departments of Pediatrics and Community Health Sciences, University of Calgary,
Calgary, Alberta, Canada; the Departments of Pediatrics & Epidemiology and
Biostatistics, McGill University, Montreal, Quebec, Canada; and the Canadian
Institutes of Health Research, Ottawa, Ontario, Canada.
This study was carried out under the auspices of the Canadian Perinatal
Surveillance System. Dr. K. S. Joseph is supported by the Child and Family
Research Institute, Vancouver, Canada.
The authors thank the Canadian Institute for Health Information for access to
the data. The authors also thank members of the Maternal Health Study Group
for data acquisition, verification, interpretation, and quality assurance, includ-
ing: John Fahey (Dalhousie University), Dr. William Fraser (University of
Montreal), Dr. Catherine McCourt (Public Health Agency of Canada), Dr.
David Young (Dalhousie University), and Juliana Wu (Canadian Institute for
Health Information).
Presented at the 3rd North American Congress of Epidemiology, June 21–24,
2011, Montreal, Quebec, Canada.
Corresponding author: Dr. Shiliang Liu, Health Surveillance and Epidemiology
Division, Centre for Chronic Disease Prevention and Control, Public Health
Agency of Canada, Building #19, AL 1910D, Tunney’s Pasture, Ottawa, ON,
Canada K1A 0K9; e-mail: Shiliang.Liu@phac-aspc.gc.ca.
Financial Disclosure
The authors have no potential conflicts of interest to disclose.
© 2011 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/11
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incidence and temporal trends have differed de-
pending on data sources, frequency of obstetric
interventions such as early delivery, and, most
recently, use of magnesium sulfate prophylaxis for
women with severe preeclampsia.6–12
Eclampsia usually occurs in women who have
established preeclampsia, although a woman can expe-
rience an eclamptic seizure with no prior warning. Only
a tiny portion of women with preeclampsia will develop
eclampsia, but the latter can be extremely serious or
even fatal. In Canada, hypertension in pregnancy (in-
cluding pre-existing hypertension, gestational hyperten-
sion, preeclampsia, eclampsia, or any combination) was
identified as a major contributor to maternal death
between 1997 and 2000.13Anticonvulsants (partic-
ularly magnesium sulfate) have been used both
therapeutically and prophylactically for women
with preeclampsia, on the basis of evidence that
they can prevent the onset of eclampsia and im-
prove outcome for both mother and newborn.14–21
Recent studies have revealed a sharp decline in
the incidence of eclampsia in Canada between 2003
and 2007, although the cause of this decline has not
been investigated.22,23Also, few recent studies have
examined risk factors and maternal and neonatal
adverse outcomes following eclampsia. The objec-
tives of the present study were to estimate the recent
trend in eclampsia incidence in Canada, to identify
maternal characteristics and other risk factors for its
occurrence, and to examine its association with severe
maternal and neonatal adverse outcomes.
MATERIALS AND METHODS
This study was based on hospital discharge records,
collated in the Discharge Abstract Database of the
Canadian Institute for Health Information from fiscal
year 2003–2004 to 2009–2010. Data on hospitaliza-
tions occurring in Quebec were not included, as
comparable information for this province was not
contained in the Discharge Abstract Database. The
database included all hospital deliveries and newborn
discharges, which accounted for more than 98% of all
births in the study jurisdictions during the study
period.
Hospital medical archivists extracted hospital dis-
charge data, including sex, age (birth date for new-
borns only), date of admission, home postal code (first
three digits), province of hospital delivery, province
issuing health care insurance, date and status at
discharge, principal diagnosis, up to 24 secondary
diagnoses (coded according to the International Sta-
tistical Classification of Diseases and Related Health
Problems, Tenth Revision, Canada [ICD-10 CA]),
and up to 20 diagnostic, therapeutic, and surgical
procedures (coded according to the Canadian Classi-
fication of Health Interventions).24,25For delivering
women and newborns, information on parity, clinical
estimate of gestational age, and birth weight was also
contained in the database. Information in the data-
base has been previously validated and has been used
extensively in perinatal health surveillance and re-
search.22,23,26,27A recent validation study showed that
the information in the Discharge Abstract Database
was accurate, with high sensitivity and specificity for
pre-existing hypertension, preeclampsia, any gesta-
tional hypertensive disorder, induction of labor, and
cesarean delivery.28
Obstetric deliveries were identified using a spe-
cific algorithm of codes that has been previously
validated by the Canadian Institute for Health Infor-
mation.26Hospital records of newborns were similarly
identified using specific codes. Eclampsia, defined as
development of convulsions during pregnancy or in
the postpartum period in women with signs and
symptoms of preeclampsia, or gestational or pre-
existing hypertension, was identified by ICD-10 CA
codes (O15.0-O15.2 or O15.9). The fourth digit of
these ICD codes was used to identify whether the
onset of eclampsia was in pregnancy, in labor, in the
puerperium, or unspecified as to time period. Mater-
nal characteristics, pregnancy conditions, and obstet-
ric conditions and outcomes were also defined using
ICD-10 CA codes. For example, existing heart dis-
ease was identified using the codes I01–I09, I20,
I23.0–I23.5, I23.8, I24.9–I51.2, I51.4–I52.9, I97.0–
I97.8, I98.0–I98.8, R00.1, R00.8, and R01.2, and
anemia was identified using codes D46.1, D64.0–
D64.3, and O99.0. To estimate the effects of eclamp-
sia on newborns, hospital discharge records of moth-
ers (with singleton gestation) and newborns were
linked using maternal-newborn identification num-
bers that were introduced by the Canadian Institute
for Health Information in fiscal year 2001–2002. The
overall success rate of such deterministic linkage for
2003–2004 to 2009–2010 was 95.0%; unlinked cases
included those with incomplete identification num-
bers (n?87,454), fetal death (n?8,101), and maternal
death (n?87). Small-for-gestational age and large-for-
gestational age newborns were defined as those whose
birth weight was, respectively, below the 10th or
above the 90th percentile of the Canadian sex-specific
birth weight for gestational age reference.29The sta-
tistical significance of crude comparisons of propor-
tion-type rates was assessed using ?2tests, and t tests
were used to compare the means of continuous
variables. Multivariable logistic regression analysis
988
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was used to identify maternal characteristics and
other risk factors for the occurrence of eclampsia
and to examine the associations between eclampsia
and maternal and neonatal mortality and severe
morbidity.
This study was carried out by the Public Health
Agency of Canada, which has a federal mandate to
monitor the health of the Canadian population. The
data source involved denominalized information
from all hospitals in Canada (excluding Quebec);
ethics review board approval was therefore not
required.
RESULTS
A total of 1,530 cases of eclampsia were observed
among 1,910,729 women who delivered in the 7-year
period, yielding an overall incidence rate of 8.0 per
10,000 deliveries. The annual rate declined by more
than 50% from 12.4 per 10,000 delivering women in
2003 to 5.9 in 2009, although all of the decline had
occurred by 2006. Seventy percent of the cases oc-
curred during pregnancy, 16% in labor, and 14% in
the puerperium (Table 1).
The frequency of eclampsia varied substantially
by maternal age, plurality, parity, and gestational age.
For instance, there was an eightfold higher rate of
eclampsia among deliveries at very preterm gestation
(47.3 cases per 10,000 deliveries at 20–31 weeks)
compared with deliveries at term and postterm gesta-
tion (5.8 cases per 10,000 deliveries at 37–42 weeks).
The incidence of eclampsia during pregnancy (calcu-
lated using pregnancies at risk as the denominator)
showed the opposite pattern; eclampsia rates in-
creased from 0.66 cases per 10,000 pregnancies at risk
Table 1. Distribution of Maternal Characteristics and Incidence of Eclampsia in Canada (Excluding
Quebec), 2003–2004 to 2009–2010
Characteristic
No. of
Deliveries
No. of Cases
of Eclampsia
Rate per 10,000
(95% CI)
Fiscal year
2003–2004
2004–2005
2005–2006
2006–2007
2007–2008
2008–2009
2009–2010
Maternal age (y)
Younger than 20
20–24
25–29
30–34
35–39
40 and older
Multiple pregnancy
Yes
No
Parity
0
1 or more
Unknown
Gestational age at delivery (wk)*
20–31
32–36
37–42
Period of occurrence†
In pregnancy
In labor
In the puerperium
Total
248,496
262,673
266,172
274,089
284,925
286,432
287,942
309
282
252
180
161
176
170
12.4 (11.1–13.9)
10.7 (9.5–12.1)
9.5 (8.3–10.7)
6.6 (5.6–7.6)
5.7 (4.8–6.6)
6.1 (5.3–7.1)
5.9 (5.0–6.9)
90,630
312,891
561,531
596,175
290,852
58,650
164
303
396
377
223
67
18.1 (15.4–21.1)
9.7 (8.6–10.8)
7.1 (6.4–7.8)
6.3 (5.7–7.0)
7.7 (6.7–8.7)
11.4 (8.9–14.5)
26,292
1,884,437
49 18.6 (13.8–24.6)
7.9 (7.5–8.3)1,481
665,077
823,661
421,991
841
416
273
12.6 (11.8–13.5)
5.1 (4.6–5.6)
6.5 (5.7–7.3)
26,650
117,877
1,766,202
126
382
1,022
47.3 (39.4–56.3)
32.4 (29.2–35.8)
5.8 (5.4–6.2)
1,910,729
1,909,664
1,909,416
1,910,729
1,065 (69.6%)
248 (16.2%)
217 (14.2%)
1,530
5.6 (5.2–5.9)
1.3 (1.1–1.5)
1.1 (1.0–1.3)
8.0 (7.6–8.4)
* Gestational age–specific rate of eclampsia calculated using number of deliveries in each gestational age category in the denominator
(see text for gestational age–specific rates calculated by the number of pregnancies at risk).
†The number of deliveries indicates women at risk of eclampsia; percent of cases of eclampsia refers to the proportion in each period
of occurrence.
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at each week between 20 and 31 weeks of gestation, to
2.03 cases per 10,000 pregnancies at risk at each week
between 32 and 36 weeks of gestation and to 5.79
cases per 10,000 pregnancies at risk at each week
between 37 and 42 weeks of gestation. The frequency
of eclampsia was twofold higher among multiple
compared with singleton pregnancies (18.6 compared
with 7.9 per 10,000 women, P?.001; Table 1).
Crude and adjusted odds ratios (ORs) showing
the relationship between maternal characteristics and
other risk factors and eclampsia are presented in
Table 2 for women with singleton pregnancies. After
adjustment for fiscal year, province or territory of
hospitalization, maternal age, parity, elderly primigra-
vidity and grand multiparity, existing heart disease
(adjusted OR 4.8; 95% confidence interval [CI] 2.9–
7.3), systemic lupus erythematosus (adjusted OR 2.9;
95% CI 1.1–8.0), anemia (adjusted OR 2.4; 95% CI
2.0–3.0), hypertension (adjusted OR 2.3; 95% CI
2.0–2.7), nulliparity (adjusted OR 2.3; 95% CI 2.0–
2.6), premature separation of the placenta (adjusted
OR 2.2; 95% CI 1.6–3.0), pre-existing or gestational
diabetes (adjusted OR 1.5; 95% CI 1.2–1.8), and
urinary tract infection (adjusted OR 1.5; 95% CI
1.1–2.2) were identified as significant risk factors for
eclampsia (Table 2).
Obstetric procedures and conditions significantly
associated with eclampsia (whether as cause or con-
sequence) in logistic models included medical (ad-
justed OR 1.8; 95% CI 1.6–2.0) or surgical induction
of labor (adjusted OR 1.7; 95% CI 1.5–2.0), cesarean
delivery (adjusted OR 3.6; 95% CI 3.2–3.9), venous
thromboembolism (adjusted OR 4.0; 95% CI 1.8–
8.5), and major puerperal infection (adjusted OR 2.2;
95% CI 1.2–4.1) (Table 3).
Five maternal deaths (2.7 per 100,000 deliveries)
resulting from eclampsia or associated complications
occurred during the study period, yielding a case
fatality rate of 3.4 per 1,000, and an adjusted OR of
26.8 (95% CI 9.7–73.8) for maternal death given
eclampsia. Occurrence of eclampsia was significantly
associated with increased risks of several subtypes of
severe maternal morbidity, including assisted ventila-
tion (adjusted OR 102.3; 95% CI 78.2–133.8), adult
respiratory distress syndrome (adjusted OR 36.2; 95%
CI 15.3–85.3), acute renal failure (adjusted OR 20.9;
95% CI 11.4–38.3), obstetric shock (adjusted OR
10.2; 95% CI 4.4–23.6), obstetric embolism (adjusted
OR 9.1; 95% CI 4.1–19.9), cardiac arrest or failure
(adjusted OR 6.3; 95% CI 3.5–11.4), antepartum or
postpartum hemorrhage requiring blood transfusion
(adjusted OR 2.9; 95% CI 2.0–4.2), and septicemia or
sepsis (adjusted OR 2.5; 95% CI 1.2–5.3) (Table 4).
Overall, women with eclampsia had longer hospital
stays for childbirth (mean 5.2 days compared with 2.5
days, P?.001) and a 15-fold higher rate (adjusted OR
15.4; 95% CI 13.4–17.7) of prolonged hospital stay (7
days or longer) compared with women who did not
have eclampsia (Table 4).
Sixteen fetal deaths (10.8 per 1,000 total births)
occurred in women with eclampsia (adjusted OR 2.4;
95% CI 1.5–3.9; Table 3 singleton pregnancies only).
Eclampsia also posed a high risk for liveborn neo-
nates; there were 10 neonatal deaths (adjusted OR
2.9; 95% CI 1.6–5.5), yielding a case fatality of 7.5 per
1,000 live births. Other adverse neonatal outcomes
included very preterm birth (fewer than 32 weeks of
gestation; adjusted OR 5.6; 95% CI 4.5–7.0), respira-
tory distress syndrome (adjusted OR 5.1; 95% CI
4.1–6.3), mild or moderate preterm birth (32–36
Table 2. Maternal Characteristics and Other Risk Factors Associated With Eclampsia Among Singleton
Deliveries (n?1,884,438) in Canada (Excluding Quebec), 2003–2004 to 2009–2010
Characteristic or Risk Factor
Rate of Eclampsia
per 10,000 (No. of Cases)
Factor Present
OR (95% CI)
Factor AbsentCrudeAdjusted*
Teen pregnancy
Nulliparity
Obesity
Anemia
Pre-existing or gestational diabetes
Hypertension
Urinary tract infection
Existing heart disease
Systemic lupus erythematosus
Premature separation of the placenta
17.9 (161)
12.4 (814)
13.9 (18)
22.3 (96)
11.8 (106)
19.9 (222)
15.8 (31)
50.3 (24)
36.1 (4)
19.8 (43)
7.7 (1,320)
5.4 (667)
7.9 (1,463)
7.5 (1,385)
7.7 (1,375)
7.1 (1,259)
7.8 (1,450)
7.7 (1,457)
7.8 (1,477)
7.7 (1,438)
2.4 (2.1–2.9)
2.3 (2.1–2.5)
1.8 (1.1–2.8)
3.0 (2.4–3.7)
1.5 (1.3–1.9)
2.8 (3.4–3.2)
2.0 (1.4–2.9)
5.6 (4.3–9.8)
4.6 (1.7–12.3)
2.6 (1.9–3.5)
2.0 (1.7–2.3)
2.3 (2.0–2.6)
1.3 (0.8–2.1)
2.4 (2.0–3.0)
1.5 (1.2–1.8)
2.3 (2.0–2.7)
1.5 (1.1–2.2)
4.8 (2.9–7.3)
2.9 (1.1–8.0)
2.2 (1.6–3.0)
OR, odds ratio; CI, confidence interval.
* ORs based on a multivariate logistic regression with adjustment for fiscal year, province or territory of hospitalization, maternal age,
parity, elderly primigravidity, and grand multiparity.
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weeks of gestation; adjusted OR 4.6; 95% CI 4.1–5.2),
admission to neonatal intensive care unit (adjusted
OR 2.8; 95% CI 2.4–3.2), small-for-gestational age
birth (adjusted OR 2.6; 95% CI 2.3–3.0), sepsis (ad-
justed OR 2.4; 95% CI 1.7–3.4), neonatal seizures
(adjusted OR 2.2; 95% CI 1.3–3.8), and a longer
average length of hospital stay (5.8 days compared
with 2.5 days; P?.001, Table 5).
The declining trend in eclampsia rates remained
unchanged after adjustment for all maternal charac-
teristics, obstetric conditions, labor induction, and
other factors considered above, that is, temporal
changes in maternal characteristics and other risk
factors could not explain the observed decline in
eclampsia rates between 2003 and 2009. Similarly,
there was no change in the gestational age distribution
of eclampsia cases between 2003 and 2009.
DISCUSSION
Our large population-based study showed an overall
incidence of eclampsia of 8.4 per 10,000 deliveries,
with a dramatic decline from 12.4 per 10,000 deliv-
eries in 2003 to 5.9 per 10,000 in 2009. A number of
factors such as maternal age, multiple pregnancy,
nulliparity, anemia, pre-existing heart disease, gesta-
tional and pre-existing diabetes, and urinary tract
infection significantly increased the risk of eclampsia.
Eclampsia was associated with significantly in-
creased risks of maternal death and several types of
severe morbidity including assisted ventilation,
Table 4. Maternal Mortality and Severe Morbidity Associated With Eclampsia Among Singleton
Deliveries (n?1,884,438) in Canada (Excluding Quebec), 2003–2004 to 2009–2010
Mortality or Morbidity
(per 1,000 or Specified)
Eclampsia OR (95% CI)
No (n?1,882,957)Yes (n?1,481)Crude Adjusted*
Maternal death (per 100,000)
Obstetric shock†
Septicemia or sepsis
Obstetric embolism
Cardiac arrest or failure
Adult respiratory distress syndrome
Assisted ventilation
Acute renal failure
Antepartum or postpartum hemorrhage requiring
blood transfusion
Postpartum length of stay 7 d or longer (per 100)
Mean postpartum length of stay (d)
4.3
0.2
1.2
0.3
0.7
0.1
0.4
0.2
4.8
337.6
4.1
4.7
4.7
9.5
4.7
52.7
8.8
23.6
78.8 (31.9–194.6)
18.8 (8.4–42.2)
4.0 (1.9–8.5)
17.1 (8.1–36.1)
13.6 (8.0–23.1)
90.3 (41.9–194.7)
141.6 (111.5–179.9)
46.4 (26.6–81.0)
5.1 (3.6–7.1)
26.8 (9.7–73.8)
10.2 (4.4–23.6)
2.5 (1.2–5.3)
9.1 (4.1–19.9)
6.3 (3.5–11.4)
36.2 (15.3–85.3)
102.3 (78.2–133.8)
20.9 (11.4–38.3)
2.9 (2.0–4.2)
1.3 19.017.5 (15.4–20.0) 15.4 (13.4–17.7)
P?.001 2.5?1.7 5.2?3.5
OR, odds ratio; CI, confidence interval.
* ORs based on separate logistic regression models with effect of eclampsia on the listed condition adjusted for maternal age, parity,
elderly primigravida, grand multipara, anemia, diabetes, urinary tract infection and exiting heart disease.
†Shock due to hemorrhage or sepsis.
Table 3. Obstetric Procedures and Conditions Associated With Eclampsia Among Singleton Deliveries
(n?1,884,438) in Canada (Excluding Quebec), 2003–2004 to 2009–2010
Procedure or Outcome
Eclampsia OR (95% CI)
No (n?1,882,957)Yes (n?1,481)CrudeAdjusted*
Very preterm delivery†(per 100)
Mild or moderate preterm delivery†(per 100)
Medical induction of labor (per 100)
Surgical induction of labor (per 100)
Cesarean delivery (per 100)
Venous thromboembolism (per 1,000)
Major puerperal infection (per 1,000)
Fetal death (per 1,000)
1.1
5.6
19.9
7.8
26.8
0.7
4.2
4.1
8.1
23.6
33.0
13.2
57.1
4.7
13.5
10.8
7.9 (6.5–9.5)
5.2 (4.6–5.9)
2.0 (1.8–2.2)
1.8 (1.5–2.1)
3.6 (3.3–4.0)
6.4 (3.1–13.5)
3.2 (2.1–5.1)
2.6 (1.6–4.3)
6.6 (5.5–8.0)
4.8 (4.2–5.4)
1.8 (1.6–2.0)
1.7 (1.5–2.0)
3.6 (3.2–3.9)
4.0 (1.8–8.5)
2.2 (1.2–4.1)
2.4 (1.5–3.9)
OR, odds ratio; CI, confidence interval.
* ORs based on separate logistic regression models with effect of eclampsia on the listed condition adjusted for maternal age, parity,
elderly primigravidity and grand multiparity, anemia, diabetes, urinary tract infection, and existing heart disease.
†Very preterm delivery denotes delivery at fewer than 32 weeks of gestation, and mild or moderate preterm delivery refers to delivery
at 32–36 weeks of gestation.
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adult respiratory distress syndrome, acute renal
failure, and obstetric embolism. Fetuses and new-
borns of women with eclampsia were at elevated
risk of fetal death, small-for-gestational-age birth,
very preterm birth, respiratory distress syndrome,
and neonatal death.
Our study provides an update regarding the
incidence, risk factors, and consequences of eclamp-
sia. Significant progress in the prevention and treat-
ment has been observed in recent years in Canada
and other countries.3,5,8–12,30,31Our study documented
an overall incidence of eclampsia for the years 2003–
2009 (8.0 per 10,000 deliveries) that was much higher
than previous estimates from Canada (3.8 per 10,000
deliveries in 1991–2001).4However, earlier estimates
for eclampsia rates in Canada were likely underesti-
mates of the true incidence because the ICD-9 coding
system did not permit a complete identification of all
cases.31–33One problem with ICD-9 codes arose be-
cause one code (642.7) included both preeclampsia
and eclampsia superimposed on pre-existing hyper-
tension. The implementation of ICD-10 for diagnostic
coding has enabled more complete identification of
eclampsia cases.
Our analysis showed that the observed decline in
eclampsia cases remained unchanged between 2003
and 2009 even after accounting for temporal changes
in maternal characteristics, pregnancy conditions, and
obstetric interventions, indicating that the decline was
independent of changes in those potential risk factors.
Further, the gestational age distribution of eclampsia
did not change between 2003 and 2009, suggesting
that increases in early delivery among women with
severe preeclampsia or eclampsia or both likely did
not cause the decline in eclampsia incidence. In-
creased use of magnesium sulfate prophylaxis in
women with severe preeclampsia is probably respon-
sible for the observed decline in eclampsia in Canada
between 2003 and 2006. Magnesium sulfate has been
recommended as the drug of choice for eclampsia
prophylaxis among women with severe preeclampsia
and other risks of eclampsia.18–20,34–38Presumably, use
of magnesium sulfate became much more widespread
in Canada following the publication of the landmark
Magpie Trial report in 2002.38An independent report
based on the British Columbia Perinatal Health Da-
tabase also showed a similar trend in eclampsia rates:
7 per 10,000 deliveries in fiscal year 2004–2005, 8 per
10,000 in 2005–2006, 3 per 10,000 in 2006–2007, and
5 per 10,000 deliveries in 2007–2008. However, the
eclampsia frequency in these data source was based
on ICD-10 CA codes as well.39Unfortunately, infor-
mation on use of magnesium sulfate was not con-
tained in the Discharge Abstract Database and we
were unable to directly assess the effect of magnesium
sulfate use on the trend in eclampsia. Some of the
decrease in eclampsia may have been due to earlier
delivery of patients with hypertensive disorders.
Our study shows that eclampsia remains an ex-
tremely serious complication of pregnancy, with sig-
nificantly increased risks of maternal death and severe
morbidity. We identified most of the maternal and
Table 5. Neonatal Outcomes Among Singleton Live Births Following Eclampsia (n?1,788,776) in
Canada (Excluding Quebec), 2003–2004 to 2009–2010
Conditions or Outcome
(per 100 or Specified)
EclampsiaOR (95% CI)
CrudeNo (n?1,787,471)Yes (n?1,325) Adjusted*
Small-for-gestational age
(lower than 10th percentile)
Large-for-gestational age
(higher than 90th percentile)
Very preterm birth (22–31 wk)
Mild preterm birth (32–36 wk)
Intubation
Seizure (per 1,000)
Respiratory distress syndrome (per 1,000)
Transient tachypnea of the newborn
Sepsis (per 1,000)
Admission to neonatal intensive care unit
Neonatal death (per 1,000)
Length of hospital stay 7 d or longer
Mean length of hospital stay (d)
8.320.62.9 (2.5–3.3) 2.6 (2.3–3.0)
11.7 11.31.0 (0.8–1.1)0.9 (0.7–1.1)
0.9
5.6
2.3
1.0
9.7
3.4
7.5
7.9
2.2
3.7
7.2
24.8
10.9
3.1
72.5
6.4
24.9
24.5
7.5
25.4
5.8?5.6
8.8 (7.2–10.9)
5.5 (4.9–6.3)
5.2 (4.3–6.1)
3.2 (1.9–5.6)
8.0 (6.5–9.8)
1.9 (1.6–2.4)
3.4 (2.4–4.8)
3.9 (3.5–4.4)
3.2 (1.7–6.2)
8.9 (7.8–10.1)
5.6 (4.5–7.0)
4.6 (4.1–5.2)
3.4 (2.9–4.1)
2.2 (1.3–3.8)
5.1 (4.1–6.3)
1.5 (1.2–1.8)
2.4 (1.7–3.4)
2.8 (2.4–3.2)
2.9 (1.6–5.5)
6.3 (5.6–7.2)
2.5?2.6P?.001
OR, odds ratio; CI, confidence interval.
* ORs based on separate logistic regression models with effect of eclampsia on the listed neonatal condition adjusted for maternal age
group, parity, anemia, existing heart disease, and cesarean delivery.
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neonatal consequences that were reported in previous
published studies.5,10–15Eclampsia, once it occurs, is
typically treated with urgent delivery, which probably
explains the observed increase in risks with labor
induction, cesarean delivery, and preterm birth.
Complications such as venous thromboembolism,
infection, sepsis, acute renal failure, and severe hem-
orrhage warrant particular attention. The high risk of
venous thromboembolism associated with eclampsia
was not surprising; conditions and procedures such as
preeclampsia and cesarean delivery (which are
strongly associated with eclampsia) are known to
increase the risk of thromboembolism.40
Some limitations inherent in our study merit
discussion. First, inaccuracies and inconsistencies in
diagnosis may exist in large administrative databases
that collate information from hospitals where obstet-
ric practices and coding system transitions are likely
to have varied. Both underdiagnosis and overdiagno-
sis of eclampsia could have had occurred. Second,
administrative data (including the Discharge Abstract
Database) are prone to a certain degree of coding
errors and incompleteness. Nevertheless, validation
studies show that serious conditions examined in this
study should have been recorded correctly and com-
pletely.26,28Data from Quebec were not included in
our analyses; this was not expected to affect our study
results as the absence of Quebec data from our data
was due to administrative reasons. Some high-risk
pregnancies in the remote northern regions of Can-
ada would have been transferred into Quebec. How-
ever, the effect of such movement into and out of
Quebec is unlikely to have had a substantial effect on
the temporal trends, risk factors, and complications
associated with eclampsia observed in our study.
Although more than 1.8 million individuals were
included in our study, few cases of rare outcomes
(such as maternal death, adult respiratory distress
syndrome, and so forth) occurred among the 1,481
eclampsia cases, giving rise to the wide 95% CIs
shown in Table 4. The parameter estimates are both
substantial (clinically important) and statistically sig-
nificant, however, and little evidence of collinearity
was observed in our logistic modeling, as judged by
the degree of variance inflation in the adjusted com-
pared with crude models. Whether the “true” OR is
50 or 100 seems less important than its very large
magnitude. Moreover, given the low and falling fre-
quency of eclampsia, future studies with as much
clinical detail as ours are unlikely to include a larger
number of cases. Finally, our study was based on
hospitalization records, and events in the postpartum
period were limited to the period before hospital
discharge. Cases of postpartum eclampsia that occurred
after hospital discharge would have been missed.
In conclusion, our study suggests that the dra-
matic decline in the incidence of eclampsia in Canada
in recent years has occurred due to increased use of
magnesium sulfate prophylaxis following publication
of the Magpie Trial. Further, our study shows that,
despite improved perinatal management of women
with eclampsia, the condition remains significantly
associated with serious adverse consequences, for
both the fetus or newborn and the mother. The high
rates of adverse outcomes associated with eclampsia
indicate the need for continued improvement in
eclampsia prophylaxis and treatment.
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