Objective
We sought to identify trends, demographics, and prepregnancy and peripartum morbidities of eclampsia in California.
Study Design
We identified cases of eclampsia by International Classification of Diseases, Ninth Revision code using California health discharge data from 2001 through 2007. Cases with missing race/ethnicity as well as age <15 years or >55 years were excluded. Among the remaining cases, patients with eclampsia (n = 1888) were compared against those without (n = 2,768,983). Adjustments were performed for potential confounding variables using logistic regression. Significance was set at P < .05.
Results
The incidence of eclampsia decreased over time, from 8.0 cases per 10,000 deliveries in 2001, to 5.6 cases per 10,000 deliveries in 2007 ( P < .001). There was a bimodal distribution in age-related risk, with the highest risks at the extremes of age. Non-Hispanic blacks were associated with the highest risk of eclampsia while Asians had the lowest risk. Several antepartum morbidities had increased associations with eclampsia, including preexisting cardiac disease (adjusted odds ratio [OR], 6.84; 95% confidence interval [CI], 5.40–8.66), lupus erythematosus (adjusted OR, 3.68; 95% CI, 1.53–8.86), and twin gestations (adjusted OR, 3.28; 95% CI, 2.70–3.99). Peripartum complications increased in eclampsia included cerebrovascular hemorrhage/disorders (adjusted OR, 112.15; 95% CI, 77.47–162.35), peripartum cardiomyopathy (adjusted OR, 12.88; 95% CI, 6.08–27.25), amniotic fluid embolism (adjusted OR, 11.94; 95% CI, 3.63–39.21), and venous thromboembolism (adjusted OR, 10.71; 95% CI, 5.14–22.32).
Conclusion
This large population database confirms that there is a decline in eclampsia over time. However, there are extremely morbid complications associated with eclampsia, emphasizing the need for its close monitoring and prevention.
Eclampsia is defined as the onset of seizures in the setting of preeclampsia and without another neurologic cause or condition. The spectrum of hypertensive disease in pregnancy, which includes preeclampsia-eclampsia, is one of the leading causes of maternal morbidity and mortality both in the United States and worldwide, resulting in 10-15% of maternal deaths. Eclampsia is further associated with increased morbidity due to risks of hypoxic-ischemic brain damage and intracranial hemorrhage from seizure activity. Of eclampsia cases, 2-20% are complicated by perinatal loss, while 1-20% are complicated by maternal fatality, with the highest rates of morbidity and mortality in developing countries. The risk of eclamptic seizures is approximately 2% in patients with untreated severe preeclampsia, while it is roughly 0.5% in patients with mild preeclampsia. Eclampsia may occur antenatally, intrapartum, or postnatally.
The incidence of eclampsia is cited to be on the order of 2-8 cases per 10,000 deliveries in developed countries and up to 16-69 cases per 10,000 in developing countries. Several recent studies from Canada and Ireland have demonstrated a decline in eclampsia incidence over time. Liu et al found a decline from 12.4 per 10,000 to 5.9 from 2003 through 2009 in Canada, while O’Connor et al found a decline from 5.4 per 10,000 to 3.5 over a span of 30 years in Ireland. It is believed that the use of magnesium sulfate prophylactically has been associated with a decrease in incidence of eclampsia.
The objective of our study was to use a large California cohort to assess the incidence of eclampsia and its trends over time. We also sought to identify antenatal risk factors and adverse outcomes associated with eclampsia.
Materials and Methods
This is a retrospective study using California health discharge data from 2001 through 2007. The database, provided by the California Office of Statewide Health Planning and Development (OSHPD), is a publicly available dataset comprising cases where a patient is treated in a licensed general acute care hospital in California. It contains information regarding demographics, hospital of treatment, diagnoses, specific procedures undergone, and details regarding the patient’s stay such as source of funding and length of stay. The dataset has undergone prior validation studies specifically in pregnancy-related conditions and has been used in prior obstetrical publications. The local institutional review board granted exempt approval because of the deidentified, retrospective design.
Of 3,556,567 deliveries extracted from inpatient California discharge data using delivery codes, we identified cases of eclampsia using International Classification of Diseases , Ninth Revision (ICD-9) coding for “eclampsia complicating pregnancy childbirth or the puerperium” (642.60, 642.61, 642.62, 642.63, 642.64). Other maternal conditions and procedures (eg, gestational diabetes, cesarean delivery) were identified using ICD-9 coding as well, with certain antepartum conditions utilizing ICD-9 codes as needed from outside of pregnancy in addition to those during pregnancy (ie, ICD-9 codes 630-677, “complications of pregnancy, childbirth, and the puerperium”). For example, thyroid disease was coded using ICD-9 codes 240.x-246.x in addition to the pregnancy-related 648.1x code. Other conditions such as hypercoagulable state only had codes available from outside of pregnancy (289.81, “primary hypercoagulable state” and 289.82, “secondary hypercoagulable state”). For peripartum cardiomyopathy, data were analyzed only from years 2003 through 2007, since its ICD-9 code (674.5x) was only available starting in 2003.
The study group of subjects with eclampsia was compared to those without eclampsia. To improve ascertainment to only reproductive-age women, we eliminated patients <15 years of age (the lower limit of reproductive age) as defined by the World Health Organization. We also eliminated patients >55 years of age to allow for morbidity analysis in the high-risk very advanced maternal age population (age >45 years) while still minimizing age-related coding error. We also eliminated cases missing age or race/ethnicity to minimize bias from omitted data in our logistic regression adjustments.
Student t test was used for calculation of continuous variables. Cochran-Armitage test was used for trends over time. Fisher exact or χ 2 test was used for comparison between discrete variables. We used a multivariable logistic regression analysis for adjustment of covariates. For antepartum morbidities, we adjusted for all factors that showed significant differences between the 2 groups: age, race/ethnicity, insurance type, and year of delivery. For peripartum morbidities, in addition to the aforementioned factors, we also adjusted for obesity, diabetes, cardiac disease, asthma, renal disease, urinary tract infection, and multiple gestations. This was done to try to establish an independent relation between eclampsia and each peripartum outcome. We also performed 2 subanalyses: an analysis of race/ethnicity risk for eclampsia using the above logistic regression adjustment, as well as an analysis of associated antepartum/peripartum factors for maternal death. Results were expressed in odds ratios (ORs) and 95% confidence intervals (CIs). A statistical software package (SPSS 20.0; IBM Corp, Armonk, NY) was used for analysis.
Results
There were 2534 cases of eclampsia of 3,556,567 deliveries, giving an incidence of 7.12 cases per 10,000 deliveries. We eliminated 3617 patients >55 or <15 years of age. In all, 782,079 cases were removed due to missing race/ethnicity. A total of 2,770,871 cases remained, composed of 1888 cases of eclampsia and 2,768,983 cases without eclampsia.
Figure 1 demonstrates the incidence of eclampsia during the study period (2001 through 2007). There was a significant decrease in incidence over time ( P < .001). The year 2001 had the highest rate at 8.0 cases per 10,000 deliveries, decreasing to the lowest rate at 5.6 cases per 10,000 deliveries in 2007. The fastest rate of decline occurred from 2005 through 2007, when the incidence declined by nearly 25%.
The characteristics of the study population with and without eclampsia are shown in Table 1 . There were differences in age, race/ethnicity, and insurance status between the 2 groups. There was a trend toward a lower percentage of subjects with advanced maternal age in the eclamptic group. The length of hospital stay for eclamptics was significantly longer, on average, by 2 days (4.54 ± 3.65 vs 2.50 ± 2.18 days, mean ± SD, P < .001).
| Baseline characteristic | Subjects with eclampsia (n = 1888) | Subjects without eclampsia (n = 2,768,983) | P value |
|---|---|---|---|
| n (prevalence) | n (prevalence) | ||
| Age, y | < .001 | ||
| 15-19 | 352 (18.6%) | 229,407 (8.3%) | |
| 20-24 | 521 (27.6%) | 647,623 (23.4%) | |
| 25-29 | 397 (21.0%) | 732,882 (26.5%) | |
| 30-34 | 318 (16.8%) | 682,994 (24.7%) | |
| 35-39 | 229 (12.1%) | 388,867 (14.0%) | |
| 40-44 | 63 (3.3%) | 82,628 (3.0%) | |
| ≥45 | 8 (0.4%) | 4582 (0.2%) | |
| Advanced maternal age (35 y) | 300 (15.9%) | 476,077 (17.2%) | .071 |
| Race/ethnicity | < .001 | ||
| Caucasian | 596 (31.6%) | 1,056,824 (38.2%) | |
| Black | 164 (7.6%) | 120,853 (3.9%) | |
| Native American/Eskimo/Aleut | 2 (0.1%) | 3685 (0.1%) | |
| Asian/Pacific Islander | 96 (4.4%) | 241,486 (7.7%) | |
| Hispanic | 1030 (54.6%) | 1,346,135 (48.6%) | |
| Private insurance | 785 (41.6%) | 1,352,917 (48.9%) | < .001 |
| Length of stay, d | 4.54 ± 3.65 | 2.50 ± 2.18 | < .001 |
Figure 2 demonstrates the prevalence of eclampsia displayed by 5-year increments of age. There was a clear bimodal distribution in age-related risk, with peaks in the youngest and oldest age groups. The eclampsia risk in subjects age <19 years was 15.71 cases per 10,000 and was 14.54 cases per 10,000 in subjects age >45 years. The nadir of age-related risk was at 4.80 cases per 10,000 in subjects aged 30-34 years.
The risk of eclampsia when compared among different races/ethnicities is demonstrated in Table 2 , after adjustment for age, insurance type, year of delivery, obesity, diabetes, cardiac disease, asthma, renal disease, urinary tract infection, multiple gestations, and tobacco use. Using Caucasians as a referent group, non-Hispanic blacks were almost twice as likely to develop eclampsia (adjusted OR, 1.81; 95% CI, 1.51–2.17) while Hispanics were about a fourth more likely (adjusted OR, 1.27; 95% CI, 1.14–1.42).
| Variable | Non-Hispanic Caucasian | Non-Hispanic black | Asian | Hispanic | Native American |
|---|---|---|---|---|---|
| Odds of eclampsia | 1 | 1.81 (1.51–2.17) P < .001 | 0.83 (0.67–1.04) | 1.27 (1.14–1.42) P < .001 | 0.73 (0.18–2.95), P = .66 |
Several antepartum obstetrical and medical complications, after adjustment for age, race/ethnicity, insurance type, and year of delivery, were associated with an increased rate of eclampsia ( Table 3 ). Preexisting cardiac disease had the highest association with an adjusted OR of 6.84 (95% CI, 5.40–8.66) followed by lupus erythematosus (adjusted OR, 3.68; 95% CI, 1.53–8.86), urinary tract infection (adjusted OR, 2.82; 95% CI, 2.23–3.55), renal disease (adjusted OR, 2.44; 95% CI, 1.09–5.44), pregestational diabetes (adjusted OR, 2.73; 95% CI, 1.98–3.76), obesity (adjusted OR, 2.32; 95% CI, 1.78–3.02), and asthma (adjusted OR, 2.23; 95% CI, 1.73–2.88). Both twins and higher-order multiple gestations had >3-fold higher associations with eclampsia as well.
| Obstetrical and medical complication | Rate of eclampsia per 10,000 (no. of cases) | Unadjusted OR (95% CI) | P value | Adjusted OR (95% CI) | P value | |
|---|---|---|---|---|---|---|
| Condition present | Condition absent | |||||
| Pregestational diabetes | 17.25 (39) | 6.73 (1849) | 2.57 (1.87–3.530 | < .001 | 2.73 (1.98–3.76) | < .001 |
| Gestational diabetes | 8.43 (124) | 6.72 (1764) | 1.25 (1.05–1.51) | .016 | 1.47 (1.22–1.78) | < .001 |
| Obesity | 14.68 (57) | 6.70 (1831) | 2.19 (1.68–2.85) | < .001 | 2.32 (1.78–3.02) | < .001 |
| Asthma | 15.10 (62) | 6.69 (1826) | 2.26 (1.75–2.91) | < .001 | 2.23 (1.73–2.88) | < .001 |
| Thyroid dysfunction | 10.85 (36) | 6.76 (1852) | 1.61 (1.15–2.23) | .006 | 1.97 (1.41–2.75) | < .001 |
| Renal disease | 16.63 (6) | 6.80 (1882) | 2.45 (1.10–5.46) | .039 | 2.44 (1.09–5.44) | .029 |
| Lupus erythematosus | 23.65 (5) | 6.80 (1883) | 3.48 (1.45–8.39) | .016 | 3.68 (1.53–8.86) | .004 |
| Urinary tract infection/asymptomatic bacteriuria | 20.72 (75) | 6.63 (1813) | 3.13 (2.48–3.94) | < .001 | 2.82 (2.23–3.55) | < .001 |
| Drug dependence | 15.68 (6) | 6.80 (1882) | 2.31 (1.03–5.15) | .049 | 2.15 (0.96–4.81) | .062 |
| Preexisting cardiac disease | 40.61 (73) | 6.59 (1815) | 6.18 (4.89–7.81) | < .001 | 6.84 (5.40–8.66) | < .001 |
| Twin gestation | 20.30 (109) | 6.54 (1779) | 3.11 (2.56–3.77) | < .001 | 3.28 (2.70–3.99) | < .001 |
| Higher-order multiple gestation (≥triplets) | 19.67 (6) | 6.80 (1882) | 2.90 (1.30–6.46) | .019 | 3.27 (1.46–7.31) | .004 |
Morbidities occurring in the peripartum period are listed in Table 4 . These were adjusted for obesity, diabetes, cardiac disease, asthma, renal disease, urinary tract infection, and multiple gestations, in addition to age, race/ethnicity, insurance type, and year of delivery. Several outcomes, whether as consequence or cause, were increased in cases of eclampsia. Cerebrovascular hemorrhage/disorders had the highest association with an adjusted OR of 112.15 (95% CI, 77.47–162.35), followed by peripartum cardiomyopathy (adjusted OR, 12.88; 95% CI, 6.08–27.25), amniotic fluid embolism (adjusted OR, 11.94; 95% CI, 3.63–39.21), venous thromboembolism (VTE) (adjusted OR, 10.71; 95% CI, 5.14–22.32), uterine rupture (adjusted OR, 5.53; 95% CI, 2.47–12.39), cesarean delivery (adjusted OR, 4.01; 95% CI, 3.64–4.41), fetal distress (adjusted OR, 3.45; 95% CI, 2.54–4.68), and intrauterine fetal demise (adjusted OR, 3.04; 95% CI, 2.06–4.49).
| Peripartum morbidity | Rate per 100 of morbidity unless otherwise specified (no. of cases) | Unadjusted OR (95% CI) | P value | Adjusted OR (95% CI) | P value | |
|---|---|---|---|---|---|---|
| Eclampsia present (n = 1888) | Eclampsia absent (n = 2,768,983) | |||||
| Fetal distress (per 1000) | 22.78 (43) | 5.93 (16,423) | 3.91 (2.89–5.29) | < .001 | 3.45 (2.54–4.68) | < .001 |
| Failed induction | 4.71 (89) | 1.54 (42,545) | 3.17 (2.56–3.92) | < .001 | 2.94 (2.37–3.64) | < .001 |
| Abnormal fetal heart rate | 19.28 (364) | 12.1 (335,427) | 1.73 (1.55–1.94) | < .001 | 1.67 (1.49–1.87) | < .001 |
| Intrauterine fetal demise (per 1000) | 13.77 (26) | 3.90 (10,804) | 3.57 (2.42–5.25) | < .001 | 3.04 (2.06–4.49) | < .001 |
| Uterine rupture (per 10,000) | 31.78 (6) | 5.3 (1477) | 5.97 (2.68–13.33) | .001 | 5.53 (2.47–12.39) | < .001 |
| Cesarean delivery | 61.86 (1168) | 29.3 (811,453) | 3.91 (3.57–4.29) | < .001 | 4.01 (3.64–4.41) | < .001 |
| Postpartum hemorrhage | 6.41 (121) | 2.6 (72,987) | 2.53 (2.10–3.04) | < .001 | 2.33 (1.94–2.80) | < .001 |
| Venous thromboembolism (per 10,000) | 42.37 (8) | 1.77 (492) | 23.95 (11.89–48.22) | < .001 | 10.71 (5.14–22.32) | < .001 |
| Amniotic fluid embolism (per 100,000) | 158.90 (3) | 4.69 (130) | 33.90 (10.78–106.57) | < .001 | 11.94 (3.63–39.21) | < .001 |
| Cerebrovascular hemorrhage/disorders (per 10,000) | 195.97 (37) | 1.21 (335) | 165.20 (117.28–232.70) | < .001 | 112.15 (77.47–162.35) | < .001 |
| Peripartum cardiomyopathy (per 10,000) a | 347.49 (9) | 6.54 (1307) | 55.04 (28.25–107.26) | < .001 | 12.88 (6.08–27.25) | < .001 |
| Death (per 100,000) | 476.69 (9) | 7.87 (218) | 60.83 (31.19–118.67) | < .001 | 16.69 (8.06–34.57) | < .001 |
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