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The incidence of preeclampsia and eclampsia and associated maternal mortality in Australia from population-linked datasets: 2000-2008
Charlene Thornton, PhD; Hannah Dahlen, PhD; Andrew Korda, FRANZCOG; Annemarie Hennessy, PhD
OBJECTIVE: To determine the incidence of preeclampsia and

eclampsia and associated mortality in Australia between 2000 and 2008.

STUDY DESIGN: Analysis of statutorily collected datasets of singleton

2008 was 1.9 (95% condence interval, 1.28e2.92) when compared with the year 2000. The relative risk of a woman with preeclampsia/ eclampsia dying in the rst 12 months following birth compared with normotensive women is 5.1 (95% condence interval, 3.07e8.60).
CONCLUSION: Falling rates of preeclampsia have not equated to a

births in New South Wales using International Classication of Disease coding. Analyzed using cross tabulation, logistic regression, and means testing, where appropriate.
RESULTS: The overall incidence of preeclampsia was 3.3% with a decrease from 4.6% to 2.3%. The overall rate of eclampsia was 8.6/ 10,000 births or 2.6% of preeclampsia cases, with an increase from 2.3% to 4.2%. The relative risk of eclampsia in preeclamptic women in

decline in the incidence of eclampsia. An accurate rate of both preeclampsia and eclampsia is vital considering the considerable contribution that these diseases make to maternal mortality. The identication and treatment of eclampsia should remain a priority in the clinical setting. Key words: eclampsia, incidence, maternal mortality, preeclampsia

Cite this article as: Thornton C, Dahlen H, Korda A, et al. The incidence of preeclampsia and eclampsia and associated maternal mortality in Australia from population-linked datasets: 2000-2008. Am J Obstet Gynecol 2013;208:476.e1-5.

eported rates of preeclampsia and eclampsia in developed countries vary signicantly. The preeclampsia rate is commonly quoted in the literature as being anywhere between 5% and 8% of all pregnancies worldwide, although more recently lower rates of 2-8% are being cited.1,2 Geographic variation, varying denitions of the disease and the size of data sources used largely account for these variations3 although seasonal variation at birth and time of conception have also been postulated as explanations of rate variations.4
From the, School of Medicine (Drs Thornton, Korda, and Hennessy), and the School of Nursing and Midwifery (Dr Dahlen), University of Western Sydney, Sydney, NSW, Australia. Received Nov. 12, 2012; revised Jan. 5, 2013; accepted Feb. 25, 2013. The authors report no conict of interest. Reprints: Charlene Thornton, PhD, University of Western Sydney, School of Medicine, Locked Bag 1797, Penrith South DC NSW, Australia 1797. c.thornton@uws.edu.au.
0002-9378/$36.00 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2013.02.042

Eclampsia rates also vary signicantly in the literature. In Europe rates of 2-3 cases per 10,000 births are quoted5,6 although rates in developing countries are between 16-69 per 10,000 births.7 Knight3 quotes 2.7/10,000 births in a 12-month surveillance of all maternity units in the United Kingdom in 2005/2006, although an earlier surveillance study in the Unitd Kingdom in 19928 resulted in a rate of 4.9/10,000. Worldwide, 12% of maternal deaths are attributed to eclampsia9 with a case fatality rate of 3-5% in developing countries.10 The Australasian Maternity Outcomes Surveillance System (AMOSS) is currently conducting a surveillance of eclampsia in Australia in 2011, although reporting of cases to AMOSS is voluntary and results are to date, not available. Effective detection and treatment of preeclampsia and eclampsia within any country or health region should at least be inuenced by clinicians knowledge of the incidence of the disease within their area of practice. The aim of this study was to determine the incidence of both preeclampsia and eclampsia in the largest populated area of Australia

(which contributes to be over one third of all Australian births), the variations over time periods and maternal mortality subsequent to diagnosis within a 12-month period following birth.

M ATERIALS

AND

M ETHODS

Data sources Birth data including maternal age, parity, delivery type, smoking status, and neonatal outcomes for the period July 1, 2000, till June 30, 2008, of all singleton births was provided by New South Wales (NSW), Australia, Department of Health as recorded in the NSW Midwives Data Collection (MDC). This population based surveillance system contains maternal and infant data on all births of greater than 400 g birthweight or 20 weeks gestation and covers over onethird of births that occur in Australia.1 The NSW MDC contains statistics on 33% of births that occur in Australia annually. This dataset (NSW MDC) was linked to the Admitted Patient Data Collection (APDC) and the NSW Registry of Births, Deaths and Marriages (BDM). The APDC records all admitted patient services provided by NSW Public

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Hospitals, Public Psychiatric Hospitals, Public Multi-Purpose Services, Private Hospitals, and Private Day Procedures Centres. The BDM is a record of all births, deaths and marriages that occur in NSW. The incidence of preeclampsia and the incidence and timing of event in relation to birth of eclampsia was provided by the APDC using the International Classication of Diseases Coding (ICD-10-Australian Modication) that has been in use in the Australian setting since 1998. The codes O14.0, O14.1, O14.2, and O14.9 were used to identify the cases of preeclampsia and are those that refer to new onset proteinuric hypertension. The codes O15.0, O15.1, O15.2, and O15.9 were used to identify the cases of eclampsia and the timing of the seizure in relation to the delivery of the infant. Cause of death was obtained from ICD-10 codes as recorded on the death certicate and located in the BDM registry. Linkage of the datasets was conducted by the New South Wales Centre for Health Record Linkage (CHeReL). Probabilistic data linkage techniques were used for these purposes and deidentied datasets were provided for analysis. Probabilistic record linkage software works by assigning a linkage weight to pairs of records. For example, records that match perfectly or nearly perfectly on rst name, surname, date of birth, and address have a high linkage weight, and records that match only on date of birth have a low linkage weight. If the linkage weight is high it is likely that the records truly match, and if the linkage weight is low it is likely that the records are not truly a match. This technique has been shown to have a false positive rate of 0.3% of records.11 Ethical approval was obtained from the NSW Population and Health Services Research Ethics Committee, protocol no. 2010/ 12/291.

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FIGURE 1

Cases of preeclampsia expressed as a percent of all births and eclampsia expressed as a percent of all preeclampsia cases

Thornton. Incidence of preeclampsia and eclampsia in Australia 2000-2008. Am J Obstet Gynecol 2013.

women who died within 12 months following delivery.

Data analysis Incidence and demographic data was calculated. Contingency table analyses, Student t tests and analyses of variance (ANOVA) were used to examine differences between the pregnancies coded as preeclamptic/eclamptic and those not. Binary logistic regression modelling was also undertaken. Signicance was determined <0.05 level. All analyses were conducted using IBM SPSS v.20 (IBM, Armonk, NY).

R ESULTS
There was an overall preeclampsia rate of 3.3% of singleton births (22,827 cases from 691 738 births) (Figure 1 for rate variations between year 2000 and 2008). There has been a decrease in the incidence of preeclampsia in this setting of 50% over this period, with a continuous trend of decline occurring (c2, P < .001). In total there were 597 episodes of seizure in 529 pregnancies. Fifty-ve women experienced >1 seizure in the 1 pregnancy and 4 women experienced a seizure in 2 pregnancies. This equates to an overall seizure event rate of 8.6/10,000 births. Between the years 2000 and

Subjects The MDC dataset for this period contains the antenatal, birth, and postnatal details on 691,738 births during this period. The APDC contains >1.7 million admissions for the same women occurring after the index pregnancy. The BDM registry contains death data on 97

2008, there has been no change in the incidence of eclampsia (0.1% of all births in 2000 and 2008) (Figure 1). The overall eclampsia rate in women with preeclampsia was 2.6% or 237/10,000 births effected by preeclampsia, with an increase from 2.3% in the year 2000 to 4.2% in 2008 (c2, P .007). The relative risk of eclampsia in women with preeclampsia in 2008 was 1.9 (95% condence interval [CI], 1.28e2.92) when compared with the year 2000. Seventythree percent of seizures occurred in primiparous women (c2, P < .0001) and when an examination of parity and the relationship to seizure occurrence was undertaken (following logistic regression adjustment for age and smoking status) the odds ratio (OR) of a primiparous woman experiencing a seizure when compared with a multiparous woman was 4.5 (95% CI, 3.55e5.63). An analysis of the risk of seizure in 2008 compared with 2000 for all women when adjusted for maternal age, gestational age at birth, smoking, and parity did not show a signicant increase in risk over the period of the study (OR, 1.86; 95% CI, 0.52e6.72). Table 1 displays the time when the event occurred, with the majority of seizures occurring during labor (44.1%). 476.e2

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TABLE 1

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examined, the median day of postnatal seizure occurrence was day 4 (range, 1e55). Maternal characteristics and neonatal outcomes are described in Table 2. This table demonstrates that women with eclampsia were younger, more likely to be primiparous, delivered at earlier gestations, and their infants suffered higher neonatal mortality. The seasonal variation of eclampsia was explored and when examined in relationship to the number of births that occurred within each season, there was no statistical difference in the incidence of eclampsia based on season of seizure occurrence (c2, P .35). Of all cause maternal deaths that occurred within the 12-month period following delivery (n 97), 18% (n 17) had experienced preeclampsia. Of the 30 early deaths (within 42 days of birth) attributed to medical causes (nonviolent deaths), 17% (n 5) had experienced preeclampsia. The recorded reason (with n 1 for each cause):

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surgical misadventure, multiorgan failure, intracranial hemorrhage, ruptured uterus, and aortic dissection. This equates to a RR for women with preeclampsia/eclampsia dying in the rst 12 months following birth when compared with normotensive women of 5.1 (95% CI, 3.07e8.60). The Neonatal Mortality Rate for infants of women with eclampsia was 22.3/1000 and 10.7/ 1000 for infants of women with preeclampsia compared with 7.9/1000 for the normotensive cohort.

Occurrence of seizure
When seizure occurred Antenatally During labor Postnatally Not specied to venue Percent of all episodes 25.1% 44.1% 26.3% 4.5%

Thornton. Incidence of preeclampsia and eclampsia in Australia 2000-2008. Am J Obstet Gynecol 2013.

The unadjusted RR of a seizure occurring in all women postnatally following a birth via caesarean section compared with a vaginal birth was 2.9 (95% CI, 2.14e3.99. An analysis of the time from birth to seizure was undertaken and displayed in Figure 2. The majority of women experienced eclampsia on the day of birth (53%). Median time for eclampsia was zero days (day of birth), range, 0e55 days. When the cases that occurred following the day of birth were

C OMMENT
This paper reports a mean preeclampsia rate of 3.3% of all singleton pregnancies over an 8-year period and eclampsia in this setting has an incidence of 8.6/ 10,000 births. These gures are similar to the world pooled estimate of 3.4%10 and comparable with that seen in Norway.12 The discrepancy in rates of preeclampsia between developed and developing countries and between developing countries is because of a number of factors including the signicant variation in the quality and accessibility of care and the variations in reporting methods and standards. The size of the dataset from which rates are calculated greatly inuence the reliability of the data and for this reason, population-based datasets such as this which rely on standardized coding and are validated for reliability are optimal for calculating disease incidence. The issue around consensus of diagnostic features is also contentious when dening preeclampsia. This paper used the research denition as established by Redman and Jefferies13 of pregnancy onset proteinuric hypertension in comparison to the denitions found within the SOMANZ guidelines14 that include nonproteinuric variations of preeclampsia, although it has been reported that in 77% of cases, women with preeclampsia diagnosed under more inclusive denitions do have proteinuria as a diagnostic factor.15 The declining rate of preeclampsia over the study period (4.6% to 2.4% of all births) is of great interest. Potential reasons for this could be an improvement in the early identication of cases over time with the initiation of

FIGURE 2

Time between birth and occurrence of eclampsia as a percentage of all cases occurring during delivery or postnatally

Thornton. Incidence of preeclampsia and eclampsia in Australia 2000-2008. Am J Obstet Gynecol 2013.

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medication at earlier gestations to maintain blood pressure control at acceptable limits or the shift away from blood pressure management from the inpatient to the outpatient setting with a subsequent decrease in the likelihood of a preeclampsia diagnosis being recorded on the birth admission. It could also be postulated that women with milder forms of disease are now less prevalent or are being omitted from the coding systems because of an increase in more women with more severe disease manifestations. Earlier treatments could also have resulted in more women receiving a diagnosis of gestational hypertension rather than preeclampsia. It could also be postulated that increasing rates of induced labors and elective caesarean sections, and associated birth at earlier mean gestations,16 are resulting in a fall in preeclampsia cases because of a reduction in the period required for women to develop and display disease manifestations, practices that effectively reduce the occurrence of cases that would have presented in postdate pregnancies. The 4.2% eclampsia rate (expressed as a percentage of preeclampsia cases) at the end of the study period was higher than that reported in the greater majority of developed countries10 with the relative risk for women with preeclampsia suffering an eclamptic seizure almost doubling between the years 2000 to 2008. This increase reects global trends reported by the World Health Organization, with an increase from 0.1% to 0.8% of live births affected by eclampsia in developing countries over a 10-year reporting period.10 In our study, this equated to an overall eclampsia rate over the 8-year period of 8.6/10,000 births with no change between 2000 and 2008. This nding is in contrast with falling eclampsia rates reported in both Canada (12.4 to 5.9/10,000 births between 2003 and 2009)17 and the United States (6.34 to 4.80/10,000 delivery hospitalizations between 1998 and 2008).18 The latter study did report an increase in postpartum eclampsia from 1.76 to 2.8 cases/10,000 delivery hospitalization during the same period. These results would also support the

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TABLE 2

Details of women with and without eclampsia

Variable Agea Primiparous
b b

Preeclampsia Eclampsia without eclampsia Nonhypertensive n [ 529 n [ 22,298 n [ 668,911 P value 28.7 (6.31) 29.5 (5.86) 73.2% 13.9% 49.8%
b

30.2 (5.58) 41.6% 14.8% 39.1 (2.06) 73.8% 7.9/1000

< .001 < .001 < .001 < .01 < .001 < .001

45.0% 8.2% 40.5% 10.7/1000

Smoked during pregnancy Gestation at deliverya Vaginal birth

a

37.6 (3.27) 37.9 (2.84) 22.3/1000

Neonatal mortality rate

Mean, standard deviation, and ANOVA; b c2 analysis.

Thornton. Incidence of preeclampsia and eclampsia in Australia 2000-2008. Am J Obstet Gynecol 2013.

argument that the incidence of preeclampsia and eclampsia are not positively correlated and that identication of impending eclampsia and treatment variations differ signicantly between obstetric units and countries. Vigilance and the use of magnesium sulphate (MgSO4) have well been identied as the most effective tools to prevent eclampsia,19 although the use of MgSO4 has come under considerable criticism because of a perceived toxicity associated with its use.20-22 In Australia there has not been any adverse drug reactions from MgSO4 reported to the Australian Government Therapeutic Goods Administration.23 In contrast, the Institute of Safe Medication Practices22 in the US maintains a database of incidents relating to MgSO4 of which there are more than 50 cases, some of which resulted in maternal death or persistent vegetative state involving the use of MgSO4 diluted in intravenous uids. There are both short- and potential long-term sequelae of having experienced an eclamptic seizure. A study that followed women 6-24 months after they experienced an eclamptic seizure24 reported that 10% of women reported persistent amnesia, 22% reported loss of memory, 11% experienced visual disturbances, and 10% had ongoing headaches. Long-term consequences may include structural changes to the white matter of the brain, with lesions seen in 40% of women and loss of cerebral tissue in 25% of women 6 weeks

postpartum.25-27 So although there was no mortality associated with eclampsia during this study, eclampsia does cause signicant long-term morbidity. Magnesium sulphate usage differed signicantly between obstetric units in New South Wales15 from 2.4%-18.0% of all women with preeclampsia. Worldwide the use of MgSO4 also varies greatly. Seasonal variation found in this study was in contrast with those found in earlier work where the incidence of eclampsia is greatest when in seasons when the temperature is lowest.4,5 There could be a number of reasons for this including the statistical power obtained from a dataset of this size or the relative narrow range of temperature experienced within the state of NSW over a 12-month period (32 F variation between mean winter and summer temperatures). In this study, almost 17% (n 5) of direct maternal deaths were in women who had preeclampsia. This gure reects what occurs worldwide, with 10-15% of direct maternal deaths attributed to preeclampsia in both developed and developing countries.2,28 Neonatal mortality rates of 22.3/1000 for infants born to mothers with eclampsia in this study compares favorably with rates of 60/1000 in other developed countries.6 This study used ICD-10-AM coding with a narrow denition of preeclampsia and a collection period encompassing 691,738 births providing robust data concerning the epidemiology of preeclampsia in Australia. The methodology 476.e4

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incidence of hypertension in pregnancy. Am J Obstet Gynecol 1988;158:80-3. 3. Knight M. Eclampsia in the United Kingdom. BJOG 2005;114:1072-8. 4. Rylander A, Lindqvist P. Eclampsia is more prevalent during the winter season in Sweden. Acta Obstet Gynecol Scand 2011;1:114-7. 5. Subramaniam V. Seasonal variation in the incidence of preeclampsia and eclampsia in tropical climatic conditions. BMC Womens Health 2007;7:18. 6. Kullberg G, Lindeberg S, Hanson U. Eclampsia in Sweden. Hypertens Pregnancy 2002;21:13-21. 7. Altman D, Carroli G, Duley L, Magpie Trial Collaboration Group. Do women with preeclampsia, and their babies, benet from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002;359:1877-90. 8. Douglas KA, Redman CWG. Eclampsia in the United Kingdom. BMJ 1994;309:1395-9. 9. World Health Organisation. The World Health Report 2005: Make every mother and child count. Geneva: World Health Organization; 2005. 10. Dolea C, AbouZahr C. Global burden of hypertensive disorders of pregnancy in the year 2000. Geneva: World Health Organisation; 2003. 11. Centre for Health Record Linkage. Quality assurance report. [Internet] 2012. Available at: http://www.cherel.org.au/media/24160/ qa_report_2012.pdf. Accessed Oct. 22, 2012. 12. Klungsoyr K, Morken NH, Irgens L, Vollset SE, Skjaerven R. Secular trends in the epidemiology of pre-eclampsia throughout 40 years in Norway: prevalence, risk factors and perinatal survival. Paed Perinat Epi 2012;26: 190-8. 13. Redman CWG, Jefferies M. Revised denition of pre-eclampsia. Lancet 1988;8589:809-15. 14. Lowe SA, Brown MA, Dekker G, et al. Guidelines for the management of hypertensive disorders of pregnancy [Internet] 2008. Available at: http://www.somanz.org/pdfs/somanz_ guidelines_2008.pdf. Accessed June 26, 2012. 15. Thornton C. Benchmarking the hypertensive disorders of pregnancy [PhD thesis]. Sydney, NSW: University of Western Sydney; 2011. 16. Mealing NM, Roberts CL, Ford JB, Simpson JM, Morris JM. Trends in induction of labour, 1998-2007: a population-based study. ANZ J Obstet Gynaecol 2009;49:599-605. 17. Liu S, Joseph KS, Liston RM. Incidence, risk factors, and associated complications of eclampsia. Obstet Gynecol 2011;118:987-94. 18. Callaghan William M, Creanga Andreea A, Kuklina Elena V. Severe maternal morbidity among delivery and postpartum hospitalizations in the United States. Obstet Gynecol 2012;120: 1029-36. 19. Duley L, Gulmezoglu AM, HendersonSmart DJ, Chou D. Magnesium sulphate

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and other anticonvulsants for women with pre-eclampsia. Cochrane Database System Rev [Internet] 2005. Available at: http://www. mrw.interscience.wiley.com.cochrane/clsysrev/ articles/CD000025/frame.html. Accessed June 26, 2012. 20. Yeast JD, Halberstadt C, Meyer BA, Cohen GR, Thorp JA. The risk of pulmonary oedema and colloids osmotic pressure changes during magnesium sulfate infusion. Am J Obstet Gynecol 1993;169:1566-71. 21. Benedetti T, Kates R, Williams V. Hemodynamic observations in severe preeclampsia complicated by pulmonary oedema. Am J Obstet Gynecol 1985;152:330-4. 22. Rice SK. Minimizing risk of magnesium sulfate overdose in obstetrics. Am J Matern Child Health 2006;31:340. 23. Australian Government Department of Health and Aging. Therapeutic goods administration Australia [Internet] 2008. Available at: http://www.tga.gov.au. Accessed June 26, 2012. 24. Andersgaard A, Herbst A, Johansen M, Borgstrom A, Bille A, Oian P. Follow-up interviews after eclampsia. Gynecol Obstet Investig 2009;67:49-52. 25. Loureiro R, Leite CC, Kahhale S. Diffusion imaging may predict reversible brain lesions in eclampsia and severe preeclampsia: initial experience. Am J Obstet Gynecol 2003;189: 1350-5. 26. Demirtas O, Gelal F, Vidinli BD. Cranial MR imaging with clinical correlation in preeclampsia and eclampsia. Diagn Interv Radiol 2005;11: 189-94. 27. Zeeman G. Neurologic Complications of pre-eclampsia. Semin Perinat 2009;33:166-72. 28. Khan KS, Wojdyla D, Say L. WHO analysis of causes of maternal death: a systematic review. Lancet 2006;367:1066-74. 29. Cliffe S, Black D, Bryant J, Sullivan E. Maternal deaths in New South Wales, Australia: a data linkage project. ANZ J Obstet Gynaecol 2008;48:255-60. 30. Roberts CL, Bell JC, Ford JB, Hadeld RM, Algert CS, Morris JM. The accuracy of reporting of the hypertensive disorders of pregnancy in population health data. Hypertens Pregnancy 2008;27:285-97. 31. Pym M, Taylor L. Validation study of the New South Wales midwives data collection 1990. Public Health Bull Suppl 1993;5-8:1-6. 32. Thornton C, Makris A, Ogle R, Hennessy A. Generic obstetric database systems are unreliable for reporting the hypertensive disorders of pregnancy. ANZ J Obstet Gynaecol 2004;44: 505-9. 33. Chen JS, Roberts CL, Simpson JM, Ford JB. Prevalence of pre-eclampsia, pregnancy hypertension and gestational diabetes in population-based data: impact of different ascertainment methods on outcomes. ANZ J Obstet Gynaecol 2012;52:91-5.

used in the work is of course only as reliable as the datasets sourced. The use of data linkage methodology has been validated previously with a false-positive rate of 0.03% of cases.11 Data linkage has improved the ascertainment of cases in other studies concerning maternal mortality, with reports of up to 55% increases in case identication using this methodology.29 The risk with all large routinely collected datasets is that more complex medical complications of pregnancy are more likely to be incorrectly coded, as supported by validation studies undertaken30-32 but previous work using population datasets to identify preeclampsia cases reported specicities >99%.33 This has to be balanced in comparison to smaller datasets, which although may have greater accuracy of diagnosis, are more likely to report Type II errors and are less likely to actually represent what is occurring on a population level. This study also does not include data on multiple pregnancies, which are affected more frequently by preeclampsia and may increase overall rates of disease. The incidence of preeclampsia has altered over the past 2 decades and current disease rates need to be used in any future discussion. Comparison of datasets such as these on an international stage would provide a statistical basis, enabling a robust disease prole to be established. Considering the role played by eclampsia in maternal and infant morbidity and mortality increasing rates should be of concern to all clinicians, as vigilance and prophylaxis are the only tools to prevent eclampsia. It would appear that more efcient surveillance of women with preeclampsia is urgently required as this will inuence treatments, including the timely use of MgSO4 where required.

REFERENCES
1. Australian Bureau of Statistics. Births 2010. ABS, Canberra, Australia. 2. World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Geographic variation in the

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