Eclampsia in the United Kingdom 2005

Authors


Dr M Knight, National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Oxford OX3 7LF, UK. Email marian.knight@npeu.ox.ac.uk

Abstract

Objectives  To estimate the national incidence of eclampsia in the UK and to describe the management and associated outcomes since the introduction of magnesium sulphate.

Design  A population-based descriptive study using the newly established UK Obstetric Surveillance System (UKOSS).

Setting  All 229 hospitals with consultant-led maternity units in the UK.

Population  All women in the UK delivering between February 2005 and February 2006.

Methods  Prospective case identification through the monthly mailing of UKOSS.

Main outcome measures  Incidence and mortality rates with 95% confidence intervals.

Results  Data collection was complete for 94% of women. The incidence of eclampsia was 2.7 cases per 10 000 births (95% CI 2.4–3.1). Thirty-eight percent of women had established hypertension and proteinuria in the week before their first fit. Ninety-nine percent of women were treated with magnesium sulphate. No women in the study died. Fifty-four women (26%) had recurrent fits. One hundred and nineteen women (56%) were admitted to intensive care or obstetric high dependency units for a median of 2 days (range 1–9). Twenty-two women (10%) were reported to have other severe morbidity after the eclamptic episode. Outcomes were known for 222 infants (204 singletons and 18 twins). Eight infants were stillborn and five died in the neonatal period (perinatal mortality 59/1000 births [95% CI 32–98]).

Conclusions  The incidence of eclampsia and its complications have decreased significantly in the UK since 1992, following the introduction of management guidelines for eclampsia and pre-eclampsia. These results are consistent with the findings of the randomised controlled trials of magnesium sulphate. This study has shown the practical benefits of the incorporation of research evidence into practice.

Introduction

Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality worldwide.1 In 2000–02, eclampsia accounted for 6% of direct maternal deaths in the UK.2 A national surveillance study in 19923 recorded a UK incidence of 4.9/10 000 maternities, with 35% of women having additional major maternal morbidity and 41% further fits. The case fatality rate was 1.8% and perinatal mortality rate was 54/1000 births. To date, this is the only population-based prospective incidence study carried out worldwide. Since this study took place, there have been major advances in the management of eclampsia. The Collaborative Eclampsia Trial4 established the efficacy of magnesium sulphate in preventing recurrent seizures following eclampsia. More recently, magnesium sulphate has been shown to halve the risk of eclampsia among women with pre-eclampsia.5 A number of evidence-based management protocols have subsequently been developed, which recommend use of magnesium sulphate as a routine and include guidance on appropriate management of hypertension and fluid balance.6–8 However, of the 14 maternal deaths due to hypertensive disorders reported in the UK in 2000–02, nearly half were associated with substandard care.2

It is now recognised that in developed countries where maternal deaths are rare, the study of severe acute maternal morbidity or ‘near miss’ events may provide more insight into factors which contribute to both morbidity and mortality. A ‘near miss’ may be defined as ‘a severe life-threatening obstetric complication necessitating an urgent medical intervention to prevent likely death of the mother’.9 Eclampsia is such an event. There are no current data on the epidemiology and management of non-fatal eclampsia in the UK to identify the extent to which appropriate management protocols have been adopted and the impact on disease incidence and outcomes. This information is key to identifying means to improve prevention and quality of care. The aim of this study was to estimate the incidence of eclampsia in the UK using the newly established UK Obstetric Surveillance System (UKOSS) and to investigate the management and outcomes of the condition to assess the effect of the introduction of management guidelines following the magnesium sulphate trials and to identify whether further improvements can be made to the care of women.

Methods

Case definition

To facilitate direct comparison, cases were defined according to the criteria used in the 1992 eclampsia survey (Box 1).3

Table Box 1. .  Case definition
Any woman with convulsion(s) during pregnancy or in the first 10 days postpartum, together with at least two of the following features within 24 hours of the convulsion(s):
 • Hypertension (a booking diastolic pressure of <90 mmHg, a maximum diastolic of ≥90 mmHg and a diastolic increment of ≥25 mmHg).
 • Proteinuria (at least + protein in a random urine sample or ≥0.3 g in a 24-hour collection).
 • Thrombocytopenia (platelet count of less than 100 × 109/l).
 • Raised plasma alanine aminotransferase concentration (≥42 iu/l) or an increased plasma aspartate aminotransferase concentration (≥42 iu/l).

Data collection

We identified cases through the monthly mailing of UKOSS10 between February 2005 and February 2006. Nominated clinicians in each hospital with a consultant-led maternity unit were sent a card each month, which, together with a series of other conditions, included a simple tick-box to indicate a case of eclampsia and a box indicating ‘nothing to report’. They were asked to return the card each month whether or not there had been any women who had an eclamptic episode. This ‘negative surveillance’ was requested to ensure verification of nil reports and hence confirmation of the appropriate denominator to be used to calculate incidence.

When a card was received indicating that there had been a case of eclampsia, the reporting clinician was sent a data collection form requesting further details to confirm the case definition and describe risk factors, management and outcomes. All data requested were anonymous. Data were double entered into a customised Access database and assessed for internal validity. Objective measures of blood pressure, proteinuria, platelets and liver enzymes were checked to confirm that each reported case met the case definition. Cases that did not meet the case definition were excluded from the analysis.

Statistical analyses

Statistical analysis was carried out according to a prespecified study protocol. All analyses were carried out using STATA v9 software (StataCorp, College Station, TX, USA).

Rates with 95% confidence intervals were calculated using as the denominator the most recently available birth data (2004) as a proxy for 2005 and 2006.11–13

Ethical approval

The UKOSS general methodology (study reference 04/MRE02/45) and specific study methodology (study reference 04/MRE02/72) were approved by the London Multicentre Research Ethics Committee.

Results

All 229 UK hospitals with consultant-led maternity units contributed data to UKOSS (100%). The mean monthly card return rate over the 13 months of the study was 91%. Three hundred and fourteen cases of eclampsia were reported; data collection was completed for 295 of these cases (94%) (Figure 1). Forty-two cases were reported by clinicians as not cases after initial notification; the majority of these cases were women who had received magnesium sulphate but had not had a fit. Completed data collection forms were received for 31 women who had a fit but did not meet the case definition for eclampsia; 18 of these women did not have hypertension and 13 had hypertension but in the absence of any other signs. Two hundred and fourteen cases met the criteria for eclampsia, representing an estimated incidence rate of 2.7 cases per 10 000 births (95% CI 2.4–3.1/10 000).

Figure 1.

Case reporting and completeness of data collection.

There were two women about whom we received little information concerning antenatal care and management. Seventy-nine percent of women had at least one premonitory symptom or sign in the week preceding the eclamptic episode (Table 1), but only 38% had established hypertension and proteinuria in this week. Forty-eight women (59%) with established hypertension and proteinuria had proteinuria ≥ 2+ on dipstick with a diastolic blood pressure of 100 mmHg or greater in the week before their fit; two-thirds of these women also had premonitory symptoms. Forty-five percent of first fits were antepartum, 19% intrapartum and 36% postpartum. Forty-four women (21%) had their first fit at home. The gestational age distribution at the time of the eclamptic episode (antepartum and intrapartum fits) or delivery (postpartum fits) is shown in Figure 2. Twelve women (6%) were given magnesium sulphate both before and after the eclamptic episode. One hundred and ninety-nine women (99%) were given magnesium sulphate only after the fit. Three women did not receive magnesium sulphate at any stage; two of these women did not receive any anticonvulsants and one was treated with a benzodiazepine alone. Forty-two women were treated with benzodiazepines, one with phenytoin and one with carbamazepine in addition to magnesium sulphate.

Table 1.  Premonitory symptoms and signs in the week preceding the eclamptic episode
Symptom or signWomen, n (%) (n = 214)
Visual disturbance48 (23)
Headaches119 (56)
Epigastric pain36 (17)
Hypertension (diastolic BP >90 mmHg)101 (48)
Proteinuria (+ or more on dipstick or >0.3 g/24 hours)97 (46)
Hypertension and proteinuria81 (38)
Any premonitory symptom or sign168 (79)
Figure 2.

Gestational age at the time of the eclamptic episode (antepartum and intrapartum fits) or delivery (postpartum fits).

No women in the study died (Table 2). Twenty-six percent of women (54) experienced one or more further fits after the initial eclamptic episode. Women with recurrent fits were more likely to be preterm at the time of their first fit than women who did not have a second seizure (median gestational age at delivery or first fit 35 weeks [range 19–41] in those with recurrent fits compared with 38 weeks [range 24–42] in those with a single fit). Women with recurrent fits were not significantly more likely to have had established hypertension and proteinuria or to have other premonitory symptoms and signs in the week before their eclampsia than women with a single fit.

Table 2.  Comparison between eclampsia survey results in 1992 and 2005 and results of RCTs of magnesium sulphate
 1992 survey (95% CI)2005 survey (95% CI)Relative risk reduction 1992–2005Relative risk reduction RCTs
  • RCTs, randomised controlled trials.

  • *

    Result from Magpie trial.

  • **

    Result from Collaborative Eclampsia trial, magnesium sulphate versus phenytoin comparison.

  • ***

    More restricted definition of associated severe morbidity used in the Collaborative Eclampsia trial.

  • ****

    Relative risk reduction not calculable as there were no deaths in 2005. Risk difference −1.8% (−3.2 to 0%).

Eclampsia incidence4.9 cases per 10 000 births (4.5–5.4)2.7 cases per 10 000 births (2.4–3.1)−45% (−53 to −34%)−58% (−71 to −40%)*
Proportion of women with associated severe morbidity35% (31–40%)10% (7–15%)−71% (−81 to −56%)−13% (−29 to +6%)**,***
Proportion of women with recurrent fits41% (36–46%)25% (20–32%)−39% (−53 to −21%)−67% (−79 to −47%)**
Case fatality rate1.8% (0.7–3.7%)0% (0–1.7%)****−50% (−76 to +5%)**
Perinatal mortality rate54/1000 births (34–81)59/1000 births (32–98)+9% (−44 to +110%)−16% (−34 to +7%)**

One hundred and nineteen women were admitted to intensive care or obstetric high dependency units for a median of 2 days (range 1–9). Twenty-two women (10%) were reported to have other severe morbidity after the eclamptic episode (Table 2). Five women had a cerebrovascular accident, four women had HELLP syndrome, three women had a postpartum haemorrhage, two women had aspiration pneumonia and two women required ventilation. Other morbidities reported in individual women included pulmonary oedema, renal failure, disseminated intravascular coagulopathy, hyperkalaemia, pulmonary embolism and persistent headaches. We were not able to detect any significant differences in features of the disease course or management in women who suffered severe morbidity compared with those who did not (data not shown).

One pregnancy was terminated at 19 weeks because of maternal eclampsia. Outcomes were known for 222 infants born to 213 women (204 singletons and 18 twins). Eight infants were stillborn and five died in the neonatal period (perinatal mortality 59/1000 births [Table 2]). Four stillbirths were associated with placental abruption; two with intrauterine growth restriction and two were unexplained. Three neonatal deaths were associated with extreme prematurity, one with infection and one with congenital anomaly. Forty-three percent of infants were delivered prior to 37 weeks of gestation.

Discussion

This is the first national incidence study to be carried out since the widespread introduction of magnesium sulphate for the treatment of eclampsia and severe pre-eclampsia. Our results indicate that both the incidence of eclampsia and the proportion of women with eclampsia experiencing further fits have nearly halved since 1992 (Table 2). The associated severe maternal morbidity has reduced by over two-thirds, although the rates of both perinatal and maternal mortality remain essentially unchanged.

Our findings are consistent with the reductions expected from the outcomes of the Collaborative Eclampsia and Magpie trials.4,14 In 1992, the majority of women with eclampsia would have been treated with either diazepam or phenytoin as a first-line treatment. In 2005, we have shown that 99% of women are treated with magnesium sulphate as first-line therapy. When comparing magnesium sulphate with either phenytoin or diazepam, the Collaborative Eclampsia trial demonstrated a reduction in the risk of recurrent convulsions of between 37 and 79% and a nonsignificant reduction in maternal mortality. We have shown a similar reduction in the risk of recurrent convulsions in the UK between 1992 and 2005, which we attribute to the widespread introduction of guidelines for the management of eclampsia, including the use of magnesium sulphate therapy.6 The Magpie trial of magnesium sulphate for prevention of eclampsia in women with pre-eclampsia demonstrated a 58% lower risk of eclampsia, with a nonsignificant reduction in maternal mortality (relative risk reduction 45%) when magnesium sulphate was used compared with placebo. We do not have the information from this UKOSS study to assess how many women with pre-eclampsia in the UK were treated with magnesium sulphate and did not develop eclampsia. However, only 37% of women had established hypertension and proteinuria during the week before their eclampsia, a significantly lower proportion than the 57% in the 1992 study, and only 5% of women with eclampsia were reported to have had magnesium sulphate before the fit. This indicates that a smaller proportion of women in 2005 had established pre-eclampsia before their eclampsia and suggests that very few women who were managed with magnesium sulphate for pre-eclampsia went on to have an eclamptic fit. We therefore believe that the reduction in incidence of eclampsia has occurred because women with severe pre-eclampsia are being managed better according to guidelines including the use of magnesium sulphate and are thus prevented from having an eclamptic fit. Neither the Collaborative Eclampsia trial nor the Magpie trial showed any difference in perinatal mortality, which is consistent with our finding of no significant change in perinatal mortality between 1992 and 2005.

We have not been able to conduct any formal assessment of case ascertainment in this study because other sources of data do not exist with which to validate our data. Although eclamptic episodes are collected as part of routine hospital statistics,15 clinical coding is known to be inaccurate,16 and particularly so for eclampsia.17 However, it is possible that the apparent differences observed in the incidence and outcomes of eclampsia in 2005 compared with 1992 are due to different study methodologies. We used the UKOSS dedicated reporting obstetricians, midwives, anaesthetists and risk management midwives to identify cases in 2005. In the 1992 survey, a dedicated midwife in each unit was recruited to report cases, and additionally requests for notifications were sent to all UK obstetricians every 3 months. Negative reporting was requested. Reporters were asked to notify all cases of eclampsia; the investigators conducted a detailed case note review to ascertain whether each reported case met the case definition and 26% of cases were excluded after this review. In contrast, we provided reporting clinicians with the case definition and asked them to report only cases meeting the definition. As in the 1992 survey, we did not undertake any further validation of cases, which were investigated by reporting clinicians and found not to be cases of eclampsia. Nevertheless, we still excluded over one-seventh of cases after review of the completed data collection forms because they did not meet the case definition suggesting over rather than underreporting. We used the same case definition as that used in 1992, which includes objective measures of the associated clinical signs of eclampsia, which are measured in comparable ways in 2005. Hence, differential application of the definitions between the two time periods is unlikely to have caused a bias sufficient to account for the difference in reported incidence. There is a widespread system of obstetric risk management in the UK, which requires detailed internal investigation of certain ‘trigger’ conditions. Eclampsia is one such trigger condition, and by including risk management midwives among the UKOSS reporters, we believe it is unlikely that we have failed to be notified of significant numbers of cases and certainly not sufficient to account for this degree of difference in incidence. We believe, therefore, that the reporting systems are sufficiently similar and that the difference in incidence cannot be explained by significant underreporting in 2005.

It is possible that the reduction in incidence of eclampsia is consequent on a general reduction in the underlying condition of pre-eclampsia. Neither this study nor the 1992 survey included any estimate of the incidence of pre-eclampsia. Few studies have been undertaken to investigate temporal trends in the incidence of pre-eclampsia; those that have reported inconsistent results, including decreasing,18,19 static20 and increasing incidence.21 However, none of the studies has reported a declining incidence of pre-eclampsia sufficient to account for this degree of reduction in eclampsia.

While there have been no other national population-based studies of eclampsia undertaken in the UK, a Yorkshire regional study undertaken between 1999 and 2003 reported an incidence of eclampsia of 3.9/10 000 births (95% CI 3.1–4.8).22 Although the confidence intervals are wide because of the smaller numbers of women included in the Yorkshire study, this provides supporting evidence for a declining incidence of eclampsia over time. This study was carried out at the time of the introduction of detailed regional management guidelines for eclampsia and severe pre-eclampsia, including introduction of the use of magnesium sulphate for severe pre-eclampsia. The incidence rate reported might therefore be expected to be between that of the 1992 and 2005 surveys as the change in practice occurred while it was being carried out.

Although the absolute number of women with eclampsia has decreased between 1992 and 2005, the pattern of presentation appears similar. In 2005, there were more antenatal than postnatal cases; the converse was observed in 1992. However, there is no significant difference between the proportions observed in the two surveys. The gestational age distribution is also very similar, with the majority of antepartum cases occurring preterm, whereas the intrapartum and postpartum cases tend to occur at term.

Overall, this study has identified few major deficiencies in the care of women with eclampsia in the UK. UK guidelines6 advise that all women with eclampsia should be treated with magnesium sulphate to prevent further fits. Ninety-nine percent of women were managed with magnesium sulphate as recommended. We were not able to detect any difference in the treatment of women who had a single fit and those who had more than one, although we had limited power to do so. However, we did not collect any information about the dose, route of administration or blood levels of magnesium sulphate. It is possible that there may have been a difference in any of these parameters, but this would require further investigation. Women who suffered severe morbidities also had no clear distinctions from women without such sequelae in the course of their disease or their management, but again, we had limited power to detect any differences. The range of morbidities suffered were, however, very variable, and it is perhaps not surprising that this heterogeneous group have no specific differences from the group of women with eclampsia as a whole. Only one woman was reported to have suffered from pulmonary oedema, which suggests that fluid balance in women with eclampsia is being managed effectively.

Only 6% of women received magnesium sulphate before their eclamptic fit. We do not have any information about the number of women with pre-eclampsia in the UK who were treated with magnesium sulphate and did not go on to have a fit. Without this information, it is difficult to make any inferences from these data. However, our data are comparable with those of the Yorkshire Obstetric Critical Care Group Study.22 None of the 82 women with eclampsia in that study received magnesium sulphate before their fit; eight were potentially eligible, but their eclampsia occurred before magnesium sulphate was included in treatment guidelines. However, 37% of women in the UKOSS study had established pre-eclampsia before developing eclampsia, and 59% of these women with pre-eclampsia had established proteinuria ≥ 2+ on dipstick with a diastolic blood pressure of 100 mmHg or greater in the week before their fit. There were thus a significant number of women in the UK with moderate to severe pre-eclampsia who went on to develop eclampsia and were not treated preventatively with magnesium sulphate. There may therefore be scope for further consideration of the criteria used to determine which women with pre-eclampsia are managed preventatively with magnesium sulphate. Conversely, 63% of women did not have established pre-eclampsia, and over 20% of women had their first fits at home; the potential for early intervention in these women is likely to be limited.

In summary, the incidence of eclampsia has decreased significantly in the UK following the introduction of management guidelines for eclampsia and pre-eclampsia based on the results of the Collaborative Eclampsia and Magpie trials. Although these trials were conducted largely in developing countries, the application of the results to a developed country setting appears to have led to considerable benefits for women. The majority of women in the UK are managed with magnesium sulphate according to national protocols and maternal morbidity has been significantly reduced as a consequence. However, neither perinatal nor maternal mortality has decreased. Further investigation is needed of the factors influencing perinatal mortality. There may be scope for further development of the guidelines for preventative use of magnesium sulphate in women with pre-eclampsia. This study has shown the practical benefits of the incorporation of research evidence into practice through the widespread use of evidence-based guidelines.

Acknowledgements

This study would not have been possible without the contribution and enthusiasm of the UKOSS reporting clinicians who notified cases and completed the data collection forms. We would also like to acknowledge the members of the UKOSS Steering Committee and Prof Chris Redman who provided advice on the study and paper. The support of the Royal College of Obstetricians and Gynaecologists, Royal College of Midwives, Obstetric Anaesthetists Association, Faculty of Public Health, National Childbirth Trust, and the Confidential Enquiry into Maternal and Child Health contributed greatly to the success of the study and UKOSS in general.

Funding

M.K. is funded by the Oxford Deanery public health training programme and the National Coordinating Centre for Research Capacity Development of the Department of Health. J.J.K. was partially funded by a National Public Health Career Scientist Award from the Department of Health and NHS R&D (PHCS 022). The National Perinatal Epidemiology Unit is funded by the Department of Health in England. The views expressed in this paper are those of the authors and do not necessarily reflect those of the Department of Health. All researchers are independent of their funding sources.

Writing Committee

M.K., Jennifer J Kurinczuk, Patsy Spark, Peter Brocklehurst, National Perinatal Epidemiology Unit.

UKOSS Steering Committee

Catherine Nelson-Piercy (Chair), Guys and St Thomas’ Hospital; Jenny Furniss (Vice-chair), Lay Member; Sabaratnam Arulkumaran, Royal College of Obstetricians and Gynaecologists; Jean Chapple, Faculty of Public Health; Cynthia Clarkson, National Childbirth Trust; Andrew Dawson, Nevill Hall Hospital; James Dornan, Royal College of Obstetricians and Gynaecologists; Kate Fleming, Confidential Enquiry into Maternal and Child Health; Shona Golightly, Confidential Enquiry into Maternal and Child Health; Ian Greer, Department of Obstetrics and Gynaecology, University of Glasgow; Mervi Jokinen, Royal College of Midwives; Gwyneth Lewis, Department of Health; Richard Lilford, Department of Public Health and Epidemiology, University of Birmingham; Mary Mackintosh, Confidential Enquiry into Maternal and Child Health; Margaret McGuire, Scottish Executive Health Department; Richard Pebody, Health Protection Agency; Kate Taylor-Weetman, National Childbirth Trust; Derek Tuffnell, Bradford Hospitals NHS Trust; James Walker, National Patient Safety Agency; Steve Yentis, Chelsea and Westminster Hospital; Carole Harris, National Perinatal Epidemiology Unit; Marian Knight, National Perinatal Epidemiology Unit; Jennifer Kurinczuk, National Perinatal Epidemiology Unit; Peter Brocklehurst, National Perinatal Epidemiology Unit.

Contribution to authorship

M.K. designed the study, coordinated data collection, coded the data, carried out the analysis and wrote the first draft of the paper. J.J.K. assisted with the design of the study and supervised the data collection and analysis and contributed to writing the paper. P.S. assisted with data coding, conducted validation of the data and some analysis. P.B. had the original idea for the surveillance system, provided advice at every stage of the study and contributed to the writing and editing of the paper. P.B. will act as study guarantor.

Ancillary