Volume 98, Issue 3 p. 342-350
ORIGINAL RESEARCH ARTICLE
Free Access

A national surveillance approach to monitor incidence of eclampsia: The Netherlands Obstetric Surveillance System

Timme P. Schaap

Corresponding Author

Timme P. Schaap

Department of Obstetrics, Birth Center Wilhelmina's Children Hospital, University Medical Center Utrecht, Utrecht, the Netherlands

Correspondence

Timme P. Schaap, Department of Obstetrics, Birth Center, Utrecht, the Netherlands.

Email: [email protected]

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Thomas van den Akker

Thomas van den Akker

Department of Obstetrics, Leiden University Medical Center, Leiden, the Netherlands

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Joost J. Zwart

Joost J. Zwart

Department of Obstetrics and Gynecology, Deventer Hospital, Deventer, the Netherlands

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Jos van Roosmalen

Jos van Roosmalen

Department of Obstetrics, Leiden University Medical Center, Leiden, the Netherlands

Athena Institute, VU University, Amsterdam, the Netherlands

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Kitty W. M. Bloemenkamp

Kitty W. M. Bloemenkamp

Department of Obstetrics, Birth Center Wilhelmina's Children Hospital, University Medical Center Utrecht, Utrecht, the Netherlands

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First published: 22 October 2018
Citations: 27

Abstract

Introduction

There have been many efforts in the last decade to decrease the incidence of eclampsia and its related complications in the Netherlands, such as lowering thresholds for treatment of hypertension and mandatory professional training. To determine the impact of these policy changes on incidence and outcomes, we performed a nationwide registration of eclampsia, 10 years after the previous registration.

Material and methods

Cases of eclampsia were prospectively collected using the Netherlands Obstetric Surveillance System (NethOSS; 2013-2016) in all hospitals with a maternity unit in the Netherlands. Complete case file copies were obtained for comparative analysis of individual level data with the previous cohort (2004-2006). Primary outcome measure was incidence of eclampsia; main secondary outcomes were antihypertensive and magnesium sulfate use, and maternal and perinatal mortality.

Results

NethOSS identified 88 women with eclampsia. The incidence decreased from 6.2/10 000 in 2004-2006 to 1.8/10 000 births (relative risk [RR] 0.28, 95% confidence interval [CI] 0.22-0.36). Increases in the use of antihypertensive medication (61/82 vs 35/216; RR 18.4, 95% CI 9.74-34.70) and magnesium sulfate treatment (82/82 vs 201/216; RR 1.08, 95% CI 1.04-1.12) were observed. There was one intrauterine death following termination of pregnancy. No cases of neonatal mortality were reported in NethOSS compared with 11 in the LEMMoN. Maternal death occurred in one woman compared vs three in the previous registration.

Conclusions

There has been a strong reduction of eclampsia and associated perinatal mortality in the Netherlands over the last decade. Management changes and increased awareness may have contributed to this reduction.

Abbreviations

  • CI
  • confidence intervals
  • HDP
  • hypertensive disorders of pregnancy
  • INOSS
  • International Network of Obstetric Survey Systems
  • LEMMoN
  • Nationwide Study into Ethnic Determinants of Maternal Morbidity in the Netherlands
  • NethOSS
  • Netherlands Obstetric Surveillance System
  • RR
  • relative risks
  • Key Message

    Many efforts have been made to reduce the high incidence of eclampsia in the Netherlands. This prospective national surveillance shows a considerable reduction (70%) in incidence, while uncovering clues to achieving an even larger reduction in the future.

    1 INTRODUCTION

    Hypertensive disorders of pregnancy (HDP) have multiple clinical expressions and complicate approximately 10% of all pregnancies.1 A decade ago, both the UK and the Netherlands performed nationwide prospective registrations of eclampsia, a state of convulsions in women with HDP.2, 3 Comparative analysis showed that the incidence of eclampsia in the Netherlands was twice as high as in the UK.4 Individual case-by-case analysis indicated that women with HDP and (pre)eclampsia in the Netherlands were managed less proactively, meaning that management options such as administration of antihypertensive medication and magnesium sulfate, and delivery by induction or cesarean section were not applied as frequently. HDP-related maternal mortality was found to be considerably higher in the Netherlands,5 although differences in classification of underlying causes of maternal deaths between the confidential enquiries in both countries complicate comparisons.6

    Following these alarming signals there have been many efforts to reduce the incidence of eclampsia in the Netherlands, including: (1) lowering the threshold for the definition of severe hypertensive disease and explicitly mentioning the need for tight blood pressure control in the national guideline (Supporting Information Table S1); (2) introducing the mandatory Managing Obstetric Emergencies and Trauma course for all obstetric trainees;7 (3) inducing labor in women with gestational hypertension and mild preeclampsia at (early) term, following the results of the HYPITAT-1-trial.8

    To determine the impact of increased awareness and these policy changes, we performed a new nationwide registration of eclampsia, 10 years after the Nationwide Study into Ethnic Determinants of Maternal Morbidity in the Netherlands (LEMMoN; 2004-2006).9 Secondly, we aimed to compare management strategies between these two time frames and assessed adherence to national guidelines.

    2 MATERIAL AND METHODS

    Since there was no international consensus definition for eclampsia at the start of this registration, we purposefully used a broad definition for case ascertainment in order to facilitate comparisons with women from both the previous LEMMoN registration and the United Kingdom Obstetric Surveillance System (UKOSS) (Supporting Information Table S2). We applied a maximum postpartum interval between the onset of convulsions and delivery of 10 days, since the LEMMoN study yielded no cases beyond 8 days postpartum. Systolic cut-off values for severe hypertensive disease were changed between the two time periods from a systolic blood pressure of 170 to 160 mm Hg; the diastolic cut-off remained 110 mm Hg as per national guidelines. Both the old and the new systolic cut-off were used to compare the prevalence of severe hypertensive disease.

    Cases were ascertained using the Netherlands Obstetric Surveillance System (NethOSS), the nationwide registration system of severe maternal morbidity and mortality that is used by the Dutch Society of Obstetrics and Gynecology (NVOG) Audit Committee on Maternal Mortality and Morbidity. Through this system, an email that includes a link for online registration is sent out every month to nominated clinicians in all hospitals with an obstetrician-led maternity unit in the country. These clinicians are asked to report any case meeting inclusion criteria or reply with “nothing to report,” in order to ascertain validity of the registration system and confirm the appropriate denominator for calculated incidence. Cases of eclampsia were registered from 1 September 2013 up to and including 31 August 2016. All women with eclampsia are referred to one of the obstetrician-led units.

    Upon receiving a case notification, reporting hospitals were contacted to supply anonymized case file copies to NethOSS, which were scanned and archived in a NEN-7510 certified database for clinical research (ProMISe). Relevant data were extracted from case files and entered into an aggregated dataset containing data from both the LEMMoN and the NethOSS registrations. We compared possible risk factors where available. The primary outcome measure was population-based incidence of eclampsia. Secondary outcomes were differences in putative risk factors and management modalities such as treatment of severe hypertension and use of magnesium sulfate. We also compared mode and timing of birth, occurrence of severe maternal morbidity, and mortality and perinatal mortality.

    2.1 Statistical analyses

    Statistical analyses were carried out according to a prespecified study protocol, using IBM SPSS 24 (SPSS Inc., Chicago, IL, USA). Proportions are presented as percentages and skewed distributions as medians with interquartile ranges. For categorical data, differences are presented as relative risks (RR) with 95% confidence intervals (95% CI). Continuous data that were not normally distributed were analyzed using the Mann-Whitney U test.

    2.2 Ethical approval

    The study was centrally approved by the medical ethics committee of Leiden University Medical Center (P12-216/SH/sh, 12 March 2013).

    3 RESULTS

    All obstetric units in the Netherlands contributed data to both the LEMMoN and NethOSS registries. The LEMMoN study collected cases between August 2004 and August 2016, covering 371 021 births. In all, 97% of the monthly notification cards were received, representing 358 874 births. Between September 2013 and September 2016, 518 103 women gave birth in the Netherlands. NethOSS received 3012 (97%) monthly registrations, representing 502 559 births, including 108 reported cases of eclampsia. Individual level data for four cases (3.7%) could not be retrieved; 16 cases were excluded since these did not meet the definition (n = 9), occurred outside the time frame (n = 1) or were reported twice (n = 6) (Figure 1). In total, 88 cases met the criteria for eclampsia, resulting in an incidence of 1.8 (95% CI 1.4-2.2) per 10 000 births in 2013-2016 vs 6.2 (95% CI 5.4-7.1) per 10 000 births in 2004-2006 (RR 0.28, 95% CI 0.22-0.36).6

    Details are in the caption following the image
    Flowchart of cases of eclampsia. LEMMoN, Nationwide Study into Ethnic Determinants of Maternal Morbidity in the Netherlands; NethOSS, Netherlands Obstetric Surveillance System [Color figure can be viewed at wileyonlinelibrary.com]

    NethOSS contained one woman (1.3%) with a multiple pregnancy who developed eclampsia in comparison with 21 women (9.7%) in the previous registration (RR 0.13, 95% CI 0.02-0.98). Maternal age, nulliparity, smoking, body mass index >30 kg/m2, ethnicity and a diagnosis of preexisting hypertension were comparable between the two periods (Table 1). In NethOSS, 54 of 82 (65.9%) women were admitted prior to developing eclampsia, compared with 175 of 216 (81.0%) women in LEMMoN (RR 0.81, 95% CI 0.69-0.96). A comparable proportion of women were admitted due to HDP (LEMMoN 131/175 [74.9%] vs NethOSS 38/54 [70.4%]), as was the number of women with recurrent eclampsia. There were no differences in the presence of premonitory signs and symptoms prior to developing eclampsia. Laboratory markers were less abnormal in the more recent time frame with regard to maximum lactate dehydrogenase, maximum creatinine, and the lowest hemoglobin levels and lowest platelet count (Table 1).

    Table 1. Incidence and characteristics of women with eclampsia
    LEMMoN (2004-2006), N = 216 NethOSS (2013-2016), N = 88 RR 95% CI P value
    Eclampsia
    Incidence (all) 6.2/10 000 1.8/10 000 0.28 0.22 0.36
    Singleton pregnancy 5.5/10 000 1.7/10 000 0.41 0.32 0.52
    Multiple pregnancy 0.6/10 000 0.02/10 000 0.03 0.00 0.25
    Recurrent eclampsia 52/216 (24.1%) 24/76 (31.6%) 1.29 0.73 2.28
    First fit antepartum 85/216 (39.4%) 37/82 (45.1%) 1.15 0.86 1.53
    First fit intra partum 69/216 (31.9%) 20/82 (24.4%) 0.76 0.50 1.17
    First fit postpartum 62/216 (28.7%) 25/82 (30.5%) 1.06 0.72 1.57
    Location of first eclampsia
    At home 38/216 (17.6%) 28/82 (34.1%) 1.9 1.28 2.94
    Delivery ward Not available 44/82 (53.7%)
    Operating theater Not available 7/82 (8.5%)
    Hospital (other) Not available 3/82 (3.7%)
    Maternal characteristics
    Woman's age [Q1, Q3] 30 [26-34] 28 [25-34] 0.25
    Nulliparous (%) 151/215 (70.2%) 63/82 (76.8%) 1.41 0.78 2.54
    Ethnicity
    Dutch 147/213 (69.0%) 45/66 (68.2%) 0.35
    Other western 11/213 (5.2%) 3/66 (4.6%)
    Northern Africa 11/213 (5.2%) 3/66 (4.5%)
    Sub-Saharan Africa 14/213 (6.6%) 5/66 (7.6%)
    Surinam/Dutch Caribbean immigrant 16/213 (7.5%) 2/66 (3.0%)
    Other non-Western 14/213 (6.6%) 3/66 (4.5%)
    Multiple pregnancy 21/216 (9.7%) 1/82 (1.2%) 0.12 0.02 0.87
    Smoking 17/139 (12.2%) 11/74 (14.9%) 1.25 0.55 2.84
    Body mass index (≥30) 19/140 (13.6%) 7/57 (12.3%) 0.89 0.35 2.25
    Preexisting hypertension 13/213 (6.1%) 3/76 (4.0%) 0.65 0.19 2.21
    Antenatal care and admission
    Level of antenatal care at 20 wka Not available Primary: 57/82 (69.5%)
    Hospital: 22/82 (26.8%)
    No antenatal care: 3/82 (3.7%)
    Level of antenatal care directly prior to eclampsia if not admitteda Not available Primary: 15/28 (53.6%)
    Hospital: 10/28 (35.7%)
    No antenatal care: 3/28 (10.7%)
    Admission prior to eclampsia 175/216 (81.0%) 54/82 (65.9%) 0.81 0.69 0.96
    Admission diagnosis of HDP if admitted prior to eclampsia 131/175 (74.9%) 38/54 (70.4%) 0.94 0.78 1.14
    Premonitory signs and symptoms
    Diagnosis of HDP prior to E 128/216 (59.3%) 44/82 (53.7%) 0.80 0.48 1.33
    Abdominal tenderness (%) 68/151 (55.0%) 36/67 (46.3%) 0.84 0.63 1.11
    Headaches (%) 110/161 (68.3%) 48/68 (70.6%) 1.11 0.60 2.07
    Visual disturbance (%) 52/132 (39.4%) 27/60 (45.0%) 1.26 0.68 2.33
    Nausea (%) 71/148 (48.0%) 42/70 (60.0%) 1.63 0.91 2.90
    Vomiting (%) 40/143 (28.0%) 22/63 (34.9%) 1.38 0.73 2.60
    Paresthesia (%) 28/119 (23.5%) 11/48 (22.9%) 0.97 0.44 2.14
    Edema (%) 93/127 (73.2%) 34/57 (59.6%) 0.54 0.28 1.05
    Hyper-reflexia (%) 61/113 (54.0%) 20/49 (40.8%) 0.59 0.30 1.16
    At least one prodromal sign 176/176 (100%) 63/73 (86.3%) 0.93 0.75 1.14
    AST maximum [Q1, Q3] 72 [32-268] 72 [45-198] 0.99
    ALT maximum [Q1, Q3] 51 [17-188] 50 [25-150] 0.91
    LD maximum [Q1, Q3] 633 [494-1503] 494 [282-620] <0.001
    Uric acid maximum [Q1, Q3] 0.48 [0.40-0.57] 0.48 [0.38-0.55] 0.24
    Creatinine maximum [Q1, Q3] 89 [71-103] 77 [66-104] 0.04
    Hb lowest [Q1, Q3] 7.8 [6.8-8.6] 6.5 [5.8-6.9] <0.001
    Thrombocyte [Q1, Q3] 118 [68-194] 131 [102-172] 0.02
    Proteinuria present 123/216 (55.48%) 44/88 (49.4%) 0.88 0.69 1.11
    • N, number available for analysis; E, eclampsia; RR, relative risk; CI, confidence interval; Q1, first interquartile; Q3, third interquartile; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LD, lactate dehydrogenase; Hb, hemoglobin.
    • Antenatal check received in primary (midwife), secondary (non-academic hospital) or tertiary (academic hospital) care.

    The number of women meeting the criteria of severe hypertension was similar between both time frames when using either a cut-off of 160 mm Hg for both studies or a cut-off for systolic blood pressure advised in the national guideline at the time of each registration. Of women who were admitted prior to their first eclamptic fit, 28 of 50 (56.0%) met the criteria for severe hypertension just before the onset of eclampsia, with a median interval between fit and previous blood pressure measurement of 35 minutes (interquartile range to 142). Of the 43 women in whom severe hypertension was confirmed based on two consecutive measurements, 16 (37.2%) were started on (additional) antihypertensive medication. The median interval between the first severe blood pressure recording and the first subsequent blood pressure measurement was 25 minutes (interquartile range 11-60). The median interval between the first measurement of severe hypertension and reaching the target blood pressure defined as a systolic blood pressure <160 mm Hg and a diastolic blood pressure <110 mm Hg, was 2 hours and 25 minutes (interquartile range 74-322 minutes). Of the 62 women diagnosed with severe hypertension based on one measurement, 22 (35.5%) women developed eclampsia before subsequent blood pressure measurement showed persistent severe hypertension. Data on timing of severe hypertension were not available for the LEMMoN registration. In the NethOSS registration, 61 of 69 (88.4%) women with severe hypertension received antihypertensive medication as compared with 35 of 170 (20.6%) in the LEMMoN registration (RR 4.29, 95% CI 3.16-5.84) (Table 2). The use of magnesium sulfate prophylaxis among women with preeclampsia or severe hypertension was low and there was no reported difference over time in the use of prophylactics.

    Table 2. Diagnosis and management of women with eclampsia
    LEMMoN (2004-2006), N = 216 NethOSS (2013-2016), N = 88 RR 95% CI P value
    Diagnosis and management of hypertension
    Severe hypertension (based on 2012 criteria) 179/197 (90.9%) 69/78 (88.5%) 0.77 0.33 1.80
    Severe hypertension (based on 2005 criteria) 170/197 (86.3%) 63/78 (80.8%) 0.67 0.33 1.34
    Severe hypertension directly prior to E (if admitted) Not available 28/50 (56.0%)
    Antihypertensive medication started 35/216 (16.2%) 61/82 (74.4%) 18.4 9.74 34.70
    Antihypertensive medication started in severe hypertension (based on respective guidelines) 35/170 (20.6%) 61/69 (88.4%) 4.29 3.16 5.84
    Interval eclampsia to prior blood pressure measured (min.; Q1, Q3) Not available 35 [8-142]
    Median blood pressure prior to E (mm Hg; Q1, Q3)
    Systolic Not available 160 [146-173]
    Diastolic 95 [85-106]
    Interval first BP high and second BP measured (min.; Q1, Q3) Not available 25 [11-60]
    Women with interval >15 min between first BP high and subsequent BP measured (% of women with one measurement of severe BP) Not available 36/62 (40.9%)
    Women with severe BP on subsequent BP measured (% of women with one measurement of severe BP) Not available 43/62 (69.4%)
    (additional) antihypertensive medication started in women with two consecutive severe BP's Not available 16/43 (37.2%)
    Time to target BP after first BP high (min.; Q1, Q3) Not available 145 [74-322]
    Women with eclampsia following severe BP, before first BP below severe threshold (%) Not available 22/62 (35.5%)
    Prevention and treatment of eclampsia
    MgSO4 prophylaxis (%) 21/216 (9.7%) 6/82 (7.3%) 0.73 0.29 1.89
    MgSO4 prophylaxis in admitted patients (%) Not available 6/54 (11.1%)
    MgSO4 treatment (%) 201/216 (93.1%) 82/82 (100%) 1.08 1.04 1.12
    Benzodiazepines (%) 111/216 (51.4%) 24/80 (30.0%) 0.41 0.23 0.70
    Benzodiazepines prior to MgSO4 (%)
    All women Not available 21/80 (26.3%)
    If admitted prior to E 9/54 (16.7%)
    Stabilization before delivery
    Patient was stable Not available 15/56 (21.4%)
    No attempt was made 14/56 (25.0%)
    Need not recognized 11/14 (78.6%)
    Attempt was made 29/56 (51.8%)
    Successful 26/29 (89.7%)
    • N, number available for analysis; E, eclampsia; RR, relative risk; CI, confidence interval; Q1, first interquartile; Q3, third interquartile; BP, blood pressure; MgSO4, magnesium sulfate.

    The use of magnesium sulfate treatment was high and increased from 93% to 100% (RR 1.08, 95% CI 1.04-1.12). In nine (16.7%) women who were admitted prior to their first eclamptic fit, benzodiazepines were prescribed as the initial treatment following the onset of seizures before magnesium sulfate was started. In 14 (25.0%) women with eclampsia prior to delivery, no attempt was made to stabilize the condition of the patient (eg, starting MgSO4 and treating severe hypertension) before birth (Table 2).

    There were no differences in induction of labor or cesarean delivery in women who had eclampsia prior to, during or after delivery. Gestational age at birth and interval between first eclamptic fit and birth showed no difference over time. In women with a diagnosis of HDP, 26 of 42 (61.9%) were beyond 37 weeks of gestational age (Table 3).

    Table 3. Characteristics of delivery
    LEMMoN (2004-2006), N = 216 NethOSS (2013-2016), N = 88 RR 95% CI P value
    Delivery
    GA at delivery [Q1, Q3] 264 [241-279] 262 [239-275] 0.13
    GA at delivery >37 wk 126/211 (59.7%) 42/78 (53.8%) 0.90 0.74 1.14
    Induced to prevent E 33/82 (40.2%)
    Of whom ≥37 wk 22/33 (66.7%)
    Women with eclampsia beyond 37 wk gestational age, among women with HDP prior to eclampsia (%) 73/127 (57.5%) 26/42 (61.9%) 1.20 0.59 2.46
    Pregnancy ended by (%)
    Labor induction 81/215 (37.7%) 31/82 (37.8%) 1.00 0.60 1.70
    CS (without labor) 70/215 (32.6%) 33/82 (40.2%) 1.40 0.83 2.36
    Pregnancy ended in antepartum cases by (%)
    Labor induction 21/84 (25.0%) 7/37 (18.9%) 0.70 0.27 1.83
    CS (without labor) 58/84 (69.0%) 28/37 (75.7%) 1.40 0.58 3.37
    Anesthesia during CS (%)
    Spinal anesthesia Not available 18 (45.0%)
    General anesthesia 18 (45.0%)
    Conversion spinal → general anesthesia 2 (5.0%)
    Epidural anesthesia 1 (2.5%)
    Fit – Delivery interval [min.; Q1, Q3]
    First fit antepartum OR intrapartum 170 [60-558] 199 [39-378] 0.14
    First fit antepartum 450 [175-2493] 315 [190-728] 0.07
    First fit intrapartum 69 [30-154] 39 [19-107] 0.34
    First fit postpartum 315 [60-846] 234 [31-1044] 0.67
    • N, number available for analysis; E, eclampsia; RR, relative risk; CI, confidence interval; Q1, first interquartile; Q3, third interquartile; GA, gestational age; CS, cesarean section; HDP, hypertensive disorders of pregnancy.

    Outcome of women was comparable with regard to proportions with placental abruption, major obstetric hemorrhage (defined as >1000 mL), acute respiratory distress syndrome, cerebrovascular accidents and intensive care unit admission (Table 4). There were no cases of pulmonary embolism in the current registration compared with three in the previous study. There was one maternal death in the 3-year NethOSS registration (2013-2016) vs three in the 2-year LEMMoN registration (2004-2006; case fatality rate 1.1% vs 1.4%, respectively). One maternal death in NethOSS had developed severe hypertension after spontaneous vaginal delivery at term, followed shortly by recurrent eclampsia. Computer tomography showed extensive intracerebral hemorrhage in the right hemisphere due to preexisting arteriovenous malformations, without possible therapeutic options. There was one case of intrauterine death following termination of pregnancy for severe HDP at 24 weeks’ gestational age in NethOSS. There were no cases of neonatal mortality reported to NethOSS compared with 11 cases in the LEMMoN registration (Table 4).

    Table 4. Outcome of women with eclampsia
    LEMMoN (2004-2006), N = 216 NethOSS (2013-2016), N = 88 RR 95% CI
    Placental abruption (%) 5/216 (2.3%) 1/82 (1.2%) 0.53 0.06-4.44
    MOH (>1000 ml; %) 21/216 (9.7%) 9/82 (11.0%) 1.15 0.50-2.62
    ARDS (%) 3/216 (1.4%) 1/82 (1.2%) 0.88 0.09-8.32
    Pulmonary embolism (%) 3/216 (1.4%) 0/82 (0.0%)
    ICU admission (%) 89/216 (41.2%) 25/82 (30.5%) 0.63 0.36-1.08
    Cerebral vascular incident (%) 7 1.9 per 100 000 3 0.68 per 100 000 0.36 0.09-1.40
    Maternal deaths (CFR) 3 (1.4%) 0.81 per 100 000 1 (1.1%) 0.19 per 100 000 0.88 0.09-8.55
    Intrauterine death (CFR) 7 (3.2%) 0.02 per 1000 1 (1.1%) 0.002 per 1000 0.08 0.01-0.60
    Neonatal death (CFR) 4 (1.9%) 0.01 per 1000
    • N, number available for analysis; RR, relative risk; CI, confidence interval; MOH, major obstetric hemorrhage; ARDS, acute respiratory distress syndrome; ICU, intensive care unit; CFR, case fatality rate.

    4 DISCUSSION

    There has been a considerable reduction in the incidence of eclampsia over 10 years in the Netherlands. Both intrauterine and neonatal mortality in association with eclampsia also decreased. The decrease of eclampsia is similar to a reduction seen in the UK.2 Our findings demonstrate that management strategies advocated in recent years, such as rapid administration of antihypertensive medication and magnesium sulfate, and timely birth, are likely to have had a positive impact at the population level in the Netherlands. There was a trend toward less severe maternal morbidity due to cerebrovascular accidents, likely resulting from increased awareness and improved treatment of severe hypertension.

    There was only one woman with a multiple pregnancy as well as a trend toward lower maternal age in the recent registration. Though the rate of multiple pregnancies has decreased in the time period between both studies from 18.6 to 15.9 per 1000 births, this cannot account for the reduction of eclampsia. This reduction may in fact, like lower maternal age, result from increased awareness of hypertensive complications.10 Better laboratory parameters also reflect more pro-active management. A comparable proportion of women were admitted prior to eclampsia for HDP, contradicting the assumption that in a setting of lower incidence the cases that are “easier to predict” would have been identified. This is supported by the presence of at least one prodromal symptom prior to eclampsia in almost all cases in NethOSS. Since the LEMMoN study, the overall percentage of home deliveries decreased from 32% to 13%, while the percentages of women with eclampsia at home increased.11 Whether these cases are unexpected events in previously healthy women or a consequence of insufficient risk assessment is unclear and should be determined in future case-by-case audits.

    Comparing both time frames, we found similar percentages of women with eclampsia meeting the criteria for severe hypertension, of which a higher proportion had received antihypertensive treatment in the last time period (Table S1). The 3rd quartile (Q3) of 60 minutes between the first measurement of severe hypertension and subsequent measurement is indicative of the absence of clear algorithms for triage and response to such hypertensive episodes. More than a third of women were started on (additional) antihypertensive medication only after a second reading of severe hypertension, whereas almost half of women developed eclampsia after the first measurement of severe hypertension, before blood pressure was normalized. In these women there was considerable delay in reducing blood pressure, illustrating the need for specific algorithms and goal-directed therapy, for instance by using Preeclampsia Toolkits.12-14 Dutch national guidelines still include repeated measurements following a first measurement of severe hypertension, and include no target blood pressure levels or time intervals. Goal-directed therapy in blood pressure management has previously been shown to reduce mortality in congenital heart surgery and could serve as an example of a plan-do-check-act approach in women with severe hypertension.15 In all but one woman who received benzodiazepines, these appeared to have been administered while preparing magnesium sulfate, which was then started after a relatively short interval. The percentage of women with magnesium sulfate prophylaxis remained low in the NethOSS while dosing recommendation stayed identical in the last decade. The increase in antihypertensive treatment could be suggestive of more active management for all women with HDP, including a more liberal use of magnesium sulfate prophylaxis and subsequently less women with eclampsia in the NethOSS. Still, the 70% of women who were diagnosed and admitted for HDP prior to their first eclampsia, implies that better and continuous risk stratification during admission, including timely administration of magnesium sulfate prophylaxis, could further decrease the incidence of eclampsia. The opportunities of better protocol adherence are supported by 25% of women in whom no attempt was made for stabilization before proceeding with delivery.

    Strength of this study is the prospective, nationwide design and participation of all Dutch hospitals with a maternity unit. Underreporting was thought to be minimized by the use of the “nothing to report” option in the monthly mailing and repetitive inquiries if no report was received. Furthermore, availability of complete case files copies enabled us to perform detailed analysis of management strategies. Despite this, our study was limited by the fact that we did not have the option to cross-reference collected cases with a nationwide routine registration system. Furthermore, not all variables were available in the previous registration of eclampsia, limiting comparison of timing of various treatment options. Since neither study included control data regarding women with HDP who did not develop eclampsia, it is impossible to determine compliance to national guidelines in women without eclampsia or quantify the effects of timely intervention. This also hindered a stratified analysis to determine precisely which clinical management strategies and to what extent, have resulted in the decreased incidence.

    Since the publication of the HYPITAT trial in 2009 there has been a slow uptake of induction of labor at varying levels throughout the country in women with HDP beyond 37 weeks of gestational age.16, 17 This analysis, however, does not demonstrate an altered distribution of gestational age in cases of eclampsia in recent years compared with the “pre-HYPITAT” LEMMoN registration, as presumed by Van der Tuuk et al.18 Although there was a decrease in overall perinatal mortality in the Netherlands, this could never explain the much larger reduction of perinatal mortality in the subgroup of women with eclampsia.19 Results from the recent Control of Hypertension in Pregnancy Study (CHIPS) have alleviated concerns on adverse neonatal outcomes in strict hypertension control,20 although a recent Cochrane meta-analysis showed an increased risk of infant respiratory distress syndrome in women with near-term induction of labor for HDP.21

    Our data show the added value of a specific data collection system over routine data monitoring.22-25 Such a system may feed into a Plan-Do-Check-Act cycle at a (inter)national level as well as provide an instrument for rapid response to emerging (obstetric) health issues. To enable comparisons, standardized disease definitions are needed, such as the definitions recently developed by the International Network of Obstetric Survey Systems (INOSS) and included as part of the Core Outcomes in Women's and Newborn health (CROWN) initiative.26, 27 Since our registration was started prior to the development of this INOSS consensus definition we purposefully used a broader definition to enable future comparisons.

    5 CONCLUSION

    This study reports the first outcomes of the newly established NethOSS network for sustainable registration and analysis of maternal morbidity and mortality in the Netherlands. It demonstrated a considerable reduction in the incidence of eclampsia and implies the potential success of management strategies suggested by emerging evidence in recent years. At the same time, there is a possibility for further reduction in incidence by introducing specific algorithms for a goal-directed management approach, focusing on recommendations with respect to timing of subsequent blood pressure reading and interval in which to start magnesium sulfate prophylaxis and achieve stabilization

    ACKNOWLEDGMENTS

    The authors thank all 88 hospitals and their local coordinators who developed their own strategy for case ascertainment and data collection.

      CONFLICT OF INTEREST

      The authors have nothing to disclose.