ORIGINAL ARTICLE Questionnaire-based study of cerebrovascular complications during pregnancy in Aichi Prefecture, Japan

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1 Hypertension Research Eclampsia and stroke In Pregnancy during pregnancy 40 ORIGINAL ARTICLE Questionnaire-based study of cerebrovascular complications during pregnancy in Aichi Prefecture, Japan Yasumasa Ohno 1, Kaoru Ishikawa 2, Shigeaki Kaseki 3, Fumitaka Kikkawa 4 Reprint request to: Yasumasa Ohno, M.D., Ph.D., Ohno Ladies Clinic, 10 Takahata, Inari-cho, Iwakuracity, Aichi, , Japan. yasumasa@ohno-clinic.jp Key words: eclampsia, etiological research, pregnancy, pregnancy induced hypertension, stroke Received: December 7, 2012 Revised: December 29, 2012 Accepted: January 13, Ohno Ladies Clinic, 2 Department of Regeneration of Medicine in Kuwana District, Suzuka University of Medical Science, 3 Kaseki Hospital, 4 Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine Aim: Our aim was to establish a therapeutic strategy for eclampsia and stroke during pregnancy. Methods: We performed a questionnaire-based study of eclampsia and stroke during pregnancy from 2005 to 2009 that targeted all obstetric institutions in Aichi Prefecture. The survey inquired about characteristics of eclampsia and stroke during pregnancy, management of hypertension during labor, and the current situation surrounding the maternal transport system as well as that for collaboration with neurosurgeons. Results: Our survey revealed that 66% of deliveries, 40% of eclampsia episodes, and 31% of stroke incidents occurred at primary medical institutions. With the exception of strokes, most cases were diagnosed by brain magnetic resonance imaging (MRI) and/or computed tomography (CT) at intensive medical institutions. Most medical institutions measured blood pressure during labor. However, other management strategies, including those involving the use of hypotensors, varied by institution. Conclusions: The present study is the first long-term etiological research project to address eclampsia and pregnancyassociated stroke in Japan. From our survey data, we were able to obtain detailed information and assess several issues regarding the maternal transport system, blood pressure management during labor, and collaboration with neurosurgeons. Introduction Eclampsia and stroke during pregnancy are major causes of maternal and neonatal death in many countries. 1 3) Despite the ubiquity of these conditions and their public health impacts, neither their etiologies nor therapeutic strategies for their treatment have been established. The lack of etiological information about eclampsia and stroke makes it difficult to propose appropriate management strategies for them. Close collaboration with neurosurgeons is necessary to prevent stroke; however, some medical institutions fail to establish good relationships with neurosurgeons, which can affect the prognoses for pregnant women who suffer strokes. In addition, some pregnant women develop hypertension after labor onset; unfortunately, hypertension is difficult to diagnose during early labor, and often overlooked, sometimes resulting in eclampsia and/or stroke. We performed a questionnaire-based study of eclampsia and stroke during pregnancy involving all obstetric institutions in Aichi Prefecture. Survey data were thereby named AICHI DATA. Aichi Prefecture accounts for 7% of the Japanese population as well as 7% of annual births in Japan. Therefore, AICHI DATA could provide useful etiological information regarding eclampsia and stroke during pregnancy in Japanese mothers. Our study results may also contribute to the development of therapeutic strategies for eclampsia and stroke during pregnancy. Materials and methods We performed a questionnaire-based study of eclampsia 40 Hypertens Res Pregnancy 2013; 1: The Authors Hypertension Research in Pregnancy 2013 Japan Society for the Study of Hypertension in Pregnancy

2 Y. Ohno et al. and stroke during pregnancy that targeted all obstetric institutions in Aichi Prefecture from at 2007 (166 institutions) and 2010 (155 institutions). From the time we began the survey to the end, the number of medical institutions decreased from 166 to 155. All institutions responded to our questionnaire, which was designed to obtain detailed information about cases of eclampsia and stroke during pregnancy. Financial support was provided by the Perinatal Care Association of the Aichi Prefectural Government. Results Characteristics of eclampsia and stroke Between 2005 and 2009 in Aichi Prefecture, 322,599 deliveries occurred. Of these, 126 cases of eclampsia (0.04%) and 26 cases of stroke (0.008%) were reported. Forty percent of the eclampsia cases and 31% of strokes occurred at primary medical institutions, while 19% of strokes occurred at home. Most eclampsia cases (92.8%) and all strokes were managed at intensive medical Table 1. Eclampsia and stroke during pregnancy in Aichi Prefecture from 2005 to 2009 Total Intensive institutions Primary institutions Home Institutions* Delivery 322,599 (100%) 110,997 ( 34.4%) 211,602 (65.6%) Eclampsia (onset) 126 (100%) 75 ( 59.6%) 50 (39.7%) 1 ( 0.7%) Eclampsia (managed) 126 (100%) 117 ( 92.8%) 9 ( 7.2%) Stroke (onset) 26 (100%) 13 ( 50.0%) 8 (30.8%) 5 (19.2%) Stroke (managed) 26 (100%) 26 (100.0%) 0 * The number of all institutions were decreasing from 166 in 2007 to 155 in 2010, intensive from 52 to 50, primary from 114 to 105. Table 2. Characteristics of annual eclampsia in Aichi Prefecture Total Delivery 322,599 63,512 67,311 62,431 65,007 64,338 Eclampsia Onset antepartum 21 (16.7%) during labor 50 (39.7%) postpartum 55 (43.6%) Neuroimaging CT MRI CT + MRI no imaging Therapy anticonvulsants* MgSO 4 * hydralazine* Ca blockers* glycerine* PGE 1 * Prognosis further episodes ( ) further episodes ( + ) death * data obtained between 2007 and 2009 Hypertens Res Pregnancy 2013; 1:

3 Eclampsia and stroke during pregnancy institutions. Forty percent of pregnant women who suffered strokes at home died (Table 1). The majority of eclampsia episodes occurred during labor (39.7%) or postpartum (43.6%). In 87% of eclampsia cases, brain computed tomography (CT) and/ or magnetic resonance imaging (MRI) was performed for Table 3. Characteristics of annual stroke during pregnancy Total No. of deliveries 322,599 63,512 67,311 62,431 65,007 64,338 Stroke Onset antepartum 9 (34.6%) during labor 3 (11.5%) postpartum 14 (53.9%) CH SAH MD CI CVT PRES others Prognosis further episodes ( ) further episodes ( + ) death CH: cerebral hemorrhaging, SAH: subarachnoid hemorrhaging, MD: moyamoya disease, CI: cerebral infarction, CVT: cerebral venous thrombosis, PRES: posterior reversible encephalopathy syndrome Table 4. Classification with stroke during pregnancy Total CH SAH MD CI CVT PRES Other Onset institution intensive primary home Onset antepartum during labor postpartum Therapy conservative surgery Prognosis further episodes ( ) further episodes ( + ) death CH: cerebral hemorrhaging, SAH: subarachnoid hemorrhaging, MD: moyamoya disease, CI: cerebral infarction, CVT: cerebral venous thrombosis, PRES: posterior reversible encephalopathy syndrome 42 Hypertens Res Pregnancy 2013; 1: 40 45

4 Y. Ohno et al. diagnosis. Thus, neuroimaging techniques can reveal the pathophysiology of patients with abnormal neurological symptoms and can also detect and localize cerebral edema, hemorrhaging, and infarction. All patients with eclampsia showed good prognoses except for one patient who suffered a second episode of eclampsia (Table 2). The majority of strokes occurred either antepartum (34.6%) or postpartum (53.9%). Surgery was performed in 4 of 26 cases. Six of the stroke patients died (2 cerebral hemorrhages, 3 subarachnoid hemorrhages, and 1 cerebral venous thrombosis), while 6 patients suffered further strokes (Tables 3 and 4). Management of eclampsia and stroke With regard to blood pressure (BP) measurement during labor, 46.5% of institutions measured BP for all patients, 31.6% only measured BP for patients who presented with BP values greater than 140/90 mmhg on admission, and 14.2% allowed supporting medical staff to decide when to take BP measurements. Regarding the criteria for reporting BP data to doctors, 9.7% of institutions reported all data, 45.2% only reported BP values greater than 140/90 mmhg, and 22.6% left reporting decisions to the supporting medical staff. These findings revealed that the BP measurement strategies during labor were left in the hands of the supporting medical staff in roughly 20% of Table 5. Blood pressure measurement during labor Total Intensive Primary institutions institutions Measurement all cases 72 (46.5%) 30 (60.0%) 42 (40.0%) BP > 140/90 mmhg at admission 49 (31.6%) 8 (16.0%) 41 (39.0%) decided by supporting medical staff 22 (14.2%) 8 (16.0%) 14 (13.3%) none 4 ( 2.6%) 1 ( 2.0%) 3 (2.9%) Report to doctor all cases 15 ( 9.7%) 0 15 (14.3%) BP > 140/ 90 mmhg 70 (45.2%) 21 (42.0%) 49 (46.7%) BP > 150/100 mmhg 21 (13.5%) 6 (12.0%) 15 (14.3%) BP > 160/110 mmhg 4 ( 2.6%) 2 ( 4.0%) 2 (1.9%) decided by supporting medical staff 35 (22.6%) 15 (30.0%) 20 (19.0%) Table 6. Therapy for hypertension during labor Total Intensive Primary institutions institutions Cut-off point for hypertensive therapy 140/ 90 mmhg 9 (5.8%) 1 ( 2.0%) 8 ( 7.6%) 150/100 mmhg 25 (16.1%) 5 (10.0%) 20 (19.0%) 160/110 mmhg 58 (37.4%) 21 (42.0%) 37 (35.2%) 180/ mmhg 47 (30.3%) 18 (36.0%) 29 (27.6%) Antihypertensive agent methyldopa hydralazine nifedipine nicardipine MgSO 4 usage cases without convulsions 29 (18.7%) 15 (30.0%) 14 (13.3%) cases with convulsions 25 (16.1%) 12 (24.0%) 13 (12.4%) none 92 (59.4%) 21 (42.0%) 71 (67.6%) Hypertens Res Pregnancy 2013; 1:

5 Eclampsia and stroke during pregnancy Table 7. Action (transport or collaboration with neurosurgeons) in response to convulsions during labor Total Intensive Primary institutions institutions Immediately 76 (49.0%) 16 (32.0%) 60 (57.1%) When repeated convulsions or neurological abnormalities occurred 77 (49.7%) 35 (70.0%) 42 (40.0%) Continue managing patient 2 ( 1.3%) 1 ( 2.0%) 1 ( 1.0%) institutions (Table 5). In antihypertensive therapy for hypertension during labor, 37.4% of institutions started using hypotensors when patient BP reached 160/110 mmhg, and 30.3% started using them when it reached 180 mmhg of systolic BP. Nicardipine and hydralazine were the most frequently used hypotensors. In addition, 18.7% of institutions used MgSO 4 in hypertensive patients without convulsions, 16.1% used it after convulsions occurred, and 59.4% did not use it at all (Table 6). Present state of the transport system for pregnant women with eclampsia and stroke Our survey revealed that 32.0% of intensive medical institutions initiated a collaborative management strategy with a neurosurgeon at the first convulsion, while 70.0% of them started only after repeated convulsions. In addition, 57.1% of primary medical institutions transported eclamptic patients at the first convulsion, while 40.0% of them transported the patient only after repeated convulsions (Table 7). Discussion The present study has been named AICHI DATA, as it collected detailed information pertaining to 322,599 deliveries in Aichi Prefecture. Of these, 126 cases of eclampsia (0.04%) and 26 cases of stroke (0.008%) were reported, corresponding to similar rates reported in other countries. 1 4) The lack of sufficient etiological data and the absence of a consensus regarding optimal treatment for eclampsia and stroke make it difficult to establish therapeutic strategies for these conditions. AICHI DATA is the first long-term etiological study of eclampsia and pregnancy-associated stroke in Japan. We obtained useful information from these data, which pertained to patients treated at both primary and intensive medical institutions. Forty percent of eclampsia cases and 31% of strokes occurred at primary medical institutions, which highlights the importance of not only appropriate diagnoses at primary medical institutions, but the establishment of efficient inter-institution transport systems as well. The majority of eclampsia episodes occurred during labor or postpartum, and the majority of strokes occurred antepartum or postpartum. This indicates that the possibility of eclampsia and/or stroke is relevant during all stages of pregnancy. Management of BP levels during labor was left up to the supporting medical staff at roughly 20% of the institutions, even though hypertension during labor can result in eclampsia or stroke. If a patient shows signs of hypertension, it is critical for the supporting medical staff to report the patient s BP to a doctor immediately, so that the necessary medical interventions can be discussed. Thirty-seven percent of institutions started using hypotensors when patient BP reached 160/110 mmhg, and 30% started using them when BP reached 180 mmhg of systolic BP. Nicardipine and hydralazine were the most frequently used hypotensors. If patient BP is greater than 160/110 mmhg, MgSO 4 can be used to decrease the risk of convulsions and reduce their BP to mmhg/ mmhg. The Joint National Committee in America and European Society of Hypertension proposed to reduce BP in patients with BP greater than 180/120 mmhg. 5 8) Methyldopa, hydralazine, nifedipine, labetalol, and nicardipine can be used as antihypertensive drugs during labor. Among them, nicardipine is likely the most common. Hydralazine is not suitable for patients with active cerebral hemorrhaging. Brain CT is an optimal method for stroke detection. When a stroke is detected, collaborative treatment with a neurosurgeon should be started as soon as possible. In the present study, 41% of primary medical institutions only transported eclamptic patients after repeated convulsions. If a stroke is suspected at a primary medical institution, rapid maternal transport to an intensive medical institution is necessary. Discrimination between eclampsia and stroke is difficult, but strokes are often characterized by the presence of facial or arm muscle 9, 10) weakness, or a speech deficit. This study provided detailed information and highlighted several issues, including the poor current state of maternal transport between primary and intensive 44 Hypertens Res Pregnancy 2013; 1: 40 45

6 Y. Ohno et al. medical institutions, the necessity of educating the staff of primary medical institutions about stroke, the lack of established criteria for BP reporting during labor, and the importance of collaborating with neurosurgeons. AICHI DATA provides important Japanese etiological data and might be used to revise the associated guidelines. Acknowledgements This work was supported in part by the Perinatal Care Association of the Aichi Prefectural Government. Conflict of interest The authors have no conflicts of interest to report. References 1. Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ. 1994; 309: Kullberg G, Lindeberg S, Hanson U. Eclampsia in Sweden. Hypertens Pregnancy. 2002; 21: Sidorov EV, Feng W, Caplan LR. Stroke in pregnant and postpartum women. Expert Rev Cardiovasc Ther. 2011; 9: Knight M. Eclamlpsia in the United Kingdom BJOG. 2007; 114: Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003; 42: European Society of Hypertension-European Society of Cardiology Guidelines Committee European Society of Hypertension- European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003; 21: Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet. 2000; 356: The Joint National Committee. The fifth report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure (JNC V). Arch Intern Med. 1993; 153: Kothari RU, Pancioli A, Liu T, Brott T, Broderick J. Cincinnati prehospital stroke scale: reproducibility and validity. Ann Emerg Med. 1999; 33: Hurwitz AS, Brice JH, Overby BA, Evenson KR. Directed use of the Cincinnati prehospital stroke scale by laypersons. Prehosp Emerg Care. 2005; 9: Hypertens Res Pregnancy 2013; 1: