2015 年 3 巻 1 号 p. 32-37
Aim: In order to establish more effective therapeutic strategies and for preventing maternal death (MD), this study investigated the causes of MD in Aichi Prefecture, Japan.
Methods: Questionnaire surveys were sent to all obstetric institutions in Aichi Prefecture to collect information on all cases of MD occurring between 2006 and 2012. Follow-up questionnaires were sent to institutions in which cases of MD had been reported.
Results: We found a total of 42 cases of MD. The annual maternal mortality rate (MMR) in Aichi Prefecture, which has been decreasing since 2010 was higher than that of all of Japan.. Among the 42 cases of MD, causes included the following: stroke (11 cases); severe obstetric hemorrhage (8 cases); and obstetric pulmonary embolism (PE; 10 cases). In addition, severe hypertension was observed in 5 of the 11 stroke patients. Amniotic fluid embolism was present in 5 of the 8 severe obstetric hemorrhage cases and in 6 of the 10 obstetric PE cases.
Conclusions: The MMR was higher in Aichi Prefecture than that in Japan. The leading causes of maternal death in Aichi Prefecture were stroke, severe obstetric hemorrhage and PE.
In 2013, an estimated 293,000 women worldwide died as a result of pregnancy-related conditions.1) Maternal death is defined as death while pregnant or within 42 days of a terminated pregnancy, irrespective of its duration or site, from any non-accidental or non-incidental cause related to or aggravated by the pregnancy or its management.2) The maternal mortality rate (MMR) refers to the number of maternal deaths per 100,000 live births during a given period of time. In 2013, the global MMR was 209/100,000, which reflects a reduction of 1.3% annually since 1990,1) and the MMRs for developed and developing countries were approximately 12/100,000 and 233/100,000, respectively. In Japan, 42 cases of maternal death were reported in 2012, resulting in an MMR of 4/100,000.3) Therefore, Japan currently has one of the lowest reported MMRs in the world.
Maternal death is commonly classified as resulting from either direct or indirect causes. Direct causes consist of obstetric complications from interventions, omissions, or incorrect treatments during pregnancy, or any chain of events from pregnancy, labor, delivery, or postpartum conditions that lead to death. Indirect causes consist of preexisting diseases such as diabetes, cardiac disease, malaria, tuberculosis, or human immunodeficiency virus (HIV),4) or unrelated diseases that develop during pregnancy. In developed countries, direct causes such as hemorrhage, hypertensive disorders, and embolism account for about 75% of all maternal deaths;5) the remaining 25% are due to indirect causes.5) Recently, stroke, postpartum hemorrhage (PPH) and obstetric pulmonary embolism (PE) have been reported as the leading overall causes, either direct or indirect, of maternal death are in developed countries. However, stroke is generally classified as an indirect cause, while PPH and PE are classified as direct causes. Therefore, to help avoid inconsistencies, maternal deaths should have a simpler structure.
In the present study, we investigated the incidence and causes of maternal death in a prefecture in Japan with the aim of finding a more effective therapeutic strategy.
We conducted a questionnaire-based study on maternal death in Aichi Prefecture, Japan. We sent questionnaire surveys to all prefectural obstetric institutions in 2009, 2010, and 2014 to collect information on cases of maternal death occurring between 2006 and 2012. Questionnaires were re-sent to institutions that did not reply to the first mailing, and follow-up questionnaires (Table 1) were sent to institutions that reported cases of maternal death.
| Basic maternal characteristics Age, parity (primiparous or multiparous), BMI at non-pregnancy, body weight at onset, singleton or multiple pregnancy Details of MD Onset: during pregnancy (gestational weeks), during labor, postpartum within 3 or more than 4 days Symptoms: headache, dyspnea, nausea and vomiting, syncope, respiratory/cardiac arrest Place: home, primary or secondary institution, maternal transport Obstetric disorders Preeclampsia/eclampsia, gestational hypertension, HELLP syndrome, pulmonary edema, placental abruption Severe bleeding (atonic bleeding, DIC, AFE, uterine rupture, ectopic pregnancy), pre-term labor Complications Hypertension, antiphospholipid antibody syndrome, renal failure, sepsis, shock, others Delivery information Gestational weeks, vaginal (spontaneous, vacuum, forceps) or cesarean section, birth weight Diagnosis Stroke (hemorrhage, infarction), PPH, PE, others (suicide, accident, cancer, etc.) Autopsy Findings by autopsy or autopsy imaging |
AFE, amniotic fluid embolism; BMI, body mass index; DIC, disseminated intravascular coagulation; HELLP, hemolysis, elevated liver enzymes, and low platelets; MD, maternal death; PE, pulmonary embolism; PPH, postpartum hemorrhage.
All reported causes of maternal death, which consisted of stroke, severe obstetric hemorrhage (associated with atonic bleeding, disseminated intravascular coagulation [DIC] in amniotic fluid embolism [AFE], placental abruption and uterine rupture), PE, ectopic pregnancy, sepsis, other diseases, suicide, cancer and accidents, were classified according to the existing guidelines. Japanese guidelines for the prevention of venous thrombosis and severe obstetric hemorrhage were published in 20046) and 2010,7) respectively.
Statistical analysisAll data were evaluated using the unpaired t-test using Excel Toukei 2012 (SSRI Co., Ltd., Tokyo, Japan). The level of significance was set at P<0.05.
Among the questionnaires sent, the response rate was 93%. Between 2006 and 2012, the number of institutions in operation ranged from 143 to 163. There were 108, 120 and 99 primary institutions, 25, 20 and 15 in secondary institutions and 24, 23 and 29 in tertiary care centers in 2008, 2009, and 2013, respectively (Table 2).
| Year | 2007 | 2008 | 2009 | 2010 | 2011 | 2012 | 2013 |
|---|---|---|---|---|---|---|---|
| Number of institutions | |||||||
| Primary | 108 | 120 | 99 | ||||
| Secondary | 25 | 20 | 15 | ||||
| Tertiary | 24 | 23 | 29 | ||||
| Total | 157 | 157 | 163 | 143 | 143 | 144 | 143 |
| Questionnaire response | |||||||
| MD (+) | 10 | 13 | 12 | 3 | 7 | 9 | 10 |
| MD (−) | 140 | 137 | 119 | 133 | 129 | 128 | 128 |
| No reply | 7 | 7 | 32 | 7 | 7 | 5 | 5 |
MD, maternal death.
Among these institutions, a total of 484,418 live births were recorded and among these births, 42 cases of maternal death were reported. The number of annual maternal deaths reported ranged from 3 to 13, with a rate between 2 and 9 per year (Table 2).
A total of 22 (52%) cases had symptom onset in primary or secondary institutions and were subsequently transferred to a tertiary care center (Table 3). During the period, covered in this study, the annual MMR in Aichi Prefecture, which has been steadily decreasing since 2010 (12.3±0.8 from 2007 to 2009 vs. 6.9±0.9 from 2011 to 2013, P=0.0016), was 8.7±3.8/100,000 (Table 3), a value more than twice that (4.0±0.6/100,000) of all of Japan during the same period (P=0.0089) (Table 4).
| Year | 2007 | 2008 | 2009 | 2010 | 2011 | 2012 | 2013 | Average | Total |
|---|---|---|---|---|---|---|---|---|---|
| Aichi Prefecture | |||||||||
| Live births | 70,218 | 71,029 | 69,768 | 69,872 | 68,793 | 67,913 | 66,825 | 69,202±1,450 | 484,418 |
| MDs | 8 | 9 | 9 | 2 | 4 | 5 | 5 | 6±2.7 | 42 |
| MMR | 11.4 | 12.7 | 12.9 | 2.9 | 5.8 | 7.4 | 7.5 | 8.7±3.8 | |
| Transportation to the tertiary care center | 1 | 3 | 4 | 2 | 4 | 4 | 3 | 3±1.2 | 21 |
Data are expressed as mean±SD. MMR refers to the number of MDs per 100,000 live births.
MD, maternal death; MMR, maternal mortality rate.
| Year | 2007 | 2008 | 2009 | 2010 | 2011 | 2012 | 2013 | Average | Total |
|---|---|---|---|---|---|---|---|---|---|
| Maternal and Child Health Statistics of Japan | |||||||||
| MDs | 35 | 39 | 53 | 45 | 41 | 42 | 42.5±6.1 | 255 | |
| MMR | 3.2 | 3.6 | 5.0 | 4.2 | 3.9 | 4.0 | 4.0±0.6 |
Data are expressed as mean±SD. MMR refers to the number of MDs per 100,000 live births.
MD, maternal death; MMR, maternal mortality rate.
As shown in Table 5, the leading causes of maternal death in this study were as follows: stroke (11 cases); severe obstetric hemorrhage (associated with atonic bleeding, DIC in AFE, placental abruption and uterine rupture) (8 cases); PE (10 cases); and ectopic pregnancy (3 cases).
| Year | 2007 | 2008 | 2009 | 2010 | 2011 | 2012 | 2013 | Total |
|---|---|---|---|---|---|---|---|---|
| Stroke | 0 | 2 | 3 (2*) | 1 | 1 | 1 (1*) | 3 (2*) | 11 (5*) |
| Severe obstetric hemorrhage | 1 | 1 (1†) | 4 (3†) | 0 | 0 | 2 (1†) | 0 | 8 (5†) |
| Obstetric PE | 2 (1†) | 2 (1†) | 1 (1*) | 1 (1†) | 2 (1†) | 1 (1†) | 1 (1†) | 10 (6†) (1*) |
| Ectopic pregnancy | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 3 |
| Sepsis | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Other disease | 1 | 0 | 0 | 0 | 1 | 0 | 1 (1*) | 3 |
| Suicide | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 2 |
| Cancer | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Accident | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 3 |
| Total | 8 | 9 | 9 | 2 | 4 | 5 | 5 | 42 |
Severe obstetric hemorrhage includes atonic bleeding, precedence of disseminated intravascular coagulation (DIC) in amniotic fluid embolism (AFE), placental abruption, and uterine rupture. For other disease, causes were unknown, except for a case of intestinal ischemia reported in 2007 and a case of primary pulmonary hypertension in 2010.
* Number of patients with hypertension, †number of patients with AFE. PE, pulmonary embolism.
Stroke occurred during the antepartum period in 2 cases, intrapartum period in 2 and postpartum period in 7 (2 cases immediately after delivery, 2 within a few days delivery and 3 within a few weeks delivery). The causes of stroke were subarachnoid hemorrhage (5 cases), brain hemorrhage (1 case), brain stem hemorrhage (1 case), Moyamoya disease (1 case) and eclampsia or hypertensive encephalopathy (3 cases). Severe hypertension was noted in 5 of the 11 stroke patients.
One of cases complicated by stroke involved a 35-year-old multiparous woman. Although no signs of hypertension had been detected on home blood pressure measuring (HBPM), hypertension (≥140/90 mmHg) was observed in clinic outpatient at 20 weeks of gestation. At 40 weeks of gestation, HBPM showed elevated values and severe hypertension (≥160/110 mmHg) was observed at the outpatient clinic. She was subsequently admitted hospital for termination of pregnancy. She chose to orally have prostaglandin E2 tablet for induction of labor. Cervical os was 6 cm open without complaining about symptoms, such as headache and vomiting. Blood pressure (BP) fluctuated between 140–180 mmHg in systolic and 80–100 mmHg in diastolic. Her systolic BP then sharply increased to more than 180 mmHg in two occurrences convulsion syncope. Her cervical os was then fully open, and her delivery was terminated by vacuum extraction. Although she was administered nicardipine 1 mg i.v. immediately after delivery, BP fluctuated. She was transferred to a tertiary care center, where head CT scan revealed extensive brain hemorrhage. She died 7 days after delivery. The case highlights the need for appropriate management of hypertension during the ante- and intrapartum periods in primary institution.
AFE was present in 5 of the severe 8 obstetric hemorrhage cases and in 6 of the 10 obstetric PE cases. The remaining causes were as follows: sepsis (1 case), other disease (3 cases), suicide (2 cases), cancer (1 case) and accidents (2 anesthesia-related accidents and 1 traffic accident).
Aichi Prefecture comprises 6% of the total Japanese population and 7% of the annual number of live births in Japan. The questionnaire results allowed us to obtain significant findings on maternal death that are expected to aid its prevention and the establishment of more effective therapeutic strategies.
Although the MMR in Aichi Prefecture has been steadily decreasing since 2010, it was significantly higher from 2007 to 2013 than from 1996 to 1998 (6.8 in 1996, 5.5 in 1997 and 4.0 in 1998; mean during the period, 5.4±1.4). Furthermore, during the period covered in this study, the annual MMR in Aichi prefecture (8.7±3.8) was significantly higher than that of Japan (4.0±0.6 in all of Japan, P=0.0089). However, we are unable to explain this result.
About half of the cases had symptom at home, or in primary or secondary obstetric institutions and were subsequently transferred to tertiary care centers. This may add validation to the Aichi Prefecture.
In the present study, the leading causes (>85%) of maternal death were stroke, obstetric PE and severe obstetric hemorrhage. The remaining causes included suicide, cancer, and unrelated accidents.
During nearly the same period as our study, a questionnaire-based survey regarding eclampsia and stroke during pregnancy (AICHI DATA) was conducted in all obstetric institutions in Aichi Prefecture.8) In that study, 203 cases of eclampsia (0.04%) and 51 cases of stroke (0.01%) were found to have occurred between 2005 and 2012. Although no eclampsia-related maternal death was reported, 7 patients died from stroke (3 cases of cerebral hemorrhage, 3 cases of subarachnoid hemorrhage, and 1 case of cerebral venous thrombosis). Roughly 40% of the eclampsia and stroke cases occurred at primary obstetric institutions, while another 26% of the stroke cases occurred at the patients’ home.
About 45% of the stroke cases in this study were accompanied by severe hypertension. Appropriate management of hypertension should therefore be performed during ante- and intrapartum periods in primary institutions. Hypertension should be checked regularly at home and controlled aggressively at the patient’s primary obstetric institution.
Severe obstetric hemorrhage is estimated to occur in 1 out of every 300 live births in Japan. It is defined as excessive bleeding leading to symptoms such as lightheadedness, confusion, palpitations and sweating, or signs of hypovolemia such as hypotension, tachycardia, oliguria, and decreased oxygen saturation. The most common causes of severe obstetric hemorrhage are atonic bleeding, DIC in AFE, placental abruption, placenta previa, uterine rupture and acquired or congenital coagulation defects.
Japanese guidelines for severe obstetric hemorrhage were published in 2010.7) Despite the publication of those guidelines, no decrease in cases involving hemorrhage was observed in the present study. Recently, the use of uterine artery embolization and various balloon tamponade techniques9) for the management of severe obstetric hemorrhage has steadily increased. This is expected to lead to a decrease in maternal deaths from this complication.
AFE is a catastrophic condition that occurs during pregnancy or shortly after delivery. In the present study, AFE was noted in the uterus in more than half of the patients with severe obstetric hemorrhage. Because management of AFE requires early detection and aggressive therapy, it should be kept in mind when treating patients with severe obstetric hemorrhage.
Japanese guidelines for the prevention of venous thromboembolism were published in 2004;6) however decrease in the number of obstetric PE cases reported in Aichi Prefecture was not evident. Broader acceptance of these guidelines may lead to a reduction in the number of thrombosis-related obstetric PE cases. Furthermore, AFE was also noted in more than half of the patients with obstetric PE.
“Near miss” maternal deaths were defined as cases in which the nearly died from, but eventually survived a complication that occurred during pregnancy, delivery or within 42 days of termination of pregnancy.10) Information on “near miss” maternal deaths can be useful for determining the quality of maternal care necessary for women experiencing life-threatening events during pregnancy; this type of information can also serve as an indirect indicator for the evaluation of maternal death.11,12) Since there are more “near misses” than actual maternal deaths, more analyzable data is available.13,14,15) Assessment of “near misses” can also provide useful information regarding determinants of obstetric death, and may indicate trends concerning management and outcomes.13,16) Studies including an analysis of “near miss” cases should be conducted in the future.
The peer review about the present research was practiced by the member of the Perinatal Care Association of the Aichi Prefectural Government in March, 2015. It proposed the clinical opinions due to reduced maternal death in Aichi Prefecture as follows: 1) in obstetrics hemorrhage, strict obedience of “Japanese guidelines for severe obstetric hemorrhage”, rapid transportation to tertiary care institutions and establishment of network of transportation, and 2) in stroke, the adequate management of severe hypertension and spreading “Best Practice Guide 2015 for care and treatment of Hypertension in Pregnancy” by Japan Society for the Study of Hypertension in Pregnancy.17)
In conclusion, MMR was higher in Aichi Prefecture than that in Japan, although we were unable to explain the reason from the present research. The leading causes of maternal death in Aichi Prefecture were stroke, severe obstetric hemorrhage and PE.
This work was supported in part by a 2014 Grant-in-Aid from the Perinatal Care Association of the Aichi Prefectural Government.
None.
