Potential prevention of stillbirth caused by placental abruption: a regional population-based study in Japan

Abstract

Objective

Placental abruption is associated with adverse perinatal outcomes including intrauterine fetal demise, which subsequently results in stillbirth. However, few studies have demonstrated the preventability of stillbirth due to placental abruption. Therefore, we evaluated the possibility of preventing stillbirth caused by placental abruption by reviewing all stillbirths in our region.

Methods

This study reviewed all stillbirths after 22 weeks of gestation in Shiga Prefecture, Japan from 2010 to 2019, excluding lethal disorders. We evaluated 350 stillbirth cases, with and without placental abruption.

Results

There were 32 stillbirths with PA and 318 without placental abruption. The probability of preventing stillbirth was significantly higher in patients with placental abruption than in those without (30% vs. 8%, p < 0.001). We also determined the recommendations for preventing stillbirths with placental abruption.

Conclusion

Some stillbirths caused by placental abruption can be prevented. We recommend improvements to perinatal maternal-fetal care and perinatal emergency transport systems.

Keywords:

• Placental abruption
• stillbirth
• intrauterine fetal death
• preventable death
• population-based study

Introduction

Placental abruption, a premature separation of the placenta from the uterus before delivery, occurs in 0.4%-1.0% of all pregnancies [1–3]. The major clinical findings of placental abruption are vaginal bleeding and abdominal pain, often accompanied by uterine contractions, uterine tenderness, and a non-reassuring fetal heart rate pattern [4,5]. Placental abruption is associated with intrauterine fetal death (IUFD) and is one of the leading causes of stillbirth. The fetal mortality rate due to placental abruption ranges from 5% to 25%. Placental abruption often occurs suddenly, making it difficult to avoid it [6,7].

The rate of stillbirth, defined as death before delivery after 22 weeks of gestation, in Japan is one of the lowest in the world [8]. However, although stillbirth rates have declined more slowly since 2000 than rates of maternal mortality and mortality in children under five years of age, there have been few population-based studies on stillbirth audits in high-income countries [9,10]. Our previous population-based study on stillbirths in a Japanese region showed that placental abruption was the second most common cause of stillbirth [11].

Many studies have indicated that placental abruption is a high-risk factor for stillbirth [12–14]. However, few studies have discussed the preventability of stillbirth due to placental abruption. Therefore, we evaluated the perinatal background and possibility of preventing stillbirth caused by placental abruption by reviewing all stillbirths in our region.

Materials and methods

Data collection

This population-based study of stillbirths was performed in Shiga Prefecture, Japan. There are approximately 12,000 births in Shiga annually.

First, we directly investigated all stillbirth certificates from 2010 to 2019 with permission from the Japanese Ministry of Health, Labor, and Welfare. Second, we prepared and sent a questionnaire to each facility that had submitted a stillbirth certificate. A peer-reviewed team of experienced obstetricians and neonatologists retrospectively reviewed the questionnaires returned from the facilities, identified the primary cause of stillbirth, and assessed the possibility of stillbirth prevention. The peer review team consisted of 12 perinatal experts, including 6 obstetricians and 6 neonatologists, and held face-to-face discussions about every stillbirth case in the prefecture based on a questionnaire. Preventability was determined comprehensively based on the clinical course and laboratory findings of each case without using standardized definitions or checklists. Even when there were disagreements in the initial judgment results, repeated discussions led to a final consensus regarding the possibility of prevention. For cases of stillbirth due to multiple causes, the cause estimated to have had the greatest impact on fetal death was determined to be the primary cause.

There were 392 stillbirths after 22 weeks of gestation in the Shiga Prefecture from 2010 to 2019. We excluded the following 42 cases of lethal disorders: trisomy 18 (n = 13), hydrops fetalis (n = 10), trisomy 21 (n = 4), Potter sequence (n = 3), acardiac fetus (n = 3), cystic hygroma (n = 2), and others (n = 7). We divided the remaining 350 stillbirths into 2 groups: abruption and non-abruption, according to whether or not the primary cause of stillbirth was placental abruption (Figure 1).

Figure 1. Overview flow chart of this study.

Definition of placental abruption

Placental abruption was defined as partial or complete separation of the placenta before fetal delivery. The cases were diagnosed on the basis of clinical symptoms, echography, or pathological examination. In this study, we retrospectively examined the clinical course and pathological findings of the placenta in stillbirth cases and comprehensively identified cases with placental abruption as the cause of death by a peer review team of perinatal experts.

Judgment of preventability

The peer review team classified all stillbirths into two groups according to the possibility of prevention: preventable and preventable. There were no specific definitions or criteria set for determining whether or not stillbirth was preventable, and decisions were made based on consensus among all reviewers. Unpreventable cases included pregnant women who regularly visited an obstetrician as well as those who went immediately after abnormal hemorrhaging or unusual abdominal pain. Pregnant women with maternal complications that were not severe and were well-controlled by the obstetrician, as well as those with a standard diagnosis or medical management in obstetric care, were also assessed as unpreventable. In addition, high-risk pregnant women who were transferred in a timely manner to higher perinatal centers were identified as unpreventable. Except for these unpreventable cases, all other cases were classified as preventable. Such cases included those involving inadequate perinatal management, subsequent delay in referral to a higher perinatal center, and failure to evaluate despite the presence of symptoms.

Statistical analyses

For the comparison of the abruption and non-abruption groups, continuous variables are shown as the mean and standard deviation or n (%) and were assessed using the Mann-Whitney U test. The frequencies of other subjects and ratios are shown as n (%) and were assessed using the chi-square test. A P value of <0.05 indicated a significant difference.

All statistical analyses were performed using the Bell Curve for Excel (Social Survey Research Information Co., Ltd., Tokyo, Japan).

Ethical statement

This study was approved by the Institutional Review Board of Shiga University of Medical Science (R2017-151).

Results

Perinatal background of stillbirths

As shown in Table 1,350, stillbirths occurred, 32 of which were due to placental abruption. The median maternal age was 34 years; 14 women (44%) were primipara, and 9 (28%) had fetal growth restriction in stillbirths with abruption, which was not significantly different from those without abruption. The median gestational age at birth was 35 weeks in the abruption group, which was significantly higher than that of the non-abruption group (31 weeks). Infant birth weight in the abruption group was also significantly greater than that in the non-abruption group (2236 g vs. 1105 g). Six pregnant women (19%) had a hypertensive disorder of pregnancy in the abruption group, which was significantly more common than that in the non-abruption group (4%).

Table 1. Perinatal background of stillbirth with or without placental abruption.

Maternal characteristics	All n = 350	Abruption n = 32	Non-abruption n = 318	p-value
Age (year)	32(28–35)	34(30–35)	31(28–35)	0.23
Gestational age (weeks)	32(25–37)	35(32–37)	32(24–37)	<0.001
Birth weight (g)	1280(524–2332)	2236(1638–2622)	1105(493–2308)	<0.001
Parity, primi	172(49)	14(44)	158(50)	0.52
HDP	18(5)	6(19)	12(4)	<0.001
FGR	111(32)	9(28)	102(32)	0.63

HDP: hypertensive disorders of pregnancy; FGR: fetal growth restriction.

Data are expressed as the number (%) or inter-quartile range.

Possibility of preventing stillbirth with placental abruption

We assessed the possibility of stillbirth prevention in 337 cases, excluding 13 that could not be judged because of insufficient information. We conclude that 34 stillbirths (10%) were preventable. There were nine preventable stillbirths (30%) in the abruption group, which was significantly higher than that in the non-abruption group (25 cases, 8%) (Table 2).

Table 2. Judgment of stillbirth prevention.

Assessment	Abruption, n = 30*	Non-abruption, n = 307**	p-value
Preventable	9 (30)	25 (8)	< 0.001
Unpreventable	21 (70)	282 (92)

Excluding 2* and 11** cases that could not be judged due to lack of sufficient information.

Data are shown as the number (%).

Recommendation for prevention of stillbirth caused by placental abruption

We aimed to prevent stillbirths caused by placental abruption, and concurrently made recommendations for preventing stillbirth caused by placental abruption. The recommendations were divided into three categories (Table 3).

Table 3. Recommendations for preventing stillbirths caused by placental abruption.

Recommendations	n
Improvement of the diagnosis or medical management	5
Appropriate management of HDP
Careful management of chronic placental abruption
Accurate diagnosis of placental abruption
Improvement of fetal monitoring	2
Appropriate fetal heart monitoring
Perinatal transport system	2
Development of an emergency maternal transport system
Total	9

The most common factors were related to improvements in diagnosis and medical management of placental abruption. We had five cases related to the substandard management of hypertensive disorders of pregnancy (HDP) and chronic placental abruption, as well as failure to diagnose placental abruption. The next most common recommendation is fetal heart rate monitoring. There were two stillbirth cases due to the lack of fetal heart rate monitoring. Other recommendations were related to perinatal transport systems, as we had two stillbirths with placental abruption resulting from failed emergency maternal transport due to perinatal transport system failure.

Discussion

We evaluated the perinatal background of stillbirths caused by placental abruption by analyzing 350 stillbirths in our region over 10-year period. We found that some stillbirths caused by placental abruption were preventable and their preventability was higher than that of stillbirths caused by other causes.

First, we evaluated the perinatal background of the stillbirths due to placental abruption. Our finding that placental abruption occurred at an average of 34 weeks of gestation is consistent with the report by Ananth et al. [15] that delivery with placental abruption is more likely to occur in the preterm period than in normal delivery. However, our results regarding the gestational age at placental abruption onset differ from those of Elkafrawi et al. [16], who reported that placental abruption with a poor outcome develops at an average of 31 weeks of gestation. The difference in the results of these studies may be explained by the fact that our analysis included only IUFD cases, while Elkafrawi et al. included poor prognosis cases, including those with a neonatal arterial umbilical cord pH at birth <7.15, IUFD, perinatal death, and Apgar score <7 at the first and fifth minute after birth. Furthermore, HDP was significantly more common in placental abruption stillbirths than in non-placental abruption stillbirths, which is consistent with HDP being a risk factor for the development of PA [17,18]. This is in agreement with a report that placental abruption with HDP is associated with poor perinatal prognosis [19].

We found that some stillbirths caused by placental abruption were preventable and that this preventability was higher than that of stillbirths from other causes. Although placental abruption is associated with a high risk of stillbirth [15,20], we showed that 30% of stillbirths were avoidable. To our knowledge, this is the first report to mention the possibility of avoiding stillbirth caused by placental abruption. Two studies examined the preventability of stillbirth in Jordan and Sweden. Our preventable rate, including placental abruption and non-placental abruption cases (34/337, 10%), was close to that of Sweden (17%) but much lower than that of Jordan (35%). The difference between these rates may be due to the use of different criteria for determining stillbirth preventability [21,22]. Our estimate of the rate of preventable stillbirths caused by placental abruption is unique because previous studies reported stillbirth prevention rates without categorizing them according to the cause of stillbirth.

In addition to determining the possibility of preventing stillbirth caused by placental abruption, we made recommendations for its prevention. Since we identified several stillbirths caused by placental abruption due to inadequate management of pregnancy complications, including HDP, and inadequate fetal monitoring evaluation, we believe that further stillbirths could be prevented by informing obstetricians in the region about the recommendations for more careful management of pregnancy complications and appropriate assessment of fetal well-being.

The present study has several limitations. First, we only included stillbirth cases and did not analyze live birth cases of placental abruption. Because we made our recommendations for preventing stillbirths caused by placental abruption without comparing live birth cases with placental abruption, these recommendations may not be sufficiently effective in avoiding stillbirths caused by placental abruption. Further comparisons of live and stillbirth cases will clarify the factors associated with fetal death due to placental abruption. Second, stillbirths of unknown cause were also included in the analysis; we did not exclude them, as they accounted for 47% of the total number of stillbirths. Several studies have shown that the percentage of unexplained stillbirths is not small, accounting for 25%-60% of all stillbirths [23–26]. We excluded stillbirths of unknown cause from our analysis and found a significantly higher prevalence of stillbirths caused by placental abruption than caused by other primary causes (data not shown). Finally, the possibility for preventing stillbirth was not uniformly determined. It was not made according to any predefined criteria. We instead made the final decision on the possibility for prevention after carefully reviewing each case.

Conclusions

We concluded that some stillbirths caused by placental abruption are potentially preventable. To prevent stillbirths caused by placental abruption, improvements should be implemented in obstetric management and assessment of fetal well-being, as well as in establishing a regional perinatal emergency transport system.

Acknowledgements

We would like to express our appreciation to the peer review team.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

Data available on request from the corresponding author.

Additional information

Funding

This study was supported by the JSPS KAKENHI [grant number JP15K08803].