Research Article
Analysis of Factors Affecting Postpartum Hemorrhage in Twin Pregnancy
Zheng JS, Wang Y, Xu S, Hong HJ, Sun WJ, Xin G, Xiao J and Hong FZ*
The Second Hospital of Shandong University, Jinan, China
*Corresponding author: Hong FZ, The Second Hospital of Shandong University, 247 Beiyuan Road, Jinan 250010, China
Received: March 03, 2022; Accepted: March 29, 2022; Published: April 05, 2022
Abstract
Objective: To explore the factors affecting postpartum hemorrhage in twin pregnancy.
Methods: The clinical data of 839 twin pregnancy patients who delivered at the Second Hospital of Shandong University from May 2010 to July 2020 were retrospectively analyzed. According to the amount of postpartum hemorrhage, patients were divided into postpartum hemorrhage group (PPH group) and non- PPH group. The basic population information and clinical data during pregnancy were compared between the two groups.
Results: A total of 839 women with twin pregnancy were included in this study, and hemorrhage occurred in 11% (n=96). The Binary logistic regression model predicts the risk of factor of postpartum hemorrhage in twin pregnancy: gestation week of delivery, placenta previa, polyhydramnios, acute delivery, anemia, placental adhesions and DIC (disseminated intravascular coagulation).
Conclusions: There are many factors that affect postpartum hemorrhage in twin pregnancy. Choosing the right gestational week for delivery, strengthening pregnancy management, and improving pregnancy complications can reduce the risk of postpartum hemorrhage in twin pregnancy.
Keywords: Postpartum hemorrhage; Pregnancy; Pregnancy; Twin; Retrospective studies; Risk factor
Abbreviations
PPH: Postpartum Hemorrhage; DIC: Disseminated Intravascular Coagulation; BMI: Body Mass Index
Introduction
Postpartum hemorrhage (PPH) is classically defined as a blood loss of >500mL after vaginal birth or that of >1000mL after cesarean delivery, with no adjustment for multiple pregnancies [1]. According to the World Health Organization, PPH is the leading cause of maternal mortality in developing countries (close to 30%) and the second leading cause of maternal mortality in developed countries (approximately 13%) [2]. PPH is responsible for approximately 68000 annual deaths in pregnant women, which means that one pregnant woman dies every 8 min due to PPH [3]. The 2014 National Maternal and Child Health Inspection Report described the main causes of maternal mortality in China. Although maternal mortality due to obstetric hemorrhage (more than 80% of PPH) has been declining for more than a decade, it is still the most common cause of maternal mortality [4]. Studies have reported uterine weakness, birth canal injury, placental factor, and coagulation dysfunction as the four major causes of PPH. Of these, uterine weakness is the most common cause of PPH that accounts for approximately 70%-80% of PPH [4,5]. Twin pregnancy leads to uterine smooth muscle overextension, which affects the uterine contraction after delivery and increases uterine weakness. Additionally, the circulating blood volume and uterine blood flow in women pregnant with twins increase to ensure adequate blood supply to the uterus, placenta, and fetal tissues. Thus, twin pregnancy is a significant risk factor for PPH [1,5-8]. With the wide application of assisted reproductive technology and the increase in maternal age, the twin pregnancy rate is increasing every year [9-11]. Factors affecting PPH in singleton pregnancy have been investigated in numerous studies [2,4]. However, the risk factors for PPH in twin pregnancy remain unknown. The present study attempts to explore the risk factors for PPH in twin pregnancy through a retrospective analysis of the clinical data of patients with twin pregnancy.
Materials and Methods
Study population
The present retrospective study analyzed the data of 839 patients after obtaining institutional ethical clearance. All the patients had twin pregnancy with >26 weeks of gestation, and they delivered at the Second Hospital of Shandong University between May 2010 and July 2020.
Diagnostic criteria and statistical indicators
The World Health Organization’s definition of PPH, that is, the bleeding volume of vaginal delivery exceeding 500mL or that of cesarean section delivery exceeding 1000mL, without adjusting for the bleeding volume of multiple pregnancy, was considered [1,3]. The diagnostic criteria of pregnancy complications were adopted from Gynecology and Obstetrics, edited by Xie Xing et al., 9th edition of Human Health Publishing House [4].
According to the estimated bleeding volume, the patients were divided into the PPH group (n=96) and the control group (non-PPH group; n=743). The basic information of the population included age, body mass index (BMI), number of pregnancies, number of miscarriages, and whether to having a live birth. Clinical data during pregnancy included pregnancy method, gestational week of delivery, delivery method, total fetal birth weight, and complications during pregnancy.
Statistical analysis
Statistical analysis was performed using the SPSS 22.0 software. The measurement data are expressed as percentiles, whereas the count data are expressed as percentages (%). The Kruskal–Wallis test was used to compare the means between the groups, and Chi-square test was used to compare the rates between the groups. Finally, the binary logistic regression model was used to predict the risk factors for PPH in twin pregnancy. A P value of <0.05 was considered statistically significant.
Results
The present study was conducted in 839 patients, of which 96 patients exhibited PPH mainly due to uterine weakness, accounting for 71.88% of the PPH cases (Table 1).
Bleeding Cause
Cases (%)
Uterine Inertia
69 (71.88)
Tissue Lesion
4 (4.17)
Placenta Factor
6 (6.25)
Mixed Factors
9 (9.37)
Unknown Reason
8 (8.33)
Total
96 (100)
Table 1: Statistics of the cause of bleeding.
All the patients with PPH were treated with oxytocin; 31.25% patients were treated with carboprost suppositories, 70.83% patients were treated with carboprost tromethamine injection, and 28.12% patients were treated with arterial ligation and suture (Table 2).
Hemostasis Method
PPH (%)
No PPH (%)
Total (%)
Oxytocin
96 (100)
743 (100)
839 (100)
Carboprost Suppositories
30 (31.25)
220 (29.61)
250 (29.80)
Carprost Tromethamine Injection
68 (70.83)
328 (44.15)
396 (47.20)
Misoprostol
3 (3.13)
7 (0.94)
10 (1.19)
Arterial Ligation
16 (16.67)
22 (2.96)
38 (4.52)
Evacuation of Uterus
0 (0)
2 (0.27)
2 (0.24)
Partial Suture
2 (2.08)
0 (0)
2 (0.24)
B-lynch Suture
7 (7.29)
0 (0)
7 (0.83)
Quadrilateral Suture
2 (2.08)
1 (0.13)
3 (0.36)
Total
96 (100)
743 (100)
839 (100)
Table 2: Statistics of the method of hemostasis.
The average age of the patients was 30 years (range: 27, 33), and the average BMI was 30.07kg/m² (range: 27.73, 32.7221). No significant difference was observed in the demographic factors between the two groups (P >0.05). The PPH group exhibited fewer patients (33.3%) with a history of miscarriage than the non-PPH group (47%), and this difference was statistically significant (P <0.05). The number of primipara patients in the PPH group (45.8%) was higher than that in the non-PPH group (33.6%), and this difference was statistically significant (P <0.05) (Table 3) [12].
Parameter
No PPH
PPH
Total
P Value
Age
30 (27, 33)
30 (28, 32)
30 (27, 33)
0.559
BMI
30.01 (27.73, 32.74)
30.51 (27.84, 32.56)
30.07 (27.73, 32.7221)
0.392
G(%)
0.017
G0
33.5 (249/743)
45.8 (44/96)
34.9 (293/839)
G1
66.5 (494/743)
54.2 (52/96)
65.1 (546/839)
A(%)
0.012
A0
53.0 (394/743)
66.7 (64/96)
54.6 (458/839)
A1
47.0 (349/743)
33.3 (32/96)
45.4 (381/839)
Birth History (%)
0.017
Primipara
33.5 (249/743)
45.8 (44/96)
34.9 (293/839)
Maternal
66.5 (494/743)
54.2 (52/96)
65.1 (546/839)
*Note: G: =1 = 0 > 1 = 1; A: =0 = 0; > 0 = 1 (Chi-square test).
Table 3: Statistics of the basic information of the population.
In this study, 21.1% of the patients received treatment with the assisted reproductive technology, and no significant difference in this parameter was observed between the PPH and non-PPH groups (20.5% and 26.0%, respectively; P >0.05). Most patients (93.7%) underwent elective cesarean section to deliver, and no significant difference in this parameter was observed between the PPH and non- PPH groups (93.9% and 91.7%, respectively; P >0.05). The gestational week of delivery was greater in the PPH group than in the non-PPH group, and the difference was statistically significant (37 (36, 37) and 36 (35, 37), respectively; P <0.05). The total weight of two newborns was higher in the PPH group than in the non-PPH group (5167.5 (4645, 5775)g and 5090 (4540, 5570)g, respectively; P = 0.076). The number of patients who required blood transfusion was significantly higher in the PPH group than in the non-PPH group (36.5% and 4.4%, respectively; P <0.05). The analysis of complications during pregnancy indicated that gestational diabetes mellitus, premature membrane rupture, placenta previa, polyhydramnios, anemia, and placental adhesions may be the risk factors for PPH, whereas patients with a scarred uterus are at a relatively low risk of having PPH (Table 4).
Parameter
No PPH (n=743)
PPH (n=96)
Total (N=839)
P Value
Pregnancy Method (%)
0.207
IVF
152 (20.5)
25 (26.0)
177 (21.1)
Natural Pregnancy
591 (79.5)
71 (74.0)
662 (78.9)
Gestational age
36 (35, 37)
37 (36, 37)
37 (35, 37)
0.008
Delivery Method (%)
0.388
Spontaneous Deliver
45 (6.1)
8 (8.3)
53 (6.3)
Cesarean Section
698 (93.9)
88 (91.7)
786 (93.7)
Total Fetal Birth Weight
5090 (4540, 5570)
5167.5 (4645, 5727.5)
5100 (4550, 5600)
Bleeding Volume
300 (250, 400)
800 (400, 1000)
300 (250, 400)
<0.05
Whether Blood Transfusion (%)
<0.05
No Blood Transfusion
710 (95.6)
61 (63.5)
771 (91.9)
Blood Transfusion
33 (4.4)
35 (36.5)
68 (8.1)
Complication (%)
Placental Abruption
9 (1.2)
1 (1.0)
10 (1.2)
1
GDM
69 (9.3)
4 (4.2)
73 (8.7)
0.094
Hypertension in Pregnancy
166 (22.3)
24 (25.0)
190 (22.6)
0.558
Chronic Hypertension
5 (0.7)
1 (1)
6 (0.7)
0.519
Premature Rupture of Membranes
157 (21.1)
14 (14.6)
171 (20.4)
0.134
Scarred Uterus
139 (18.7)
8 (8.3)
147 (17.5)
0.012
Placenta Previa
17 (2.3)
8 (8.3)
25 (3.0)
0.003
Placental Placenta
3 (0.4)
0 (0)
3 (0.4)
1
Uterine Fibroids
20 (2.7)
3 (3.1)
23 (2.7)
1
Polyhydramnios
7 (0.9)
5 (5.2)
12 (1.4)
0.004
Oligohydramnios
8 (1.1)
0 (0)
8 (1.0)
0.607
Heart Disease
22 (3.0)
4 (4.2)
26 (3.1)
0.742
Elderly Primipara
13 (1.7)
4 (4.2)
17 (2.0)
0.231
Emergency Delivery
8 (1.1)
4 (4.2)
12 (1.4)
0.052
Thyroid Disease
24 (3.2)
4 (4.2)
28 (3.3)
0.858
Choroiditis
2 (0.3)
0 (0)
2 (0.2)
1
Anemia
373 (50.2)
79 (82.3)
452 (53.9)
0
Hepatitis B
30 (4.0)
5 (5.2)
35 (4.2)
0.788
DIC
1 (0.1)
2 (2.1)
3 (0.4)
0.036
Placental Adherence
21 (2.8)
7 (7.3)
28 (3.3)
0.047
Others
129 (17.4)
17 (17.7)
146 (17.4)
0.933
Table 4: Clinical features of the population.
After adjusting for confounding factors, the logistic regression model exhibited that the number of miscarriages and a scarred uterus were the protective factors for PPH. Moreover, the patients with a history of miscarriage exhibited a reduced risk of PPH during twin pregnancy (odds ratio (OR) = 0.524; 95% confidence interval (CI): 0.322-0.853), similar to patients with a scarred uterus (OR = 0.352; 95% CI = 0.159-0.781). The risk factors for PPH identified were: gestational age (OR = 1.237; 95% CI: 1.084-1.412), placenta previa (OR = 4.586; 95% CI: 1.686-12.473), polyhydramnios (OR = 7.168; 95% CI: 1.963-26.167), acute labor (OR = 15.165; 95% CI: 3.352-68.606), anemia (OR = 4.918; 95% CI: 2.794-8.657), placental adhesions (OR = 3.367; 95% CI: 1.277-8.876), and disseminated intravascular coagulation (DIC) (OR = 20.951; 95% CI: 1.481-296.373) (Table 5).
Parameter
OR (95% CI)
P Value
Number of Abortions
0.009
Gestational Week of Delivery
0.002
Scarred Uterus
0.01
Placenta Previa
0.003
Polyhydramnios
0.003
Emergency Delivery
<0.05
Anemia
<0.05
Placental Adherence
0.014
DIC
0.024
Table 5: Results of multivariable logistic regression model to predict postpartum hemorrhage after a forward selection algorithm.
Discussion
Twin pregnancies increase the risk of unhealthy pregnancy and PPH [1]. The widespread use of ovulation-stimulating drugs, increase in maternal age, and emergence and promotion of assisted reproductive technology have resulted in an increase in the rate of twin pregnancy [9-11,13,14]. Studies have exhibited that the incidence of PPH in twin pregnancy is significantly higher than that in singleton pregnancy [13,15-17].
The increased risk of PPH is due to the loss of normal contraction and retraction of uterine muscle fibers due to excessive extension, excessive expansion of the uterus to postpartum uterine fatigue, increased placental attachment area, and difficulty in normal closing of blood sinusoids [18,19]. PPH may lead to severe complications such as shock, renal failure, respiratory failure, DIC, pituitary infarction, hysterectomy, and death. Serious secondary anterior pituitary hypofunction sequelae may be observed if the shock is severe and prolonged, despite revival. In the absence of timely and appropriate medical treatment, a woman may die from PPH in an average of 2h [5,17,20]. Therefore, the identification of the risk factors for PPH in twin pregnancy is vital for optimal treatment.
The present study exhibited that prior pregnancy (including childbirth and miscarriage) reduces the risk of PPH. This finding is consistent with those of Lisonkova et al. and may be attributed to changes in the hormones or other aspects of the uterus caused by the previous pregnancy [12]. Studies have reported that women with twin pregnancies achieved through in vitro fertilization are more prone to PPH [1,9,21-23]. This finding is in contrast with those of the present study, which revealed a nonsignificant difference in the incidence of PPH between assisted reproduction-based and natural twin pregnancies (P >0.05). Studies have reported that cesarean section increases the risk of PPH [2,6,12,16,17]. Conversely, some studies have reported that PPH risk in women with twin pregnancy is higher in vaginal trial delivery than in cesarean section [24,25]. In the present study, most patients chose elective cesarean section to deliver, and no significant difference in PPH was observed between these patients and those who opted for vaginal delivery (P >0.05). This finding is consistent with those of Nwankwo et al. and Yang et al. [11,22]. This result may be related to low number cases of vaginal delivery in the present study, and further research is required to confirm this finding. Studies by Seow et al. and Shunji et al. exhibited that the incidence of PPH increases with an increase in gestational age [6,26]. The present study indicated that the estimated bleeding volume increases with an increase in gestational age, reaching a peak at approximately 34 weeks. The estimated bleeding volume was relatively smaller at approximately 36 weeks, after which the upward trend reappeared. This may be related to a gradual decrease in the activity of antithrombin-III and the number of platelets in the last month of twin pregnancy [7]. In the present study, the average estimated bleeding volume at 39-40 weeks was low, which may be due to the low delivery volume in this gestational week. The uterus stops growing at 39 weeks in twin pregnancy, and the placental weight stabilizes after 37 weeks. Therefore, we suggest that the decision of delivery at approximately 36 weeks in case of twin pregnancy will reduce the risks of PPH and other complications [26].
The present study exhibited that a scarred uterus is a protective factor for PPH. This finding is in contrast to those of Lisonkova et al. and Rissanen et al [12,16]. Further studies with a larger sample size are required to confirm the findings of the present study. The present study considered placenta previa, polyhydramnios, acute labor, anemia, placental adhesions, and DIC as complications related to increased risk of PPH [6,22,27]. This may be related to factors such as excessive uterine inflation, weak contraction, soft birth canal laceration, and coagulation dysfunction [23,28].
Clinical Implications
Through this study, we have discovered the risk factors and the protective factors of postpartum hemorrhage in twin pregnancy. Provided a scientific basis for clinical diagnosis and treatment. The risk of complications associated with twin pregnancy could be reduced with timely diagnosis and treatment. Selection of the right time and method of delivery may reduce the incidence of PPH.
Research Implications
The amount of bleeding volume of PPH depends only on the clinical estimation and measurement, which may underestimate the actual amount of blood loss by 30%-50%. Difficulty accurately estimating the amount of bleeding and misdiagnosis of PPH have been identified as the factors restricting an accurate reporting of PPH, and the present study suffers from these limitations [4,16].
Strengths and Limitations
This study is based on a large sample of China, collected clinical data of twin pregnancy patients in the past ten years, and thoroughly analyzed the relationship between various pregnancy complications and postpartum hemorrhage.
In this study, the blood routine examinations of the patients before and after delivery were not perfect. The use of estimated bleeding volume to study postpartum hemorrhage has certain limitations.
Conclusion
The present study exhibited that prior pregnancy (including childbirth and miscarriage) and the scarred uterus in twin pregnancy are protective factors for PPH, whereas the gestational week, placenta previa, polyhydramnios, acute labor, anemia, placental adhesions, and DIC are risk factors for PPH. The risk of complications associated with twin pregnancy could be reduced with timely diagnosis and treatment. Selection of the right time and method of delivery may reduce the incidence of PPH.
Acknowledgement
We thank TopEdit (www.topeditsci.com) for its linguistic assistance during the preparation of this manuscript.
References
- Blitz MJ, Yukhayev A, Pachtman SL, et al. Twin pregnancy and risk of postpartum hemorrhage. J Matern Fetal Neonatal Med. 2020; 33: 3740-3745.
- Kramer M S, Berg C, Abenhaim H, et al. Incidence, risk factors, and temporal trends in severe postpartum hemorrhage. Am J Obstet Gynecol. 2013; 209: 449.e1-7.
- Sotillo L, De la Calle M, Magdaleno F, Bartha JL. Efficacy of carbetocin for preventing postpartum bleeding after cesarean section in twin pregnancy. J Matern Fetal Neonatal Med. 2020; 33: 267-271.
- Lin X, Zhang Li, Zhang Jing. Interpretation of Guideline on the Prophylaxis and Treatment of Postpartum Hemorrhage (2009 and 2014). Chin J Obstet Gynecol Pediatr (Electron Ed). 2015; 11: 433-447.
- Hong X, Zhang H, He L. Study on the effect of bilateral internal iliac artery balloon occlusion combined with carprostol tromethamine injection to prevent postpartum hemorrhage after cesarean section in twin pregnancy. Chin J Mod Drug Appl. 2020; 14: 67-69.
- Kok-Min Seow, Kuo-Hu Chen, Peng-Hui Wang, Yu-Hung Lin, Jiann-Loung Hwang. Carbetocin versus oxytocin for prevention of postpartum hemorrhage in infertile women with twin pregnancy undergoing elective cesarean delivery. Taiwan J Obstet Gynecol. 2017; 56: 273-275.
- Shunji Suzuki, Yoshie Hiraizumi, Hidehiko Miyake. Risk factors for postpartum hemorrhage requiring transfusion in cesarean deliveries for Japanese twins: comparison with those for singletons. Arch Gynecol Obstet. 2012; 286: 1363- 1367.
- Zhou N. Preventive effect of uterine artery ligation combined with capecitabine on bleeding after cesarean section in twins. Contemporary Medicine. 2020; 26: 23-24.
- Emily Werder, Pauline Mendola, Tuija Mannisto, Jennifer O’Loughlin, S Katherine Laughon. Effect of maternal chronic disease on obstetric complications in twin pregnancies in a United States cohort. Fertil Steril. 2013; 100: 142-149.e1-e2.
- Madar H, Goffinet F, Seco A, et al. Severe Acute Maternal Morbidity in Twin Compared With Singleton Pregnancies. Obstet Gynecol. 2019; 133: 1141- 1150.
- TO Nwankwo, UU Aniebue, E Ezenkwele, MI Nwafor. Pregnancy outcome and factors affecting vaginal delivery of twins at University of Nigeria Teaching Hospital, Enugu. Niger J Clin Pract. 2013; 16: 490-495.
- Lisonkova S, Mehrabadi A, Allen VM, et al. Atonic Postpartum Hemorrhage: Blood Loss, Risk Factors, and Third Stage Management. J Obstet Gynaecol Can. 2016; 38: 1081-1090.e2.
- Wu W. Clinical effect of Xinmupei combined with oxytocin on prevention of bleeding after cesarean section in twin pregnancy. Contemporary Medicine. 2020; 26: 55-57.
- Drassinower D, Timofeev J, Huang CC, Landy HJ. Racial disparities in outcomes of twin pregnancies: elective cesarean or trial of labor? Am J Obstet Gynecol. 2014; 211: 160.e1-7.
- Wu Y. The effect of delivery method of twin pregnancy on neonatal asphyxia and postpartum hemorrhage. China Maternal and Child Health. 2005; 15: 1942-1943.
- Rissanen AS, Jernman RM, Gissler M, Nupponen I, Nuutila ME. Maternal complications in twin pregnancies in Finland during 1987-2014: a retrospective study. BMC Pregnancy Childbirth. 2019; 19: 337.
- Li X, Pan L, Miu L. The effect of controlling the time between delivery of twins on postpartum hemorrhage. Jiangxi Medical Journal. 2019; 6: 641-642.
- Li YD, Liu WW, Zeng WL. Clinical Analysis of Carboprost Tromethamine in Prevention of Postpartum Hemorrhage with Twin Pregnancy. Jilin Medicine. 2016; 12: 2860-2861.
- Yang Jun. Clinical observation of prostaglandin tromethamine injection combined with uterine artery ligation in prevention of postpartum hemorrhage in cesarean section of twin pregnancy. Contemporary Medicine. 2019; 13: 110-112.
- Chen Y. Observation on the effect of carprostol tromethamine in preventing bleeding during and after cesarean section of twin pregnancy. Shandong Medicine. 2017; 42: 77-79.
- Bamberg C, Christina Fotopoulou, Philipp Neissner, et al. Maternal characteristics and twin gestation outcomes over 10 years: impact of conception methods. Fertil Steril. 2012; 98: 95-101.
- Yang X, Zhou W. Clinical analysis of related risk factors of postpartum hemorrhage in twin pregnancy. Chongqing Medicine. 2018; 23: 3105-3111.
- Jin Ping. Analysis of the Effect of Carbetocin in Preventing Postpartum Hemorrhage after Cesarean Section in Twin Pregnancy. China &Foreign Medical Treatment. 2020; 28: 1-3.
- Easter SR, Robinson JN, Lieberman E, Carusi D. Association of Intended Route of Delivery and Maternal Morbidity in Twin Pregnancy. Obstet Gynecol. 2017; 129: 305-310.
- Dana Sadeh-Mestechkin, Yair Daykan, Mor Bustan, Ofer Markovitch, Gil Shechter-Maor, Tal Biron-Shental. Trial of vaginal delivery for twins - is it safe? A single center experience. J Matern Fetal Neonatal Med. 2018; 31: 1967-1971.
- Shunji S, Kikuchi F, Ouchi N, et al. Risk Factors for Postpartum Hemorrhage after Vaginal Delivery of Twins. J Nippon Med Sch. 2007; 74: 414-417.
- Xiao X, Li S, Zhang N. Analysis and nursing experience of postpartum hemorrhage in twin pregnancy and single pregnancy. Journal of Cardiovascular Pulmonary. 2010; 6: 836-837.
- Xiao Y, Zeng Q. Risk factors and intervention measures of postpartum hemorrhage. Journal of Baotou Medical College. 2016; 6: 59-60.