- Email: [email protected]
Size of uterine leiomyoma is a predictor for massive haemorrhage during caesarean delivery
European Journal of Obstetrics & Gynecology and Reproductive Biology 223 (2018) 60–63
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Full length article
Size of uterine leiomyoma is a predictor for massive haemorrhage during caesarean delivery Kiguna Seia , Kenichi Masuib,c,* , Hidenori Sasaa , Kenichi Furuyaa a
Department of Obstetrics and Gynecology, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359-8513, Japan Department of Anesthesiology, Showa University School of Medicine, Hatanodai 1-5-8, Sinagawa, Tokyo, 142-8666, Japan c Department of Anesthesiology, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359-8513, Japan b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 June 2017 Received in revised form 18 November 2017 Accepted 15 February 2018 Available online xxx
Background: Uterine leiomyoma is a common benign tumour, and a risk factor for various complications during pregnancy and peripartum period. Peripartum haemorrhage is the most critical complication that can cause maternal death. Although the relationship of leiomyoma and peripartum haemorrhage has been indicated, little is known about the characteristics of leiomyoma as predictors for massive haemorrhage in caesarean delivery. Objective: We examined whether characteristics of leiomyoma and pregnant patients could predict massive haemorrhage in women undergoing caesarean delivery. Study design: This is a single-institution, retrospective cohort study. We reviewed singleton caesarean deliveries between January 2005 and December 2011. We excluded women with the following risk factors for massive haemorrhage: abnormality of placental position, abruptio placentae, haemorrhagic diseases, hydramnios, and labour arrest after induction. Myomectomy was not performed during delivery. Multivariate logistic regression analysis was performed to identify predictors of massive intraoperative haemorrhage (1000 ml). The following predictors were evaluated: maternal age, body mass index, parity, gestational week, birth weight, number of leiomyomas, and volume of the largest leiomyoma. Detailed characteristics of leiomyomas were evaluated using sonography or magnetic resonance imaging. Results: Seven hundred and fifty-nine women were included; 55 women (7.25%) had leiomyoma. Thirtyeight women with leiomyoma underwent magnetic resonance imaging scan. The median intraoperative haemorrhage was 939 ml (395–5296 ml) in women with leiomyoma and 689 ml (129–3060 ml) in women without. Multivariate analysis revealed that a largest leiomyoma 175 cm3 (odds ratio 6.4 [95% confidence interval: 1.5–27], P = 0.007), birth weight of 2500 g (2.3 [1.53.6], P < 0.001), and primipara (1.5 [1.1–2.1], P = 0.025) were significant predictors of massive intraoperative haemorrhage. Conclusions: The presence of a leiomyoma of 175 cm3, birth weight of 2500 g, and primipara were found to be predictors for massive intraoperative haemorrhage during caesarean delivery. A leiomyoma 175 cm3 which is equivalent volume to a 7 cm diameter sphere can be diagnosed in the first trimester using sonography. In cases of cesarean delivery with these predictors, preparation for massive haemorrhage, including storage of autologous blood, may be considered. © 2018 Elsevier B.V. All rights reserved.
Keywords: Caesarean section Haemorrhage Leiomyoma
Introduction Uterine leiomyoma is one of the most common solid benign tumours of the uterus, developing in 20–40% of reproductive-age women [1]. The prevalence of leiomyoma during pregnancy was reported as approximately 11% in early studies [2–4], and seems to be increasing today due to improvements in diagnostic
* Corresponding author at: Department of Anesthesiology, Showa University School of Medicine, Hatanodai 1-5-8, Sinagawa, Tokyo, 142-8666, Japan. E-mail address: [email protected] (K. Masui). https://doi.org/10.1016/j.ejogrb.2018.02.014 0301-2115/© 2018 Elsevier B.V. All rights reserved.
approaches. Several studies revealed that leiomyomas cause complications including miscarriage, preterm labour, and haemorrhage during pregnancy, labour, and delivery [5–8]. Among various complications in deliveries, haemorrhage is the most critical and can cause maternal death [9]. Leiomyoma is recognized as a risk factor for caesarean delivery. Some studies have reported that larger leiomyomas could increase the rate of caesarean delivery [4,10]. Caesarean delivery itself is a risk for massive peripartum haemorrhage when compared to transvaginal delivery8. As leiomyomas can cause haemorrhage during delivery, the risk of massive haemorrhage in caesarean deliveries in women with leiomyomas may be higher than that in
K. Sei et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 223 (2018) 60–63
women without leiomyomas. Although some studies examined the risk of peripartum haemorrhage in women with leiomyomas, they examined the risk in caesarean and transvaginal deliveries simultaneously [6,10]. One study reported the presence of leiomyomas can be a risk factor for massive haemorrhage in caesarean delivery [11]. However, a small uterine leiomyoma is unlikely to cause massive haemorrhage. If characteristics of leiomyomas are a predictor of intraoperative haemorrhage during caesarean delivery, it would be helpful to identify these features in order to decrease the risk of massive peripartum haemorrhage. The aims of this study were, first, to examine whether the size and number of leiomyomas can predict massive haemorrhage during caesarean delivery, and second, to evaluate whether characteristics of the patient or baby could predict massive haemorrhage during caesarean delivery. Materials and methods Study population This was a single-institution, retrospective cohort study. The study was approved by the institutional review board of our medical college (KAN-201, National Defense Medical College, Saitama, Japan); the board judged that written informed consent was not required since the data of this study was collected from hospital medical records. We reviewed the medical records of women undergoing caesarean singleton delivery between January 2005 and December 2011. We excluded women who had an abnormality of placental position, abruptio placentae, and haemorrhagic diseases (such as HELLP syndrome, idiopathic thrombocytopenic purpura, and disseminated intravascular coagulation) [12]. We also excluded women who had hydramnios and women who experienced labour arrest, because these may result in massive postpartum haemorrhage due to uterine atony [13]. Clinical procedures Leiomyoma was diagnosed by transvaginal sonography in all women during prenatal check-up. When a woman had a leiomyoma obstructing the birth canal or located in the area of uterine incision for caesarean delivery, magnetic resonance imaging (MRI) was performed at 34–35 gestational weeks. In these patients, we used the MRI findings to evaluate detailed characteristics of the leiomyomas, recognizing that MRI examination is not generally performed in pregnant women. The uterine incision was performed in the same manner, avoiding incision into a leiomyoma. Simultaneous myomectomy at caesarean delivery was not performed, except in women who had small subserosal leiomyomas that could be excised easily without massive bleeding.
61
Collected variables Based on the delivery records, we collected the following characteristics of women for our analysis: parity, age at delivery, maternal body weight, maternal height, body mass index (BMI), gestational week, birth weight, and intraoperative haemorrhage, which was determined as the sum of suction volume and gauze counting. We determined the three major axes of the leiomyoma based on MRI findings, and the number of leiomyomas based on MRI or sonographic findings during the pregnancy. We calculated the volume of the leiomyomas using the following equation: volume ¼
4pabc 3
where a, b, and c are the lengths of the three major axes of a leiomyoma. We regarded subserosal leiomyomas not to be leiomyomas in the analysis because several studies have revealed that subserosal leiomyomas are usually asymptomatic and have little or no influence on intraoperative haemorrhage [14]. Multivariate logistic regression analysis We selected the following dichotomous variables as factors examined with univariate logistic regression analysis: age at delivery >35 or 35 years, maternal BMI 25 or <25 kg m2, primipara or multipara, gestational week 38 or <38, birth weight >2500 or 2500 g, volume of the largest leiomyoma in each patient x or
Table 1 Patient and baby characteristics. Characteristics
All patients (n = 759)
Leiomyoma (n = 55)
No leiomyoma (n = 704)
P value for Leiomyoma vs No leiomyoma
Age, year Maternal body weight, kg Maternal height, cm Maternal body mass index, kg/m2 Gestational week Primipara Birth weight of baby, g Intraoperative haemorrhage, mL Intraoperative haemorrhage 1000 mL
33 (19–45) 63 (41–125) 157 (140–190) 25 (17–49) 37 (27–42) 267 (35%) 2740 (400–4440) 700 (129–5296) 182 (24%)
35 (26–45) 63 (44–82) 159 (150–172) 25 (20–34) 37 (31–41) 31 (56%) 2750 (1416–3725) 939 (395–5296) 25 (45%)
33 (19–45) 63 (41–125) 157 (140–190) 25 (17–49) 37 (27–42) 236 (34%) 2738 (400–4440) 689 (129–3060) 157 (22%)
<0.001 0.994 0.013 0.133 0.415 0.001 0.845 <0.001 <0.001
Data are expressed as median (range). Primipara and intraoperative haemorrhage are expressed number (%).
62
K. Sei et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 223 (2018) 60–63
Table 2 Univariate analysis of intraoperative haemorrhage 1000 ml. Factors
Number
Intraoperative haemorrhage 1000 ml, Number (%)
Yes No
239 520
64 (27) 118 (23)
Yes No
410 349
108 (26) 74 (21)
Yes No
228 531
60 (26) 122 (23)
Yes No
267 492
77 (29) 105 (21)
Yes No
541 218
150 (28) 32 (15)
Yes No
16 743
12 (75) 170 (23)
Yes No
13 746
7 (54) 175 (24)
Age >35 year
Body mass index 25 kg/m2
Gestational week 38 weeks
Primipara
Birth weight of baby 2500 g
Volume of largest leiomyoma 175 cm3
Number of leiomyomas 3
Odds ratio
95% confidential interval
P value
1.2
0.9–1.8
0.221
1.3
0.9–1.9
0.099
1.2
0.8–1.7
0.323
1.5
1.1–2.1
0.021
2.2
1.5–3.4
<0.001
10.1
3.2–31.8
<0.001
3.8
1.3–11.5
0.018
Data are expressed as number (percentage) for each factor. Odds ratio with 95% confidential interval and P value are expressed for each factors. P value <0.05 is considered to be significant.
NY, USA) and JMP Pro version 13 (SAS Institute Japan, Co., Ltd., Tokyo, Japan) was used for statistical analyses. A P value less than 0.05 was regarded as significant. Results There were 4736 singleton deliveries during the study period, including 1079 by caesarean delivery. Seven hundred fifty-nine women met the inclusion criteria; of these, 55 women had one or more leiomyomas and 38 women underwent MRI examinations at 34–35 gestational weeks. The prevalence of leiomyoma in singleton delivery women and women undergoing caesarean deliveries was 3.3% and 7.2%, respectively. Patient and baby characteristics are shown in Table 1. Intraoperative haemorrhage in women with leiomyoma (939 (395–5296) ml) was larger than that in women without leiomyoma (689 (129–3060) ml). The proportion of primipara among women with leiomyoma was higher than that among women without leiomyoma (56% vs. 34%). Age, maternal body weight, maternal height, maternal BMI, gestational week, and birth weight were similar between women with versus without leiomyoma. Volume of the maximum leiomyoma was 139 (4–1633) cm3 in 38 women with MRI findings, and the number of leiomyomas was 1 (1–12) in 55 women. Thirty-two, 10, and 13 women had 1, 2, and 3 leiomyomas, respectively. The cut-off value of the volume of the maximum leiomyoma was 175 cm3. In 17 women without MRI examination, sonographic findings revealed that no patient had a leiomyoma 175 cm3.
Table 3 Significant predictors for intraoperative haemorrhage 1000 ml by multivariate analysis. Significant predictors
Odds ratio
95% confidential interval
P value
Primipara Birth weight of baby 2500 g Volume of largest leiomyoma 175 cm3
1.5 2.4 9.7
1.0–2.1 1.6–3.7 3.0–31.4
0.031 <0.001 <0.001
Data are expressed as number (percentage) for each significant predictor. Odds ratio with 95% confidential interval and P value are expressed for each significant predictors. P value <0.05 is considered to be significant.
Table 2 shows factors examined in the univariate logistic regression analysis for massive intraoperative haemorrhage and number of women with massive intraoperative haemorrhage. Body mass index 25 kg/m2, primipara, birth weight 2500 g, presence of a 175-cm3 volume leiomyoma, and number of leiomyomas 3 were identified as the possible predictors. Multivariate logistic regression analysis demonstrated that primipara (OR 1.5 [95%CI 1.0–2.1]), birth weight 2500 g (OR 2.4 [95% CI 1.6–3.7]), and presence of a 175-cm3 volume leiomyoma (OR 9.7 [95%CI 3.0–31.4]) were significant predictors for intraoperative haemorrhage 1000 ml (Table 3). A bootstrap analysis confirmed the internal validity of the final regression model with 95% CI of 1.0-2.1 for primipara (P = .028), 1.6–4.1 for birth weight 2500 g (P < 0.001), and 4.0-50.7 for the presence of a 175-cm3 volume leiomyoma (P < 0.001). Discussion We found that intramural or submucosal leiomyoma was a risk factor for massive intraoperative haemorrhage (1000 ml) in caesarean delivery. The presence of a large-sized leiomyoma 175 cm3, birth weight 2500 g, and primipara were found to be significant predictors. A large-sized leiomyoma 175 cm3, which is equivalent in volume to a 7 cm diameter sphere, was found to be a clear risk factor for massive intraoperative haemorrhage (OR 9.7 [95%CI 3.0– 31.4]). A previous study found a decreased blood flow rate in leiomyomas and adjacent normal myometrium, as compared with myometrium of the normal uterus [15]. The low blood perfusion may decrease the distribution of oxytocin, which can result in uterine atony. Another study observed haphazard bundles of smooth muscle with focal smooth muscle necrosis and hyaline changes [16]. Irregular lines in the entire myometrium might inhibit muscular contraction of the uterus. Birth weight 2500 g was also a predictor for massive intraoperative haemorrhage (OR 2.1 [95%CI 1.6–3.7]). The mechanism of the increased risk of haemorrhage with a larger baby would be based on uterine atony. Several studies reported that babies greater than 4000 g cause an over-distended uterus and uterine atony may be induced [8,17,18]. The influence of overweight in neonates is unknown in this study because the
K. Sei et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 223 (2018) 60–63
birth weights born from pregnant women with leiomyoma was below 4000 g; however, our results also indicate that a heavier birth weight causes more severe intraoperative haemorrhage in caesarean delivery. Primipara was found to be another predictor for massive intraoperative haemorrhage (OR 1.5 [95%CI 1.0–2.1]). This result is supported by an early population-based cohort study showing that primipara was a risk factor for massive postpartum haemorrhage due to uterine atony [17]. As oxytocin is the primary hormone for uterine contraction, the effect of oxytocin might be related to uterine atony in primiparous women. A study revealed that plasma oxytocin concentrations during pregnancy in multipara women were lower than that in primipara women [19]. This result implies that oxytocin plasma level might have less effect on uterine contraction in primiparous women. Maternal BMI was found not to be a predictor of intraoperative haemorrhage in our population, where the maximum BMI was 34.1 kg m2 in women with leiomyoma. A previous study showed that maternal obesity with BMI 40 kg/m2 was a risk factor for postpartum haemorrhage [20]. Overweight but not obese may not be a risk factor for haemorrhage during caesarean delivery. In the present study, the sizes of leiomyomas were evaluated at 34–35 gestational weeks using MRI images. Although MRI examination would not be performed in daily clinical practice, it was useful to accurately assess leiomyoma volume. The determined volume of a leiomyoma of 175 cm3, as a risk factor for massive haemorrhage, can be diagnosed by transvaginal sonography in the first trimester of pregnancy [2,6]. One may consider whether the size of leiomyoma changes during pregnancy. A previous study demonstrated that the size of leiomyoma increased in the second trimester and decreased in the third trimester [21]. Another study showed that the size of leiomyoma in the third trimester was similar to that in the first trimester [2]. Accordingly, sizes of leiomyomas determined by ultrasound in the first trimester can be used as predictors of massive intraoperative haemorrhage in caesarean delivery. The present study has limitations. We only analysed intraoperative haemorrhage because the medical records did not include data on total haemorrhage after caesarean delivery in some cases. As massive postpartum haemorrhage can occur at the bedside after caesarean delivery, postpartum haemorrhages might be more severe than intraoperative haemorrhages in women with leiomyoma who underwent caesarean delivery. In women with the largest leiomyoma <175 cm3, postpartum haemorrhages might exceed 1000 ml because of additional bleeding after caesarean delivery. A large intramural or submucosal leiomyoma 175 cm3 (equivalent in volume to a 7 cm-diameter sphere), birth weight 2500 g, and primipara were found to be significant predictors of massive haemorrhage (1000 ml) during caesarean delivery. Estimation of leiomyoma volume in the first trimester of pregnancy using sonography and foetal body weight just before delivery may be useful to predict massive intraoperative haemorrhage in caesarean delivery. When a pregnant patient with a significant risk factor is scheduled for caesarean delivery, preparation for haemorrhage is recommended, including storage of autologous blood. Author contributions’ Kiguna Sei planned the study, collected the data, and draw the manuscript. Kenichi Masui planned the study, analysed the data, and draw the manusctipt. Hidenori Sasa and Kenichi Furuya critically appraised the manuscript.
63
Funding This work was supported by the Department of Obstetrics and Gynecology and the Department of Anesthesiology, National Defense Medical College. Previous presentations This report was previously presented in part at the Euroanaesthesia 2014 in Stockholm, Sweden on 2 June, 2014. Conflicts of interest All authors declare no conflict of interest. Acknowledgement None. References [1] [Rice JP, Kay HH, Mahony BS. The clinical significance of uterine leiomyomas in pregnancy. Am J Obstet Gynecol 1989;160(5):1212–6. [2] Eze C, Odumeru E, Ochie K, Nwadike U, Agwuna K. Sonographic assessment of pregnancy co-existing with uterine leiomyoma in Owerri, Nigeria. Afr Health Sci 2013;13(2):453–60. [3] Vitale SG, Tropea A, Rossetti D, Carnelli M, Cianci A. Management of uterine leiomyomas in pregnancy: review of literature. Updates Surg 2013;65(3):179– 82. [4] Klatsky PC, Tran ND, Caughey AB, Fujimoto VY. Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. Am J Obstet Gynecol 2008;198(4):357–66. [5] Vergani P, Ghidini A, Strobelt N, Roncaglia N, Locatelli A, Lapinski RN, et al. Do uterine leiomyomas influence pregnancy outcome? Am J Perinatol 1994;11 (5):356–8. [6] ExacoustÒs C, Rosati P. Ultrasound diagnosis of uterine myomas and complications in pregnancy. Obstet Gynecol 1993;82(1):97–101. [7] Sheiner E, Sarid L, Levy A, Seidman DS, Hallak M. Obstetric risk factors and outcome of pregnancies complicated with early postpartum hemorrhage: a population-based study. J Matern Fetal Neonatal Med 2005;18(3):149–54. [8] American College of Obstetricians and Gynecologists. ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists number 76, October 2006: postpartum hemorrhage. Obstet Gynecol 2006;108(4):1039. [9] Caughey AB, Cahill AG, Guise J-M, Rouse DJ. Obstetricians ACo, Gynecologists Safe prevention of the primary cesarean delivery. Am J Obstet Gynecol 2014;210(3):179–93. [10] Magann EF, Evans S, Hutchinson M, Collins R, Lanneau G, Morrison JC. Postpartum hemorrhage after cesarean delivery: an analysis of risk factors. South Med J 2005;98(7):681–6. [11] Sheiner E, Sarid L, Levy A, Seidman DS, Hallak M. Obstetric risk factors and outcome of pregnancies complicated with early postpartum hemorrhage: a population-based study. J Matern Fetal Neonatal Med 2005;18(3):149–54. [12] Belghiti J, Kayem G, Dupont C, Rudigoz RC, Bouvier-Colle MH, Deneux-Tharaux C. Oxytocin during labour and risk of severe postpartum haemorrhage: a population-based, cohort-nested case-control study. BMJ Open 2011;1(2): e000514. [13] Murase E, Siegelman ES, Outwater EK, Perez-Jaffe LA, Tureck RW. Uterine leiomyomas: histopathologic features, MR imaging findings, differential diagnosis, and treatment. Radiographics 1999;19(5):1179–97. [14] Roman AS, Tabsh KM. Myomectomy at time of cesarean delivery: a retrospective cohort study. BMC Pregnancy Childbirth 2004;4(1):14. [15] Forssman L. Distribution of blood flow in myomatous uteri as measured by locally injected 133Xenon. Acta Obstet Gynecol Scand 1976;55(2):101–4. [16] Grignon D, Carey M, Kirk M, Robinson M. Diffuse uterine leiomyomatosis: a case study with pregnancy complicated by intrapartum hemorrhage. Obstet Gynecol 1987;69(3 Pt. 2):477–80. [17] Driessen M, Bouvier-Colle M-H, Dupont C, Khoshnood B, Rudigoz R-C, DeneuxTharaux C. Postpartum hemorrhage resulting from uterine atony after vaginal delivery: factors associated with severity. Obstet Gynecol 2011;117(1):21. [18] Sosa CG, Althabe F, Belizán JM, Buekens P. Risk factors for postpartum hemorrhage in vaginal deliveries in a Latin-American population. Obstet Gynecol 2009;113(6):1313. [19] de Geest K, Thiery M, Piron-Possuyt G, Vanden Driessche R. Plasma oxytocin in human pregnancy and parturition. J Perinat Med 1985;13(1):3–13. [20] Blomberg M. Maternal obesity and risk of postpartum hemorrhage. Obstet Gynecol 2011;118(3):561–8. [21] Lev-Toaff AS, Coleman BG, Arger PH, Mintz MC, Arenson RL, Toaff ME. Leiomyomas in pregnancy: sonographic study. Radiology 1987;164(2):375– 80.
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Full length article
Size of uterine leiomyoma is a predictor for massive haemorrhage during caesarean delivery Kiguna Seia , Kenichi Masuib,c,* , Hidenori Sasaa , Kenichi Furuyaa a
Department of Obstetrics and Gynecology, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359-8513, Japan Department of Anesthesiology, Showa University School of Medicine, Hatanodai 1-5-8, Sinagawa, Tokyo, 142-8666, Japan c Department of Anesthesiology, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama, 359-8513, Japan b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 June 2017 Received in revised form 18 November 2017 Accepted 15 February 2018 Available online xxx
Background: Uterine leiomyoma is a common benign tumour, and a risk factor for various complications during pregnancy and peripartum period. Peripartum haemorrhage is the most critical complication that can cause maternal death. Although the relationship of leiomyoma and peripartum haemorrhage has been indicated, little is known about the characteristics of leiomyoma as predictors for massive haemorrhage in caesarean delivery. Objective: We examined whether characteristics of leiomyoma and pregnant patients could predict massive haemorrhage in women undergoing caesarean delivery. Study design: This is a single-institution, retrospective cohort study. We reviewed singleton caesarean deliveries between January 2005 and December 2011. We excluded women with the following risk factors for massive haemorrhage: abnormality of placental position, abruptio placentae, haemorrhagic diseases, hydramnios, and labour arrest after induction. Myomectomy was not performed during delivery. Multivariate logistic regression analysis was performed to identify predictors of massive intraoperative haemorrhage (1000 ml). The following predictors were evaluated: maternal age, body mass index, parity, gestational week, birth weight, number of leiomyomas, and volume of the largest leiomyoma. Detailed characteristics of leiomyomas were evaluated using sonography or magnetic resonance imaging. Results: Seven hundred and fifty-nine women were included; 55 women (7.25%) had leiomyoma. Thirtyeight women with leiomyoma underwent magnetic resonance imaging scan. The median intraoperative haemorrhage was 939 ml (395–5296 ml) in women with leiomyoma and 689 ml (129–3060 ml) in women without. Multivariate analysis revealed that a largest leiomyoma 175 cm3 (odds ratio 6.4 [95% confidence interval: 1.5–27], P = 0.007), birth weight of 2500 g (2.3 [1.53.6], P < 0.001), and primipara (1.5 [1.1–2.1], P = 0.025) were significant predictors of massive intraoperative haemorrhage. Conclusions: The presence of a leiomyoma of 175 cm3, birth weight of 2500 g, and primipara were found to be predictors for massive intraoperative haemorrhage during caesarean delivery. A leiomyoma 175 cm3 which is equivalent volume to a 7 cm diameter sphere can be diagnosed in the first trimester using sonography. In cases of cesarean delivery with these predictors, preparation for massive haemorrhage, including storage of autologous blood, may be considered. © 2018 Elsevier B.V. All rights reserved.
Keywords: Caesarean section Haemorrhage Leiomyoma
Introduction Uterine leiomyoma is one of the most common solid benign tumours of the uterus, developing in 20–40% of reproductive-age women [1]. The prevalence of leiomyoma during pregnancy was reported as approximately 11% in early studies [2–4], and seems to be increasing today due to improvements in diagnostic
* Corresponding author at: Department of Anesthesiology, Showa University School of Medicine, Hatanodai 1-5-8, Sinagawa, Tokyo, 142-8666, Japan. E-mail address: [email protected] (K. Masui). https://doi.org/10.1016/j.ejogrb.2018.02.014 0301-2115/© 2018 Elsevier B.V. All rights reserved.
approaches. Several studies revealed that leiomyomas cause complications including miscarriage, preterm labour, and haemorrhage during pregnancy, labour, and delivery [5–8]. Among various complications in deliveries, haemorrhage is the most critical and can cause maternal death [9]. Leiomyoma is recognized as a risk factor for caesarean delivery. Some studies have reported that larger leiomyomas could increase the rate of caesarean delivery [4,10]. Caesarean delivery itself is a risk for massive peripartum haemorrhage when compared to transvaginal delivery8. As leiomyomas can cause haemorrhage during delivery, the risk of massive haemorrhage in caesarean deliveries in women with leiomyomas may be higher than that in
K. Sei et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 223 (2018) 60–63
women without leiomyomas. Although some studies examined the risk of peripartum haemorrhage in women with leiomyomas, they examined the risk in caesarean and transvaginal deliveries simultaneously [6,10]. One study reported the presence of leiomyomas can be a risk factor for massive haemorrhage in caesarean delivery [11]. However, a small uterine leiomyoma is unlikely to cause massive haemorrhage. If characteristics of leiomyomas are a predictor of intraoperative haemorrhage during caesarean delivery, it would be helpful to identify these features in order to decrease the risk of massive peripartum haemorrhage. The aims of this study were, first, to examine whether the size and number of leiomyomas can predict massive haemorrhage during caesarean delivery, and second, to evaluate whether characteristics of the patient or baby could predict massive haemorrhage during caesarean delivery. Materials and methods Study population This was a single-institution, retrospective cohort study. The study was approved by the institutional review board of our medical college (KAN-201, National Defense Medical College, Saitama, Japan); the board judged that written informed consent was not required since the data of this study was collected from hospital medical records. We reviewed the medical records of women undergoing caesarean singleton delivery between January 2005 and December 2011. We excluded women who had an abnormality of placental position, abruptio placentae, and haemorrhagic diseases (such as HELLP syndrome, idiopathic thrombocytopenic purpura, and disseminated intravascular coagulation) [12]. We also excluded women who had hydramnios and women who experienced labour arrest, because these may result in massive postpartum haemorrhage due to uterine atony [13]. Clinical procedures Leiomyoma was diagnosed by transvaginal sonography in all women during prenatal check-up. When a woman had a leiomyoma obstructing the birth canal or located in the area of uterine incision for caesarean delivery, magnetic resonance imaging (MRI) was performed at 34–35 gestational weeks. In these patients, we used the MRI findings to evaluate detailed characteristics of the leiomyomas, recognizing that MRI examination is not generally performed in pregnant women. The uterine incision was performed in the same manner, avoiding incision into a leiomyoma. Simultaneous myomectomy at caesarean delivery was not performed, except in women who had small subserosal leiomyomas that could be excised easily without massive bleeding.
61
Collected variables Based on the delivery records, we collected the following characteristics of women for our analysis: parity, age at delivery, maternal body weight, maternal height, body mass index (BMI), gestational week, birth weight, and intraoperative haemorrhage, which was determined as the sum of suction volume and gauze counting. We determined the three major axes of the leiomyoma based on MRI findings, and the number of leiomyomas based on MRI or sonographic findings during the pregnancy. We calculated the volume of the leiomyomas using the following equation: volume ¼
4pabc 3
where a, b, and c are the lengths of the three major axes of a leiomyoma. We regarded subserosal leiomyomas not to be leiomyomas in the analysis because several studies have revealed that subserosal leiomyomas are usually asymptomatic and have little or no influence on intraoperative haemorrhage [14]. Multivariate logistic regression analysis We selected the following dichotomous variables as factors examined with univariate logistic regression analysis: age at delivery >35 or 35 years, maternal BMI 25 or <25 kg m2, primipara or multipara, gestational week 38 or <38, birth weight >2500 or 2500 g, volume of the largest leiomyoma in each patient x or
Table 1 Patient and baby characteristics. Characteristics
All patients (n = 759)
Leiomyoma (n = 55)
No leiomyoma (n = 704)
P value for Leiomyoma vs No leiomyoma
Age, year Maternal body weight, kg Maternal height, cm Maternal body mass index, kg/m2 Gestational week Primipara Birth weight of baby, g Intraoperative haemorrhage, mL Intraoperative haemorrhage 1000 mL
33 (19–45) 63 (41–125) 157 (140–190) 25 (17–49) 37 (27–42) 267 (35%) 2740 (400–4440) 700 (129–5296) 182 (24%)
35 (26–45) 63 (44–82) 159 (150–172) 25 (20–34) 37 (31–41) 31 (56%) 2750 (1416–3725) 939 (395–5296) 25 (45%)
33 (19–45) 63 (41–125) 157 (140–190) 25 (17–49) 37 (27–42) 236 (34%) 2738 (400–4440) 689 (129–3060) 157 (22%)
<0.001 0.994 0.013 0.133 0.415 0.001 0.845 <0.001 <0.001
Data are expressed as median (range). Primipara and intraoperative haemorrhage are expressed number (%).
62
K. Sei et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 223 (2018) 60–63
Table 2 Univariate analysis of intraoperative haemorrhage 1000 ml. Factors
Number
Intraoperative haemorrhage 1000 ml, Number (%)
Yes No
239 520
64 (27) 118 (23)
Yes No
410 349
108 (26) 74 (21)
Yes No
228 531
60 (26) 122 (23)
Yes No
267 492
77 (29) 105 (21)
Yes No
541 218
150 (28) 32 (15)
Yes No
16 743
12 (75) 170 (23)
Yes No
13 746
7 (54) 175 (24)
Age >35 year
Body mass index 25 kg/m2
Gestational week 38 weeks
Primipara
Birth weight of baby 2500 g
Volume of largest leiomyoma 175 cm3
Number of leiomyomas 3
Odds ratio
95% confidential interval
P value
1.2
0.9–1.8
0.221
1.3
0.9–1.9
0.099
1.2
0.8–1.7
0.323
1.5
1.1–2.1
0.021
2.2
1.5–3.4
<0.001
10.1
3.2–31.8
<0.001
3.8
1.3–11.5
0.018
Data are expressed as number (percentage) for each factor. Odds ratio with 95% confidential interval and P value are expressed for each factors. P value <0.05 is considered to be significant.
NY, USA) and JMP Pro version 13 (SAS Institute Japan, Co., Ltd., Tokyo, Japan) was used for statistical analyses. A P value less than 0.05 was regarded as significant. Results There were 4736 singleton deliveries during the study period, including 1079 by caesarean delivery. Seven hundred fifty-nine women met the inclusion criteria; of these, 55 women had one or more leiomyomas and 38 women underwent MRI examinations at 34–35 gestational weeks. The prevalence of leiomyoma in singleton delivery women and women undergoing caesarean deliveries was 3.3% and 7.2%, respectively. Patient and baby characteristics are shown in Table 1. Intraoperative haemorrhage in women with leiomyoma (939 (395–5296) ml) was larger than that in women without leiomyoma (689 (129–3060) ml). The proportion of primipara among women with leiomyoma was higher than that among women without leiomyoma (56% vs. 34%). Age, maternal body weight, maternal height, maternal BMI, gestational week, and birth weight were similar between women with versus without leiomyoma. Volume of the maximum leiomyoma was 139 (4–1633) cm3 in 38 women with MRI findings, and the number of leiomyomas was 1 (1–12) in 55 women. Thirty-two, 10, and 13 women had 1, 2, and 3 leiomyomas, respectively. The cut-off value of the volume of the maximum leiomyoma was 175 cm3. In 17 women without MRI examination, sonographic findings revealed that no patient had a leiomyoma 175 cm3.
Table 3 Significant predictors for intraoperative haemorrhage 1000 ml by multivariate analysis. Significant predictors
Odds ratio
95% confidential interval
P value
Primipara Birth weight of baby 2500 g Volume of largest leiomyoma 175 cm3
1.5 2.4 9.7
1.0–2.1 1.6–3.7 3.0–31.4
0.031 <0.001 <0.001
Data are expressed as number (percentage) for each significant predictor. Odds ratio with 95% confidential interval and P value are expressed for each significant predictors. P value <0.05 is considered to be significant.
Table 2 shows factors examined in the univariate logistic regression analysis for massive intraoperative haemorrhage and number of women with massive intraoperative haemorrhage. Body mass index 25 kg/m2, primipara, birth weight 2500 g, presence of a 175-cm3 volume leiomyoma, and number of leiomyomas 3 were identified as the possible predictors. Multivariate logistic regression analysis demonstrated that primipara (OR 1.5 [95%CI 1.0–2.1]), birth weight 2500 g (OR 2.4 [95% CI 1.6–3.7]), and presence of a 175-cm3 volume leiomyoma (OR 9.7 [95%CI 3.0–31.4]) were significant predictors for intraoperative haemorrhage 1000 ml (Table 3). A bootstrap analysis confirmed the internal validity of the final regression model with 95% CI of 1.0-2.1 for primipara (P = .028), 1.6–4.1 for birth weight 2500 g (P < 0.001), and 4.0-50.7 for the presence of a 175-cm3 volume leiomyoma (P < 0.001). Discussion We found that intramural or submucosal leiomyoma was a risk factor for massive intraoperative haemorrhage (1000 ml) in caesarean delivery. The presence of a large-sized leiomyoma 175 cm3, birth weight 2500 g, and primipara were found to be significant predictors. A large-sized leiomyoma 175 cm3, which is equivalent in volume to a 7 cm diameter sphere, was found to be a clear risk factor for massive intraoperative haemorrhage (OR 9.7 [95%CI 3.0– 31.4]). A previous study found a decreased blood flow rate in leiomyomas and adjacent normal myometrium, as compared with myometrium of the normal uterus [15]. The low blood perfusion may decrease the distribution of oxytocin, which can result in uterine atony. Another study observed haphazard bundles of smooth muscle with focal smooth muscle necrosis and hyaline changes [16]. Irregular lines in the entire myometrium might inhibit muscular contraction of the uterus. Birth weight 2500 g was also a predictor for massive intraoperative haemorrhage (OR 2.1 [95%CI 1.6–3.7]). The mechanism of the increased risk of haemorrhage with a larger baby would be based on uterine atony. Several studies reported that babies greater than 4000 g cause an over-distended uterus and uterine atony may be induced [8,17,18]. The influence of overweight in neonates is unknown in this study because the
K. Sei et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 223 (2018) 60–63
birth weights born from pregnant women with leiomyoma was below 4000 g; however, our results also indicate that a heavier birth weight causes more severe intraoperative haemorrhage in caesarean delivery. Primipara was found to be another predictor for massive intraoperative haemorrhage (OR 1.5 [95%CI 1.0–2.1]). This result is supported by an early population-based cohort study showing that primipara was a risk factor for massive postpartum haemorrhage due to uterine atony [17]. As oxytocin is the primary hormone for uterine contraction, the effect of oxytocin might be related to uterine atony in primiparous women. A study revealed that plasma oxytocin concentrations during pregnancy in multipara women were lower than that in primipara women [19]. This result implies that oxytocin plasma level might have less effect on uterine contraction in primiparous women. Maternal BMI was found not to be a predictor of intraoperative haemorrhage in our population, where the maximum BMI was 34.1 kg m2 in women with leiomyoma. A previous study showed that maternal obesity with BMI 40 kg/m2 was a risk factor for postpartum haemorrhage [20]. Overweight but not obese may not be a risk factor for haemorrhage during caesarean delivery. In the present study, the sizes of leiomyomas were evaluated at 34–35 gestational weeks using MRI images. Although MRI examination would not be performed in daily clinical practice, it was useful to accurately assess leiomyoma volume. The determined volume of a leiomyoma of 175 cm3, as a risk factor for massive haemorrhage, can be diagnosed by transvaginal sonography in the first trimester of pregnancy [2,6]. One may consider whether the size of leiomyoma changes during pregnancy. A previous study demonstrated that the size of leiomyoma increased in the second trimester and decreased in the third trimester [21]. Another study showed that the size of leiomyoma in the third trimester was similar to that in the first trimester [2]. Accordingly, sizes of leiomyomas determined by ultrasound in the first trimester can be used as predictors of massive intraoperative haemorrhage in caesarean delivery. The present study has limitations. We only analysed intraoperative haemorrhage because the medical records did not include data on total haemorrhage after caesarean delivery in some cases. As massive postpartum haemorrhage can occur at the bedside after caesarean delivery, postpartum haemorrhages might be more severe than intraoperative haemorrhages in women with leiomyoma who underwent caesarean delivery. In women with the largest leiomyoma <175 cm3, postpartum haemorrhages might exceed 1000 ml because of additional bleeding after caesarean delivery. A large intramural or submucosal leiomyoma 175 cm3 (equivalent in volume to a 7 cm-diameter sphere), birth weight 2500 g, and primipara were found to be significant predictors of massive haemorrhage (1000 ml) during caesarean delivery. Estimation of leiomyoma volume in the first trimester of pregnancy using sonography and foetal body weight just before delivery may be useful to predict massive intraoperative haemorrhage in caesarean delivery. When a pregnant patient with a significant risk factor is scheduled for caesarean delivery, preparation for haemorrhage is recommended, including storage of autologous blood. Author contributions’ Kiguna Sei planned the study, collected the data, and draw the manuscript. Kenichi Masui planned the study, analysed the data, and draw the manusctipt. Hidenori Sasa and Kenichi Furuya critically appraised the manuscript.
63
Funding This work was supported by the Department of Obstetrics and Gynecology and the Department of Anesthesiology, National Defense Medical College. Previous presentations This report was previously presented in part at the Euroanaesthesia 2014 in Stockholm, Sweden on 2 June, 2014. Conflicts of interest All authors declare no conflict of interest. Acknowledgement None. References [1] [Rice JP, Kay HH, Mahony BS. The clinical significance of uterine leiomyomas in pregnancy. Am J Obstet Gynecol 1989;160(5):1212–6. [2] Eze C, Odumeru E, Ochie K, Nwadike U, Agwuna K. Sonographic assessment of pregnancy co-existing with uterine leiomyoma in Owerri, Nigeria. Afr Health Sci 2013;13(2):453–60. [3] Vitale SG, Tropea A, Rossetti D, Carnelli M, Cianci A. Management of uterine leiomyomas in pregnancy: review of literature. Updates Surg 2013;65(3):179– 82. [4] Klatsky PC, Tran ND, Caughey AB, Fujimoto VY. Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. Am J Obstet Gynecol 2008;198(4):357–66. [5] Vergani P, Ghidini A, Strobelt N, Roncaglia N, Locatelli A, Lapinski RN, et al. Do uterine leiomyomas influence pregnancy outcome? Am J Perinatol 1994;11 (5):356–8. [6] ExacoustÒs C, Rosati P. Ultrasound diagnosis of uterine myomas and complications in pregnancy. Obstet Gynecol 1993;82(1):97–101. [7] Sheiner E, Sarid L, Levy A, Seidman DS, Hallak M. Obstetric risk factors and outcome of pregnancies complicated with early postpartum hemorrhage: a population-based study. J Matern Fetal Neonatal Med 2005;18(3):149–54. [8] American College of Obstetricians and Gynecologists. ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists number 76, October 2006: postpartum hemorrhage. Obstet Gynecol 2006;108(4):1039. [9] Caughey AB, Cahill AG, Guise J-M, Rouse DJ. Obstetricians ACo, Gynecologists Safe prevention of the primary cesarean delivery. Am J Obstet Gynecol 2014;210(3):179–93. [10] Magann EF, Evans S, Hutchinson M, Collins R, Lanneau G, Morrison JC. Postpartum hemorrhage after cesarean delivery: an analysis of risk factors. South Med J 2005;98(7):681–6. [11] Sheiner E, Sarid L, Levy A, Seidman DS, Hallak M. Obstetric risk factors and outcome of pregnancies complicated with early postpartum hemorrhage: a population-based study. J Matern Fetal Neonatal Med 2005;18(3):149–54. [12] Belghiti J, Kayem G, Dupont C, Rudigoz RC, Bouvier-Colle MH, Deneux-Tharaux C. Oxytocin during labour and risk of severe postpartum haemorrhage: a population-based, cohort-nested case-control study. BMJ Open 2011;1(2): e000514. [13] Murase E, Siegelman ES, Outwater EK, Perez-Jaffe LA, Tureck RW. Uterine leiomyomas: histopathologic features, MR imaging findings, differential diagnosis, and treatment. Radiographics 1999;19(5):1179–97. [14] Roman AS, Tabsh KM. Myomectomy at time of cesarean delivery: a retrospective cohort study. BMC Pregnancy Childbirth 2004;4(1):14. [15] Forssman L. Distribution of blood flow in myomatous uteri as measured by locally injected 133Xenon. Acta Obstet Gynecol Scand 1976;55(2):101–4. [16] Grignon D, Carey M, Kirk M, Robinson M. Diffuse uterine leiomyomatosis: a case study with pregnancy complicated by intrapartum hemorrhage. Obstet Gynecol 1987;69(3 Pt. 2):477–80. [17] Driessen M, Bouvier-Colle M-H, Dupont C, Khoshnood B, Rudigoz R-C, DeneuxTharaux C. Postpartum hemorrhage resulting from uterine atony after vaginal delivery: factors associated with severity. Obstet Gynecol 2011;117(1):21. [18] Sosa CG, Althabe F, Belizán JM, Buekens P. Risk factors for postpartum hemorrhage in vaginal deliveries in a Latin-American population. Obstet Gynecol 2009;113(6):1313. [19] de Geest K, Thiery M, Piron-Possuyt G, Vanden Driessche R. Plasma oxytocin in human pregnancy and parturition. J Perinat Med 1985;13(1):3–13. [20] Blomberg M. Maternal obesity and risk of postpartum hemorrhage. Obstet Gynecol 2011;118(3):561–8. [21] Lev-Toaff AS, Coleman BG, Arger PH, Mintz MC, Arenson RL, Toaff ME. Leiomyomas in pregnancy: sonographic study. Radiology 1987;164(2):375– 80.