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Pregnancy outcomes and ultrasonographic diagnosis in patients with histologically-proven placental chorioangioma
Placenta 32 (2011) 671e674
Contents lists available at ScienceDirect
Placenta journal homepage: www.elsevier.com/locate/placenta
Pregnancy outcomes and ultrasonographic diagnosis in patients with histologically-proven placental chorioangiomaq,qq K. Wou a, M.F. Chen b, A. Mallozzi a, R.N. Brown a, A. Shrim a, * a b
Department of Obstetrics and Gynaecology, McGill University Health Center, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada Department of Pathology, McGill University Health Center, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada
Condensation: Many chorioangiomas are not identified by routine prenatal sonogram. Even in the absence of ultrasonic abnormalities, Neonatal Intensive Care Unit admission rate is increased.
a r t i c l e i n f o
a b s t r a c t
Article history: Accepted 13 June 2011
Objective: To evaluate pregnancy outcome and ultrasound diagnosis in patients with histologicallyconfirmed placental chorioangioma. Study design: Placentas with histological diagnosis of chorioangioma were identified and medical charts were reviewed for findings of ultrasound examinations. Pregnancy outcomes were compared with all singleton deliveries without chorioangioma in the same time period. Main outcome measures: Primary outcome was Neonatal Intensive Care Unit admission rate. Secondary outcome was ultrasound detection rate of chorioangioma. Results: Among 14,725 singleton deliveries, 23 placentas were diagnosed with chorioangioma (0.16%). The control group included all singleton deliveries without chorioangioma (n ¼ 14702). Neonates in the study group were more likely to be admitted to the Neonatal Intensive Care Unit (OR ¼ 4.45) and to have smaller birth weight (p ¼ 0.006). Only 2 of 7 larger chorioangiomas (2 cm) with available ultrasound reports were identified by ultrasound (29% detection rate). All cases demonstrated normal fetal growth and wellbeing. Conclusion: Chorioangiomas are not always identified by routine prenatal sonography. Even in the absence of ultrasonic abnormalities, neonatal morbidity, as measured by NICU admission rate, is increased. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Antenatal complications Chorioangioma Placenta tumors Ultrasound
1. Introduction Placental chorioangioma is the most frequent non-trophoblastic tumor of the placenta being a benign tumor derived from primitive chorionic mesenchyme and typically being vascular. Its incidence has been reported as 1% in placentas examined by microscopy [1], however chorioangiomas that are clinically evident are less common with an incidence estimated between 1:3500 and 1:9000 births [1]. Small tumors are usually asymptomatic but large tumors may be associated with arterio-venous shunting within the placenta, and may result in the development of fetal anemia, thrombocytopenia,
q Presented at the 66th SOGC (Society of Obstetricians and Gynecologists of Canada) Annual Clinical Meeting, June 2010, Montreal, Quebec, Canada. qq This study was financed within the department. * Corresponding author. Tel.: þ1 5145183210. E-mail address: [email protected] (A. Shrim). 0143-4004/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.placenta.2011.06.007
hydrops, polyhydramnios, antepartum hemorrhage, preterm labor and birth, intrauterine fetal growth restriction (IUGR) and increased perinatal mortality [2e5]. Although the majority of chorioangiomas are diagnosed postnataly, antenatal sonographic diagnosis may allow a higher risk pregnancy to be appropriately monitored with improved outcomes. Our objectives were to assess pregnancy outcomes in patients with histologically-proven placental chorioangiomas as well as to evaluate the antenatal detection of these tumors. 2. Materials and methods This was a retrospective cohort study. All placentas from pregnancies delivered at the McGill University Health Center (MUHC) are routinely examined within our pathology department by experienced perinatal pathology technicians and pathologists. All placental pathology reports demonstrating a histological diagnosis of chorioangioma from singleton pregnancies delivered between January 2003 and July 2007 were identified from the placenta pathology database. Relevant information on the placental morphology was collected from the pathology report including: placental
672
K. Wou et al. / Placenta 32 (2011) 671e674
weight and size, and abnormal findings on the fetal or maternal surfaces. The medical charts from these pregnancies as well as the “McGill Obstetrical and Neonatal Database” (MOND e a comprehensive computerized database of obstetrical and neonatal data for all pregnancies delivered at the MUHC in Montreal, Canada) were then reviewed to obtain baseline demographic characteristics as well as obstetric and neonatal outcome variables. These included the results of ultrasound examinations from which fetal biometry, fetal weight estimations, morphology evaluations of both the fetus and the placenta, amniotic fluid assessment; Doppler studies and fetal biophysical profile evaluations were extracted. Only ultrasound charts of patients that were scanned in our department during the third trimester were reviewed. At our institution during the time period of the study all pregnant women were offered ultrasound examinations between 11 and 13 weeks of gestational age, to confirm dating and for aneuploidy screening by nuchal translucency, at 20e23 weeks, for morphological assessment, and at 32 weeks for fetal growth. However not all women delivering at the institution have their ultrasound examinations undertaken within our department. As controls, we included all singleton deliveries in the same medical center that did not have chorioangioma. Patients with chorioangiomas that were 2 cm or larger (largest diameter) were sub-analyzed with emphasis on the third trimester ultrasound findings and antenatal diagnosis of the lesions. Admission to the neonatal intensive care unit (NICU) was used as an indicator of neonatal morbidity, as was the number of hospital admission days. Preterm delivery was defined as delivery before the beginning of the 37th week of gestation. Hypertension complicating pregnancy was defined as any hypertensive disorder during pregnancy, whether chronic (prior to 20 weeks of gestational age), pregnancy-induced hypertension or preeclampsia. Operative vaginal delivery was defined as a vaginal delivery that was assisted by either forceps or vacuum of any type. IRB Approval for the study was granted by the Research Institute of the McGill University Health Center (10-322-SDR). Continuous variables were all described by mean values and standard deviations. Categorical variables were described by frequency and percentage. Statistical analysis was performed with SPSS statistical software (PASW 18, IBM, Armonk, NY, USA) version 10. Odds ratios, 95% confidence intervals and differences between categorical variables were analyzed using chi-square or Fisher tests as appropriate. Differences between continuous variables were tested using independent sample t tests if normally distributed otherwise by the ManneWhitney U tests. P values of <0.05 (two-sided) were considered to indicate statistical significance.
3. Results During the study period, 14,725 singleton babies were delivered; of these, 23 cases were diagnosed with chorioangioma (0.16%). The Control group included all deliveries during period without chorioangioma (n ¼ 14,702). Except for Parity, both groups had similar baseline demographic characteristics (Table 1). Mean maternal age was 30.6 4.6 years for the chorioangioma group versus 31.6 5.1 years for the control group (p value ¼ 0.22). Gravidity as well as rates of infertility and spontaneous or therapeutic abortions did not differ between the Table 1 Baseline maternal characteristics and pregnancy outcomes.
Baseline Characteristics Maternal Age, years (mean S.D.) Gravidity (mean) Parity (mean) Rates of smokers, n(%) Rates of alcohol users, n(%) Primiparous, n(%) Pregnancy Outcomes Gestational age at delivery, weeks (Mean S.D) Hypertension, n(%) Diabetes, n(%) Spontaneous Vaginal Deliveries, n(%) Operative Deliveries, n(%) Cesarean Sections, n(%) a
Statistically significant.
Chorioangioma Group (N ¼ 23)
Control Group (N ¼ 14702)
30.6 4.6
31.6 5.1
0.22
2.22 0.70 1 (4.4%) 3 (13.0%) 13 (56.5%)
2.46 1.36 1018 (6.9%) 937 (6.4%) 6997 (47.6)
0.4 0.005a 0.62 0.81 0.4
38.9
39.1
0.47
2 (8.7%) 1 (4.4%) 14 (60.9%)
802 (5.5%) 1099 (7.5%) 1033 (68.8%)
0.36 0.9 <0.001a
4 (17.4%) 5 (21.7%)
871 (5.9%) 3718 (25.3%)
0.04a 0.81
P value
two groups (all p value > 0.4). Parity was significantly lower in the chorioangioma group compared with the control group (Average parity ¼ 0.7 vs. 1.36 in the chorioangioma and control group respectively, p ¼ 0.005). However, the higher rate of primiparous women in the chorioangioma group did not reach statistical significance (56.5% vs 47.6%, p ¼ 0.4). Rates of hypertension (8.7% vs. 5.5% in the chorioangioma and control group respectively, p ¼ 0.36) and diabetes during pregnancy (4.4% and 7.5% in the chorioangioma and control group respectively, p ¼ 0.9) were not different between the two groups. The chorioangioma group had a higher rate of operative vaginal deliveries (17.4% versus 5.9%, p value ¼ 0.04) and lower rate of spontaneous vaginal deliveries (60.9% versus 68.8%, p value < 0.001). Although the cesarean section rate was higher in the chorioangioma group, the difference did not reach statistical significance (21.7% versus 25.3%, p value ¼ 0.81). Neonates in the study group were more likely to be female (OR ¼ 2.42, 95% CI 0.90e6.90), to have a lower average birth weight (3008 822 g vs. 3356 624 g, p ¼ 0.006) and to have a preterm birth (OR 2.97, 95% CI 0.80e8.30). Only birth-weights, however, reached statistical significance. The rate of NICU admission was significantly increased for the chorioangioma group (OR ¼ 4.45, 95% CI 1.41e11.80). Of the 6 admissions to NICU in this group, the diagnoses were respiratory distress syndrome (2 cases), cardiac malformation (1 case), hypoglycemia (1 case) and prematurity with IUGR (2 cases). The chorioangioma group had a mean hospital stay of 6.2 13.7 days Vs. 3.6 8.2 days for the control group (p value ¼ 0.12). There were no significant differences in either the one-minute and five-minute APGAR scores nor in the umbilical cord pH (p values ¼ 0.96, 0.67 and 0.89 respectively) (Table 2). Nine patients had large chorioangiomas defined as largest diameter 2 cm, (39% of study cases and 0.06% of all singleton deliveries) with these ranging in size from 6 cm3 to 475 cm3 in volume. The maximal diameter of the largest chorioangioma measured 10 cm (overall size 10 9.5 5 cm), and the average maximal diameter of these nine cases was 5.3 cm. Out of 7 larger chorioangioma cases for which ultrasound reports were available for both second and third trimesters, only two had been recognized by routine antenatal ultrasound in the third trimester (32 1/7 weeks) (29% detection rate). All seven cases had normal amniotic fluid, appropriate fetal growth, biophysical profile and umbilical artery Doppler studies. For the 14 cases with a chorioangioma <2 cm in size, ultrasound reports were available for 11 patients (8 with ultrasound reports in both second and third trimesters and 3 with reports for third trimester ultrasounds only). None of these had been detected antenatally. Table 2 Neonatal outcomes. Chorioangioma Group (N ¼ 23)
Control Group (N ¼ 14702)
Odds Ratio (95% CI) or P value
Female Gender, n(%)
16 (69.6%)
7130 (48.5%)
Prematurity < 37 weeks, n(%)
5 (21.7%)
1254 (8.5%)
Birthweight, grams (mean SD) NICU Admission, n(%)
3008 822 6 (26.1%)
3356 624 1066 (7.3%)
Baby Stay in Hospital, days (mean SD) Apgar Score at 1-min (mean) Apgar Score at 5-min (mean) Cord pH (mean)
6.2 13.7
3.6 8.2
2.42 (0.9e6.9) 2.97 (0.8e8.3) 0.006a 4.45a (1.4e11.8) 0.12
8.1 8.9 7.25
8.2 9.0 7.26
0.96 0.67 0.89
a
Statistically significant.
K. Wou et al. / Placenta 32 (2011) 671e674
When comparing the “large chorioangioma” subgroup with the control group, no statistically significant differences in the baseline demographic characteristics or in the rates of hypertension and diabetes during pregnancy were found (Table 3). Patients in the large chorioangioma group had a significantly lower rate of spontaneous vaginal delivery (44.0% versus 68.8%, p value ¼ 0.002) with non-significant increases in both cesarean section (44.0% versus 25.3%, p value ¼ 0.24) and operative vaginal delivery rates (11.0% versus 5.9%, p value ¼ 0.42) when compared with the control group. Neonates in the larger chorioangioma group were again more likely to be female (OR ¼ 8.49, 95% CI 1.10e377.0). The rate of preterm birth, average birth weight, APGAR scores at 1-min and 5-min and cord pH were not significantly different between the two groups. Only one of the neonates in the larger chorioangioma group was admitted to the NICU, with a total hospital stay of 26 days (Table 4). Chorioangioma correlated with placental weight (r ¼ 0.718693, p ¼ 0.0001) but not with birth weight, Apgar score or presence of post partum hemorrhage. 4. Discussion At our institution the placentas of all deliveries are examined within our pathology service. This therefore is one of the first cohort studies to evaluate pregnancy outcomes and the frequency of prenatal diagnosis of this entity based upon the histopathological diagnosis of the presence of a chorioangioma. Examining all placentas might explain the relatively lower incidence of chorioangioma in our study as the population we studied was a more normal-risk homogeneous population compared to other more high-risk populations where the cited incidence is 1%. There are more than 70 cases of placental chorioangioma associated with adverse perinatal findings including hydramnios and severe fetal distress, abnormal Dopplers studies suggestive of fetal anemia, cardiac failure and hydrops reported in the literature [6e8]. Chatterjee et al. reported a case of a 55-mm chorioangioma of the placenta confirmed by sonogram and illustrated several associated complications: polyhydramnios, preterm premature rupture of membranes, and preterm delivery with associated respiratory distress syndrome and necrotizing enterocolitis [9]. Other reported complications have included uterine atony, post partum hemorrhage, fetal anemia, cardiac enlargement and failure, and hydrops fetalis [9,10]. Sepulveda et al. described 11 cases of placental chorioangioma diagnosed prenatally by ultrasound and color flow Doppler imaging [2]. Five of the nine singleton cases were complicated by polyhydramnios, oligohydramnios, fetal growth restriction or non-immune hydrops; four of these nine cases delivered before 35 weeks. In 7 of the 9 singleton cases, the size of Table 3 Baseline maternal characteristics and pregnancy outcomes of larger chorioangioma group.
Baseline Characteristics Maternal Age (mean S.D.) Gravidity (mean) Parity (mean) Pregnancy Outcomes Hypertension, n(%) Diabetes, n(%) Spontaneous Vaginal Deliveries, n(%) Operative Deliveries, n(%) Cesarean Sections, n(%) a
Statistically significant.
Larger Chorioangioma Group (N ¼ 9)
Control Group (N ¼ 14702)
P value
32.2 5.4 2.89 0.78
31.6 5.1 2.46 1.36
0.70 0.43 0.34
1 (11.0%) 0 (0.0%) 4 (44.0%)
802 (5.5%) 1099 (7.5%) 1033 (68.8%)
0.39 0.9 0.002a
1 (11.0%) 4 (44.0%)
871 (5.9%) 3718 (25.3%)
0.42 0.24
673
Table 4 Neonatal outcomes of the larger chorioangioma group. Larger Chorioangioma Group (N ¼ 9)
Control Group (N ¼ 14702)
Odds Ratio (95% CI) or P value
Female Gender, n(%)
8 (88.9%)
7130 (48.5%)
Prematurity <37 weeks, n(%)
1 (11.1%)
1254 (8.5%)
Birthweight, grams (mean SD) NICU Admission, n(%)
3286 739 1 (11.0%)
3356 624 1066 (7.3%)
Baby Stay in Hospital, days (mean SD) Apgar Score at 1-min, (mean) Apgar Score at 5-min, (mean) Cord pH, (mean)
5.1 7.8
3.6 8.2
8.49a (1.1e377.0) 1.34 (0.03e10.0) 0.69 1.59 (0.03e11.9) 0.56
7.9 9.1 7.23
8.2 9.0 7.26
0.68 0.80 0.82
a
Statistically significant.
the chorioangioma was greater than 60 mm, the other 2 being 43 mm or smaller without there being any sonographicallydetected complications other than an increasing tumor size. Tumor size appears to be the most important factor, not only in the antenatal diagnosis but also in influencing the prognosis of affected pregnancies. Zanardini et al. conducted a retrospective study of 19 cases of giant chorioangioma and described a wide variety of fetal complications such as polyhydramnios, growth restriction, hyperdynamic circulation, cardiomegaly, anemia and non-immune hydrops [11]. Due to the nature of our study that is based on post partum histological diagnosis, most of the lesions in our study were relatively small (average maximal diameter in the larger chorioangioma group was 53 mm). This probably explains why all the cases were asymptomatic. However, Jauniaux et al. also studied the use of Color Doppler in the diagnosis and management of chorioangiomas and found that the vascularity of the tumor, mapped by color flow, may be an independent factor for fetal complications, such as polyhydramnios, regardless of the tumor size [12]. A limitation of our study with regards to statistical analysis of such factors is the relatively small sample size, which is consequent to the low prevalence of chorioangioma. As shown in our study, placental chorioangiomas are not always associated with bad outcomes. Taori et al. described the sonographic features of a large placental chorioangioma (5.5 4.7 cm) with normal outcomes [13]. In addition, in a study by Isaacs et al. looking at fetal hydrops associated with tumors; placental chorioangiomas represented a small number of cases and had the best outcomes when compared with pericardial teratomas and hepatic hemangiomas [14]. In recent years there has been renewed interest in chorioangiomas due to greater opportunities for antenatal diagnosis with developments in ultrasonography and Doppler imaging [3]. In pregnancies where elevated levels of maternal serum alpha-fetoprotein (MSAFP) are identified, detailed sonographic evaluation including not only the fetus but the placenta is indicated [15]. Chorioangiomas may be distinguished from other placental masses by applying color Doppler and demonstrating increased blood flow [16e20]. Possible modalities in the treatment of chorioangiomas have been widely reported [21e23] but are beyond the scope of this study. The present cohort study shows that although many of the histologically-proven placental chorioangiomas may not be associated with significant adverse perinatal outcomes such as hydramnios, hydrops or fetal anemia, they might be associated with increased rates of NICU admission, smaller birth weight and operative delivery. Attention should be focused on prenatal diagnosis; despite advances in ultrasonography the detection rate for small placental
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chorioangiomas is low and this might represent the relatively less thorough examination afforded to the placenta as compared to the fetus. Although the incidence of this condition is low, detailed interrogation of the placenta by ultrasound, preferably incorporating modalities such as color flow imaging might allow a larger proportion of cases to be identified. Earlier diagnosis might result in improved outcomes with closer follow-up of affected pregnancies and the use of therapeutic interventions as indicated, in cases where complications arise. References [1] Guschmann M, Henrich W, Dudenhausen JW. Chorioangiomasenew insights into a well-known problem. II. An immuno-histochemical investigation of 136 cases. J Perinat Med 2003;31(2):170e5. [2] Sepulveda W, Alcalde JL, Schnapp C, Bravo M. Perinatal outcome after prenatal diagnosis of placental chorioangioma. Obstet Gynecol 2003;102(5 Pt 1): 1028e33. [3] Rech F, Salernitano D, Patella A. Placental chorioangioma. Minerva Ginecol 2002;54(5):417e33. [4] Bashiri A, Furman B, Erez O, Wiznitzer A, Holcberg G, Mazor M. Twelve cases of placental chorioangioma. Pregnancy outcome and clinical significance. Arch Gynecol Obstet 2002;266(1):53e5. [5] Garcia-Flores J, Vega-Malagon G, Vega-Malagon JA, Galvan-Aguilera A, Salmon-Velez F. Giant chorioangioma: presentation of a case. Rev Med Inst Mex Seguro Soc 2005;43(6):503e6. [6] Hurwitz A, Milwidsky A, Yarkoni S, Palti Z. Severe fetal distress with hydramnios due to chorioangioma. Acta Obstet Gynecol Scand 1983;62(6):633e5. [7] Panaccione JL, Esposito WJ, Haller JO. Acute polyhydramnios associated with chorioangioma. A case report. J Reprod Med 1991;36(3):210e2. [8] Imakita M, Yutani C, Ishibashi-Ueda H, Murakami M, Chiba Y. A case of hydrops fetalis due to placental chorioangioma. Acta Pathol Jpn 1988;38(7): 941e5. [9] Chatterjee Molly S. MDAJMLBCMLIMGJGMGMJMMVMJMMBNM. Chorioangioma. thefetus net. Available from: URL, http://www.sonoworld.com/ fetus/page.aspx?id¼164; 1993.
[10] Schmitz T, Opgen-Rhein B, Kroschwald P, Schroeder G, Weber S, Czernik C, et al. Severe transient cardiac failure caused by placental chorangiosis. Neonatology 2007;91(4):271e4. [11] Zanardini C, Papageorghiou A, Bhide A, Thilaganathan B. Giant placental chorioangioma: natural history and pregnancy outcome. Ultrasound Obstet Gynecol 2010;35(3):332e6. [12] Jauniaux E, Ogle R. Color Doppler imaging in the diagnosis and management of chorioangiomas. Ultrasound Obstet Gynecol 2000 Jun;15(6):463e7. [13] Taori K, Patil P, Attarde V, Singh A, Rangankar V. Chorioangioma of placenta: sonographic features. J Clin Ultrasound 2008;36(2):113e5. [14] Isaacs Jr H. Fetal hydrops associated with tumors. Am J Perinatol 2008;25(1): 43e68. [15] Maymon R, Hermann G, Reish O, Herman A, Strauss S, Sherman D, et al. Chorioangioma and its severe infantile sequelae: case report. Prenat Diagn 2003 15;23(12):976e80. [16] Prapas N, Liang RI, Hunter D, Copel JA, Lu LC, Pazkash V, et al. Color Doppler imaging of placental masses: differential diagnosis and fetal outcome. Ultrasound Obstet Gynecol 2000;16(6):559e63. [17] Zalel Y, Gamzu R, Weiss Y, Schiff E, Shalmon B, Dolizky M, et al. Role of color Doppler imaging in diagnosing and managing pregnancies complicated by placental chorioangioma. J Clin Ultrasound 2002;30(5):264e9. [18] Durin L, Barjot P, Herlicoviez M. Placental chorioangioma, value of ultrasonography: report of two cases. J Radiol 2002;83(6 Pt 1):739e41. [19] Zalel Y, Weisz B, Gamzu R, Schiff E, Shalmon B, Achiron R. Chorioangiomas of the placenta: sonographic and Doppler flow characteristics. J Ultrasound Med 2002 Aug;21(8):909e13. [20] Sepulveda W, Aviles G, Carstens E, Corral E, Perez N. Prenatal diagnosis of solid placental masses: the value of color flow imaging. Ultrasound Obstet Gynecol 2000 Nov;16(6):554e8. [21] Bhide A, Prefumo F, Sairam S, Carvalho J, Thilaganathan B. Ultrasound-guided interstitial laser therapy for the treatment of placental chorioangioma. Obstet Gynecol 2003;102(5 Pt 2):1189e91. [22] Sepulveda W, Wong AE, Herrera L, Dezerega V, Devoto JC. Endoscopic laser coagulation of feeding vessels in large placental chorioangiomas: report of three cases and review of invasive treatment options. Prenat Diagn 2009; 29(3):201e6. [23] Mendez-Figueroa H, Papanna R, Popek EJ, Byrd RH, Goldaber K, Moise Jr KJ, et al. Endoscopic laser coagulation following amnioreduction for the management of a large placental chorioangioma. Prenat Diagn 2009;29(13): 1277e8.
Contents lists available at ScienceDirect
Placenta journal homepage: www.elsevier.com/locate/placenta
Pregnancy outcomes and ultrasonographic diagnosis in patients with histologically-proven placental chorioangiomaq,qq K. Wou a, M.F. Chen b, A. Mallozzi a, R.N. Brown a, A. Shrim a, * a b
Department of Obstetrics and Gynaecology, McGill University Health Center, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada Department of Pathology, McGill University Health Center, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada
Condensation: Many chorioangiomas are not identified by routine prenatal sonogram. Even in the absence of ultrasonic abnormalities, Neonatal Intensive Care Unit admission rate is increased.
a r t i c l e i n f o
a b s t r a c t
Article history: Accepted 13 June 2011
Objective: To evaluate pregnancy outcome and ultrasound diagnosis in patients with histologicallyconfirmed placental chorioangioma. Study design: Placentas with histological diagnosis of chorioangioma were identified and medical charts were reviewed for findings of ultrasound examinations. Pregnancy outcomes were compared with all singleton deliveries without chorioangioma in the same time period. Main outcome measures: Primary outcome was Neonatal Intensive Care Unit admission rate. Secondary outcome was ultrasound detection rate of chorioangioma. Results: Among 14,725 singleton deliveries, 23 placentas were diagnosed with chorioangioma (0.16%). The control group included all singleton deliveries without chorioangioma (n ¼ 14702). Neonates in the study group were more likely to be admitted to the Neonatal Intensive Care Unit (OR ¼ 4.45) and to have smaller birth weight (p ¼ 0.006). Only 2 of 7 larger chorioangiomas (2 cm) with available ultrasound reports were identified by ultrasound (29% detection rate). All cases demonstrated normal fetal growth and wellbeing. Conclusion: Chorioangiomas are not always identified by routine prenatal sonography. Even in the absence of ultrasonic abnormalities, neonatal morbidity, as measured by NICU admission rate, is increased. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Antenatal complications Chorioangioma Placenta tumors Ultrasound
1. Introduction Placental chorioangioma is the most frequent non-trophoblastic tumor of the placenta being a benign tumor derived from primitive chorionic mesenchyme and typically being vascular. Its incidence has been reported as 1% in placentas examined by microscopy [1], however chorioangiomas that are clinically evident are less common with an incidence estimated between 1:3500 and 1:9000 births [1]. Small tumors are usually asymptomatic but large tumors may be associated with arterio-venous shunting within the placenta, and may result in the development of fetal anemia, thrombocytopenia,
q Presented at the 66th SOGC (Society of Obstetricians and Gynecologists of Canada) Annual Clinical Meeting, June 2010, Montreal, Quebec, Canada. qq This study was financed within the department. * Corresponding author. Tel.: þ1 5145183210. E-mail address: [email protected] (A. Shrim). 0143-4004/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.placenta.2011.06.007
hydrops, polyhydramnios, antepartum hemorrhage, preterm labor and birth, intrauterine fetal growth restriction (IUGR) and increased perinatal mortality [2e5]. Although the majority of chorioangiomas are diagnosed postnataly, antenatal sonographic diagnosis may allow a higher risk pregnancy to be appropriately monitored with improved outcomes. Our objectives were to assess pregnancy outcomes in patients with histologically-proven placental chorioangiomas as well as to evaluate the antenatal detection of these tumors. 2. Materials and methods This was a retrospective cohort study. All placentas from pregnancies delivered at the McGill University Health Center (MUHC) are routinely examined within our pathology department by experienced perinatal pathology technicians and pathologists. All placental pathology reports demonstrating a histological diagnosis of chorioangioma from singleton pregnancies delivered between January 2003 and July 2007 were identified from the placenta pathology database. Relevant information on the placental morphology was collected from the pathology report including: placental
672
K. Wou et al. / Placenta 32 (2011) 671e674
weight and size, and abnormal findings on the fetal or maternal surfaces. The medical charts from these pregnancies as well as the “McGill Obstetrical and Neonatal Database” (MOND e a comprehensive computerized database of obstetrical and neonatal data for all pregnancies delivered at the MUHC in Montreal, Canada) were then reviewed to obtain baseline demographic characteristics as well as obstetric and neonatal outcome variables. These included the results of ultrasound examinations from which fetal biometry, fetal weight estimations, morphology evaluations of both the fetus and the placenta, amniotic fluid assessment; Doppler studies and fetal biophysical profile evaluations were extracted. Only ultrasound charts of patients that were scanned in our department during the third trimester were reviewed. At our institution during the time period of the study all pregnant women were offered ultrasound examinations between 11 and 13 weeks of gestational age, to confirm dating and for aneuploidy screening by nuchal translucency, at 20e23 weeks, for morphological assessment, and at 32 weeks for fetal growth. However not all women delivering at the institution have their ultrasound examinations undertaken within our department. As controls, we included all singleton deliveries in the same medical center that did not have chorioangioma. Patients with chorioangiomas that were 2 cm or larger (largest diameter) were sub-analyzed with emphasis on the third trimester ultrasound findings and antenatal diagnosis of the lesions. Admission to the neonatal intensive care unit (NICU) was used as an indicator of neonatal morbidity, as was the number of hospital admission days. Preterm delivery was defined as delivery before the beginning of the 37th week of gestation. Hypertension complicating pregnancy was defined as any hypertensive disorder during pregnancy, whether chronic (prior to 20 weeks of gestational age), pregnancy-induced hypertension or preeclampsia. Operative vaginal delivery was defined as a vaginal delivery that was assisted by either forceps or vacuum of any type. IRB Approval for the study was granted by the Research Institute of the McGill University Health Center (10-322-SDR). Continuous variables were all described by mean values and standard deviations. Categorical variables were described by frequency and percentage. Statistical analysis was performed with SPSS statistical software (PASW 18, IBM, Armonk, NY, USA) version 10. Odds ratios, 95% confidence intervals and differences between categorical variables were analyzed using chi-square or Fisher tests as appropriate. Differences between continuous variables were tested using independent sample t tests if normally distributed otherwise by the ManneWhitney U tests. P values of <0.05 (two-sided) were considered to indicate statistical significance.
3. Results During the study period, 14,725 singleton babies were delivered; of these, 23 cases were diagnosed with chorioangioma (0.16%). The Control group included all deliveries during period without chorioangioma (n ¼ 14,702). Except for Parity, both groups had similar baseline demographic characteristics (Table 1). Mean maternal age was 30.6 4.6 years for the chorioangioma group versus 31.6 5.1 years for the control group (p value ¼ 0.22). Gravidity as well as rates of infertility and spontaneous or therapeutic abortions did not differ between the Table 1 Baseline maternal characteristics and pregnancy outcomes.
Baseline Characteristics Maternal Age, years (mean S.D.) Gravidity (mean) Parity (mean) Rates of smokers, n(%) Rates of alcohol users, n(%) Primiparous, n(%) Pregnancy Outcomes Gestational age at delivery, weeks (Mean S.D) Hypertension, n(%) Diabetes, n(%) Spontaneous Vaginal Deliveries, n(%) Operative Deliveries, n(%) Cesarean Sections, n(%) a
Statistically significant.
Chorioangioma Group (N ¼ 23)
Control Group (N ¼ 14702)
30.6 4.6
31.6 5.1
0.22
2.22 0.70 1 (4.4%) 3 (13.0%) 13 (56.5%)
2.46 1.36 1018 (6.9%) 937 (6.4%) 6997 (47.6)
0.4 0.005a 0.62 0.81 0.4
38.9
39.1
0.47
2 (8.7%) 1 (4.4%) 14 (60.9%)
802 (5.5%) 1099 (7.5%) 1033 (68.8%)
0.36 0.9 <0.001a
4 (17.4%) 5 (21.7%)
871 (5.9%) 3718 (25.3%)
0.04a 0.81
P value
two groups (all p value > 0.4). Parity was significantly lower in the chorioangioma group compared with the control group (Average parity ¼ 0.7 vs. 1.36 in the chorioangioma and control group respectively, p ¼ 0.005). However, the higher rate of primiparous women in the chorioangioma group did not reach statistical significance (56.5% vs 47.6%, p ¼ 0.4). Rates of hypertension (8.7% vs. 5.5% in the chorioangioma and control group respectively, p ¼ 0.36) and diabetes during pregnancy (4.4% and 7.5% in the chorioangioma and control group respectively, p ¼ 0.9) were not different between the two groups. The chorioangioma group had a higher rate of operative vaginal deliveries (17.4% versus 5.9%, p value ¼ 0.04) and lower rate of spontaneous vaginal deliveries (60.9% versus 68.8%, p value < 0.001). Although the cesarean section rate was higher in the chorioangioma group, the difference did not reach statistical significance (21.7% versus 25.3%, p value ¼ 0.81). Neonates in the study group were more likely to be female (OR ¼ 2.42, 95% CI 0.90e6.90), to have a lower average birth weight (3008 822 g vs. 3356 624 g, p ¼ 0.006) and to have a preterm birth (OR 2.97, 95% CI 0.80e8.30). Only birth-weights, however, reached statistical significance. The rate of NICU admission was significantly increased for the chorioangioma group (OR ¼ 4.45, 95% CI 1.41e11.80). Of the 6 admissions to NICU in this group, the diagnoses were respiratory distress syndrome (2 cases), cardiac malformation (1 case), hypoglycemia (1 case) and prematurity with IUGR (2 cases). The chorioangioma group had a mean hospital stay of 6.2 13.7 days Vs. 3.6 8.2 days for the control group (p value ¼ 0.12). There were no significant differences in either the one-minute and five-minute APGAR scores nor in the umbilical cord pH (p values ¼ 0.96, 0.67 and 0.89 respectively) (Table 2). Nine patients had large chorioangiomas defined as largest diameter 2 cm, (39% of study cases and 0.06% of all singleton deliveries) with these ranging in size from 6 cm3 to 475 cm3 in volume. The maximal diameter of the largest chorioangioma measured 10 cm (overall size 10 9.5 5 cm), and the average maximal diameter of these nine cases was 5.3 cm. Out of 7 larger chorioangioma cases for which ultrasound reports were available for both second and third trimesters, only two had been recognized by routine antenatal ultrasound in the third trimester (32 1/7 weeks) (29% detection rate). All seven cases had normal amniotic fluid, appropriate fetal growth, biophysical profile and umbilical artery Doppler studies. For the 14 cases with a chorioangioma <2 cm in size, ultrasound reports were available for 11 patients (8 with ultrasound reports in both second and third trimesters and 3 with reports for third trimester ultrasounds only). None of these had been detected antenatally. Table 2 Neonatal outcomes. Chorioangioma Group (N ¼ 23)
Control Group (N ¼ 14702)
Odds Ratio (95% CI) or P value
Female Gender, n(%)
16 (69.6%)
7130 (48.5%)
Prematurity < 37 weeks, n(%)
5 (21.7%)
1254 (8.5%)
Birthweight, grams (mean SD) NICU Admission, n(%)
3008 822 6 (26.1%)
3356 624 1066 (7.3%)
Baby Stay in Hospital, days (mean SD) Apgar Score at 1-min (mean) Apgar Score at 5-min (mean) Cord pH (mean)
6.2 13.7
3.6 8.2
2.42 (0.9e6.9) 2.97 (0.8e8.3) 0.006a 4.45a (1.4e11.8) 0.12
8.1 8.9 7.25
8.2 9.0 7.26
0.96 0.67 0.89
a
Statistically significant.
K. Wou et al. / Placenta 32 (2011) 671e674
When comparing the “large chorioangioma” subgroup with the control group, no statistically significant differences in the baseline demographic characteristics or in the rates of hypertension and diabetes during pregnancy were found (Table 3). Patients in the large chorioangioma group had a significantly lower rate of spontaneous vaginal delivery (44.0% versus 68.8%, p value ¼ 0.002) with non-significant increases in both cesarean section (44.0% versus 25.3%, p value ¼ 0.24) and operative vaginal delivery rates (11.0% versus 5.9%, p value ¼ 0.42) when compared with the control group. Neonates in the larger chorioangioma group were again more likely to be female (OR ¼ 8.49, 95% CI 1.10e377.0). The rate of preterm birth, average birth weight, APGAR scores at 1-min and 5-min and cord pH were not significantly different between the two groups. Only one of the neonates in the larger chorioangioma group was admitted to the NICU, with a total hospital stay of 26 days (Table 4). Chorioangioma correlated with placental weight (r ¼ 0.718693, p ¼ 0.0001) but not with birth weight, Apgar score or presence of post partum hemorrhage. 4. Discussion At our institution the placentas of all deliveries are examined within our pathology service. This therefore is one of the first cohort studies to evaluate pregnancy outcomes and the frequency of prenatal diagnosis of this entity based upon the histopathological diagnosis of the presence of a chorioangioma. Examining all placentas might explain the relatively lower incidence of chorioangioma in our study as the population we studied was a more normal-risk homogeneous population compared to other more high-risk populations where the cited incidence is 1%. There are more than 70 cases of placental chorioangioma associated with adverse perinatal findings including hydramnios and severe fetal distress, abnormal Dopplers studies suggestive of fetal anemia, cardiac failure and hydrops reported in the literature [6e8]. Chatterjee et al. reported a case of a 55-mm chorioangioma of the placenta confirmed by sonogram and illustrated several associated complications: polyhydramnios, preterm premature rupture of membranes, and preterm delivery with associated respiratory distress syndrome and necrotizing enterocolitis [9]. Other reported complications have included uterine atony, post partum hemorrhage, fetal anemia, cardiac enlargement and failure, and hydrops fetalis [9,10]. Sepulveda et al. described 11 cases of placental chorioangioma diagnosed prenatally by ultrasound and color flow Doppler imaging [2]. Five of the nine singleton cases were complicated by polyhydramnios, oligohydramnios, fetal growth restriction or non-immune hydrops; four of these nine cases delivered before 35 weeks. In 7 of the 9 singleton cases, the size of Table 3 Baseline maternal characteristics and pregnancy outcomes of larger chorioangioma group.
Baseline Characteristics Maternal Age (mean S.D.) Gravidity (mean) Parity (mean) Pregnancy Outcomes Hypertension, n(%) Diabetes, n(%) Spontaneous Vaginal Deliveries, n(%) Operative Deliveries, n(%) Cesarean Sections, n(%) a
Statistically significant.
Larger Chorioangioma Group (N ¼ 9)
Control Group (N ¼ 14702)
P value
32.2 5.4 2.89 0.78
31.6 5.1 2.46 1.36
0.70 0.43 0.34
1 (11.0%) 0 (0.0%) 4 (44.0%)
802 (5.5%) 1099 (7.5%) 1033 (68.8%)
0.39 0.9 0.002a
1 (11.0%) 4 (44.0%)
871 (5.9%) 3718 (25.3%)
0.42 0.24
673
Table 4 Neonatal outcomes of the larger chorioangioma group. Larger Chorioangioma Group (N ¼ 9)
Control Group (N ¼ 14702)
Odds Ratio (95% CI) or P value
Female Gender, n(%)
8 (88.9%)
7130 (48.5%)
Prematurity <37 weeks, n(%)
1 (11.1%)
1254 (8.5%)
Birthweight, grams (mean SD) NICU Admission, n(%)
3286 739 1 (11.0%)
3356 624 1066 (7.3%)
Baby Stay in Hospital, days (mean SD) Apgar Score at 1-min, (mean) Apgar Score at 5-min, (mean) Cord pH, (mean)
5.1 7.8
3.6 8.2
8.49a (1.1e377.0) 1.34 (0.03e10.0) 0.69 1.59 (0.03e11.9) 0.56
7.9 9.1 7.23
8.2 9.0 7.26
0.68 0.80 0.82
a
Statistically significant.
the chorioangioma was greater than 60 mm, the other 2 being 43 mm or smaller without there being any sonographicallydetected complications other than an increasing tumor size. Tumor size appears to be the most important factor, not only in the antenatal diagnosis but also in influencing the prognosis of affected pregnancies. Zanardini et al. conducted a retrospective study of 19 cases of giant chorioangioma and described a wide variety of fetal complications such as polyhydramnios, growth restriction, hyperdynamic circulation, cardiomegaly, anemia and non-immune hydrops [11]. Due to the nature of our study that is based on post partum histological diagnosis, most of the lesions in our study were relatively small (average maximal diameter in the larger chorioangioma group was 53 mm). This probably explains why all the cases were asymptomatic. However, Jauniaux et al. also studied the use of Color Doppler in the diagnosis and management of chorioangiomas and found that the vascularity of the tumor, mapped by color flow, may be an independent factor for fetal complications, such as polyhydramnios, regardless of the tumor size [12]. A limitation of our study with regards to statistical analysis of such factors is the relatively small sample size, which is consequent to the low prevalence of chorioangioma. As shown in our study, placental chorioangiomas are not always associated with bad outcomes. Taori et al. described the sonographic features of a large placental chorioangioma (5.5 4.7 cm) with normal outcomes [13]. In addition, in a study by Isaacs et al. looking at fetal hydrops associated with tumors; placental chorioangiomas represented a small number of cases and had the best outcomes when compared with pericardial teratomas and hepatic hemangiomas [14]. In recent years there has been renewed interest in chorioangiomas due to greater opportunities for antenatal diagnosis with developments in ultrasonography and Doppler imaging [3]. In pregnancies where elevated levels of maternal serum alpha-fetoprotein (MSAFP) are identified, detailed sonographic evaluation including not only the fetus but the placenta is indicated [15]. Chorioangiomas may be distinguished from other placental masses by applying color Doppler and demonstrating increased blood flow [16e20]. Possible modalities in the treatment of chorioangiomas have been widely reported [21e23] but are beyond the scope of this study. The present cohort study shows that although many of the histologically-proven placental chorioangiomas may not be associated with significant adverse perinatal outcomes such as hydramnios, hydrops or fetal anemia, they might be associated with increased rates of NICU admission, smaller birth weight and operative delivery. Attention should be focused on prenatal diagnosis; despite advances in ultrasonography the detection rate for small placental
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chorioangiomas is low and this might represent the relatively less thorough examination afforded to the placenta as compared to the fetus. Although the incidence of this condition is low, detailed interrogation of the placenta by ultrasound, preferably incorporating modalities such as color flow imaging might allow a larger proportion of cases to be identified. Earlier diagnosis might result in improved outcomes with closer follow-up of affected pregnancies and the use of therapeutic interventions as indicated, in cases where complications arise. References [1] Guschmann M, Henrich W, Dudenhausen JW. Chorioangiomasenew insights into a well-known problem. II. An immuno-histochemical investigation of 136 cases. J Perinat Med 2003;31(2):170e5. [2] Sepulveda W, Alcalde JL, Schnapp C, Bravo M. Perinatal outcome after prenatal diagnosis of placental chorioangioma. Obstet Gynecol 2003;102(5 Pt 1): 1028e33. [3] Rech F, Salernitano D, Patella A. Placental chorioangioma. Minerva Ginecol 2002;54(5):417e33. [4] Bashiri A, Furman B, Erez O, Wiznitzer A, Holcberg G, Mazor M. Twelve cases of placental chorioangioma. Pregnancy outcome and clinical significance. Arch Gynecol Obstet 2002;266(1):53e5. [5] Garcia-Flores J, Vega-Malagon G, Vega-Malagon JA, Galvan-Aguilera A, Salmon-Velez F. Giant chorioangioma: presentation of a case. Rev Med Inst Mex Seguro Soc 2005;43(6):503e6. [6] Hurwitz A, Milwidsky A, Yarkoni S, Palti Z. Severe fetal distress with hydramnios due to chorioangioma. Acta Obstet Gynecol Scand 1983;62(6):633e5. [7] Panaccione JL, Esposito WJ, Haller JO. Acute polyhydramnios associated with chorioangioma. A case report. J Reprod Med 1991;36(3):210e2. [8] Imakita M, Yutani C, Ishibashi-Ueda H, Murakami M, Chiba Y. A case of hydrops fetalis due to placental chorioangioma. Acta Pathol Jpn 1988;38(7): 941e5. [9] Chatterjee Molly S. MDAJMLBCMLIMGJGMGMJMMVMJMMBNM. Chorioangioma. thefetus net. Available from: URL, http://www.sonoworld.com/ fetus/page.aspx?id¼164; 1993.
[10] Schmitz T, Opgen-Rhein B, Kroschwald P, Schroeder G, Weber S, Czernik C, et al. Severe transient cardiac failure caused by placental chorangiosis. Neonatology 2007;91(4):271e4. [11] Zanardini C, Papageorghiou A, Bhide A, Thilaganathan B. Giant placental chorioangioma: natural history and pregnancy outcome. Ultrasound Obstet Gynecol 2010;35(3):332e6. [12] Jauniaux E, Ogle R. Color Doppler imaging in the diagnosis and management of chorioangiomas. Ultrasound Obstet Gynecol 2000 Jun;15(6):463e7. [13] Taori K, Patil P, Attarde V, Singh A, Rangankar V. Chorioangioma of placenta: sonographic features. J Clin Ultrasound 2008;36(2):113e5. [14] Isaacs Jr H. Fetal hydrops associated with tumors. Am J Perinatol 2008;25(1): 43e68. [15] Maymon R, Hermann G, Reish O, Herman A, Strauss S, Sherman D, et al. Chorioangioma and its severe infantile sequelae: case report. Prenat Diagn 2003 15;23(12):976e80. [16] Prapas N, Liang RI, Hunter D, Copel JA, Lu LC, Pazkash V, et al. Color Doppler imaging of placental masses: differential diagnosis and fetal outcome. Ultrasound Obstet Gynecol 2000;16(6):559e63. [17] Zalel Y, Gamzu R, Weiss Y, Schiff E, Shalmon B, Dolizky M, et al. Role of color Doppler imaging in diagnosing and managing pregnancies complicated by placental chorioangioma. J Clin Ultrasound 2002;30(5):264e9. [18] Durin L, Barjot P, Herlicoviez M. Placental chorioangioma, value of ultrasonography: report of two cases. J Radiol 2002;83(6 Pt 1):739e41. [19] Zalel Y, Weisz B, Gamzu R, Schiff E, Shalmon B, Achiron R. Chorioangiomas of the placenta: sonographic and Doppler flow characteristics. J Ultrasound Med 2002 Aug;21(8):909e13. [20] Sepulveda W, Aviles G, Carstens E, Corral E, Perez N. Prenatal diagnosis of solid placental masses: the value of color flow imaging. Ultrasound Obstet Gynecol 2000 Nov;16(6):554e8. [21] Bhide A, Prefumo F, Sairam S, Carvalho J, Thilaganathan B. Ultrasound-guided interstitial laser therapy for the treatment of placental chorioangioma. Obstet Gynecol 2003;102(5 Pt 2):1189e91. [22] Sepulveda W, Wong AE, Herrera L, Dezerega V, Devoto JC. Endoscopic laser coagulation of feeding vessels in large placental chorioangiomas: report of three cases and review of invasive treatment options. Prenat Diagn 2009; 29(3):201e6. [23] Mendez-Figueroa H, Papanna R, Popek EJ, Byrd RH, Goldaber K, Moise Jr KJ, et al. Endoscopic laser coagulation following amnioreduction for the management of a large placental chorioangioma. Prenat Diagn 2009;29(13): 1277e8.