Introduction

Vasa praevia(VP) is a rare condition in which the fetal vessels run through the free placental membranes . It is associated with significant perinatal morbidity and mortality. The risk factors associated with VP are placenta praevia, velamentous cord insertion (VCI), bi-lobed placenta, succenturiate lobes, procedures such as in vitro fertilization (IVF) and multiple pregnancies.

Objective: To analyse the existing literature evidence on the risk factors and role of prenatal screening in VP.

Materials and methods: Databases such as Pub Med, MEDLINE, the Cochrane Library, UpToDate, EBSCO host, and Trip medical database have been searched for systematic reviews, meta-analysis, randomized control trials, case reports, case-control and cohort studies on incidence, associated risk factors and role of prenatal screening in VP.

Results: Following the initial search of the afore-mentioned databases, 229 articles were found related to the terms that were searched. With further perusal of articles ,113 of most relevant articles were selected for the literature review. From the short listed literature we have found that the most common risk factors are velamentous insertion of cord, low cord insertion and singleton pregnancies that started off as multiple gestation. The role of ultrasound with colour doppler in diagnosing VP was established in the literature and targeted screening and elective delivery has been found to improve the fetal outcome.

Conclusion: A majority of cases with VP are associated with one or more high risk factors such as VCI, bilobed, succenturiate placenta, IVF, multiple pregnancies, low lying placenta in second trimester cord insertion in the lower third of the uterus. Prenatal screening of VP allows for safe delivery of the baby electively prior to labour. A universal targeted screening protocol for VP could be the way forward in future obstetric practice.

Keywords: Vasa Praevia, placenta praevia, velamentous insertion of cor, low lying placenta, in vitro fertilization, colour doppler

Vasa praevia (VP) is a rare condition in which the fetal vessels run through the free placental membranes. These vessels are unprotected by placental tissue or Wharton's jelly of the umbilical cord.¹ There are two types of VP, Type 1 is with velamentous insertion of the umbilical cord, where the cord gets inserted into the membranes, and in Type 2, vessels run through the membranes between the lobes of a bi-lobed placenta.^2,3 Certain pregnancy related factors are implicated in the development of this condition. The factors found to be associated with the increased incidence of VP are placenta praevia, velamentous cord insertion, bi-lobed placenta, succenturiate lobes, procedures such as in vitro fertilization (IVF) and multiple pregnancies.⁴ In a systematic review of 325 cases, these risk factors were found to be present in 83% of VP cases.⁵

The incidence of VP has been found to be 1:2500 pregnancies, with 1:513 to 1:6000 in naturally conceived pregnancies, and a much higher incidence amounting to 1:293 in those who have undergone IVF treatment.^6–8 Following either spontaneous or artificial rupture of membranes, trauma to the vessels lead to the exsanguination of fetal blood, eventually resulting in perinatal morbidity or mortality.⁹

The perinatal mortality rate associated with VP was calculated to be 60%.¹⁰ The challenges faced by the health care providers and the patient in regards to this condition is its rarity and the variation in opinion regarding prenatal screening and management. VP can be diagnosed prenatally with the help of ultrasonography. Adverse perinatal outcomes can be mitigated by prenatal diagnosis and early elective delivery. However, currently, there is no general consensus regarding the need for routine prenatal screening in high risk cases due to the paucity of available evidences.

Studies have determined that if the condition is left undetected, the fetal mortality rate is 44%, and if it is detected prenatally, the fetal survival rate is 97%.¹¹

 In this literature review, we aim to analyse the existing evidence on the associated risk factors of VP, prenatal screening in high risk individuals and the appropriate management required to reduce fetal morbidity and mortality.

Search strategy

The search for materials for this literature review was started on the 14th of November 2020. Various literatures addressing vasa praeiva, risk factors, prenatal diagnosis using ultrasonography and its management were analysed. The data bases used were PubMed, Medline, EBSCO, Cochrane and Trip database.

The various terms used for the search were ‘vasa previa’, ‘vasa praevia’, ‘velamentous’, ‘bilobed placenta’, ‘succenturiate placenta’ , ‘in vitro fertilization’, ‘fetal outcome’, ‘prenatal screening’ multiple pregnancy and ‘abnormal placentation’. The literature included systematic reviews, meta -analysis, case control and cohort studies (both prospective and retrospective), clinical guidelines and literature reviews. We have excluded articles in languages other than English and those that were published before the year 2000. This restriction was put in place to ensure that only the most recent publications were included to offer the best relevant results which can be considered for application in current obstetric settings.

Data review and analysis

Following the initial search of the afore-mentioned databases, 229 articles were found related to the terms that were searched. With further perusal of articles ,113 of most relevant articles were selected for the literature review. There were no randomized controlled trials, however, 2 metanalysis, 7 systematic reviews and 33 reviews were included. The remainder were cohort and case control studies and case reports.

Risk factors

Velamentous cord insertion. (VCI): is the most common risk factor associated with VP and its coexistence is known to cause significant perinatal morbidity and mortality. In VCI, the cord attaches to the membranes surrounding the placenta rather than inserting into the substance of placenta leaving umbilical vessels unprotected and vulnerable to both iatrogenic and spontaneous rupture of membrane resulting in fetal exsanguination and sudden fetal death. In a prospective population based cohort study the coexistence of VCI and VP was noted in 62% of cases.¹² A recent systematic review on VCI noted that the proportion of VP cases with concomitant VCI ranged from 20/49 (40.8%) to 3/3 (100%), with a median reported percentage of 76%¹³ and the same study also highlighted the fact that though the chances of VP coexisting with VCI is significantly high , the chances of VIC coexisting with VP is found only in minority of cases. In the literature, the association of VP with VCI ranges from 1.8% to 10.7%.^14,15

Resolved Placenta praevia or low lying placenta in second trimester: A study that analysed the outcomes of pregnancies with low-lying placenta diagnosed at second trimester sonography had found that 98.4% of cases has resolved with 1.6% of cases persisting as either low lying (within 2cm from the internal os) or placenta praevia at term. Among them that persisted, 15% of cases were found to be VP.¹⁶ A retrospective study of the incidence of VP in a series of 12,063 deliveries, found that the second trimester placenta praevia is a high risk factor for VP with an odds ratio of 22.86.¹⁷ A population-based study comparing all singleton pregnancies of women with and without placenta praevia had noted that placenta praevia is associated with a number of adverse outcomes, one of which is VP (0.5 vs. 0.1%; p < 0.001).¹⁸ According to a systematic review, 63 women with placenta praevia needed to be screened in order to detect a single case of VP.¹⁹ A prospective population-based cohort study noted that sixty percent of cases of VP are associated with low lying placenta in second trimester.¹²

In vitro fertilization (IVF) is a risk factor for VP as the assisted reproductive techniques are associated with increased incidence of placental and umblical cord abnormalities due to higher incidence of multiple pregnancies among IVF pregnancies. Retrospective studies have shown that the incidence of VP in assisted conception varies from 10% to 41%.^20,21 The incidence of VP in IVF pregnancies is quoted as 1 in 293 while the overall incidence of VP is 1in 6000 deliveries.^22,23 The reason for increase in incidence of VP or placental abnormalities in assisted reproduction are considered to be due to high estradiol in the endometrium at the time of implantation.^24,25 It was also noted that conception with fresh embryo transfer are at risk of placental abnormalities rather than frozen embryo transfer, which again points towards the high concentration of estradiol in stimulated cycles.²⁶ The overall incidence of VP is increasing due to many factors but mostly due to increasing assisted conception owing to major advances in the assisted reproduction and increasing access and availability to these reproductive techniques globally.

Placental structural abnormalities: Bilobed and succenturiate placenta: Morphological abnormalities is regarded as a perquisite for VP along with velamentous insertion of cord. The frequency of maternal age more than or equal to 35 years and history of using in vitro fertilization in patients complicated by succenturiate lobes of placenta were significantly higher than those in control patients (p < 0.01).²⁷ According to a systematic review it was found that women with a bilobed or succenturiate placenta had an increased risk of VP compared to women with a normally developed placenta (common OR 71; 95% CI 14–349, heterogeneity I2 = 0%). Same study also pointed out that 37 women with a bilobed or succenturiate placenta needed to be screened to detect one case of VP.¹⁹According to a retrospective study the association between VP and bilobed or succenturiate placenta had an odds ratio of 22.1.¹⁷

Multiple pregnancy: According to a systematic review on prenatal diagnosis and management of VP in twin pregnancies, the incidence of VP diagnosed antenatally was 11.0%. VCI was the most common associated finding.²⁸ A literature review indicates that the estimated incidence of VCI was 0.4-11% in singleton pregnancies and higher incidence in twin pregnancies (1.6-40%).¹³A retrospective cohort study found that there was a statistically significant difference in the prevalence of VP in pregnancies that started as multiple gestations but continued later as singletons compared to multiple pregnancies (8.0% vs. 0.2% respectively, p < 0.0001 OR 41.1). Therefore the authors recommended that it may be prudent to consider all twins at the beginning of pregnancy to be at risk for VP, irrespective of the actual number of live fetuses at later stages of gestation.²⁹

Cord insertion in the lower third of uterus in first trimester: is considered as a high risk factor. A case control study found 2.2% of cases of low cord insertion in first trimester were diagnosed with VP when compared to controls (p = 0.001).³⁰ The authors have recommended that screening sonography in the late first or early second trimesters and follow up in the second trimester of cases with low cord insertion is a useful way to detect VP. A case control study on analysis of the ultrasonographic findings predictive of VP noted that a low cord insertion in the uterus was found in 90%of cases with VP.¹⁵

Role of prenatal screening

It has been established that an undiagnosed VP can endanger the fetus and may result in either intrauterine fetal death, neonatal death or hypoxic ischemic encephalopathy with its long term and short term consequences. The literature in the past had presented this condition as an unpreventable obstetric tragedy due to lack of awareness regarding the risk factors, rarity of the condition mostly with a retrospective diagnosis, lack of advanced imaging modalities and paucity of evidence regarding screening.^21.

Over the years the imaging technology and training has improved exponentially with increased awareness of the implications of VP. Despite the global aim of decreasing the rate of stillbirths, there is no universal consensus regarding routine screening or a targeted screening in order to diagnose VP prenatally. This lack of consensus may be due to impact of screening on the manpower and economic resources, debatable diagnostic accuracy of ultrasound, knowledge gap and lack of training among health care providers and paucity of level 1 evidence regarding the positive impact of prenatal diagnosis of VP due to rarity of this condition. If VP is not diagnosed prenatally 56% of affected babies will die while survival rate increases approximately by 100% with prenatal screening.²¹ A multicentric retrospective cohort study of 136 cases have suggested that outcomes in antenatally diagnosed cases of VP were excellent.³¹

A systematic review of accuracy of ultrasound in the diagnosis of VP found that transvaginal colour Doppler performed during the second trimester detected all cases of VP (sensitivity, 100%, specificity 99.0-99.8%). They concluded that the accuracy of ultrasound in the diagnosis of VP is high when performed transvaginally in combination with colour Doppler.¹⁹

A retrospective study done in 2019 highlighted the fact that a 2 step routine prenatal screening for    VP at 11-13 weeks & 20 – 22 weeks could have prevented stillbirth in 10.6%of stillbirths in that population.³² A retrospective review of prenatal detection of VP and its subsequent impact on neonatal outcomes in two 10-year periods (1988-1997 versus 1998-2007) revealed that VP were diagnosed prenatally in 10 (52.6%) cases. In cases without prenatal diagnosis, there was a higher proportion of neonates with 1' Apgar score less than or equal to 5 and cord blood pH <7 compared with cases diagnosed prenatally (66.7% versus 10%, p </= 0.05, and 33.3% versus 0%, p < 0.05, respectively). The prenatal detection rate of VP increased from 25 to 60% between the 2 time periods (p > 0.05), whereas perinatal mortality decreased from 25% to 0% and 1' Apgar scores </= 5 decreased from 50 to 33.3% which was statistically significant.³³ The author concluded that the prenatal sonographic screening using targeted scans for VP in women at risk or as part of routine mid-gestation scanning may significantly impact its obstetric outcome.

A retrospective descriptive study of 35 cases of VP, showed that routine ultrasound screening for VP will lead to good outcomes and prevent perinatal mortality.³⁴ Another cohort study also suggested that the prenatal diagnosis of VP during screening ultrasound using transvaginal scan with colour doppler appears easy to perform and can improve obstetrical and neonatal outcomes.This study had only 8 cases of VP out of 18000 deliveries but no neonatal adverse outcome noted in these prenatally diagnosed cases.³⁵ A survey of opinion and practice regarding prenatal diagnosis of VP among obstetricians from Australia and New Zealand suggest that most of the obstetricians strongly support targeted screening.³⁶

A study of 68 cases that investigated the diagnosis and management of VP showed that 87% of cases had a risk factor for VP and recommended that a targeted screening would improve the perinatal outcome.³¹ However there are documentation of cases of VP without risk factors have been documented and the incidence of VP without risk factors ranged from 6%- 14.3% of cases.^34,37 Pre existing guidelines of Society of Obstetricians and Gynaecologists of Canada (SOGC) and Royal Australian and New Zealand College of Obstetricians and Gynaecologists recommends targeted screening in high risk cases.^38,39 A systematic review concluded that though the data on the diagnosis and management of VP in twin pregnancies are limited but there is enough evidence to warrant guidelines for targeted screening.²⁸

Taking into consideration the benefit of prenatal screening and its implication on cost effectiveness, it would be advantageous if a universal consensus regarding targeted screening is proposed As the World Health Organization has called for ending preventable still births, targeted screening for VP can be one of the steps that can be taken globally to mitigate still births and to improve perinatal outcome^.40

From the literature review, it has been established that the perinatal mortality is high if VP is not diagnosed prenatally. Majority of cases with VP are associated with one or more high risk factors such as VCI, bilobed, succenturiate placenta, IVF, multiple pregnancies, low lying placenta in second trimester and cord insertion in the lower third of the uterus. The gold standard for diagnosing VP is considered to be transvaginal sonography with colour Doppler due to its high accuracy. Prenatal screening of VP allows for safe delivery of the baby electively prior to labour.  A universal targeted screening protocol for VP could be the way forward in future obstetric practice.

Details of ethics approval: Not applicable.

Author statement: RER has done the literature review, writing up the manuscript under the guidance of MD.

None.

Authors state no conflict of interest.

None.

1. Jauniaux E, Alfirevic Z, Bhide AG, et al. Vasa Praevia: diagnosis and management: green–top guideline No. 27b. BJOG. 2019;126(1):e49–e61.
2. Catanzarite V, Maida C, Thomas W, et al. Prenatal sonographic diagnosis of vasa previa: ultrasound findings and obstetric outcome in ten cases. Ultrasound Obstet Gynecol. 2001;18(2):109–115.
3. Daly–Jones E, John A, Leahy A, et al. Vasa praevia: a preventable tragedy. Ultrasound. 2008;16(1): 8–14.
4. Royal College of Obstetricians and Gynaecologists. RCOG Greentop Guideline No. 27: Placenta praevia, placenta praevia accreta and vasa praevia: Diagnosis and Management.
5. Ruiter L, Kok N, Limpens J, et al. Incidence of and risk indicators for vasa praevia: A systematic review. BJOG. 2015;123:1278–1287.
6. Gagnon R. Guidelines for the management of vasa previa. J Obstet Gynaecol Can. 2009;31:748–753.
7. Kanda E, Matsuda Y, Kamitomo M, et al. Prenatal diagnosis and management of vasa previa: A 6–year review. J Obstet Gynaecol Res. 2011;37(10):1391–96.
8. Schachter M, Tovbin Y, Arieli S, et al. In vitro fertilization is a risk factor for vasa previa. Fertil Steril. 2002;78(3):642–43.
9. Oyelese KO, Turner M, Lees C, et al. Vasa previa: an avoidable obstetric tragedy. Obstet Gynecol Surv. 1999;54:138–145.
10. Fung TY and Lau TK. Poor perinatal outcome associated with vasa previa: Is it preventable? A report of three cases and review of the literature. Ultrasound Obstet Gynecol. 1998;12:430–433.
11. Mukherjee S, Bhide A. Antepartum haemorrhage. Obstet Gynaecol Reprod Med. 2008;18:335–339.
12. Sullivan EA, Javid N, Duncombe G, et al. Vasa previa diagnosis, clinical practice, and outcomes in Australia. Obstet Gynecol. 2017;130(3):591–598.
13. Buchanan–Hughes A, Bobrowsk A, Visintin C, et al. Velamentous cord insertion: results from a rapid review of incidence, risk factors, adverse outcomes and screening. Syst Rev. 2020;9:147.
14. Suzuki S, Kato M. Clinical significance of pregnancies complicated by velamentous umbilical cord insertion associated with other umbilical cord/placental abnormalities. J Clin Med Res. 2015;7(11):853–856.
15. Hasegawa J, Farina A, Nakamura M, et al. Analysis of the ultrasonographic findings predictive of vasa previa. Prenat Diagn. 2010;30(12–13):1121–1125.
16. Heller HT, Mullen KM, Gordon RW, et al. Outcomes of pregnancies with a low–lying placenta diagnosed on second–trimester sonography. J Ultrasound Med. 2014;33(4):691–696.
17. Baulies S, Maiz N, Muñoz A, et al. Prenatal ultrasound diagnosis of vasa praevia and analysis of risk factors. Prenat Diagn. 2007;27(7):595–599.
18. Rosenberg T, Pariente G, Sergienko R, et al. Critical analysis of risk factors and outcome of placenta previa. Arch Gynecol Obstet. 2011;284(1):47–51.
19. Ruiter L, Kok N, Limpens J, et al. Incidence of and risk indicators for vasa praevia: a systematic review. BJOG. 2016;123:1278–1287.
20. Oyelese Y, Catanzarite V, Prefumo F, et al. Vasa previa: the impact of prenatal diagnosis on outcomes. Obstet Gynecol. 2004;103:937–942.
21. Rebarber A, Dolin C, Fox NS, et al. Natural history of vasa previa across gestation using a screening protocol. J Ultrasound Med. 2014;33: 141–147.
22. Donnolley N, Halliday LE, Oyelese Y. Vasa Praevia: a descriptive review of existing literature and the evolving role of ultrasound in prenatal screening. Australas J Ultrasound Med. 2013;16(2):71–76.
23. Schachter M, Tovbin Y, Arieli S, et al. In vitro fertilization is a risk factor for vasa previa. Fertil Steril. 2002;78(3):642–643.
24. Farhi J, Ben–Haroush A, Andrawus N, et al. High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation. Reprod Biomed Online. 2010;21(3):331–337.
25. Healy DL, Breheny S, Halliday J, et al. Prevalence and risk factors for obstetric haemorrhage in 6730 singleton births after assisted reproductive technology in Victoria Australia. Hum Reprod. 2010; 25(1):265–274.
26. Korosec S, Ban Frangez H, Verdenik I, et al. Singleton pregnancy outcomes after in vitro fertilization with fresh or frozen–thawed embryo transfer and incidence of placenta praevia. Biomed Res Int. 2014;431797.
27. Suzuki S, Igarashi M. Clinical significance of pregnancies with succenturiate lobes of placenta. Arch Gynecol Obstet. 2008;277:299–301.
28. Jauniaux E, Melcer Y, Maymon R. Prenatal diagnosis and management of vasa previa in twin pregnancies: a case series and systematic review. Am J Obstet Gynecol. 2017;216(6):568–575.
29. Melcer Y, Pekar–Zlotin M, Wolf B, et al. Is scanning for vasa previa important for singleton pregnancies that started as multiple conceptions? Eur J Obstet Gynecol Reprod Biol. 2019;238:100–103.
30. Hasegawa J, Nakamura M, Sekizawa A, et al. Prediction of risk for vasa previa at 9–13 weeks' gestation. J Obstet Gynaecol Res. 2011;37(10):1346–1351.
31. Erfani H, Haeri S, Shainker SA, et al. Vasa previa: a multicenter retrospective cohort study. Am J Obstet Gynecol. 2019;221(6):644.e1–644.e5.
32. Zhang W, Geris S, Beta J, et al. Prevention of stillbirth: impact of two–stage screening for vasa previa. Ultrasound Obstet Gynecol. 2020;55(5):605–612.
33. Smorgick N, Tovbin Y, Ushakov F, et al. Is neonatal risk from vasa previa preventable? The 20–year experience from a single medical center. J Clin Ultrasound. 2010;38(3):118–122.
34. Kulkarni A, Powel J, Aziz M, et al. Vasa Previa: prenatal diagnosis and outcomes: thirty–five cases from a single maternal–fetal medicine practice. J Ultrasound Med. 2018;37(4):1017–1024.
35. Nohuz E, Boulay E, Gallot D, et al. Can we perform a prenatal diagnosis of vasa previa to improve its obstetrical and neonatal outcomes? J Gynecol Obstet Hum Reprod. 2017;46(4):373–377.
36. Javid N, Hyett JA, Walker SP, et al. A survey of opinion and practice regarding prenatal diagnosis of vasa previa among obstetricians from Australia and New Zealand. Int J Gynaecol Obstet. 2019;144(3):252–259.
37. Klahr R, Fox NS, Zafman K, et al. Frequency of spontaneous resolution of vasa previa with advancing gestational age. Am J Obstet Gynecol. 2019;221(6):646.e1–646.e7.
38. Society of Obstetricians and Gynaecologists of Canada. Clinical practice guideline no. 231: guidelines for the management of vasa previa. Ottawa: SOGC, 2009.
39. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. C–Obs 47: vasa praevia. Melbourne: RANZCOG, 2016.
40. Luc de Bernis, Mary V Kinney, Prof William Stones, et al. The lancet ending preventable stillbirths series study group, ending preventable stillbirths. The Lancet. 2016;387(10019):P703–716.