{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:01:11Z","timestamp":1772244071951,"version":"3.50.1"},"update-to":[{"DOI":"10.3310\/nihropenres.13696.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000}}],"reference-count":29,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"crossref","award":["NIHR303806"],"award-info":[{"award-number":["NIHR303806"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIHR UCLH Research Capability Fund","award":["RCF68\/PB\/2014 5990"],"award-info":[{"award-number":["RCF68\/PB\/2014 5990"]}]}],"content-domain":{"domain":["openresearch.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["NIHR Open Res"],"abstract":"<ns4:p>Background Vasa praevia is an obstetric condition in which the fetal vessels run through the membrane over the internal cervical os, unprotected by the placenta or umbilical cord. It is associated with perinatal mortality if not diagnosed antenatally. We estimated the incidence and investigated outcomes of vasa praevia in the UK. Methods We conducted a population-based descriptive study using the UK Obstetric Surveillance System (UKOSS). Cases were identified prospectively through monthly UKOSS submissions from all UK hospitals with obstetrician-led maternity units. All women diagnosed with vasa praevia who gave birth between 1st December 2014 and 30th November 2015 were included. The main outcome was estimated incidence of vasa praevia with 95% confidence intervals, using 2015 maternities as the denominator. Results Fifty-one women met the case definition. The estimated incidence of diagnosed vasa praevia was 6.64 per 100,000 maternities (95% CI 5.05-8.73). Of 198 units, 10 (5%) had a vasa praevia screening programme; one of these 10 units identified 25% of the antenatally diagnosed cases. Among women who had vasa praevia diagnosed or suspected antenatally (n=28, 55%), there were no perinatal deaths or hypoxic ischaemic encephalopathy (HIE). Twenty-four women with antenatal diagnosis were hospitalised at a median 32 weeks\u2019 gestation and caesarean section was scheduled at a median 36 weeks\u2019 gestation. When vasa praevia was diagnosed peripartum (n=23, 45%), the perinatal mortality rate was 37.5% and 47% of survivors developed HIE. Conclusions The incidence of diagnosed vasa praevia was lower than anticipated. There was high perinatal mortality and morbidity for cases not diagnosed antenatally. The incidence of antenatally identified cases was much higher in the few centres that actively screened for this condition, and the perinatal outcomes were better. However, this group were all delivered by caesarean section and may include women who would not have experienced any adverse perinatal outcome.<\/ns4:p>","DOI":"10.3310\/nihropenres.13696.2","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T08:45:07Z","timestamp":1733388307000},"page":"49","update-policy":"https:\/\/doi.org\/10.3310\/nihropenres.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Incidence and outcomes of vasa praevia in the United Kingdom"],"prefix":"10.3310","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9757-952X","authenticated-orcid":false,"given":"George","family":"Attilakos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna  L","family":"David","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1187-1808","authenticated-orcid":false,"given":"Ruth","family":"Tunn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1984-4575","authenticated-orcid":false,"given":"Marian","family":"Knight","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Brocklehurst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6221","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"591-8","DOI":"10.1097\/AOG.0000000000002198","article-title":"Vasa previa diagnosis, clinical practice, and outcomes in Australia.","volume":"130","author":"E Sullivan","year":"2017","journal-title":"Obstet Gynecol."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"556-557","DOI":"10.1002\/uog.20347","article-title":"Type-3 vasa previa: normal umbilical cord insertion cannot exclude vasa previa in cases with abnormal placental location.","volume":"55","author":"T Suekane","year":"2020","journal-title":"Ultrasound Obstet Gynecol."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"937-42","DOI":"10.1097\/01.AOG.0000123245.48645.98","article-title":"Vasa previa: the impact of prenatal diagnosis on outcomes.","volume":"103","author":"Y Oyelese","year":"2004","journal-title":"Obstet Gynecol."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"710-9","DOI":"10.1002\/uog.22166","article-title":"Perinatal outcome of pregnancies with prenatal diagnosis of vasa previa: systematic review and meta-analysis.","volume":"57","author":"W Zhang","year":"2021","journal-title":"Ultrasound Obstet Gynecol."},{"key":"ref-5","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-075630","article-title":"Neurological development in children born moderately or late preterm: national cohort study.","volume":"384","author":"A Mitha","year":"2024","journal-title":"BMJ."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"e49-e61","DOI":"10.1111\/1471-0528.15307","article-title":"Vasa praevia: diagnosis and management: green-top guideline no. 27b.","volume":"126","author":"E Jauniaux","year":"2019","journal-title":"BJOG."},{"key":"ref-7","article-title":"Screening for vasa praevia in the second trimester of pregnancy: external review against programme appraisal criteria for the UK National Screening Committee (UK NSC)","year":"2017"},{"key":"ref-8","article-title":"Screening for Vasa Praevia: an evidence map to outline the volume and type of evidence related to screening for vasa praevia for the UK National Screening Committee","year":"2023"},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"638.e1-638.e24","DOI":"10.1016\/j.ajog.2024.03.013","article-title":"Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.","volume":"231","author":"Y Oyelese","year":"2024","journal-title":"Am J Obstet Gynecol."},{"key":"ref-10","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2023-075245","article-title":"Incidence of vasa praevia: a systematic review and meta-analysis.","volume":"13","author":"W Zhang","year":"2023","journal-title":"BMJ Open."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"2642-8","DOI":"10.1080\/14767058.2019.1670797","article-title":"First trimester ultrasound prediction of velamentous cord insertions: a prospective study.","volume":"34","author":"S Derisbourg","year":"2021","journal-title":"J Matern Fetal Neonatal Med."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"109-15","DOI":"10.1046\/j.1469-0705.2001.00448.x","article-title":"Prenatal sonographic diagnosis of vasa previa: ultrasound findings and obstetric outcome in ten cases.","volume":"18","author":"V Catanzarite","year":"2001","journal-title":"Ultrasound Obstet Gynecol."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"475-80","DOI":"10.1038\/s41372-019-0319-8","article-title":"Vasa previa and extreme prematurity: a population-based study.","volume":"39","author":"A Yeaton-Massey","year":"2019","journal-title":"J Perinatol."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"605-12","DOI":"10.1002\/uog.21953","article-title":"Prevention of stillbirth: impact of two-stage screening for vasa previa.","volume":"55","author":"W Zhang","year":"2020","journal-title":"Ultrasound Obstet Gynecol."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"1466-73","DOI":"10.1111\/aogs.14839","article-title":"Incorporation of vasa previa screening into a routine anomaly scan: a single center cohort study.","volume":"103","author":"M Nwandison","year":"2024","journal-title":"Acta Obstet Gynecol Scand."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"263-5","DOI":"10.1111\/j.1471-0528.2005.00609.x","article-title":"The UK Obstetric Surveillance System for rare disorders of pregnancy.","volume":"112","author":"M Knight","year":"2005","journal-title":"BJOG."},{"key":"ref-17","article-title":"Births in England and Wales: summary tables. 2015 edition of this dataset","year":"2016"},{"key":"ref-18","article-title":"Vital events reference tables 2015","year":"2015"},{"key":"ref-19","article-title":"Registrar general Northern Ireland: annual report 2015","year":"2016"},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"436-42","DOI":"10.1097\/OGX.0000000000000692","article-title":"Diagnosis and management of vasa previa: a comparison of 4 national guidelines.","volume":"74","author":"I Tsakiridis","year":"2019","journal-title":"Obstet Gynecol Surv."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"615-9","DOI":"10.1016\/j.ajog.2015.08.031","article-title":"#37: diagnosis and management of vasa previa.","volume":"213","author":"R Sinkey","year":"2015","journal-title":"Am J Obstet Gynecol."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"506-518","DOI":"10.1016\/j.jogc.2023.05.009","article-title":"Guideline no. 439: diagnosis and management of vasa previa.","volume":"45","author":"V Jain","year":"2023","journal-title":"J Obstet Gynaecol Can."},{"key":"ref-23","article-title":"Vasa praevia.","year":"2019"},{"key":"ref-24","article-title":"Antenatal screening programme: vasa praevia.","year":"2023"},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"1278-87","DOI":"10.1111\/1471-0528.13829","article-title":"Incidence of and risk indicators for vasa praevia: a systematic review.","volume":"123","author":"L Ruiter","year":"2016","journal-title":"BJOG."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"927-41","DOI":"10.1097\/01.AOG.0000207559.15715.98","article-title":"Placenta previa, placenta accreta, and vasa previa.","volume":"107","author":"Y Oyelese","year":"2006","journal-title":"Obstet Gynecol."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"297-312","DOI":"10.1111\/cch.12320","article-title":"Long-term cognitive and school outcomes of late-preterm and early-term births: a systematic review.","volume":"42","author":"E Chan","year":"2016","journal-title":"Child Care Health Dev."},{"key":"ref-28","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.h2183","article-title":"Tests to predict imminent delivery in threatened preterm labour.","volume":"350","author":"N Hezelgrave","year":"2015","journal-title":"BMJ."},{"key":"ref-29","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2393-14-318","article-title":"\"Wrapping myself in cotton wool\": Australian women's experience of being diagnosed with vasa praevia.","volume":"14","author":"N Javid","year":"2014","journal-title":"BMC Pregnancy Childbirth."}],"container-title":["NIHR Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T08:45:12Z","timestamp":1733388312000},"score":1,"resource":{"primary":{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,5]]},"references-count":29,"URL":"https:\/\/doi.org\/10.3310\/nihropenres.13696.2","relation":{"has-version":[{"id-type":"doi","id":"10.3310\/nihropenres.13696.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.3310\/nihropenres.14995.r33986","asserted-by":"object"},{"id-type":"doi","id":"10.3310\/nihropenres.14995.r34164","asserted-by":"object"}]},"ISSN":["2633-4402"],"issn-type":[{"value":"2633-4402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,5]]},"assertion":[{"value":"Indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.3310\/nihropenres.14872.r32946, Antonios Siargkas, Aristotle University of Thessaloniki, Thessaloniki, 18 Sep 2024, version 1, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v1#referee-response-32946","order":0,"name":"referee-response-32946","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ruth Tunn<\/b>; \n<i>Posted: 26 Nov 2024<\/i>; Thank you for your supportive comments.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v2#referee-comment-3388","order":1,"name":"referee-comment-3388","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.14872.r32819, Ramesha Papanna, Neha Agarwal, Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School, The University of Texas, Houston, TX, 27 Sep 2024, version 1, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v1#referee-response-32819","order":2,"name":"referee-response-32819","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ruth Tunn<\/b>; \n<i>Posted: 26 Nov 2024<\/i>; \n<i>1. Limited Scope of Screening Analysis:&nbsp; While the article mentions that only 5% of obstetric units in the UK had screening programs for vasa previa, it does not provide sufficient detail about the methods or criteria used for these screenings. Although there are significant differences in outcomes between hospitals with and without screening programs, the study lacks a detailed exploration of the specific screening strategies that could help reduce perinatal mortality and morbidity. A more in-depth investigation into the screening protocols used by the 10 units with programs would be beneficial. This additional detail could help inform future recommendations for the implementation of nationwide screening programs.<\/i>  Response: Unfortunately, we do not have further details of the screening protocols used at the centres in question at the time of the study. UKOSS reporting operates on a volunteer basis, and to avoid overburdening reporters and maximise return rates, we limit the amount of information requested. This study did not have evaluation of screening as a main objective, so we limited data collection about screening programmes to the simple yes\/no question described in the methods. We present data about screening programmes in relation to diagnosis in Table 5 to encourage and inform future research into this important issue, but do not seek to draw recommendations from the limited information collected.   \n<i>2. Exclusion of cases in antepartum vs postpartum: Need this distinction made to help improve the clarity of case selection. Of those 22 excluded cases are from antenatal diagnosis group, due to lack of sufficient details, it would help to make a better determination of the incidence.<\/i>  Response: We provide additional information about the excluded \u201ccases\u201d in Figure 1. Of the 22 reports of apparent cases that were excluded, one fell outside the study period and seven were found when reviewed to not meet the case definition (two were cases of cord prolapse, two were placenta praevia, and three were other non-vasa praevia reports). It would therefore be inappropriate to consider these in calculation of vasa praevia incidence.  Of the remaining fourteen reports received but not confirmed as vasa praevia, four were of women who had antepartum haemorrhage, fetal anaemia, or other poor outcomes. These outcomes are sometimes associated with vasa praevia but could be due to a range of other causes, and there was no indication that vasa praevia was suspected antenatally. Because UKOSS reporters are asked to identify and report all cases of the condition in question, they will sometimes err on the side of caution and include reports of observations that might be of interest, \u201cjust in case\u201d, to allow the UKOSS researchers on the specific study to make the final adjudication. However, there was insufficient evidence in these cases to suspect vasa praevia specifically.  The remaining ten excluded reports were of women in whom vasa praevia was suspected antenatally and who underwent planned caesarean section because of this suspicion, but there was no documented confirmation of the condition after women gave birth. We could therefore not include these under our case definition in the primary estimate of incidence; however, we do discuss the possible impact of their exclusion in the Discussion: \u201c\n<i>Even if the 10 planned caesarean sections with no postnatal confirmation were included, the estimated incidence would still be relatively low at 7.94 per 100,000 maternities (1 case for every 12,593 maternities)<\/i>.\u201d  We have expanded on the reasons for exclusion in Figure 1 and changed the terminology of unconfirmed \u201ccases\u201d to \u201creports\u201d in the text for clarity.   \n<i>3. Underestimation of the vasa previa. As authors acknowledge in the weakness of the study, there is high probability of underestimation of vasa previa due to nature of reporting in this large-scale study. There is lack of rigorous methods to determine the true incidence of vasa previa. Consider avoiding \u201cincidence\u201d in the title, objective, and use \u201cestimates\u201d .<\/i>  Response: We have retained the term \u201cincidence\u201d, as this was the metric that the study was designed to investigate, but have added \u201cestimated\u201d at relevant points in the text to reflect the uncertainty arising from the acknowledged limitations. The important point to note is the difference between diagnosed vasa praevia based on screening, and diagnosed vasa praevia based on adverse outcome. As few hospitals in the UK have vasa praevia screening programmes, the estimate of incidence is more reflective of the latter.   \n<i>4. Confirmation of vasa previa: Lack of details in the diagnosis of vasa previa including exposed fetal vessels on clinical examination. How often is clinical examination performed of the placenta? Is this universal? Are there standard protocols that require post-delivery placental evaluation to ensure optimal case capture?&nbsp;&nbsp; <\/i> \n<i>5. Confirmation of pathologic examination of the placenta\u201d&nbsp; How many in this cohort? How can you confirm that without information on placental orientation within the uterine environment?<\/i>  Response: Visual examination of all placentas post-birth is standard practice in the UK, to ensure completeness as well as to identify abnormal vessels. As indicated in Table 3, the placenta was examined in 100% of antenatally diagnosed cases (noting that this was required to establish the case definition) and 91% of peripartum-diagnosed cases; it was sent to pathology for further examination in 32% of antenatally diagnosed cases and 65% of peripartum-diagnosed cases. As the reviewer notes, in placentas of women who have had no suspicion of vasa praevia antenatally and no adverse outcome, the observation of fetal vessels in the membranes postnatally cannot be used to confirm vasa praevia as it would be unknown as to whether those vessels crossed the cervix, although the position of membrane rupture may be an indication. However, ruptured fetal vessels are readily detectable and, in women with antenatal suspicion in whom the orientation will have been confirmed on scan, fetal vessels running through the membranes can be confirmed postnatally.   \n<i>6. It is recommended that for the authors to estimates of effect of universal screening for vasa previa similar to 6% of hospitals on the obstetrical outcomes- number of c-sections to prevent one perinatal death and hypoxic ischemic encephalopathy. Does this justify the national guidelines for universal screening for vasa previa.<\/i>  Response: We agree that this would be useful information to have. However, we do not think that our study design and the limited amount of data from the few centres with screening programmes can support such analyses or would yield robust conclusions\/recommendations. The numbers involved are small, association between screening and antenatal diagnosis was not consistent across centres with programmes and, and as you identified in a previous comment, we have limited details of the exact composition of the screening programmes that the screening centres had in place at the time of the study, so a recommendation would lack necessary details of any advocated intervention. We say in the discussion, \u201cTable 5 illustrates that the number of reported cases of vasa praevia was substantially higher if there was antenatal screening. Large, well-designed prospective screening studies may elucidate this observation further; our study was not designed to evaluate screening efficiency or accuracy\u201d. We agree that future studies should investigate screening in more depth to be able to provide guidance on this issue.   \n<i>Below are the minor concerns of the article:<\/i> \n<i>1. In the Methods section of the abstract, there is a spelling error in line 3. The word &quot;form&quot; should be corrected to &quot;from.&quot;<\/i>  Response: Thank you, we have corrected this error.   \n<i>2. 48% of the cases of peripartum identification had an antepartum admission. What were the indications for admission? Was this preterm labor? Vaginal bleeding? Unrelated medical indications (e.g., preeclampsia)?<\/i>  Response: Of the 11 women in the peripartum diagnosis group admitted to hospital antenatally, three were admitted for reasons relating to the position or movement of the fetus; four for maternal indications unrelated to vasa praevia, such as elevated blood pressure; and two for antepartum haemorrhage that progressed to birth. Notably, two women were admitted for antepartum bleeding earlier in the pregnancy, which could indicate a missed opportunity for vasa praevia diagnosis.  We have added this information to the manuscript.   \n<i>3. Irrespective of universal screening recommendation, are there recommendations for screening among those with risk factors considering 43% of the cases with peripartum identification had low-lying placenta and\/or velamentous cord insertion and 100% had at least 1 risk factor.<\/i>  Response: Our study suggests that targeted screening may be appropriate, although we are cautious about making firm recommendations on the basis of this evidence alone. National guidelines in the US, Canada and Australia all advocate targeted screening for women with risk factors for vasa praevia. We mentioned these guidelines in broader terms in the fourth paragraph of the Discussion, but have now emphasised the relevant recommendations again where we reflect on risk factors in the cases in our study, by adding the sentence in bold below:  \u201cMost previous studies (20) demonstrated the presence of risk factors in most vasa praevia cases; in our study all cases had at least one risk factor. This might suggest that targeted screening for cases with risk factors, particularly low placenta and velamentous cord insertion, might be useful as one or both of these were present in almost half of the cases in our study. \n<b>This would be consistent with current US, Canadian and Australian guidelines, all of which recommend targeted screening (19).<\/b>\u201d  19. Tsakiridis I, Mamopoulos A, Athanasiadis A, Dagklis T. Diagnosis and Management of Vasa previa: a comparison of 4 national guidelines. Obstetrical &amp; Gynecological Survey. 2019;74(7):436-42.   \n<i>4. In the 7th paragraph of the Results section, why term \u201cno antenatal diagnosis\u201d rather than \u201cperipartum\u201d as is otherwise used throughout the article?<\/i>  Response: Thank you for pointing this out, we have made the terminology consistent.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v2#referee-comment-3389","order":3,"name":"referee-comment-3389","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.14872.r32941, Paolo Ivo Cavoretto, Vita-Salute San Raffaele University, Milan, 30 Sep 2024, version 1, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v1#referee-response-32941","order":4,"name":"referee-response-32941","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ruth Tunn<\/b>; \n<i>Posted: 26 Nov 2024<\/i>; \n<i>1. Type III vasa previa was not considered enough by the authors and this in an important reticence to be corrected. Type III vasa previa is a rare form of VP, not necessarily associated with other placental or vascular anomalies, in which aberrant vessels run from the placenta to the amniotic membranes, near the internal cervical os, before returning to the placenta.&nbsp; It was object of a recent systematic review published in UOG that should be considered by the authors (ref 1).<\/i> \n<i>Were type III VP accounted for? Were they excluded from the study? This is very interesting to be added for readers. A wide dissemination on knowledge around type III vasa previa is required as this is not yet a well-known topic.<\/i>  Response: When this study was designed and conducted (2014\u20132015), type III vasa praevia had not been described as a distinct subtype. It was therefore not explicitly considered as a sub-type in the case definition or eligibility criteria. However, cases of VP of this type would have been captured by the case definition. Indeed, in some scientific presentations before 2014, the term &quot;type III vasa praevia\u201d was used to describe vasa praevia of a second twin when its membranes were presenting after the birth of the first twin. This type of vasa praevia would also have been captured by the case definition.  We have added a mention of type III vasa praevia to the Introduction.   \n<i>2. The authors state that in 10 cases &quot;no documentation of the placenta being examined or sent to histopathology after birth, so there was no confirmation of vasa praevia&quot;. However I am afraid that anatomopatological diagnosis simply cannot&nbsp; rule out or rule in vasa previa, as the relationship with the uterine structures is only available as an intraoperative surgical macroscopic diagnosis. This diagnosis can be documented with pictures and videos or with clinical diagnosis during delivery Anatomopatologists can only diagnose velamentous cord insertion, bilobate\/succenturiate or type III extraplacental aberrant vessels as well as placental structural or morpholigcal aberrations associated (but not patognominic) to vasa previa. This comment is not against the authors findings but instead it may be useful to reinforce their message (there is an extent of wrong prenatal diagnosis but this risk in expert hands is very low).<\/i>  Response: Thank you, we have added to the discussion the consideration of the potential value of intra-operative photographic documentation.   \n<i>3. Methods. Among risk factors for VP multiple pregnancies should be included.<\/i>  Response: Data were collected on multiple pregnancies, but numbers were too small to be meaningfully analysed as only one woman with a multiple pregnancy was affected. We have added a link to the full data collection form for the study. Furthermore, in the meta-analysis by Ruiter et al, multiple pregnancy was not found to be a statistically significant risk factor.   \n<i>4. The issue of cervical screening for cervical length, to be used to screen also for vasa previa screening may be considered and mentioned with pros and cons.<\/i>  Response: As indicated in Table 3, cervical length was measured in 36% of antenatally diagnosed cases but used in the decision to admit the woman to hospital in only 11%. Cervical length was not measured in any of the peripartum-diagnosed women.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v2#referee-comment-3390","order":5,"name":"referee-comment-3390","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.14872.r32820, Cristina Trilla, Department of Obstetrics and Gynaecology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Catalonia, 30 Sep 2024, version 1, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v1#referee-response-32820","order":6,"name":"referee-response-32820","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ruth Tunn<\/b>; \n<i>Posted: 26 Nov 2024<\/i>; \n<i><b>Reviewer Comments:&nbsp;<\/b> Methods: the authors describe a screening program for vasa previa in some of the institutions involved in this survey. Please, provide more accurate information on these screening programs (universal? Risk-based?), as this could significantly affect prenatal diagnosis.<\/i>  \n<b>Author Response: <\/b>Unfortunately, we do not have further details of the screening protocols used at the centres in question at the time of the study. UKOSS reporting operates on a volunteer basis, and to avoid overburdening reporters and maximise return rates, we limit the amount of information requested. This study did not have evaluation of screening as a main objective, so we limited data collection about screening programmes to the simple yes\/no question described in the methods. We present data about screening programmes in relation to diagnosis in Table 5 to encourage and inform future research into this important issue, but do not seek to draw recommendations from the limited information collected. ------------- \n<i><b>Reviewer Comments:&nbsp;<\/b><\/i> \n<i>The definition criteria and confirmation criteria for vasa previa was very strict. Sometimes vasa previa is difficult to diagnose post-partum, even with a careful examination of the placenta and the cord. This could explain the unexpected low rate of vasa previa in the study. The authors have included this as a limitation of the study, but I would ask the authors to elaborate more regarding the added value of this research considering this limitation. I understand that the aim of the study was to provide accurate information on vasa previa incidence in the UK, but these results are not concordant with previous research on the topic in other countries, and there is no clear explanation for this very low incidence in the UK. In any case, vasa previa incidence should be increasing, mainly due to the increase of ART among other risk factors. This should be mentioned and discussed more clearly in the manuscript, as such data may impact management policies for the condition if the incidence is really this low.<\/i>&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; \n<b>Author Response:&nbsp;<\/b>As we note in the discussion, the clearly defined criteria we used meant that suspected cases diagnosed following screening could not be included if there was no postnatal examination of the placenta and membranes to confirm an abnormal vessel. As we describe in our response to reviewer 2 concerning incidence, the important point to note is the difference between diagnosed VP based on screening, and diagnosed VP based on adverse outcome. As few hospitals in the UK have VP screening programmes, the estimate of incidence is more reflective of the latter, which may partly explain why it is lower than some other estimates, although notably similar to studies using similar methodology (Sullivan EA, Javid N, Duncombe G, Li Z, Safi N, Cincotta R, et al. Vasa previa diagnosis, clinical practice, and outcomes in Australia. Obstetrics &amp; Gynecology. 2017;130(3):591-8). Both our study and the AMOSS study are nationwide population studies in contrast to single centre VP screening studies, which report higher incidence.  ------------- \n<i><b>Reviewer Comments:&nbsp;<\/b><\/i> \n<i>Many cases were excluded (22 out of 73, which represents 30% of the suspected cases). I do not clearly understand the exclusion criteria for these, and I would suggest revising this, as I believe it has greatly affected the final numbers. Examination of the placenta was apparently a requirement for diagnosis, but how often is this really performed?<\/i>  \n<b>Author Response:&nbsp;<\/b>UKOSS collects data prospectively, meaning clinicians are asked to be alert to cases of the specified conditions being studied at any given time and to report them. This potentially increased the frequency of confirmatory examination of the placenta beyond that seen in normal clinical practice, helping to ensure cases were captured. As indicated in Table 3, the placenta was examined in 100% of antenatally diagnosed cases and 91% of peripartum-diagnosed cases; it was sent to pathology for further examination in 32% of antenatally diagnosed cases and 65% of peripartum-diagnosed cases.  We provide additional information about the excluded \u201ccases\u201d in Figure 1. Of the 22 reports of apparent cases that were excluded, one fell outside the study period and seven were found when reviewed to not meet the case definition (two were cases of cord prolapse, two were placenta praevia, and three were other non-vasa praevia reports). It would therefore be inappropriate to consider these in calculation of vasa praevia incidence.  Of the remaining fourteen reports received but not confirmed as vasa praevia, four were of women who had antepartum haemorrhage, fetal anaemia, or other poor outcomes. These outcomes are sometimes associated with vasa praevia but could be due to a range of other causes, and there was no indication that vasa praevia was suspected antenatally. Because UKOSS reporters are asked to identify and report all cases of the condition in question, they will sometimes err on the side of caution and include reports of observations that might be of interest, \u201cjust in case\u201d, to allow the UKOSS researchers on the specific study to make the final adjudication. However, there was little evidence in these cases to suspect vasa praevia specifically.  The remaining ten excluded reports were of women in whom vasa praevia was suspected antenatally and who underwent caesarean section indicated by vasa praevia, but there was no documented confirmation of the condition. We could therefore not include these under our case definition in the primary estimate of incidence; however, we do discuss the possible impact of their exclusion in the Discussion: \u201c\n<i>Even if the 10 planned caesarean sections with no postnatal confirmation were included, the estimated incidence would still be relatively low at 7.94 per 100,000 maternities (1 case for every 12,593 maternities)<\/i>.\u201d  We have expanded on the reasons for exclusion in Figure 1 and changed the terminology of unconfirmed \u201ccases\u201d to \u201creports\u201d in the text for clarity.  ------------- \n<i><b>Reviewer Comments:&nbsp;<\/b><\/i> \n<i>Please, provide accurate definition for urgency categories for CS in methods.<\/i>  \n<b>Author Response:&nbsp;<\/b>We have added a link to the full data collection form in the Methods, which includes the classification of urgency as provided to the reporting clinicians, in the \u201cDefinitions\u201d section. We have also provided the definitions in the footnote to Table 3.  ------------- \n<i><b>Reviewer Comments:&nbsp;<\/b><\/i> \n<i>If I understand correctly, 2015 maternity centers participated in the study. As such, many maternity centers did not report any cases of vasa previa. Did the number of deliveries per maternity center correlate with the number of vasa previa diagnosed (either antenatally or postnatally)? Please, provide more data regarding the number the deliveries per center and the number of cases diagnosed.<\/i>  \n<b>Author Response:&nbsp;<\/b>We apologise for any confusion. In total, there are 193 consultant-led maternity units in the UK, all of which participate in UKOSS. The 2015 annual statistics for the constituent countries of the UK were used as the denominator for the incidence calculation, rather than data on the number of deliveries per individual maternity centre being collected in this study. Examining case distribution by centre would risk identification of sensitive information given the small numbers involved, and would be unlikely to be informative given the very limited statistical power of this analysis.  ------------- \n<i><b>Reviewer Comments:&nbsp;<\/b><\/i> \n<i>I believe one of the main conclusions should be that a more clear definition of vasa previa and its diagnosis is needed, rather than that its incidence in the UK is lower than in other countries.<\/i>  \n<b>Author Response:&nbsp;<\/b>We state in the Discussion that differing thresholds and screening protocols for detecting vasa praevia antenatally are likely to explain the apparent differences in the overall reported incidence between countries. For example, a variable distance of 2-5 cm from the internal cervical os is used to diagnose vasa praevia in ultrasound screening. We also discuss other possible reasons for the apparent differences between countries (under-diagnosis, underreporting, mis-diagnosis).  ------------- \n<i><b>Reviewer Comments:&nbsp;<\/b><\/i> \n<i>My minor concerns are presented below:<\/i> \n<i>Introduction: the authors are only referring to vasa previa type 1 and 2, but a third type has been described. This should be mentioned in the introduction<\/i>  \n<b>Author Response:&nbsp;<\/b>When this study was designed and conducted (2014\u20132015), type III vasa praevia had not been described as a distinct subtype. It was therefore not explicitly considered as a sub-type in the case definition or eligibility criteria. However, cases of VP of this type would have been captured by the case definition.  We have added a mention of type III vasa praevia to the Introduction.  ------------- \n<i><b>Reviewer Comments:&nbsp;<\/b><\/i> \n<i>Underreporting of vasa previa: They state there is no reason to believe there were any underreported cases, but this is impossible to ascertain and should be listed as a limitation for the study.<\/i>  \n<b>Author Response:&nbsp;<\/b>We state in the Discussion section: \u201cAlthough we had multiple reporters in each hospital, we cannot be certain all cases were identified. In particular, the diagnosis may never have been considered as there is a possibility that ruptured vasa praevia mimics other conditions (e.g., abruption) and there is no \u201cgold\u201d standard to confirm the diagnosis after birth if the vessels are not ruptured.\u201d  We also mention that misattribution of cases to other causes, and cases not being reported or not recognised during the study period, are possible reasons for the lower-than-expected estimate of incidence.  As mentioned above, the important point to note is the difference between diagnosed vasa praevia based on screening, and diagnosed vasa praevia based on adverse outcome. As few hospitals in the UK have vasa praevia screening programmes, the estimate of incidence is more reflective of the latter.  ------------- \n<i><b>Reviewer Comments:&nbsp;<\/b><\/i> \n<i>Minor spelling error in the Methods section of the abstract: \u201cform\u201d should be spelled \u201cfrom\u201d. I did not find any other spelling concerns.<\/i>  \n<b>Author Response:&nbsp;<\/b>Thank you, we have corrected this error.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-49\/v2#referee-comment-3391","order":7,"name":"referee-comment-3391","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This project is part-funded by the National Institute for Health and Care Research (NIHR) under its University College London Hospitals NHS Foundation Trust Research Capability Fund (Grant Reference Number RCF68\/PB\/2014 5990), which was used to cover the UKOSS fee for a year. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. No other funding or financial support was obtained for the study. MK is an NIHR Senior Investigator; award reference NIHR303806. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":8,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}