Incidence, outcomes and management of spontaneous haemoperitoneum in pregnancy: a UK population-based study

Spontaneous haemoperitoneum in pregnancy (SHiP), haemorrhage, pregnancy, incidence, surveillance, UK Obstetric Surveillance System (UKOSS), International Network of Obstetric Survey Systems (INOSS) ALL Metrics - Views Downloads How to cite this article Tunn R, Ramakrishnan R, Engjom HM and Knight M. Incidence, outcomes and management of spontaneous haemoperitoneum in pregnancy: a UK population-based study [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2025, 5:40 (https://doi.org/10.3310/nihropenres.13960.1) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente Select a format first ▬ ✚ Research Article [version 1; peer review: 1 approved, 1 approved with reservations] Ruth Tunn https://orcid.org/0000-0003-1187-1808 1, Rema Ramakrishnan https://orcid.org/0000-0002-6784-8319 1, Hilde Marie Engjom https://orcid.org/0000-0003-1582-4283 2, Marian Knight https://orcid.org/0000-0002-1984-4575 1Ruth Tunn https://orcid.org/0000-0003-1187-1808 1, Rema Ramakrishnan https://orcid.org/0000-0002-6784-8319 1, Hilde Marie Engjom https://orcid.org/0000-0003-1582-4283 2, Marian Knight https://orcid.org/0000-0002-1984-4575 1 PUBLISHED 28 Apr 2025 Author details Author details 1 National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Headington, Oxford, OX3 7LF, UK 2 Department of Health Promotion, Division Public Health and Prevention, Norwegian Institute of Public Health, Zander Kaaesgate 7, 5015 Bergen, Norway 2 Department of Health Promotion, Division Public Health and Prevention, Norwegian Institute of Public Health, Zander Kaaesgate 7, 5015 Bergen, Norway Ruth Tunn Roles: Validation, Writing – Original Draft Preparation Roles: Validation, Writing – Original Draft Preparation Rema Ramakrishnan Roles: Data Curation, Formal Analysis, Writing – Review & Editing Roles: Data Curation, Formal Analysis, Writing – Review & Editing Hilde Marie Engjom Roles: Validation, Writing – Review & Editing Roles: Validation, Writing – Review & Editing Marian Knight Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Supervision, Writing – Review & Editing Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Supervision, Writing – Review & Editing OPEN PEER REVIEW REVIEWER STATUS Spontaneous haemoperitoneum in pregnancy (SHiP) is the occurrence during pregnancy of sudden intra-abdominal haemorrhage unrelated to extrauterine pregnancy, trauma or uterine rupture. SHiP is uncommon but is associated with preterm birth, high perinatal mortality and, more rarely, maternal mortality. We investigated the incidence of SHiP in the UK and its diagnosis, management and outcomes. This two-year, prospective surveillance study used the UK Obstetric Surveillance System to collect anonymous data on all women who gave birth in a UK consultant-led maternity unit in 2016 and 2017 and who experienced SHiP. We confirmed 20 cases of SHiP, giving an estimated incidence of 1.3 cases per 100,000 maternities, or 1 per 75,614 maternities. The median gestational age at diagnosis was 35.7 weeks (IQR 29.9–38.4 weeks). A minority of affected women were receiving anticoagulant agents for prophylaxis (2/20) or treatment (4/20). The most common initial suspected diagnosis was placental abruption (7/20), followed by intra-abdominal bleeding, uterine rupture, or infection. SHiP was diagnosed using ultrasound in four women, using CT in five, and solely at surgery in 14. Aneurysms (4/20) and organ rupture or haematoma (5/20) were the most common bleeding source, and the condition was most commonly diagnosed and treated by laparotomy (11/20). Perinatal morbidity and mortality were high, with 16% of infants stillborn, an over 80% admission rate to the neonatal unit among the 16 live-born infants, major complications in a third of these infants, and one neonatal death. Maternal morbidity was also high, with 60% of women admitted to the intensive care unit, over half of whom experienced major morbidity, and one maternal death. SHiP is rare in the UK but when it occurs, it can be associated with major maternal morbidity and mortality, and perinatal outcomes are poor. International comparisons are complicated by differing definitions of SHiP. Spontaneous haemoperitoneum in pregnancy, or “SHiP”, is a rare but serious condition that can happen during pregnancy. It involves sudden internal bleeding into the belly that is not caused by an injury and does not come from the womb. We wanted to understand how common SHiP is in the UK, how women who experience it are diagnosed and treated, and what happens to them and their babies. We worked with a national network of doctors and midwives who work in UK hospital maternity units to collect information for our study. They told us about every woman who gave birth in 2016 and 2017, and who experienced SHiP. In the two years of our study, about 1.5 million women gave birth in the UK. Of these, 20 women experienced SHiP – about one in 75,000. The most common symptom was belly pain. Over half of the women’s unborn babies’ heart rates were affected, and several women collapsed. A few women had an ultrasound or CT scan to diagnose the problem, but for most women, SHiP was diagnosed during surgery. Bleeding most often came from a burst blood vessel or damaged organ. SHiP was very dangerous for the women’s babies: three of the babies were stillborn and one died after birth. Most of the babies who survived needed to be cared for in the neonatal intensive care unit. SHiP was also very serious for the women themselves: one woman died, and over half needed treatment in the intensive care unit. Our study showed that SHiP is very rare in the UK. However, when it does happen, in many cases it results in serious illness, and it can be fatal, for both mum and baby. Healthcare workers need to be alert for signs of SHiP. Spontaneous haemoperitoneum in pregnancy (SHiP), haemorrhage, pregnancy, incidence, surveillance, UK Obstetric Surveillance System (UKOSS), International Network of Obstetric Survey Systems (INOSS) Corresponding Author(s) Marian Knight ([email protected]) Grant information: This project is funded by the National Institute for Health and Care Research (NIHR) under an NIHR Professorship to Marian Knight, Grant Reference Number NIHR-RP-011-032. The views expressed are those of the author(s) and not necessarily those of the NIHR, the University of Oxford or the Department of Health and Social Care. Hilde Marie Engjom participated in this work as part of an international mobility grant from the Norwegian Research Council (grant no 320181). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Tunn R et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Tunn R, Ramakrishnan R, Engjom HM and Knight M. Incidence, outcomes and management of spontaneous haemoperitoneum in pregnancy: a UK population-based study [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2025, 5:40 (https://doi.org/10.3310/nihropenres.13960.1) First published: 28 Apr 2025, 5:40 (https://doi.org/10.3310/nihropenres.13960.1) Latest published: 06 Jun 2025, 5:40 (https://doi.org/10.3310/nihropenres.13960.2) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There is a newer version of this article available. of this article available. Spontaneous haemoperitoneum in pregnancy (SHiP) is the occurrence during pregnancy of sudden intra-abdominal haemorrhage that is unrelated to extrauterine pregnancy, trauma, or uterine rupture. SHiP most commonly occurs in the third trimester but can occur at any time during pregnancy or in the weeks after birth1,2, and is associated with preterm birth, high perinatal mortality and, more rarely, maternal mortality1–3. Known maternal risk factors for SHIP are maternal age over 35 years2 and factors associated with endometriosis1,4,5, including pregnancies conceived via artificial reproductive techniques (ART)6–8 as well as multiple pregnancy2. Women experiencing SHiP typically present with sudden acute abdominal pain, frequently in combination with hypovolaemic shock, decreased haemoglobin levels, and/or signs of fetal distress7. Bleeding may originate from abdominal parenchymal organs, abdominal arterial or venous vessels such as splenic artery aneurysms or pelvic varicose veins, from extrauterine endometroid or decidual tissue implants, or other causes1,9,10. Often, placental abruption is initially suspected1,7. Diagnosis usually involves detection of free peritoneal fluid by ultrasound1, sometimes in combination with other modalities such as computed tomography2,3,5. Management is typically surgical, with laparotomy the most common intervention1,2, although expectant management was the most frequently used treatment approach in the Netherlands3. The mode of birth is caesarean section in a majority of cases2,3,7. Because of the rarity of the condition, it is challenging to estimate the incidence of SHiP. Most reports of SHiP in the literature are individual case studies or small case series1. The MBRRACE-UK surveillance programme identified six maternal deaths attributed to spontaneous intra-abdominal bleeding in the three years from 2019 to 20219, but information on non-fatal case incidence and morbidity related to SHiP in the UK is lacking. In light of the evidence gap, International Network of Obstetric Survey Systems (INOSS) initiated a series of prospective nationwide surveillance studies in multiple countries11. A two-year study in the Netherlands found an estimated incidence of SHiP of 4.9 per 100,000 births, with no maternal mortality among 14 women, and three perinatal deaths3. A similar study in Italy estimated the incidence at 4 per 100,000 births, with two maternal deaths, one neonatal death, and five stillbirths among 29 cases2. Here, we present the findings of the UK Obstetric Surveillance System (UKOSS) study of SHiP. The aim of this two-year, prospective, UK population-based surveillance study was to describe the incidence, diagnosis, and management of SHiP, and the characteristics and outcomes of affected women and their babies. Patients were not directly involved in the design of this study. Two members of the public were indirectly involved in the design of the study as representatives on the UKOSS Steering Committee, which reviews, comments on, and approves the choice of conditions to be investigated and the design and data collection forms for all studies to be run through UKOSS. Patients and the public were not involved in dissemination plans for the study. For this national, two-year, prospective, population-based surveillance study the source population was 1,512,289 women giving birth in the UK from 2016 to 201712–14. Women were included if they had SHiP between 1 January 2016 and 31 December 2017. The UKOSS infrastructure was used for reporting and collection of clinical information; this methodology has been described in detail elsewhere15. Briefly, nominated clinicians at all UK consultant-led maternity units complete a monthly return reporting the number of cases of specified uncommon conditions diagnosed in pregnant women by their managing clinicians (including zero values). Where a case is identified, UKOSS send a data collection form to gather data on the characteristics of the woman, her pregnancy, and the birth; potential risk factors for the specified condition; diagnosis and management of the condition; and maternal and neonatal outcomes. Data are double-entered into a study-specific database, with any queries directed back to the reporting centre. Where data collection forms are not returned, up to five reminders are sent to the reporting centre to minimise missing data. Cases were defined as any woman at 20 weeks or more gestation with sudden intra-abdominal haemorrhage requiring surgery (CS, laparotomy, laparoscopy), without preceding trauma. Women with extrauterine pregnancy, trauma, or uterine rupture were excluded. The study-specific data collected included information about maternal socio-demographic characteristics, known risk factors (history of endometriosis, prior abdominal surgery, treatment with anticoagulants), information about diagnosis and treatment of intraabdominal haemorrhage including the use of blood products, and maternal and neonatal outcomes. The full data collection form for this study can be found here: https://www.npeu.ox.ac.uk/assets/downloads/ukoss/forms/UKOSS-SHiP-v10---12-Apr-2016.pdf We calculated the incidence of SHiP with 95% confidence interval (CI) using the total number of maternities in the UK in 2016 and 2017 as the denominator12–14. Demographic characteristics of the women and the diagnosis, management and outcomes of SHiP are summarised using descriptive statistics. Categorical data are presented as counts and as percentages of women for whom data were available for each variable; continuous data are summarized as medians with interquartile range (IQR). Analyses were conducted using StataNow MP 18.516. The UK Obstetric Surveillance System general methodology was approved by the London Multi-Centre Research Ethics Committee (04/MRE02/45; 24 September 2004) and ethics approval for the current study as a substantial amendment was granted by the North London REC1 (study reference 10/H0717/20, 19 August 2015). Consent was not required for the collection of anonymous routine data. During the two years of the study, UKOSS representatives reported 27 women as having potential SHiP. Of these, seven did not meet the case definition, leaving 20 confirmed cases of SHiP. The total number of maternities in the UK in 2016 and 2017 was 1,512,28912–14, giving an incidence of SHiP of 1.3 cases per 100,000 maternities (95% CI 0.81–2.24) or 1 case per 75,614 maternities. Demographic and clinical characteristics of the 20 women are summarised in Table 1. The median age was 34.5 years (IQR 32–37 years). Two women had a history of endometriosis; four women had had a previous caesarean section, and seven had previous abdominal surgery of any kind. Two women had a known genetic bleeding tendency or haemoglobinopathy. Five women had a history of previous pregnancy problems; these included preeclampsia, intrauterine growth restriction, and placenta accreta. | Characteristic | Total (N = 20) | |---|---| | Maternal age (years), median (IQR) | 34.5 (32 – 37) | | Ethnic group, n (%) | | | White | 15 (78.9) | | Asian or Asian British | 2 (10.5) | | Black or Black British | 2 (10.5) | | Missing | 1 | | Employed, n (%) | | | No | 7 (36.8) | | Yes | 12 (63.2) | | Missing | 1 | | Body mass index at booking (kg/m2), median (IQR) | 26.0 (23.4 –29.5) | | Smoking status during pregnancy, n (%) | | | Yes/gave up during pregnancy | 3 (15.8) | | No/gave up prior to pregnancy | 16 (84.2) | | Missing | 1 | | Problems in previous pregnancy/ pregnancies, n (%) | | | No | 8 (42.1) | | Yes | 5 (26.3) | | Not applicable (nulliparous) | 6 (31.6) | | Missing | 1 | | Pre-existing medical problems, n (%) | | | No | 10 (52.6) | | Yes | 9 (47.4) | | Missing | 1 | | History of endometriosis, n (%) | | | No | 17 (89.5) | | Yes | 2 (10.5) | | Missing | 1 | | Prior abdominal surgery*, n (%) | | | No | 12 (63.2) | | Yes | 7 (36.8) | | Missing | 1 | | Previous caesarean birth, n (%) | | | No | 15 (78.9) | | Yes | 4 (21.1) | | Missing | 1 | Characteristics of the index pregnancy are summarised in Table 2. All were singleton pregnancies. Thirteen of the women had given birth previously. Prior to diagnosis of SHiP, the planned mode of birth was elective caesarean section in four women, vaginal in birth in fourteen, and missing in two. Problems reported during the index pregnancy included thrombotic events in three women, two women with HELLP and one woman with gestational diabetes. Six women received anticoagulants during the index pregnancy: four received low molecular weight heparin (LMWH) only, one received acetylsalicylic acid, and one woman received both. LMWH was given prophylactically in one of these women and therapeutically in four. No other anticoagulant use was recorded. Details of the diagnosis and management of SHiP are summarised in Table 3. The median gestational age at diagnosis was 35.7 weeks (IQR 29.9–38.4 weeks). Of the 20 women, 18 presented with abdominal pain. Other symptoms prior to diagnosis included abnormal fetal heart rate in over half of women (12/20, 60%); and less frequently, collapse, shoulder tip pain, altered uterine contractions, and vaginal bleeding. The most common initial suspected diagnosis was placental abruption (7/20, 35%), followed by intra-abdominal bleeding, uterine rupture, or infection. SHiP was diagnosed using ultrasound in four women, using CT in five, and solely at surgery in 14. | Characteristic | Total (N = 20) | |---|---| | Gestational age at diagnosis (weeks), median (IQR) | 35.7 (29.9 – 38.4) | | Missing | 1 | | Symptoms prior to SHiP diagnosis* | | | Abdominal pain | 18 (90.0) | | Altered uterine contractions | 2 (10.0) | | Haematuria | 1 (5.0) | | Vaginal bleeding | 2 (10.0) | | Fetal heart rate abnormality | 12 (60.0) | | Shoulder tip pain | 2 (10.0) | | Collapse | 4 (20.0) | | Other | 5 (25.0) | | Initial presumed diagnosis | | | Placental abruption | 7 (35.0) | | Intra-abdominal bleed | 3 (15.0) | | Uterine rupture | 3 (15.0) | | Infection | 3 (15.0) | | Other | 4 (20.0) | | Haemoperitoneum diagnosed* | | | Peritoneal lavage | 0 (0.0) | | Ultrasound | 4 (20.0) | | CT | 5 (25.0) | | CTPA | 0 (0.0) | | MRI | 0 (0.0) | | Solely at surgery | 14 (70.0) | | Mode of surgery for haemorrhage management | | | Laparoscopy | 1 (5.3) | | Planned† caesarean or hysterotomy | 4 (21.1) | | Laparotomy | 11 (57.9) | | Emergency‡ caesarean or hysterotomy | 3 (15.8) | | Missing | 1 | | Signs of active endometriosis at surgery | | | No | 15 (88.2) | | Yes | 2 (11.8) | | Missing | 3 | | Site of pregnancy | | | Intrauterine | 18 (100.0) | | Missing | 2 | | Source of bleeding | | | Arterial aneurism§ | 4 (20.0) | | Organ rupture/haematoma¶ | 5 (25.0) | | Endometriosis | 1 (5.0) | | Other | 7 (35.0) | | None/none identified | 3 (15.0) | | Estimated total blood loss (mL), median (IQR) | 3500 (2000 – 6000) | | Missing | 2 | | Estimated intraperitoneal blood loss | | | <500ml | 1 (5.0) | | ≥500 ml | 19 (95.0) | | Blood products given* | | | Whole blood/packed red cells | 18 (100.0) | | Total units, median (IQR) | 5 (4 – 15) | | Missing | 2 | | Fresh frozen plasma | 12 (70.6) | | Total units, median (IQR) | 4 (1 – 7.5) | | Missing | 3 | | Platelets | 12 (75.0) | | Total units, median (IQR) | 1.5 (1 – 2) | | Missing | 4 | | Cryoprecipitate | 6 (46.2) | | Total units, median (IQR) | 2 (2 –5) | | Missing | 7 | | Cell salvaged blood | 2 (20.0) | | Total units (ml), median (IQR) | 1399 (600 – 2198) | | Missing | 10 | | Haemostatic drugs given | | | No | 7 (35.0) | | Yes* | 13 (65.0) | | Fibrinogen | 1 (7.7) | | Factor VII | 3 (23.1) | | Tranexamic acid | 13 (100.0) | The most common bleeding sources were aneurysms, rupture or hematoma in the spleen, liver or kidney (9/20 women, 45%). This was followed by pelvic sources associated with the internal genital tract and scar tissue after previous surgery. Only one woman had endometriosis as a source of bleeding. Median blood loss was 3500 mL (IQR 2000–6000 mL). Around two-thirds of women (13/20) received haemostatic drugs, all of whom received tranexamic acid, with additional factor VIII and fibrinogen used in a minority of cases (n = 3 and n = 1, respectively). The most common mode of surgery for management of the haemorrhage was laparotomy, in 11 women (58%). Seven women (37%) had a caesarean or hysterotomy, which was planned from the start of the surgery in four women and followed conversion from laparotomy in three. Twelve women (60%) were admitted to intensive care, with a median duration of stay of 3 days (IQR 1–10 days, data missing for one woman). Of these women, one had a miscarriage in the second trimester, and one died. Six women (30%) experienced major morbidity, including renal failure (n = 2), disseminated intravascular coagulation and multiorgan failure (n = 1) and cardiac arrest (n = 1). Two women required mechanical ventilation and two underwent a splenectomy. Perinatal outcomes are summarised in Table 4. Of the 19 women whose pregnancies proceeded beyond 24 weeks, three gave birth vaginally and 16 gave birth by caesarean section with urgency grade 1 (indicating immediate threat to life of woman or fetus; n=15, one of which was a resuscitative hysterotomy [perimortem CS]) or grade 2 (indicating maternal or fetal compromise not immediately life-threatening; n=1). The majority of caesarean sections (n=12) were performed under general anaesthesia. Indications for caesarean section included fetal bradycardia, distress or compromise (in nine women); placental abruption or suspected abruption (in three women); abdominal pain (in three women); and uterine rupture subsequent to SHiP management by laparotomy (in one woman). | Characteristic | Total (N = 19* unless otherwise stated) | |---|---| | Stillbirth | | | No | 16 (84.2) | | Yes | 3 (15.8) | | Mode of birth | | | Spontaneous vaginal | 2 (10.5) | | Operative vaginal | 1 (5.3) | | Pre-labour caesarean | 15 (78.9) | | Caesarean after labour onset | 1 (5.3) | | Induced labour | | | No | 18 (100.0) | | Missing | 1 | | Caesarean birth | | | No | 3 (15.8) | | Yes | 16 (84.2) | | Grade of urgency (n = 16) | | | Immediate threat to life of woman or fetus | 15 (93.8) | | Maternal or fetal compromise not immediately life-threatening | 1 (6.2) | | Method of anaesthesia (n = 16) | | | Regional | 3 (20.0) | | General | 12 (80.0) | | Missing | 1 | | Placental abnormality identified | | | No | 17 (94.4) | | Yes | 1 (5.6) | | Missing | 1 | | Birthweight (g), median (IQR) | 2855 (1322 – 3485) | | Missing | 1 | | Apgar @5 minutes, median (IQR) (n = 16) | 6 (4 – 9) | | Missing | 1 | | Umbilical artery pH (n = 16) | | | Not measured | 4 (28.6) | | Measured | 10 (71.4) | | Median (IQR) pH | 6.9 (6.8 –7.0) | | Missing | 2 | | Neonatal unit admission (n = 16) | | | No | 3 (18.8) | | Yes | 13 (81.3) | | Major infant complications (n = 16) | | | No | 10 (66.7) | | Yes | 5 (33.3) | | Missing | 1 | | Neonatal death (n = 16) | | | No | 14 (93.3) | | Yes | 1 (6.7) | | Missing | 1 | The median birthweight of the 19 infants born at or after 24 weeks was 2855g (IQR 1322–3485g). There were three recorded stillbirths. Among live-born infants, the median 5-minute Apgar score was 6 (IQR 4–9). The median umbilical artery pH was 6.9 (IQR 6.8–7.0) in the ten infants for whom this information was recorded. Thirteen infants were admitted to the neonatal intensive care unit, with five experiencing major complications that included respiratory distress syndrome, hypoxia, jaundice, hypokalaemia, and suspected sepsis. One infant subsequently died of hypoxic-ischemic encephalopathy. This two-year, prospective, UK population-based surveillance study estimated the incidence of SHiP as 1.3 cases per 100,000 maternities, equating to 1 case per 75,614 maternities. Aneurysms and rupture or haematoma in the liver, spleen or kidney were the most common sources of bleeding. The diagnosis was most commonly made and treated during open abdominal surgery. A minority of affected women were receiving anticoagulant agents for prophylaxis (2/20) or treatment (4/20) of thromboembolism. Severe maternal and perinatal outcomes were common; these included stillbirths, neonatal intensive care unit admission, maternal intensive care unit admission, and one maternal death. This estimated incidence of SHiP is considerably lower than that estimated using similar national surveillance systems in the Netherlands (4.9 cases per 100,000 births) and Italy (4 cases per 100,000 births). All countries collaborate in the INOSS network and based their study on a joint definition of SHIP. However, local adaptations to this definition need to be considered in interpretation of differences across countries. The Dutch study ultimately deviated from the INOSS definition of SHiP11 and decided to exclude abdominal bleeding from aneurysms or liver, spleen and kidney. After these exclusions the management was expectant in over a third of included women, while fewer than two thirds underwent either surgery (6/14) or embolisation (2/14)3. Our study also deviated from the INOSS definition, but by including only cases requiring surgery (rather than those requiring either surgery or embolisation), which could have led us to underestimate incidence. Management by endovascular intervention depends on availability of expertise, including in interventional radiology, in the hospital. Our inclusion criteria may account for the some of the disparity between our findings and those of the Italian surveillance2, which used the INOSS definition, although the authors do not report the number of women who were eligible for inclusion as a result of having undergone embolisation. Subjectivity of diagnosis may also be a contributing factor in the differing estimates of incidence – in the Dutch study, auditors disagreed initially as to whether a SHiP diagnosis was appropriate in almost half (9/20) of potential cases submitted by reporters. There may also be underlying differences between the three countries in the risk profile of the pregnant population: for example, ART, an established risk factor for SHiP6,7, contributes to 4.2% of births in Italy17 and 3.0% in the Netherlands18 versus 1.2% in the UK19. Unfortunately, we did not explicitly request data on ART in our study, although IVF was mentioned in the supplementary notes of one woman; five of the 14 women in the Dutch study and five of the 29 in the Italian study had conceived by ART. We found that aneurysms, rupture or hematoma in the spleen, liver or kidney were the most common causes of SHiP. Pregnancy is associated with vascular wall and hemodynamic changes, and also increases the risk of haemorrhage/rupture of intracerebral and aortic aneurysms20–22. Vascular changes and hypertension in preeclampsia may aggravate this, but only two women in our study had pre-existing hypertensive disorders during the index pregnancy. Only one woman was diagnosed with endometriosis; this low frequency is striking even when exempting from the denominator cases arising from liver hematoma/rupture known to be associated with hypertensive disorders of pregnancy and HELLP-syndrome. By contrast, endometriosis was present in around a fifth of women with SHiP identified by the Italian surveillance2 and a third of women identified in the Netherlands3. SHiP was diagnosed by imaging prior to surgery in fewer than half of the women in our study: five of 20 were diagnosed using CT scan, four using ultrasound and none by MRI. This is in contrast to diagnosis in the Netherlands, where all affected women in a 2-year surveillance study underwent ultrasound, around a third (4/13) underwent CT, and a third (4/13) underwent MRI. This likely reflects the higher proportion of hemodynamically stable women included under the Dutch definition of SHiP, whereas CT or MRI is unlikely to be appropriate in the more emergent cases captured by the case definition in our study. The diagnostic modalities in Italy more closely resembled that in the UK: 14 of 29 women underwent ultrasound, six underwent CT and none MRI. Focused assessment sonography for trauma (FAST), used effectively in non-pregnant trauma patients with suspected haemoperitoneum23, offers a more rapid alternative to MRI or CT that may be more appropriate for diagnosing SHiP in haemodynamically unstable women. Almost a third of women in our study (6/20) were receiving anticoagulant agents, and only four were receiving therapeutic high-dose LMWH for thrombosis or thromboembolism. Thrombosis and thromboembolism are now the leading cause of maternal deaths in the UK during pregnancy or in the six weeks following birth24. Royal College of Obstetricians and Gynaecologists guidelines recommend prophylactic LMWH during pregnancy for women with previous venous thromboembolism or certain combinations of risk factors25, and LMWH treatment in clinically suspected pulmonary embolism or deep vein thrombosis26, unless strongly contraindicated. Awareness of the potential for SHiP, albeit rare, in these women, is important. SHiP is rare in the UK but when it does occur, it can be associated with major maternal morbidity and mortality, and perinatal outcomes are poor. Healthcare providers should be aware of the possible range of symptoms and consider it as a possible alternative diagnosis to placental abruption, intra-abdominal pain, uterine rupture, or abdominal infection, particularly in pregnant women presenting with abdominal pain and/or circulatory compromise. Future research would benefit from a strengthened consensus on the definition of SHiP. Data cannot be shared openly because of confidentiality issues and the potential identifiability of sensitive data. Requests to access the data can be made by contacting the National Perinatal Epidemiology Unit data access committee via [email protected]. The Research Ethics Committee approved the study on the basis that access will only be allowed after review of the request by the UK Obstetric Surveillance System Steering Committee. The estimated response time for requests is 4 weeks. Data sharing outside the UK or European Union may require consultation with the UK Health Research Authority. For more information, please refer to the National Perinatal Epidemiology Unit Data Sharing Policy available at https://www.npeu.ox.ac.uk/assets/downloads/npeu/policies/Data_Sharing_Policy.pdf. For the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. All statistical analyses were performed using StataNow MP v18.5, a commercial software. All analyses in this study can be replicated using freely available statistical software such as R. The authors would like to thank the United Kingdom Obstetric Surveillance System (UKOSS) reporting clinicians. Faculty Opinions recommendedReferences - 1. Lier MCI, Malik RF, Ket JCF, et al.: Spontaneous hemoperitoneum in pregnancy (SHiP) and endometriosis — a systematic review of the recent literature. Eur J Obstet Gynecol Reprod Biol. 2017; 219: 57–65. PubMed Abstract | Publisher Full Text - 2. Mazzocco MI, Donati S, Maraschini A, et al.: Spontaneous hemoperitoneum in pregnancy: Italian prospective population-based cohort study. Acta Obstet Gynecol Scand. 2022; 101(11): 1220–1226. PubMed Abstract | Publisher Full Text | Free Full Text - 3. Schreurs AMF, Overtoom EM, de Boer MA, et al.: Spontaneous hemoperitoneum in pregnancy: nationwide surveillance and Delphi audit system. BJOG. 2023; 130(13): 1620–8. PubMed Abstract | Publisher Full Text - 4. Brosens IA, Fusi L, Brosens JJ: Endometriosis is a risk factor for spontaneous hemoperitoneum during pregnancy. Fertil Steril. 2009; 92(4): 1243–1245. PubMed Abstract | Publisher Full Text - 5. Bazzurini L, Ornaghi S, Colciago E, et al.: Endometriosis-related spontaneous hemoperitoneum in pregnancy: a case series. J Obstet Gynaecol Res. 2023; 49(2): 744–52. PubMed Abstract | Publisher Full Text - 6. Brosens IA, Lier MC, Mijatovic V, et al.: Severe spontaneous hemoperitoneum in pregnancy may be linked to in vitro fertilization in patients with endometriosis: a systematic review. Fertil Steril. 2016; 106(3): 692–703. PubMed Abstract | Publisher Full Text - 7. Hagimoto M, Tanaka H, Osuga Y, et al.: Nationwide survey (Japan) on spontaneous hemoperitoneum in pregnancy. J Obstet Gynaecol Res. 2021; 47(8): 2646–2652. PubMed Abstract | Publisher Full Text - 8. de Ziegler D, Pirtea P, Carbonnel M, et al.: Assisted reproduction in endometriosis. Best Pract Res Clin Endocrinol Metab. 2019; 33(1): 47–59. PubMed Abstract | Publisher Full Text - 9. Knight M, Bunch K, Felker A, (Eds.), et al.: Saving lives, improving mothers’ care core report - lessons learned to inform maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2019-21. Oxford: National Perinatal Epidemiology Unit, University of Oxford, 2023. Reference Source - 10. Lier MCI, Brosens IA, Mijatovic V, et al.: Decidual bleeding as a cause of spontaneous hemoperitoneum in pregnancy and risk of preterm birth. Gynecol Obstet Invest. 2017; 82(4): 313–21. PubMed Abstract | Publisher Full Text - 11. Schaap T, Bloemenkamp K, Deneux-Tharaux C, et al.: Defining definitions: a Delphi study to develop a core outcome set for conditions of severe maternal morbidity. BJOG. 2019; 126(3): 394–401. PubMed Abstract | Publisher Full Text - 12. National Records of Scotland: Vital events reference tables: archive - historical data back to 2001. [Accessed 26 September 2024]. Reference Source - 13. Northern Ireland Statistics and Research Agency: Registrar general annual reports 2011-2019. [Accessed 26 September 2024]. Reference Source - 14. Office for National Statistics: Births in England and Wales: summary tables. [Accessed 26 September 2024]. Reference Source - 15. Knight M, Kurinczuk JJ, Tuffnell D, et al.: The UK Obstetric Surveillance System for rare disorders of pregnancy. BJOG. 2005; 112(3): 263–5. PubMed Abstract | Publisher Full Text - 16. StataCorp: StataNow MP statistical software: release 18.5. College Station, TX: StataCorp LLC, 2024. - 17. Listorti E, Torbica A, Esposito G, et al.: Determinants of the economic burden of ART on the Italian NHS: insights from the Lombardy region. Health Econ Rev. 2024; 14(1): 107. PubMed Abstract | Publisher Full Text | Free Full Text - 18. European IVF Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE), Smeenk J, Wyns C: ART in Europe, 2019: results generated from European registries by ESHRE†. Hum Reprod. 2023; 38(12): 2321–2338. PubMed Abstract | Publisher Full Text | Free Full Text - 19. Hua X, Rivero-Arias O, Quigley MA, et al.: Long-term healthcare utilization and costs of babies born after assisted reproductive technologies (ART): a record linkage study with 10-years’ follow-up in England. Human Reprod. 2023; 38(12): 2507–15. PubMed Abstract | Publisher Full Text | Free Full Text - 20. Braverman AC, Mittauer E, Harris KM, et al.: Clinical features and outcomes of pregnancy-related acute aortic dissection. JAMA Cardiol. 2021; 6(1): 58–66. PubMed Abstract | Publisher Full Text | Free Full Text - 21. Muiño Mosquera L, De Backer J: Managing aortic aneurysms and dissections during pregnancy. Expert Rev Cardiovasc Ther. 2015; 13(6): 703–14. PubMed Abstract | Publisher Full Text - 22. Nussbaum ES, Goddard JK, Davis AR: A systematic review of intracranial aneurysms in the pregnant patient ― a clinical conundrum. Eur J Obstet Gynecol Reprod Biol. 2020; 254: 79–86. PubMed Abstract | Publisher Full Text - 23. Gamberini L, Scquizzato T, Tartaglione M, et al.: Diagnostic accuracy for hemoperitoneum, influence on prehospital times and time-to-definitive treatment of prehospital FAST: a systematic review and individual participant data meta-analysis. Injury. 2023; 54(6): 1421–31. Publisher Full Text - 24. Felker A, Patel R, Kotnis R, (Eds.), et al.: Saving lives, improving mothers’ care compiled report - lessons learned to inform maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2020-22. Oxford: National Perinatal Epidemiology Unit, University of Oxford, 2024. Reference Source - 25. Royal College of Obstetricians and Gynaecologists: Reducing the risk of thrombosis and embolism during pregnancy and the puerperium (Green-top Guideline No. 37a). 3rd ed. (accessed 21 January 2025). Reference Source - 26. Royal College of Obstetricians and Gynaecologists: Thrombosis and embolism during pregnancy and the puerperium: acute management (Green-top Guideline No. 37b). 3rd ed. (accessed 21 January 2025). Reference Source Version 2 VERSION 2 PUBLISHED 06 Jun 2025 Revised Version 1 VERSION 1 PUBLISHED 28 Apr 2025

is closed on this version, please comment on the latest version above. - Author Response 06 Jun 2025Ruth Tunn, National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Headington, OX3 7LF, UK06 Jun 2025Author ResponseReviewer comment: It was a well-written study. Why has it taken over 8 years since the end of data collection to index this work? Since the authors had such a long ... Continue reading Reviewer comment: It was a well-written study. Why has it taken over 8 years since the end of data collection to index this work? Since the authors had such a long intervening time, why was data collection not extended? There is much literature on this subject from the UK between 2017 and now. Including this data would have added to the strength of this study. These recent studies show endometriosis to be a common risk factor among patients who have suffered SHiP. More women are being diagnosed with endometriosis in the last 5 years due to more campaigns and awareness, and so that's a huge data point missing in this study. Authors' response: Thank you for your constructive comments. We regret the extended delay in dissemination of the findings. Publication was initially delayed because we were hoping that our UK data would form part of an international study; however, this did not come to fruition. We could not extend the data collection in the interim because the UKOSS platform collects data on a number of conditions at any given time; therefore, to minimise reporting burden and avoid impeding research into other conditions we limit studies to a duration expected to yield meaningful data. From early 2020, the majority of UKOSS’s resources were then redirected to focus on maternal and neonatal SARS-CoV-2, and it has taken some time to get suspended projects back on track. We are acutely aware that we have a responsibility to disseminate the data and seek to do so now, albeit belatedly. As you point out, more women are being diagnosed in recent years with endometriosis because of awareness campaigns. However, this welcome improved awareness does not affect the underlying prevalence of this potential risk factor, just its detection. The serious and life-threatening presentation of SHiP means that lack of a prior diagnosis of endometriosis is unlikely to affect SHiP case ascertainment. Indeed, the one woman in our study who had endometriosis as the source of her bleeding did not have a prior diagnosis of endometriosis. Our data collection form asked whether there were signs of active endometriosis at surgery; only one other woman, who did have a prior diagnosis of endometriosis, had such activity detected. We therefore do not think that a higher current rate of endometriosis diagnosis compared with the diagnosis rate during our data collection period impedes the relevance of our conclusions about SHiP incidence, or the lack of a detectable link between endometriosis and SHiP. However, our study design and sample size do not allow us to rule out endometriosis as a risk factor; we suggest only that it is not a prerequisite and may appear less frequently in women who experience SHiP than other studies have suggested. It is also worth considering that cases of bleeding arising from endometriosis might be less severe than cases arising from aneurism or organ rupture and therefore might not meet our threshold for diagnosing SHiP if they could be managed expectantly. The differences in diagnostic criteria that we discuss could explain differences between our study and others in terms of the apparent prevalence of endometriosis in women with SHiP. We have revised the statement in the discussion that “Only one woman was diagnosed with endometriosis” to clarify that this refers to one woman having endometriosis as the source of her bleeding.Reviewer comment: It was a well-written study. Why has it taken over 8 years since the end of data collection to index this work? Since the authors had such a long intervening time, why was data collection not extended? There is much literature on this subject from the UK between 2017 and now. Including this data would have added to the strength of this study. These recent studies show endometriosis to be a common risk factor among patients who have suffered SHiP. More women are being diagnosed with endometriosis in the last 5 years due to more campaigns and awareness, and so that's a huge data point missing in this study.Competing Interests: See declarations in article Close Authors' response: Thank you for your constructive comments. We regret the extended delay in dissemination of the findings. Publication was initially delayed because we were hoping that our UK data would form part of an international study; however, this did not come to fruition. We could not extend the data collection in the interim because the UKOSS platform collects data on a number of conditions at any given time; therefore, to minimise reporting burden and avoid impeding research into other conditions we limit studies to a duration expected to yield meaningful data. From early 2020, the majority of UKOSS’s resources were then redirected to focus on maternal and neonatal SARS-CoV-2, and it has taken some time to get suspended projects back on track. We are acutely aware that we have a responsibility to disseminate the data and seek to do so now, albeit belatedly. As you point out, more women are being diagnosed in recent years with endometriosis because of awareness campaigns. However, this welcome improved awareness does not affect the underlying prevalence of this potential risk factor, just its detection. The serious and life-threatening presentation of SHiP means that lack of a prior diagnosis of endometriosis is unlikely to affect SHiP case ascertainment. Indeed, the one woman in our study who had endometriosis as the source of her bleeding did not have a prior diagnosis of endometriosis. Our data collection form asked whether there were signs of active endometriosis at surgery; only one other woman, who did have a prior diagnosis of endometriosis, had such activity detected. We therefore do not think that a higher current rate of endometriosis diagnosis compared with the diagnosis rate during our data collection period impedes the relevance of our conclusions about SHiP incidence, or the lack of a detectable link between endometriosis and SHiP. However, our study design and sample size do not allow us to rule out endometriosis as a risk factor; we suggest only that it is not a prerequisite and may appear less frequently in women who experience SHiP than other studies have suggested. It is also worth considering that cases of bleeding arising from endometriosis might be less severe than cases arising from aneurism or organ rupture and therefore might not meet our threshold for diagnosing SHiP if they could be managed expectantly. The differences in diagnostic criteria that we discuss could explain differences between our study and others in terms of the apparent prevalence of endometriosis in women with SHiP. We have revised the statement in the discussion that “Only one woman was diagnosed with endometriosis” to clarify that this refers to one woman having endometriosis as the source of her bleeding. - Discussion is closed on this version, please comment on the latest version above. Author details Author details 1 National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Headington, Oxford, OX3 7LF, UK 2 Department of Health Promotion, Division Public Health and Prevention, Norwegian Institute of Public Health, Zander Kaaesgate 7, 5015 Bergen, Norway 2 Department of Health Promotion, Division Public Health and Prevention, Norwegian Institute of Public Health, Zander Kaaesgate 7, 5015 Bergen, Norway Ruth Tunn Roles: Validation, Writing – Original Draft Preparation Roles: Validation, Writing – Original Draft Preparation Rema Ramakrishnan Roles: Data Curation, Formal Analysis, Writing – Review & Editing Roles: Data Curation, Formal Analysis, Writing – Review & Editing Hilde Marie Engjom Roles: Validation, Writing – Review & Editing Roles: Validation, Writing – Review & Editing Marian Knight Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Supervision, Writing – Review & Editing Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Supervision, Writing – Review & Editing Competing interests Marian Knight is an NIHR Senior Investigator; award reference NIHR303806. Hilde Marie Engjom participated in this work as part of an international mobility grant from the Norwegian Research Council (grant no 320181). All other authors: no conflicts reported. Grant information This project is funded by the National Institute for Health and Care Research (NIHR) under an NIHR Professorship to Marian Knight, Grant Reference Number NIHR-RP-011-032. The views expressed are those of the author(s) and not necessarily those of the NIHR, the University of Oxford or the Department of Health and Social Care. Hilde Marie Engjom participated in this work as part of an international mobility grant from the Norwegian Research Council (grant no 320181). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (2) Copyright © 2025 Tunn R et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. metrics VIEWS $counts.viewCount downloads Citations CITE how to cite this article Tunn R, Ramakrishnan R, Engjom HM and Knight M. Incidence, outcomes and management of spontaneous haemoperitoneum in pregnancy: a UK population-based study [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2025, 5:40 (https://doi.org/10.3310/nihropenres.13960.1) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. track receive updates on this article Track an article to receive email alerts on any updates to this article. Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 28 Apr 2025 Views 0 How to cite this report: Sanders J. Reviewer Report For: Incidence, outcomes and management of spontaneous haemoperitoneum in pregnancy: a UK population-based study [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2025, 5:40 (https://doi.org/10.3310/nihropenres.15176.r35752) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/5-40/v1#referee-response-35752 https://openresearch.nihr.ac.uk/articles/5-40/v1#referee-response-35752 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 03 Jun 2025 Approved VIEWS 0 The paper presents results of a study to explore the incidence and outcomes of Spontaneous Hemoperitoneum in Pregnancy (SHiP) using the established UK Obstetric Surveillance System. A total of 20 cases meeting eligibility definitions were reported across ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close A total of 20 cases meeting eligibility definitions were reported across ... Continue reading The paper presents results of a study to explore the incidence and outcomes of Spontaneous Hemoperitoneum in Pregnancy (SHiP) using the established UK Obstetric Surveillance System. A total of 20 cases meeting eligibility definitions were reported across UK obstetric units in the years 2016 and 2017, giving an incidence of 1 per 75,614 maternities. The characteristics of women and the outcomes for women and their babies are reported. One maternal death was attributable to SHiP in 2016 and 2017, compared to six maternal deaths attributable to SHiP in the MBRRACE-UK surveillance programme during the three years from 2019 to 2021. It cannot be determined if the differences across these time periods was due to underreporting in the UKOSS study or reflected normal variation of a rare event. Median blood loss was 3500ml with sources of bleeding including arterial aneurysm (n=4), organ rupture (n=5) and endometriosis (n=1). Despite the severity of SHIP no particular risk factors were sufficiently evident to inform clinical practice. In the event of severe abdominal pain in pregnancy, in the absence of a confirmed alternative diagnosis, clinicians need to remain aware of the potential for this alternative but rare cause of abdominal bleeding, and all obstetric units need facilities and access to trained staff to deal with surgically complex massive haemorrhage during pregnancy. A total of 20 cases meeting eligibility definitions were reported across UK obstetric units in the years 2016 and 2017, giving an incidence of 1 per 75,614 maternities. The characteristics of women and the outcomes for women and their babies are reported. One maternal death was attributable to SHiP in 2016 and 2017, compared to six maternal deaths attributable to SHiP in the MBRRACE-UK surveillance programme during the three years from 2019 to 2021. It cannot be determined if the differences across these time periods was due to underreporting in the UKOSS study or reflected normal variation of a rare event. Median blood loss was 3500ml with sources of bleeding including arterial aneurysm (n=4), organ rupture (n=5) and endometriosis (n=1). Despite the severity of SHIP no particular risk factors were sufficiently evident to inform clinical practice. In the event of severe abdominal pain in pregnancy, in the absence of a confirmed alternative diagnosis, clinicians need to remain aware of the potential for this alternative but rare cause of abdominal bleeding, and all obstetric units need facilities and access to trained staff to deal with surgically complex massive haemorrhage during pregnancy. - Is the work clearly and accurately presented and does it cite the current literature? Yes - Is the study design appropriate and is the work technically sound? Yes - Are sufficient details of methods and analysis provided to allow replication by others? Yes - If applicable, is the statistical analysis and its interpretation appropriate? Yes - Are all the source data underlying the results available to ensure full reproducibility? Yes - Are the conclusions drawn adequately supported by the results? Yes

1. Tunn R, Ramakrishnan R, Engjom H, Knight M: Incidence, outcomes and management of spontaneous haemoperitoneum in pregnancy: a UK population-based study. NIHR Open Research. 2025; 5. Publisher Full TextCompeting Interests: No competing interests were disclosed. Reviewer Expertise: Midwifery and Maternity CITE HOW TO CITE THIS REPORT Sanders J. Reviewer Report For: Incidence, outcomes and management of spontaneous haemoperitoneum in pregnancy: a UK population-based study [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2025, 5:40 (https://doi.org/10.3310/nihropenres.15176.r35752) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/5-40/v1#referee-response-35752 https://openresearch.nihr.ac.uk/articles/5-40/v1#referee-response-35752 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Views 0 How to cite this report: Mamah JE. Reviewer Report For: Incidence, outcomes and management of spontaneous haemoperitoneum in pregnancy: a UK population-based study [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2025, 5:40 (https://doi.org/10.3310/nihropenres.15176.r35564) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/5-40/v1#referee-response-35564 https://openresearch.nihr.ac.uk/articles/5-40/v1#referee-response-35564 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 26 May 2025 Approved with Reservations VIEWS 0 It was a well-written study. Why has it taken over 8 years since the end of data collection to index this work? Since the authors had such a long intervening time, why was data collection not extended? There is much ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close It was a well-written study. Why has it taken over 8 years since the end of data collection to index this work? Since the authors had such a long intervening time, why was data collection not extended? There is much literature on this subject from the UK between 2017 and now. Including this data would have added to the strength of this study. These recent studies show endometriosis to be a common risk factor among patients who have suffered SHiP. More women are being diagnosed with endometrosis in the last 5 years due to more campaigns and awareness, and so that's a huge data point missing in this study. - Is the work clearly and accurately presented and does it cite the current literature? Yes - Is the study design appropriate and is the work technically sound? Yes - Are sufficient details of methods and analysis provided to allow replication by others? Yes - If applicable, is the statistical analysis and its interpretation appropriate? Yes - Are all the source data underlying the results available to ensure full reproducibility? Yes - Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Benign gynaecology CITE HOW TO CITE THIS REPORT Mamah JE. Reviewer Report For: Incidence, outcomes and management of spontaneous haemoperitoneum in pregnancy: a UK population-based study [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2025, 5:40 (https://doi.org/10.3310/nihropenres.15176.r35564) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/5-40/v1#referee-response-35564 https://openresearch.nihr.ac.uk/articles/5-40/v1#referee-response-35564 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Version 2 VERSION 2 PUBLISHED 06 Jun 2025 Revised Version 1 VERSION 1 PUBLISHED 28 Apr 2025

is closed on this version, please comment on the latest version above. - Author Response 06 Jun 2025Ruth Tunn, National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Headington, OX3 7LF, UK06 Jun 2025Author ResponseReviewer comment: It was a well-written study. Why has it taken over 8 years since the end of data collection to index this work? Since the authors had such a long ... Continue reading Reviewer comment: It was a well-written study. Why has it taken over 8 years since the end of data collection to index this work? Since the authors had such a long intervening time, why was data collection not extended? There is much literature on this subject from the UK between 2017 and now. Including this data would have added to the strength of this study. These recent studies show endometriosis to be a common risk factor among patients who have suffered SHiP. More women are being diagnosed with endometriosis in the last 5 years due to more campaigns and awareness, and so that's a huge data point missing in this study. Authors' response: Thank you for your constructive comments. We regret the extended delay in dissemination of the findings. Publication was initially delayed because we were hoping that our UK data would form part of an international study; however, this did not come to fruition. We could not extend the data collection in the interim because the UKOSS platform collects data on a number of conditions at any given time; therefore, to minimise reporting burden and avoid impeding research into other conditions we limit studies to a duration expected to yield meaningful data. From early 2020, the majority of UKOSS’s resources were then redirected to focus on maternal and neonatal SARS-CoV-2, and it has taken some time to get suspended projects back on track. We are acutely aware that we have a responsibility to disseminate the data and seek to do so now, albeit belatedly. As you point out, more women are being diagnosed in recent years with endometriosis because of awareness campaigns. However, this welcome improved awareness does not affect the underlying prevalence of this potential risk factor, just its detection. The serious and life-threatening presentation of SHiP means that lack of a prior diagnosis of endometriosis is unlikely to affect SHiP case ascertainment. Indeed, the one woman in our study who had endometriosis as the source of her bleeding did not have a prior diagnosis of endometriosis. Our data collection form asked whether there were signs of active endometriosis at surgery; only one other woman, who did have a prior diagnosis of endometriosis, had such activity detected. We therefore do not think that a higher current rate of endometriosis diagnosis compared with the diagnosis rate during our data collection period impedes the relevance of our conclusions about SHiP incidence, or the lack of a detectable link between endometriosis and SHiP. However, our study design and sample size do not allow us to rule out endometriosis as a risk factor; we suggest only that it is not a prerequisite and may appear less frequently in women who experience SHiP than other studies have suggested. It is also worth considering that cases of bleeding arising from endometriosis might be less severe than cases arising from aneurism or organ rupture and therefore might not meet our threshold for diagnosing SHiP if they could be managed expectantly. The differences in diagnostic criteria that we discuss could explain differences between our study and others in terms of the apparent prevalence of endometriosis in women with SHiP. We have revised the statement in the discussion that “Only one woman was diagnosed with endometriosis” to clarify that this refers to one woman having endometriosis as the source of her bleeding.Reviewer comment: It was a well-written study. Why has it taken over 8 years since the end of data collection to index this work? Since the authors had such a long intervening time, why was data collection not extended? There is much literature on this subject from the UK between 2017 and now. Including this data would have added to the strength of this study. These recent studies show endometriosis to be a common risk factor among patients who have suffered SHiP. More women are being diagnosed with endometriosis in the last 5 years due to more campaigns and awareness, and so that's a huge data point missing in this study.Competing Interests: See declarations in article Close Authors' response: Thank you for your constructive comments. We regret the extended delay in dissemination of the findings. Publication was initially delayed because we were hoping that our UK data would form part of an international study; however, this did not come to fruition. We could not extend the data collection in the interim because the UKOSS platform collects data on a number of conditions at any given time; therefore, to minimise reporting burden and avoid impeding research into other conditions we limit studies to a duration expected to yield meaningful data. From early 2020, the majority of UKOSS’s resources were then redirected to focus on maternal and neonatal SARS-CoV-2, and it has taken some time to get suspended projects back on track. We are acutely aware that we have a responsibility to disseminate the data and seek to do so now, albeit belatedly. As you point out, more women are being diagnosed in recent years with endometriosis because of awareness campaigns. However, this welcome improved awareness does not affect the underlying prevalence of this potential risk factor, just its detection. The serious and life-threatening presentation of SHiP means that lack of a prior diagnosis of endometriosis is unlikely to affect SHiP case ascertainment. Indeed, the one woman in our study who had endometriosis as the source of her bleeding did not have a prior diagnosis of endometriosis. Our data collection form asked whether there were signs of active endometriosis at surgery; only one other woman, who did have a prior diagnosis of endometriosis, had such activity detected. We therefore do not think that a higher current rate of endometriosis diagnosis compared with the diagnosis rate during our data collection period impedes the relevance of our conclusions about SHiP incidence, or the lack of a detectable link between endometriosis and SHiP. However, our study design and sample size do not allow us to rule out endometriosis as a risk factor; we suggest only that it is not a prerequisite and may appear less frequently in women who experience SHiP than other studies have suggested. It is also worth considering that cases of bleeding arising from endometriosis might be less severe than cases arising from aneurism or organ rupture and therefore might not meet our threshold for diagnosing SHiP if they could be managed expectantly. The differences in diagnostic criteria that we discuss could explain differences between our study and others in terms of the apparent prevalence of endometriosis in women with SHiP. We have revised the statement in the discussion that “Only one woman was diagnosed with endometriosis” to clarify that this refers to one woman having endometriosis as the source of her bleeding. - Discussion is closed on this version, please comment on the latest version above. Alongside their report, reviewers assign a status to the article: - Approved - Approved with reservations - Not approved | Invited Reviewers | || |---|---|---| | 1 | 2 | | | Version 2 (revision) 06 Jun 25 | read | | | Version 1 28 Apr 25 | read | read | Sign up for content alerts You are now signed up to receive this alert Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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