A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.

BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).

Clinical practice guidelines for the antenatal management of dichorionic diamniotic twin pregnancies: a systematic review.

OBJECTIVE: This review aimed to identify guidelines with recommendations applicable to the antenatal management of dichorionic diamniotic twin pregnancies within high-income countries, appraise their methodological quality, and discuss the similarities and variability across guidelines. METHOD: A systematic literature review of electronic databases was performed. Manual searches of guideline repositories and websites of professional organisations were performed to identify additional guidelines. The protocol for this systematic review was registered on PROSPERO (CRD42021248586, 25 June 2021). AGREE II and AGREE-REX tools were applied to assess the quality of eligible guidelines. A narrative and thematic synthesis described and compared the guidelines and their recommendations. RESULTS: Twenty-four guidelines were included, from which 483 recommendations were identified across 4 international organisations and 12 countries. Guidelines addressed eight themes and recommendations were classified accordingly: chorionicity and dating (103 recommendations), fetal growth (105 recommendations), termination of pregnancy (12 recommendations), fetal death (13 recommendations), fetal anomalies (65 recommendations), antenatal care (65 recommendations), preterm labour (56 recommendations) and birth (54 recommendations). Guidelines showed significant variability in recommendations, with conflicting recommendations regarding non-invasive preterm testing, definitions surrounding selective fetal growth restriction, screening for preterm labour and the timing of birth. Guidelines lacked a focus on standard antenatal management of DCDA twins, management of discordant fetal anomaly and single fetal demise. CONCLUSIONS: Specific guidance for dichorionic diamniotic twins is overall indistinct and access to guidance regarding the antenatal management of these pregnancies is currently difficult. Management of discordant fetal anomaly or single fetal demise needs greater consideration.

Twin Gestation With Spontaneous Reduction To Singleton.

Twin gestations are at increased risk of single intrauterine fetal death. A first-trimester loss is a common complication in twin gestations. The rate of co-twin morbidity and mortality is higher when a single demise occurs in the second and third trimesters. Monochorionicity strongly influences the prognosis for the surviving co-twin. Fetal ultrasound combined with MRI may be able to help predict neurological injury to the surviving co-twin. The rate of co-twin demise decreases with advancing gestation. After single intrauterine fetal demise, monochorionic gestations should be delivered by 34 weeks and dichorionic by 36 to 37 weeks gestation.

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

Universal gestational diabetes screening and antepartum stillbirth rates in Austria-A population-based study.

INTRODUCTION: Occult or untreated gestational diabetes (GDM) is a well-known risk factor for adverse perinatal outcomes and may contribute to antepartum stillbirth. We assessed the impact of screening for GDM on the rate of antepartum stillbirths in non-anomalous pregnancies by conducting a population-based study in 974 889 women in Austria. MATERIAL AND METHODS: Our database was derived from the Austrian Birth Registry. Inclusion criteria were singleton live births and antepartum stillbirths ≥24+0 gestational weeks, excluding fetal congenital malformations, terminations of pregnancy and women with pre-existing type 1 or 2 diabetes. Main outcome measures were (a) overall stillbirth rates and (b) stillbirth rates in women at high risk of GDM (i.e., women with a body mass index ≥30 kg/m2 , history of previous intrauterine fetal death, GDM, previous macrosomic offspring) before (2008-2010, "phase I") and after (2011-2019, "phase II") the national implementation of universal GDM screening with a 75 g oral glucose tolerance test in Austrian pregnant women by 2011. RESULTS: In total, 940 373 pregnancies were included between 2008 and 2019, of which 2579 resulted in intrauterine fetal deaths at 33.51 ± 5.10 gestational weeks. After implementation of the GDM screening, a statistically significant reduction in antepartum stillbirth rates among non-anomalous singletons was observed only in women at high risk for GDM (4.10‰ [95% confidence interval (CI) 3.09-5.43] in phase I vs. 2.96‰ [95% CI 2.57-3.41] in phase II; p = 0.043) but not in the general population (2.76‰ [95% CI 2.55-2.99] in phase I vs. 2.74‰ [95% CI 2.62-2.86] in phase II; p = 0.845). The number needed to screen with the oral glucose tolerance test to subsequently prevent one case of (non-anomalous) intrauterine fetal death was 880 in the high-risk and 40 000 in the general population. CONCLUSIONS: The implementation of a universal GDM screening program in Austria in 2011 has not led to any significant reduction in antenatal stillbirths among non-anomalous singletons in the general population. More international data are needed to strengthen our findings.

Risk of recurrent stillbirth: a cohort study.

OBJECTIVES: To evaluate the recurrence risk of stillbirth. DESIGN: Retrospective cohort study. SETTING AND POPULATION: All births 1992-2017, Alberta, Canada. METHODS: Retrospective cohort study. MAIN OUTCOME MEASURES: Stillbirth was defined as the death in utero of a fetus with gestational age ≥20 weeks or weighing ≥500 g. Stillbirths were further subdivided into those occurring before labour and those in labour. RESULTS: We identified 744 897 births from 308 478 women. Of these, 3698 women experienced a stillbirth and, of these, 97.7%, experienced only one. For women with a small-for-gestational- age stillbirth in the first birth, their risk of a subsequent antepartum stillbirth was increased substantially: 4.09%, relative risk (RR) 10.39, 95% CI 5.81-18.59. For women with a first birth appropriate-for-gestational-age stillbirth with no risk factors such as pregnancy induced hypertension, the risk with pre-existing diabetes mellitus or hypertension was also increased but to a much lesser degree (RR 2.46, 95% CI 1.23-4.91). For women who had experienced a first birth intrapartum stillbirth, the risk of another intrapartum stillbirth was very high (3.59%, RR 36.50, 95% CI 20.17-66.05). Most of these births also occurred prior to 24 weeks' gestation: 83% (10/12). CONCLUSIONS: The risk of recurrent antepartum stillbirth is low. The increase in risk in instances where the antepartum stillbirth was not growth-restricted is not clinically meaningful. Given the very low risk in any given gestational week, fetal surveillance is unlikely to be effective and may lead to unnecessary interventions. Intrapartum stillbirth has a very high recurrence risk but may not be preventable. TWEETABLE ABSTRACT: Stillbirth recurrence is rare.

Preventable stillbirths in India and Pakistan: a prospective, observational study.

OBJECTIVE: Stillbirths occur 10-20 times more frequently in low-income settings compared with high-income settings. We created a methodology to define the proportion of stillbirths that are potentially preventable in low-income settings and applied it to stillbirths in sites in India and Pakistan. DESIGN: Prospective observational study. SETTING: Three maternity hospitals in Davangere, India and a large public hospital in Karachi, Pakistan. POPULATION: All cases of stillbirth at ≥20 weeks of gestation occurring from July 2018 to February 2020 were screened for participation; 872 stillbirths were included in this analysis. METHODS: We prospectively defined the conditions and gestational ages that defined the stillbirth cases considered potentially preventable. Informed consent was sought from the parent(s) once the stillbirth was identified, either before or soon after delivery. All information available, including obstetric and medical history, clinical course, fetal heart sounds on admission, the presence of maceration as well as examination of the stillbirth after delivery, histology, and polymerase chain reaction for infectious pathogens of the placenta and various fetal tissues, was used to assess whether a stillbirth was potentially preventable. MAIN OUTCOME MEASURES: Whether a stillbirth was determined to be potentially preventable and the criteria for assignment to those categories. RESULTS: Of 984 enrolled, 872 stillbirths at ≥20 weeks of gestation met the inclusion criteria and were included; of these, 55.5% were deemed to be potentially preventable. Of the 649 stillbirths at ≥28 weeks of gestation and ≥1000 g birthweight, 73.5% were considered potentially preventable. The most common conditions associated with a potentially preventable stillbirth at ≥28 weeks of gestation and ≥1000 g birthweight were small for gestational age (SGA) (52.8%), maternal hypertension (50.2%), antepartum haemorrhage (31.4%) and death that occurred after hospital admission (15.7%). CONCLUSIONS: Most stillbirths in these sites were deemed preventable and were often associated with maternal hypertension, antepartum haemorrhage, SGA and intrapartum demise. TWEETABLE ABSTRACT: Most stillbirths are preventable by better care for women with hypertension, growth restriction and antepartum haemorrhage.

Implementing a modified World Health Organization safe childbirth checklist in health centers of Ethiopia: a pre and post intervention study.

BACKGROUND: Childbirth is a complex process, and checklists are useful tools to remember steps of such complex processes. The World Health Organization safe childbirth checklist is a tool used to improve the quality of care provided to women giving birth. The checklist was modified by Ministry of Health and was introduced to health centers in Ethiopia by the USAID Transform: Primary Health Care Activity. METHODS: A pre and post intervention study design with prospective data collection was employed. The availability of essential childbirth supplies and adherence of health care providers to essential birth practices were compared for the pre and post intervention periods. RESULTS: The pre and post intervention assessments were conducted in 247 and 187 health centers respectively. A statistically significant improvement from 63.6% pre intervention to 83.5% post intervention was observed in the availability of essential childbirth supplies, t (389.7) = - 7.1, p = 0.000. Improvements in adherence of health care providers to essential birth practices were observed with the highest being at pause point three (26.2%, t (306.3) = - 10.6, p = 0.000) followed by pause point four (21.1%, t (282.5) = - 8.0, p = 0.000), and pause point two (18.2%, t (310.8) = - 9.7, p = 0.000). The least and statistically non-significant improvement was observed at pause point one (3.3%, t (432.0) = - 1.5, p = 0.131). CONCLUSION: Improvement in availability of essential childbirth supplies and adherence of health care providers towards essential birth practices was observed after introduction of a modified World Health Organization safe childbirth checklist. Scale up of the use of the checklist is recommended.

Prompt evaluation and treatment of third-trimester bleeding.

ABSTRACT: Third-trimester bleeding is an obstetric emergency and is associated with significant maternal and fetal morbidity and mortality. The two most common causes for third-trimester bleeding are placental abruption and placenta previa, which account for about half of all cases. Clinicians should have a thorough understanding of the risk factors, clinical presentation, and appropriate management of these conditions. Timely management is necessary for the survival of mother and fetus and to reduce the incidence of neonatal complications.

Prevention of stillbirth: impact of two-stage screening for vasa previa.

OBJECTIVES: To examine the feasibility and effectiveness of a two-stage ultrasound screening strategy for detection of vasa previa and to estimate the potential impact of screening on prevention of stillbirth. METHODS: This was a retrospective study of data from prospective screening for vasa previa in singleton pregnancies, undertaken at the Fetal Medicine Unit at Medway Maritime Hospital, UK, between 2012 and 2018. Women booked for prenatal care and delivery in our hospital had routine ultrasound examinations at 11-13 and 20-22 weeks' gestation. Those with velamentous cord insertion at the inferior part of the placenta at the first-trimester scan and those with low-lying placenta at the second-trimester scan were classified as high-risk for vasa previa and had transvaginal sonography searching specifically for vasa previa, at the time of the 20-22-week scan. The management and outcome of cases with suspected vasa previa is described. We excluded cases of miscarriage or termination at < 24 weeks' gestation. RESULTS: The study population of 26 830 singleton pregnancies included 21 (0.08%; 1 in 1278) with vasa previa. In all cases of vasa previa, the diagnosis was made at the 20-22-week scan and confirmed postnatally by gross and histological examination of the placenta. At the 11-13-week scan, cord insertion was classified as central in 25 071 (93.4%) cases, marginal in 1680 (6.3%), and velamentous in 79 (0.3%). In 16 (76.2%) of the 21 cases of vasa previa, cord insertion at the first-trimester scan was classified as velamentous at the inferior part of the placenta, in two cases (9.5%) as marginal and in three cases (14.3%) as central. The 21 cases of vasa previa were managed on an outpatient basis with serial scans for measurement of cervical length and elective Cesarean section at 34 weeks' gestation; all babies were liveborn but there was one neonatal death. In the study population, there were 83 stillbirths, none of which had evidence of vasa previa on postnatal examination. On the assumption that, if we had not diagnosed prenatally all 21 cases of vasa previa in our population, half of these cases would have resulted in stillbirth, then the potential impact of screening is prevention of 10.6% (10/94) of stillbirths. CONCLUSION: A two-stage strategy of screening for vasa previa can be incorporated into routine clinical practice, and such a strategy could potentially reduce the rate of stillbirth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Antenatal interventions for preventing stillbirth, fetal loss and perinatal death: an overview of Cochrane systematic reviews.

BACKGROUND: Stillbirth is generally defined as a death prior to birth at or after 22 weeks' gestation. It remains a major public health concern globally. Antenatal interventions may reduce stillbirths and improve maternal and neonatal outcomes in settings with high rates of stillbirth. There are several key antenatal strategies that aim to prevent stillbirth including nutrition, and prevention and management of infections. OBJECTIVES: To summarise the evidence from Cochrane systematic reviews on the effects of antenatal interventions for preventing stillbirth for low risk or unselected populations of women. METHODS: We collaborated with Cochrane Pregnancy and Childbirth's Information Specialist to identify all their published reviews that specified or reported stillbirth; and we searched the Cochrane Database of Systematic Reviews (search date: 29 Feburary 2020) to identify reviews published within other Cochrane groups. The primary outcome measure was stillbirth but in the absence of stillbirth data, we used perinatal mortality (both stillbirth and death in the first week of life), fetal loss or fetal death as outcomes. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. We assigned interventions to categories with graphic icons to classify the effectiveness of interventions as: clear evidence of benefit or harm; clear evidence of no effect or equivalence; possible benefit or harm; or unknown benefit or harm or no effect or equivalence. MAIN RESULTS: We identified 43 Cochrane Reviews that included interventions in pregnant women with the potential for preventing stillbirth; all of the included reviews reported our primary outcome 'stillbirth' or in the absence of stillbirth, 'perinatal death' or 'fetal loss/fetal death'. AMSTAR quality was high in 40 reviews with scores ranging from 8 to 11 and moderate in three reviews with a score of 7. Nutrition interventions Clear evidence of benefit: balanced energy/protein supplementation versus no supplementation suggests a probable reduction in stillbirth (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.39 to 0.94, 5 randomised controlled trials (RCTs), 3408 women; moderate-certainty evidence). Clear evidence of no effect or equivalence for stillbirth or perinatal death: vitamin A alone versus placebo or no treatment; and multiple micronutrients with iron and folic acid versus iron with or without folic acid. Unknown benefit or harm or no effect or equivalence: for all other nutrition interventions examined the effects were uncertain. Prevention and management of infections Possible benefit for fetal loss or death: insecticide-treated anti-malarial nets versus no nets (RR 0.67, 95% CI 0.47 to 0.97, 4 RCTs; low-certainty). Unknown evidence of no effect or equivalence: drugs for preventing malaria (stillbirth RR 1.02, 95% CI 0.76 to 1.36, 5 RCTs, 7130 women, moderate certainty in women of all parity; perinatal death RR 1.24, 95% CI 0.94 to 1.63, 4 RCTs, 5216 women, moderate-certainty in women of all parity). Prevention, detection and management of other morbidities Clear evidence of benefit: the following interventions suggest a reduction: midwife-led models of care in settings where the midwife is the primary healthcare provider particularly for low-risk pregnant women (overall fetal loss/neonatal death reduction RR 0.84, 95% CI 0.71 to 0.99, 13 RCTs, 17,561 women; high-certainty), training versus not training traditional birth attendants in rural populations of low- and middle-income countries (stillbirth reduction odds ratio (OR) 0.69, 95% CI 0.57 to 0.83, 1 RCT, 18,699 women, moderate-certainty; perinatal death reduction OR 0.70, 95% CI 0.59 to 0.83, 1 RCT, 18,699 women, moderate-certainty). Clear evidence of harm: a reduced number of antenatal care visits probably results in an increase in perinatal death (RR 1.14 95% CI 1.00 to 1.31, 5 RCTs, 56,431 women; moderate-certainty evidence). Clear evidence of no effect or equivalence: there was evidence of no effect in the risk of stillbirth/fetal loss or perinatal death for the following interventions and comparisons: psychosocial interventions; and providing case notes to women. Possible benefit: community-based intervention packages (including community support groups/women's groups, community mobilisation and home visitation, or training traditional birth attendants who made home visits) may result in a reduction of stillbirth (RR 0.81, 95% CI 0.73 to 0.91, 15 RCTs, 201,181 women; low-certainty) and perinatal death (RR 0.78, 95% CI 0.70 to 0.86, 17 RCTs, 282,327 women; low-certainty). Unknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined. Screening and management of fetal growth and well-being Clear evidence of benefit: computerised antenatal cardiotocography for assessing infant's well-being in utero compared with traditional antenatal cardiotocography (perinatal mortality reduction RR 0.20, 95% CI 0.04 to 0.88, 2 RCTs, 469 women; moderate-certainty). Unknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined. AUTHORS' CONCLUSIONS: While most interventions were unable to demonstrate a clear effect in reducing stillbirth or perinatal death, several interventions suggested a clear benefit, such as balanced energy/protein supplements, midwife-led models of care, training versus not training traditional birth attendants, and antenatal cardiotocography. Possible benefits were also observed for insecticide-treated anti-malarial nets and community-based intervention packages, whereas a reduced number of antenatal care visits were shown to be harmful. However, there was variation in the effectiveness of interventions across different settings, indicating the need to carefully understand the context in which these interventions were tested. Further high-quality RCTs are needed to evaluate the effects of antenatal preventive interventions and which approaches are most effective to reduce the risk of stillbirth. Stillbirth (or fetal death), perinatal and neonatal death need to be reported separately in future RCTs of antenatal interventions to allow assessment of different interventions on these rare but important outcomes and they need to clearly define the target populations of women where the intervention is most likely to be of benefit. As the high burden of stillbirths occurs in low- and middle-income countries, further high-quality trials need to be conducted in these settings as a priority.

Implementation and evaluation of a quality improvement initiative to reduce late gestation stillbirths in Australia: Safer Baby Bundle study protocol.

BACKGROUND: In 2015, the stillbirth rate after 28 weeks (late gestation) in Australia was 35% higher than countries with the lowest rates globally. Reductions in late gestation stillbirth rates have steadily improved in Australia. However, to amplify and sustain reductions, more needs to be done to reduce practice variation and address sub-optimal care. Implementing bundles for maternity care improvement in the UK have been associated with a 20% reduction in stillbirth rates. A similar approach is underway in Australia; the Safer Baby Bundle (SBB) with five elements: 1) supporting women to stop smoking in pregnancy, 2) improving detection and management of fetal growth restriction, 3) raising awareness and improving care for women with decreased fetal movements, 4) improving awareness of maternal safe going-to-sleep position in late pregnancy, 5) improving decision making about the timing of birth for women with risk factors for stillbirth. METHODS: This is a mixed-methods study of maternity services across three Australian states; Queensland, Victoria and New South Wales. The study includes evaluation of 'targeted' implementer sites (combined total approximately 113,000 births annually, 50% of births in these states) and monitoring of key outcomes state-wide across all maternity services. Progressive implementation over 2.5 years, managed by state Departments of Health, commenced from mid-2019. This study will determine the impact of implementing the SBB on maternity services and perinatal outcomes, specifically for reducing late gestation stillbirth. Comprehensive process, impact, and outcome evaluations will be conducted using routinely collected perinatal data, pre- and post- implementation surveys, clinical audits, focus group discussions and interviews. Evaluations explore the views and experiences of clinicians embedding the SBB into routine practice as well as women's experience with care and the acceptability of the initiative. DISCUSSION: This protocol describes the evaluation of the SBB initiative and will provide evidence for the value of a systematic, but pragmatic, approach to strategies to reduce the evidence-practice gaps across maternity services. We hypothesise successful implementation and uptake across three Australian states (amplified nationally) will be effective in reducing late gestation stillbirths to that of the best performing countries globally, equating to at least 150 lives saved annually. TRIAL REGISTRATION: The Safer Baby Bundle Study was retrospectively registered on the ACTRN12619001777189 database, date assigned 16/12/2019.

Could a multidisciplinary regional audit identify avoidable factors and delays that contribute to stillbirths? A retrospective cohort study.

BACKGROUND: The annual rate of stillbirth in Sweden has remained largely unchanged for the past 30 years. In Sweden, there is no national audit system for stillbirths. The aim of the study was to determine if a regional multidisciplinary audit could help in identifying avoidable factors and delays associated with stillbirths. METHODS: Population-based retrospective cohort study. SETTINGS: Six labour wards in Stockholm County. PARTICIPANTS: Women delivering a stillbirth > 22 weeks of gestation in Stockholm during 2017. INTERVENTION: A multidisciplinary team was convened. Each team member independently assessed the medical chart of each case of stillbirth regarding causes and preventability, level of delay, the standard of healthcare provided, the investigation of maternal/foetal diseases and if any recommendations were given for the next pregnancy. A decision was based on the agreement of all five members. If no agreement was reached, a reassessment of the case was done and the medical record was scrutinized again until a mutual decision was made. Primary outcomes: The frequency of probably/possibly preventable factors associated with a stillbirth and the level of delay (patient/caregiver). SECONDARY OUTCOMES: The causes of death, the standard of antenatal/intrapartum/postpartum care, whether a summary of possible causes of the stillbirth was made and if any plans for future pregnancies were noted. RESULTS: Thirty percent of the stillbirths were assessed as probably/possibly preventable. More frequent ultrasound/clinical check-ups, earlier induction of labour and earlier interventions in line with current guidelines were identified as possibly preventable factors. A possibly preventable stillbirth was more common among non-Swedish-speaking women (p = 0.03). In 15% of the cases, a delay by the healthcare system was identified. Having multiple caregivers, absence of continuity in terms of attending the antenatal clinic and not following the basic monitoring program for antenatal care were also identified as risk factors for a delay. CONCLUSION: A national/regional multidisciplinary audit group retrospectively identified factors associated with stillbirth. Access to good translation services or a more innovative approach to the problem regarding communication with mothers could be an important factor to decrease possible patient delays contributing to stillbirths. TRIAL REGISTRATION: NCT04281368 .

Postmortem examination protocol and systematic re-evaluation reduce the proportion of unexplained stillbirths.

Background Stillbirth often remains unexplained, mostly due to a lack of any postmortem examination or one that is incomplete and misinterpreted. Methods This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, Helsinki University Hospital, Finland, and comprised 214 antepartum singleton stillbirths from 2003 to 2015. Maternal and fetal characteristics and the results of the systematic postmortem examination protocol were collected from medical records. Causes of death were divided into 10 specific categories. Re-evaluation of the postmortem examination results followed. Results Based on our systematic protocol, the cause of death was originally defined and reported as such to parents in 133 (62.1%) cases. Re-evaluation of the postmortem examination results revealed the cause of death in an additional 43 (20.1%) cases, with only 23 (10.7%) cases remaining truly unexplained. The most common cause of stillbirth was placental insufficiency in 56 (26.2%) cases. A higher proportion of stillbirths that occurred at ≥39 gestational weeks remained unexplained compared to those that occurred earlier (24.1% vs. 8.6%) (P = 0.02). Conclusion A standardized postmortem examination and a re-evaluation of the results reduced the rate of unexplained stillbirth. Better knowledge of causes of death may have a major impact on the follow-up and outcome of subsequent pregnancies. Also, closer examination and better interpretation of postmortem findings is time-consuming but well worth the effort in order to provide better counseling for the grieving parents.

Furcate insertion of the umbilical cord: pathological and clinical characteristics in 132 cases.

Objectives Furcate cord insertion is a rare abnormality affecting approximately 0.1% of all pregnancies. Macroscopically, the umbilical vessels separate before reaching the placenta, lose their Wharton's jelly, and insert at the placenta centrally, eccentrically, or marginally. The aim of this retrospective study was to determine the prevalence of furcate cord insertion more accurately, the pathological characteristics, and clinical outcomes. Methods We conducted a retrospective study of 132 cases of furcate insertion of the umbilical cord using the pathological database of the Charité University Hospital Berlin, Germany, between 1993 and 2016. This included 99 cases, including one termination of pregnancy within our institution and 33 cases from external hospitals. An analysis of the pathological features of the 132 cases and the perinatal outcome of the 98 cases within our institution were performed. Results Furcate cord insertion occurred in 0.16% pregnancies. Of the 132 cases, seven cases of intrauterine fetal deaths were observed. Three of those could be linked to the furcate cord insertion. In two of those cases, single umbilical vessel rupture was identified as the cause of fetal death. Conclusions In most cases of furcate cord insertion, the outcome is good; however, intrauterine fetal death occurs in approximately 1.02% of cases.

Can We Prevent Stillbirth?

OBJECTIVE: This study aimed to identify the frequency of potentially preventable causes of stillbirth in a large heterogeneous population. STUDY DESIGN: This is a retrospective study of all stillbirth cases between January 2011 and December 2016 at a single tertiary medical center. Deliveries resulting from a nonviable fetus prior to 24 weeks of gestation, intrapartum fetal death, and incomplete stillbirth workup were excluded. Potentially preventable stillbirth was defined as that of a nonanomalous fetus that most likely resulted from one or more of the following: (1) placental-mediated complications, (2) postterm pregnancy, (3) monochorionicity-associated complications, (4) cholestasis of pregnancy, (5) preventable or treatable infections, and (6) isoimmunization. RESULTS: During the study period, 312 stillbirths were identified, 228 of which met the inclusion criteria. Of the 110 cases with a recognized cause, 47 (20.6%) were potentially preventable. The most common causes were placental-mediated complications and preventable or treatable infections, accounting for 75 and 9% of all potentially preventable causes, respectively. There were no recognizable maternal risk factors for potentially preventable stillbirth. CONCLUSION: One-fifth of all causes of stillbirth are potentially preventable. Due to the significant contribution of placental-mediated complications to preventable stillbirth, close sonographic surveillance and timely delivery may decrease risk substantially.

A Decade of Experience with the Ovine Model of Myelomeningocele: Risk Factors for Fetal Loss.

INTRODUCTION: The ovine model is the gold standard large animal model of myelomeningocele (MMC); however, it has a high rate of fetal loss. We reviewed our experience with the model to determine risk factors for fetal loss. METHODS: We performed a retrospective review from 2009 to 2018 to identify operative factors associated with fetal loss (early fetal demise, abortion, or stillbirth). Operative risk factors included gestational age at operation, operative time, reduction of multiple gestations, amount of replaced amniotic fluid, ambient temperature, and method of delivery. RESULTS: MMC defects were created in 232 lambs with an overall survival rate of 43%. Of the 128 fetuses that died, 53 (42%) had demise prior to repair, 61 (48%) aborted, and 14 (11%) were stillborn. Selective reduction of multiple gestations in the same uterine horn was associated with increased fetal demise (OR 3.03 [95% CI 1.29-7.05], p = 0.01). Later gestational age at MMC repair and Cesarean delivery were associated with decreased abortion/stillbirth (OR 0.90 [95% CI 0.83-0.90], p = 0.03, and OR 0.37 [95% CI 0.16-0.31], p = 0.02), respectively. CONCLUSION: Avoiding selective reduction, repairing MMC later in gestation, and performing Cesarean delivery decreases the rate of fetal loss in the ovine MMC model.

Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM): a stepped wedge, cluster-randomised trial.

BACKGROUND: 2·6 million pregnancies were estimated to have ended in stillbirth in 2015. The aim of the AFFIRM study was to test the hypothesis that introduction of a reduced fetal movement (RFM), care package for pregnant women and clinicians that increased women's awareness of the need for prompt reporting of RFM and that standardised management, including timely delivery, would alter the incidence of stillbirth. METHODS: This stepped wedge, cluster-randomised trial was done in the UK and Ireland. Participating maternity hospitals were grouped and randomised, using a computer-generated allocation scheme, to one of nine intervention implementation dates (at 3 month intervals). This date was concealed from clusters and the trial team until 3 months before the implementation date. Each participating hospital had three observation periods: a control period from Jan 1, 2014, until randomised date of intervention initiation; a washout period from the implementation date and for 2 months; and the intervention period from the end of the washout period until Dec 31, 2016. Treatment allocation was not concealed from participating women and caregivers. Data were derived from observational maternity data. The primary outcome was incidence of stillbirth. The primary analysis was done according to the intention-to-treat principle, with births analysed according to whether they took place during the control or intervention periods, irrespective of whether the intervention had been implemented as planned. This study is registered with www.ClinicalTrials.gov, number NCT01777022. FINDINGS: 37 hospitals were enrolled in the study. Four hospitals declined participation, and 33 hospitals were randomly assigned to an intervention implementation date. Between Jan 1, 2014, and Dec, 31, 2016, data were collected from 409 175 pregnancies (157 692 deliveries during the control period, 23 623 deliveries in the washout period, and 227 860 deliveries in the intervention period). The incidence of stillbirth was 4·40 per 1000 births during the control period and 4·06 per 1000 births in the intervention period (adjusted odds ratio [aOR] 0·90, 95% CI 0·75-1·07; p=0·23). INTERPRETATION: The RFM care package did not reduce the risk of stillbirths. The benefits of a policy that promotes awareness of RFM remains unproven. FUNDING: Chief Scientist Office, Scottish Government (CZH/4/882), Tommy's Centre for Maternal and Fetal Health, Sands.

Inpatient vs outpatient management and timing of delivery of uncomplicated monochorionic monoamniotic twin pregnancy: the MONOMONO study.

OBJECTIVES: Monoamniotic twin pregnancies are at increased risk of perinatal complications, primarily owing to the risk of cord entanglement. There is no recommendation on whether such pregnancies should be managed in hospital or can be safely managed in an outpatient setting, and the timing of planned delivery is also a subject of debate. The aim of this study was to compare the perinatal outcomes of inpatient vs outpatient fetal surveillance approaches employed among 22 participating study centers, and to calculate the fetal and neonatal death rates according to gestational age, in non-anomalous monoamniotic twins from 26 weeks' gestation. METHODS: The MONOMONO study was a multinational cohort study of consecutive women with monochorionic monoamniotic twin pregnancies, who were referred to 22 university hospitals in Italy, the USA, the UK and Spain, from January 2010 to January 2017. Only non-anomalous uncomplicated monoamniotic twin pregnancies with two live fetuses at 26 + 0 weeks' gestation were included in the study. In 10 of the centers, monoamniotic twins were managed routinely as inpatients, whereas in the other 12 centers they were managed routinely as outpatients. The primary outcome was intrauterine fetal death. We also planned to assess fetal and neonatal death rates according to gestational age per 1-week interval. Outcomes are presented as odds ratio (OR) with 95% CIs. The main outcome was analyzed using both standard logistic regression analysis, in which each fetus was treated as an independent unit, and a generalized mixed-model approach, with each twin pair treated as a cluster unit, considering that the outcome for a twin is not independent of that of its cotwin. RESULTS: 195 consecutive pregnant women with a non-anomalous uncomplicated monoamniotic twin gestation (390 fetuses) were included. Of these, 75 (38.5%) were managed as inpatients and 120 (61.5%) as outpatients. The overall perinatal loss rate was 10.8% (42/390) with a peak fetal death rate of 4.3% (15/348) occurring at 29 weeks' gestation. There was no significant difference in mean gestational age at delivery (31 weeks), birth weight (∼1.6 kg), or emergency delivery rate between the inpatient and outpatient surveillance groups. Based on generalized mixed-model analysis, there was no statistically significant difference in fetal death rates between inpatient management commencing from around 26 weeks compared with outpatient surveillance protocols from 30 weeks (3.3% vs 10.8%; adjusted OR 0.21 (95% CI, 0.04-1.17)). Maternal length of stay in the hospital was 42.1 days in the inpatient group, and 7.4 days in the outpatient group (mean difference 34.70 days (95% CI, 31.36-38.04 days). From 32 + 0 to 36 + 6 weeks, no fetal or neonatal death in either group was recorded. 46 fetuses were delivered after 34 + 0 weeks, and none of them died in utero or within the first 28 days postpartum. CONCLUSION: In uncomplicated monoamniotic twins, inpatient surveillance is associated with similar fetal mortality as outpatient management. After 31 + 6 weeks, and up to 36 + 6 weeks, there were no intrauterine fetal deaths or neonatal deaths. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Patient costs and outcomes before and after the institution of a pre-eclampsia quality improvement initiative in a southwestern tertiary facility.

The study objective was to evaluate the effect of the California Maternal Quality Care Collaborative (CMQCC) initiative, as implemented in a southwestern U.S. tertiary hospital, on associated patient costs and outcomes. Using a quasi-experimental study design, we collected existing data (cost and patient outcomes) comparing two six-month period at the baseline and one-year follow-up. Following descriptive statistics, Chi-square tests and t-tests were used to compare categorical and continuous variables, respectively. One hundred and eighty-nine women met the inclusion criteria for the study (93 and 96 women in the baseline and follow-up period, respectively). There was no significant difference in maternal health outcomes between both periods. However, there was a significant difference for newborns with almost 90% (95%CI = 0.06-0.92; p = .027) reduction in stillbirths in the follow-up period. There was also a significant reduction in the days between discharge and follow-up appointments (p < .01). Importantly, the initiative bears no additional financial burden on patients, as hospitalisation cost was unchanged. Impact statement What is already known on this subject? In 2013, the California Maternal Quality Care Collaborative (CMQCC) set up a task force to develop guidelines for managing patients with preeclampsia based on global best practices. A previous study showed that despite system-level implementation challenges, the initiative led to significant increase in blood pressure treatments within one-hour and reduced severe maternal morbidity. What do the results of this study add? This study follows patients from admission, beyond the one-hour post-treatment and into the post-partum phase, to understand if outcomes of the initiative extend beyond the admission. While the study findings do not show any statistically significant difference in readmission before and after the initiative, nor any marked difference in maternal outcomes, it shows a significant difference in the prevalence of stillbirths at no additional cost to the patient. What are the implications of these findings for clinical practice and/or further research? Based on these findings, there is a case for scaling-up the initiative as in addition to its evidenced improvements in maternal outcomes; it is effective in improving newborn health outcomes at no additional cost. Further research, using larger sample size and exploring different care levels would be useful to verify these findings.