Characterising delayed villous maturation: A narrative literature review.

The normal development of the placenta is vital for fetal growth and a healthy pregnancy outcome. Delayed villous maturation (DVM) is a placental lesion that has been implicated in stillbirth. In DVM, villi do not maturate adequately for their gestational age. DVM is characterised by larger and fewer terminal placental villi, low numbers of syncytial knots, and thicker and fewer vasculosyncytial membranes. DVM is most commonly reported in conjunction with maternal diabetes; however, the occurrence of idiopathic DVM suggests that there may be multiple mechanistic pathways that contribute to DVM. DVM can only be diagnosed through histopathological examination after birth, and there is significant interobserver variability in diagnosis. Establishing objective criteria to distinguish between DVM and healthy placentas is key to increasing the understanding of DVM. Vasculosyncytial membrane count, numbers of syncytial knots and CD15, among others, have been presented as potential diagnostic criteria in the literature. This review aims to compile information on DVM, including the pathophysiology, conditions that have reported associations with DVM and potential markers that could be used as criteria to differentiate between DVM and healthy placentas.

Impact of health literacy on pregnancy outcomes in socioeconomically disadvantaged and ethnic minority populations: A scoping review.

BACKGROUND: Health literacy, influenced by sociodemographic characteristics such as ethnicity, economic means and societal factors, affects the ways in which pregnant women maintain their health; this in turn may increase risk of adverse pregnancy outcomes. OBJECTIVE: To explore what is known about the impact of personal health literacy on prevention of stillbirth and related adverse outcomes in pregnant women of low socioeconomic status or from ethnic minority backgrounds. SEARCH STRATEGY: MEDLINE, CINAHL, PsychINFO, and CENTRAL were searched as well as reference lists of included studies and gray literature. SELECTION CRITERIA: Included studies focused on personal health literacy and stillbirth prevention in women from low socioeconomic or ethnic minority backgrounds in the perinatal period. DATA COLLECTION AND ANALYSIS: A meta-summary approach was adopted for qualitative, observational, descriptive, and audit studies. Findings of intervention studies were extracted, and meta-analyses were conducted where possible. The primary outcome was stillbirth; maternal mortality and neonatal mortality were secondary outcomes. MAIN RESULTS: Forty-one studies were included from diverse geographical settings. The meta-summary synthesized five abstracted statements. These recognized lower personal health literacy and greater difficulty interacting with healthcare services in the studied populations, primarily as the result of limited health knowledge, lack of positive perception towards health services, language barriers, illiteracy, and relying on friends or family members for health information. Meta-analysis of intervention studies revealed no association between current interventions that aimed to increase personal health literacy and the risk of stillbirth (relative risk [RR] 1.04, 95% confidence interval [CI] 0.96-1.12), neonatal mortality (RR 0.88, 95% CI 0.75-1.03), and maternal mortality (RR 0.87, 95% CI 0.63-1.22). CONCLUSIONS: Various factors suggest lower personal health literacy in women of low socioeconomic status or ethnic minority, which can increase the risk of stillbirth. However, this review identified no significant impact of current health education interventions on the risk of stillbirth, or neonatal or maternal mortality. Although not directly measured, the health education interventions were anticipated to increase personal health literacy. Further research on the topic of this scoping review is warranted, particularly in lower-resource settings and regarding the potential role of e-literacy and organizational health literacy to improve pregnancy outcomes. To address deficits in health literacy, efforts must be made to provide pregnant women with health information in novel, accessible ways.

Virtual crossmatching reveals upregulation of placental HLA-Class II in chronic histiocytic intervillositis.

Chronic histiocytic intervillositis (CHI) is a recurrent placental lesion where maternal macrophages infiltrate the intervillous space. Its cause is unknown, though due to similarities to rejected allografts one hypothesis is that CHI represents maternal-fetal rejection. Here, virtual crossmatching was applied to healthy pregnancies and those with a history of CHI. Anti-HLA antibodies, measured by Luminex, were present in slightly more controls than CHI (8/17 (47.1%) vs 5/14 (35.7%)), but there was no significant difference in levels of sensitisation or fetal specific antibodies. Quantification of immunohistochemical staining for HLA-Class II was increased in syncytiotrophoblast of placentas with CHI (Grade 0.44 [IQR 0.1-0.7]) compared to healthy controls (0.06 [IQR 0-0.2]) and subsequent pregnancies (0.13 [IQR 0-0.3]) (P = 0.0004). HLA-Class II expression was positively related both to the severity of CHI (r = 0.67) and C4d deposition (r = 0.48). There was no difference in overall C4d and HLA-Class I immunostaining. Though increased anti-HLA antibodies were not evident in CHI, increased expression of HLA-Class II at the maternal-fetal interface suggests that they may be relevant in its pathogenesis. Further investigation of antibodies immediately after diagnosis is warranted in a larger cohort of CHI cases to better understand the role of HLA in its pathophysiology.

Swedish massage as an adjunct approach to Help suppOrt individuals Pregnant after Experiencing a prior Stillbirth (HOPES): a convergent parallel mixed-methods single-arm feasibility trial protocol.

BACKGROUND: Women experiencing pregnancy after stillbirth experience high levels of anxiety, fear and depression. Standard antenatal care may be emotionally unsuitable for many women at this time, and there is a lack of evidence on what interventions or approaches to care might benefit these women. Therapeutic massage may assist women after stillbirth by decreasing anxiety, worry and stress. OBJECTIVE: This paper outlines the objectives, methodology, outcome and assessment measures for the Helping suppOrt individuals Pregnant after Experiencing a Stillbirth (HOPES) feasibility trial which evaluates massage as an adjunct approach to care for pregnant women who have experienced a prior stillbirth. It also outlines data collection timing and considerations for analysing the data. METHODS: HOPES will use a convergent parallel mixed-methods, single-arm repeated measures trial design in trained massage therapists' private clinics across Australia. HOPES aims to recruit 75 individuals pregnant after a previous stillbirth. The intervention is massage therapy treatments, and participants will receive up to five massages within a 4-month period at intervals of their choosing. Primary quantitative outcomes are the feasibility and acceptability of the massage intervention. Secondary outcomes include determining the optimal timing of massage therapy delivery and the collection of measures for anxiety, worry, stress and self-management. A thematic analysis of women's experiences undertaking the intervention will also be conducted. A narrative and joint display approach to integrate mixed-methods data is planned. DISCUSSION: The HOPES study will determine the feasibility and preliminary evidence for massage therapy as an intervention to support women who are pregnant after a stillbirth. CLINICALTRIALS: gov NCT05636553. Registered on December 3, 2022, and the trial is ongoing.

Measuring EQ-5D-5L utility values in parents who have experienced perinatal death.

BACKGROUND: Policymakers use clinical and cost-effectiveness evidence to support decisions about health service commissioning. In England, the National Institute for Health and Care Excellence (NICE) recommend that in cost-effectiveness analyses "effectiveness" is measured as quality-adjusted life years (QALYs), derived from health utility values. The impact of perinatal death (stillbirth/neonatal death) on parents' health utility is currently unknown. This knowledge would improve the robustness of cost-effectiveness evidence for policymakers. OBJECTIVE: This study aimed to estimate the impact of perinatal death on parents' health utility. METHODS: An online survey conducted with mothers and fathers in England who experienced a perinatal death. Participants reported how long ago their baby died and whether they/their partner subsequently became pregnant again. They were asked to rate their health on the EQ-5D-5L instrument (generic health measure). EQ-5D-5L responses were used to calculate health utility values. These were compared with age-matched values for the general population to estimate a utility shortfall (i.e. health loss) associated with perinatal death. RESULTS: There were 256 survey respondents with a median age of 40 years (IQR 26-40). Median time since death was 27 months (IQR 8-71). The mean utility value of the sample was 0.774 (95% CI 0.752-0.796). Utility values in the sample were 13% lower than general population values (p < 0.05). Over 10 years, this equated to a loss of 1.1 QALYs. This reduction in health utility was driven by anxiety and depression. CONCLUSIONS: Perinatal death has important and long-lasting health impacts on parents. Mental health support following perinatal bereavement is especially important.

Risk of stillbirth after a previous caesarean delivery: A Swedish nationwide cohort study.

OBJECTIVES: To investigate the risk of stillbirth in relation to (1) a previous caesarean delivery (CD) compared with those following a vaginal birth (VB); and (2) vaginal birth after caesarean (VBAC) compared with a repeat CD. DESIGN: Population-based cohort study. SETTING: The Swedish Medical Birth registry. POPULATION: Women with their first and second singletons between 1982 and 2012. METHODS: Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) of the association between CD in the first pregnancy and stillbirth in the second pregnancy and the association between VBAC and stillbirth. Sub-group analyses were performed by types of CD and timing of stillbirth (antepartum and intrapartum). MAIN OUTCOME MEASURES: Stillbirth (antepartum and intrapartum fetal death). RESULTS: Of the 1 771 700 singleton births from 885 850 women, 117 114 (13.2%) women had a CD in the first pregnancy, and 51 755 had VBAC in the second pregnancy. We found a 37% increased odds of stillbirth (aOR 1.37; 95% CI 1.23-1.52) in women with a previous CD compared with VB. The odds of intrapartum stillbirth were higher in the previous pre-labour CD group (aOR 2.72; 95% CI 1.51-4.91) and in the previous in-labour CD group (aOR 1.35; 95% CI 0.76-2.40), although not statistically significant in the latter case. No increased odds were found for intrapartum stillbirth in women who had VBAC (aOR 0.99; 95% CI 0.48-2.06) compared with women who had a repeat CD. CONCLUSIONS: This study confirms that a CD is associated with an increased risk of subsequent stillbirth, with a greater risk among pre-labour CD. This association is not solely mediated by increases in intrapartum asphyxia, uterine rupture or attempted VBAC. Further research is needed to understand this association, but these findings might help healthcare providers to reach optimal decisions regarding mode of birth, particularly when CD is unnecessary.

The carbon footprint of different modes of birth in the UK and the Netherlands: An exploratory study using life cycle assessment.

OBJECTIVE: To compare the carbon footprint of caesarean and vaginal birth. DESIGN: Life cycle assessment (LCA). SETTING: Tertiary maternity units and home births in the UK and the Netherlands. POPULATION: Birthing women. METHODS: A cradle-to-grave LCA using openLCA software to model the carbon footprint of different modes of delivery in the UK and the Netherlands. MAIN OUTCOME MEASURES: 'Carbon footprint' (in kgCO2 equivalents [kgCO2 e]). RESULTS: Excluding analgesia, the carbon footprint of a caesarean birth in the UK was 31.21 kgCO2 e, compared with 12.47 kgCO2 e for vaginal birth in hospital and 7.63 kgCO2 e at home. In the Netherlands the carbon footprint of a caesarean was higher (32.96 kgCO2 e), but lower for vaginal birth in hospital and home (10.74 and 6.27 kgCO2 e, respectively). Emissions associated with analgesia for vaginal birth ranged from 0.08 kgCO2 e (with opioid analgesia) to 237.33 kgCO2 e (nitrous oxide with oxygen). Differences in analgesia use resulted in a lower average carbon footprint for vaginal birth in the Netherlands than the UK (11.64 versus 193.26 kgCO2 e). CONCLUSION: The carbon footprint of a caesarean is higher than for a vaginal birth if analgesia is excluded, but this is very sensitive to the analgesia used; use of nitrous oxide with oxygen multiplies the carbon footprint of vaginal birth 25-fold. Alternative methods of pain relief or nitrous oxide destruction systems would lead to a substantial improvement in carbon footprint. Although clinical need and maternal choice are paramount, protocols should consider the environmental impact of different choices.

Characterizing Histopathologic Features in Pregnancies With Chronic Histiocytic Intervillositis Using Computerized Image Analysis.

CONTEXT.­: Chronic histiocytic intervillositis (CHI) is a rare condition characterized by maternal immune cell infiltration into the human placenta. CHI is strongly associated with fetal growth restriction, miscarriage, and stillbirth, and knowledge of its etiology, and consequently effective treatment, is limited. Currently, diagnosis is largely subjective and varies between centers, making comparison between studies challenging. OBJECTIVE.­: To objectively quantify and interrelate inflammatory cells and fibrin in placentas with CHI compared with controls and determine how pathology may be altered in subsequent pregnancies following diagnosis. Macrophage phenotype was also investigated in untreated cases of CHI. DESIGN.­: Computerized analysis was applied to immunohistochemically stained untreated (index) cases of CHI, subsequent pregnancies, and controls. Index placentas were additionally stained by immunofluorescence for M1 (CD80 and CD86) and M2 macrophage markers (CD163 and CD206). RESULTS.­: Quantification revealed a median 32-fold increase in macrophage infiltration in index cases versus controls, with CHI recurring in 2 of 11 (18.2%) subsequent pregnancies. A total of 4 of 14 placentas (28.6%) with a diagnosis of CHI did not exhibit infiltration above controls. Macrophages in index pregnancies strongly expressed CD163. There was no significant difference in fibrin deposition between index cases and controls, although subsequent pregnancies displayed a 2-fold decrease compared with index pregnancies. CD3+ T cells were significantly elevated in index pregnancies; however, they returned to normal levels in subsequent pregnancies. CONCLUSIONS.­: In CHI, intervillous macrophages expressed CD163, possibly representing an attempt to resolve inflammation. Computerized analysis of inflammation in CHI may be useful in determining how treatment affects recurrence, and alongside pathologist expertise in grading lesion severity.

Assessment of the association between ambient air pollution and stillbirth in the UK: Results from a secondary analysis of the MiNESS case-control study.

OBJECTIVE: We examined whether the risk of stillbirth was related to ambient air pollution in a UK population. DESIGN: Prospective case-control study. SETTING: Forty-one maternity units in the UK. POPULATION: Women who had a stillbirth ≥28 weeks' gestation (n = 238) and women with an ongoing pregnancy at the time of interview (n = 597). METHODS: Secondary analysis of data from the Midlands and North of England Stillbirth case-control study only including participants domiciled within 20 km of fixed air pollution monitoring stations. Pollution exposure was calculated using pollution climate modelling data for NO2 , NOx and PM2.5 . The association between air pollution exposure and stillbirth risk was assessed using multivariable logistic regression adjusting for household income, maternal body mass index (BMI), maternal smoking, Index of Multiple Deprivation quintile and household smoking and parity. MAIN OUTCOME MEASURE: Stillbirth. RESULTS: There was no association with whole pregnancy ambient air pollution exposure and stillbirth risk, but there was an association with preconceptual NO2 exposure (adjusted odds ratio [aOR] 1.06, 95% CI 1.01-1.08 per microg/m3 ). Risk of stillbirth was associated with maternal smoking (aOR 2.54, 95% CI 1.38-4.71), nulliparity (aOR 2.16, 95% CI 1.55-3.00), maternal BMI (aOR 1.05, 95% CI 1.01-1.08) and placental abnormalities (aOR 4.07, 95% CI 2.57-6.43). CONCLUSIONS: Levels of ambient air pollution exposure during pregnancy in the UK, all of were beneath recommended thresholds, are not associated with an increased risk of stillbirth. Periconceptual exposure to NO2 may be associated with increased risk but further work is required to investigate this association.

Risk of stillbirth and adverse pregnancy outcomes in a third pregnancy when an earlier pregnancy has ended in stillbirth.

INTRODUCTION: Our study evaluated how a history of stillbirth in either of the first two pregnancies affects the risk of having a stillbirth or other adverse pregnancy outcomes in the third subsequent pregnancy. MATERIAL AND METHODS: We used the Swedish Medical Birth Register to define a population-based cohort of women who had at least three singleton births from 1973 to 2012. The exposure of interest was a history of stillbirth in either of the first two pregnancies. The primary outcome was subsequent stillbirth in the third pregnancy. Secondary outcomes included: preterm birth, preeclampsia, placental abruption and small-for-gestational-age infant. Adjusted logistic regression was performed including maternal age, body mass index, smoking, diabetes and hypertension. A sensitivity analysis was performed excluding stillbirths associated with congenital anomalies, pregestational and gestational diabetes, hypertension and preterm stillbirths. RESULTS: The study contained data on 1 316 175 births, including 8911 stillbirths. Compared with women who had two live births, the highest odds of stillbirth in the third pregnancy were observed in women who had two stillbirths (adjusted odds ratio [aOR] 11.40, 95% confidence interval [95% CI] 2.75-47.70), followed by those who had stillbirth in the second birth (live birth-stillbirth) (aOR 3.59, 95% CI 2.58-4.98), but the odds were still elevated in those whose first birth ended in stillbirth (stillbirth-live birth) (aOR 2.35, 1.68, 3.28). Preterm birth, pre-eclampsia and placental abruption followed a similar pattern. The odds of having a small-for-gestational-age infant were highest in women whose first birth ended in stillbirth (aOR 1.93, 95% CI 1.66-2.24). The increased odds of having a stillbirth in a third pregnancy when either of the earlier births ended in stillbirth remained when stillbirths associated with congenital anomalies, pregestational and gestational diabetes, hypertension or preterm stillbirths were excluded. However, when preterm stillbirths were excluded, the strength of the association was reduced. CONCLUSIONS: Even when they have had a live-born infant, women with a history of stillbirth have an increased risk of adverse pregnancy outcomes; this cannot be solely accounted for by the recurrence of congenital anomalies or maternal medical disorders. This suggests that women with a history of stillbirth should be offered additional surveillance for subsequent pregnancies.

Decreased fetal movements: Report from the International Stillbirth Alliance conference workshop.

Maternal reports of decreased fetal movement (DFM) are a common reason to present to maternity care and are associated with stillbirth and other adverse outcomes. Promoting awareness of fetal movements and prompt assessment of DFM has been recommended to reduce stillbirths. However, evidence to guide clinical management of such presentations is limited. Educational approaches to increasing awareness of fetal movements in pregnant women and maternity care providers with the aim of reducing stillbirths have recently been evaluated in a several large clinical trials internationally. The International Stillbirth Alliance Virtual Conference in Sydney 2021 provided an opportunity for international experts in fetal movements to share reports on the findings of fetal movement awareness trials, consider evidence for biological mechanisms linking DFM and fetal death, appraise approaches to clinical assessment of DFM, and highlight research priorities in this area. Following this workshop summaries of the sessions prepared by the authors provide an overview of understandings of fetal movements in maternity care at the current time and highlights future directions in fetal movement research.

Subsequent pregnancy outcomes after second trimester miscarriage or termination for medical/fetal reason: A systematic review and meta-analysis of observational studies.

INTRODUCTION: Women with a prior stillbirth or a history of recurrent first trimester miscarriages are at increased risk of adverse pregnancy outcomes. However, little is known about the impact of a second trimester pregnancy loss on subsequent pregnancy outcome. This review investigated if second trimester miscarriage or termination for medical reason or fetal anomaly (TFMR/TOPFA) is associated with future adverse pregnancy outcomes. MATERIAL AND METHODS: A systematic review of observational studies was conducted. Eligible studies included women with a history of a second trimester miscarriage or termination for medical reasons and their pregnancy outcomes in the subsequent pregnancy. Where comparative studies were identified, studies which compared subsequent pregnancy outcomes for women with and without a history of second trimester loss or TFMR/TOPFA were included. The primary outcome was livebirth, and secondary outcomes included: miscarriage (first and second trimester), termination of pregnancy, fetal growth restriction, cesarean section, preterm birth, pre-eclampsia, antepartum hemorrhage, stillbirth and neonatal death. Studies were excluded if exposure was nonmedical termination or if related to twins or higher multiple pregnancies. Electronic searches were conducted using the online databases (MEDLINE, Embase, PubMed and The Cochrane Library) and searches were last updated on June 16, 2023. Risk of bias was assessed using the Newcastle-Ottawa scale. Where possible, meta-analysis was undertaken. PROSPERO registration: CRD42023375033. RESULTS: Ten studies were included, reporting on 12 004 subsequent pregnancies after a second trimester pregnancy miscarriage. No studies were found on outcomes after second trimester TFMR/TOPFA. Overall, available data were of "very low quality" using GRADE assessment. Meta-analysis of cohort studies generated estimated outcome frequencies for women with a previous second trimester loss as follows: live birth 81% (95% CI: 64-94), miscarriage 15% (95% CI: 4-30, preterm birth 13% [95% CI: 6-23]).The pooled odds ratio for preterm birth in subsequent pregnancy after second trimester loss in case-control studies was OR 4.52 (95% CI: 3.03-6.74). CONCLUSIONS: Very low certainty evidence suggests there may be an increased risk of preterm birth in a subsequent pregnancy after a late miscarriage. However, evidence is limited. Larger, higher quality cohort studies are needed to investigate this potential association.

Care in pregnancy after stillbirth.

Pregnancy after stillbirth is associated with increased risk of stillbirth and other adverse pregnancy outcomes including fetal growth restriction, preeclampsia, and preterm birth in subsequent pregnancies. In addition, pregnancy after stillbirth is associated with emotional and psychological challenges for women and their families. This manuscript summarizes information available to guide clinicians for how to manage a pregnancy after stillbirth by appreciating the nature of the increased risk in future pregnancies, and that these are not affected by interpregnancy interval. Qualitative studies have identified clinician behaviors that women find helpful during subsequent pregnancies after loss which can be implemented into practice. The role of peer support and need for professional input from the antenatal period through to after the birth of a live baby is discussed. Finally, areas for research are highlighted to develop care further for this group of women at increased risk of medical and psychological complications.

The effect of prone positioning on maternal haemodynamics and fetal wellbeing in the third trimester-A primary cohort study with a scoping review.

INTRODUCTION: Supine sleep position is associated with stillbirth, likely secondary to inferior vena cava compression, and a reduction in cardiac output (CO) and uteroplacental perfusion. Evidence for the effects of prone position in pregnancy is less clear. This study aimed to determine the effect maternal prone position on maternal haemodynamics and fetal heart rate, compared with left lateral position. METHODS: Twenty-one women >28 weeks' gestation underwent non-invasive CO monitoring (Cheetah) every 5 minutes and continuous fetal heart rate monitoring (MONICA) in left lateral (20 minutes), prone (30 minutes), followed by left lateral (20 minutes). Anxiety and comfort were assessed by questionnaires. Regression analyses (adjusted for time) compared variables between positions. The information derived from the primary study was used in an existing mathematical model of maternal circulation in pregnancy, to determine whether occlusion of the inferior vena cava could account for the observed effects. In addition, a scoping review was performed to identify reported clinical, haemodynamic and fetal effects of maternal prone position; studies were included if they reported clinical outcomes or effects or maternal prone position in pregnancy. Study records were grouped by publication type for ease of data synthesis and critical analysis. Meta-analysis was performed where there were sufficient studies. RESULTS: Maternal blood pressure (BP) and total vascular resistance (TVR) were increased in prone (sBP 109 vs 104 mmHg, p = 0.03; dBP 74 vs 67 mmHg, p = 0.003; TVR 1302 vs 1075 dyne.s-1cm-5, p = 0.03). CO was reduced in prone (5.7 vs 7.1 mL/minute, p = 0.003). Fetal heart rate, variability and decelerations were unaltered. However, fetal accelerations were less common in prone position (86% vs 95%, p = 0.03). Anxiety was reduced after the procedure, compared to beforehand (p = 0.002), despite a marginal decline in comfort (p = 0.04).The model predicted that if occlusion of the inferior vena cava occurred, the sBP, dBP and CO would generally decrease. However, the TVR remained relatively consistent, which implies that the MAP and CO decrease at a similar rate when occlusion occurs. The scoping review found that maternal and fetal outcomes from 47 included case reports of prone positioning during pregnancy were generally favourable. Meta-analysis of three prospective studies investigating maternal haemodynamic effects of prone position found an increase in sBP and maternal heart rate, but no effect on respiratory rate, oxygen saturation or baseline fetal heart rate (though there was significant heterogeneity between studies). CONCLUSION: Prone position was associated with a reduction in CO but an uncertain effect on fetal wellbeing. The decline in CO may be due to caval compression, as supported by the computational model. Further work is needed to optimise the safety of prone positioning in pregnancy. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov (NCT04586283).

Murine models of advanced maternal age: a systematic review and meta-analysis.

In brief: Animal models have been developed to aid understanding of the increased incidence of adverse pregnancy complications observed in women of advanced maternal age (AMA). This systematic review of murine models of AMA demonstrates consistent effects of decreased litter size and fetal weight; this supports the future use of these models to determine pathophysiological mechanisms and test therapeutic strategies to improve poor pregnancy outcomes in AMA. Abstract: Advanced maternal age (AMA; ≥35 years of age) is associated with an increased risk of adverse pregnancy outcomes. To explore causes of adverse pregnancy outcomes in AMA, and to test candidate therapies, an increasing number of murine AMA models have been developed. The aim of this study was to systematically review the literature to assess whether murine AMA models demonstrate a reproducible effect on pregnancy outcomes. PubMed, Ovid, Web of Science and Google Scholar were searched. Studies that reported on pregnancy outcomes in AMA mice and rats were included; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool evaluated the risk of bias. Eleven mouse and six rat studies were included. AMA mice and rats had reduced litter size (standardised mean difference (SMD): -1.59, 95% confidence interval (CI): -1.84, -1.34 for mice; SMD: -1.66, 95% (CI): -2.09, -1.23 for rats) and reduced fetal weight (SMD: -0.87, 95% CI: -1.24, -0.49 for mice; SMD: -1.05, 95% CI: -1.40, -0.69 for rats). Placental weight was increased in AMA mice (SMD: 0.62, 95% CI: 0.16, 1.08). Subgroup analysis indicated that C57Bl/6 mice had less heterogeneity than other, mostly outbred, mouse strains with regards to litter size (C57 strain I2 = 68.2% vs other strain types I2 = 85.7%). The risk of bias was high, mostly due to the lack of methodological detail and unclear reporting of findings. Murine models of AMA demonstrate similar adverse pregnancy outcomes to those observed in large human epidemiological studies. The reproducible phenotypes in AMA murine models allow the exploration of mechanisms underpinning poor pregnancy outcomes and the pursuit of therapeutic interventions.

Does fetal size affect maternal perception of fetal movements? Evidence from an individual participant data meta-analysis.

INTRODUCTION: Maternal perception of fetal movements during pregnancy are reassuring; however, the perception of a reduction in movements are concerning to women and known to be associated with increased odds of late stillbirth. Prior to full term, little evidence exists to provide guidelines on how to proceed unless there is an immediate risk to the fetus. Increased strength of movement is the most commonly reported perception of women through to full term, but perception of movement is also hypothesized to be influenced by fetal size. The study aimed to assess the pattern of maternal perception of strength and frequency of fetal movement by gestation and customized birthweight quartile in ongoing pregnancies. A further aim was to assess the association of stillbirth to perception of fetal movements stratified by customized birthweight quartile. MATERIAL AND METHODS: This analysis was an individual participant data meta-analyses of five case-control studies investigating factors associated with stillbirth. The dataset included 851 cases of women with late stillbirth (>28 weeks' gestation) and 2257 women with ongoing pregnancies who then had a liveborn infant. RESULTS: The frequency of prioritized fetal movement from 28 weeks' gestation showed a similar pattern for each quartile of birthweight with increased strength being the predominant perception of fetal movement through to full term. The odds of stillbirth associated with reduced fetal movements was increased in all quartiles of customized birthweight centiles but was notably greater in babies in the lowest two quartiles (Q1: adjusted OR: 9.34, 95% CI: 5.43, 16.06 and Q2: adjusted OR: 6.11, 95% CI: 3.11, 11.99). The decreased odds associated with increased strength of movement was present for all customized birthweight quartiles (adjusted OR range: 0.25-0.56). CONCLUSIONS: Increased strength of fetal movements in late pregnancy is a positive finding irrespective of fetal size. However, reduced fetal movements are associated with stillbirth, and more so when the fetus is small.

Risk factors for adverse outcomes in twin pregnancies: a narrative review.

PURPOSE: Globally, the incidence of twin pregnancies is rising owing to the use of assisted reproductive technologies (ART), emigration and deferment of pregnancy until advanced maternal age (AMA). While twin pregnancies have higher absolute risks of adverse outcomes, including miscarriage, stillbirth, neonatal death and preterm delivery, the impact of specific exposures and risk factors related to these outcomes may differ between twin pregnancies and singleton pregnancies. Regarding modifiable factors, data are sometimes based on evidence extrapolated from singleton or whole obstetric populations. Therefore, targeted evidence is required to provide care tailored to twin pregnancies to prevent adverse outcomes. We aimed to comprehensively review the association between different risk factors and adverse outcomes in twin pregnancies, including data on chorionicity, and to compare these to singletons. MATERIALS AND METHODS: This review examines the risks associated with chorionicity, AMA, body mass index (BMI), socioeconomic and ethnic inequalities, maternal smoking, use of ART, maternal perception of fetal movement, and maternal comorbidities, including hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM). Adverse outcomes reported were preterm birth, admission to the neonatal intensive care unit (NICU), stillbirth and neonatal mortality. As such, fetal mortality and morbidity will be under-represented, as pregnancy loss before 22-24 weeks is omitted. RESULTS: Monochorionicity increases the risk of stillbirth, NICU admission, and preterm delivery in twin pregnancy. AMA predisposes twin pregnancies to higher risks of mortality, admission to the NICU, and preterm birth than singleton pregnancies do. Conversely, the impact of BMI, socioeconomic inequalities, smoking, ART, and HDP on adverse outcomes appears to be lower in twin pregnancies than in singleton pregnancies. This attenuation might be explained by the higher baseline risk of adverse outcomes such as preterm birth in twin pregnancies. Some exposures, such as ART use and GDM, appear to be "protective" against perinatal mortality in twin pregnancies, despite being established risk factors for adverse outcomes in singleton pregnancies, potentially related to access to specialist care. There is a paucity of evidence available to counsel mothers of twin pregnancies regarding reduced fetal movement. CONCLUSIONS: Overall, the risk factors for adverse pregnancy outcomes differ between twin and singleton pregnancies. This highlights the need for further studies to examine the association between risk factors and adverse outcomes in twin pregnancies. The resulting data would facilitate tailored guidance for twin pregnancies, contribute to improved antenatal care, and inform wider public health strategies.

Ending preventable stillbirths and improving bereavement care: a scorecard for high- and upper-middle income countries.

BACKGROUND: Despite progress, stillbirth rates in many high- and upper-middle income countries remain high, and the majority of these deaths are preventable. We introduce the Ending Preventable Stillbirths (EPS) Scorecard for High- and Upper Middle-Income Countries, a tool to track progress against the Lancet's 2016 EPS Series Call to Action, fostering transparency, consistency and accountability. METHODS: The Scorecard for EPS in High- and Upper-Middle Income Countries was adapted from the Scorecard for EPS in Low-Income Countries, which includes 20 indicators to track progress against the eight Call to Action targets. The Scorecard for High- and Upper-Middle Income Countries includes 23 indicators tracking progress against these same Call to Action targets. For this inaugural version of the Scorecard, 13 high- and upper-middle income countries supplied data. Data were collated and compared between and within countries. RESULTS: Data were complete for 15 of 23 indicators (65%). Five key issues were identified: (1) there is wide variation in stillbirth rates and related perinatal outcomes, (2) definitions of stillbirth and related perinatal outcomes vary widely across countries, (3) data on key risk factors for stillbirth are often missing and equity is not consistently tracked, (4) most countries lack guidelines and targets for critical areas for stillbirth prevention and care after stillbirth and have not set a national stillbirth rate target, and (5) most countries do not have mechanisms in place for reduction of stigma or guidelines around bereavement care. CONCLUSIONS: This inaugural version of the Scorecard for High- and Upper-Middle Income Countries highlights important gaps in performance indicators for stillbirth both between and within countries. The Scorecard provides a basis for future assessment of progress and can be used to help hold individual countries accountable, especially for reducing stillbirth inequities in disadvantaged groups.

Assessing safe and personalised maternity and neonatal care through a pandemic: a case study of outcomes and experiences in two trusts in England using the ASPIRE COVID-19 framework.

BACKGROUND: The COVID-19 pandemic has resulted in profound and far-reaching impacts on maternal and newborn care and outcomes. As part of the ASPIRE COVID-19 project, we describe processes and outcome measures relating to safe and personalised maternity care in England which we map against a pre-developed ASPIRE framework to establish the potential impact of the COVID-19 pandemic for two UK trusts. METHODS: We undertook a mixed-methods system-wide case study using quantitative routinely collected data and qualitative data from two Trusts and their service users from 2019 to 2021 (start and completion dates varied by available data). We mapped findings to our prior ASPIRE conceptual framework that explains pathways for the impact of COVID-19 on safe and personalised care. RESULTS: The ASPIRE framework enabled us to develop a comprehensive, systems-level understanding of the impact of the pandemic on service delivery, user experience and staff wellbeing, and place it within the context of pre-existing challenges. Maternity services experienced some impacts on core service coverage, though not on Trust level clinical health outcomes (with the possible exception of readmissions in one Trust). Both users and staff found some pandemic-driven changes challenging such as remote or reduced antenatal and community postnatal contacts, and restrictions on companionship. Other key changes included an increased need for mental health support, changes in the availability and uptake of home birth services and changes in induction procedures. Many emergency adaptations persisted at the end of data collection. Differences between the trusts indicate complex change pathways. Staff reported some removal of bureaucracy, which allowed greater flexibility. During the first wave of COVID-19 staffing numbers increased, resolving some pre-pandemic shortages: however, by October 2021 they declined markedly. Trying to maintain the quality and availability of services had marked negative consequences for personnel. Timely routine clinical and staffing data were not always available and personalised care and user and staff experiences were poorly captured. CONCLUSIONS: The COVID-19 crisis magnified pre-pandemic problems and in particular, poor staffing levels. Maintaining services took a significant toll on staff wellbeing. There is some evidence that these pressures are continuing. There was marked variation in Trust responses. Lack of accessible and timely data at Trust and national levels hampered rapid insights. The ASPIRE COVID-19 framework could be useful for modelling the impact of future crises on routine care.