Stillbirths preceded by reduced fetal movements are more frequently associated with placental insufficiency:a retrospective cohort study

Objectives: Maternal report of reduced fetal movements (RFM) is a means of identifying fetal compromise in pregnancy. In live births RFM is associated with altered placental structure and function. Here, we explored associations between RFM, pregnancy characteristics, and the presence of placental abnormalities and fetal growth restriction (FGR) in cases of stillbirth. Methods: A retrospective cohort study was carried out in a single UK tertiary maternity unit. Cases were divided into three groups: 109 women reporting RFM, 33 women with absent fetal movements (AFM) and 159 who did not report RFM before the diagnosis of stillbirth. Univariate and multivariate logistic regression was used to determine associations between RFM/AFM, pregnancy characteristics, placental insufficiency and the classification of the stillbirth. Results: AFM or RFM were reported prior to diagnosis of stillbirth in 142 (47.2%) of cases. Pregnancies with RFM prior to diagnosis of stillbirth were independently associated with placental insufficiency (Odds Ratio (OR) 2.79, 95% Confidence Interval (CI) 1.84, 5.04) and were less frequently associated with maternal proteinuria (OR 0.16, 95% CI 0.07, 0.62) and previous pregnancy loss Conclusions: The association between RFM and placental insufficiency was confirmed in cases of stillbirth. This provides further evidence that RFM is a symptom of placental insufficiency. Therefore, investigation after RFM should aim to identify placental dysfunction

Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements

Background Maternal perception of reduced fetal movements (RFM) is associated with increased risk of fetal growth restriction (FGR) and stillbirth, mediated by placental insufficiency. The maternally expressed imprinted gene PHLDA2 controls fetal growth, placental development and placental lactogen production in a mouse model. A number of studies have also demonstrated abnormally elevated placental PHLDA2 expression in human growth restricted pregnancies. This study examined whether PHLDA2 was aberrantly expressed in placentas of RFM pregnancies resulting in delivery of an FGR infant and explored a possible relationship between PHLDA2 expression and placental lactogen release from the human placenta. Methods Villous trophoblast samples were obtained from a cohort of women reporting RFM (N = 109) and PHLDA2 gene expression analysed. hPL levels were assayed in the maternal serum (N = 74). Results Placental PHLDA2 expression was significantly 2.3 fold higher in RFM pregnancies resulting in delivery of an infant with FGR (p < 0.01), with highest levels of PHLDA2 expression in the most severe cases. Placental PHLDA2 expression was associated with maternal serum hPL levels (r = −0.30, p = 0.008, n = 74) although this failed to reach statistical significance in multiple linear regression analysis controlling for birth weight (p = 0.07). Conclusions These results further highlight a role for placental PHLDA2 in poor perinatal outcomes, specifically FGR associated with RFM. Furthermore, this study suggests a potential relationship between placental PHLDA2 expression and hPL production by the placenta, an association that requires further investigation in a larger cohort

Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-08-04, accepted 2021-09-23, epub 2021-10-18Publication status: PublishedChronic histiocytic intervillositis (CHI) is a rare, but highly recurrent inflammatory placental lesion wherein maternal macrophages infiltrate the intervillous space. Pregnancies with CHI are at high risk of fetal growth restriction, miscarriage or stillbirth. Presently, the diagnosis can only be made after histopathological examination of the placenta. Given its proposed immunological etiology, current treatments include aspirin, heparin, and immunomodulatory agents. However, the rationale for these medications is largely based upon small case series and reports as there is a lack of larger studies investigating treatment efficacy. Therefore, this study sought to determine whether inclusion of immunomodulatory medications was effective at reducing the severity of lesions and improving pregnancy outcomes in subsequent pregnancies. Thirty-three women with a history of CHI in at least one pregnancy (index case) were identified retrospectively through medical records. Twenty-eight participants presented with a first subsequent pregnancy and a further 11 with a second subsequent pregnancy at a specialist clinic for pregnancy after loss. Data on maternal demographics, medical history, medication, pregnancy outcome, and placental pathology was collected and compared between pregnancies. Twenty-seven (69%) subsequent pregnancies were treated with at least one or both of prednisolone and hydroxychloroquine. Inclusion of at least one immunomodulatory agent in treatment regimen resulted in an almost 25% increase in overall livebirth rate (61.5 vs. 86.2%). In women treated with immunomodulatory medication a greater proportion of placentas had reduced severity of lesions compared to those treated without (86.7 vs. 33.3%, respectively). A reduction in CHI severity was associated with a 62.3% improvement in livebirth rate compared to those where severity remained unchanged in relation to the index case. These data provide preliminary evidence that the use of immunomodulatory medication in the management of CHI improves histopathological lesions and the chance of livebirth in subsequent pregnancies. Due to CHI's rarity and ethical and feasibility issues, randomized controlled trials in affected women are challenging to conduct. As a result, collaboration between centers is required in future to increase study sample sizes and elucidate the mechanisms of hydroxychloroquine and prednisolone in reducing pathology

Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM)::a trial-based and model-based cost-effectiveness analysis from a stepped wedge, cluster-randomised trial

Abstract Background The AFFIRM intervention aimed to reduce stillbirth and neonatal deaths by increasing awareness of reduced fetal movements (RFM) and implementing a care pathway when women present with RFM. Although there is uncertainty regarding the clinical effectiveness of the intervention, the aim of this analysis was to evaluate the cost-effectiveness. Methods A stepped-wedge, cluster-randomised trial was conducted in thirty-three hospitals in the United Kingdom (UK) and Ireland. All women giving birth at the study sites during the analysis period were included in the study. The costs associated with implementing the intervention were estimated from audits of RFM attendances and electronic healthcare records. Trial data were used to estimate a cost per stillbirth prevented was for AFFIRM versus standard care. A decision analytic model was used to estimate the costs and number of perinatal deaths (stillbirths + early neonatal deaths) prevented if AFFIRM were rolled out across Great Britain for one year. Key assumptions were explored in sensitivity analyses. Results Direct costs to implement AFFIRM were an estimated £95,126 per 1,000 births. Compared to standard care, the cost per stillbirth prevented was estimated to be between £86,478 and being dominated (higher costs, no benefit). The estimated healthcare budget impact of implementing AFFIRM across Great Britain was a cost increase of £61,851,400/year. Conclusions Perinatal deaths are relatively rare events in the UK which can increase uncertainty in economic evaluations. This evaluation estimated a plausible range of costs to prevent baby deaths which can inform policy decisions in maternity services. Trial registration The trial was registered with www.ClinicalTrials.gov, number NCT01777022. </jats:sec

Interventions for supporting parents' decisions about autopsy after stillbirth (Review)

Background: Stillbirth remains one of the least understood areas of infant death and accurate data on the causes of stillbirth are the cornerstone of stillbirth prevention. An autopsy examination remains the gold standard post-mortem investigation for stillbirth. However, decisions about post-mortem investigations, particularly autopsy are difficult. The purpose of this review is to examine the effectiveness of methods to help parents who have experienced a stillbirth decide whether to have post-mortem investigations, including whether to have an autopsy performed. Objectives: The primary objectives were a) to examine the effectiveness of interventions to support parents' decisions about autopsy consent after a stillbirth on outcomes for parents, and b) to determine autopsy rates. Secondary objectives were to identify issues related to the acceptability of any interventions to parents and the feasibility of their implementation. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 October 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10), MEDLINE (1966 to 24 July 2012) and EMBASE (1980 to 24 July 2012), Current Controlled Trials metaRegister (mRCT) (18 September 2012) and the WHO International Clinical Trials Registry Platform Search Portal (ICTRP) (18 September 2012). We also searched the websites of the Stillbirth and Neonatal Death Charity (SANDS) and International Stillbirth Alliance (ISA) (18 September 2012) and then subsequently searched the websites of all the ISA member organisations. Selection criteria: Randomised controlled trials (RCTs) of interventions designed specifically to support parents who have experienced a stillbirth make decisions about their options for post-mortem investigations including all investigations after stillbirth compared with usual care. Data collection and analysis: Two review authors independently screened citations against the selection criteria. Main results: No studies meeting the review inclusion criteria were identified. A search of 40 websites associated with supporting parents who experience stillbirth also found little reference to, or information about autopsy or other post-mortem examinations. Authors' conclusions: Support for parents making decisions about autopsy or other post-mortem examinations after stillbirth must rely on the ad hoc knowledge and experience of those involved at the time

Exploring the intangible economic costs of stillbirth

BACKGROUND: Compared to other pregnancy-related events, the full cost of stillbirth remains poorly described. In the UK one in every 200 births ends in stillbirth. As a follow-up to a recent study which explored the direct costs of stillbirth, this study aimed to explore the intangible costs of stillbirth in terms of their duration and economic implication. METHODS: Systematic searches identified relevant papers on the psychological consequences of stillbirth. A narrative review of the quantitative studies was undertaken. This was followed by a qualitative synthesis using meta-ethnography to identify over-arching themes common to the papers. Finally, the themes were used to generate questions proposed for use in a questionnaire to capture the intangible costs of stillbirth. RESULTS: The narrative review revealed a higher level of anxiety and depression in couples with stillbirth compared to those without stillbirth. The qualitative synthesis identified a range of psychological effects common to families that have experienced stillbirth. Both methods revealed the persistent nature of these effects and the subsequent economic burden. CONCLUSIONS: The psychological effects of stillbirth adversely impacts on the daily functioning, relationships and employment of those affected with far-reaching economic implications. Knowledge of the intangible costs of stillbirth is therefore important to accurately estimate the size of the impact on families and health services and to inform policy and decision making. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12884-015-0617-x) contains supplementary material, which is available to authorized users

The CErebro Placental RAtio as indicator for delivery following perception of reduced fetal movements, protocol for an international cluster randomised clinical trial; the CEPRA study

Background: Routine assessment in (near) term pregnancy is often inaccurate for the identification of fetuses who are mild to moderately compromised due to placental insufficiency and are at risk of adverse outcomes, especially when fetal size is seemingly within normal range for gestational age. Although biometric measurements and cardiotocography are frequently used, it is known that these techniques have low sensitivity and specificity. In clinical practice this diagnostic uncertainty results in considerable ‘over treatment’ of women with healthy fetuses whilst truly compromised fetuses remain unidentified. The CPR is the ratio of the umbilical artery pulsatility index over the middle cerebral artery pulsatility index. A low CPR reflects fetal redistribution and is thought to be indicative of placental insufficiency independent of actual fetal size, and a marker of adverse outcomes. Its utility as an indicator for delivery in women with reduced fetal movements (RFM) is unknown. The aim of this study is to assess whether expedited delivery of women with RFM identified as high risk on the basis of a low CPR improves neonatal outcomes. Secondary aims include childhood outcomes, maternal obstetric outcomes, and the predictive value of biomarkers for adverse outcomes. Methods: International multicentre cluster randomised trial of women with singleton pregnancies with RFM at term, randomised to either an open or concealed arm. Only women with an estimated fetal weight ≥ 10th centile, a fetus in cephalic presentation and normal cardiotocograph are eligible and after informed consent the CPR will be measured. Expedited delivery is recommended in women with a low CPR in the open arm. Women in the concealed arm will not have their CPR results revealed and will receive routine clinical care. The intended sample size based on the primary outcome is 2160 patients. The primary outcome is a composite of: stillbirth, neonatal mortality, Apgar score < 7 at 5 min, cord pH < 7.10, emergency delivery for fetal distress, and severe neonatal morbidity. Discussion: The CEPRA trial will identify whether the CPR is a good indicator for delivery in women with perceived reduced fetal movements. Trial registration: Dutch trial registry (NTR), trial NL7557. Registered 25 February 2019