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.

Effect of encouraging awareness of reduced fetal movement and subsequent clinical management on pregnancy outcome: a systematic review and meta-analysis.

OBJECTIVE: Reduced fetal movement, defined as a decrease in the frequency or strength of fetal movements as perceived by the mother, is a common reason for presentation to maternity care. Observational studies have demonstrated an association between reduced fetal movement and stillbirth and fetal growth restriction related to placental insufficiency. However, individual intervention studies have described varying results. This systematic review and meta-analysis aimed to determine whether interventions aimed at encouraging awareness of reduced fetal movement and/or improving its subsequent clinical management reduce the frequency of stillbirth or other important secondary outcomes. DATA SOURCES: Searches were conducted in MEDLINE, Embase, CINAHL, The Cochrane Library, Web of Science, and Google Scholar. Guidelines, trial registries, and gray literature were also searched. Databases were searched from inception to January 20, 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and controlled nonrandomized studies were eligible if they assessed interventions aimed at encouraging awareness of fetal movement or fetal movement counting and/or improving the subsequent clinical management of reduced fetal movement. Eligible populations were singleton pregnancies after 24 completed weeks of gestation. The primary review outcome was stillbirth; a number of secondary maternal and neonatal outcomes were specified in the review. METHODS: Risk of bias was assessed using the Cochrane Risk of Bias 2 and Risk of Bias in Non-Randomized Studies I tools for randomized controlled trials and nonrandomized studies, respectively. Variation caused by heterogeneity was assessed using I2. Data from studies employing similar interventions were combined using random effects meta-analysis. RESULTS: A total of 1609 citations were identified; 190 full-text articles were evaluated against the inclusion criteria, 18 studies (16 randomized controlled trials and 2 nonrandomized studies) were included. The evidence is uncertain about the effect of encouraging awareness of fetal movement on stillbirth when compared with standard care (2 studies, n=330,084) with a pooled adjusted odds ratio of 1.19 (95% confidence interval, 0.96-1.47). Interventions for encouraging awareness of fetal movement may be associated with a reduction in neonatal intensive care unit admissions and Apgar scores of <7 at 5 minutes of age and may not be associated with increases in cesarean deliveries or induction of labor. The evidence is uncertain about the effect of encouraging fetal movement counting on stillbirth when compared with standard care with a pooled odds ratio of 0.69 (95% confidence interval, 0.18-2.65) based on data from 3 randomized controlled trials (n=70,584). Counting fetal movements may increase maternal-fetal attachment and decrease anxiety when compared with standard care. When comparing combined interventions of fetal movement awareness and subsequent clinical management with standard care (1 study, n=393,857), the evidence is uncertain about the effect on stillbirth (adjusted odds ratio, 0.86; 95% confidence interval, 0.70-1.05). CONCLUSION: The effect of interventions for encouraging awareness of reduced fetal movement alone or in combination with subsequent clinical management on stillbirth is uncertain. Encouraging awareness of fetal movement may be associated with reduced adverse neonatal outcomes without an increase in interventions in labor. The meta-analysis was hampered by variations in interventions, outcome reporting, and definitions. Individual studies are frequently underpowered to detect a reduction in severe, rare outcomes and no studies were included from high-burden settings. Studies from such settings are needed to determine whether interventions can reduce stillbirth.

Development of a core outcome set (COS) for studies relating to awareness and clinical management of reduced fetal movement: study protocol.

BACKGROUND: Concerns regarding reduced fetal movements (RFM) are reported in 5-15% of pregnancies, and RFM are associated with adverse pregnancy outcomes including fetal growth restriction and stillbirth. Studies have aimed to improve pregnancy outcomes by evaluating interventions to raise awareness of RFM in pregnancy, such as kick counting, evaluating interventions for the clinical management of RFM, or both. However, there is not currently a core outcome set (COS) for studies of RFM. This study aims to create a COS for use in research studies that aim to raise awareness of RFM and/or evaluate interventions for the clinical management of RFM. METHODS: A systematic review will be conducted, to identify outcomes used in randomised and non-randomised studies with control groups that aimed to raise awareness of RFM (for example by using mindfulness techniques, fetal movement counting, or other tools such as leaflets or mobile phone applications) and/or that evaluated the clinical management of RFM. An international Delphi consensus will then be used whereby stakeholders will rate the importance of the outcomes identified in the systematic review in (i) awareness and (ii) clinical management studies. The preliminary lists of outcomes will be discussed at a consensus meeting where one final COS for awareness and management, or two discrete COS (one for awareness and one for management), will be agreed upon. DISCUSSION: A well-developed COS will provide researchers with the minimum set of outcomes that should be measured and reported in studies that aim to quantify the effects of interventions.

A Systematic Review of the Safety of Blocking the IL-1 System in Human Pregnancy.

Blockade of the interleukin-1 (IL-1) pathway has been used therapeutically in several inflammatory diseases including arthritis and cryopyrin-associated periodic syndrome (CAPS). These conditions frequently affect women of childbearing age and continued usage of IL-1 specific treatments throughout pregnancy has been reported. IL-1 is involved in pregnancy complications and its blockade could have therapeutic potential. We systematically reviewed all reported cases of IL-1 blockade in human pregnancy to assess safety and perinatal outcomes. We searched several databases to find reports of specific blockade of the IL-1 pathway at any stage of pregnancy, excluding broad spectrum or non-specific anti-inflammatory intervention. Our literature search generated 2439 references of which 22 studies included, following extensive review. From these, 88 different pregnancies were assessed. Most (64.8%) resulted in healthy term deliveries without any obstetrical/neonatal complications. Including pregnancy exposed to Anakinra or Canakinumab, 12 (15.0%) resulted in preterm birth and one stillbirth occurred. Regarding neonatal complications, 2 cases of renal agenesis (2.5%) were observed, and 6 infants were diagnosed with CAPS (7.5%). In conclusion, this systematic review describes that IL-1 blockade during pregnancy is not associated with increased adverse perinatal outcomes, considering that treated women all presented an inflammatory disease associated with elevated risk of pregnancy complications.

A systematic scoping review to identify the design and assess the performance of devices for antenatal continuous fetal monitoring.

BACKGROUND: Antepartum fetal monitoring aims to assess fetal development and wellbeing throughout pregnancy. Current methods utilised in clinical practice are intermittent and only provide a 'snapshot' of fetal wellbeing, thus key signs of fetal demise could be missed. Continuous fetal monitoring (CFM) offers the potential to alleviate these issues by providing an objective and longitudinal overview of fetal status. Various CFM devices exist within literature; this review planned to provide a systematic overview of these devices, and specifically aimed to map the devices' design, performance and factors which affect this, whilst determining any gaps in development. METHODS: A systematic search was conducted using MEDLINE, EMBASE, CINAHL, EMCARE, BNI, Cochrane Library, Web of Science and Pubmed databases. Following the deletion of duplicates, the articles' titles and abstracts were screened and suitable papers underwent a full-text assessment prior to inclusion in the review by two independent assessors. RESULTS: The literature searches generated 4,885 hits from which 43 studies were included in the review. Twenty-four different devices were identified utilising four suitable CFM technologies: fetal electrocardiography, fetal phonocardiography, accelerometry and fetal vectorcardiography. The devices adopted various designs and signal processing methods. There was no common means of device performance assessment between different devices, which limited comparison. The device performance of fetal electrocardiography was reduced between 28 to 36 weeks' gestation and during high levels of maternal movement, and increased during night-time rest. Other factors, including maternal body mass index, fetal position, recording location, uterine activity, amniotic fluid index, number of fetuses and smoking status, as well as factors which affected alternative technologies had equivocal effects and require further investigation. CONCLUSIONS: A variety of CFM devices have been developed, however no specific approach or design appears to be advantageous due to high levels of inter-device and intra-device variability.

A structured review of placental morphology and histopathological lesions associated with SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, was first identified after a cluster of cases in Wuhan, China in December 2019. Whether vertical transmission or placental pathology might occur following maternal infection during pregnancy remains unknown. This review aimed to summarise all studies that examined the placenta or neonates following infection with SARS-CoV-2, or closely related highly pathogenic coronavirus (SARS-CoV-1, or the Middle East respiratory syndrome coronavirus (MERS-CoV)). Structured literature searches found 50 studies that met the inclusion criteria. Twenty studies reported placental histopathology findings in third trimester placentas following maternal SARS-CoV-2 infection. Using the Amsterdam Consensus criteria to categorise the histopathology results, evidence of both fetal vascular malperfusion (35.3% of cases; 95% Confidence Interval (CI) 27.7-43.0%) and maternal vascular malperfusion (46% of cases; 95% CI 38.0-54.0%) were reported, along with evidence of inflammation in the placentas (villitis 8.7% cases, intervillositis 5.3% of cases, chorioamnionitis 6% of cases). The placental pathologies observed in SARS-CoV-2 were consistent with findings following maternal SARS-CoV-1 infection. Of those tested, a minority of neonates (2%) and placental samples tested positive for SARS-CoV-2 infection (21%). Limited conclusions can be drawn about the effect of maternal SARS-CoV-2 infection on placental pathology as most lack control groups and the majority of reports followed third trimester infection. Collaboration to maximise the number of samples examined will increase the reliability and generalisability of findings. A better understanding of the association between maternal SARS-CoV-2 infection and placental pathology will inform maternity care during the coronavirus pandemic.

Umbilical cord characteristics and their association with adverse pregnancy outcomes: A systematic review and meta-analysis.

OBJECTIVE: Current data on the role of the umbilical cord in pregnancy complications are conflicting; estimates of the proportion of stillbirths due to cord problems range from 3.4 to 26.7%. A systematic review and meta-analysis were undertaken to determine which umbilical cord abnormalities are associated with stillbirth and related adverse pregnancy outcomes. METHODS: MEDLINE, EMBASE, CINAHL and Google Scholar were searched from 1960 to present day. Reference lists of included studies and grey literature were also searched. Cohort, cross-sectional, or case-control studies of singleton pregnancies after 20 weeks' gestation that reported the frequency of umbilical cord characteristics or cord abnormalities and their relationship to stillbirth or other adverse outcomes were included. Quality of included studies was assessed using NIH quality assessment tools. Analyses were performed in STATA. RESULTS: This review included 145 studies. Nuchal cords were present in 22% of births (95% CI 19, 25); multiple loops of cord were present in 4% (95% CI 3, 5) and true knots of the cord in 1% (95% CI 0, 1) of births. There was no evidence for an association between stillbirth and any nuchal cord (OR 1.11, 95% CI 0.62, 1.98). Comparing multiple loops of nuchal cord to single loops or no loop gave an OR of 2.36 (95% CI 0.99, 5.62). We were not able to look at the effect of tight or loose nuchal loops. The likelihood of stillbirth was significantly higher with a true cord knot (OR 4.65, 95% CI 2.09, 10.37). CONCLUSIONS: True umbilical cord knots are associated with increased risk of stillbirth; the incidence of stillbirth is higher with multiple nuchal loops compared to single nuchal cords. No studies reported the combined effects of multiple umbilical cord abnormalities. Our analyses suggest specific avenues for future research.

Effects of hydroxychloroquine on the human placenta-Findings from in vitro experimental data and a systematic review.

Hydroxychloroquine (HCQ), a toll like receptor (TLR) 7 and 9 antagonist, is used during pregnancy for inflammatory conditions with limited understanding of its placental toxicology. We hypothesized that HCQ does not have toxic effects on the placenta and can modulate cytokine release in response to TLR7/9 activation. A systematic review was conducted and no studies of HCQ on multicellular human placental tissue were identified. Accordingly, placental villous explants were cultured for 7 days with HCQ +/- TLR7/9 agonists. HCQ did not affect cell turnover, nutrient transport or cytokine release but increased IL-10 (anti-inflammatory) secretion and promoted syncytiotrophoblast regeneration. Cytokine release stimulated by TLR7/9 agonists was unaffected by HCQ. In conclusion, HCQ did not adversely affect placental tissue and may have a protective anti-inflammatory function. Further research is needed to determine the mechanisms of HCQ actions on human placenta and whether they could be utilized to improve pregnancy outcomes.

The effect of Ramadan fasting during pregnancy on perinatal outcomes: a systematic review and meta-analysis.

BACKGROUND: Although exempt, many pregnant Muslim women partake in the daily fast during daylight hours during the month of Ramadan. In other contexts an impoverished diet during pregnancy impacts on birth weight. The aim of this systematic review was to determine whether Ramadan fasting by pregnant women affects perinatal outcomes. Primary outcomes investigated were perinatal mortality, preterm birth and small for gestational age (SGA) infants. Secondary outcomes investigated were stillbirth, neonatal death, maternal death, hypertensive disorders of pregnancy, gestational diabetes, congenital abnormalities, serious neonatal morbidity, birth weight, preterm birth and placental weight. METHODS: Systematic review and meta-analysis of observational studies and randomised controlled trials was conducted in EMBASE, MEDLINE, CINAHL, Web of Science, Google Scholar, the Health Management Information Consortium and Applied Social Sciences Index and Abstracts. Studies from any year were eligible. Studies reporting predefined perinatal outcomes in pregnancies exposed to Ramadan fasting were included. Cohort studies with no comparator group or that considered fasting outside pregnancy were excluded, as were studies assuming fasting practice based solely upon family name. Quality of included studies was assessed using the ROBINS-I tool for assessing risk of bias in non-randomised studies. Analyses were performed in STATA. RESULTS: From 375 records, 22 studies of 31,374 pregnancies were included, of which 18,920 pregnancies were exposed to Ramadan fasting. Birth weight was reported in 21 studies and was not affected by maternal fasting (standardised mean difference [SMD] 0.03, 95% CI 0.00 to 0.05). Placental weight was significantly lower in fasting mothers (SMD -0.94, 95% CI -0.97 to -0.90), although this observation was dominated by a single large study. No data were presented for perinatal mortality. Ramadan fasting had no effect on preterm delivery (odds ratio 0.99, 95% CI 0.72 to 1.37) based on 5600 pregnancies (1193 exposed to Ramadan fasting). CONCLUSIONS: Ramadan fasting does not adversely affect birth weight although there is insufficient evidence regarding potential effects on other perinatal outcomes. Further studies are needed to accurately determine whether Ramadan fasting is associated with adverse maternal or neonatal outcome.