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).

Personalising cardiovascular network models in pregnancy: A two-tiered parameter estimation approach.

Uterine artery Doppler waveforms are often studied to determine whether a patient is at risk of developing pathologies such as pre-eclampsia. Many uterine waveform indices have been developed, which attempt to relate characteristics of the waveform with the physiological adaptation of the maternal cardiovascular system, and are often suggested to be an indicator of increased placenta resistance and arterial stiffness. Doppler waveforms of four patients, two of whom developed pre-eclampsia, are compared with a comprehensive closed-loop model of pregnancy. The closed-loop model has been previously validated but has been extended to include an improved parameter estimation technique that utilises systolic and diastolic blood pressure, cardiac output, heart rate, and pulse wave velocity measurements to adapt model resistances, compliances, blood volume, and the mean vessel areas in the main systemic arteries. The shape of the model-predicted uterine artery velocity waveforms showed good agreement with the characteristics observed in the patient Doppler waveforms. The personalised models obtained now allow a prediction of the uterine pressure waveforms in addition to the uterine velocity. This allows for a more detailed mechanistic analysis of the waveforms, eg, wave intensity analysis, to study existing clinical indices. The findings indicate that to accurately estimate arterial stiffness, both pulse pressure and pulse wave velocities are required. In addition, the results predict that patients who developed pre-eclampsia later in pregnancy have larger vessel areas in the main systemic arteries compared with the two patients who had normal pregnancy outcomes.

Evaluating the accuracy and precision of sonographic fetal weight estimation models in extremely early-onset fetal growth restriction.

INTRODUCTION: Birthweight is a critical predictor of survival in extremely early-onset fetal growth restriction (diagnosed pre-28 weeks' gestation, with abnormal umbilical/uterine artery Doppler waveforms), therefore accurate fetal weight estimation is a crucial component of antenatal management. Currently available sonographic fetal weight estimation models were predominantly developed in populations of mixed gestational age and varying fetal weights, but not specifically tested within the context of extremely early-onset fetal growth restriction. This study aimed to determine the accuracy and precision of fetal weight estimation in this population and investigate whether model performance is affected by other factors. MATERIAL AND METHODS: Cases where a growth scan was performed within 48 hours of delivery (n = 65) were identified from a cohort of extremely early-onset fetal growth-restricted pregnancies at a single tertiary maternity center (n = 159). Fetal biometry measurements were used to calculate estimated fetal weight using 21 previously published models. Systematic and random errors were calculated for each model and used to identify the best performing model, which in turn was used to explore the relationship between error and gestation, estimated fetal weight, fetal presentation, fetal asymmetry and amniotic fluid volume. RESULTS: Both systematic (median 8.2%; range -44.1 to 49.5%) and random error (median 11.6%; range 9.7-23.8%) varied widely across models. The best performing model was Hadlock head circumference-abdominal circumference-femur length (HC-AC-FL), regardless of gestational age, fetal size, fetal presentation or asymmetry, with an overall systematic error of 1.5% and random error of 9.7%. Despite this, it only calculated the estimated fetal weight within 10% of birthweight in 64.6% of cases. There was a weak negative relation between mean percentage error with Hadlock HC-AC-FL and amniotic fluid volume, suggesting fetal weight is overestimated at lower liquor volumes and underestimated at higher liquor volumes (P = 0.002, adjusted R2  = 0.08). CONCLUSIONS: Hadlock HC-AC-FL is the most accurate model currently available to estimate fetal weight in extremely early-onset fetal growth restriction independent of gestation or fetal size, asymmetry or presentation. However, for 35.4% of cases in this study, estimated fetal weight calculated using this model deviates by more than 10% from birthweight, highlighting a need for an improved model.

A mixed-methods evaluation of continuous electronic fetal monitoring for an extended period.

INTRODUCTION: Continuous fetal monitoring is used to objectively record the fetal heart rate and fetal activity over an extended period of time; however, its feasibility and acceptability to women is currently unknown. The study addressed the hypothesis that continuous fetal monitoring is feasible and acceptable to pregnant women. MATERIAL AND METHODS: Pregnant participants (n = 22) were monitored using a continuous fetal electrocardiography device, the Monica AN24. Signal quality, duration of recording and cardiotocography findings were correlated with maternal and fetal factors. Participants' change in anxiety before and after monitoring was assessed using validated questionnaires. Participants' experiences were explored through a questionnaire (n = 20) and semi-structured interview (n = 13). RESULTS: Recordings were successfully obtained in 19 of the 22 participants (86.3%). The mean recording quality of fetal heart rate was 69.0% (range 17.4%-99.4%) and maternal heart rate was 99.0% (90.9%-100.0%). Recording quality was positively correlated with gestational age (P = 0.05) and negatively correlated with uterine activity and maternal movement (P < 0.001). Overall, participants were satisfied with their experience of continuous fetal monitoring; 30% considered it preferable to intermittent monitoring. Continuous fetal monitoring did not significantly increase maternal anxiety, with a trend towards a reduction in Pregnancy Specific Anxiety score (P = 0.07). Qualitative analysis grouped women's responses into three themes: (a) reassurance and anxiety, (b) the physical device and (c) future developments in continuous fetal monitoring. CONCLUSIONS: Continuous fetal monitoring is a feasible and acceptable form of monitoring to pregnant women although further practical improvements could be incorporated. Further research is required to assess the ability of continuous fetal monitoring to detect fetal compromise.

A simple flashcard: big impact for junior doctors!

BACKGROUND: Reducing prescribing errors is key to ensuring patient safety. Foundation-year doctors (FYs) have been found to be major contributors to prescribing errors, and often feel poorly prepared for prescribing by their undergraduate education. Numerous studies have reported these findings; however, few studies have introduced meaningful interventions. METHODS: A questionnaire was sent to FY2s (n = 20) to determine the 15 most commonly prescribed medications on call. These medications and instructions were incorporated into a flashcard that was disseminated to new FY1s at a teaching hospital in the UK. The FY1s were asked to complete a pre- and post-flashcard questionnaire, giving instructions for 10 medications and their confidence in prescribing these medications. A control group at another teaching hospital were given the same questionnaires, but not the flashcard. RESULTS: No significant difference in confidence was seen in FY1s at either hospital before the flashcard was issued. Both groups at week 4 demonstrated significant improvements in confidence in prescribing, with those who received the flashcard demonstrating a significantly higher level of confidence in a greater range of medications, compared with those who did not (p < 0.05). At week 4, 93 per cent of FY1s still used the flashcard 2.2 times per day, claiming that it saved time on call (9.2/10). DISCUSSION: We have introduced an inexpensive and simple prescribing aid, which has been statistically shown to improve prescribing confidence in FY1s. Foundation-year doctors have been found to be major contributors to prescribing errors.

Predictors of poor perinatal outcome following maternal perception of reduced fetal movements--a prospective cohort study.

BACKGROUND: Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). RFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. OBJECTIVE: To identify predictors of poor perinatal outcome after maternal perception of reduced fetal movements (RFM). DESIGN: Prospective cohort study. METHODS: 305 women presenting with RFM after 28 weeks of gestation were recruited. Demographic factors and clinical history were recorded and ultrasound performed to assess fetal biometry, liquor volume and umbilical artery Doppler. A maternal serum sample was obtained for measurement of placentally-derived or modified proteins including: alpha fetoprotein (AFP), human chorionic gonadotrophin (hCG), human placental lactogen (hPL), ischaemia-modified albumin (IMA), pregnancy associated plasma protein A (PAPP-A) and progesterone. Factors related to poor perinatal outcome were determined by logistic regression. RESULTS: 22.1% of pregnancies ended in a poor perinatal outcome after RFM. The most common complication was small-for-gestational age infants. Pregnancy outcome after maternal perception of RFM was related to amount of fetal activity while being monitored, abnormal fetal heart rate trace, diastolic blood pressure, estimated fetal weight, liquor volume, serum hCG and hPL. Following multiple logistic regression abnormal fetal heart rate trace (Odds ratio 7.08, 95% Confidence Interval 1.31-38.18), (OR) diastolic blood pressure (OR 1.04 (95% CI 1.01-1.09), estimated fetal weight centile (OR 0.95, 95% CI 0.94-0.97) and log maternal serum hPL (OR 0.13, 95% CI 0.02-0.99) were independently related to pregnancy outcome. hPL was related to placental mass. CONCLUSION: Poor perinatal outcome after maternal perception of RFM is closely related to factors which are connected to placental dysfunction. Novel tests of placental function and associated fetal response may provide improved means to detect fetuses at greatest risk of poor perinatal outcome after RFM.

Maternal perception of reduced fetal movements is associated with altered placental structure and function.

BACKGROUND: Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). DFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. To date there have been no studies of placental structure in cases of DFM. OBJECTIVE: To determine whether maternal perception of reduced fetal movements (RFM) is associated with abnormalities in placental structure and function. DESIGN: Placentas were collected from women with RFM after 28 weeks gestation if delivery occurred within 1 week. Women with normal movements served as a control group. Placentas were weighed and photographs taken. Microscopic structure was evaluated by immunohistochemical staining and image analysis. System A amino acid transporter activity was measured as a marker of placental function. Placentas from all pregnancies with RFM (irrespective of outcome) had greater area with signs of infarction (3.5% vs. 0.6%; p<0.01), a higher density of syncytial knots (p<0.001) and greater proliferation index (p<0.01). Villous vascularity (p<0.001), trophoblast area (p<0.01) and system A activity (p<0.01) were decreased in placentas from RFM compared to controls irrespective of outcome of pregnancy. CONCLUSIONS: This study provides evidence of abnormal placental morphology and function in women with RFM and supports the proposition of a causal association between placental insufficiency and RFM. This suggests that women presenting with RFM require further investigation to identify those with placental insufficiency.

A metabolomic approach identifies differences in maternal serum in third trimester pregnancies that end in poor perinatal outcome.

Metabolomics offers a powerful holistic approach to examine the metabolite composition of biofluids to identify disruptions present in disease. We used ultra performance liquid chromatography-mass spectroscopy on the maternal serum obtained in the third trimester to address the hypothesis that pregnancies ending in poor outcomes (small for gestational age infant, preterm birth, or neonatal intensive care admission, n = 40) would have a different maternal serum metabolic profiles to matched healthy pregnancies (n = 40). Ninety-eight identified metabolic features differed between normal and poor pregnancy outcomes. Classes of metabolites perturbed included free fatty acids, glycerolipids, progesterone metabolites, sterol lipids, vitamin D metabolites, and sphingolipids; these highlight potential molecular mechanisms associated with pregnancy complications in the third trimester linked by placental dysfunction. In this clinical setting, metabolomics has the potential to describe differences in fetoplacental and maternal metabolites in pregnancies with poor pregnancy outcomes compared with controls.

Identifying placental dysfunction in women with reduced fetal movements can be used to predict patients at increased risk of pregnancy complications.

Maternal perception of fetal movements has historically been used to indicate fetal wellbeing, and has been used with varying success in recent years to identify those pregnancies at increased risk of stillbirth, and other placental pathologies. We present a hypothesis that links reduced fetal movements (RFM) to fetal growth restriction (FGR) and stillbirth through placental dysfunction, and suggests the possibility that this can allow development of a reliable method to identify those women experiencing RFM who are at increased risk of adverse outcome. Reduced fetal movement is thought to represent fetal compensation in a chronic hypoxic environment due to inadequacies in the placental supply of oxygen and nutrients. Placental analysis in FGR and in stillbirth has revealed a number of structural abnormalities and an imbalance in cell turnover, and in terms of function, FGR is also associated with reduced nutrient transport. Both FGR and stillbirth are linked to changes in maternal levels of placental hormones. However, no such studies have been performed in samples from pregnancies affected by RFM. Currently, there are no formal guidelines to direct the management of such women, although it is recommended they undergo measurement of symphysis-fundal height and cardiotocography, and possibly Doppler ultrasound and biophysical profiling. Novel tests could involve the measurement of placental-derived hormones in maternal serum. To address this hypothesis, macroscopic and microscopic analysis of placental samples from both normal pregnancies and those affected by RFM is needed to detect any changes in structure. Placental function could be evaluated by levels of placental hormones in maternal blood. If placental dysfunction can be linked to RFM, and a robust method of identifying those women with placental insufficiency can be developed; screening patients with RFM could lead to a reduction in perinatal morbidity and mortality.