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BACKGROUND: Fetal two-dimensional speckle tracking echocardiography (2D-STE) is an emerging technique for assessing fetal cardiac function by measuring global longitudinal strain. Alterations in global longitudinal strain may serve as early indicator of pregnancy complications, making 2D-STE a potentially valuable tool for early detection. Early detection can facilitate timely interventions to reduce fetal and maternal morbidity and mortality. Therefore, the aim of this study was to investigate the feasibility of performing 2D-STE at 16 weeks gestational age.METHODS: This pilot study utilized 50 ultrasound clips of the fetal four-chamber view recorded between 15+5 and 16+2 weeks gestational age from a prospective cohort study. A strict protocol assessed three parameters essential for 2D-STE analysis: fetal four-chamber view ultrasound clip quality, region of interest, and frame rates. Two independent researchers measured global longitudinal strain in all adequate fetal four-chamber view ultrasound clips to determine inter- and intra-operator reliability.RESULTS: Out of the 50 ultrasound clips, 37 (74%) were feasible for 2D-STE analysis. The inter-operator reliability for global longitudinal strain measurements of the left and right ventricles was moderate (ICC of 0.64 and 0.74, respectively), while the intra-operator reliability was good (ICC of 0.76 and 0.79, respectively).CONCLUSIONS: Our findings demonstrate that fetal 2D-STE analysis at 16 weeks gestational age is feasible when adhering to a strict protocol. However, further improvements are necessary to enhance the inter- and intra-operator reliability of 2D-STE at this gestational age.

Introduction:Twin pregnancies have a high risk of extreme preterm birth (PTB) at less than 28 weeks of gestation, which is associated with increased risk of neonatal morbidity and mortality. Currently there is a lack of effective treatments for women with a twin pregnancy and a short cervix or cervical dilatation. A possible effective surgical method to reduce extreme PTB in twin pregnancies with an asymptomatic short cervix or dilatation at midpregnancy is the placement of a vaginal cerclage. Methods and analysis: We designed two multicentre randomised trials involving eight hospitals in the Netherlands (sites in other countries may be added at a later date). Women older than 16 years with a twin pregnancy at <24 weeks of gestation and an asymptomatic short cervix of ≤25 mm or cervical dilatation will be randomly allocated (1:1) to both trials on vaginal cerclage and standard treatment according to the current Dutch Society of Obstetrics and Gynaecology guideline (no cerclage). Permuted blocks sized 2 and 4 will be used to minimise the risk of disbalance. The primary outcome measure is PTB of <28 weeks. Analyses will be by intention to treat. The first trial is to demonstrate a risk reduction from 25% to 10% in the short cervix group, for which 194 patients need to be recruited. The second trial is to demonstrate a risk reduction from 80% to 35% in the dilatation group and will recruit 44 women. A cost-effectiveness analysis will be performed from a societal perspective. Ethics and dissemination: This study has been approved by the Research Ethics Committees in the Netherlands on 3/30/2023. Participants will be required to sign an informed consent form. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results.

OBJECTIVE: To assess whether artificial intelligence, inspired by clinical decision-making procedures in delivery rooms, can correctly interpret cardiotocographic tracings and distinguish between normal and pathological events.STUDY DESIGN: A method based on artificial intelligence was developed to determine whether a cardiotocogram shows a normal response of the fetal heart rate to uterine activity (UA). For a given fetus and given the UA and previous FHR, the method predicts a fetal heart rate response, under the assumption that the fetus is still in good condition and based on how that specific fetus has responded so far. We hypothesize that this method, when having only learned from fetuses born in good condition, is incapable of predicting the response of a compromised fetus or an episode of transient fetal distress. The (in)capability of the method to predict the fetal heart rate response would then yield a method that can help to assess fetal condition when the obstetrician is in doubt. Cardiotocographic data of 678 deliveries during labor were selected based on a healthy outcome just after birth. The method was trained on the cardiotocographic data of 548 fetuses of this group to learn their heart rate response. Subsequently it was evaluated on 87 fetuses, by assessing whether the method was able to predict their heart rate responses. The remaining 43 cardiotocograms were segment-by-segment annotated by three experienced gynecologists, indicating normal, suspicious, and pathological segments, while having access to the full recording and neonatal outcome. This future knowledge makes the expert annotations of a quality that is unachievable during live interpretation.RESULTS: The comparison between abnormalities detected by the method (only using past and present input) and the annotated CTG segments by gynecologists (also looking at future input) yields an area under the curve of 0.96 for the distinction between normal and pathological events

To improve care for extremely premature infants, the development of an extrauterine environment for newborn development is being researched, known as Artificial Placenta and Artificial Womb (APAW) technology. APAW facilitates extended development in a liquid-filled incubator with oxygen and nutrient supply through an oxygenator connected to the umbilical vessels. This setup is intended to provide the optimal environment for further development, allowing further lung maturation by delaying gas exposure to oxygen. This innovative treatment necessitates interventions in obstetric procedures to transfer an infant from the native to an artificial womb, while preventing fetal-to-neonatal transition. In this narrative review we analyze relevant fetal physiology literature, provide an overview of insights from APAW studies, and identify considerations for the obstetric procedure from the native uterus to an APAW system. Lastly, this review provides suggestions to improve sterility, fetal and maternal well-being, and the prevention of neonatal transition.

Background: Owing to the association between dysfunctional maternal autonomic regulation and pregnancy complications, assessing non-invasive features reflecting autonomic activity-e.g., heart rate variability (HRV) and the morphology of the photoplethysmography (PPG) pulse wave-may aid in tracking maternal health. However, women with early pregnancy complications typically receive medication, such as corticosteroids, and the effect of corticosteroids on maternal HRV and PPG pulse wave morphology is not well-researched. Methods: We performed a prospective, observational study assessing the effect of betamethasone (a commonly used corticosteroid) on non-invasively assessed features of autonomic regulation. Sixty-one women with an indication for betamethasone were enrolled and wore a wrist-worn PPG device for at least four days, from which five-minute measurements were selected for analysis. A baseline measurement was selected either before betamethasone administration or sufficiently thereafter (i.e., three days after the last injection). Furthermore, measurements were selected 24, 48, and 72 h after betamethasone administration. HRV features in the time domain and frequency domain and describing heart rate (HR) complexity were calculated, along with PPG morphology features. These features were compared between the different days. Results: Maternal HR was significantly higher and HRV features linked to parasympathetic activity were significantly lower 24 h after betamethasone administration. Features linked to sympathetic activity remained stable. Furthermore, based on the PPG morphology features, betamethasone appears to have a vasoconstrictive effect. Conclusions: Our results suggest that administering betamethasone affects maternal autonomic regulation and cardiovasculature. Researchers assessing maternal HRV in complicated pregnancies should schedule measurements before or sufficiently after corticosteroid administration.

Pregnancy complications are associated with abnormal maternal autonomic regulation. Subsequently, thoroughly understanding maternal autonomic regulation during healthy pregnancy may enable the earlier detection of complications, in turn allowing for the improved management thereof. Under healthy autonomic regulation, reciprocal interactions occur between the cardiac and respiratory systems, i.e., cardiorespiratory coupling (CRC). Here, we investigate, for the first time, the differences in CRC between healthy pregnant and nonpregnant women. We apply two algorithms, namely, synchrograms and bivariate phase-rectified signal averaging, to nighttime recordings of ECG and respiratory signals. We find that CRC is present in both groups. Significantly less ( P < 0.01) cardiorespiratory synchronization occurs in pregnant women (11% vs. 15% in nonpregnant women). Moreover, there is a smaller response in the heart rate of pregnant women corresponding to respiratory inhalations and exhalations. In addition, we stratified these analyses by sleep stages. As each sleep stage is governed by different autonomic states, this stratification not only amplified some of the differences between groups but also brought out differences that remained hidden when analyzing the full-night recordings. Most notably, the known positive relationship between CRC and deep sleep is less prominent in pregnant women than in their nonpregnant counterparts. The decrease in CRC during healthy pregnancy may be attributable to decreased maternal parasympathetic activity, anatomical changes to the maternal respiratory system, and the increased physiological stress accompanying pregnancy. This work offers novel insight into the physiology of healthy pregnancy and forms part of the base knowledge needed to detect abnormalities in pregnancy. NEW & NOTEWORTHY We compare CRC, i.e., the reciprocal interaction between the cardiac and respiratory systems, between healthy pregnant and nonpregnant women for

OBJECTIVES: Two-dimensional speckle tracking echocardiography has been considered an angle-independent modality. However, current literature is limited and inconclusive on the actual impact of angle of insonation on strain values. Therefore, the primary objective of this study was to assess the impact of angles of insonation on the estimation of fetal left ventricular and right ventricular global longitudinal strain. Secondarily, the impact of different definitions for angles of insonation was investigated in a sensitivity analysis.METHODS: This is a retrospective analysis of a prospective longitudinal cohort study with 124 healthy subjects. The analyses were based on the four-chamber view ultrasound clips taken between 18+0 and 21+6 weeks of gestation. Angles of insonation were categorized into three groups: up/down, oblique and perpendicular. The mean fetal left and right ventricular and global longitudinal strain values corresponding to these three groups were compared by an ANOVA test corrected for heteroscedasticity.RESULTS: Fetal left and right ventricular global longitudinal strain values were not statistically different between the three angles of insonation (p-value >0.062 and >0.149, respectively). When applying another definition for angles of insonation in the sensitivity analysis, the mean left ventricular global longitudinal strain value was significantly decreased for the oblique compared to the up/down angle of insonation (p-value 0.041).CONCLUSIONS: There is no evidence of a difference in fetal left and right ventricular global longitudinal strain between the different angles of insonation in fetal two-dimensional speckle tracking echocardiography.

BACKGROUND: Researchers have long suspected a mutual interaction between maternal and fetal heart rhythms, referred to as maternal-fetal cardiac coupling (MFCC). While several studies have been published on this phenomenon, they vary in terms of methodologies, populations assessed, and definitions of coupling. Moreover, a clear discussion of the potential clinical implications is often lacking. Subsequently, we perform a scoping review to map the current state of the research in this field and, by doing so, form a foundation for future clinically oriented research on this topic.METHODS: A literature search was performed in PubMed, Embase, and Cochrane. Filters were only set for language (English, Dutch, and German literature were included) and not for year of publication. After screening for the title and the abstract, a full-text evaluation of eligibility followed. All studies on MFCC were included which described coupling between heart rate measurements in both the mother and fetus, regardless of the coupling method used, gestational age, or the maternal or fetal health condition.RESULTS: 23 studies remained after a systematic evaluation of 6,672 studies. Of these, 21 studies found at least occasional instances of MFCC. Methods used to capture MFCC are synchrograms and corresponding phase coherence indices, cross-correlation, joint symbolic dynamics, transfer entropy, bivariate phase rectified signal averaging, and deep coherence. Physiological pathways regulating MFCC are suggested to exist either via the autonomic nervous system or due to the vibroacoustic effect, though neither of these suggested pathways has been verified. The strength and direction of MFCC are found to change with gestational age and with the rate of maternal breathing, while also being further altered in fetuses with cardiac abnormalities and during labor.CONCLUSION: From the synthesis of the available literature on MFCC presented in this scoping review, it seems evid

INTRODUCTION: Fetal electrocardiography (NI-fECG) and electrohysterography (EHG) have been proven more accurate and reliable than conventional non-invasive methods (doppler ultrasound and tocodynamometry) and are less affected by maternal obesity. It is still unknown whether NI-fECG and EHG will eliminate the need for invasive methods, such as the intrauterine pressure catheter and fetal scalp electrode. We studied whether NI-fECG and EHG can be successfully used during labor.MATERIAL AND METHODS: A prospective clinical pilot study was performed in a tertiary care teaching hospital. A total of 50 women were included with a singleton pregnancy with a gestational age between 36 +0 and 42 +0 weeks and had an indication for continuous intrapartum monitoring. The primary study outcome was the percentage of women with NI-fECG and EHG monitoring throughout the whole delivery. Secondary study outcomes were reason and timing of a switch to conventional monitoring methods (i.e., tocodynamometry and fetal scalp electrode or doppler ultrasound), repositioning of the abdominal electrode patch, success rates (i.e., the percentage of time with signal output), and obstetric and neonatal outcomes. CLINICAL TRIAL REGISTRATION: Dutch trial register (NL8024).RESULTS: In 45 women (90%), NI-fECG and EHG monitoring was used throughout the whole delivery. In the other five women (10%), there was a switch to conventional methods: in two women because of insufficient registration quality of uterine contractions and in three women because of insufficient registration quality of the fetal heart rate. In three out of five cases, the switch was after full dilation was reached. Repositioning of the abdominal electrode patch occurred in two women. The overall success rate was 94.5%. In 16% (n = 8) of women, a cesarean delivery was performed due to non-progressing dilation (n = 7) and due to suspicion of fetal distress (n = 1). Neonatal metabolic acidosis did not occur. Two

INTRODUCTION: This study aims to investigate non-invasive electrocardiography as a method for the detection of congenital heart disease (CHD) with the help of artificial intelligence.MATERIAL AND METHODS: An artificial neural network was trained for the identification of CHD using non-invasively obtained fetal electrocardiograms. With the help of a Bayesian updating rule, multiple electrocardiographs were used to increase the algorithm's performance.RESULTS: Using 122 measurements containing 65 healthy and 57 CHD cases, the accuracy, sensitivity, and specificity were found to be 71%, 63%, and 77%, respectively. The sensitivity was however 75% and 69% for CHD cases requiring an intervention in the neonatal period and first year of life, respectively. Furthermore, a positive effect of measurement length on the detection performance was observed, reaching optimal performance when using 14 electrocardiography segments (37.5 min) or more. A small negative trend between gestational age and accuracy was found.CONCLUSIONS: The proposed method combining recent advances in obtaining non-invasive fetal electrocardiography with artificial intelligence for the automatic detection of CHD achieved a detection rate of 63% for all CHD and 75% for critical CHD. This feasibility study shows that detection rates of CHD might improve by using electrocardiography-based screening complementary to the standard ultrasound-based screening. More research is required to improve performance and determine the benefits to clinical practice.

While the effect of antenatally administered corticosteroids on fetal heart rate (HR) and heart rate variability (HRV) is well established, little information is available on how these drugs affect maternal physiology. In this secondary analysis of a prospective, observational cohort study, we quantify how corticosteroids affect maternal HR and HRV, which serve as a proxy measure for autonomic regulation. Abdominal ECG measurements were recorded before and in the five days following the administration of betamethasone-a corticosteroid commonly used for fetal maturation-in 46 women with singleton pregnancies. Maternal HR and HRV were determined from these recordings and compared between these days. HRV was assessed with time- and frequency-domain features, as well as non-linear and complexity features. In the 24 h after betamethasone administration, maternal HR was significantly increased (p < 0.01) by approximately 10 beats per minute, while HRV features linked to parasympathetic activity and HR complexity were significantly decreased (p < 0.01 and p < 0.001, respectively). Within four days after the initial administration of betamethasone, HR decreases and HRV features increase again, indicating a diminishing effect of betamethasone a few days after administration. We conclude that betamethasone administration results in changes in maternal HR and HRV, despite the heterogeneity of the studied population. Therefore, its recent administration should be considered when evaluating these cardiovascular metrics.

Changes in the maternal autonomic nervous system are essential in facilitating the physiological changes that pregnancy necessitates. Insufficient autonomic adaptation is linked to complications such as hypertensive diseases of pregnancy. Consequently, tracking autonomic modulation during progressing pregnancy could allow for the early detection of emerging deteriorations in maternal health. Autonomic modulation can be longitudinally and unobtrusively monitored by assessing heart rate variability (HRV). Yet, changes in maternal HRV (mHRV) throughout pregnancy remain poorly understood. In previous studies, mHRV is typically assessed only once per trimester with standard HRV features. However, since gestational changes are complex and dynamic, assessing mHRV comprehensively and more frequently may better showcase the changing autonomic modulation over pregnancy. Subsequently, we longitudinally (median sessions = 8) assess mHRV in 29 healthy pregnancies with features that assess sympathetic and parasympathetic activity, as well as heart rate (HR) complexity, HR responsiveness and HR fragmentation. We find that vagal activity, HR complexity, HR responsiveness, and HR fragmentation significantly decrease. Their associated effect sizes are small, suggesting that the increasing demands of advancing gestation are well tolerated. Furthermore, we find a notable change in autonomic activity during the transition from the second to third trimester, highlighting the dynamic nature of changes in pregnancy. Lastly, while we saw the expected rise in mean HR with gestational age, we also observed increased autonomic deceleration activity, seemingly to counter this rising mean HR. These results are an important step towards gaining insights into gestational physiology as well as tracking maternal health via mHRV.

Cerclages can be used to prevent preterm birth, although their effectiveness and safety is disputed. We aimed to describe obstetric outcomes after cerclage procedures. We included 156 singleton pregnancies and six multiple pregnancies. In singleton pregnancies with history-indicated, short cervix-indicated and emergency cerclages, respectively 84.6, 76.5 and 43.8% resulted in late preterm or term deliveries. In singletons, the following complications were reported: excessive bleeding in one emergency cerclage procedure and three re-cerclage procedures in the history-indicated cerclage group. No perioperative rupture of membranes occurred in singletons. When comparing results of experienced and less-experienced gynaecologists, a remarkably smaller take home child rate was observed for singletons treated by less-experienced gynaecologists: 90.7% and 94.4% for the two experienced gynaecologist as compared to 85.0% for the group of less-experienced gynaecologists. In conclusion, cerclages in singletons result in few cerclage-associated complications and a high take home child rate, when performed by experienced gynaecologists. Impact statementWhat is already known on this subject? Prematurity is the leading cause of perinatal and neonatal mortality and morbidity worldwide. Cervical cerclages can be used to prevent preterm birth, although their effectiveness and safety is disputed.What the results of this study add? In our cohort study, singleton pregnancies with cerclages seem to have satisfactory obstetric outcomes. We found a very low prevalence of cerclage-associated complications in singleton pregnancies, for both history-indicated, short cervix-indicated and emergency cerclages. Additionally, take home child rates in singleton pregnancies were remarkably higher when cerclage procedures were performed by experienced gynaecologists, compared to less experienced gynaecologists.What the implications are of these findings for clinical practice and/or further research

Objective: To determine the prevalence of depression, anxiety, and posttraumatic stress disorder (PTSD) years after hyperemesis gravidarum (HG) and its association with HG severity. Material and methods: This prospective cohort study consisted of a follow-up of 215 women admitted for HG, who were eligible to participate in a randomized controlled trial and either declined or agreed to be randomized between 2013 and 2016 in 19 hospitals in the Netherlands. Participants completed the Hospital Anxiety and Depression Scale (HADS) six weeks postpartum and during follow-up and the PTSD checklist for DSM-5 (PCL-5) during follow-up. An anxiety or depression score ≥8 is indicative of an anxiety or depression disorder and a PCL-5 ≥ 31 indicative of PTSD. Measures of HG severity were symptom severity (PUQE-24: Pregnancy Unique Quantification of Emesis), weight change, duration of admissions, readmissions, and admissions after the first trimester. Results: About 54/215 participants completed the HADS six weeks postpartum and 73/215 participants completed the follow-up questionnaire, on average 4.5 years later. Six weeks postpartum, 13 participants (24.1%) had an anxiety score ≥8 and 11 participants (20.4%) a depression score ≥8. During follow-up, 29 participants (39.7%) had an anxiety score ≥8, 20 participants (27.4%) a depression score ≥8, and 16 participants (21.9%) a PCL-5 ≥ 31. Multivariable logistic regression analysis showed that for every additional point of the mean PUQE-24 three weeks after inclusion, the likelihood of having an anxiety score ≥8 and PCL-5 ≥ 31 at follow-up increased with OR 1.41 (95% CI: 1.10;1.79) and OR 1.49 (95% CI: 1.06;2.10) respectively. Conclusion: Depression, anxiety, and PTSD symptoms are common years after HG occurred.

BACKGROUND: The value of ST analysis of the fetal electrocardiogram during labor to lower asphyxia and cesarean section rates is uncertain. Physiological variation of the electrical heart axis between fetuses may explain false alarms in conventional ST analysis (absolute ST analysis). ST events (alarms) based on relative T/QRS rises (relative ST analysis) correct for this variation and may improve diagnostic accuracy of ST analysis.AIMS: To compare the diagnostic accuracy of absolute and relative ST analysis with regard to fetal acidemia.STUDY DESIGN: Retrospective case-control study.SUBJECTS: 20 healthy women with an uncomplicated pregnancy monitored with ST analysis during labor: 10 cases (umbilical cord artery pH < 7.05) and 10 controls (pH > 7.20).OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratio.RESULTS: In 16 of the 20 patients a total of 54 absolute ST events were reported. Two reviewers classified the cardiotocograms; in cases 29% of the absolute ST events were significant, in the controls it was 19%. Relative ST analysis versus absolute ST analysis showed a sensitivity of 90% (55-100%) vs. 70% (35-93%), a specificity of 100% (69-100%) vs. 70% (35-93%), a positive likelihood ratio of infinity vs. 2.3 (0.8-6.5), a negative likelihood ratio of 0.1 (0.0-0.6) vs. 0.4 (0.2-1.2), and diagnostic odds ratio of infinity vs. 5.4 (0.8-36.9). McNemar showed no statistical significant difference between the sensitivity and specificity of the methods.CONCLUSIONS: We observed higher positive and lower negative likelihood ratios for relative ST analysis in comparison to absolute ST analysis. In this small study we found no statistical difference. Relative ST analysis should be studied in a larger study.

INTRODUCTION: A fetal anomaly scan in mid-pregnancy is performed, to check for the presence of congenital anomalies, including congenital heart disease (CHD). Unfortunately, 40% of CHD is still missed. The combined use of ultrasound and electrocardiography might boost detection rates. The electrical heart axis is one of the characteristics which can be deduced from an electrocardiogram (ECG). The aim of this study was to determine reference values for the electrical heart axis in healthy fetuses around 20 weeks of gestation.MATERIAL AND METHODS: Non-invasive fetal electrocardiography was performed subsequent to the fetal anomaly scan in pregnant women carrying a healthy singleton fetus between 18 and 24 weeks of gestation. Eight adhesive electrodes were applied on the maternal abdomen including one ground and one reference electrode, yielding six channels of bipolar electrophysiological measurements. After removal of interferences, a fetal vectorcardiogram was calculated and then corrected for fetal orientation. The orientation of the electrical heart axis was determined from this normalized fetal vectorcardiogram. Descriptive statistics were used on normalized cartesian coordinates to determine the average electrical heart axis in the frontal plane. Furthermore, 90% prediction intervals (PI) for abnormality were calculated.RESULTS: Of the 328 fetal ECGs performed, 281 were included in the analysis. The average electrical heart axis in the frontal plane was determined at 122.7° (90% PI: -25.6°; 270.9°).DISCUSSION: The average electrical heart axis of healthy fetuses around mid-gestation is oriented to the right, which is, due to the unique fetal circulation, in line with muscle distribution in the fetal heart.

In this paper we present an initial roadmap for the ethical development and eventual implementation of artificial amniotic sac and placenta technology in clinical practice. We consider four elements of attention: (1) framing and societal dialogue; (2) value sensitive design, (3) research ethics and (4) ethical and legal research resulting in the development of an adequate moral and legal framework. Attention to all elements is a necessary requirement for ethically responsible development of this technology. The first element concerns the importance of framing and societal dialogue. This should involve all relevant stakeholders as well as the general public. We also identify the need to consider carefully the use of terminology and how this influences the understanding of the technology. Second, we elaborate on value sensitive design: the technology should be designed based upon the principles and values that emerge in the first step: societal dialogue. Third, research ethics deserves attention: for proceeding with first-in-human research with the technology, the process of recruiting and counseling eventual study participants and assuring their informed consent deserves careful attention. Fourth, ethical and legal research should concern the status of the subject in the AAPT. An eventual robust moral and legal framework for developing and implementing the technology in a research setting should combine all previous elements. With this roadmap, we emphasize the importance of stakeholder engagement throughout the process of developing and implementing the technology; this will contribute to ethically and responsibly innovating health care.

Objective: The aim of this study was to study whether STE is a suitable method to detect differences in cardiac function in pregnant women with HPD compared with normotensive pregnant women or between women with a history of a pregnancy complicated by HPD compared with women with a history of an uncomplicated pregnancy. Evidence acquisition: The databases Medline, EMBASE, and Central were systematically searched for studies comparing cardiac function measured with STE in pregnant women with HPD or women with a history of HPD and women with a history of normotensive pregnancies. Results: The search identified 16 studies, including 870 women with a history of HPD and 693 normotensive controls. Most studies during pregnancy (n = 12/13) found a decreased LV-GLS (left ventricular global longitudinal strain) in HPD compared with normotensive pregnant controls. LV-GRS (left ventricular global radial strain) and LV-GLCS (left ventricular global circumferential strain) are decreased in women with early-onset and severe preeclampsia. Women with a history of early-onset preeclampsia show lasting myocardial changes, with significantly decreased LV-GLS, LV-GLCS, and LV-GRS. Conclusions and relevance: LV-GLS is significantly decreased in pregnant women with HPD compared with normotensive pregnant women. Other deformation values show a significant decrease in women with severe or early-onset preeclampsia, with lasting myocardial changes after early-onset preeclampsia.

Fetal well-being is commonly assessed by monitoring the fetal heart rate (fHR). In clinical practice, the de facto standard technology for fHR monitoring is based on the Doppler ultrasound (US). Continuous monitoring of the fHR before and during labor is performed using a US transducer fixed on the maternal abdomen. The continuous fHR monitoring, together with simultaneous monitoring of the uterine activity, is referred to as cardiotocography (CTG). In contrast, for intermittent measurements of the fHR, a handheld Doppler US transducer is typically used. In this article, the technology of Doppler US for continuous fHR monitoring and intermittent fHR measurements is described, with emphasis on fHR monitoring for CTG. Special attention is dedicated to the measurement environment, which includes the clinical setting in which fHR monitoring is commonly performed. In addition, to understand the signal content of acquired Doppler US signals, the anatomy and physiology of the fetal heart and the surrounding maternal abdomen are described. The challenges encountered in these measurements have led to different technological strategies, which are presented and critically discussed, with a focus on the US transducer geometry, Doppler signal processing, and fHR extraction methods.

Importance: The introduction of the cardiotocogram (CTG) during labor has not been found to improve neonatal outcome. The search for a more reliable, less invasive, and patient-friendly technique is ongoing. The noninvasive fetal electrocardiogram (NI-fECG) has been proposed as one such alternative.Objectives: The aim of this study was to review the literature on the performance of NI-fECG for fetal monitoring during labor. Following the PRISMA guidelines, a systematic search in MEDLINE, EMBASE, and Cochrane Library was performed. Studies involving original research investigating the performance of NI-fECG during labor were included. Animal studies and articles in languages other than English, Dutch, or German were excluded. The QUADAS-2 checklist was used for quality assessment. A descriptive analysis of the results is provided.Results: Eight articles were included. Pooled analysis of the results of the separate studies was not possible due to heterogeneity. All studies demonstrate that it is possible to apply NI-fECG during labor. Compared with Doppler ultrasound, NI-fECG performs equal or better in most studies.Conclusions and Relevance: NI-fECG for fetal monitoring is a promising noninvasive and patient-friendly technique that provides accurate information. Future studies should focus on signal quality throughout labor, with the aim to further optimize technical development of NI-fECG.

Background: Myocardial deformation imaging offers the potential to measure myocardial function. Remodelling, the change in size, shape and function, appears as a result of pressure or volume changes and is thought to be the first sign of fetal adaptation to placental dysfunction. Deformation can be measured using speckle tracking echocardiography (STE). STE in the fetus might be useful for detection and follow up of the fetus endangered by placental dysfunction. Reference values for fetal myocardial deformation during gestation have not been comprehensively described and need further investigation before STE can be introduced in daily clinical practice. The aim of this study is to determine reference values for fetal myocardial deformation throughout gestation in uncomplicated pregnancies. Methods: A longitudinal cohort will be performed. 150 Women, pregnant from a non-anomalous singleton, will be included from 19 to 21 + 6 weeks gestational age. Thereafter, fetal heart ultrasounds will be performed 4 weekly, until 41 weeks gestational age or delivery. Ultrasound data will be analysed using STE software to determine reference values for fetal cardiac deformation during gestation. Discussion: Measuring cardiac deformation changes in pregnancy can be a promising tool to detect preclinical cardiac adaptation to placental dysfunction. However, previous studies used different ultrasound scans and STE software resulting in incomparable and contradictory results on deformation values. In this prospective study reference values during pregnancy, cardiac deformation values will be assessed with the same ultrasound and software package in 150 uncomplicated pregnancies.

Background Fetal monitoring based on electrocardiographic (ECG) morphology is obtained from a single unipolar fetal scalp electrode. Ideally, it should be obtained from multiple leads, as ECG waveform depends on alignment between electrode and electrical heart axis. This alignment is unknown in fetuses. Besides, fetuses are surrounded by conductive media, which may influence ECG waveform. We explored the influence of electrode position and head orientation on ECG waveforms of unipolar and bipolar scalp ECGs recorded in air and in conductive medium. Methods We recorded ECGs in one adult subject at five different scalp positions in five different head orientations both in dry and immersed conditions. The ratio between T-amplitude and QRS-amplitude (T/QRS ratio) of unipolar and bipolar scalp ECGs was determined and compared between all conditions. Results In the dry condition, we observed in the unipolar leads little to no difference between different electrode positions (maximal T/QRS difference 0.00–0.01) and minor differences between head orientations (0.02–0.03), whereas bipolar leads showed no recognizable ECG signal at all. During the immersed condition, we found variation in the unipolar leads, both between electrode positions (maximal T/QRS difference 0.02–0.05) and between head orientations (0.03–0.06). Bipolar leads showed different ECG signals in contrasting head orientations. Conclusions Both unipolar and bipolar scalp lead-derived ECG waveforms are influenced by electrode position and head orientation when the subject is submerged in a conductive medium. Fetal monitoring based on single scalp lead ECG waveform might be suboptimal, as it lacks correction for fetal head orientation and electrode position.

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics

The conclusion of our recent paper that performance of the STAN device in clinical practice is potentially limited by high false-negative and high false-positive STAN-event rates and loss of ST waveform assessment capacity during severe hypoxemia, evoked comments by Kjellmer, Lindecrantz and Rosén. These comments can be summarized as follows: 1) STAN analysis is based on a unipolar lead but the authors used a negative aVF lead, and they did not validate this methodology; 2) The fetuses used in the study were too young to display the signals that the authors were trying to detect. In response to these comments we now provide both a theoretical and an experimental underpinning of our approach. In an in vivo experiment in human we placed several electrodes over the head (simulating different places of a scalp electrode), simultaneously recorded Einthoven lead I and II, and constructed -aVF from these two frontal leads. Irrespective of scalp electrode placement, the correlation between any of unipolar scalp electrode-derived signals and constructed-aVF was excellent (≥ 0.92). In response to the second comment we refer to a study which demonstrated that umbilical cord occlusion resulted in rapid increase in T/QRS ratio that coincided with initial hypertension and bradycardia at all gestational ages which were tested from 0.6-0.8 gestation. The animals of our study were in this gestational range and, hence, our experimental setup can be used to assess STAN's quality to detect fetal hypoxia. In conclusion, we have clearly demonstrated the appropriateness of using-aVF as a proxy for a scalp electrode-derived signal in STAN in these preterm lambs. Investigation why STAN could not detect relevant ST-changes and instead produced erroneous alarms in our experimental setup is hampered by the fact that the exact STAN algorithm (signal processing and analysis) is not in the public domain.

INTRODUCTION: The additional value of ST analysis during labour is uncertain. In ST analysis, a T/QRS baseline value is calculated from the fetal electrocardiogram and successive T/QRS ratios are compared to this baseline. However, variation in the orientation of the electrical heart axis between fetuses may yield different T/QRS baseline values. In case of a higher T/QRS baseline value more ST events are encountered, although not always related to perinatal outcome. We hypothesised that we can partly correct for this effect by analysing T/QRS rises as a percentage from baseline (relative ST analysis). This study aimed to explore whether relative ST analysis has better diagnostic value for cord acidaemia compared to conventional ST analysis, where predefined fixed T/QRS ratios are used.METHODS AND MATERIALS: A case-control study was performed in 20 term human fetuses during labour; 10 cases (umbilical cord artery pH <7.05 at birth, defining acidaemia) and 10 controls (pH >7.20) were included. The fetal electrocardiogram was recorded using a STAN monitor. We electronically extracted all T/QRS values, baseline and episodic ST events from the STAN monitor and calculated the relative T/QRS changes. The cut-off for relative ST events was determined in a receiver operator characteristic (ROC) curve at optimal specificity for cord acidaemia. Parameters of interest were area under the curve (AUC) of the ROC curve for relative ST events and test performance of both conventional and relative ST analysis.RESULTS: Relative ST analysis showed an AUC of 0.99. The optimal cut-off value for relative T/QRS rise was determined at 0.70. Relative vs conventional (absolute) ST analysis showed a specificity of 100% vs 40% (p = 0.031); sensitivity 90% vs 90%; positive likelihood ratio infinity vs 1.5; negative likelihood ratio 0.10 vs 0.25, respectively.CONCLUSION: Relative ST analysis seems to be a promising method to detect impending fetal acidaemia during

Fetal heart rate (fHR) monitoring using Doppler Ultrasound (US) is a standard method to assess fetal health before and during labor. Typically, an US transducer is positioned on the maternal abdomen and directed towards the fetal heart. Due to fetal movement or displacement of the transducer, the relative fetal heart location (fHL) with respect to the US transducer can change, leading to frequent periods of signal loss. Consequently, frequent repositioning of the US transducer is required, which is a cumbersome task affecting clinical workflow. In this research, a new flexible US transducer array is proposed which allows for measuring the fHR independently of the fHL. In addition, a method for dynamic adaptation of the transmission power of this array is introduced with the aim of reducing the total acoustic dose transmitted to the fetus and the associated power consumption, which is an important requirement for application in an ambulatory setting. The method is evaluated using an in-vitro setup of a beating chicken heart. We demonstrate that the signal quality of the Doppler signal acquired with the proposed method is comparable to that of a standard, clinical US transducer. At the same time, our transducer array is able to measure the fHR for varying fHL while only using 50% of the total transmission power of standard, clinical US transducers.

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics

Introduction The inconclusive clinical results for ST-waveform analysis (STAN) in detecting fetal hypoxemia may be caused by the signal processing of the STAN-device itself. We assessed the performance of a clinical STAN device in signal processing and in detecting hypoxemia in a fetal sheep model exposed to prolonged umbilical cord occlusion (UCO). Methods Eight fetal lambs were exposed to 25 minutes of UCO. ECG recordings were analyzed during a baseline period and during UCO. STAN-event rates and timing of episodic T/QRS rise, baseline T/QRS rise and the occurrence of biphasic ST-waveforms, as well as signal loss, were assessed. Results During baseline conditions of normoxemia, a median of 40 (IQR, 25–70) STAN-events per minute were detected, compared to 10 (IQR, 2–22) during UCO. During UCO STAN-events were detected in five subjects within 10 minutes and in six subjects after 18 minutes, respectively. Two subjects did not generate any STAN-event during UCO. Biphasic ST event rate was reduced during UCO (median 0, IQR 0–5), compared to baseline (median 32, IQR, 6–55). ST-waveforms could not be assessed in 62% of the recording time during UCO, despite a good quality of the ECG signal. Conclusions The STAN device showed limitations in detecting hypoxemia in fetal sheep after prolonged UCO. The STAN device produced high false positive event rates during baseline and did not detect T/QRS changes adequately after prolonged fetal hypoxemia. During 14% of baseline and 62% of the UCO period, the STAN-device could not process the ECG signal, despite its good quality. Resolving these issues may improve the clinical performance of the STAN device.

Background: Betamethasone is widely used to enhance fetal lung maturation in case of threatened preterm labour. Fetal heart rate variability is one of the most important parameters to assess in fetal monitoring, since it is a reliable indicator for fetal distress. Aim: To describe the effect of betamethasone on fetal heart rate variability, by applying spectral analysis on non-invasive fetal electrocardiogram recordings. Study design: Prospective cohort study. Subjects: Patients that require betamethasone, with a gestational age from 24 weeks onwards. Outcome measures: Fetal heart rate variability parameters on day 1, 2, and 3 after betamethasone administration are compared to a reference measurement. Results: Following 68 inclusions, 12 patients remained with complete series of measurements and sufficient data quality. During day 1, an increase in absolute fetal heart rate variability values was seen. During day 2, a decrease in these values was seen. All trends indicate to return to pre-medication values on day 3. Normalised high- and low-frequency power show little changes during the study period. Conclusions: The changes in fetal heart rate variability following betamethasone administration show the same pattern when calculated by spectral analysis of the fetal electrocardiogram, as when calculated by cardiotocography. Since normalised spectral values show little changes, the influence of autonomic modulation seems minor.