Fetal electrocardiography and artificial intelligence for prenatal detection of congenital heart disease.

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.

Implementation of the combined use of non-invasive fetal electrocardiography and electrohysterography during labor: A prospective clinical study.

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 neonates (4%) were admitted to the neonatal intensive care unit for complications not related to intrapartum monitoring. CONCLUSIONS: NI-fECG and EHG can be successfully used during labor in 90% of women. Future research is needed to conclude whether implementation of electrophysiological monitoring can improve obstetric and neonatal outcomes.

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. METHODS AND FINDINGS: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. CONCLUSIONS: In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. TRIAL REGISTRATION: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.

Hyperemesis gravidarum severity, enteral tube feeding and cardiometabolic markers in offspring cord blood.

This study aimed to investigate the association between hyperemesis gravidarum (HG) severity and early enteral tube feeding on cardiometabolic markers in offspring cord blood. We included women admitted for HG, who participated in the MOTHER randomised controlled trial (RCT) and observational cohort. The MOTHER RCT showed that early enteral tube feeding in addition to standard care did not affect symptoms/birth outcomes. Among RCT and cohort participants, we assessed how HG severity affected lipid, c-peptide, glucose and free thyroxine cord blood levels. HG severity measures were severity of vomiting at inclusion and 3 weeks after inclusion, pregnancy weight gain and 24-h energy intake at inclusion, readmissions and duration of hospital admissions. Cord blood measures were also compared between RCT participants allocated to enteral tube feeding and those receiving standard care. Between 2013-2016, 215 women were included: 115 RCT and 100 cohort participants. Eighty-one cord blood samples were available. Univariable not multivariable regression analysis showed that lower maternal weight gain was associated with higher cord blood glucose levels (ß: -0·08, 95% CI -0·16, -0·00). Lower maternal weight gain was associated with higher Apo-B cord blood levels in multivariable regression analysis (ß: -0·01, 95% CI -0·02, -0·01). No associations were found between other HG severity measures or allocation to enteral tube feeding and cord blood cardiometabolic markers. In conclusion, while lower maternal weight gain was associated with higher Apo-B cord blood levels, no other HG severity measures were linked with cord blood cardiometabolic markers, nor were these markers affected by enteral tube feeding.

Recurrence, postponing pregnancy, and termination rates after hyperemesis gravidarum: Follow up of the MOTHER study.

INTRODUCTION: Hyperemesis gravidarum (HG) complicates 1% of pregnancies and has a major impact on maternal quality of life and well-being. We know very little about HG's long-term impact after an affected pregnancy, including recurrence rates in future pregnancies, which is essential information for women considering subsequent pregnancies. In this study, we aimed to prospectively measure the recurrence rate of HG and the number of postponed and terminated subsequent pregnancies due to HG. We also aimed to evaluate if there were predictive factors that could identify women at increased risk for HG recurrence, and postponing and terminating subsequent pregnancies. MATERIAL AND METHODS: We conducted a prospective cohort study. A total of 215 women admitted for HG to public hospitals in the Netherlands were enrolled in the original MOTHER randomized controlled trial and associated observational cohort. Seventy-three women were included in this follow-up study. Data were collected through an online questionnaire. Recurrent HG was defined as vomiting symptoms accompanied by any of the following: multiple medication use, weight loss, admission, tube feeding or if nausea and vomiting symptoms were severe enough to affect life and/or work. Outcome measures were recurrence, postponing, and termination rates due to HG. Univariable logistic regression analysis was used to identify predictive factors associated with HG recurrence, and postponing and terminating subsequent pregnancies. RESULTS: Thirty-five women (48%) became pregnant again of whom 40% had postponed their pregnancy due to HG. HG recurred in 89% of pregnancies. One woman terminated and eight women (23%) considered terminating their pregnancy because of recurrent HG. Twenty-four out of 38 women did not get pregnant again because of HG in the past. Univariable logistic regression analysis identifying possible predictive factors found that having a western background was associated with having weight loss due to recurrent HG in subsequent pregnancies (odds ratio 12.9, 95% CI 1.3-130.5, p = 0.03). CONCLUSIONS: High rates of HG recurrence and a high number of postponed pregnancies due to HG were observed. Women can be informed of a high chance of recurrence to enable informed family planning.

Thyroid-stimulating hormone and free thyroxine fail to predict the severity and clinical course of hyperemesis gravidarum: A prospective cohort study.

INTRODUCTION: Little is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG. MATERIAL AND METHODS: We conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4. RESULTS: Between 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg; ß = 2.00, 95% CI 0.47-3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion (ß = 1.74, 95% CI 0.36-3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty-one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis (p = 0.03). CONCLUSIONS: Our findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG.

Right ventricular dysfunction identified by abnormal strain values precedes evident growth restriction in small for gestational age fetuses.

OBJECTIVES: Small for gestational age (SGA) fetuses have an increased risk for adverse outcome. Placental insufficiency leads to changes in the circulation, with secondary adaptation of the fetal heart resulting in changed cardiac deformation. This deformation can be measured with 2D speckle tracking echocardiography (2D-STE). SGA is antenatally often undiagnosed. The measurement of deformation changes in the fetal heart might help in the prediction of SGA and identify fetuses in need of more intensive surveillance. METHODS: In this longitudinal prospective cohort study, global longitudinal strain (GLS) and strain rate (GLSR), measured before 23 weeks gestational age were compared between SGA and appropriate for gestational age (AGA) fetuses, based on birthweight corrected for gestational age at birth. RESULTS: The fetal heart rate was significantly increased in SGA; 158 beats per minute (146-163) vs 148 (134-156); P = 0.035 in AGA. Right ventricle GLS (RV-GLS) values were significantly increased in SGA; -15.87% (-11.69% to -20.55%) vs -20.24% (-16.29% to -24.28%); p = 0.024, respectively. CONCLUSION: RV-GLS values, measured with 2D-STE, were significantly increased in SGA, indicating systolic RV dysfunction before 23 weeks gestational age in fetuses who will become SGA later in pregnancy. A large longitudinal prospective cohort study is needed to confirm these findings.

Feasibility of non-invasive Foetal electrocardiography in a twin pregnancy.

BACKGROUND: Twin pregnancy is associated with increased perinatal mortality. Close foetal monitoring is therefore warranted. Doppler Ultrasound cardiotocography is currently the only available method to monitor both individual foetuses. Unfortunately, the performance measures of this method are poor and erroneous monitoring of the same twin with both transducers may occur, leaving the second twin unmonitored. In this study we aimed to determine the feasibility of monitoring both foetuses simultaneously in twin gestation by means of non-invasive foetal electrocardiography (NI-fECG), using an electrode patch on the maternal abdomen. METHODS: A NI-fECG recording was performed at 25 + 3 weeks of gestation on a multiparous woman pregnant with dichorionic diamniotic twins. An electrode patch consisting of eight adhesive electrodes was applied on the maternal abdomen, yielding six channels of bipolar electrophysiological measurements. The output was digitized and stored for offline processing. The recorded signals were preprocessed by suppression of high-frequency noise, baseline wander, and powerline interference. Secondly, the maternal ECG was subtracted and segmentation into individual ECG complexes was performed. Finally, ensemble averaging of these individual ECG complexes was performed to suppress interferences. RESULTS: Six different recordings were obtained from each of the six recording channels. Depending on the orientation and distance of the fetal heart with respect to each electrode, a distinction could be made between each fetus based on the morphology of the signals. Yielding of the fetal ECGs was performed manually based on the QRS complexes of each fetus. CONCLUSION: NI-fECG with multiple electrodes allows for monitoring of the fetal heart rate and ECG of both individual fetuses in twin pregnancies.

The diagnostic value of fetal fibronectin testing in clinical practice.

AIM: To evaluate the clinical management to withhold treatment for preterm labor in symptomatic women with an intermediate cervical length and negative fetal fibronectin (fFN) testing. METHODS: A retrospective cohort study was performed in a tertiary care teaching hospital in the Netherlands. Pregnant women with a gestational age between 23+5 to 34+0 weeks, with the presence of regular uterine contractions accompanied by a cervical length between 15 and 30 mm and intact membranes, who underwent fFN testing were included to obtain the diagnostic value of fFN testing for preterm delivery within 7 days. RESULTS: Fetal fibronectin testing has an extremely high negative predictive value (100%) and sensitivity (100%) for delivery within 7 days, in singleton and multiple pregnancies. However, specificity (64%) and positive predictive value (10%) of fFN testing in singleton pregnancies are low. Blood present on the fFN sample does not affect the reliability of the fFN test; the negative predictive value remains 100%. CONCLUSION: Women with symptoms of early preterm labor, intact membranes, a cervical length between 15 and 30 mm and negative fFN testing do not deliver within 7 days. Administration of corticosteroids and tocolytics can safely be withhold. Furthermore, blood on the fFN sample does not change the reliability of the fFN test.

Normal fetal cardiac deformation values in pregnancy; a prospective cohort study protocol.

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. TRIAL REGISTRATION: National Trial Register number: NTR7132. Date of inclusion: 2018/04/06.

Fetal Heart Rate Monitoring Implemented by Dynamic Adaptation of Transmission Power of a Flexible Ultrasound Transducer Array.

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.

Normal ranges for fetal electrocardiogram values for the healthy fetus of 18-24 weeks of gestation: a prospective cohort study.

BACKGROUND: The fetal anomaly ultrasound only detects 65 to 81 % of the patients with congenital heart disease, making it the most common structural fetal anomaly of which a significant part is missed during prenatal life. Therefore, we need a reliable non-invasive diagnostic method which improves the predictive value for congenital heart diseases early in pregnancy. Fetal electrocardiography could be this desired diagnostic method. There are multiple technical challenges to overcome in the conduction of the fetal electrocardiogram. In addition, interpretation is difficult due to the organisation of the fetal circulation in utero. We want to establish the normal ranges and values of the fetal electrocardiogram parameters in healthy fetuses of 18 to 24 weeks of gestation. METHODS/DESIGN: Women with an uneventful singleton pregnancy between 18 and 24 weeks of gestation are asked to participate in this prospective cohort study. A certified and experienced sonographist performs the fetal anomaly scan. Subsequently, a fetal electrocardiogram recording is performed using dedicated signal processing methods. Measurements are performed at two institutes. We will include 300 participants to determine the normal values and 95 % confidence intervals of the fetal electrocardiogram parameters in a healthy fetus. We will evaluate the fetal heart rate, segment intervals, normalised amplitude and the fetal heart axis. Three months postpartum, we will evaluate if a newborn is healthy through a questionnaire. DISCUSSION: Fetal electrocardiography could be a promising tool in the screening program for congenital heart diseases. The electrocardiogram is a depiction of the intimate relationship between the cardiac nerve conduction pathways and the structural morphology of the fetal heart, and therefore particularly suitable for the detection of secondary effects due to a congenital heart disease (hypotrophy, hypertrophy and conduction interruption).

Fetal heart rate variability during pregnancy, obtained from non-invasive electrocardiogram recordings.

OBJECTIVE: Non-invasive spectral analysis of fetal heart rate variability is a promising new field of fetal monitoring. To validate this method properly, we studied the relationship between gestational age and the influence of fetal rest-activity state on spectral estimates of fetal heart rate variability. DESIGN: Prospective longitudinal study. SETTING: Tertiary care teaching hospital. POPULATION: Forty healthy women with an uneventful singleton pregnancy. METHODS: Non-invasive fetal electrocardiogram measurements via the maternal abdomen were performed at regular intervals between 14 and 40 weeks of gestation and processed to detect beat-to-beat fetal heart rate. Simultaneous ultrasound recordings were performed to assess fetal rest-activity state. MAIN OUTCOME MEASURES: Absolute and normalized power of fetal heart rate variability in the low (0.04-0.15 Hz) and high (0.4-1.5 Hz) frequency band were obtained, using Fourier Transform. RESULTS: 14% of all measurements and 3% of the total amount of abdominal data (330 segments) was usable for spectral analysis. During 21-30 weeks of gestation, a significant increase in absolute low and high frequency power was observed. During the active state near term, absolute and normalized low frequency power were significantly higher and normalized high frequency power was significantly lower compared with the quiet state. CONCLUSIONS: The observed increase in absolute spectral estimates in preterm fetuses was probably due to increased sympathetic and parasympathetic modulation and might be a sign of autonomic development. Further improvements in signal processing are needed before this new method of fetal monitoring can be introduced in clinical practice.

Changes in Maternal Heart Rate Variability and Photoplethysmography Morphology after Corticosteroid Administration: A Prospective, Observational Study.

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.

Transferring an extremely premature infant to an extra-uterine life support system: a prospective view on the obstetric procedure.

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.

Feasibility and reliability of fetal two dimensional speckle tracking echocardiography at 16 weeks gestational age: A pilot study.

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.

Study protocol for two randomised controlled trials evaluating the effects of Cerclage in the reduction of extreme preterm birth and perinatal mortality in twin pregnancies with a short cervix or dilatation: the TWIN Cerclage studies.

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. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT05968794.

Changes in Maternal Heart Rate and Autonomic Regulation following the Antenatal Administration of Corticosteroids: A Secondary Analysis.

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 betamethasone­a corticosteroid commonly used for fetal maturation­in 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.

Prognostic model on niche development after a first caesarean section: development and internal validation.

OBJECTIVE: To develop and internally validate a prognostic prediction model for development of a niche in the uterine scar after a first caesarean section (CS). STUDY DESIGN: Secondary analyses on data of a randomized controlled trial, performed in 32 hospitals in the Netherlands among women undergoing a first caesarean section. We used multivariable backward logistic regression. Missing data were handled using multiple imputation. Model performance was assessed by calibration and discrimination. Internal validation using bootstrapping techniques took place. The outcome was 'development of a niche in the uterus', defined as an indentation of ≥ 2 mm in the myometrium. RESULTS: We developed two models to predict niche development: in the total population and after elective CS. Patient related risk factors were: gestational age, twin pregnancy and smoking, and surgery related risk factors were double-layer closure and less surgical experience. Multiparity and Vicryl suture material were protective factors. The prediction model in women undergoing elective CS revealed similar results. After internal validation, Nagelkerke R2 ranged from 0.01 to 0.05 and was considered low; median area under the curve (AUC) ranged from 0.56 to 0.62, indicating failed to poor discriminative ability. CONCLUSIONS: The model cannot be used to accurately predict the development of a niche after a first CS. However, several factors seem to influence scar healing which indicates possibilities for future prevention such as surgical experience and suture material. The search for additional risk factors that play a role in development of a niche should be continued to improve the discriminative ability.

Evidence and clinical relevance of maternal-fetal cardiac coupling: A scoping review.

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 evident that MFCC does indeed exist and may have clinical relevance in tracking fetal well-being and development during pregnancy.