mHealth intervention to improve the continuum of maternal and perinatal care in rural Guatemala: a pragmatic, randomized controlled feasibility trial.

BACKGROUND/OBJECTIVE: Guatemala's indigenous Maya population has one of the highest perinatal and maternal mortality rates in Latin America. In this population most births are delivered at home by traditional birth attendants (TBAs), who have limited support and linkages to public hospitals. The goal of this study was to characterize the detection of maternal and perinatal complications and rates of facility-level referral by TBAs, and to evaluate the impact of a mHealth decision support system on these rates. METHODS: A pragmatic one-year feasibility trial of an mHealth decisions support system was conducted in rural Maya communities in collaboration with TBAs. TBAs were individually randomized in an unblinded fashion to either early-access or later-access to the mHealth system. TBAs in the early-access arm used the mHealth system throughout the study. TBAs in the later-access arm provided usual care until crossing over uni-directionally to the mHealth system at the study midpoint. The primary study outcome was the monthly rate of referral to facility-level care, adjusted for birth volume. RESULTS: Forty-four TBAs were randomized, 23 to the early-access arm and 21 to the later-access arm. Outcomes were analyzed for 799 pregnancies (early-access 425, later-access 374). Monthly referral rates to facility-level care were significantly higher among the early-access arm (median 33 referrals per 100 births, IQR 22-58) compared to the later-access arm (median 20 per 100, IQR 0-30) (p = 0.03). At the study midpoint, the later-access arm began using the mHealth platform and its referral rates increased (median 34 referrals per 100 births, IQR 5-50) with no significant difference from the early-access arm (p = 0.58). Rates of complications were similar in both arms, except for hypertensive disorders of pregnancy, which were significantly higher among TBAs in the early-access arm (RR 3.3, 95% CI 1.10-9.86). CONCLUSIONS: Referral rates were higher when TBAs had access to the mHealth platform. The introduction of mHealth supportive technologies for TBAs is feasible and can improve detection of complications and timely referral to facility-care within challenging healthcare delivery contexts. TRIAL REGISTRATION: Clinicaltrials.gov NCT02348840 .

Doppler-based fetal heart rate analysis markers for the detection of early intrauterine growth restriction.

INTRODUCTION: One indicator for fetal risk of mortality is intrauterine growth restriction (IUGR). Whether markers reflecting the impact of growth restriction on the cardiovascular system, computed from a Doppler-derived heart rate signal, would be suitable for its detection antenatally was studied. MATERIAL AND METHODS: We used a cardiotocography archive of 1163 IUGR cases and 1163 healthy controls, matched for gestation and gender. We assessed the discriminative power of short-term variability and long-term variability of the fetal heart rate, computed over episodes of high and low variation aiming to separate growth-restricted fetuses from controls. Metrics characterizing the sleep state distribution within a trace were also considered for inclusion into an IUGR detection model. RESULTS: Significant differences in the risk markers comparing growth-restricted with healthy fetuses were found. When used in a logistic regression classifier, their performance for identifying IUGR was considerably superior before 34 weeks of gestation. Long-term variability in active sleep was superior to short-term variability [area under the receiver operator curve (AUC) of 72% compared with 71%]. Most predictive was the number of minutes in high variation per hour (AUC of 75%). A multivariate IUGR prediction model improved the AUC to 76%. CONCLUSION: We suggest that heart rate variability markers together with surrogate information on sleep states can contribute to the detection of early-onset IUGR.

Unsupervised hidden semi-Markov model for automatic beat onset detection in 1D Doppler ultrasound.

OBJECTIVE: One dimensional (1D) Doppler ultrasound (DUS) is commonly used for fetal health assessment, during both regular prenatal visits and labor. It is used in preference to ECG and other modalities because of its simplicity and cost. To date, all analysis of such data has been confined to a smoothed, windowed heart rate estimation derived from the 1D DUS signal, reducing the potential of short-term variability information. A first step in improving the assessment of short-term variability of the fetal heart rate (FHR) is through implementing an accurate beat detector for 1D DUS signals. APPROACH: This work presents an unsupervised probabilistic segmentation method enabled by a hidden semi-Markov model (HSMM). The proposed method employs envelope and spectral features for an online segmentation of fetal 1D DUS signal. The beat onsets and fetal cardiac beat-to-beat intervals are then estimated from the segmentations. For this work, two data sets were used, including 1D DUS recordings from five fetuses recorded in Germany, comprising 6521 beats and 45.06 minutes of data (dataset 1). Simultaneous fetal ECG (fECG) was used as the reference for beat timing. Dataset 2, comprising 4044 beats captured from 17 subjects in the UK was hand scored for beat location and was used as an independent held-out test set. Leave-one-out subject cross-validation was used for parameter tuning on dataset 1. No retraining was performed for dataset 2. To assess the performance of the beat onset detection, the root mean square error (RMSE), F1 score, sensitivity, positive predictivity (PPV) and the error in several standard common heart rate variability metrics were used. These metrics were evaluated on three fiducial points: (1) beat onset, (2) beat offset, and (3) middle of beat interval. MAIN RESULTS: In dataset 1, the proposed method provided an RMSE of 20 ms, F1 score of 97.5 %, a Se of 97.6%, and a PPV of 97.3%. In dataset 2, the proposed method achieved an RMSE of 26 ms, an F1 score of 98.5 %, a Se of 98.0 % and a PPV of 98.9 %. It was also determined that the best beat-to-beat interval was derived from the onset of each beat. For the dataset 2, significant correlations were found in all short term heart rate variability metrics tested, both in the time and frequency domain. Only the proportion of successive normal-to-normal interval differences greater than 20 ms (pNN20) exhibited a significant absolute difference. SIGNIFICANCE: This work presents the first-ever description of an algorithm to identify cardiac beats with 1D DUS, closely matching the fetal ECG-derived beats, to enable short-term heart rate variability analysis. The novel algorithm proposed requires no human labeling of data, and could have applicability beyond 1D DUS to other similar highly variable time series.

An open source autocorrelation-based method for fetal heart rate estimation from one-dimensional Doppler ultrasound.

OBJECTIVE: Open research on fetal heart rate (FHR) estimation is relatively rare, and evidence for the utility of metrics derived from Doppler ultrasound devices has historically remained hidden in the proprietary documentation of commercial entities, thereby inhibiting its assessment and improvement. Nevertheless, recent studies have attempted to improve FHR estimation; however, these methods were developed and tested using datasets composed of few subjects and are therefore unlikely to be generalizable on a population level. The work presented here introduces a reproducible and generalizable autocorrelation (AC)-based method for FHR estimation from one-dimensional Doppler ultrasound (1D-DUS) signals. APPROACH: Simultaneous fetal electrocardiogram (fECG) and 1D-DUS signals generated by a hand-held Doppler transducer in a fixed position were captured by trained healthcare workers in a European hospital. The fECG QRS complexes were identified using a previously published fECG extraction algorithm and were then over-read to ensure accuracy. An AC-based method to estimate FHR was then developed on this data, using a total of 721 1D-DUS segments, each 3.75 s long, and parameters were tuned with Bayesian optimization. The trained FHR estimator was tested on two additional (independent) hand-annotated Doppler-only datasets recorded with the same device but on different populations: one composed of 3938 segments (from 99 fetuses) acquired in rural Guatemala, and another composed of 894 segments (from 17 fetuses) recorded in a hospital in the UK. MAIN RESULTS: The proposed AC-based method was able to estimate FHR within 10% of the reference FHR values 96% of the time, with an accuracy of 97% for manually identified good quality segments in both of the independent test sets. SIGNIFICANCE: This is the first work to publish open source code for FHR estimation from 1D-DUS data. The method was shown to satisfy estimations within 10% of the reference FHR values and it therefore defines a minimum accuracy for the field to match or surpass. Our work establishes a basis from which future methods can be developed to more accurately estimate FHR variability for assessing fetal wellbeing from 1D-DUS signals.

Cardiotocography and beyond: a review of one-dimensional Doppler ultrasound application in fetal monitoring.

One-dimensional Doppler ultrasound (1D-DUS) provides a low-cost and simple method for acquiring a rich signal for use in cardiovascular screening. However, despite the use of 1D-DUS in cardiotocography (CTG) for decades, there are still challenges that limit the effectiveness of its users in reducing fetal and neonatal morbidities and mortalities. This is partly due to the noisy, transient, complex and nonstationary nature of the 1D-DUS signals. Current challenges also include lack of efficient signal quality metrics, insufficient signal processing techniques for extraction of fetal heart rate and other vital parameters with adequate temporal resolution, and lack of appropriate clinical decision support for CTG and Doppler interpretation. Moreover, the almost complete lack of open research in both hardware and software in this field, as well as commercial pressures to market the much more expensive and difficult to use Doppler imaging devices, has hampered innovation. This paper reviews the basics of fetal cardiac function, 1D-DUS signal generation and processing, its application in fetal monitoring and assessment of fetal development and wellbeing. It also provides recommendations for future development of signal processing and modeling approaches, to improve the application of 1D-DUS in fetal monitoring, as well as the need for annotated open databases.

Template-based Quality Assessment of the Doppler Ultrasound Signal for Fetal Monitoring.

One dimensional Doppler Ultrasound (DUS) is a low cost method for fetal auscultation. However, accuracy of any metrics derived from the DUS signals depends on their quality, which relies heavily on operator skills. In low resource settings, where skill levels are sparse, it is important for the device to provide real time signal quality feedback to allow the re-recording of data. Retrospectively, signal quality assessment can help remove low quality recordings when processing large amounts of data. To this end, we proposed a novel template-based method, to assess DUS signal quality. Data used in this study were collected from 17 pregnant women using a low-cost transducer connected to a smart phone. Recordings were split into 1990 segments of 3.75 s duration, and hand labeled for quality by three independent annotators. The proposed template-based method uses Empirical Mode Decomposition (EMD) to allow detection of the fetal heart beats and segmentation into short, time-aligned temporal windows. Templates were derived for each 15 s window of the recordings. The DUS signal quality index (SQI) was calculated by correlating the segments in each window with the corresponding running template using four different pre-processing steps: (i) no additional preprocessing, (ii) linear resampling of each beat, (iii) dynamic time warping (DTW) of each beat and (iv) weighted DTW of each beat. The template-based SQIs were combined with additional features based on sample entropy and power spectral density. To assess the performance of the method, the dataset was split into training and test subsets. The training set was used to obtain the best combination of features for predicting the DUS quality using cross validation, and the test set was used to estimate the classification accuracy using bootstrap resampling. A median out of sample classification accuracy on the test set of 85.8% was found using three features; template-based SQI, sample entropy and the relative power in the 160 to 660 Hz range. The results suggest that the new automated method can reliably assess the DUS quality, thereby helping users to consistently record DUS signals with acceptable quality for fetal monitoring.

Agile Development of a Smartphone App for Perinatal Monitoring in a Resource-Constrained Setting.

Technology provides the potential to empower frontline healthcare workers with low levels of training and literacy, particularly in low- and middle-income countries. An obvious platform for achieving this aim is the smartphone, a low cost, almost ubiquitous device with good supply chain infrastructure and a general cultural acceptance for its use. In particular, the smartphone offers the opportunity to provide augmented or procedural information through active audiovisual aids to illiterate or untrained users, as described in this article. In this article, the process of refinement and iterative design of a smartphone application prototype to support perinatal surveillance in rural Guatemala for indigenous Maya lay midwives with low levels of literacy and technology exposure is described. Following on from a pilot to investigate the feasibility of this system, a two-year project to develop a robust in-field system was initiated, culminating in a randomized controlled trial of the system, which is ongoing. The development required an agile approach, with the development team working both remotely and in country to identify and solve key technical and cultural issues in close collaboration with the midwife end-users. This article describes this process and intermediate results. The application prototype was refined in two phases, with expanding numbers of end-users. Some of the key weaknesses identified in the system during the development cycles were user error when inserting and assembling cables and interacting with the 1-D ultrasound-recording interface, as well as unexpectedly poor bandwidth for data uploads in the central healthcare facility. Safety nets for these issues were developed and the resultant system was well accepted and highly utilized by the end-users. To evaluate the effectiveness of the system after full field deployment, data quality, and corruption over time, as well as general usage of the system and the volume of application support for end-users required by the in-country team was analyzed. Through iterative review of data quality and consistent use of user feedback, the volume and percentage of high quality recordings was increased monthly. Final analysis of the impact of the system on obstetrical referral volume and maternal and neonatal clinical outcomes is pending conclusion of the ongoing clinical trial.

Monitoring fetal maturation-objectives, techniques and indices of autonomic function.

Monitoring the fetal behavior does not only have implications for acute care but also for identifying developmental disturbances that burden the entire later life. The concept, of 'fetal programming', also known as 'developmental origins of adult disease hypothesis', e.g. applies for cardiovascular, metabolic, hyperkinetic, cognitive disorders. Since the autonomic nervous system is involved in all of those systems, cardiac autonomic control may provide relevant functional diagnostic and prognostic information. The fetal heart rate patterns (HRP) are one of the few functional signals in the prenatal period that relate to autonomic control and, therefore, is predestinated for its evaluation. The development of sensitive markers of fetal maturation and its disturbances requires the consideration of physiological fundamentals, recording technology and HRP parameters of autonomic control. Based on the ESGCO2016 special session on monitoring the fetal maturation we herein report the most recent results on: (i) functional fetal autonomic brain age score (fABAS), Recurrence Quantitative Analysis and Binary Symbolic Dynamics of complex HRP resolve specific maturation periods, (ii) magnetocardiography (MCG) based fABAS was validated for cardiotocography (CTG), (iii) 30 min recordings are sufficient for obtaining episodes of high variability, important for intrauterine growth restriction (IUGR) detection in handheld Doppler, (iv) novel parameters from PRSA to identify Intra IUGR fetuses, (v) evaluation of fetal electrocardiographic (ECG) recordings, (vi) correlation between maternal and fetal HRV is disturbed in pre-eclampsia. The reported novel developments significantly extend the possibilities for the established CTG methodology. Novel HRP indices improve the accuracy of assessment due to their more appropriate consideration of complex autonomic processes across the recording technologies (CTG, handheld Doppler, MCG, ECG). The ultimate objective is their dissemination into routine practice and studies of fetal developmental disturbances with implications for programming of adult diseases.

An mHealth monitoring system for traditional birth attendant-led antenatal risk assessment in rural Guatemala.

Limited funding for medical technology, low levels of education and poor infrastructure for delivering and maintaining technology severely limit medical decision support in low- and middle-income countries. Perinatal and maternal mortality is of particular concern with millions dying every year from potentially treatable conditions. Guatemala has one of the worst maternal mortality ratios, the highest incidence of intra-uterine growth restriction (IUGR), and one of the lowest gross national incomes per capita within Latin America. To address the lack of decision support in rural Guatemala, a smartphone-based system is proposed including peripheral sensors, such as a handheld Doppler for the identification of foetal compromise. Designed for use by illiterate birth attendants, the system uses pictograms, audio guidance, local and cloud processing, SMS alerts and voice calling. The initial prototype was evaluated on 22 women in highland Guatemala. Results were fed back into the refinement of the system, currently undergoing RCT evaluation.