Deep learning identifies cardiac coupling between mother and fetus during gestation

In the last two decades, stillbirth has caused around 2 million fetal deaths worldwide. Although current ultrasound tools are reliably used for the assessment of fetal growth during pregnancy, it still raises safety issues on the fetus, requires skilled providers, and has economic concerns in less developed countries. Here, we propose deep coherence, a novel artificial intelligence (AI) approach that relies on 1 min non-invasive electrocardiography (ECG) to explain the association between maternal and fetal heartbeats during pregnancy. We validated the performance of this approach using a trained deep learning tool on a total of 941 one minute maternal-fetal R-peaks segments collected from 172 pregnant women (20–40 weeks). The high accuracy achieved by the tool (90%) in identifying coupling scenarios demonstrated the potential of using AI as a monitoring tool for frequent evaluation of fetal development. The interpretability of deep learning was significant in explaining synchronization mechanisms between the maternal and fetal heartbeats. This study could potentially pave the way toward the integration of automated deep learning tools in clinical practice to provide timely and continuous fetal monitoring while reducing triage, side-effects, and costs associated with current clinical devices

Ultrasound Imaging of Mouse Fetal Intracranial Hemorrhage Due to Ischemia/Reperfusion

Despite vast improvement in perinatal care during the 30 years, the incidence rate of neonatal encephalopathy remains unchanged without any further Progress towards preventive strategies for the clinical impasse. Antenatal brain injury including fetal intracranial hemorrhage caused by ischemia/reperfusion is known as one of the primary triggers of neonatal injury. However, the mechanisms of antenatal brain injury are poorly understood unless better predictive models of the disease are developed. Here we show a mouse model for fetal intracranial hemorrhage in vivo developed to investigate the actual timing of hypoxia-ischemic events and their related mechanisms of injury. Intrauterine growth restriction mouse fetuses were exposed to ischemia/reperfusion cycles by occluding and opening the uterine and ovarian arteries in the mother. The presence and timing of fetal intracranial hemorrhage caused by the ischemia/reperfusion were measured with histological observation and ultrasound imaging. Protein-restricted diet increased the risk of fetal intracranial hemorrhage. The monitoring of fetal brains by ultrasound B-mode imaging clarified that cerebral hemorrhage in the fetal brain occurred after the second ischemic period. Three-dimensional ultrasound power Doppler imaging visualized the disappearance of main blood flows in the fetal brain. These indicate a breakdown of cerebrovascular autoregulation which causes the fetal intracranial hemorrhage. This study supports the fact that the ischemia/reperfusion triggers cerebral hemorrhage in the fetal brain. The present method enables us to noninvasively create the cerebral hemorrhage in a fetus without directly touching the body but with repeated occlusion and opening of the uterine and ovarian arteries in the mother

Evaluation of Abdominal Fetal Electrocardiography in Early Intrauterine Growth Restriction

Objectives: This descriptive study was performed to evaluate the capability of a non-invasive transabdominal electrocardiographic system to extract clear fetal electrocardiographic (FECG) measurements from intrauterine growth restricted (IUGR) fetuses and to assess whether abdominal FECG parameters can be developed as markers for evaluating the fetal cardiac status in IUGR.Methods: Transabdominal FECG was attempted in 20 controls and 15 IUGR singleton pregnancies at 20+0−33+6 weeks gestation. Standard ECG parameters were compared between the study groups and evaluated for their correlation. Accuracy for the prediction of IUGR by cut off values of the different FECG parameters was also determined.Results: Clear P-QRST complexes were recognized in all cases. In the IUGR fetuses, the QT and QTc intervals were significantly prolonged (p = 0.017 and p = 0.002, respectively). There was no correlation between ECG parameters and Doppler or other indices to predict IUGR. The generation of cut off values for detecting IUGR showed increasing sensitivities but decreasing specificities with the prolongation of ECG parameters.Conclusion: The study of fetal electrocardiophysiology is now feasible through a non-invasive transabdominal route. This study confirms the potential of FECG as a clinical screening tool to aid diagnosis and management of fetuses after key limitations are addressed. In the case of IUGR, both QT and QTc intervals were significantly prolonged and thus validate earlier study findings where both these parameters were found to be markers of diastolic dysfunction. This research is a useful prelude to a test of accuracy and Receiver Operating Characteristics (ROC) study

Estimating Gestational Age From Maternal-Fetal Heart Rate Coupling Parameters

Maternal and fetal heartbeat couplings are evident throughout fetal development. Most of the published work, however, did not consider maternal physiological factors such as Heart Rate Variability (HRV), and did not investigate the interrelationships of maternal-fetal coupling parameters. The aims of this study are to investigate whether: 1) maternal-fetal Heart Rate (HR) coupling ( λ-based) parameters are associated with fetal development, and 2) fetal gold standard Gestational Age (GA) can be estimated using maternal-fetal HR coupling and variability of various recording lengths. The study considered Electrocardiogram (ECG) signals from 60 healthy pregnant women with no records of fetal abnormalities. HRV and λ parameters at various Maternal:Fetal coupling ratios were calculated, and stepwise regression was utilized to create generalized linear regression models considering various lengths of recorded signals (1 and 5 min) to produce a robust estimate of fetal age. Cross-validation performances were evaluated by the mean square root of the average of squared errors (mRMSE) between age values estimated by the proposed models and gold standard GA identified by Crown-Rump Length (CRL). Effect of Fetal Behavioral States (FBSes) on proposed models with different recording lengths was considered to examine the highly nonstationary nature of signals. We found that HR coupling strength for a specific ratio is not constant throughout gestation. Results showed that ratios of 2:3 and 2:4 were common between the proposed models. The value of λ[2:3] was found to be positively correlated with GA, while λ[2:4] had a negative correlation. Compared with gold standard GA identified by CRL, the proposed regression model resulted in mRMSE of 2.67 and 3.69 weeks for the recordings of 5 and 1 min, respectively. However, when FBS was considered, both models produced lower estimation errors. Fetal GA can be more reliably estimated by a multivariate model incorporating fetal and maternal HR coupling and HRV parameters using 5 min of ECG signals

Intrauterine Ischemic Reperfusion Switches the Fetal Transcriptional Pattern from HIF-1α- to P53-Dependent Regulation in the Murine Brain

<div><p>Ischemic reperfusion (IR) during the perinatal period is a known causative factor of fetal brain damage. So far, both morphologic and histologic evidence has shown that fetal brain damage can be observed only several hours to days after an IR insult has occurred. Therefore, to prevent fetal brain damage under these circumstances, a more detailed understanding of the underlying molecular mechanisms involved during an acute response to IR is necessary. In the present work, pregnant mice were exposed to IR on day 18 of gestation by clipping one side of the maternal uterine horn. Simultaneous fetal electrocardiography was performed during the procedure to verify that conditions resulting in fetal brain damage were met. Fetal brain sampling within 30 minutes after IR insult revealed molecular evidence that a fetal response was indeed triggered in the form of inhibition of the Akt-mTOR-S6 synthesis pathway. Interestingly, significant changes in mRNA levels for both HIF-1<i>α</i> and p53 were apparent and gene regulation patterns were observed to switch from a HIF-1<i>α</i>-dependent to a p53-dependent process. Moreover, pre-treatment with pifithrin-<i>α</i>, a p53 inhibitor, inhibited protein synthesis almost completely, revealing the possibility of preventing fetal brain damage by prophylactic pifithrin-<i>α</i> treatment.</p></div

P53 mRNA was increased response to IR in the fetal brain.

<p>Within 30 minutes post-IR, the mRNA levels of <i>Mapk associated proteins,</i> except <i>Jnk2</i> and <i>Trp53</i> (<i>p53</i>), were noted to have increased, while <i>Hif-1α, Mdm2</i> and <i>Ccm3/Pdcd10</i> were not increased as compared to the housekeeping gene <i>Hprt1</i>. (<i>n</i> = 12 from at least 3 individual pregnant mice). <i>p</i><0.05 indicated as single star and <i>p</i><0.01 indicated as two stars.</p

IR changed signaling pathways in the fetal brain.

<p>(A) The phosphorylation of JNK1/2 was activated in the fetal brain without (−) or with IR (+). The phosphorylation of both Akt and ERK1/2 were suppressed in the fetal brain by IR. (B, C, D) Measurement and Graph data <i>p</i><0.01 indicated as two stars (<i>n</i>  = 5 fetuses from at least 3 individual pregnant mice). White means fetal brain and black means fetal heart.</p

An ischemic reperfusion in pregnant mice.

<p>(A) Experimental design (B) No IR treatment pregnant mice and Ischemic reperfusion (IR) mice underwent surgery on day 18 of gestation. (C). Fetal electrocardiography (FECG) was used to monitor the conditions of both the mother and the fetuses in either clipped or non-clipped uterine horns (<i>n</i> = 5 fetuses from at least 5 individual pregnant mice). (C) Measurement of oxygen concentration in the amniotic fluid before and after IR (<i>p</i><0.01 indicated as two stars, <i>n</i> = 5 fetuses from at least 3 individual pregnant mice).</p