Artificial intelligence based cardiotocogram assessment during labor.

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 in majority-voted annotations. CONCLUSION: The developed method can distinguish between normal and pathological events in near real-time, with a performance close to the agreement between three gynecologists with access to the entire CTG tracing and fetal outcome. The method has a strong potential to support clinicians in assessing fetal condition in clinical practice.

Peroxisome Metabolism Contributes to PIEZO2-Mediated Mechanical Allodynia.

Mutations in the peroxisomal half-transporter ABCD1 cause X-linked adrenoleukodystrophy, resulting in elevated very long-chain fatty acids (VLCFA), progressive neurodegeneration and an associated pain syndrome that is poorly understood. In the nervous system of mice, we found ABCD1 expression to be highest in dorsal root ganglia (DRG), with satellite glial cells (SGCs) displaying higher expression than neurons. We subsequently examined sensory behavior and DRG pathophysiology in mice deficient in ABCD1 compared to wild-type mice. Beginning at 8 months of age, Abcd1-/y mice developed persistent mechanical allodynia. DRG had a greater number of IB4-positive nociceptive neurons expressing PIEZO2, the mechanosensitive ion channel. Blocking PIEZO2 partially rescued the mechanical allodynia. Beyond affecting neurons, ABCD1 deficiency impacted SGCs, as demonstrated by high levels of VLCFA, increased glial fibrillary acidic protein (GFAP), as well as genes disrupting neuron-SGC connectivity. These findings suggest that lack of the peroxisomal half-transporter ABCD1 leads to PIEZO2-mediated mechanical allodynia as well as SGC dysfunction. Given the known supportive role of SGCs to neurons, this elucidates a novel mechanism underlying pain in X-linked adrenoleukodystrophy.

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.

Computer-based intrapartum fetal monitoring and beyond: A review of the 2nd Workshop on Signal Processing and Monitoring in Labor (October 2017, Oxford, UK).

The second Signal Processing and Monitoring in Labor workshop gathered researchers who utilize promising new research strategies and initiatives to tackle the challenges of intrapartum fetal monitoring. The workshop included a series of lectures and discussions focusing on: new algorithms and techniques for cardiotocogoraphy (CTG) and electrocardiogram acquisition and analyses; the results of a CTG evaluation challenge comparing state-of-the-art computerized methods and visual interpretation for the detection of arterial cord pH <7.05 at birth; the lack of consensus about the role of intrapartum acidemia in the etiology of fetal brain injury; the differences between methods for CTG analysis "mimicking" expert clinicians and those derived from "data-driven" analyses; a critical review of the results from two randomized controlled trials testing the former in clinical practice; and relevant insights from modern physiology-based studies. We concluded that the automated algorithms performed comparably to each other and to clinical assessment of the CTG. However, the sensitivity and specificity urgently need to be improved (both computerized and visual assessment). Data-driven CTG evaluation requires further work with large multicenter datasets based on well-defined labor outcomes. And before first tests in the clinic, there are important lessons to be learnt from clinical trials that tested automated algorithms mimicking expert CTG interpretation. In addition, transabdominal fetal electrocardiogram monitoring provides reliable CTG traces and variability estimates; and fetal electrocardiogram waveform analysis is subject to promising new research. There is a clear need for close collaboration between computing and clinical experts. We believe that progress will be possible with multidisciplinary collaborative research.

Intrathecal Adeno-Associated Viral Vector-Mediated Gene Delivery for Adrenomyeloneuropathy.

Mutations in the gene encoding the peroxisomal ATP-binding cassette transporter (ABCD1) cause elevations in very long-chain fatty acids (VLCFAs) and the neurodegenerative disease adrenoleukodystrophy (ALD). In most adults, this manifests as the spinal cord axonopathy adrenomyeloneuropathy (AMN). A challenge in virus-based gene therapy in AMN is how to achieve functional gene correction to the entire spinal cord while minimizing leakage into the systemic circulation, which could contribute to toxicity. In the present study, we used an osmotic pump to deliver adeno-associated viral (AAV) vector into the lumbar cerebrospinal fluid space in mice. We report that slow intrathecal delivery of recombinant AAV serotype 9 (rAAV9) achieves efficient gene transfer across the spinal cord and dorsal root ganglia as demonstrated with two different transgenes, GFP and ABCD1. In the Abcd1-/- mouse, gene correction after continuous rAAV9-CBA-hABCD1 delivery led to a 20% decrease in VLCFA levels in spinal cord compared with controls. The major cell types transduced were astrocytes, vascular endothelial cells, and neurons. Importantly, rAAV9 delivered intrathecally by osmotic pump, in contrast to bolus injection, reduced systemic leakage into peripheral organs, particularly liver and heart tissue.

Absence of harmful effects of magnetic resonance exposure at 1.5 T in utero during the third trimester of pregnancy: a follow-up study.

In this study the possible adverse effects of in utero exposure to magnetic resonance (MR) conditions at 1.5 Tesla were examined. Thirty-five children between 1 and 3 years of age, and nine children between 8 and 9 years of age, that were exposed to MR during the third trimester of pregnancy, were checked for possible adverse effects in a follow-up study. Data on pregnancy and birth, the results of a neurological examination at 3 months, their medical documentary with emphasis on eye and ear functioning, and a questionnaire answered by their mothers were collected and evaluated. In five children abnormal test results were observed, that had no relation to the MR exposure. No harmful effects of prenatal MR exposure in the third trimester of pregnancy were detected in this study.

Antenatal proton MR spectroscopy of the human brain in vivo.

INTRODUCTION: The assessment of metabolites in the human fetal brain in utero could have diagnostic value. We explored the feasibility and potentials of proton magnetic resonance spectroscopy ((1)H MRS) for this purpose. RESULTS: (1)H MRS was successfully performed in the third trimester of pregnancy without using sedation. Signals for inositol, choline, creatine, and N-acetylasparatate (NAA) compounds were detected in MR spectra from single voxels in the brain. Absolute tissue levels of these metabolites resemble values measured in preterm and term babies, especially of relatively more mature brain regions, from which most of the MR spectra have been obtained. Brain maturation between 30 and 41 weeks of gestation was most clearly reflected by increasing levels of the neuronal marker NAA. CONCLUSION: With proper care for the methodological aspects, antenatal (1)H MRS clearly has the potential to evolve into a clinical tool for assessing a number of key metabolites in the human fetal brain in utero.

Decreased relative brain tissue levels of inositol in fetal hydrocephalus.

OBJECTIVE: Inositol seems to play a role in the development of the central nervous system. In this study, the brain tissue level of inositol in fetal hydrocephalus was compared with that of healthy control subjects. STUDY DESIGN: Proton magnetic resonance spectroscopy was used to examine the inositol over creatine ratio in the brain of 10 hydrocephalic human fetuses and 36 normal control subjects. RESULTS: Resolved signals for inositol and creatine were detected successfully in six hydrocephalic fetuses and in all control subjects. The inositol over creatine ratio was significantly lower in fetuses with hydrocephalus (P <.01). CONCLUSION: This result supports speculations concerning the role of inositol in central nervous system development.

Maturation of the human fetal brain as observed by 1H MR spectroscopy.

Proton MRS was used to monitor cerebral metabolite tissue levels in 35 normal fetuses during development in the gestational age range of 30-41 weeks. First, MRI in three orthogonal orientations was performed. A volume of interest (VOI) (15-43 cc) of fetal brain tissue was then selected for (1)H MRS. For localization, two pulse sequences (stimulated echo acquisition mode (STEAM) at TE = 20 ms, and point-resolved spectroscopy (PRESS) at TE = 135 ms) were applied. The MR spectra of the brain showed signals for inositol (Ino), choline (Cho), creatine (Cr), and N-acetyl (NA) compounds. From 30 to 41 weeks the absolute tissue level of NA, and the ratios of NA/Cr and NA/Cho increased, whereas the ratio of Cho/Cr decreased. These changes reflect maturation of the brain. Considering the diagnostic value of proton MRS in pediatric neurology, this new approach may also be useful for characterizing pathological conditions in the fetal brain.